28 Spinal cord disorders

This and Chapter 29 address non-traumatic, pathological disorders involving the spinal cord, cauda equina, and nerve roots within the vertebral canal. The systems are anatomically close, lying within the vertebral canal, so there is an introductory section on the anatomy of these nerve structures. The innervation of the bladder, rectum, corpus cavernosum, and seminal vesicles is reviewed in Chapter 29, but pathological disorders outside the vertebral canal, which affect sphincter function, are discussed in Section 22.7.

Non-traumatic spinal cord disease may be caused by compression due to tumour, infection or haematoma, inflammation, infection or post-infection, metabolic disturbances, infarction, and degeneration. The diagnosis is often made easier by the clinical assessment: the patient’s age, the speed of onset of the disease, severity of the deficits, the pattern of motor and sensory involvement, and presence of pain and sphincter symptoms are all important in making an assessment of the site and likely nature of the spinal disease.

Investigations are obligatory to confirm a diagnosis and to direct therapy. MRI is the most useful investigation. It has largely replaced myelography which should now only be considered in patients with indwelling cardiac pacing wires. Additional investigations including examination of the cerebrospinal fluid, evoked potentials, and specific blood tests may be required and the value of plain X-rays, CT scan, and, in some instances, angiography should not be overlooked.

The remainder of this chapter will consider specific disorders, identifying pathology, clinical presentation, investigation, and management. Acute and chronic conditions are considered separately and those affecting the cauda equina, spinal root, and sphincters are considered in the Chapter 29.

The spinal cord extends from the foramen magnum, where it joins the medulla oblongata, to the level of the first or second lumbar vertebra; it is within the vertebral canal throughout is length. It is oval, flattened in the antero-posterior axis, and has two enlargements, one in the cervical and one in the lumbar region, corresponding to the outflow of nerves to the upper and lower limbs. At its lower end it terminates in the conus medullaris from the end of which the filum terminale continues downwards to the posterior surface of the coccyx. The surface of the spinal cord shows several longitudinal grooves; there is a deep anterior fissure and a shallower posterior medium sulcus and on the lateral aspect two sulci, termed antero-lateral and postero-lateral. From these lateral sulci a series of root filaments emerge anteriorly and posteriorly on each side. At intervals several filaments from the postero-lateral sulcus unite to form a dorsal root upon which is situated the dorsal root ganglion; similarly, those from the antero-lateral sulcus unite to form a ventral root. The dorsal and ventral roots are paired, they join just distal to the dorsal root ganglion and form the spinal nerve which exits the canal through the intervertebral foramen.

The spinal cord is organized into segments, one corresponding to each pair of spinal nerves. There are eight cervical, twelve dorsal or thoracic, five lumbar, five sacral, and one coccygeal segment. The spinal cord ends at the first or second lumbar vertebra and all the nerves below the first lumbar descend to their respective foramina in a bundle of nerves which resembles a horse’s tail and is called the cauda equina.

The spinal cord, like the brain, is surrounded by three meninges: the pia mater, a fibrous membrane, forms the immediate covering of the cord and fine septa penetrate into the cord substance; the arachnoid mater is a delicate, transparent membrane lying superficially to the pia mater from which it is separated by the sub-arachnoid space, containing cerebrospinal fluid, CSF, and being bridged by trabeculae; outside the arachnoid is the dura mater which lines the vertebral canal, from which it is separated by the epidural space containing fat and the internal vertebral venous plexus. The arachnoid extends to the second sacral vertebra, the dura to the third sacral vertebra. The spinal cord is suspended within the dural sheath by a series of ligamenta denticulata, which extend laterally from each side of the cord terminating in tooth-like attachments to the inner aspect of the dura.

On transverse section the spinal cord is divided into the central grey matter, which has an H-shape, and the peripheral white matter. The grey matter consists of ganglion cells and nerve fibres and the white matter of ascending and descending fibres with their myelin sheaths.

The white matter, which consists of longitudinal bundles of nerve fibres, is divided into three columns on each side. The anterior column lies between the anterior fissure and the anterior horn of grey matter, the lateral column lies laterally to the grey matter between the ventral and dorsal roots, which is between the antero-lateral and postero-lateral sulci, and the posterior column lies between the posterior medium septum and the posterior horn of grey matter.

The anterior column contains ascending and crossed fibres in the ventral spino-thalamic tract, together with descending fibres in the olivo-spinal, vestibulo-spinal, tecto-spinal, and ventral cortico-spinal tracts. The lateral column contains the major descending motor pathway, the lateral cortico-spinal tract, with the smaller descending rubro-spinal tract and the ascending and crossed lateral spino-thalamic tract, and the ventral and dorsal spino-cerebellar tracts. The dorsal column contains the ascending, uncrossed gracile and cuneate fascicles carrying axons sub-serving proprioceptive and vibration sensation to their first synapse in the respective nuclei in the brainstem. In the lateral cortico-spinal tract the descending motor neurones destined for the lumbo-sacral segments run laterally to those destined for the cervical segment and a similar layered relationship exists for ascending fibres in the crossed spino-thalamic tracts. However, in the posterior columns fibres from the lower limbs lie more medial than those ascending from the upper limbs so the dorsal column enlarges progressively from the lower thoracic to the cervical region.

Descending sympathetic autonomic fibres travel in the intermedio-lateral columns of the grey matter on each side of the thoracic cord and in the upper lumbar segments. Parasympathetic neurones lie in the anterior horns of the grey matter of the sacral segments.

The fact that the spinal cord ends at the first or second lumbar vertebra explains why the segmental organization of the cord is anatomically higher in each of its levels than the spinal nerves. In the cervical region the cord segment is 1–2 vertebrae above the level of the exiting nerve root, in the thoracic region 3–4 vertebrae higher and even more in the lumbo-sacral and coccygeal segments. The H-shaped mass of grey matter within the spinal cord consists of anterior and posterior horns on each side, united by a grey commissure in the middle of which lies the central canal. The anterior horns contain ganglion cells, the axons of which enter the anterior roots and form the lower motor neurone running to the effector muscle. The alpha motor neurones which innervate skeletal muscles are larger than the gamma motor neurones which run to the muscle spindles. The motor neurones are arranged in groups transversely and columns longitudinally and these specific groups and columns in the cervical and lumbar enlargements innervate specific muscle groups and individual muscles via the relevant spinal nerves. The total number of lower motor neurones in the anterior horns of the spinal cord is remarkably consistent, both from side to side and between individuals (Tomlinson et al. 1973). The nerve cell groups in the posterior horn of the grey matter comprise the substantia gelatinosa which are the cell bodies of axons entering through the dorsal roots and which synapse with other neurones whose axons cross the mid-line to ascend in the contralateral spinothalamic tracts. Other cells in the dorsal funicular group, or nucleus proprius, may have similar function whereas the neurones of the nucleus dorsalis synapse and send axons into the dorsal spino-cerebellar tracts.

At each segmental level the entering dorsal root sends some axons to synapse in the dorsal horn but others, which have their cell bodies in the dorsal root ganglion, remain ipsilateral and ascend in the posterior funiculus.

At each segmental level the dorsal, sensory nerve root with its appendage, the dorsal root ganglion, separates from the ventral motor root just inside the intervertebral foramen, the two uniting distally to form the individual spinal nerve root and, in the cervical and lumbo-sacral levels become part of the nerve plexus.

The spinal cord is richly supplied with blood. There are two posterior spinal arteries, each derived from the corresponding vertebral or posterior inferior cerebellar artery at the level of the foramen magnum. These two posterior vessels traverse the length of the spinal cord lying just in front of, or just behind, the dorsal nerve roots. There is a single anterior spinal artery formed by the union of a branch from each vertebral artery which descends throughout the length of the spinal cord in the anterior median fissure. The spinal arteries are reinforced at each intervertebral foramen by segmental arteries derived from the vertebral costo-cervical trunk, intercostal and lumbar arteries. Two of these segmental arteries tend to be larger than the rest and of greater importance, one in the lower cervical region, commonly at C6, and one, the great anterior radicular artery of Adamkiewicz, which usually enters the spinal cord between the T5 and T8 segments on the left side (Fig. 28.1).

At each segmental level the cord is surrounded by small circumferential vessels that run over the surface, form anastomoses between the anterior and posterior spinal vessels and send horizontal branches into the cord to supply the white matter and part of the posterior horns of the grey matter.

The direction of blood flow in the anterior spinal artery may not be the same throughout its length (Bolton 1939). Flow can be in both rostral and caudal directions, is variable from one individual to another, and may be modified by vascular disease. The measurement of spinal cord blood flow in animals has confirmed that both motor and sensory activity at a spinal segmental level is associated with temporary vasodilatation and increased blood flow in the relevant portion of the cord, cauda equina, and nerve roots (Blau and Rushworth 1958). The anterior spinal artery supplies all but the posterior part of the posterior columns and the posterior horns, which are supplied by the posterior spinal arteries. Occlusion of the anterior spinal artery therefore results in massive infarction of the spinal cord whereas damage to the posterior spinal arteries is less significant.

Descending branches from the spinal arteries supply the cauda equina and the vessels in the lowest segments of the cord and the roots and cauda equina receive tributaries from the ilio-lumbar and lateral sacral branches of the internal iliac arteries.

The spinal veins derived from the spinal cord substance terminate in a plexus in the pia mater where there are six tortuous, often plexiform longitudinal channels, one along the anterior median fissure, a second along the posterior median sulcus, and two others situated on either side, one pair just behind and the other just in front of the line of attachment of the ventral and dorsal nerve roots. These six vessels communicate freely with one another and above pass into the corresponding veins of the medulla oblongata and drain into the intracranial venous sinuses. The posterior half of the cord is drained by posterior medullary veins; the anterior medullary group has one lateral and two medial groups, and the anastomotic pattern may explain the clinical features of venous infarction of the cord (Hughes 1971).

There is an internal vertebral venous plexus which lies within the vertebral canal between the dura and the vertebra, this receives tributaries from the spinal cord and is arranged as four longitudinal veins. These vessels communicate with the external vertebral venous plexus, via the foramina and, though this is relatively unimportant in the normal situation. However thrombophlebitis may reach the spinal veins by this route and back pressure from abdominal and thoracic contents can cause venous thrombosis.

This section considers the general features of spinal cord lesions and specific findings according to the segmental level of the cord lesion. The signs and symptoms of spinal cord disorders are dependent upon the level, longitudinal and transverse extent, and pathological nature of the underlying cause. Because there are many potentially treatable causes of spinal cord dysfunction, and because delays in diagnosis may have an adverse effect on outcome, a thorough knowledge of the clinical manifestations is essential.

The classical features of spinal cord disease involve sensory, motor, and sphincter manifestations, but partial, or early, lesions may involve only one or two of these functions. Symptoms described by patients include weakness below the level of the lesion, with difficulties in walking and/or in upper limb function. The gait may be described as weak, stiff, a tendency to drag the legs or unsteady and there may be symptoms of painful muscle spasms or cramps. Sensory symptoms include numbness, tingling, pins and needles, hypersensitivity, burning sensations, altered sensation of temperature, and tight band like feelings or the sensation of swelling below the lesion. When a cord lesion is complete loss of all voluntary movement and sensation will occur below it. Pain may occur at the level of the lesion, particularly when there is spinal cord compression from extrinsic disease involving the vertebral column. The most common sphincter disturbances, due to spinal cord disease are urgency, frequency, and incontinence of urine. Hesitancy or urinary retention is less common except in acute transverse spinal cord lesions where retention, as part of ‘spinal shock’ is the rule. Constipation is common and faecal incontinence rare. In males erectile dysfunction is a common symptom and other autonomic changes, such as postural hypotension, excessive sweating, and vasomotor disturbances occur below the site of the lesion; Horner’s syndrome may occur with lesions in the cervical spinal cord.

Clinical symptoms and signs can be divided into those occurring at the level of the lesion and those below the level of the lesion due to interruption of the long tracts. At the level of the lesion there may be lower motor neurone signs with focal muscle wasting, fasciculation, and hypo or areflexia due to damage to anterior horn cells. This pattern of motor involvement will be focal and segmental. Radicular pain or dermatomal sensory loss may occur due to damage to sensory nerve roots. Damage to the long tracts is usually the most serious consequence of spinal cord disease. Damage to the lateral and anterior columns causes upper motor neurone signs below the level of the lesion with pyramidal pattern of weakness, being greater in the anti-gravity muscles, or the extensors of the arms and flexors of the legs, spasticity and hyper-reflexia with absent abdominal reflexes and extensor plantar responses. Acute, severe spinal cord lesions produce a flaccid paraplegia below the level of the lesion with a temporary phase of hypotonia and areflexia, sometimes called ‘spinal shock’, before the appearance of more characteristic upper motor neurone signs. The differential diagnosis in this setting is of an acute inflammatory polyneuropathy or Guillain–Barré Syndrome (Section 21.10.1) but the sensory findings and the involvement of sphincter function, which is rare in polyneuropathy, are helpful in making the distinction.

A complete cord syndrome results in loss of all sensory modalities below the level of the lesion. Partial syndromes may produce variable findings; damage to the posterior columns causes loss of joint position sense, vibration, and two-point discrimination ipsilateral to the lesion, with a positive Romberg’s sign and an ataxic gait. In the upper limb pseudo-athetoid movements may occur when the hands are held out-stretched with the eyes closed. When damage affects the spino-thalamic pathways there is contralateral loss of pain and temperature sensation below the level of the lesion.

Lesions at the level of the foramen magnum are characterized by upper motor neurone weakness and sensory loss affecting any modality below the level of the cranium. Rarely there may be deficits affecting the lowest cranial nerves. The only manifestation may be a high spinal cord syndrome but commonly neck stiffness and pain radiating into a shoulder, occipital headache with weakness of the upper or lower extremities, numbness of the hands or arms, and clumsiness may be described. It is common to find an upper motor neurone monoparesis, hemiparesis, or quadriparesis, and the loss of sensation may involve all modalities though it can be ‘cape like’ and as high as the second cervical dermatome. There may be pseudo-athetosis of the fingers due to loss of joint position sense and there can be proximal atrophy of muscles in the upper extremities. Sometimes ‘electric shock’-like sensation is described by the patient, similar to Lhermitte’s symptom. Rarely, down-beat nystagmus will be found and more rarely involvement of the twelfth cranial nerve. Classically symptoms may begin in one limb then spread in a ‘clockwise’ or ‘counter-clockwise’ direction to the ipsilateral lower limb, contralateral lower limb, then contralateral upper limb, or to the contralateral upper limb, contralateral lower limb, then ipsilateral lower limb.

The differential diagnosis is often between a foramen magnum and upper cervical cord tumour. The importance of the syndrome is that it may be due to benign tumours such as a meningioma or neurofibroma, although severe pain raises the possibility of metastases (Fig. 28.2). Arnold Chiari malformations may occasionally present in this way.

Neck pain is common, there will be both sensory and motor problems affecting the upper and lower limbs, there will be tetraparesis or tetraplegia and, if the lesion is above the level of C4, the diaphragm may be affected, compromising respiration when lying. Sensory impairment will involve all four limbs and the trunk. With extrinsic lesions pressing upon the cord or with inflammation in the cord reflexes will be brisk with extensor plantar responses, but if the lesion is central within the cervical spinal cord, as in syringomyelia, upper limb reflexes may be depressed and associated with a suspended sensory disturbance.

Damage between the third and sixth cervical vertebra will affect the fifth, sixth, and seventh cervical nerve roots. There will be atrophy and weakness of muscles innervated by those roots, particularly the rhomboids, deltoids, spinati, biceps, brachioradialis, and triceps. There will be spastic paralysis of the lower limbs and of the C8 and T1 innervated muscles in the upper limbs. Biceps, brachioradialis, and triceps reflexes will be diminished or lost and there may be ‘inversion’ of reflexes; striking the biceps tendon resulting in flexion of the fingers. C8 reflexes will be brisk. Sensory symptoms occur in the lower limbs, trunk, and medial aspects of the upper limbs, including the ring and little fingers.

When damage is at the level of the lower cervical spine the eighth cervical and first thoracic nerve roots are likely to be involved. There will be relatively normal power above the level of the lesion but weakness and atrophy of the flexors of the wrists and fingers and of the small muscles of the hand. There may be a Horner’s syndrome, though this is more commonly seen with lesions affecting the first thoracic nerve root peripherally. Tendon reflexes in the upper limbs will be retained though the finger jerk may be absent. There will be spastic paralysis of the trunk and lower limbs, sparing of the bladder, and sensory abnormality in the lower limbs, trunk, and medial arm, probably involving the medial forearm and digits.

Damage in the upper thoracic spine will manifest as atrophic paralysis confined to the intercostal muscles innervated by the segments involved. Movements of the diaphragm will be normal but there will be spastic paralysis of the muscles of the abdomen and lower limbs and a sensory level demonstrable on the trunk.

When damage occurs below the mid-thoracic spine cord involvement is likely to be below the 10th thoracic segment. Sensory loss will reach the level of the umbilicus, the lower abdominal recti will be paralysed, and when the patient lying on a bed is asked to raise the head from the bed, the umbilicus should be drawn upwards, Beevor’s sign. The upper abdominal reflexes will be preserved, the lower abdominal reflexes lost, and there should be spastic paralysis of the lower limbs.

If the lesion occurs lower, affecting the 12th thoracic and first lumbar segments the abdominal muscles will be spared, the abdominal reflexes will be intact, but the cremasteric reflexes will be diminished or lost and there will be spastic paralysis of the lower limbs.

When damage occurs at the lowest part of the thoracic spine, involvement of the bottom of the spinal cord and conus medularis is likely. If the third and fourth lumbar segments are involved hip flexion will remain intact, but there will be wasting and weakness of quadriceps and hip adductors with reduction or loss of knee jerks, but a spastic paralysis below that level. The ankle jerks will be brisk and the plantar responses extensor. Sensory loss will be present below the level of the knees, spreading onto the posterior calves, thighs, buttocks, and perineum.

When the lesion affects the first and second sacral segments then flexion of the hip, adduction of the thigh and extension of the knee and dorsiflexion of the foot will be preserved. There will be atrophic paralysis of the intrinsic muscles of the foot and calf with weakness of knee flexion and hip abduction and extension. The knee jerks will be present, the ankle jerks absent, and the plantar responses mute. The anal and bulbo-cavernosus reflexes will be retained and sensory loss will involve the buttocks and perineum, extending down the posterior aspect of the lower limbs to the soles of the feet.

When the third and fourth sacral segments are involved the large bowel and bladder are paralysed with retention of urine and constipation, due to the uninhibited action of the sympathetic nerve supply. The external sphincters are paralysed and the anal and bulbo-cavernosus reflexes are lost. There is usually sensory loss in the perineum and in the buttocks in a ‘saddle’ distribution. Power in the lower limbs and the reflexes are normal.

Motor symptoms due to damage to the spinal cord are of two types. At the level of the cord injury there will be damage to the anterior horn cells and anterior roots and, depending upon the length of the lesion, lower motor neurone signs will be evident at segmental levels. The spinal cord or nerve root damage may be lateralized indicating the site of the lesion and will involve flaccid weakness, ultimately muscle wasting and the loss of relevant deep tendon reflexes.

Below the level of the spinal cord lesion there may initially, in severe lesions, be an acute flaccid paresis due to ‘spinal shock’ but within a matter of hours to days the signs of spastic weakness will emerge with increased tone, brisk reflexes, and a pyramidal distribution of the motor weakness affecting, predominantly, the flexors of the lower limbs and the extensors of the upper limbs. The most helpful signs of spinal cord damage are the plantar responses. When there has been spinal injury and the plantar responses can be demonstrated to be extensor then, because the spinal cord ends at second or third lumbar vertebra, the damage is almost invariably in the cervico-dorsal spine and radiology of the lumbar spine is unlikely to be relevant.

In the cervical spine the combination of radicular and lower motor neurone signs with upper motor signs below the level of the lesion may be enhanced by the finding of ‘inversion’ of reflexes. Most commonly this occurs where damage at C5/6 root level also affects the spinal cord, rendering hyperactive the anterior horn cell pool below that level. Striking the C5/6 reflex with a tendon hammer results in absence of the C5/6 reflex, but demonstrates enhancement of the C8 reflex in finger flexion and, on rare occasions, even triceps causing elbow extension. This combination of upper and lower motor lesions in the cervical spinal cord is very suggestive of cervical spondylosis causing a radiculo-myelopathy.

Ultimately there may be the development of contractures in a chronically spastic limb and trophic change in the colour and appearance of the skin.

Although motor symptoms are most important in identifying the site of the lesion sensory symptoms are helpful in identifying its completeness. When a spinal cord lesion is total all sensory modalities below the level of the lesion will be affected. If the lesion is partial affecting the posterior aspect of the cord, then there may only be loss of proprioception and if partial affecting one or other side of the cord, then crossed anaesthesia with ipsilateral proprioceptive loss as in the Brown–Sequard syndrome can be identified.

In keeping with the symptoms and signs of motor disturbance there may be acute pain in a radicular distribution at the site of the lesion with loss of sensory modalities below it. Occasionally spinal cord lesions cause hyperpathia, or increased sensitivity, below the level of the lesion, most classically after trauma or ischaemia.

In addition to the immediate symptoms and signs of sensory disturbance with a spinal cord lesion there may be the development of trophic changes in the skin and ultimately ulceration due to anaesthesia together with the finding of Charcot joints.

Lesions in the cervical region may be associated with Horner’s syndrome and those affecting the T1 root may result in loss of sweating in the ipsilateral hand. Occasionally central cord lesions, such as syringomyelia, may present with hyperhydrosis due to sympathetic malfunction in one or both upper limbs.

Vasomotor changes are common below the level of a spinal cord injury. Those affecting the cervical or dorsal spine and damaging the sympathetic nervous outflow may result in disturbances of bowel motility, vasomotor changes and postural hypotension, and damage to bladder and bowel control, most commonly causing urgency and frequency of micturition and constipation. Impotence is a common symptom of spinal injury in the male.

When there is major injury to the cervical or upper thoracic spinal cord the clinical syndrome of ‘spinal shock’ may occur. It is characterized by loss of motor, sensory and autonomic function below the level of the lesion. The more severe and the higher the spinal cord injury the greater the duration and severity of the ‘spinal shock’.

Most commonly patients have flaccid paralysis with loss of cutaneous and deep tendon reflexes and anaesthesia to all sensory modalities below the level of the injury. There may also be systemic hypotension, cutaneous hyperaemia, and bradycardia as a result of autonomic dysfunction and unopposed vagal tone. Whether the syndrome occurs due to vascular hypoperfusion of the spinal cord after trauma, or is due to abnormal neurotransmitter production is uncertain.

Clinically problems are caused by the difficulty in assessing the nature of the spinal injury and the uncertainty about the duration of the syndrome. Usually ‘spinal shock’ resolves within hours and weakness or numbness which persists is likely to be due to physical cord injury. There are, however, reports of both absent reflexes and autonomic changes lasting for days then resolving, particularly with high cervical lesions. In practical terms it is important that clinicians do not mistake ‘spinal shock’ for hypovolaemic shock. The latter is due to fluid loss and responds to volume repletion, the former responds to sympathomimetic agents, rather than to volume replacement.

Though best exemplified by traumatic cord injury, acute inflammatory or ischaemic disease can cause identical effects to transection. The level of the cord damage is apparent and below it all sensory modalities are lost, bladder and bowel function is affected, and there is total paralysis with the eventual development of increased tone and hyper-reflexia below the level of the lesion. There may also be significant postural hypotension and, if the lesion is high, quadriplegia and possible loss of diaphragmatic control (Fig. 28.3).

Damage in the mid to low cervical region is common following a fall in an elderly person with hyperextension of the neck which was previously the site of cervical spondylosis. It may also be seen with acute inflammatory lesions and acute ischaemic lesions. It is characterized by weakness that is more marked in the arms than in the legs, there is patchy sensory loss with dysaesthesiae and a-reflexia in the upper limbs. The preferred investigation is MRI of the cervical spine and, in those cases due to trauma, prognosis depends upon evidence of ischaemia or haematoma within the spinal cord. Central lesions due to inflammatory transverse myelopathies are frequently necrotic and prognosis is guarded, the use of steroids is recommended, and plasmapheresis may be considered.

Damage or disease affecting the anterior part of the spinal cord is most commonly seen in ischaemic anterior spinal artery occlusion or trauma. It may follow large disc herniations and fractures with retro-pulsed bone fragments. It is characterized by complete paralysis below the level of the lesion with hypalgesia at the level of the injury and loss of spinothalamic sensation beneath. Posterior column sensation is preserved due to the separate blood supply from the posterior spinal arteries.

Prognosis for recovery of motor function is poor, though some sensory improvement can occur. Surgical intervention may be required, interventional angiography has little to offer.

Inflammatory disease of the central nervous system, particularly multiple sclerosis, may cause focal damage to the posterior columns, often towards their lateral elements, in the cervical spine. This can result in lack of proprioception and, in multiple sclerosis, the bilateral ‘useless hands of Oppenheim’ may result where there is sensory ataxia of both hands. If a posterior cord syndrome is more extensive, following infarction of the posterior spinal arteries, then there may be sparing of pinprick and thermal sensation below the level of the lesion but there will be paralysis and total loss of proprioception below that level. Posterior cord syndromes may also occur with vitamin B12 deficiency.

Defined as hemi-section of the cord this may follow trauma but is more commonly seen with inflammatory demyelinating disease as in multiple sclerosis. It is occasionally seen with tumours where one half of a spinal cord is damaged. The patient has ipsilateral loss of motor control and posterior column function below the level of the injury, but contra lateral loss of pain and temperature sensation, usually from one or two dermatomes below the level of the proprioceptive loss, due to the crossing fibres (Section 2.5.3, Fig. 2.54). This loss of sensory function may be called ‘dissociated’, that is with ‘posterior column’ and ‘spinothalamic’ loss on opposite sides of the body. There is variable loss of sphincter function and the prognosis for recovery is usually good.

One of the most common clinical situations faced by the neurologist results from acute or chronic spinal cord injury. Often it results in permanent neurological deficit. There are few areas of neurology in which delayed or missed diagnosis, poor initial management, and lack of timely investigation, have more significant effects upon disability (Table 28.1).

Approximately half of spinal cord injury occurs in the cervical region, the remainder is distributed in the thoracic, lumbar, and sacral regions. In developed countries road traffic accidents and high-risk sports have now overtaken work-related and domestic accidents as the leading cause of spinal cord injury. Pre-hospital emergency care is essential and immobilization of the cervical spine is a major part of out of hospital management following injury in which the spine may have been damaged.

The severity of the injury varies considerably. At one end of the spectrum are mild and transient phenomena such as ‘stingers’ which are recognized by most professional sportsmen and ‘transient paraplegia’ seen in contact sports and with falls. The other end of the spectrum includes immediate irreversible paralysis due to spinal cord transection or compression with vascular injury resulting in infarction (Fig. 28.4).

Spinal cord injury, even when due to trauma, is usually associated with pre-existing conditions, such as a congenitally narrow spinal canal, cervical spondylosis, spondylolisthesis, or osteopenia, all of which make trauma more likely to result in significant spinal cord injury.

Spinal cord injury frequently occurs in the setting of multi- system injury and only 20 per cent of patients have isolated cord injury, the great majority also sustaining traumatic brain injury, haemo-pneumothorax, or fractures of long bones. It is important that the emergency room physician and neurologist called to assess such a patient recognize the effect of multiple traumas in worsening spinal cord injury and the converse effects of spinal cord injury creating hypotension and shock thereby worsening more diffuse injury.

The severity of the injury to the spinal cord varies depending upon the amount of sub-arachnoid space surrounding the spinal cord. There is relatively more space available at the foramen magnum and in the upper cervical spine, at which level fractures rarely injure the cord, except in the case of atlanto-axial dislocation, than in the mid to the lower cervical canal where the subarachnoid space is narrower, anterior and posterior dimensions may be reduced by the development of cervical spondylosis and folding of the ligamentum flavum and more minor injuries result in major trauma to the cord.

Lower in the spine there is gradually increasing spinal arachnoid space and consequently injury to the lower spinal cord, conus medullaris, and cauda equina is relatively less common. Once again the pre-existence of lumbar spondylosis, disc disease, or canal narrowing is likely to worsen outcome from trauma.

Acute spinal cord compression is a medical and surgical emergency and differentiation from non-compressive myelopathy is vital. When there is compression of the spinal cord by a disc protrusion or epidural haematoma the prognosis for recovery is inversely related to the time taken to establish the diagnosis and relieve the compression. Prognosis is also affected by the severity of the compression, pre-existing spinal conditions, and the age of the patient.

Prolapse of an intervertebral disc in the cervical region, or in the dorsal region can impinge upon and compress the spinal cord. Lesions in the lumbar region may affect the conus medullaris but are more likely to compress nerve roots.

Most disc prolapses occur laterally and in the cervical region result in root symptoms and signs, extending into an upper limb. Central disc prolapse in the cervical spine does occur, most commonly in the situation of acute hyperextension of the neck, as in falling forwards; thoracic disc protrusions can be central and compress the cord which is ‘bowstringed’ over the dorsal kyphosis.

Direct and acute central disc prolapse can cause a transverse cord syndrome with a motor and sensory level but asymmetrical prolapse may cause a partial Brown Sequard syndrome which may vary in severity.

The investigation of choice is MRI with both sagittal and axial views; the MRI scan can also reveal the degree of damage within the cord as high signal areas on T2-weighted images in the cord parenchyma (Fig. 28.5).

Acute central disc protrusion of a cervical or thoracic intervertebral disc causing spinal cord symptoms and signs is a surgical emergency. The neck should be immobilized, surgical opinion sought, and decompression performed when indicated.

Bleeding within the spinal canal but outside the dura may occur following blunt trauma or after surgical procedures, such as lumbar puncture in people who are anticoagulated or thrombocytopenic. For reasons described above haematomata are more likely to cause pressure when in the cervical or dorsal region than in the lumbar region and should always be considered when a sub-acute deterioration occurs following blunt or open trauma.

Spontaneous epidural haematoma is a rare condition which is usually seen in the thoracic region and can be due to a vascular malformation (Hernandez 1982). It is a surgical emergency. The site of the haematoma will be identified by the presence of pain and discomfort and the level of spinal injury identified clinically. MR scanning is the investigation of choice and haematomas that are more than a few days old produce a characteristic high signal on T2 MR images due to formation of methaemoglobin.

Spinal epidural abscess is potentially a neurosurgical emergency; if untreated irreversible paraplegia may develop due to cord compression and consequent ischaemia. The most common infectious agent is Staphylococcus aureus and the most common association is within discitis or infection of the relatively avascular intervertebral disc. Occasionally infection may occur with anaerobes, streptococci, and gram negative bacilli. There are two main sources of infection into the spinal epidural space, the most common is via bacteraemia or septicaemia, sometimes following an innocuous skin infection and at other times associated with endocarditis or profound septicaemia. Increasingly, haematogenous spread to the intervertebral discs is seen in intravenous drug abusers. The organism almost certainly spreads via the blood stream to the vascular endplates of the vertebra, then infiltrating the avascular intervertebral disc and rarely begins directly within the epidural space. The second source of epidural infection is following a direct and open procedure on the spine. It may occur after surgery, local injection and, rarely, the performance of lumbar puncture or epidural anaesthesia. Although open trauma to the spine is a potential cause of epidural abscess there is no evidence that closed trauma causes discitis or epidural infection.

The patient usually presents with fever and localized back pain, radicular pain at the level of infection may occur and is followed by the development of a transverse cord syndrome with sensory, motor, and sphincter deficits below the level of the lesion. The clinical features may occur sub-acutely and both fever and leucocytosis may be absent. An elevated ESR and focal tenderness to palpation of the spinal column at the level of infection may be helpful clues but the physician must have a high level of suspicion in all patients who have had septicaemia and those who have undergone recent instrumentation to the spine.

MRI is the investigation of choice and will demonstrate the extradural compressive lesion and frequently demonstrate abnormalities in the adjacent vertebra and intervertebral disc. Gadolinium enhancement of the infection may be demonstrated (Fig. 28.6). The CSF, if taken from a site below the lesion, will usually reveal a mild pleocytosis, slightly elevated protein, and a normal glucose, the typical pattern for a para-meningeal focus of infection. Lumbar puncture is not, however, a necessary investigation in this situation, rarely gives useful information about the nature of the infection, and may potentially be dangerous if the abscess is causing complete occlusion of the spinal canal.

MRI diagnosis should be followed by neurosurgical intervention with laminectomy and abscess drainage when indicated. Intravenous antibiotics are required and should be started as soon as the epidural mass is demonstrated. Blood cultures should be taken and may reveal the cause of the infection.

The prognosis is variable, being better when there is rapid diagnosis and surgical intervention where necessary and worse when there is a delay in diagnosis or surgery allowing pressure upon the cord to result in infarction of the tissue. Rarely a subdural abscess may develop, often in association with local infective lesions. Its presentation and management is the same as for extradural abscess.

When spinal infections, such as vertebral osteomyelitis, discitis, and non-compressive epidural or paraspinal abscesses are identified radiologically but not causing significant neurological dysfunction and compression they can usually be managed without surgery. Appropriate antibiotic therapy is all that is required with monitoring to ensure that, should signs of instability, progressive bone destruction, or neurological dysfunction arise, surgery can be performed urgently.

Increasingly, acute injury to the spinal cord is seen with missile injury, particularly gunshot and stab wounds. These are both surgical emergencies, with missile injuries foreign material must be removed and potential CSF leaks corrected. Where there is complete or partial transection of the cord from a missile injury it will be irreparable. Antibiotic treatment is required.

Stab wounds to the spine are usually deflected to one side and may result in a Brown–Sequard syndrome with dural laceration and CSF leak. Once again they are surgical emergencies; require appropriate imaging in a neurosurgical centre and the provision of antibiotics prior to operation.

Acute inflammatory lesions affecting the spinal cord are demyelinating, post-infective or vasculitic. The distinction between the different types may not be immediately apparent but some attempt at differentiation is important because the treatment may differ. In all cases the investigation of choice is MRI of the affected spinal area and extensive scanning of the whole spine can be important, both diagnostically and in excluding other lesions.

The spinal cord is involved pathologically and clinically at some stage of the disease in almost all patients (Section 37.5). In about 50 per cent of patients the initial presentation is of a spinal cord disturbance. Sensory, motor, and sphincter symptoms may all occur in any combination, though typically the symptoms indicate only partial disturbance of spinal cord function and sometimes only explicable on the basis of more than one lesion. Focal demyelinating lesions due to multiple sclerosis almost always occupy only part of the cross section of the spinal cord (Oppenheim 1978) (Fig. 28.7).

Common sensory symptoms include Lhermitte’s symptom tingling or electrical shock-like sensations spreading down the back and into the limbs on neck flexion. This is a common manifestation of demyelinating lesions involving the posterior columns in the cervical cord and may occur in isolation or in association with other cord symptoms. It is rarely seen in association with cervical spondylosis or other structural cervical pathology and usually indicates inflammatory disease in the cervical cord. Other sensations, which may be unilateral or bilateral, involve only the lower limbs or only the upper limbs, or be associated with a sensory level on the torso, include tingling, numbness, dysaesthesiae, loss of temperature sensation, or a tight ‘elastic band like’ sensation. A common sensory symptom in the upper limbs is loss of proprioception in both hands, ‘the useless hand of Oppenheim’ which indicates two postero-lateral cervical spine lesions and is almost diagnostic of multiple sclerosis.

Motor symptoms include limb weakness and spasms, cramps and the sensation of heaviness, unsteadiness on walking and dragging or stiffness of the lower limbs. They too may be unilateral or bilateral and symmetrical or asymmetrical.

Sphincter disturbance is most commonly manifest as increased frequency and urgency of micturition and occasional incontinence. Constipation may occur and, rarely, faecal urgency or incontinence. Impotence is a common symptom of cord demyelination in males.

The pattern of evolution of the initial attack in multiple sclerosis is usually over a few days, then stabilizing for a few weeks and resolving gradually. Examination may be surprisingly normal, though frequently there will be signs such as extensor plantar responses, brisk deep tendon reflexes, loss of vibration sensation, and absence of the abdominal reflexes. A Brown–Sequard syndrome, deafferentation of one or both hands, or the signs of a partial spinal cord lesion affecting both lower limbs and with a segmental level on the torso is most common. There may be pyramidal weakness of muscles as a monoparesis, hemiparesis, paraparesis, tri-or tetraparesis associated with the expected reflex changes.

Although the partial nature of the spinal cord involvement and other associated features, such as retrobulbar neuritis, an internuclear ophthalmoplegia, or a relevant past history may indicate the probability of the diagnosis, the investigation of the patient seen with an acute spinal episode must include an urgent spinal MRI, both to confirm the presence of demyelinating lesions and exclude other pathology, particularly compression. Multiple sclerosis most commonly causes small areas of high signal on T2-weighted images of the spinal cord, usually less than one segment in length and almost always less than three segments. There may be apparent swelling of the cord and gadolinium enhancement can be demonstrated.

Sometimes more than one focal cord lesion can be identified which may indicate dissemination of lesions in space. When this is seen it is advisable to obtain additional MRI brain since, in about 50 per cent of cases, this will reveal cerebral white matter lesions typical of multiple sclerosis. Such lesions are prognostically important, their presence indicating a substantial risk of the development of clinically definite multiple sclerosis within 5–10 years (O’Riordan et al. 1998) and fulfilling some of the requirements for the new diagnostic criteria of multiple sclerosis (Polman et al. 2005).

The indications for further investigation including evoked potentials, CSF examination, and repeated MRI in an attempt to confirm the diagnosis of multiple sclerosis and determine the indications for the use of disease modifying therapy are discussed under multiple sclerosis (Sections 37.5.5; 37.5.8).

Recurrent acute spinal cord relapses are common during the course of multiple sclerosis and, when the diagnosis is secure, do not indicate the need for further MRI. Nonetheless, the occurrence of a complete transverse cord lesion or the association with other symptoms such as pain, fever, or local tenderness in the spine indicates the need for further imaging to exclude the possibility of a second pathology.

Some patients with multiple sclerosis will not show recovery from the original episode of spinal disturbance and may progress to primary progressive multiple sclerosis. In this situation repeat MR imaging is appropriate, examination of CSF to search for oligoclonal bands is obligatory, and evoked potentials may be helpful in establishing the diagnosis (McDonald et al. 2001).

The initial treatment of a partial spinal cord lesion in multiple sclerosis is with high dose steroids in the form of methyl prednisolone given in a dose of 0.5–1g intravenously, daily for 3–5 days. If symptoms become persistent then therapy with the spasmolytics baclofen, tizanidine, dantrolene, or gabapentin should be considered and where painful dysaesthesiae or paraesthesiae persist the use of gabapentin, pregabalin, amitriptyline, or carbamazepine can be considered. Where there is sustained urgency of micturition a bladder relaxant such as oxybutinin or detrusitol may be considered, after assessing residual urine by ultrasound, and ultimately the use of intravesical botulinum toxin. Sildenafil can be considered for erectile dysfunction in males.

Patients who show frequent relapses affecting the spine and relapsing remitting multiple sclerosis, but retain ambulation, should be considered for long-term treatment with disease modifying therapy, including the beta-interferons and glatiramer acetate.

Transverse myelitis may occur as a post-infectious inflammatory process causing acute or sub-acute complete spinal cord dysfunction (Section 37.4.3). Most cases are preceded by an infectious illness and are thought to have an immuno-pathogenic basis. Rarely transverse myelitis may follow vaccination and in a proportion of cases no prior event can be identified.

Some people with transverse myelitis are shown to have high levels of autoantibodies or collagen vascular disorders, particularly systemic lupus erythematosis, the primary antiphospholipid syndrome and Sjogren’s syndrome. In these situations the pathological basis may be inflammatory or vasculitic.

In the majority of cases transverse myelitis is a monophasic disorder, but there are occasional reports, particularly in non-Caucasian populations, where multiple, recurrent episodes occur.

In the most common setting of post-infectious transverse myelitis, the preceding infection may be identified clinically or serologically, usually varicella, Epstein–Barr virus, mycoplasma, campylobacter, but there may simply have been a non-specific upper respiratory tract or gastrointestinal tract infection. People of all ages can be affected and the presentation is seen in childhood and the elderly.

The onset may be with discomfort and pain in the spine, but this symptom is usually not prominent. Weakness and paraesthesiae develop in the lower limbs and early urinary retention or incontinence is common. Symptoms evolve rapidly, typically reaching their peak within hours to days. The most common areas affected are the cervical or thoracic spinal cord and the upper level of symptoms and signs vary accordingly. Occasionally, even when a complete transverse lesion has developed clinically continuing disease activity is manifest by an ascending level of motor and sensory loss.

The investigation of choice is MRI which reveals swelling and signal change, high signal on T2-weighted images, which is typically extensive over more than three cord segments and involving the whole antero-posterior diameter of the spinal cord on the sagittal images (Fig. 28.8). In the acute phase there is patchy gadolinium enhancement.

CSF examination usually shows a moderate mono-nuclear pleocytosis, though may be a-cellular, the protein level is moderately elevated but the glucose is normal. Oligoclonal bands are sometimes present but may disappear with time. Those cases which have been examined pathologically show perivascular inflammation, sometimes with demyelination and in more severe cases with widespread inflammation and necrosis.

Brain MRI occasionally shows disseminated white matter lesions suggesting a more diffuse asymptomatic acute demyelinating encephalo-myelitis-like picture but more often brain imaging is normal. It is imperative that further microbiological investigations, including polymerase chain reaction, studies, are undertaken to identify infection and serology performed to identify collagen vascular disease or autoantibodies.

In the acute stage therapy is usually a short course of high dose corticosteroids with intravenous methyl prednisolone 0.5–1 g daily for 3–5 days with or without oral steroids thereafter. There is some evidence that plasma exchange and intravenous immunoglobulin may help but the role of these therapies remains uncertain. The prognosis is variable, some people make an excellent recovery despite complete paraplegia in the acute stage, but others are left with a permanent transection of the spinal cord.

In those cases where acute transverse myelopathy has been shown to be associated with systemic lupus erythematosis or other autoimmune conditions, vigorous immunosuppression with high dose steroids and cytotoxic agents may be employed. It should be recognized that such therapy is predominantly directed to the prevention of further lesions and is unlikely to reverse any established neurological deficit. In those cases thought to have a primary anti-phospholipid syndrome or where a coagulopathy is thought to be contributing to the spinal cord disorder, anticoagulation with heparin then with oral anticoagulants and the use of anti-platelet agents should be considered.

This is probably a variant of transverse myelitis. It is rarer and characterized by the development of acute complete transverse myelopathy followed by permanent severe disability with flaccid paraplegia or quadriplegia, areflexia, and an atonic bladder. Pathologically there is widespread necrotic change over a number of segments of the spinal cord involving both white and grey matter. It may be seen as the severe end of the spectrum of post-infectious or autoantibody related myelopathy, but it has also been reported in people who have been successfully treated for pulmonary tuberculosis.

The nosological status of Devic’s neuromyelitis optica is controversial, partially because of difference in definitions (Section 37.4.4). Originally, Devic’s disease was applied to a severe, almost complete extensive transverse myelitis in association with severe and permanent optic neuritis, the events occurring within months of one another.

More recently neuromyelitis optica has been applied to conditions with inflammatory lesions in the spinal cord and optic nerves, typically sparing the brain, and with longitudinal extensive lesions in the cord, pleocytosis in CSF, frequent autoantibodies, and negative oligoclonal bands (Wingerchuck 2007). A significant proportion of these patients have been demonstrated to have a specific neuromyelitis optica IgG which is believed to be directed against the aquaporin-4 epitope on water channels distributed throughout the axial portion of the nervous system (Lennon et al. 2005) (Fig. 28.9).

Uncertainty persists as to whether the non-Caucasian variant of inflammatory demyelination optico-spinal multiple sclerosis, which in many cases resembles neuromyelitis optica, but which may have lesions within the cerebrum, is the same disease.

In terms of the spinal cord these conditions cause central and almost complete transverse myelitis which is longer than three segments and associated with the presence of systemic autoantibodies. The prognosis for recovery from neuromyelitis optica is poor; there is often permanent paraparesis and visual loss. The suggested therapies of plasmaphoresis and cytotoxic agents with long-term steroids have been partially effective, the humoral antibody detected in a proportion of these patients now raises the question of treatment with the specific anti-CD20 monoclonal antibody rituximab, though any potential efficacy awaits demonstration in a controlled, therapeutic trial.

Pathologically lesions in Devic’s disease differ from those of inflammatory demyelination, including hyalinization of blood vessels, extensive necrotic change, and the presence of eosinophils. It is assumed that immunopathological mechanisms are likely to be important and the recently discovered antibody may be causative, though further experiments to establish transmission are awaited.

Spinal cord ischaemia and infarction may occur with embolism, occlusion, or dissection of the anterior spinal artery due to atheroma, aortic disease, or a period of hypotension. Rarely may it complicate aortography or angiography. Posterior spinal artery occlusion has been described after the intrathecal use of astringents such as phenol. When ischaemia occurs the neurones and central spinal grey matter are usually more vulnerable than the long white matter tracts.

Occlusion of the anterior spinal artery causes infarction of the anterior and lateral columns of the cord. When occlusion occurs in the cervical region there is infarction from the fourth cervical to the third thoracic segments (Spiller 1909). Clinically, there is neck pain with paraesthesiae extending into the upper limbs followed by a flaccid paralysis of both arms with loss of pain and temperature sensation below the level of the lesion but with preservation of light touch, vibration, and joint position sense due to the integrity of the posterior columns. Initially there is a flaccid paralysis of the lower limbs, spinal shock, but, if the patient survives, spastic weakness of the lower limbs develops with increased reflexes and extensor plantar responses. There is usually retention of urine and faeces in the early stages but automatic bladder and bowel control may be achieved. In severe cases paralysis remains complete and prognosis is poor but when infarction is less extensive or the ischaemia is reversible the lower limbs may show a variable degree of recovery.

In the thoracic region anterior spinal artery occlusion is usually a complication of dissecting aneurysm of the aorta, though it may follow emboli from an atheromatous plaque, vascular surgical procedures, or a drop in perfusion pressure. It is seen following cardiac arrest and as a rare complication of angiography. Rarer causes include the inadvertent injection of contrast into the thyrocervical trunk during cerebral angiography, emboli of fibro-cartilage from intervertebral disc degeneration entering the bone marrow, atrial myxoma, Sickle cell anaemia, and non-compressive Paget’s disease causing a spinal artery steal phenomenon due to arteriovenous connections (Herzberg and Bayliss 1980).

Fibro-cartilaginous embolism often occurs in the healthy athlete in association with pain in the back followed by the rapid development of a severe transverse myelopathy or the syndrome of anterior spinal artery occlusion. There may be a history of exertion or back injury during sporting activities a day or so before the syndrome begins. Such cases have been shown to be due to occlusion of small vessels within the spinal cord with fibro-cartilage, consequent infarction of the cord in association with local herniation of nucleus pulposus of an intervertebral disc into an adjacent vertebral body. It is thought that the pressure of this herniation forces disc material into vessels within the bone marrow causing subsequent embolization locally (Tosi et al. 1996).

With the more common anterior spinal cord infarction due to dissecting aortic aneurysm there is usually pain in the abdomen and back followed by total permanent flaccid paralysis of the lower limbs, sphincter paralysis, and loss of pain and temperature sensation to a level at about the umbilicus, the 10th thoracic segment of the cord. There is usually some preservation of light touch and vibration and joint position sense in the classical anterior spinal artery syndrome.

Thrombosis of posterior spinal arteries, though more rare, causes loss of proprioception, vibration sensation and light touch and venous infarction may occur commonly in the presence of the dural spinal arteriovenous malformation (Fig. 28.10).

When a complete anterior spinal artery occlusion occurs the clinical syndrome is usually apparent, but partial infarction or ischaemia of the cord may be more difficult to recognize when due to occlusion of a posterior spinal artery or a feeding radicular vessel. There may then be weakness, sensory impairment, and discomfort restricted to one limb, or asymmetrically in both lower limbs and

there may be considerable recovery after such a localized infarction. Recurrent transient episodes of spinal ischaemia, like cerebral transient ischaemic attacks, are extremely uncommon, but may be important prognostic symptoms preceding infarction.

Collagen vascular disorders such as systemic lupus erythematosis or polyarteritis nodosa may cause infarction of the spinal cord and emboli may occur from bacterial endocarditis or as part of decompression sickness, Caisson disease (Section 5.10.4). This is usually seen in underwater divers when, with decompression, nitrogen bubbles form in spinal vessels, usually in the upper thoracic cord. Symptoms may be mild and transient but can be devastating with a complete transverse myelopathy. This is a medical emergency and the patient should be treated with immediate recompression in a hyperbaric chamber; when the acute deficit is severe prognosis is variable but remarkable recovery may be seen with recompression.

In general the diagnosis of spinal cord infarction is made from the clinical features, but should always be supported by spinal MRI. This is important to rule out alternative, compressive pathology and in most instances will demonstrate the area of the infarction. Infarction is seen as a high signal region within the cord on T2-weighted images, sometimes associated with swelling, and extending over a variable number of segments. The lesion may be seen predominantly in the distribution of the anterior spinal artery and there may be changes in adjacent vertebra due to ischaemia.

Management of spinal cord infarction includes identification of the cause, search for sources of embolization, and exclusion of a coagulation disorder. Anticoagulation or interventional angiography may be indicated with venous infarction secondary to thrombosis in an arteriovenous malformation.

Haemorrhage into the spinal cord occurs much less commonly than bleeding into the brain. It is usually the result of trauma but non-traumatic causes include arteriovenous vascular malformations, bleeding into an intramedullary metastasis, a primary coagulation disorder, or the abuse of anti-coagulants. Very rarely no underlying cause can be found.

The presentation is of a sudden spinal cord syndrome, usually with pain at the level of the haemorrhage, followed by the development of a transverse cord syndrome with loss of motor and sensory function below the level of the lesion. The clinical symptoms are indistinguishable from those due to epidural or sub-dural haemorrhage and from acute infarction of the spinal cord, apart from the distribution of symptoms.

The diagnosis must be made with MRI, the cord will be swollen at the level of the haemorrhage and there will be signal loss on a T2-weighted sequence MRI scan due to the presence of deoxyhaemoglobin. Surgical evacuation of a discrete haematoma is generally advised, though the benefits are unproven.

Direct infection of the spinal cord itself is rare. By contrast bacterial infections commonly invade the tissues around the cord. Viral infections are more common and protozoal and parasitic infections occur.

Intramedullary pyogenic spinal abscess is a rare disorder which requires early diagnosis and treatment. The source of infection is usually blood borne, from bacteraemia or septicaemia, though it may occur from a local skin infection with contiguous spread through local tissues to the spinal cord (Fig. 28.11). The infecting organism is usually Staphylococcus aureus. The presentation is with fever, elevated peripheral white cell count, focal spinal pain, and a rapidly developing transverse cord lesion. Rarely the presentation may be sub-acute and there may not be systemic manifestations of infection.

Investigation is by MRI which will show a high signal intramedullary lesion on T2-weighted images with gadolinium enhancement, classically in a ‘ring’ pattern. The radiological appearances are often indistinguishable from primary intraspinal tumour, intraspinal metastasis, or an acute demyelinating lesion. CSF examination will show mild pleocytosis, moderate elevation of protein, and normal glucose. The diagnosis depends upon a high index of clinical suspicion in patients who have had bacteraemia or septicaemia, or those with local surgical procedures close to the spine. The need for surgery is important to achieve the diagnosis and to drain the abscess. High dose intravenous antibiotics should be given as soon as the diagnosis is suspected.

Viral infections of the spinal cord include poliomyelitis, coxsackie viruses, herpes zoster, herpes simplex, HIV, Epstein–Barr virus, cytomegalovirus, and HTLV1 (Section 42.4). The latter produces a characteristic chronic evolving paraparesis and is considered in the section on chronic myelopathies. All of the viruses which can cause acute infective myelitis may be associated with a post-infective myelitis which is likely to be due to immune mediated responses triggered by the viral antigen. Both poliomyelitis and coxsackie viruses produce an acute inflammatory meningomyelitis with cord involvement, predominantly affecting the anterior horn cells, leading to patchy multi-focal or sometimes extensive muscle

weakness and wasting. There is corresponding reflex loss but no sensory disturbance. In the acute phase the CSF contains a mononuclear pleocytosis with elevation of protein. Varicella zoster virus causes a sensory dermatomal effect, often with marked pain due to predominant involvement of the dorsal root ganglia. The associated dermatomal vesicular rash will normally establish the diagnosis. More extensive involvement of the adjacent spinal cord or roots can lead to features of myelopathy and segmental myotomal defects with weakness, wasting, and areflexia.

A transverse myelitis due to viral infection, such as those described, is rare but is indistinguishable from a post-infectious transverse myelitis. Such infections are most likely to occur in immuno- compromised states, including people with HIV infection (Section 43.3.6). The diagnosis is confirmed by the isolation of the viral antigen from CSF by polymerase chain reaction; high dose acyclovir is indicated for cord infections due to herpes simplex or zoster.

In patients with AIDS, a vacuolar myelopathy sometimes develops (Section 43.3.6). The tempo is sub-acute with symptoms typically evolving over weeks. Motor, sensory, and sphincter abnormalities all appear, sometimes asymmetrical and predominantly in the legs, though the arms may also be involved. Pathologically, there is vacuolation in the spinal cord white matter which is most marked in the thoracic region. This manifestation is seen in patients with AIDS, rather than asymptomatic HIV positive individuals, and therefore Highly Active Anti-Retroviral agents, HAART, should delay or prevent its occurrence.

Schistosomiasis is an important cause of spinal cord syndromes in Africa, South America, and the Far East (Section 43.2.10). The most common cause of acute myelitis is Schistosoma mansonii, but infection may also occur with S. haematobium or S. japonicum. The thoraco-lumbar cord is the most likely area of involvement, either by a localized granulomatous process or due to ova in the arteries and veins causing ischaemic damage (Fig. 28.12). An acute necrotic myelitis has also been reported (Queiroz et al. 1979). MRI reveals a high signal intrinsic cord lesion on T2-weighted images and gadolinium enhancement on T1-weighted images. The spinal cord may be swollen and the CSF may contain pleocytosis with an elevated protein. The diagnosis may be made by the identification of schistosoma ova in the faeces or tissues or by demonstrating a positive serological response to shistosomes in the CSF. Treatment is with praziquantel and should prevent progression of the disease but existing neurological deficits will not reverse.

Sarcoidosis is the only common granulomatous disease to affect the spinal cord. Intramedullary masses of granuloma may present with an acute, sub-acute, or chronic myelopathy. Lepto-meningeal involvement with sarcoid can also occur and gadolinium enhanced MRI, the investigation of choice, may show granulomatous tissue enhancing within the spinal cord and highlighting the meninges and roots.

The granuloma can occur at any level in the spinal cord and may be associated with involvement of the optic nerve, facial nerve, auditory nerves, hypothalamus, brainstem, and hemispheres. Most patients have evidence of sarcoidosis outside the nervous system. The serum angiotensin converting enzyme tends to be positive and enzyme levels can be detected in CSF, though they are not essential for diagnosis. CSF will normally contain a pleocytosis and a high protein.

The treatment of acute sarcoid granulomata in the nervous system is with corticosteroids, initially in high doses. Long-term maintenance of steroids may be required to prevent a relapse of cord or central nervous system disease and long-term maintenance steroids can be coupled with immunosuppressive therapy to reduce the steroid effect.

Brucellosis causes meningitis and meningo-encephalitis and may cause intrinsic cord lesions (Section 42.5.11). It can present with an acute myelopathy when diagnosis is established by MRI and positive Brucella serology in the CSF.

Neurosyphilis is another cause of acute or chronic spinal cord syndromes and may be identified by blood and CSF serology (Section 42.5.1).

Toxic myelopathies are rare, but the use of clioquinol in excessive doses causes sub-acute myelo-optic neuropathy which can present with an acute spinal cord syndrome.

Chronic lesions affecting the spinal cord may be due to either compressive or non-compressive lesions (Table 28.2) with contrasting symptomatology. Compression of the spinal cord is classically associated with pain at the site of the pressure, the slow evolution of motor and sensory disturbances which may be a symmetrical and associated with lower motor neurone signs and lower sensory neurone symptoms at the site of the lesion and the relative sparing of bladder and bowel until late in the disease. Intrinsic spinal cord lesions, or non-compressive disease, tend to affect bladder and bowel early, be relatively painless, and not associated with lower motor neurone signs at the site of the lesion.

Chronic compression of the spinal cord occurs with diseases of the vertebral column and from other lesions pressing upon the spinal cord. The two most common vertebral column conditions leading to chronic spinal compression are firstly spondylosis together with protrusion of intervertebral discs and the formation of osteophytes reducing size of the spinal canal, and secondly, metastases from distant carcinoma. Less frequent causes include neoplasms arising from the vertebra, such as sarcoma, myeloma, osteoma, cordoma, and haemangioma; vertebral infections due to tuberculosis, staphylococcal osteomyelitis or sphylitic osteitis; the osteitis deformans of Paget’s disease; and, rarely, achondroplasia, mucopolysacaridoses, and severe kyphoscoliosis. Bone marrow swelling in thalassaemia can occasionally compress the spinal cord and aneurysms may erode vertebra and cause pressure upon the cord. Atlanto-axial subluxation, particularly in rheumatoid arthritis, or spondylolisthesis at any level in the spine may narrow the spinal canal.

Other causes of chronic compression include extra-dural abscess following systemic infection or vertebral osteitis, arachnoiditis due to syphilis, tuberculosis, sarcoidosis or other granulomatous processes, infiltration of the meninges with leukaemia or lymphoma or other en-plaque malignancy. Developmental arachnoid cysts and parasitic cysts such as hydatid and cystercercosis are rare causes of chronic compression. Intra and extra-medullarly tumours may compress the cord chronically and dural herniation of the spinal cord through a spontaneous or created defect in the meninges can result in a progressing cord deficit.

Lesions in the region of the foramen magnum, most commonly a neurofibroma or meningioma, usually produce a slowly evolving quadriparesis with a characteristic cluster of associated physical signs. These include pain in the neck and occipital region with radiation of pain and sensory loss in the distribution of the C2 to C4 dermatomes. This may be accompanied by sensory loss in the first division of the trigeminal nerve which may be central and extend gradually due to involvement of the descending spinal tract of the fifth nerve in its intra-medullary spinal course. There may also be contralateral loss of pain and temperature sensation, stiffness of the neck muscles, and the head may be held rigidly. A Horner’s syndrome ipsilateral to the lesion may occur and there may be the diagnostic sign of down-beat nystagmus made worse on lateral gaze. Involvement of the 11th and 12th cranial nerves can cause weakness of trapezius and the tongue. The weakness which gradually evolves in the arms and legs is often asymmetrical and may extend from one arm to the contralateral arm, leg, then ipsilateral leg in a circular way. It is important to remember that lesions at the level of the foramen magnum can interfere with the phrenic nerve and cause problems with respiration, particularly in the recumbent position.

Such lesions are commonly due to structural abnormality at the foramen magnum. MRI will differentiate between neurofibroma or meningioma and an Arnold Chiari malformation (Fig. 28.13) and also demonstrate anterior atlanto-axial sub-luxation in rheumatoid arthritis, psoriatic arthropathy, and the mucopolysaccharoidoses.

The most common cause of progressing cervical myelopathy in adult life is cervical spondylosis. Chronic disc protrusions both

lateral and central, combined with osteophyte formation on the vertebral bodies and soft tissue changes in the paravertebral tissue frequently result in compression of the cervical cord with or without root involvement. This slowly progressive degenerative process is ‘cervical spondylosis’ and becomes increasingly common with age. The widespread use of MRI scan has confirmed a high prevalence in the normal population, albeit usually without symptoms. Spondylotic changes are most common in the mid to lower cervical spine with the maximal frequency and severity of involvement at C5/6 (Fig. 28.14).

The effect of cervical spondylosis upon the spinal cord is complex. There is direct compression, the protruding disc or osteophyte may interfere with the blood supply, and tethering of the cord by the ligamentum denticulata and spinal roots may cause narrowing of the intervertebral foramina allowing ordinary neck movements to produce cumulative trauma. The ligamentum flavum, lying posteriorly, may become corrugate. The result is a condition of patchy degeneration in the cervical cord, termed ‘cervical myelopathy’ (Wilkinson 1973).

The clinical picture of cervical spondylosis may be indistinguishable from the progressive spastic paraplegia seen in multiple sclerosis and, since the former is so common, it is not unusual to find the two disorders co-existing. The presence of radicular signs in the upper limbs is most consistent with cervical spondylosis; sometimes extensive lower motor neurone signs in the arms, including wasting, fasciculation, and areflexia, may raise the possibility of motor neurone disease.

Though neurophysiology may help in determining radicular disease from anterior horn cell disease, MRI is the diagnostic investigation of choice. It must be remembered that many healthy older adults will have moderate spondylotic changes with mild cord indentation or compression and that it is only when the cord compression is moderate or marked, sometimes associated with signal change within the cord, that it is to be regarded as the sole cause of significant myelopathic functional deficits. The presence of high signal in the cord on T2-weighted images at the level of compression indicates structural damage to the cord parenchyma by the compression and associated ischaemia. The older investigation of myelography is now only necessary when MRI is contraindicated as in those with cardiac pacemakers, intracranial aneurysm clips, or orbital metal fragments.

The natural history of cervical myelopathy due to cervical spondylosis is of a fluctuating condition in which there are periods of deterioration interwoven with periods of stability and even mild improvement. Pain in the neck radiating to the arms fluctuates and though some people have severe disability which increases remorselessly, most are left with a varying degree of residual disability. In some cases immobilization of the neck in a hard or soft collar has been said to arrest clinical progression, but immobilization is less effective in this condition than in acute cervical disc prolapse.

Surgical decompression should always be considered when spinal cord damage is progressing, particularly when there is evidence of severe compression radiologically. When there is multi-level disease or significant canal stenosis laminectomy may be the operation of choice, where there is a single or two adjacent disc levels anterior removal of the disc or discs with either spinal fusion or replacement of disc material should be considered (Cloward 1980).

Separation of the odontoid process of the axis, sometimes seen as a congenital abnormality or as the result of trauma, rheumatoid arthritis, psoriatic arthropathy or mucopolysaccharoidoses may permit abnormal movement of the atlas on the axis leading, in time, sometimes gradually after years, sometimes more acutely, to a myelopathy due to compression of the cord (Stevens et al. 1971). The sub luxation can be demonstrated on CT myelography or by MRI and can be detected clinically by movement of the head on the neck in the Sharp and Purser test. The preferred treatment is occipital cervical fusion, though immobilization in a position of flexion may be considered. Operative decompression of the upper cervical cord can be complicated by haematomyelia.

Though most commonly seen in the lumbar spine as a cause of lumbo-sacral radiculopathy, spondylolisthesis can also occur in the cervical spine, resulting in reduction of the antero-posterior diameter of the spinal canal and consequent compression of the spinal cord. The signs are similar to those of cervical spondylosis, the investigation identical, and the treatment involves fusion of the relevant vertebra.

Paget’s disease, or osteitis deformans, is a primary bone disease in which there is both resorption of normal bone and formation of abnormal new bone (Section 27.6.6). Its cause is uncertain; diagnosis is established on the basis of characteristic radiographic findings together with an elevated serum alkaline phosphatase. Neurological symptoms result from bony overgrowth in the skull and deformity of the skull shape, together with deformity and overgrowth in the vertebral column leading to compression of neural structures. Occasionally the Paget’s bone may show sarcomatous change and the highly vascular abnormal bone may also reduce blood supply to adjacent neural structures by a ‘steal’ phenomenon.

Spinal cord compression may occur at any level but is most common in the upper thoracic region. In keeping with extrinsic compression pain is prominent, fractures and dislocations may occur, and myelopathies can be seen without compression and are assumed to be ischaemic and vascular. When cord compression is demonstrated treatment with calcitonin, mythramycin, and diphosphonates have been shown to reduce pain and improve neurological function. Rarely surgical decompression may be indicated.

This is now rare in developed countries, but used to be seen in children and young adults. It was thought due to the consumption of unpasteurized milk and was frequently due to the bovine tubercle bacillus. In the developing world tuberculous spinal infection is still a common problem, it most usually affects the thoracic spinal cord, the infective process begins in the vertebral body, spreads across the disc to adjacent bodies, leading to their collapse and the formation of an angular deformity of the spine. The deformity as such is rarely the cause of compression of the cord which is more usually affected by an extra-dural tuberculous abscess or the development of tuberculous meningomyelitis. In addition to compression of the cord interference with the blood supply of adjacent segments either by compression of radicular arteries or by tuberculous endarteritis is an important factor in producing myelopathy and paraplegia.

Conservative treatment with anti-tuberculous chemotherapy rather than surgical decompression, often gives remarkably good outcome even in severe cases.

A similar, but much less common osteitis may occur with syphilis, spinal compression, and cord ischaemia is created in a similar pathological way and the response to appropriate conservative therapy is also excellent.

A variety of primary and secondary tumours and swellings of the spinal bones can result in chronic compression. These are commoner than intrinsic tumours of the spinal cord or soft tissue swellings related to the meninges as the cause of chronic compression.

Secondary carcinoma is the most common vertebral neoplasm. It is rare in those under the age of 35 years and the commonest primary is derived from lung, breast, thyroid, or prostate. Less commonly primaries from the uterus, stomach, kidney, and large bowel may metastasize to spine. The vertebral metastasis is usually blood borne, but sometimes when the spinal lesion is at the same segmental level as the primary growth peri-neural lymphatic drainage is believed to be the cause. Carcinomatous deposits eat into and erode the spongy portions of the vertebral body which then collapses (Fig. 28.15). The spinal cord may be compressed either as the result of the ensuing spinal deformity or by an extradural extension of the growth. Usually the spinal roots are compressed before the cord so that the typical local and radicular pain indicating an extrinsic lesion may be present for some time before the development of the cord syndrome.

When multiple vertebrae are involved treatment may be palliative and in such circumstances adequate analgesia with opiates and the use of radiotherapy should be considered. Chemotherapy appropriate to the particular form of cancer may be indicated and in many cases of acute compression a single level emergency laminectomy, decompression, and bone replacement is considered. The prime indication for surgery used to be to relieve pressure and obtain a surgical biopsy prior to radiotherapy and chemotherapy but modern techniques allow some degree of reconstitution of the spine prior to radiotherapy and chemotherapy.

The decision about the method of treatment of the metastasis depends upon its nature, the management of the primary tumour, and the evidence for more metastases. Radiotherapy sometimes has remarkable effect on pain relief and in some cord compression relief is achieved with a combination of steroids and radiotherapy. Powerful analgesics and, in some cases, surgical pain relief with cordotomy, stereotactic thalamotomy, or spinal cord stimulation may be required.

Tumours within the spine are conveniently divided into extra-dural and intra-dural. The latter can further be divided into those arising outside the spinal cord, extra-medullary tumours, and those lying within the cord, intra-medullary tumours. About 20 per cent of spinal tumours are extra-dural, 60 per cent intra-dural but extra-medullary, and 20 per cent intra-medullary. Extra-dural tumours, those due to involvement of the vertebra and paraspinal tissues, are commonly secondary and have been described above.

The most common extra-medullary, intra-dural tumours are meningiomas and neurofibromas (Alter 1975). Meningiomas are more common in the middle-aged female. In the spine extra-medullary, intra-dural tumours are about three times as common as intra-medullary tumours.

Intra-medullary spinal tumours may mimic any of the cerebral gliomas (Kernohan et al. 1931). Ependymomas are most common, accounting for more than 40 per cent of tumours (Fig. 29.1). The next most common intra-medullary tumour is an astrocytoma, but in children medulloblastoma are found and at all ages, oligodendrogliomata, ganglioneuromata, and haemangioblastomata may be seen. Intra-medullary metastases from carcinoma are rare. Leukaemic and lymphomatous deposits may occur in the cord, as can tuberculomas.

Metastases from primary spinal neoplasm are rare but ependymoma of the filum terminale has been reported to metastasize into the body. By contrast intra and extra-medullary spinal deposits from intracranial gliomas, particularly medulloblastomata, are not uncommon, especially in children.

Apart from the meningioma, which is much more common in elderly females, other spinal tumours show no sex bias. Tumours may develop at any age, though the majority occur between the ages of 20 and 60 years. Meningiomas are rare in childhood as are all spinal tumours, compared to those found within the cerebrum.

The thoracic cord is the most common site for extra-dural and extra-medullary tumours, approximately 2/3 of all extra-medullary tumours are situated in the dorsal or dorso-lateral aspect of the cord and approximately 1/3 in the ventral or ventro-lateral aspects.

Intrinsic tumours of the spinal cord tend to be painless and present with early involvement of bladder and bowel. Extrinsic tumours tend to cause local pain, local lower motor neurone and lower sensory neurone signs, and are late to involve the bladder and bowel.

MRI is the investigation of choice for the diagnosis of all forms of spinal tumour. Neurofibromas are usually hyperintense on T2-weighted images, meningiomas may be isointense on T1- and T2-weighted images and show prominent gadolinium enhancement. Lipomas produce a characteristic high signal on T1-weighted images and low on T2-weighted, and intra-medullary tumours are usually associated with swelling of the cord and with gadolinium enhancement.

Extra-medullary, intra-dural tumours, which are usually benign and cause cord compression resulting in a progressing spastic paraplegia, should be surgically removed. In general, a good prognosis can be predicted if the diagnosis is made promptly and the pre-surgical deficit is not severe. Intra-medullary gliomas or ependymomas may be indolent with a history evolving over years or decades. Surgical debulking of ependymomas may be possible in some instances and some cases of intramedullary glioma may benefit from radiotherapy and chemotherapy.

Arachnoid cysts, which are presumed to be developmental in origin, differ from the neuroenteric cysts in not being associated with spina bifida. They are an occasional cause of cord compression, most commonly in children, adolescents, and young adults. They are extrinsic and therefore associated with radicular pain, together with signs of spinal cord dysfunction developing in a step-like manner. Most are in the dorsal region posterior to the cord and communicate with the sub-arachnoid space by a narrow orifice which used to be demonstrated on myelography (Fig. 28.19).

Nowadays the lesions are diagnosed by MRI which shows the presence of a cyst-like structure with the signal characteristics of CSF. They are particularly common in Marfan’s syndrome and ankylosing spondylosis and may be found in the sacral canal. Surgical decompression and excision of the cyst is indicated, alternatively the cyst may be marsupialized.

Rarely the meninges may be torn as the result of trauma or surgical intervention. Even more rarely a tear may appear in the dura where there is no prior history of trauma or operation. Such a dural defect is most commonly seen in the upper or mid-thoracic region and usually lies on the ventral aspect of the cord. There may be herniation of the spinal cord through the dural defect into the extra-dural space (Fig. 28.19). The clinical presentation is with a progressive thoracic cord syndrome with motor and sensory features, often asymmetric and not causing complete paraplegia. MRI reveals a characteristic abnormality with the extra-dural herniation being shown separate from the normal spinal cord (Housmann and Moseley 1996). Surgical treatment aims to return the cord to its correct location and close the dural defect; the possibility of ischaemic injury to the cord must not be overlooked.

Although many viruses cause acute myelitis chronic and progressing myelopathy is seen only with retroviral infection.

In the late stages of infection with HIV1, frequently in association with AIDS–dementia complex, patients with AIDS may develop a slowly progressing myelopathy combined with a neuropathy (Section 43.3.6). There may be a combination of a paraparesis with increased tone, peripheral sensory loss, sphincter disturbance, and impotence. Most commonly the chronic myelopathy affects the thoracic spinal cord and MRI scan may show atrophy of the cord. Pathologically there is evidence of vacuolar change within the cord, though the pathogenesis of this change is uncertain. Highly active anti-retroviral therapy, HAART, does not prevent disease progression, suggesting that the myelopathy is not due to direct infection, but rather to indirect ‘bystander’ effects of the immune condition. There is some suggestion that the mechanism may be analogous to that seen in vitamin B12 deficiency. Therapy with l-methionine has been attempted.

Infection with human T-lymphotrophic virus type 1, HTLV-1, is endemic in Japan and the Caribbean. It causes a progressive paraparesis which clinically resembles primary progressive multiple sclerosis (Section 42.4.1). When such a progressing non-compressive myelopathy occurs in a patient of a non-Caucasian origin HTLV-1 infection should be considered (Cruickshank et al. 1989). Although most common in the Caribbean, southern United States, southern Japan, South America, and Africa it has been reported in Afro-Caribbean migrants in the UK and may occur many years after migration.

The clinical picture is that of a gradually progressive spinal cord syndrome evolving over years with increasing paraparesis, spasticity, brisk reflexes in the lower limbs, and extensor plantar responses. Disturbance of sphincter control occurs early, in keeping with intrinsic disease of the cord, and is prominent. Paraesthesiae and dysaesthetic pain is prominent in some patients, often radiating from the buttocks downwards to the feet and sometimes described as aching, tingling, burning, and sharp. It may be made worse by activity. It is rarely accompanied by low back pain but objective sensory signs are usually absent; there may be reduction in pin prick sensation, light touch sensation, and vibration in the distal part of the legs.

Symptoms and signs in the upper limbs are uncommon, the brain is not involved. MRI will show spinal cord atrophy, most marked in the thoracic region. Cerebral MRI may show mild abnormalities in the white matter which are non-specific and usually age related.

The CSF often contains a mild mononuclear pleocytosis of between 5 and 50 cells per cubic millimetre with a normal glucose and normal or slightly increased protein, but with oligoclonal bands that are not matched in the serum. All patients have antibodies to HTLV1 in the CSF and serum.

Pathologically the disease has been shown to be due to perivascular and meningeal inflammation, areas of demyelination, gliosis, and necrosis. The central grey matter, posterior columns, and cortico-spinal tracts are preferentially involved and it has been suggested that it is due to HTLV1 infection of lymphocytes causing an aberrant auto-immune reaction that damages the cord. The pathological changes may be mediated by HTLV1 specific cytotoxic T-cells rather than due to direct viral injury. These immune cells appear to become activated in response to interactions with retroviral ENV and TAX proteins.

At present no anti-viral agent effectively controls HTLV1. The most effective therapies seem to involve the use of immunomodulating agents, such as steroids and interferon alpha, or plasmapheresis. Future therapies are likely to target the pathogenetic effects of HTLV1 reactive T-cells.

There is a separate and antigenically distinct human T-lymphotropic virus type 2, HTLV-2, which is seen increasingly in intravenous drug users. It has been suggested that the myelopathy in this situation is usually due to a combined infection, but there has recently been the suggestion that spastic paraparesis, hyper-reflexia, spastic bladder and atrophic myelopathy can be seen in people infected with HTLV-2 but not HTLV-1. Both agents can be identified by appropriate polymerase chain reaction amplification of viral DNA in the CSF.

Although the haematological effects of copper deficiency have been recognized for years, only relatively recently has copper deficiency been recognized as a cause of myelopathy, with a spastic gait and prominent sensory ataxia, central nervous system demyelination, peripheral neuropathy, and optic neuritis. The cause of the copper deficiency may not be apparent, though most patients have undergone gastric surgery. The picture mimics the myeloneuropathy of vitamin B12 deficiency (Section 28.5.10) and there can be an associated myelodysplasia which resolves with copper supplementation, and the neurological deficits stabilize but do not recover (Kumar et al. 2005).

Lathyrism is a chronic toxic nutritional disease caused by long-term ingestion of large quantities of flour made from the drought resistant chickling pea, Lathyrus sativus (Section 23.6.1). During times of famine in some regions of Africa and India when there is a shortage of wheat and other grains the diet involves the regular ingestion of chickling peas for months.

A characteristic sub-acute or chronic spinal cord syndrome develops with weakness and spasticity of the lower limbs, pins and needles, and numbness in the legs. There may be urinary urgency or incontinence and erectile dysfunction. Tremor and other involuntary movements can occur in the upper limbs.

Pathologically there is degeneration of the white matter tracts in the spinal cord and the responsible neurotoxin is beta-N- oxyalylamino-l-alanine, BOAA, which is a glutamate receptor agonist. It causes increased intracellular levels of reactive oxygen species and subsequent impairment of mitochondrial oxidative phosphorylation (Spencer et al. 1986). The condition is irreversible, though the toxin should of course be removed; it tends to be self-limiting and does not appear to affect life expectancy.

The chronic dietary ingestion of a neurotoxin derived from flour made from short-soaked cassava roots is endemic in eastern Africa (Section 23.6.1). The clinical syndrome is very similar to lathyrism, causing a spastic paraparesis with hyper-reflexia and the complaints of cramps and dysaesthesiae. The upper limbs are less affected.

The condition is thought due to the liberation of cyanohydrins from the flour which are metabolized to thiocyanate which in turn stimulates the AMPA glutamate receptor sub-type causing excito-toxic neuronal injury.

Vitamin B12 deficiency causes a characteristic sub-acute myelopathic syndrome associated with large fibre peripheral neuropathy, known as sub-acute combined degeneration of the spinal cord. It is rare, but it its importance lies in its response to treatment which must be instituted quickly to minimize the extent of permanent neurological deficit.

Vitamin B12 myelopathy usually occurs in middle life, the average age of onset is 50 years. It may begin in the 20s or as late as the 70s and affects the sexes equally. Familial occurrence is rare and although most cases of B12 myelopathy are associated with megaloblastic anaemia the association is not inevitable: anaemia may be slight or absent in spite of severe spinal degeneration, and only 10–15 per cent of patients with pernicious anaemia suffer the neurological disorder.

Symptoms of confusion, depression, and dementia have been reported due to B12 deficiency with normal blood and bone marrow findings. Some cases of tobacco–alcohol amblyopia have been linked to traces of cyanide in tobacco smoke which interferes with the utilization of vitamin B12; thus hydroxycobalamine but not cyanocobalamine is given to treat this condition. Vitamin B12 deficiency is usually associated with gastric achylia causing a lack of intrinsic factor, secreted by the normal stomach to facilitate the absorption of vitamin B12. The only function of instrinsic factor is to make possible the absorption of vitamin B12 in the terminal ileum via specific receptors on ileal muscosal cells. The absence of intrinsic factor is often associated with circulating serum antibodies to gastric parietal cells which are the source of the intrinsic factor, and strongly suggest that pernicious anaemia is an autoimmune disease.

There is considerable evidence that methyl group transfer, necessary in metabolism of myelin, requires the presence of both vitamin B12 and methyl tetrahydrofolic acid via the methyalanine synthetase reaction which is dependent upon B12; methylalanine may possibly have a protective effect.

The commonest cause of vitamin B12 deficiency is absence of the instrinsic factor, but impaired absorption of the intrinsic factor B12 complex may also occur in coeliac disease, small bowel lymphoma, or after resection of the terminal ileum. True dietary deficiency of vitamin B12 is uncommon but occurs in some vegans, a strict vegetarian group who do not eat any animal products. Lack of intrinsic factor is commonly due to autoimmune disease, but may also follow partial or total gastrectomy, small bowel disease, and diverticulosis or fisutulae of the small intestine as in Crohn’s disease. Malabsorption will also occur if the intrinsic factor is biologically inert, due to pancreatic disease, or the effects of drugs, particularly colchicine. Chronic addiction to nitrous oxide inhalation can also produce a myelo-neuropathy indistinguishable from that due to B12 deficiency (So and Simon 1991).

When a megaloblastic anaemia is diagnosed it may be due either to folic acid deficiency or vitamin B12 deficiency. If folic acid is given alone for the anaemia this may aggravate the neurological symptoms of vitamin B12 deficiency. Megaloblastic anaemia has also been reported in infancy due to hereditary transcobalamine deficiency even though the serum B12 was normal. Improvement in this situation may follow administration of large doses of parenteral B12 (Thomas et al. 1982).

Macroscopic changes in the nervous system are few, though there may be slight cerebral atrophy and thinning of the posterior columns of the spinal cord. When the spinal cord is sectioned there is demyelination in the posterior and lateral columns. Histologically there is focal demyelination scattered throughout the white matter associated with the accumulation of lipid filled macrophage and gemistocytic astrocytes. The changes are most striking in the heavily myelinated fibres of the posterior columns and lateral columns (Fig. 28.20). There is secondary degeneration of the long tracts, again most marked in the posterior columns and cortico-spinal tracts. In the most severely affected areas, both myelin sheaths and axon cylinders are lost leaving vacuolated spaces separated by a fine glial meshwork. Rarely similar areas of degeneration may be found in the cerebral white matter, with degenerative changes, especially in association fibres. In the peripheral nerves there can be loss of the larger myelinated fibres and evidence of axonal degeneration. Segmental demyelination of the peripheral nerve is also seen.

Systemic pathological changes associated with pernicious anaemia include glossitis, hyperplasia of the bone marrow in the long bones, slight enlargement of the spleen, excess iron in the reticulo-endothelial system, and atrophy of all coats of the stomach wall.

The clinical presentation is due to the combined features of posterior column, cortico-spinal tract, and peripheral nerve degeneration. Involvement of the optic nerves and brain may also occur. The onset of symptoms is usually gradual but can be remarkably rapid. Initial symptoms consist of paraesthesiae with tingling sensations often in the fingers before the toes: the involvement of upper limbs before lower limbs in an apparently peripheral neuropathic process should always raise the possibility of sub-acute combined degeneration of the spinal cord. There may be sensations of numbness, coldness, and tightness with sharp stabbing pains occasionally reported and the sensation of the extremities being swollen or encased in tight bandages or constricting bands. The paraesthesiae may spread from the feet and legs onto the trunk, giving a sense of constriction around the chest or abdomen.

Motor symptoms occur later, initially being reported as a sensation of tiredness on walking, then a feeling of instability, particularly when walking in the dark or standing with eyes closed, a liability to stumble, and ultimately weakness of the legs.

Objective sensory changes are usually present, predominantly affecting posterior column sensation. Postural sense and appreciation of passive movement and vibration sense are impaired in the feet and later in the fingers. Cutaneous sensation to light touch, pin prick, heat and cold is impaired in the periphery causing the characteristic ‘glove and stocking’ distribution of superficial sensory loss. The calves may be tender to pressure and the proximal border of the anaesthesia may ascend.

In some cases weakness and stiffness, in others sensory ataxia predominates in the lower limbs, but objectively both weakness and sensory ataxia are usually demonstrable in all four limbs, being most severe in the lower limbs where there is a positive Romberg’s sign. There may be peripheral muscle wasting as the peripheral neuropathy progresses (Section 21.22.4).

Tendon reflexes vary considerably; in about 50 per cent of cases the ankle jerks are absent when the patient is first seen, the knee jerks are lost less commonly and in some instances both may be increased. The plantar reflexes are initially flexor but become extensor in the great majority of patients. When degeneration is confined to the posterior columns sensory ataxia is the predominant feature. Conversely spastic paraparesis may be the sole presentation in some and in others the signs of peripheral neuropathy predominate.

Sphincter disturbance tends to occur late, initially causing hesitancy or precipitancy of micturition and later retention or incontinence. Impotence may occur early.

Bilateral primary optic atrophy, with some visual impairment, is seen in about 5 per cent of cases and can be the presenting feature with central scotoma. Nystagmus is relatively common, the pupils may be small but react normally, and otherwise the cranial nerves are normal. Dysarthria is rarely identified.

Mental changes are common and their importance has been stressed, they may be present before anaemia or signs of spinal cord disease. There may be a mild dementia without impaired memory and intellectual capacity or a confusional psychosis with disorientation and paranoid tendencies, Korsakoff’s syndrome. Alternatively the mental disorder may be affective, manifesting as irritability or severe depression.

The EEG may show diffuse activity but returns to normal after appropriate treatment. The CSF is normal. MRI scans show high signal in the spinal cord white matter (Fig. 28.21), particularly in the posterior columns on axial scans and there may be diffuse signal abnormalities in the cerebral white matter. These imaging changes in the cord and white matter of the brain have shown striking resolution when B12 therapy is instituted (Hemmer et al. 1998).

Gastric achlorhydria is constant in pernicious anaemia but free acid may be present in the gastric juice when the deficiency is due to low dietary intake or malabsorption. There is usually macrocytic anaemia with a high mean cell volume, megalocytes or even megaloblasts in the circulating blood, poikilocytosis, anisocytosis, polychromatophillia, and leucopenia with a relative lymphocytosis may all occur. Even when the peripheral blood count is normal the bone marrow may be abnormal.

Glossitis is common but can be slight or absent when the anaemia is mild. Other symptoms, which may be apparent when the anaemia is severe, include dyspnoea, the characteristic lemon tint of the skin and sclera, cardiac dilatation, haemic murmurs over the heart, and oedema most marked in the lower limbs. The spleen may be palpable and gastrointestinal symptoms are common, especially anorexia, flatulence, and diarrhoea, particularly when the deficiency is due to intestinal disease.

The neurological picture must be distinguished from tabes dorsalis, multiple sclerosis, spinal cord compression, other intrinsic myelopathies, and other causes of polyneuropathy. Neuro-syphilis is usually identified by the presence of reflex irido-plegia and appropriate serological tests in blood, CSF, or both. Multiple sclerosis often has evidence of more diffuse disease with both optic disc pallor and nystagmus and the ankle jerks are usually exaggerated. The difficulty in distinction is most likely to occur in those patients with a slowly progressive spastic paraplegia, but the course of multiple sclerosis is usually more chronic, there should not be anaemia, and the serum B12 level should be normal. The MRI appearance of the conditions is different. Spinal cord compression can cause an ataxic paraplegia of gradual onset. There is usually a well-defined upper level of motor disability and sensory loss, a finding which is rare in B12 deficiency. MRI is of crucial importance in detecting compressive lesions and though cervical spondylotic myelopathy may produce signs closely resembling those of B12 myeloneuropathy, it should be distinguished by MRI scan. Both conditions may co-exist and vitamin B12 levels should be assessed if there is doubt.

Other peripheral neuropathies are relatively easy to distinguish from B12 deficiency because of the associated symptoms and signs of spinal cord disease. If neuropathy is the sole or the predominant manifestation the distinction may be entirely dependent upon estimation of the serum B12 and other serologic tests. There may be a co-existing deficiency of other B vitamins, but usually in B12 deficiency the sensory manifestations are more severe, relatively painless, and the electrophysiological findings are predominantly those of an axonal neuropathy with partial denervation. Visual evoked potentials may show significant conduction delay.

Whenever B12 deficiency is suspected on neurological grounds, a blood count should be performed and serum B12 should be estimated. Some phenothiazines, notably chlorpromazine, may interfere with the estimation of serum B12 and give falsely low levels and the assay may be further complicated by the presence of other myeloproliferative or hepatic disorders. Investigation of absorption of B12 by using radioactive B12 in the Schilling test with and without intrinsic factor may provide additional diagnostic help. The presence of elevated titres of gastric parietal cell antibodies in serum provides useful confirmatory evidence and when doubt remains marrow biopsy may be indicated.

The average survival of patients with pernicious anaemia prior to the introduction of liver treatment was about 2 years. The prescription of hydroxycobalamine given parenterally restores the blood to normal and the health of the patient should be maintained indefinitely. Such patients, with adequate treatment, should never develop neurological complications.

When myeloneuropathy is already present it can be arrested by introducing vitamin B12 therapy, but the degree of recovery depends upon the stage at which the disease has reached, therefore creating the need for urgency in diagnosis.

Although peripheral nerves can sometimes regenerate this is not possible in the spinal cord, though some remyelination can occur as shown by MRI. The patient may therefore expect considerable improvement in the symptoms of polyneuropathy with loss of pins and needles and dysaesthesiae, improvement in the glove and stocking anaesthesia, and return of muscle strength but the extensor plantar responses and spastic weakness of the lower limbs may persist. Even when the disease has been arrested by treatment intercurrent infection may lead to exacerbation.

Vitamin B12 must be given intramuscularly; oral treatment requires very large doses and even when intrinsic factor is given the results are inconsistent. Treatment should be begun with 1000 µg of vitamin B12 given every 2 or 3 days for five doses to restore the tissue stores. After this 1000 µg should be given weekly for 6 months, then 1000 µg per month is usually sufficient. The dose may need to be increased if infection or renal insufficiency develops. Vitamin B12 must be given for the rest of the patient’s life.

Folic acid is not only ineffective in treating vitamin B12 deficiency but may be deleterious as the administration of a folate load can produce a secondary B12 deficiency with exacerbation of neurological symptoms. Where there are severe residual disabilities appropriate symptomatic management will be needed with physiotherapy and anti-spasticity medication.

Dural arteriovenous malformations are acquired and increase in prevalence with age. They are most often found over the surface of the spinal cord and are less often intramedullary. The characteristic clinical presentation is in late middle age or older, though rarely they may occur in young adults. Males are affected far more often than females. Most dural arteriovenous malformations are found in the mid to lower thoracic cord, sometimes extending to the conus and less often more rostrally in the cervical area. Dural arteriovenous malformations extend over a number of segments and macroscopically appear as large tortuous veins lying on the dorsal aspect of the cord. The feeding vessel is usually one of the radicular arteries, commonly the artery of Adamkiewicz, or one of the other dorsal branches arising from the aorta and feeding the spinal artery system.

The clinical presentation is of a late middle-aged male who develops a slowly progressive thoracic cord syndrome. There may be a history of exercise intolerance with weakness and sensory disturbance in the lower limbs, followed by difficulties with sphincter control and impotence. Examination reveals upper motor neurone signs in the lower limbs, but in addition there may be some lower motor neurone signs involving the highest lumbar segments, such as wasting, fasciculation, and weakness of quadriceps with reduced or absent knee responses. This is thought to represent the commonly found caudal extension of the malformation into the conus, causing the combination of upper and lower motor neurone signs. Auscultation of the spine may detect the rare finding of a spinal bruit.

Although the aetiology of dural arteriovenous malformations is uncertain they are seen following venous thrombosis in paravertebral venous sinuses and, since they are acquired, probably relate to the development of back pressure into the venous system. It is rare to identify an underlying coagulopathy in these patients.

Although the diagnosis used to require supine myelography and spinal angiography recent advances in MRI have superseded these investigations. High resolution MRI now reveals a characteristic, diagnostic combination of abnormalities in almost all cases and spinal angiography is rarely required for diagnostic purposes. MRI typically reveals increased signal with swelling of the cord on T2-weighted images, usually involving several segments in the lower thoracic region. There may be patchy gadolinium enhancement and the pathognomic finding is of multiple, serpiginous, small signal voids closely applied to the dorsal surface of the cord at the same level as the intrinsic cord signal abnormality. These are thought to represent the dilated and tortuous dural veins (Fig. 28.22). MR angiography or rapid MR imaging after a bolus of gadolinium may show the lesion more directly. Spinal angiography is required to determine the level of the fistula and the suitability of the lesion for embolization.

The natural history of dural arteriovenous malformations is one of gradual progression in clinical defects, typically over a number of years. Acute decompensation does occur, probably due to venous infarction, but it is less common. Haemorrhage is a very rare complication. Because of the poor prognosis therapeutic intervention is recommended once a neurological deficit has been identified. The main aim of active treatment is to prevent further deterioration, although occasionally there may be improvement in existing symptoms. Most cases are considered suitable for embolization, an important criterion being that there should be adequate alternative arterial supply to the cord separate from the artery which is to be catheterized. In experienced hands the results of embolization are very good with partial or complete obliteration of the malformation. There is a risk of inducing cord infarction acutely and recurrences of the malformation may occur. Surgical extirpation of the malformation can be achieved in some cases but is now only used when embolization is unsuccessful or unsuitable because it carries a higher morbidity. In some cases where an underlying coagulation disorder is identified or if there has been venous infarction in the cord due to thrombosis, anticoagulation may be considered. This inevitably increases the risk of haemorrhage from the malformation.

Although more common within the cerebrum there are reports of isolated cavernomas or cavernous angiomas being identified as intramedullary lesions within the cervical, dorsal, and lumbar spine. They present a variety of symptoms, depending upon their site and are not usually susceptible to surgery. They may rarely bleed and cause an increase in symptoms.

Both inherited and acquired conditions occur which appear to cause degeneration of long tracts and neurones within the spinal cord.

There are several different types of hereditary spastic paraplegia presenting clinically with different ages of onset and different modes of inheritance (Section 23.4.2). Many different genetic loci have been identified and there is no single genetic test for this condition.

Hereditary spastic paraplegia tends to present as a chronic syndrome with almost purely motor involvement, though there is occasional sphincter disturbance. Both autosomal dominant and recessive forms exist; the former is more common in young adults, the latter in childhood.

In the absence of a positive family history it is difficult to differentiate hereditary spastic paraplegia from other progressive, predominantly or entirely upper motor neurone syndromes, including the primary progressive form of multiple sclerosis and amyotrophic lateral sclerosis. One useful feature is that in hereditary spastic paraplegia there is great disproportion between the spasticity, which is severe, and the weakness, which is minimal. In addition, the gait is very spastic, often with a marked lumbar lordosis, but power in the lower limb muscles is remarkably retained. Reflexes are pathologically brisk, plantar responses are extensor, and there is commonly pes cavus.

In hereditary spastic paraplegia the CSF is a cellular and there are no oligoclonal bands, but there may be a mild elevation in protein. MRI of the spinal cord shows no focal signal change, unlike multiple sclerosis, and the cord size may be normal or show diffuse atrophy. Brain imaging is normal, again unlike multiple sclerosis, but in the absence of specific genetic markers the diagnosis remains one of exclusion.

Genetic counselling should be offered to the patient and family, the course is usually one of slow progression, though patients typically remain ambulant. Spasticity may be helped by the use of baclofen, tizanidine, or dantrolene sodium; intrathecal baclofen may be considered. Physiotherapy should be offered and, where necessary, advice about bladder control provided.

This X-linked perioxysomal disorder is most commonly seen as a progressive cerebral syndrome in boys (Sections 10.2.4; 37.7.2). It has a uniformly poor prognosis. Some individuals present with a slowly progressive myelopathy during adult life and this milder clinical picture may occur in carriers of the X-linked abnormality.

Onset is usually in young adulthood, between the ages of 20 and 40 years. Males are more frequently affected, though a progressive spastic paraparesis can be seen in heterozygous females. The patient slowly develops a spastic paraparesis over a number of years; together with upper motor neurone signs, there may be loss of ankle jerks, indicating co-existing peripheral nerve involvement, and sensory manifestations including paraesthesiae, loss of sensation of light touch, pain, vibration, and joint position. The lower limbs are predominantly involved, but more generalized central nervous system involvement may occasionally be indicated by the presence of cerebellar signs or mild changes in cognition.

MRI of the spinal cord is normal, apart from mild atrophy, most marked in the thoracic region. Brain MRI is normal in some patients, but in others there are symmetrical cerebral white matter high signal abnormalities on T2-weighted images which are most often seen in the posterior regions around the trigone and occipital horns. They may become more extensive involving the cerebellar peduncles as well.

Some patients have co-existing Addison’s disease with skin hyperpigmentation, hypotension, a low serum cortisol, and an abnormal synacthen test. The diagnostic investigation is measurement in the plasma of very long chain fatty acids. The biochemical abnormality of fatty acids has been amended with dietary supplementation of erucic acid, but patients with established symptoms have not been convincingly demonstrated to improve. An adult presentation of progressive spastic paraparesis with cerebral MRI white matter abnormalities has been described in Krabbe’s globoid-cell leukodystrophy (Section 37.7.1).

Although the combination of upper and lower motor neurone signs in the absence of sensory disturbance is classical in the diagnosis of motor neurone disease some forms of the illness, which predominantly affect one or other cell type, can cause difficulties in diagnosis (Section 23.2).

Amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis, the usual form of motor neurone disease, manifests with both upper and lower motor neurone features in several limbs. In some instances there may be involvement of the bulbar musculature and, once the full clinical picture of upper and lower motor neurone involvement is apparent, there is little difficulty with diagnosis.

A few patients, however, present with an initial phase in which the symptoms and signs are largely, if not entirely, attributable to upper motor neurone involvement. In this situation the differential diagnosis includes other causes of progressive spastic paraplegia, especially multiple sclerosis, cervical spondylosis, which may co-exist, and primary lateral sclerosis. The presence of sensory symptoms and signs clearly points towards an alternative diagnosis, but these are not always present in either multiple sclerosis or cervical spondylosis.

In general the tempo of amyotrophic lateral sclerosis is more rapid than that for patients with progressive spastic paraparesis due to multiple sclerosis or cervical spondylosis and the degree of muscle weakness is greater.

Additional investigations often help to clarify the diagnosis. In multiple sclerosis MRI will demonstrate lesions in the cerebral white matter and spinal cord, the CSF contains oligoclonal bands and in some patients the visual evoked potentials are delayed. In amyotrophic lateral sclerosis brain and axial spinal cord images may show symmetrical high signal in the corticospinal tracts on T2-weighted images in about 60 per cent of patients (Fig. 28.23), a characteristic finding when present and entirely different from the multi-focal and asymmetrical lesions found in multiple sclerosis. The CSF may show an elevated protein level but there are no oligoclonal bands and the visual evoked potentials are normal. Although there may be no clinical signs of lower motor neurone involvement in the early stages of amyotrophic lateral sclerosis, electromyography may reveal evidence of denervation and serial studies over several months may show anterior horn cell involvement becoming more widespread.

Electromyography may also show denervation in cervical spondylosis, but this is restricted to upper limb muscles and shows little spread in myotomal involvement on follow-up. MRI is required to demonstrate cervical spondylosis, but it should be remembered that a degree of spondylosis will frequently co-exist in middle-aged patients who develop either multiple sclerosis or amyotrophic lateral sclerosis. Careful judgement of all available clinical and investigative data is needed to determine the relative importance of the spondylosis and the underlying neurological disease in contributing to the patient’s clinical state.

Particular problems may arise in patients who have a combination of cervical and lumbar spondylosis where denervation may be found in both upper and lower limbs together with upper motor neurone signs from the cervical myelopathy. In this situation the absence of sensory involvement and the evidence of progression over time on electromyography will be diagnostic of motor neurone disease.

The management of amyotrophic lateral sclerosis is discussed elsewhere (Section 23.2).

Primary lateral sclerosis. This rare progressive syndrome is generally regarded as a form of motor neurone disease (Section 23.2.1). Even after many years the clinical syndrome is entirely confined to the upper motor neurone and there is no evidence of denervation.

The presentation is usually in middle age with a slowly progressive spastic paraparesis. Sensory features are absent and the tempo is slower than that in amyotrophic lateral sclerosis, patients may survive for 10–15 years. Symptoms typically involve lower limb function first with weakness, stiffness, and difficulty in walking, but the upper limbs and bulbar muscles may all become involved. In the fully developed syndrome there is a spastic quadriparesis with pseudo-bulbar palsy.

Cognition remains intact and eye movements are unaffected. Bladder dysfunction is rare and late. MRI does not reveal the signal change in the cortico-spinal tract seen in amyotrophic lateral sclerosis but sagittal T1-weighted brain images may reveal focal atrophy of the pre-central gyrus (Pringle et al. 1992). Motor evoked potentials reveal a prolonged central motor conduction time and CSF is normal, except for mildly elevated protein.

Symptomatic treatment of spasticity is indicated, but there is no therapy known to modify the underlying course of the disease. Riluzole has not been shown to be effective in this condition.

In about 5–10 per cent of patients a progressive spinal paraplegia is the presenting manifestation of multiple sclerosis (Section 37.5). This situation in which multiple sclerosis presents as a slowly progressive neurological disorder is called primary progressive multiple sclerosis. A small number of patients in this clinical sub-group have other progressive symptoms, such as optic neuropathy, cerebellar ataxia, and dementia, but a progressive myelopathy is by far the most common syndrome.

The age of onset of primary progressive multiple sclerosis is older than the more common relapsing remitting form of the disease and patients over 50 years may present. In addition, unlike relapsing remitting disease, where there is a 2:1 predominance of females, primary progressive disease is equal in gender prevalence. The syndrome may be purely motor or combined with sensory deficits of which the most common are paraesthesiae, dysaesthesiae, and loss of vibration sensation in the lower limbs. Sphincter dysfunction is frequent in keeping with an intrinsic cord lesion and the most common symptoms are urgency and incontinence with, in males, erectile dysfunction.

Some patients may demonstrate clinical features indicative of disease above the level of the foramen magnum, optic atrophy, internuclear ophthalmoplegia, or ataxia, but the majority have symptoms confined to the spinal cord. MRI shows some cerebral white matter abnormalities in most patients but usually few lesions compared to relapsing remitting disease. Although many patients with relapsing remitting multiple sclerosis may go on to develop a progressing spinal syndrome, known as secondary progressive multiple sclerosis, they have more significant changes on MRI in the brain and spinal cord.

The real value of MRI in this condition is to exclude compression and sometimes to demonstrate intrinsic demyelinating cord lesions. Most patients have oligoclonal immunoglobulin bands in the CSF, but not in the serum and frequently abnormalities of visual or brainstem evoked responses.

The pathogenesis of progressive spastic paraplegia in multiple sclerosis includes both focal and diffuse changes. There are multiple foci of demyelination throughout the spinal cord, predominantly involving the white matter tracts and sometimes extending into the central grey matter. There is also a variable degree of axonal loss which probably contributes to the progressive, irreversible defect. Diffuse microscopic changes may also be seen in normal appearing white matter in the brain and spinal cord with areas of gliosis or peri-vascular inflammation. The spinal cord is frequently atrophic, which may be shown on MRI.

The treatment of progressive spastic paraparesis due to multiple sclerosis is symptomatic. Baclofen, tizanidine, and dantrolene sodium may all alleviate spasticity and flexor spasms and the advice of a multi-disciplinary neuro-rehabilitation team will be indicated when there are significant functional difficulties. Severe spasticity may sometimes be helped by the use of intrathecal baclofen delivered via a subcutaneous reservoir and pump and the use of botulinum toxin to relieve spasm is also considered.

In those patients in whom there is a sudden rapid decline a short course of high dose cortico-steroids may be considered, but there is no convincing evidence of efficacy and there is no evidence to show that the new disease modifying treatments which have an effect in relapsing remitting disease have any role to play in the management of primary progressive disease. Immunosuppression with agents such as azathioprine, mitoxantrone, and methotrexate has sometimes been used, but there is no evidence of efficacy from controlled clinical trials.

Myelopathy is an uncommon manifestation of paraneoplastic disease neurologically. Paraneoplastic syndromes involving the cerebellum, brainstem, limbic system, and dorsal root ganglia are established and are much more common than myelopathy (Section 38.4). A sub-acute progressive cord syndrome has been described in association with malignancy; the clinical presentation is with motor, sensory, and sphincter defects evolving over days to weeks and associated with small cell carcinoma of the lung or lymphoma. MRI of the spinal cord may be normal or there may be gadolinium enhancement over several segments, a situation not unlike that found in transverse myelitis (Mokri et al. 1998).

CSF shows a mild mononuclear pleocytosis, often with protein elevation and occasionally with oligoclonal bands. Treatment involves the extirpation of the primary malignancy and the use of immunosuppressants on the grounds that most paraneoplastic syndromes have an immunopathological basis. Usually, however, the latter approach is ineffective unless the primary tumour can be effectively removed.

There is a rare syndrome with increasing limb tone causing rigidity, myoclonic jerking, and deep tendon hyper-reflexia evolving over months. Spinal MRI is normal but CSF reveals a mono-nuclear pleocytosis, elevated protein, and oligoclonal bands. Pathological changes have been demonstrated within the cervical region where there is loss of inter-neurones and some patients have been demonstrated to have antibodies to glutamic acid decarboxylase, GAD, having features in common with the Stiff Person syndrome (Section 40.10.3). This may occasionally be a paraneoplastic manifestation and treatment involves drugs to reduce myoclonus and rigidity together with the use of immunosuppression and plasmapheresis.

Radiation injury to the central nervous system can result in a delayed pathological process in which there is vascular hyalinization and occlusion. Degeneration of fibre tracts and necrosis involving both white and grey matter may occur. In a small proportion of patients who have undergone radiation to the chest or neck a delayed myelopathy has been reported where the spinal cord was thought included in the radiation field. At post-mortem the vascular changes cause cord ischaemia and this is thought to be the major mechanism.

Three types of spinal cord syndrome have been described following radiation (Section 5.9.1). The first is a transient and benign disorder manifesting limb paraesthesiae and a positive Lhermitte’s symptom, usually appearing some 2–6 months after radiotherapy and possibly associated with swelling of the cervical spinal cord on MRI. Fortunately these symptoms subside spontaneously and the true pathological basis is unclear.

The more common and more serious problem is the development of a steadily progressive myelopathy which appears after a longer delay. The most common latent period is between 12–18 months, but symptoms have been reported to occur more than 5 years after treatment. Either the thoracic or cervical cord can be affected depending upon the level of the preceding radiotherapy. Symptoms tend to develop gradually with paraesthesiae, dysaesthesiae, weakness and stiffness of the lower and occasionally the lower limbs. Sphincter disturbance develops. The initial symptoms and signs may be asymmetrical but there is a progression over weeks to months to a more or less complete paraplegia with sensory loss below the level of the lesion. Pain is infrequent as a symptom.

The third and rarest form of post-radiation syndrome occurs at the site of radiation and causes a segmental lower motor neurone disorder with weakness, wasting, and reflex loss suggesting degeneration of the anterior horn cells in the irradiated part of the cord.

MRI in progressive radiation myelopathy reveals high signal on T2-weighted images often with swelling of the cord at the level of the irradiation. In the early clinical stages there may be gadolinium enhancement and the radiological changes are indistinguishable from other inflammatory or neoplastic lesions within the cord. The clue lies in the correspondence of the lesion level with that of previous radiation and the presence of radiation induced changes in adjacent vertebral bodies is a valuable diagnostic feature. CSF may be normal, though there can be a minor increase in protein.

It is suggested that radiation myelopathy will not occur where the total dose is less than 6000 cGy given over 30–70 days with a daily fraction of not more than 200 cGy and a weekly fraction of not more than 900 cGy (Cagan et al. 1980). Radiation myelopathy should therefore be avoidable. Although treatment with cortico-steroids and anticoagulation has been tried there is no proof of efficacy for any intervention after radiation.

Syringomyelia is a chronic disorder characterized pathologically by the presence of a long cavity, or syrinx, surrounded by gliosis, situated in the central part of the spinal cord and sometimes extending up into the medulla, syringobulbia. The principal clinical features are cutaneous analgesia and thermoanaesthesia often with preservation of light touch and postural sensibility, but with muscular wasting and trophic changes. The upper limbs are most commonly affected and associated with symptoms of cortico-spinal tract dysfunction in the lower limbs. The condition was first described by Ollivier in 1824.

For many years it was thought that syringomyelia was due to a congenital abnormality, perhaps causing abnormal closure of the central canal of the spinal cord in the embryo. Others thought that the condition was degenerative of unknown cause. It is now apparent that ‘communicating syringomyelia’ is the more common variety and is associated with congenital anomalies and other lesions in the neighbourhood of the foramen magnum. These include the Arnold Chiari type I anomaly which consists of congenital extension of the cerebellar tonsils below the foramen magnum, cranio-vertebral development abnormalities with or without occult hydrocephalus, and basal arachnoiditis (Barnett et al. 1973). It is suggested that such abnormalities, as well as the Dandy–Walker syndrome of closure of the foramina of Magendie–Luschka prevent, possibly intermittently, the egress of CSF from the fourth ventricle into the sub-arachnoid space. As a result pressure waves of fluid are forced down into the central canal of the cord which thus becomes dilated, known as hydromyelia.

This view is generally accepted, though opinions differ as to the exact nature of the hydrodynamic mechanisms involved. The fact that a syringomyelic cavity is sometimes found alongside an apparently normal spinal canal can be accounted for by the fact that with dilatation of the canal its ependymal lining quickly disappears and diverticula may form which dissect outwards, downwards, or upwards, alongside the canal in the central grey matter. In most large series the Chiari type I anomaly has been the most common congenital anomaly found, but basal arachnoiditis, developing as a sequel to previous trauma, sub-arachnoid haemorrhage, or meningitis, or no evident cause, accounts for about a quarter of cases. Arachnoiditis produced by cisternal injection of kaolin in experimental animals has been shown to produce experimental syringomyelia.

It has been suggested that perinatal trauma may either produce the cerebellar tonsillar ectopia or induce syringomyelia in the presence of such a development anomaly. It is also clear that primary cerebellar ectopia can be present without causing syringomyelia but with other neurological signs, such as hydrocephalus, paraparesis, or a cerebellar syndrome. True communicating syringomyelia has also been described as a complication of glioma in the mid-brain and upper cord.

In non-communicating syringomyelia, by contrast, the condition is more often due to or associated with spinal injury with or without paraplegia, spinal arachnoiditis, or spinal tumour. In these cases the cavity may develop in the thoracic or lumbar cord first. Indeed except in cases of spina bifida, with which hydromyelia may be associated, the discovery of a lumbar syrinx in a patient without history of injury should always raise the possibility of a spinal glioma or ependymoma, though intramedullary metastasis or extramedullary tumours are also seen. In cases of traumatic paraplegia or arachnoiditis the cavities usually ascend from the site of the lesion, but in upper cervical lesions downwards cavitation may be found. The cavitation has been attributed to a combination of factors including venous obstruction, exudation of protein, and ischaemia. Oedema may be another factor.

The prevalence of syringomyelia is 5–10 per 100 000. The pathological condition is probably more common since the widespread availability of MR scanning has identified some individuals with asymptomatic syringes which are usually small. The condition has been described in more than one member of a family and other congenital malformations, including spina bifida, have been found in families with affected members. It is more common in males than females and symptoms can appear at any age between 10 and 60 years but usually present in young adult life.

The typical pathological changes are most frequently found in the lower cervical and upper thoracic regions of the cord. Extension to the medulla is common and rarely the process may reach the pons or even as high as the internal capsule. Thoraco-lumbar and lumbo-sacral syringomyelia are rare and usually due to true hydromyelia associated with developmental anomalies, although ascending cavitation following traumatic transverse lesions of the cord or in association with cord tumours may occur.

The affected region of the cord may be enlarged, mainly in the transverse plane and in rare cases the enlargement is sufficient to cause erosion of the bones in the spinal canal, or at least widening of the anterior–posterior diameter (Fig. 28.13). Transverse section of the cord reveals a cavity surrounded by a zone of translucent gelatinous material which, microscopically, contains glial cells and fibres. The protein content of the fluid in the cavity is raised and there is little difference between the ‘communicating’ and ‘non-communicating’ syringomyelia.

The expanding cavity and surrounding gliosis affecting the less resistant grey matter in the centre of the spinal cord, more severely than the dense white matter, allows the cavity to invade the anterior horns of the grey matter causing atrophy of anterior horn cells, degeneration of their axons in the ventral roots and peripheral nerves, and consequent wasting of muscles. The reflexes are lost. Extension to the brainstem, syringobulbia, usually occurs first in the postero-lateral medulla near the spinal nucleus of the trigeminal nerve and the nucleus ambiguous, so that the earliest signs of brainstem dysfunction are usually due to the involvement of these nuclei. Compression of the long ascending and descending tracts of the cord or brainstem occurs later, giving secondary degeneration most marked in the cortico-spinal tracts then in the spino-thalamic tracts, and last in the posterior columns. Haemorrhage into a syringomyelic cavity is one uncommon form of haematomyelia.

The symptoms of syringomyelia are readily interpreted as due to a progressive lesion in the central region of the spinal cord. The onset is usually insidious, but rarely may develop rapidly and sometimes in association with an episode of coughing, sneezing, or straining. Wasting and weakness of the small muscles of the hands are common early symptoms and the patient may notice loss of feeling in the hands or recognize suffering painless injuries. Sometimes the development of scoliosis in childhood is the clue to the condition.

The commonest site and presentation is with an elongated cavity in the central grey matter extending longitudinally through several segments in the lower cervical and upper thoracic cord. The lesion may be predominantly unilateral, therefore interrupting desiccating sensory fibres on one side of the cord derived from several consecutive dorsal roots. These are the fibres which conduct impulses concerned with the appreciation of pain, heat and cold, and those forms of sensibility are therefore affected whilst others travelling in the donal columns are preserved.

This ‘dissociated’ sensory loss was described originally by Charcot and usually appears first along the ulnar border of the hand, forearm, and arm, and on the upper part of the chest and back on one side in a half cape distribution. There is a horizontal lower border on the chest wall and the sensory disturbance ends at the mid-line.

Sometimes sensory loss may be impaired in a glove distribution and when the lesion extends centrally the area of dissociated sensory loss becomes bilateral. As the lesion extends upwards and downwards in the cord so the area of sensory impairment extends to the radial sides of the upper limbs and neck, and downwards over the thorax exhibiting a distribution ‘en cuirasse’ (Fig 28.23).

When the lesion reaches the upper cervical segments it begins to involve the spinal tract and nucleus of the trigeminal nerve, receiving fibres concerned with the appreciation of pain, heat and cold on the face. There is extension of the area of dissociated sensory loss in a concentric ‘onion skinning’ manner from behind forwards onto the face, sparing the sensation at the tip of the nose and the upper lip.

The progression of the spinal lesion later causes compression of the lateral spinothalamic tracts on one or both sides, leading to loss of appreciation of pain, heat and cold over the lower parts of the body. There may be an area of normal sensibility over the abdomen intervening between the area of thoracic anaesthesiae due to interruption of the decussating fibres and sensory loss in the lower limbs due to compression of the spino-thalamic tracts. When the spino-thalamic tract is compressed at the level of the medulla appreciation of pain, heat and cold is impaired or lost over the whole of the contra lateral side of the body.

The posterior columns are usually the last of the sensory pathways to suffer, but late in evolution there may be loss of appreciation of posture, passive movement, and vibration. This is most likely to involve the lower limbs and there may be extensive anaesthesia.

Thermoanaesthesia can be detected by the patient since hot water no longer feels hot over the affected parts and analgesia exposes the patient to injuries, especially burns on the fingers which, being painless, are not noticed. Spontaneous pains, though by no means invariable, are sometimes troublesome and the patient may describe burning, aching, or shooting sensations which can resemble the lightning pains of tabes dorsalis. More commonly the pain is continuous and burning in nature and may present on the face or an upper limb.

If the lesion begins in the thoraco-lumbar or lumbo-sacral region of the cord the dissociated loss will have an appropriate distribution. In non-communicating cases, secondary to spinal cord trauma, or other lesions, an ascending sensory level after months or years should suggest the presence of an ascending syrinx.

The earliest motor manifestations are usually muscular weakness and wasting, due to compression or destruction of the anterior horn cells. Since the lesion usually begins in the cervico-thoracic cord muscular wasting usually appears in the small hand muscles. It may be bilateral or unilateral, but as the lesion extends the wasting spreads to involve hands, forearms, and arms. The shoulder girdles and upper intercostal muscles may be involved. The wasting and weakness is never as marked as that seen in motor neurone disease and fasciculation is uncommon.

Contractures may develop particularly in the hand and forearm muscles and as the lesion extends to the postero-lateral medulla there may be involvement of the nucleus ambiguous causing paresis of the soft palate, pharynx, and vocal cord occasionally giving rise to laryngeal stridor and common causing dysphagia.

The other motor functions of the cranial nerves are rarely affected, though paralysis of the mandibular muscles, facial muscles, and lateral rectus has been recorded. The tongue is commonly involved and nystagmus is often seen. The nystagmus is variable, sometimes being phasic and present in lateral gaze but may be dissociated, and vertical nystagmus on up-gaze is reported. Paralysis of the ocular sympathetic on one or both sides may cause Horner’s syndrome, though the reaction to light should be preserved.

Compression of the cortico-spinal tracts in the spinal cord causes weakness with spasticity and extensor plantar responses in the later stages. There is rarely loss of significant power in the lower limbs, but tendon reflexes are exaggerated in the lower limbs, though diminished or lost in the upper limbs. This loss of reflexes is due to interruption of the reflex arc as the syrinx extends into the lateral grey matter. The sphincters are rarely affected since the anterior columns tend to be spared.

Trophic symptoms may sometimes be very marked. True hypertrophy involving all tissues can be present in one limb, one half of the body, or even the tongue. Loss of sweating or excessive sweating may occur, usually over the face and hands. Excessive sweating may be spontaneous or excited when the patient takes hot or highly seasoned food. Twenty per cent of patients have osteoarthropathy, Charcot’s joints, the shoulders, elbows, and cervical spine are most often affected, less often the joints of the hands, the temporomandibular joints, the sterno-clavicular joints, and the acromio-clavicular joints. Atrophy and decalcification of bones around joints with erosion of surfaces and subsequent bony destruction are seen radiographically. These joint changes are anaesthetic and painless. The affected joint is often enlarged and movement evokes loud crepitus but is painless. The long bones may be brittle.

Skin changes, including cyanosis, hyperkeratosis and thickening of the sub-cutaneous tissues causing a swelling of the fingers, described as ‘la main succulente’ (Fig. 28.24). The analgesia renders the patient exceptionally liable to repeated minor injuries and healing is slow. Ulceration, infection, and necrosis of bone is not uncommon and gangrene may be seen. The scars of former injuries are usually evident on the palmar surface of the fingers.

The medulla may be involved by upward extension from the cord, or may be the primary site of the disorder when the onset of symptoms may be sudden or gradual. Trigeminal pain, vertigo,

facial, palatal, or laryngeal palsy, or wasting of the tongue may all be seen.

This title is applied to patients in whom there is progressive loss of pain sensation, ulceration, loss of soft tissue, and resorption of the phalanges with muscular atrophy, not only in the hands, but sometimes in the feet with perforating ulcers. Whilst such changes in the hands rarely occur in syringomyelia, a similar syndrome may occur in leprosy when all four extremities are involved. The most common cause is hereditary sensory neuropathy (Section 21.6).

Many developmental anomalies have been described in association with syringomyelia occurring either in affected individuals or in members of their families. Deformities of the sternum, kyphoscoliosis, asymmetry of breasts, increase in the ratio between arm and body length, acrocyanosis of the hands, curved fingers, enuresis, and anomalies of the hair and ears, particularly with low hairline and short neck are identified. There may also be cervical rib, spina bifida, basilar impression of the skull, fusion of the cervical vertebrae in the Klippel–Feil syndrome with shortening of the neck, hydrocephalus, and pes cavus. Light brown pigmentation, either in the form of spots or diffuse sheets may be seen in segmental distribution, commonly over the shoulders.

MRI is the diagnostic investigation of choice. It is now widely available and has enabled a rapid and non-invasive diagnosis to be made earlier than in the past. T2-weighted saggital and axial spin echo images reveal the low signal central cavity in the spinal cord, the longitudinal extent of which is highly variable (Fig. 28.25). Cord expansion is usually apparent. When the syrinx is associated with a Chiari malformation the latter is also readily demonstrated on saggital T1-weighted images which include the level of the foramen magnum. Where the differential diagnosis includes intrinsic spinal cord tumour, gadolinium enhancement may identify enhancing tumour tissue. Myelography followed by immediate and delayed CT scanning, the previous ‘gold standard’ diagnostic investigation has now been rendered obsolete, except where MRI is contraindicated.

The CSF shows no abnormality unless the cavity is large enough to cause a block when the protein content of the fluid is raised. Single fibre electromyographic studies have shown a relatively consistent pattern of involvement of the cervical anterior horn cells.

There is little difficulty in making the diagnosis of syringomyelia clinically in advanced cases. The combination of wasting and trophic lesions of the hands with dissociated sensory loss and long tract dysfunction in the lower limbs is distinctive (Section 22.1.4). A clinically based diagnosis is more difficult in the early stages, but MRI scan allows early and accurate diagnosis in almost all cases. There is a wide differential diagnosis:

The course of syringomyelia, if untreated, is progressive, though progress is often slow and arrest may occur sometimes lasting for years. A sudden intensification of symptoms may occur after coughing, straining, or minor trauma or be caused by haemorrhage in a syringomyelic cavity. Exceptionally, distension of the spinal cord may become so marked as to produce a complete transverse myelopathy leading to paraplegia.

Symptomatic treatment for pain and spasticity may be required, protection of analgesic areas and earlier treatment of cutaneous lesions in order to promote healing are essential. In non-communicating secondary to spinal tumour or arachnoiditis, laminectomy with partial or complete removal of the causal tumour decompression and drainage of arachnoid cysts or the tumour itself with division of fibrous bands have all been helpful.

When ascending cavitation follows a complete traumatic transverse lesion of the cord the process may be arrested by total excision of a segment of spinal cord at and below the level of the injury and with incomplete post-traumatic myelopathy and syrinx, syringostomy, which is shunting of the cavity, may relieve pain.

In those cases with an associated Chiari malformation decompression of the foramen magnum and upper cervical cord is sometimes performed. The results are variable but there may be relief of head and neck pain and sometimes reduction in long tract signs. Less often is there is a beneficial effect on the segmental sensory and motor deficits. The response may be better if surgery is performed early in the course of the disease and the value of syringostomy in cases of communicating syringomyelia is uncertain.