Diseases Of The Spinal Cord

Diseases of the spinal cord - detailed technical article.

Topics covered:

  • Essentials
  • Introduction
  • Aetiology, pathogenesis
  • Clinical features
  • Differential diagnosis
  • Clinical investigation
  • Criteria for diagnosis
  • Treatment and prognosis
  • Further reading

Essentials  

The spinal cord is subject to numerous pathological processes that can arise within (intramedullary) and/or extrinsic to the cord (extramedullary lesions).

Clinical features

Symptoms and signs suggestive of spinal cord disease include (1) motor—weakness and alteration in tone; acute cord lesions produce flaccidity (‘spinal shock’) and chronic processes spasticity, with hyper-reflexia, clonus, and upgoing plantar responses; pathological processes targeting lower motor neurons in the anterior horns typically produce early muscle wasting and fasciculation; (2) sensory—including numbness, loss of sensation, tingling, sensory ataxia; the demonstration of a sensory level and analysis of specific sensory deficit patterns are of particular importance in localizing the site, and therefore the likely cause, of any lesion; and (3) autonomic—sphincter dysfunction, most commonly affecting bladder function. Other clinical features may give clues to the cause of spinal cord disease, e.g. multiple sclerosis, systemic lupus erythematosus (SLE), neurofibromatosis.

Investigation

Intramedullary and extramedullary pathologies may produce distinguishable symptom profiles, but the clinical distinction can only ever be probabilistic. If there is acute onset of myelopathy, and/or structural disease is suspected, imaging of the cord is mandatory, with MRI the investigation of choice. Once structural lesions are excluded, further investigation depends on suspected cause (e.g. neurogenetic testing for some hereditary spastic paraplegias and spinocerebellar ataxias), and on geographical location or travel history (e.g. schistosome ova in faeces). Examination of the cerebrospinal fluid may be required.

Particular conditions affecting the spinal cord

Many diseases can affect the spinal cord. Those of particular note include (1) spondylotic myelopathy—the most common cause of progressive myelopathy due to cord compression; (2) multiple sclerosis—may present as an isolated cord syndrome, usually partial rather than complete; (3) transverse myelitis—most commonly affects the thoracic cord; there may be a preceding history of infection, and cerebrospinal fluid analysis may disclose an infective agent; (4) subacute combined degeneration of the cord—demyelination of the posterior and lateral columns due to vitamin B12 deficiency; may occur in the absence of haematological abnormality; (5) genetic disorders—hereditary spastic paraplegia is usually an autosomal dominant disorder; causative mutations have been described in several genes; (6) vascular disorders—anterior spinal artery occlusion can infarct whole or part of the anterior two-thirds of the cord; (7) syringomyelia; (8) injury/trauma—see Chapter 24.13.1; (9) motor neuron disease—see Chapter 24.15.

Treatment and prognosis

Specific medical and surgical treatments are determined by the particular cause of myelopathy. These may arrest progression, but function that has been lost does not usually recover. Prognosis of acute cord compression is directly related to the time delay between symptom onset and relief of compression. Chronic disability as a consequence of spinal cord disease requires intensive neurorehabilitation.

Introduction 

Disease within the substance of the spinal cord, intramedullary myelopathy, may result from a wide variety of pathological causes. Myelopathy may also result from pathology located outside the spinal cord (extramedullary) but within structures immediately adjacent to the cord, either intradural or extradural, affecting normal cord function (Table 1). Clinical features may sometimes give clues to both the pathological nature and anatomical location of disease (Table 2), but these have been greatly augmented with the development of MRI studies of the spinal cord.

Aetiology and pathogenesis 

The spinal cord and its addenda may be affected by inflammatory, demyelinating, metabolic, infective, neoplastic, vascular, and iatrogenic disorders (Table 1). Chronic progressive myelopathy should always prompt consideration of a structural lesion such as a tumour, intrinsic or extrinsic, but cervical spondylotic change with osteophyte formation, with or without concurrent intervertebral disc degeneration and prolapse, is the most common cause of progressive cord compression. Acute cord syndromes may result from trauma or vascular pathology, and infective disorders (myelitis) may develop rapidly. Inflammatory lesions tend to evolve over hours to days, although sometimes present in a chronic progressive fashion.

Clinical features 

The clinical features of spinal cord disease, the symptoms and signs and their temporal progression, may give clues to disease localization (Table 2) and pathogenesis. Symptoms and signs suggestive of spinal cord disease may be motor (weakness, spasticity), sensory (numbness, loss of sensation, tingling, sensory ataxia), and autonomic (sphincter dysfunction). Acute and chronic pathologies may result in differing patterns of symptoms and signs, the former sometimes evolving to the latter.

Considering motor symptoms, weakness may affect all limbs (quadriparesis) or only the legs (paraparesis). The most severe presentation, for example after cord transection, is with complete absence of power (quadriplegia, paraplegia). Exceptionally with extramedullary cervical cord lesions a triparesis may be seen, sometimes evolving in a sequential (‘round the clock’) pattern: arm, ipsilateral leg, contralateral leg. Alterations in tonus accompany weakness, in acute lesions flaccidity (‘spinal shock’) but with more chronic processes spasticity with clonus, along with pathological accentuation of myotatic (tendon, phasic) reflexes (hyperreflexia), loss of cutaneous reflexes, and upgoing plantar responses (Babinski’s sign). Muscle wasting is a late sign with upper motor neuron pathology. Concurrent radiculopathy or neuropathy may however modulate the typical upper motor neuron signs, for example the absent ankle jerks with upgoing plantars sometimes seen in subacute combined degeneration of the cord in which there is concurrent neuropathy or in motor neuron disease with both upper and lower motor neuron involvement, or the segmental reflex depression in a compressive cervical myeloradiculopathy. Inversion of reflexes (i.e. movement opposite to that usually seen, such as elbow extension when eliciting the supinator reflex) may occur when pathology affects both the local reflex arc and segments higher in the cord. High spinal cord lesions may affect segments innervating the diaphragm (C3–5) with subsequent respiratory compromise, particularly acute lesions, hence the need for respiratory monitoring in these circumstances. Because of the root values of myotatic and cutaneous reflexes, their pathological alteration may be of localizing value.

Pathological processes targeting lower motor neurons in the anterior horns of the spinal cord typically produce early muscle wasting and fasciculation. Motor neuron disease is the commonest cause of these signs, sometimes in isolation (‘progressive muscular atrophy’), but they may also occur following certain viral infections (poliomyelitis, enterovirus 71, flaviviruses such as Japanese encephalitis virus). A subacute motor neuronopathy is also described in association with underlying lymphoma.

Spinal cord pathologies are often accompanied by a localizing sensory level, which may be defined clinically as the spinal segment below which sensation is altered and above which it is intact. Because pain fibres forming the spinothalamic tracts ascend in the posterior horns for two or three segments prior to decussation through the ventral commissure, contralateral loss or reduction of pain and temperature sensation may be associated with a level two or three segments above the site of pathology. The deficit associated with a sensory level may be complete, affecting all modalities, for example in cord transection (‘sawn off’) or complete transverse myelopathies, but more often it is partial.

Specific sensory deficit patterns have particular localizing implications. Because of the anatomical separation within the cord of the pathways subserving the sensory modalities of pain and temperature (spinothalamic) and proprioception (dorsal column), dissociated sensory loss may occur. Central cord pathologies such as syringomyelia selectively involve decussating spinothalamic pathways within the ventral commissure resulting in impaired pain and temperature sensation, often in suspended (‘cape-like’, cuirasse, ‘bathing suit’) distribution, dependent on the exact level of the syrinx. Osteoarthropathy due to loss of pain fibres (Charcot joints) may also occur in syringomyelia. Anterior spinal artery syndrome also spares the dorsal columns. Conversely, the dorsal columns are preferentially affected in disorders such as subacute combined degeneration of the cord. Focal cervical cord pathology, most typically demyelination, may be accompanied by Lhermitte’s sign, tingling paraesthesia radiating like an electric shock into arms and legs on neck flexion; there may be a motor equivalent, increased limb weakness on neck flexion (McArdle’s sign). Both signs reflect mechanosensitivity and impaired impulse transmission in demyelinated axons. Preservation of pain and temperature sensation in sacral dermatomes (‘sacral sparing’) below a sensory level may be seen with intramedullary lesions as a result of the topographical lamination of fibres in the spinothalamic tracts, ventrolateral fibres of sacral origin being most external and hence later involved with expanding intramedullary lesions.

Although ataxia is sometimes thought of as a motor symptom, it may also be a consequence of sensory dysfunction, specifically when afferent proprioceptive information is degraded or lost. Sensory ataxia, as distinct from cerebellar or optic ataxia, results in falling or markedly increased sway when standing with the eyes closed (Romberg’s sign) and impaired heel–toe (tandem) walking (‘dynamic Romberg’s sign’). Pseudoathetosis, involuntary movements in the outstretched hands (‘piano-playing fingers’), may also be seen. Dorsal column pathologies are particularly associated with sensory ataxia, classically the tabes dorsalis form of neurosyphilis, also sometimes known as locomotor ataxia.

Table 1 Causes of myelopathy
Pathological processa Intramedullary Extramedullary
Structural—developmental
  • Syringomyelia related to Chiari malformation
  • Spina bifida, spinal dysraphism, diastematomyelia
  • Chiari malformation
  • Tethered cord syndrome
  • Platybasia/basilar invagination
  • Arteriovenous malformations
  • Arachnoid cysts (e.g. in Marfan syndrome)
  • Achondroplasia
Structural—acquired/trauma
  • Cord transection
  • Contusion/haematoma
  • Haematomyelia
  • Central cord syndrome (hyperextension injury)
  • Whiplash (hyperextension/flexion injury)
  • Spinal cord injury without radiologic abnormality (SCIWORA)
  • Intervertebral disc prolapse
  • Osteophytes
  • Spinal stenosis
  • Vertebral fracture (e.g. wedge fracture with vertebral metastasis)
  • Atlanto-axial subluxation (rheumatoid arthritis)
  • Ossification of the posterior longitudinal ligament
  • Dural herniation of the spinal cord
Structural—neoplasia
  • Astrocytoma/glioma
  • Ependymoma
  • Medulloblastoma
  • Metastases
  • Intradural: meningioma
  • neurofibroma; lipoma (± spina bifida)
  • Extradural: myeloma, lymphoma, sarcoma, haemangioblastoma, chordoma
  • Metastases
  • Leukaemic meningeal infiltration
Neuronal degeneration/hereditary
  • Motor neuron disease
  • Other motor neuron diseases: spinal muscular atrophies
  • Hereditary spastic paraplegia (HSP)
  • Spinocerebellar ataxias (SCA)
  • Familial Alzheimer’s disease with presenilin-1 gene deletion (exon 9)
  • Familial British dementia
N/A
Inflammation
  • Transverse myelitis (idiopathic > clinically isolated syndrome)
  • Sarcoidosis
  • Systemic lupus erythematosus
  • Sjögren’s syndrome
  • Behçet’s disease
  • Giant cell arteritis
  • Paraneoplastic myelitis
  • Necrotizing myelitis (Foix–Alajouanine syndrome)
  • Arachnoiditis (e.g. related to radiological contrast media, ankylosing spondylitis)
  • Discitis
Demyelination
  • Multiple sclerosis
  • Acute disseminated encephalomyelitis (ADEM)
  • Neuromyelitis otica (NMO)/Devic’s disease.
N/A
Metabolic/nutritional
  • Vitamin B12 deficiency (subacute combined degeneration of the cord)
  • Adrenomyeloneuropathy
  • Vitamin E deficiency
  • Copper deficiency associated myelopathy
  • Lathyrism
  • Konzo
  • ?Myelopathy associated with inflammatory bowel disease
  • Krabbe’s globoid cell leukodystrophy.
Paget’s disease (‘osteitis deformans’)
Infection
  • Viral: poliomyelitis, HIV, HTLV-1 (tropical spastic paraparesis), enterovirus, herpes simplex 1 and 2, herpes zoster, EBV, CMV, HHV6
  • Spirochaetal: neurosyphilis (tabes dorsalis)
  • Bacterial: brucellosis
  • Parasitic: schistosomiasis
  • Atypicals: mycoplasma.
  • Spinal abscess: epidural, subdural
  • Empyema
  • Osteomyelitis (e.g staphylococcal)
  • Osteitis (e.g. TB (Pott’s disease), syphilis)
  • Parasitic cysts (echinococcus)
Vascular
  • Cord ischaemia/infarction: anterior spinal artery syndrome
  • Aortic aneurysm
  • Fibrocartilaginous embolism
  • Decompression sickness
  • Haematomyelia/haematoma: into metastasis or vascular malformation, primary coagulation disorder.
Arteriovenous malformations: dural arteriovenous fistula, arteriovenous malformations, cavernous angioma
Iatrogenic
  • Surgery of aortic aneurysm: anterior spinal artery syndrome
  • Lumbar puncture: direct trauma to cord
  • Radiation myelopathy
  • Vaccination-related myelopathy
  • Drugs: anticoagulants (bleed into cord); heroin; subacute myelo-optic neuropathy (SMON) with clioquinol
Lumbar puncture: spinal subdural haematoma

CMV, cytomegalovirus; EBV, Epstein–Barr virus; HHV, human herpesvirus; HTLV-1, human T-lymphotropic virus type 1.

a NB: These are not necessarily mutually exclusive.

Table 2 Clinical clues to differentation of intramedullary from extramedullary myelopathy
Symptoms/signs Intramedullary Extramedullary
Sensory Central (funicular) distribution of pain may occur. Patterns of sensory loss may be: dissociated (spinothalamic > dorsal column modalities, or vice versa) including classic Brown-Séquard syndrome; suspended (cape-like, cuirasse); sacral sparing. Vibratory sensibility more often affected than proprioception Pain may be radicular or vertebral in distribution. Sensory signs not usually marked until the later stages and all modalities often involved. Brown-Séquard syndrome may be more common with extrinsic than intrinsic pathologies
Motor Lower motor neuron signs at the level of the lesion(s) may be prominent and diffuse; upper motor neuron signs of spastic paraparesis below the level of the lesion tend to occur late. Combination of upper and lower motor neuron signs more likely to reflect intrinsic than extrinsic pathology Sequential spastic paraparesis below the level of the lesion. Upper motor neuron signs occur early; lower motor neuron signs unusual and if present typically have segmental (radicular) distribution
Autonomic Bladder involvement common, often early symptom; slow to recover May have bladder urgency, impotence

Autonomic features associated with spinal cord pathology are most typically those related to sphincter, particularly bladder, function. Acute spinal cord lesions may result in urinary retention, e.g. cauda equina compression with central L1 disc prolapse, although sometimes the pathology may be many segments rostral to the clinical signs. Inflammatory and chronic lesions, for example multiple sclerosis, may be associated with urinary frequency, urgency and urge incontinence with urodynamic evidence of detrusor muscle hyperreflexia and detrusor sphincter dyssynergia. Loss of awareness of bladder fullness with urinary retention and overflow (atonic bladder) may result from chronic disease, as in tabes dorsalis. Cord damage may also result in constipation or faecal urgency or incontinence, and sexual (e.g. erectile) dysfunction. Loss of or excessive sweating may be observed in syringomyelia. Horner’s syndrome may be associated with cord pathology since the sympathetic afferents originate there, for example isolated Horner’s syndrome has been reported with syringomyelia.

Although the two- or three-segment mismatch between a clinically-defined pain sensory level and the location of cord pathology is easily explicable on the basis of the known anatomy of spinal cord connections, other clinical signs distant from pathology are less easy to explain. Such false localizing signs in the cord include the association of foramen magnum or upper cervical cord lesions with paraesthesia in the hands, intrinsic hand muscle wasting (‘remote atrophy’) and distal upper limb areflexia, a gestalt more suggestive of lower cervical myeloradiculopathy. Similarly, a midthoracic sensory level (‘girdle sensation’) with spastic paraparesis may occur with lower cervical or upper thoracic compressive pathology.

Intramedullary and extramedullary pathologies may produce distinguishable symptom profiles (Table 2) but the clinical distinction can only ever be probabilistic, and further investigation by means of spinal cord imaging, ideally with MRI, is indicated. The syndrome originally described by Brown-Séquard in the context of traumatic cord hemisection consists of ipsilateral spastic weakness with or without segmental lower motor neuron signs at the level of the lesion, with dissociated sensory loss comprising ipsilateral proprioceptive loss and contralateral pain and temperature loss below the level of the lesion. This pattern may occur with various pathologies including prolapsed disc, intra- and extramedullary tumours, and multiple sclerosis.

Other clinical features may give clues to the aetiological diagnosis of myelopathy. A history of hindbrain headache may indicate a Chiari malformation. Likewise other clinical signs may be informative: a segmental rash may be seen acutely with varicella zoster, and clinical stigmata may point to the diagnosis of systemic lupus erythematosus (SLE), neurofibromatosis, Paget’s disease, and rheumatoid arthritis.

Differential diagnosis 

The particular pattern of symptoms and signs may allow differentiation of myelopathy from disorders of nerve roots (radiculopathy), although because of their close proximity to the cord simultaneous segmental involvement is not uncommon (radiculomyelopathy) particularly with cervical spinal lesions; likewise peripheral nerves (neuropathy), although certain disease processes simultaneously affect both (myeloneuropathy). Lesions of the conus may be difficult to differentiate from the cauda equina syndrome of multiple radiculopathies, although often both are present.

Clinical investigation 

If there is acute onset of myelopathy, and/or structural disease is suspected, imaging of the cord is mandatory and magnetic resonance imaging (MRI) the investigation of choice, usually requiring axial and sagittal sequences with T 1- and T 2-weighting, with or without gadolinium contrast. Appearances may diagnose structural abnormalities such as spondylotic compression, disc prolapse, intrinsic or extrinsic tumours, syringomyelia, Chiari malformations, abscess, or haematoma. Arteriovenous malformations may be seen, although it remains the case that on occasion myelography will reveal vascular anomalies not seen on MRI. Further definition of these vascular lesions with selective spinal angiography or magnetic resonance (MR) angiography may be helpful in planning appropriate treatment. Neurosurgical biopsy of mass lesions may on occasion be required.

Intrinsic cord disease may have characteristic appearances on MRI. Typical demyelinating lesions of multiple sclerosis usually extend for no more than one vertebral segment and may be multiple, whereas more extensive lesions (‘longitudinal myelitis’) suggest infective, postinfectious, or vascular disease. These lesions may be associated with enhancement on post-contrast scans. Certain viral myelitides, such as poliomyelitis or enterovirus 71, may produce signal change confined to the anterior horns, consistent with a purely motor syndrome. MR spectroscopy of cord lesions may prove difficult because of partial volume effects in selected voxels.

Once structural lesions are excluded, further investigation of myelopathy will be dependent on suspected cause, and on geographical location or travel history. Blood tests may include haematological parameters such as full blood count and film, ESR, and vitamin B12 level. Biochemical analyses are seldom helpful other than for specific entities, such as angiotensin converting enzyme (ACE) for sarcoidosis, and very long chain fatty acids for adrenoleukodystrophy which may be associated with the typical electrolyte changes of Addison’s disease. Raised alkaline phosphatase may alert to a possible diagnosis of Paget’s disease. Serology for VDRL, autoantibodies including double-stranded DNA, antiphospholipid antibodies and gastric parietal cell antibodies may be required if specific diseases are suspected. Serology for infective agents may encompass viral (HIV, human T-lymphotropic virus type 1 (HTLV-1), enterovirus 71, Epstein–Barr virus (EBV), cytomegalovirus (CMV), varicella zoster, coxsackievirus, poliovirus), bacterial (brucella, tuberculosis), spirochaetal (syphilis) and parasitic (schistosomiasis) causes of myelopathy. In the appropriate geographical distribution or with positive travel history, a search for schistosome ova in faeces may be undertaken.

Neurogenetic testing, following appropriate genetic counselling, is available for some of the many genetic loci which have been defined for the hereditary spastic paraplegias (SPG) and spinocerebellar ataxias (SCA). Adrenoleukodystrophy has been linked to over 500 different mutations in the ATP-binding cassette ABCD1 gene.

Examination of the cerebrospinal fluid may be required. Depending on the clinical scenario, this may require analysis for cell count, protein, glucose, xanthochromia, oligoclonal bands, serology, cytology, angiotensin converting enzyme, and polymerase chain reaction for infective agents such as viruses and tuberculosis.

Neurophysiological investigations (electromyography (EMG), nerve conduction studies) have little direct role in the diagnosis of cord syndromes, although EMG may be diagnostic for motor neuron disease, but may help to define concurrent radiculopathies or neuropathies which may focus differential diagnostic considerations. Somatosensory evoked potential studies may confirm a clinically defined spinal cord lesion, or provide evidence of a subclinical lesion, for example in multiple sclerosis, as may visual evoked potential studies. However, MRI is more sensitive in this regard. Central motor conduction times to muscles in lower (e.g. tibialis anterior) or upper limb (e.g. abductor digiti minimi) may indicate cord pathology, often being abnormal in transverse myelopathies, but this investigation is not widely available.

Criteria for diagnosis 

Clinical features of some of the more common causes of myelopathy are briefly presented.

The spinal cord is one the sites of predilection for demyelinating diseases. Multiple sclerosis (MS) may present as an isolated cord syndrome, usually partial rather than complete. Clues to the diagnosis may be typical MRI features in the cord, concurrent demyelination on brain MRI, and acellular cerebrospinal fluid with oligoclonal bands. Distinct from this acute presentation is a progressive myelopathy, either following (secondary) or without prior relapsing episodes (primary progressive MS). Neuromyelitis optica (NMO), also known as Devic’s syndrome, is an inflammatory demyelinating disorder of spinal cord and optic nerves, sometimes associated with antibodies to aquaporin-4.

Transverse myelitis most commonly affects the thoracic cord. If complete, there is paralysis, sensory loss, and incontinence, often with an acute flaccid paraparesis or paraplegia. There may be a preceding history of infection. MRI often reveals extensive longitudinal abnormal signal over several contiguous spinal segments, unlike the pattern typical of MS. Differential diagnosis of such ‘longitudinal myelitis’ includes infective (viral), postinfectious, and postvaccination myelitides, and collagen vascular diseases. Cerebrospinal fluid analysis may disclose an infective agent, including coxsackieviruses, polioviruses, enterovirus 71, flaviviruses (Japanese encephalitis, West Nile virus), some of which have a predilection for the anterior horn cells producing a largely or exclusively motor picture and MR signal change confined to the anterior horns. HTLV-1 more typically produces a chronic spastic paraparesis, also known as HTLV-1-associated myelopathy (HAM), and was probably the agent responsible for ‘tropical spastic paraparesis’. The vacuolar myelopathy associated with HIV infection may be overlooked clinically because of other neurological involvement and is often defined only post-mortem. Postinfectious myelitis may be a variant of acute disseminated encephalomyelitis (ADEM). Collagen vascular diseases such as SLE, with or without antiphospholipid antibodies, may be associated, and sometimes presents, with an acute myelitis which, as in the case of postinfectious myelitis, is associated with raised cerebrospinal fluid cell count and protein but without oligoclonal bands. A depressed cerebrospinal fluid glucose level has sometimes been reported in SLE transverse myelitis.

A syndrome of acute necrotizing myelitis, sometimes known as Foix–Alajouanine syndrome, may merge with the severe end of the transverse myelitis spectrum. This condition may be associated with vascular pathologies (see below), or haematological or lung neoplasms, and hence represent a paraneoplastic syndrome, although more usually these latter manifest as an encephalomyelitis. Some episodes of transverse myelitis resist all diagnostic efforts to define their aetiology and hence by a process of exclusion may be classified as idiopathic transverse myelitis, diagnostic criteria for which have been published.

In subacute combined degeneration of the cord due to vitamin B12 (cobalamin) deficiency, myelopathy is due to demyelination of spinal cord white matter tracts, specifically the posterior and lateral columns. MRI of the cervical spinal cord may show evidence of posterior column high signal intensity extending over several segments, unlike the appearances of multiple sclerosis, which resolves with vitamin B12 repletion. Although vitamin B12 deficiency may occur in the context of pernicious anaemia, myelopathy may also occur in the absence of haematological abnormality. A Schilling test to examine B12 absorption may be required. Elevated serum levels of homocysteine and methylmalonic acid, the substrates for cobalamin-dependent enzymes, may be helpful when there is diagnostic uncertainty and vitamin B12 levels are borderline. A concurrent peripheral neuropathy, usually of axonal type, may be clinically and/or neurophysiologically evident. Overuse of nitrous oxide analgesia may produce a similar clinical syndrome, due to functional B12 deficiency, as may acquired copper deficiency, often in the context of intestinal resection. This disorder is associated with low serum copper and caeruloplasmin levels and increased signal in the dorsal columns on MRI. First described in 2001, this may be the human equivalent of swayback disease seen in ruminants with copper deficiency. Vitamin E deficiency may be acquired, in the context of intestinal fat malabsorption, including patients with cystic fibrosis, or result from an autosomal recessive genetic disorder due to mutations in the α-tocopherol gene (OMIM#277460). Ataxia is both cerebellar and spinal in these disorders and may respond to vitamin E supplements.

Other genetic disorders may present with a spinal cord syndrome. Hereditary spastic paraplegia is a heterogeneous group of motor system disorders typified by lower limb spasticity which greatly predominates over weakness. There may in addition be mild diminution of lower limb vibration and proprioception, and in complicated cases there may be additional clinical features such as seizures, cognitive impairment or frank dementia, peripheral neuropathy, amyotrophy, or extrapyramidal features. Most instances are inherited as autosomal dominant disorders although recessive and X-linked variants are described, with over 25 genetic loci (SPG) defined. Deterministic mutations have been discovered in genes encoding the proteins spastin, atlastin, parpalegin, and spartin.

Adrenoleukodystrophy is an X-linked recessive peroxisomal disorder (OMIM#300100) with variable clinical phenotype related to age. Whereas children and adolescents have a cerebral presentation with personality and intellectual changes leading to dementia, young adult males often present with a progressive spastic paraparesis with a mild distal polyneuropathy, adrenomyeloneuropathy (AMN), with delayed cerebral involvement. There may be additional adrenal insufficiency. Positive family history may alert clinicians to the diagnosis. Some female heterozygotes (carriers) may manifest an AMN-like syndrome with mild spastic paraparesis. Cord imaging in AMN may show atrophy but no signal abnormality.

Friedreich’s ataxia, the most common autosomal recessive cerebellar ataxia (OMIM#229300), may present with a spastic paraparesis with extensor plantars accompanied by absent ankle jerks due to the concurrent axonal sensory polyneuropathy. The autosomal dominant cerebellar ataxias form a heterogeneous group, linked to over 25 different genetic loci, many associated with trinucleotide repeat expansions. The phenotype is of a progressive cerebellar syndrome with or without additional neurological features which may include spastic paraparesis.

Although typically an exclusively cognitive disorder, variants of Alzheimer’s disease with spastic paraparesis have been described in association with mutations in the presenilin-1 gene (OMIM#104300), most particularly the exon 9 deletion. These patients also manifest a pathological phenotype, cotton wool plaques of amyloid protein, which although not totally specific are seldom seen in other cases. Familial British dementia, originally described as Worster–Drought syndrome and now characterized as one of the hereditary cerebral amyloid angiopathies, resulting from stop codon mutations in the ITM2B (A-Bri) gene (OMIM#176500), typically presents with presenile dementia which is later complicated by cerebellar ataxia and spastic paraparesis.

Vascular disorders of the spinal cord encompass both arterial infarction and haemorrhage or venous hypertension; venous infarction is uncommon. Cord ischaemia has been postulated to contribute to spondylotic myelopathy and delayed radiation myelopathy. Arterial infarction is most commonly due to anterior spinal artery occlusion, for example during thoraco-abdominal aneurysm repair. In this syndrome, because of the respective watersheds of anterior and posterior spinal arteries, the whole or part of the anterior two-thirds of the cord may be infarcted with loss of descending motor and ascending sensory pathway integrity but with preservation of dorsal column function. Hypoperfusion of the cord may be responsible for the myelopathies associated with fibrocartilaginous embolism, often associated with back injury, and with air embolism in decompression sickness (Caisson disease).

Haemorrhage and/or venous hypertension occur with spinal vascular malformations, which may broadly be divided into dural arteriovenous fistulas (AVF), usually acquired, and arteriovenous malformations (AVM), usually of developmental origin. Spinal dural AVFs typically present in middle age and beyond, most commonly in men, with a progressive painful myelopathy. Venous hypertension results in cord hypoxia which may progress to irreversible necrosis (Foix–Alajouanine syndrome; subacute necrotizing myelopathy). Stepwise progression may occur. In contrast, spinal AVMs tend to present at a younger age than AVFs, with a mean in the third decade but sometimes in childhood. AVMs may be at any cord level, on the surface, within the parenchyma, or both. High-flow lesions may also have arterial aneurysms on the supplying vessels. Spinal haemorrhage is the typical clinical manifestation, presenting with acute painful paraplegia, back pain, sciatica, with or without meningism and disturbance of consciousness; blood may track intracranially, simulating subarachnoid haemorrhage. Progressive neurological dysfunction is less often seen than with AVFs. The presence of a spinal bruit and/or segmentally related cutaneous malformations may give a clue to the presence of an intradural AVM. Spinal vascular malformations may occur in association with similar lesions in other organs or cutaneous angiomas, for example in neurofibromatosis, with haemangioblastomas or cerebral aneurysms, and in specific syndromes (Cobbs, Klippel–Trénaunay–Weber). Cavernous malformations may also occur in the spinal cord.

A syrinx is a fluid-filled cavity within the spinal cord (syringomyelia) or brainstem (syringobulbia) which may be connected to a dilated central canal or separate from it. Most are associated with Chiari-type hindbrain anomalies, sometimes with concurrent hydrocephalus, but there are also associations with spinal trauma, spinal tumours, arachnoiditis, and inflammatory/demyelinating disorders of the spinal cord such as MS and NMO.

Treatment and prognosis 

Treatment of myelopathy is, of course, dependent on establishing aetiology. Structural lesions may require neurosurgical intervention, sometimes acutely to save or salvage cord function. With acute compressive lesions, prognosis is directly related to the time delay between symptom onset and relief of compression. Infective mass lesions may require debridement and systemic antibiotics. Foramen magnum decompression may be undertaken for syringomyelia associated with Chiari malformation. Certain spinal cord vascular malformations may be amenable to endovascular treatment, or targeted (stereotactic) radiotherapy to shrink lesion size and reduce haemorrhagic risk. Radiotherapy of vertebral metastases causing cord compression is often undertaken.

Specific treatment is sometimes available. Vitamin B12 myelopathy may remit with vitamin repletion, although it is well recognized that there is an inverse relationship between duration of deficiency and extent of recovery following repletion. Dysaesthesia and proprioceptive deficits often persist, although these may be related in part to concurrent peripheral nerve involvement. Likewise, with copper deficiency myelopathy neurological decline is halted but seldom reversed by copper repletion. Cord compression with Paget’s disease may respond to specific treatment (bisphosphonates).

Steroids are often prescribed for inflammatory and necrotizing myelitides, sometimes with clinical improvement, although this may simply be a hastening of recovery which would have occurred anyway. Partial syndromes are said to be more likely to improve, complete syndromes less so, perhaps reflecting the fact that the former are more likely to be manifestations of MS. More specific immunosuppressive regimes may be required in SLE, and anticoagulation in the antiphospholipid antibody syndrome.

Residual or progressive deficits in sensorimotor and sphincter function resulting from myelopathy may benefit from targeted symptomatic and neurorehabilitation strategies, including physiotherapy and occupational therapy. Symptom management may include agents for spasticity (oral baclofen, tizanidine, dantrolene; focal injections of botulinum toxin; intrathecal baclofen), pain (antineuropathic pain medications such as pregabalin, gabapentin), bladder dysfunction (anticholinergic medications, clean intermittent self catheterization, suprapubic catheterization), and erectile dysfunction (sildenafil).

Further reading

Top

Al-Deeb SM, et al. (1997). Acute transverse myelitis. A localized form of postinfectious encephalomyelitis. Brain, 120, 1115–22.

Aminoff MJ (1976). Spinal angiomas. Blackwell Scientific, Oxford.

Critchley E, Eisen A (1992). Diseases of the spinal cord. Springer-Verlag, London.

Depienne C, et al. (2007). Hereditary spastic paraplegias: an update. Curr Opin Neurol, 20, 674–80.

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