Spinal cord

The relationships of the white matter tracts to one another and to the central grey matter are most easily appreciated in transverse section (figure 1). Within the major pathways, there is a relatively orderly somatotopic arrangement:

• ▶ In the spinothalamic tracts, the most superficial fibres are related to the sacral dermatomes. These overlie the lumbar fibres, with thoracic still deeper in the tracts, and the cervical fibres closest to the central grey matter. Pain and temperature sensation are conveyed in the lateral spinothalamic tracts whereas touch and pressure pathways are anterior (ventral).

• ▶ In the posterior (dorsal) columns, fibres from the lower limbs ascend medially in the gracile tracts, those from the upper limbs are lateral in the bulkier cuneate tracts. Pathways for position and touch sensation generally lie deep to those for vibration and pressure.

• ▶ In the lateral corticospinal tracts, descending fibres to the upper limbs are medial to those to the lower limbs.

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Figure 1

Transverse section of the spinal cord in the mid-cervical region. Many ascending and descending tracts have been omitted to emphasise the most clinically relevant.

The organisation is similar in the central grey matter of the cord where the neuronal cell bodies are arranged in 10 layers or ‘nuclei’ (Rexed's laminae):

• ▶ The laminae in the dorsal horns are where the primary cutaneous afferent fibres terminate having reached the cord via the dorsal roots of the spinal nerves. They then synapse with second order neurons in the substantia gelatinosa of the dorsal horns, directly or through interneurons. These second order neurons decussate in the ventral white commissure and ascend in the contralateral spinothalamic tract (this pathway may be contrasted with that for proprioceptive and exteroceptive information ascending in the dorsal columns where the central axons of the primary afferents remain ipsilateral and may not synapse until reaching the gracile and cuneate nuclei in the medulla).

• ▶ The lateral horns of the central grey matter are small projections in the thoracolumbar cord (T1 to L2) which contain the cell bodies of preganglionic sympathetic neurons.

• ▶ The ventral (anterior) horns are much larger and contain the cell bodies of lower motor neurons. Anterior horn cells are arranged so those whose axons are destined to innervate flexor muscles lie dorsal to those supplying the extensors; lower motor neurons to the limb muscles originate lateral to those destined for the truncal musculature in the ventral horns.

These microscopic arrangements and relationships all have clinical relevance when specific cord syndromes are considered:

Spinal roots

The ventral and dorsal roots at each spinal level unite to form mixed (sensory and motor) spinal nerves. The point of union is in or close to the intervertebral foramen. Spinal nerves and roots are numbered according to the adjacent vertebrae (figure 2). Thus in the cervical region, the nerve is the same number as the vertebra below it (eg, the right and left C7 nerves emerge from the spine at C6/7). The C8 nerves lie between the C7 and T1 vertebrae so spinal nerves below this level exit below the vertebrae with which they share a number. However, a disc prolapse in the lumbar region will still generally impinge on the root(s) with the same number as the vertebra below (because of the three-dimensional arrangement of the roots in the lower spinal canal). A lateral disc prolapse at L4/5, for example, will generally cause an L5 root lesion. It will only involve the L4 nerve if there is a far lateral protrusion.

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Figure 2

Diagram showing the relationship of the spinal cord segments and spinal nerves to the vertebrae. (Reproduced with permission from Ginsberg L. Lecture notes on neurology, 9th Edn. Wiley-Blackwell, 2010.)

A spinal cord segment is defined by the zone of attachment of the rootlets of a pair of spinal nerves (right and left, dorsal and ventral roots, 6–8 rootlets per root). As the cord occupies only the upper two-thirds of the spinal canal, there will necessarily be non-correspondence between the cord segments and the vertebrae (figure 2). This divergence becomes more marked the more caudal the segment, so that the lower roots have a longer intraspinal course than those arising more rostrally. Ultimately, with the spinal cord ending around L1/2, the neural elements in the lowest part of the theca consist solely of the roots forming the cauda equina, crowded around the filum terminale.

Genetic

• ▶ Hereditary spastic paraplegia is a neurodegenerative process primarily affecting upper motor neurons, rather than a disease of the spinal cord per se. It can resemble a ‘true’ myelopathy clinically, however, even in its relatively uncomplicated forms where there may be sphincter and sensory involvement. The pattern of inheritance is most commonly autosomal dominant but can be autosomal recessive or sex linked.

• ▶ Adrenomyeloneuropathy is one presentation of X linked adrenoleukodystrophy. Males (and occasionally female manifesting carriers) develop a slowly progressive spastic paraparesis in young adulthood, followed by sensory and sphincter involvement. Adrenal failure need not occur. Raised very long chain fatty acid levels are diagnostic in males but mutation analysis may be required in females.

• ▶ Other leukodystrophies, for example, metachromatic leukodystrophy, can have prominent upper motor neuron features, but the presence of cognitive deterioration and brain MRI changes usually help clarify the diagnosis.

• ▶ Some of the hereditary ataxias may occasionally present with a predominant spastic paraparesis. In particular, variant patients with Friedreich's ataxia may have lower limb spasticity, pyramidal weakness and retained reflexes. Similarly, some patients with spinocerebellar ataxia type 3 (Machado–Joseph disease) have clinical features resembling hereditary spastic paraplegia early in the course of their illness.

• ▶ Genetic disorders can also cause extrinsic compressive cord lesions, for example, in the mucopolysaccharidoses where the metabolic defect may lead to spinal dysostosis, dural thickening or atlanto-axial instability.

Congenital (ie, starting during fetal development)

• ▶ Syringomyelia is probably congenital, in association with a Chiari malformation.

• ▶ Spinal dysraphism varies in severity from the chance radiographic finding of spina bifida occulta to a full blown lumbar myelomeningocoele with consequent lower cord/cauda equina syndrome and neonatal hydrocephalus. Adults presenting with a partial conus or cauda equina syndrome in association with developmental lumbosacral skin changes (dimples, pits, sinuses, lipomas, haemangiomas or tufts of hair) may have a variety of underlying spinal defects, for example, tethering of the cord, or a lumbar syrinx or lipoma. Further up the spine, a bony spur can separate the cord into two halves—diastematomyelia.

• ▶ Arachnoid cysts are also probably congenital. Although usually asymptomatic, they can occasionally cause chronic cord compression, sometimes with secondary syrinx formation.

Traumatic

Missile and stab injuries to the spine are encountered in civilian life but the more common trauma is crushing of the cord consequent on fracture–dislocation of the spine, potentially exacerbated by hyperflexion/hyperextension and by any pre-existing narrowing of the spinal canal. Such injuries usually transect the cord with instantly fatal results if the lesion is in the high cervical region, unless there is immediate respiratory support (the respiratory muscles are innervated by motor fibres arising from C3 to the lower thoracic cord). More caudally, the degree of paralysis depends on the level of the lesion but there will generally be a phase of spinal shock followed by the development of hyperreflexia.

Infective

Extrinsic infective processes compressing the cord or cauda equina include epidural abscess, usually due to Staphylococcus aureus (sometimes streptococci and anaerobes). The clinical presentation is with the triad of pain (local, with tenderness and/or radicular), fever and signs of myeloradiculopathy.

Tuberculous spinal osteomyelitis (figure 3A) is encountered particularly in at risk groups (those in or from developing countries, or immunocompromised individuals) and leads to neural compression which may be associated with spinal deformity, ultimately the angular gibbus of Pott's disease of the spine.

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Figure 3

Spinal MRI. (A) Tuberculous spinal osteomyelitis and discitis—sagittal T2 weighted image of the thoracic spine showing destruction of the T8 vertebral body and extradural compression of the spinal cord. (B) Neuromyelitis optica—sagittal T2 weighted image of the cervicothoracic spine showing longitudinally extensive transverse myelitis, involving much of the cord caudally from C5. (C) Spinal meningioma—sagittal T1 weighted image of the thoracic spine post-gadolinium. The lesion was isointense with the spinal cord on the pre-contrast images but can be seen to enhance avidly post-gadolinium. (D) Spondylotic compression at C3/4—sagittal T2 weighted image of the cervicothoracic spine. There is anterior and posterior cord impingement, resulting in damage to its parenchyma (myelomalacia), shown as high signal within cord substance at the point of maximal compression. (Figure 3C is reproduced with permission from Ginsberg L. Lecture notes on neurology, 9th Edn. Wiley-Blackwell, 2010.)

Intrinsic infective myelopathies can be acute or chronic:

• ▶ Acute infective myelitis is less common in developed countries than a post-infective process (see below). It may be viral (zoster, herpes simplex, HIV at seroconversion), bacterial (tuberculosis, secondary syphilis) or, rarely, parasitic (schistosomiasis).

• ▶ Chronic infective myelopathies include the vacuolar myelopathy of advanced HIV infection. Another chronic retroviral myelopathy is associated with human T cell lymphotropic virus infection (tropical spastic paraparesis, human T lymphotropic virus type 1 associated myelopathy) which is endemic in the Caribbean, sub-Saharan Africa and the Far East. Transmission is vertical, sexual or through blood transfusion. Only a small minority of infected individuals develop neurological problems following an incubation period of many years. The clinical picture is of a progressive spastic paraparesis (usually slow) with prominent sphincter involvement and painful paraesthesiae in the legs.

Infective radiculopathies include herpes zoster and also the meningoradiculopathy of Lyme disease. A polyradiculitis of the cauda equina caused by cytomegalovirus occurs in AIDS patients with very low CD4 cell counts.

Inflammatory and demyelinating

Multiple sclerosis (MS) is the most common cause of a spastic paraparesis in young adults in temperate zones. Although a complete transverse myelitis may occur, the clinical features of a cord relapse of MS are typically asymmetrical, reflecting the likely irregular disposition of the causative plaques. The Lhermitte phenomenon is helpful in the diagnosis of MS, but not pathognomonic, because it also occurs in compressive cervical cord lesions and vitamin B₁₂ deficiency. The Uhthoff phenomenon is also useful, but may be more subtle than the patient simply complaining of worsening symptoms after a hot bath. Thus patients with spinal cord demyelination may describe exercise induced deterioration in their walking, mimicking vascular or compressive spinal lesions.

Theoretically, there is no limit to the length of a spinal plaque of MS. However, very long intrinsic cord lesions identified on MRI are increasingly being associated with other causes. This has led to the emergence of the awkwardly named but clinically useful concept of longitudinally extensive transverse myelitis (extending at least three vertebral segments, figure 3B). This can be seen in neuromyelitis optica (NMO, Devic's disease) where the clinical cord syndrome is usually much more severe than in MS.

Post-infective or post-immunisation transverse myelitis may be a forme fruste of acute disseminated encephalomyelitis. The typical presentation is with a monophasic acute or subacute transverse myelopathy a few days or weeks after an infection or immunisation. The initial trigger may be relatively trivial, for example, an upper respiratory tract infection. Often, no specific organism is identified but recognised associations include Epstein–Barr virus, varicella zoster virus and Mycoplasma. Spinal MRI may show a longitudinally extensive transverse myelitis and the CSF is usually moderately lymphocytic.

Various systemic inflammatory and autoimmune diseases have occasionally been linked to cord syndromes that resemble MS. The diagnosis is relatively straightforward if the patient already has clinical and/or paraclinical features of the systemic disease, as may occur in sarcoidosis and (rarely) Behçet's disease. A diagnosis of sarcoidosis is harder to reach if there are no systemic features. The situation is more controversial for systemic lupus erythematosus and Sjögren's syndrome. Again, there is some diagnostic security if there are systemic features of the autoimmune disease. However, if the only evidence of lupus or Sjögren's is serological, the patient may in fact have NMO with non-pathogenic antibodies.

Systemic inflammatory disorders may also cause extrinsic cord lesions. The most notorious is atlanto-axial subluxation, a rare complication of rheumatoid arthritis, where the combination of a build-up of inflammatory tissue and weakening of ligaments puts the patient at risk of a catastrophic compressive foramen magnum lesion.

Neoplastic

Spinal tumours are classified as extradural, extramedullary–intradural and intramedullary:

• ▶ Extradural tumours include metastases to the vertebrae (typically breast, lung, prostate, thyroid and kidney cancers) and other bony malignancies (myeloma, lymphoma). These lesions impinge on the cord, roots or cauda equina by invading the epidural space, or by causing vertebral collapse. Patients present with acute cord compression, back pain and tenderness, but the history can often be traced back days or even weeks. Sometimes, malignant disease can spread through the epidural space, ‘picking off’ roots and compressing the cord at multiple levels, without involving the vertebrae. This applies particularly to lymphoma and prostatic carcinoma. The result can be a confusing mixture of upper and lower motor neuron signs, even mimicking motor neuron disease. Non-malignant extradural tumours include chordomas and lipomas.

• ▶ Extramedullary–intradural tumours lie on the surface of the cord, having arisen from the meninges or a root, mainly meningiomas and neurofibromas. Spinal meningiomas (figure 3C) have a much more marked female preponderance than their intracranial counterparts. Neurofibromas may occur in isolation or in the context of neurofibromatosis. They are more likely to generate radicular symptoms than meningiomas.

• ▶ Intramedullary tumours lie within the spinal cord, sometimes with a syrinx. They are very rare and include astrocytomas, ependymomas, haemangioblastomas and metastases.

An acute necrotising myelopathy may occur as a paraneoplastic phenomenon, most commonly with small cell lung cancer. The cord syndrome may antedate the discovery of the cancer by many months. Antineuronal antibodies (anti-Hu) are usually present.

Vascular

Like the brain, the cord can be affected by both haemorrhagic and ischaemic vascular events. Bleeding into the epidural or subdural space, for example, through anticoagulant excess, will cause an acute compressive transverse myelopathy. Haemorrhage within the cord (haematomyelia) may be due to an underlying arteriovenous or cavernous malformation.

Ischaemic cord infarction most commonly affects the anterior spinal artery territory, producing a ventral cord syndrome of abrupt and painful onset. Causes include atherosclerosis of feeder vessels (in particular, the artery of Adamkiewicz), aortic dissection, and aortic surgery (especially if complicated by hypotension). Rarer possibilities are thrombosis of the anterior spinal artery itself, vasculitis, infective endocarditis, decompression sickness and fibrocartilaginous embolism.

Spinal dural arteriovenous fistula is uncommon but potentially treatable. Patients are usually male and middle-aged or elderly, presenting with a subacute or chronic, stepwise, fluctuating deterioration in gait, with pain in the back or leg, sensory disturbance and ultimately sphincter involvement. Exercise may trigger deterioration. On examination, a combination of upper and lower motor neuron signs may be seen. Although the fistula is usually in the lower cord, the sensory level may be several segments higher because of ascending venous congestion. Spinal MRI may show only subtle signal change in the lower cord and conus or an enlarged draining vein, although spinal MR angiography may be more informative. Confirmation of the diagnosis ultimately requires selective catheter angiography. The fistula may be amenable to embolisation or surgical occlusion.

Metabolic and toxic

As the name implies, subacute combined degeneration of the cord, secondary to vitamin B₁₂ deficiency, is characterised by a combination of dorsal column and corticospinal tract dysfunction, usually evolving over the course of a few weeks. There is also a significant component of peripheral neuropathy (hence the coexistence of lower motor neuron with the upper motor neuron signs from the myelopathy—absent ankle reflexes and extensor plantar responses) and, later, optic neuropathy and cognitive impairment. Vitamin B₁₂ deficiency is remarkable as one of the few causes of peripheral neuropathy where the hands may be affected before the feet, but this is largely because of the coexistent myelopathy; spinal MRI shows signal change in the dorsal columns of the cervical cord. The neurological complications of vitamin B₁₂ deficiency may occur in the absence of any haematological disorder, even with a normal mean corpuscular volume. Investigation should include measurement of serum methylmalonic acid and homocysteine as well as vitamin B₁₂ levels.

Copper deficiency has been recognised recently as a cause of a subacute combined degeneration picture. At risk patients include those who have undergone partial gastrectomy or gastric bypass surgery (hence impairing copper absorption) and individuals with excessive zinc intake (zinc competing with copper for absorption in the proximal duodenum). The diagnosis is confirmed by very low serum copper and caeruloplasmin levels. The haematological findings of copper deficiency are different from vitamin B₁₂ deficiency, sideroblastic anaemia with neutropenia.

Chronic liver failure may lead to a range of neurological deficits, including a slowly progressive myelopathy.

Toxic causes of myelopathy include:

• ▶ Nitrous oxide inhalation producing clinical features resembling subacute combined degeneration. Patients having multiple anaesthetics are at risk, as are dentists and veterinary surgeons who self-administer for recreational purposes.

• ▶ Oil based contrast medium (Myodil), previously used for myelography, causes spinal arachnoiditis with consequent cord and cauda equina damage. Arachnoiditis can also develop after spinal surgery.

• ▶ Radiation—a slowly progressive myelopathy may occur months or years after radiotherapy.

• ▶ Dietary toxins—lathyrism from consumption of the chickling vetch Lathyrus sativus, konzo from cassava.

Degenerative

Cervical spondylotic myelopathy is the most common cause of a spastic paraparesis in elderly patients. The extrinsic compression arises from a combination of degenerative disc disease, osteophyte formation and ligamentous hypertrophy, leading to myelomalacia (figure 3D). A single level in the lower or mid cervical region may be affected (as shown in figure 3) but often there is multilevel disease. The clinical features are of a spastic paraparesis, with or without sphincter and sensory involvement, in association—but not always—with neck pain and stiffness, and radicular arm pain. Upper limb signs may be a mixture of upper and lower motor neuron. It is often possible to discern the site of the lesion clinically from the presence of a ‘reflex level’. Thus an absent or inverted biceps reflex, with brisk reflexes below, implies myeloradiculopathy at C5.

Lumbar spondylosis, frequently superimposed on a congenitally stenotic spinal canal, may cause chronic cauda equina compression. Patients present with back and leg pain, with sensory and motor symptoms in the lower limbs, which may be exercise induced—intermittent claudication of the cauda equina. Neurogenic claudication is typically triggered by walking and relieved by sitting or leaning forwards for 5–15 min, considerably longer than is required to relieve claudication from peripheral vascular disease. This relationship of symptoms to posture is thought to reflect the cross sectional area of the lumbar canal, which is least on standing and walking, hence resulting in maximal compression of the cauda equina and its blood supply.

Disc protrusions usually occur spontaneously, in the context of disc degeneration, rather than being linked to a specific traumatic event. Lateral disc protrusions typically cause a cervical or lumbar monoradiculopathy. Central disc prolapse in the lumbar region may cause an acute cauda equina syndrome, a neurosurgical emergency.

Motor neuron disease (amyotrophic lateral sclerosis) occasionally presents as a spastic paraparesis—an intrinsic (neuro)degenerative cause of myelopathy. In the absence of lower motor neuron signs, the diagnosis may be supported by detecting subclinical evidence of denervation on electromyography. Primary lateral sclerosis is a virtually pure symmetrical spastic paraparesis, progressing to tetraparesis then pseudobulbar palsy, with sphincter involvement and emotional lability only occurring late in the course of the disease. Primary lateral sclerosis has a much better prognosis than amyotrophic lateral sclerosis. The diagnosis rests on a minimum disease duration of 3 years and the absence of pointers to other causes (eg, no family history to suggest hereditary spastic paraplegia, no oligoclonal bands in CSF to suggest primary progressive MS).

Investigation

The key investigation for a patient presenting with a myelopathy or lumbar polyradiculopathy is spinal MRI to identify or exclude cord or cauda equina compression. The decision to image a patient with a cervical or lumbar monoradiculopathy depends on the severity and duration of symptoms. If cord or cauda equina compression has been excluded, further investigation will be determined by the patient's clinical presentation and spinal MRI findings (table 4).

Surgery

The need for urgent surgery is not controversial for patients with cord or cauda equina compression from:

• ▶ benign extradural or extramedullary–intradural tumour

• ▶ epidural abscess

• ▶ epidural haematoma

• ▶ acute central disc prolapse.

Indeed, the last three diagnoses are neurosurgical emergencies. Malignant extradural tumours respond as well to radiotherapy with dexamethasone as they do to surgery.

Surgery for severe trauma should be restricted to spinal stabilisation where there is any risk of further injury, and to aid early rehabilitation. There is no justification for prolonged courses of corticosteroids but methylprednisolone within 8 h of injury may have some modest benefit.

Less clearcut is the surgical management of chronic spondylotic compression, where there is a serious lack of high quality evidence:

• ▶ Patients with cervical spondylotic myelopathy are often very elderly, with significant comorbidities. The course of the neurological impairment is not necessarily progressive. However, with advancing myelopathy and deteriorating disability, in a patient fit for surgery, there is a case for decompression, mainly to prevent further deterioration (any improvement being a bonus). The posterior operation of decompressive laminectomy may be preferred if multiple levels are affected. Anterior surgery (eg, Cloward's procedure) is used for predominantly discogenic disease.

• ▶ Many patients presenting with radicular pain from a lateral disc prolapse in the cervical or lumbar region are satisfactorily managed without surgery (see below). Operative intervention should be contemplated only after a failed trial of conservative therapy of at least 6 weeks, but sometimes sooner if there are significant symptoms and signs of root compression.

Medical treatment

Some medical causes of myelopathy demand treatment as urgently as those amenable to surgery, to minimise irreversible cord damage, for example, vitamin B₁₂ replacement for subacute combined degeneration or plasma exchange for a relapse of NMO.

Most patients with acute radicular pain from a lateral cervical or lumbar disc prolapse are managed successfully with analgesia, maintenance of mobility and, if necessary, the involvement of a multidisciplinary pain management team. Epidural and root directed injections of corticosteroids are of uncertain benefit but are sometimes used with the aim of delaying or avoiding surgery.

Rehabilitation

Specialist spinal units have revolutionised the prognosis for survival of patients with severe cord injury. Their environment promotes the attention to detail required to prevent potentially life threatening complications, including venous thromboembolism, pressure sores and urinary tract damage. Other important areas of management for paraplegic and tetraplegic patients are:

• ▶ prevention of contractures

• ▶ control of spasticity

• ▶ bladder, bowel and sexual function

• ▶ maintenance of nutrition

• ▶ psychological stress.

Educating and hence empowering patients in the management of their own condition is vital.

Autonomic dysreflexia is a particular complication of cervical and high thoracic spinal cord injuries. It is a reflex response to a noxious stimulus, such as bladder distension, urinary tract infection or lower body trauma. The response manifests as sympathetic overactivity with severe headache and hypertension, the latter occasionally fatal. Prevention may involve the judicious use of α-adrenergic blocking antihypertensive drugs, as well as avoidance of potential precipitants. Acute treatment of autonomic dysreflexia includes sitting the patient upright, removing the precipitant and control of hypertension, for example, with sublingual nifedipine.