Category Archives: Neurological Diseases and Diseases of Voluntary Muscle

Cervical and lumbar spondylosis

Spondylosis describes the degenerative changes within vertebrae and intervertebral discs that occur during ageing or secondarily to trauma or rheumatoid disease. The changes are common in the lower cervical and lower lumbar region.
Several, often related, factors are important in producing signs and symptoms, including:
• Osteophytes-local overgrowth of bone
• Congenital narrowing of the spinal canal
• Disc degeneration with posterior or lateral disc protrusion
• Ischaemic changes in the cord and nerve roots The commoner clinical syndromes will be described. In all these syndromes MRI is now the investigation of choice, if available, replacing myelography. Lateral cervical disc protrusion (Fig. 18.22) The patient complains of pain in the upper limb. A C7 protrusion is the commonest lesion. There is root pain (see p. 898), which radiates into the affected myotome(scapula, triceps and forearm extensors in a C7 lesion) and a sensory disturbance (tingling, numbness) in the affected dermatome. There is weakness and, later, wasting of muscles innervated by the affected root (triceps and finger extensors in a C7 lesion) and reflexes using this root will be lost (the triceps jerk in a C7 lesion). Although the initial pain is often severe, most cases recover with rest and analgesics. It is usual to immobilize the neck in a collar. Plain X-rays of the cervical spine(oblique views) show encroachment into the exit foraminae by osteophytes. In cases where recovery is delayed,

Central cervical disc protrusion (cervical myelopathy) Posterior disc protrusion (see Fig. 18.22), which is common at C4/S, CS/6 and C6/7 levels, causes spinal cord compression (see p. 898). Congenital narrowing of the canal, osteophytic bars and ischaemia are contributory
factors. The patient complains of difficulty in walking. Frequentlythere are no symptoms in the neck. A spastic paraparesis (or tetraparesis) is found, with variable sensory loss. A reflex level in the upper limbs and evidence of lateral disc protrusion may coexist.Plain films may show narrowing of the sagittal diameter  of the spinal canal and osteophytes but the changes correlate poorly with signs and symptoms. MRI or myelography is necessary to demonstrate the level and extentof cord compression.  Cervical laminectomy or anterior fusion of the vertebral bodies with removal of the disc may be necessary when the ord compression is severe or progressive. The results of surgery are often disappointing. Recovery of the ‘pyramidal’ signs is unusual, although progression may be halted.
A collar should be fitted. Manipulation of the neck should be avoided.
Thoracic disc protrusion Central protrusion of a thoracic disc is a rare cause of paraparesis.

Lateral lumbar disc protrusion

The LS and S1 roots are commonly compressed by lateral prolapse of the L4/S and LS/S1 discs, respectively. There is low back pain and ‘sciatica’ (pain radiating down the buttock and lower limb). The onset may be acute and follow lifting a heavy weight, or may be subacute and
apparently unrelated to exercise. Straight leg raising is limited. There may be loss of reflexes (ankle jerk in an S1 root lesion or knee jerk in
an L4/S lesion) and weakness of plantar flexion (S1) or extension of the great toe (LS). Sensory loss may be found in the affected dermatome.
Plain films of the lumbar spine show narrowing of the disc space, osteophytes or a narrow canal. Unsuspected malignancy or infection may be demonstrated. Most cases resolve with rest and analgesics. In the minority, MRI or myelography is necessary and laminectomy is indicated when a root lesion is shown. Central lumbar disc protrusion (cauda equina syndrome)
A central disc protrusion causes a lesion of the cauda equina with back pain, weakness of the lower limbs, sacral numbness, retention of urine, impotence and areflexia. Many nerve roots are involved.
The onset is either acute (a cause of an acute flaccid paraparesis) or chronic, when intermittent claudication occurs.

Neoplasms in the lumbosacral region cause a similar picture.
The condition should be suspected if a patient with back pain develops retention of urine. Urgent MRI or myelography followed by decompression is indicated. Spinal stenosis
Narrowing of the lumbar spinal canal produces back painand is an important cause of buttock claudication. Congenital narrowing of the cervical canal predisposes to cervical myelopathy from minor disc protrusion.

Non-metastatic manifestations of malignancy

Many neurological syndromes may accompany malignancy.
Clinical pictures include:
• Sensorimotor neuropathy
• Cerebellar syndrome
• Dementia and encephalopathy
• Myasthenic-myopathic syndrome (Eaton-Lambert syndrome)
• Progressive multifocal leucoencephalopathy
• Mononeuritis multiplex
• Cranial polyneuropathy
• MND variants
• Spastic paraparesis
The cause of most of these remains obscure. The clinical importance is that the neurological syndrome sometimes precedes clinical recognition of the neoplasm, which is often a small-cell carcinoma of the bronchus or a lymphoma. The neurological signs may recede if the tumour is resected or treated.

CLINICAL FEATURES

Fatiguability is the single most important feature. The proximal limb muscles, the extraocular muscles, and the muscles of mastication, speech and facial expression are those commonly affected in the early stages. Respiratory difficulties may occur.
Complex extraocular palsies, ptosis and a typical fluctuating proximal weakness are found. The reflexes are initially preserved but may be fatiguable Muscle wasting is sometimes seen late in the disease. been drug

INVESTIGATION

The clinical picture of fluctuating weakness may bediagnostic but many cases are initially diagnosed as  ‘hysterical’ .
Tensilon (edrophonium) test Edrophonium (an anticholinesterase) 10 mg i.v. is injected as a bolus after a test dose of 1-2 mg. Improvementin weakness occurs within seconds and lasts for 2-3 min  when the test is positive. To be certain it is wise to have an observer present and to perform a control test using an injection of saline.
Occasionally the test itself causes bronchial constriction and syncope. It should not therefore be carried out where there are no facilities for resuscitation. Serum acetylcholine receptor antibodies These are present in 90% of cases of generalized myasthenia gravis. The antibodies are found in no other condition.

Nerve stimulation

There is a characteristic decrement in the evoked muscle action potential following stimulation of the motor nerve. Other tests
Preliminary tests may show a mediastinal mass on chest X-ray that can be confirmed by mediastinal CT scanning. Routine peripheral blood studies are normal (the ESR is not raised). Autoantibodies to striated muscle, intrinsic factor or thyroid may be found. Rheumatoid factor and
antinuclear antibody tests may be positive. Muscle biopsy is usually not performed but ultrastructural abnormalities can be seen.

Diseases of voluntary muscle

Weakness is the predominant feature of a myopathy. Its distribution and pattern is of diagnostic importance. A classification of muscle disease is given in Table 18.56. Only the more common conditions are mentioned below.

PATHOPHYSIOLOGY

Muscle fibres are affected by:
1 Acute inflammation and fibre necrosis (e.g. polymyositis)
2 Chronic degeneration of muscle fibres (e.g. Duchenne muscular dystrophy)
3 Regeneration and fibre hypertrophy  Complex immune and metabolic disorders. For example:
(a) In myasthenia gravis, there is a reduction in the number of available acetylcholine receptors at the neuromuscular junction due to antibodies to the receptor protein.
(b) In myotonias, defective chloride ion membrane conductance is associated with delayed muscle relaxation.
(c) Enzyme defects in the glycolytic pathway (e.g. myophosphorylase deficiency) result in impaired force generation

Acquired myopathies
Inflammatory myopathy
Polymyositis
Alone
With skin lesions (dermatomyositis)
With collagen disease
With malignancy
Viral, bacterial and parasitic infection
Sarcoidosis
Metabolic and endocrine myopathy, due to:
Corticosteroids/Cushing’s syndrome
Thyroid disease
Calcium metabolism disorders
Hypokalaemia
Ethanol
Drugs
Myasthenic disorders
Myasthenia gravis
Myasthenic-myopathic (Eaton-Lambert) syndrome
Genetically determined myopathies
Muscular dystrophies
Duchenne muscular dystrophy
Facio-scapulo-humeral dystrophy
Limb girdle dystrophy
Myotonias
Dystrophia myotonica
Myotonia congenita
Periodic paralyses
Hypokalaemic
Hyperkalaemic
Normokalaemic
Specific metabolic myopathies, e.g.
Myophosphorylase deficiency

Other defects of glycogen and fatty acid metabolism Mitochondrial disease (ragged red muscle fibres) Malignant hyperpyrexia

INVESTIGATION

Diagnosis is possible on clinical grounds alone in some myopathies. The distribution of weakness and the consistency of the muscles should be noted. Serum muscle enzymes
Serum creatine phosphokinase (and aldolase) is greatly elevated in many dystrophies (e.g. Duchenne muscular dystrophy) and in inflammatory disorders of muscle (e.g. polymyositis). These enzymes are normal in myasthenia, and are usually normal in myotonias and chronic partialdenervation.
Electr omyography
When a muscle is weak the normal interference pattern is reduced. An electromyogram is useful to distinguish between primary muscle disease and denervation (e.g. MND). The principal abnormalities are:
MYOPATHY. Short duration ‘spiky’ polyphasic muscle action potentials are seen. Spontaneous fibrillation is occasionally recorded.
DENERVATION. Fibrillation potentials of about 1 ms in duration and 50-200 I.N. in amplitude are seen, and are evidence of reinnervation.
OTHER CHANGES. Myotonic discharges (in myotonias) consist of high-frequency activity that varies repeatedly to cause a characteristic sound on the loudspeaker. In myasthenia gravis a characteristic decrement in the evoked muscle action potential follows stimulation of the motor nerve. The reverse is seen (an increment in repetitive response) in the rare myasthenic-myopathic syndrome (Eaton-Lambert syndrome), which may accompany carcinoma of the bronchus.Muscle biopsy
Information about muscle fibre types (type 1, slow; type 2, fast), denervation, inflammation, dystrophic changes and muscle histochemistry is obtained by muscle biopsy. Electron microscopy is sometimes necessary. In chronic partial denervation, ‘fibre type grouping’, i.e. groups of atrophic fibres of the same fibre type, is seen. Hypertrophic fibres also occur. In acute denervation, small angulated fibres are seen scattered randomly between normal fibres. In dystrophies and myositis, the muscle fibres are diffusely abnormal, the nuclei become  central, and invasion by inflammatory cells and/ornecrosis occurs.  Considerable experience is required to assess these changes accurately.

INFLAMMATORY MYOPATHIES

Polymyositis

This group of disorders is characterized by non-suppurative inflammation of skeletal muscle. The muscles are weak and usually painful. In many cases there are skin changes (dermatomyositis, see p.404) or other connective tissue diseases.

CLINICAL FEATURES

‘Polymyositis alone’ is a rare disease, most common in the fourth and fifth decades. Symptoms are of difficulty in rising from a chair, climbing stairs or lifting. Weakness is typically proximal. The weak muscles ache and are sometimes tender and indurated.

As the disease progresses there may be widespread weakness and wasting, with dysphagia, respiratory muscle weakness and cardiac involvement.

INVESTIGATION

Preliminary investigations show a raised ESR and a mild normochromic normocytic anaemia. ANF is sometimes positive. The serum creatine phosphokinase is usually (but not always) elevated.
The electromyogram shows myopathic changes. Occasionally fibrillation potentials occur and may cause diagnostic difficulty.
Muscle biopsy shows inflammatory changes with infiltration of the muscle by mononuclear cells.

DIFFERENTIAL DIAGNOSIS

Muscular dystrophies rarely progress as rapidly as polymyositis and there is no muscle pain. Pseudohypertrophy does not occur in polymyositis and there is no family history.
MND is always eventually accompanied by upper motor neurone signs, and prominent fasciculation is common.

TREATMENT

Corticosteroids and/or azathioprine or cyclophosphamide reduce the symptoms in about 75% of cases. Only rarely does the disease progress to cause grave disability or death from respiratory failure or cardiac involvement. Other inflammatory myopathies Muscle pain and weakness occur in trichinosis due to the ingestion of pork infected with Trichinella spiralis. Acute myositis also occurs with Coxsackievirus infections(see p. 51) and in several other infections.  Tropical pyomyositis of Central Africa is suppurative inflammation of muscle caused by staphylococci and other organisms.
An inflammatory myopathy may occur in sarcoidosis.

METABOLIC AND ENDOCRINE

MYOPATHIES

Corticosteroids and Cushing’s syndrome Proximal muscle weakness occurs with prolonged highdose steroid therapy (particularly with 9a-fluorinated steroids such as dexamethasone and triamcinolone) and in Cushing’s syndrome. Selective type-2 fibre atrophy is seen on muscle biopsy. Thyroid disease (see p. 800) Several muscle diseases may occur:
THYROTOXICOSIs is sometimes accompanied by a severe proximal myopathy. There is also an association between thyrotoxicosis and myasthenia gravis, and between thyrotoxicosis and hypokalaemic periodic paralysis. Both associations are seen more frequently in South East Asia.

IN OPHTHALMIC GRAVES’ DISEASE, there is swelling and lymphocytic infiltration of the extraocular muscles (see p. 807).
HYPOTHYROIDISM is sometimes associated with  uscle pain and stiffness, resembling myotonia. A true proximal myopathy also occurs.
Disorders of calcium metabolism Proximal myopathy may occur in osteomalacia of any cause .

Hypokalaemia

Acute hypokalaemia (e.g. in diuretic therapy) causes a severe flaccid paralysis (periodic paralysis, see p. 510) that  s reversed by correcting the electrolyte disturbance. Chronic mild hypokalaemia (also commonly caused by diuretics) gives rise to a mild, mainly proximal, weakness. Alcohol
Severe my pathy with muscle pain, necrosis and myoglobinuriaoccurs in acute alcoholic excess. (A similar syndrome  occurs in diamorphine and amphetamine addicts.) A subacute proximal myopathy occurs with chronic alcohol abuse. Drugs Many drug-induced muscle disorders have
described . Most respond to withdrawal.

DISORDERS OF THE NEUROMUSCULAR JUNCTION

Myasthenia gravis

This acquired condition is characterized by weakness and fatiguability of proximal limb, ocular and bulbar muscles. The heart is not affected.
The cause is unknown. IgG antibodies to ac tylcholine receptor protein are found. Immune complexes (IgG and complement) are deposited at the postsynaptic membranes causing interference with and later destruction of the acetylcholine receptor.
Thymic hyperplasia is found in 70% of myasthenic patients below the age of 40 years. In 10% of patients a thymic tumour is found, the incidence increasing with age; antibodies to striated muscle can be demonstrated in these patients. Young patients without a thymoma havean increased association with HLA-B8, DR3.
There is an association between myasthenia gravis and thyroid disease, rheumatoid disease, pernicious anaemia and SLE. Myasthenia gravis is sometimes caused by Dpenicillamine treatment in rheumatoid disease.
The prevalence is about 4 in 100000. It is twice as common in women as in men, with a peale incidence around the age of 30 years.

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CLINICAL FEATURES

Fatiguability is the single most important feature. The proximal limb muscles, the extraocular muscles, and the muscles of mastication, speech and facial expression are those commonly affected in the early stages. Respiratory difficulties may occur.
Complex extraocular palsies, ptosis and a typical fluctuating roximal weakness are found. The reflexes are initially preserved but may be fatiguable. Muscle wasting is sometimes seen late in the disease.
been drug
INVESTIGATION
The clinical picture of fluctuating weakness may be diagnostic but many cases are initially diagnosed as ‘hysterical’ .
Tensilon (edrophonium) test Edrophonium (an anticholinesterase) 10 mg i.v. is injected as a bolus after a test dose of 1-2 mg. Improvement in weakness occurs within seconds and lasts for 2-3 min when the test is positive. To be certain it is wise to have an observer present and to perform a control test using an injection of saline.
Occasionally the test itself causes bronchial constriction and syncope. It should not therefore be carried out where there are no facilities for resuscitation. Serum acetylcholine receptor antibodies These are present in 90% of cases of generalized myasthenia gravis. The antibodies are found in no other condition.

Nerve stimulation

There is a characteristic decrement in the evoked muscle action potential following stimulation of the motor nerve. Other tests
Preliminary tests may show a mediastinal mass on chest X-ray that can be confirmed by mediastinal CT scanning. Routine peripheral blood studies are normal (the ESR is not raised). Autoantibodies to striated muscle, intrinsic factor or thyroid may be found. Rheumatoid factor and
antinuclear antibody tests may be positive. Muscle biopsy is usually not performed but ultrastructural abnormalities can be seen.

COURSE AND MANAGEMENT

The severity of myasthenia gravis fluctuates but most cases have a protracted course. It is important to recognize respiratory impairment, dysphagia and nasal regurgitation; emergency assisted ventilation may be required in myasthenic crises.
Exacerbations are usually unpredictable but may be brought on by infections, by aminoglycosides or other drugs. Enemas (magnesium sulphate) may provoke severe weakness.
Oral anticholinesterases
Pyridostigmine (60 mg tablet) is the most widely used drug. Its duration of action is 3-4 hours. The dose (usually 4-16 tablets daily) is determined by the patient’s esponse. This drug prolongs the action of acetylcholine by inhibiting th e action of the enzyme cholinesterase. Overdose of anticholinesterase causes severe weakness (cholinergic crisis). Colic and diarrhoea may occur with antich linesterases. Oral atropine 0.5 mg with each dose may reduce his.
Although anticholinesterases are of value in treating the weakness, they do not alter the natural history of the disease.

Thymectomy

Thymectomy offers long-term benefit, though the reason is uncertain. It improves the prognosis, particularly in patients below 40 years with positive receptor antibodies and in those who have had the disease for less than 10 years.
Following thymectomy, some 60% of non-thymoma cases improve. If a thymoma is present, surgery is necessary to remove a potentially malignant tumour, but it is unusual for the myasthenia to improve.
Immunosuppressant drugs Corticosteroids are used when there is an incomplete response to anticholinesterases. There is improvement in70% of cases, although this may be preceded by anin itial relapse.
Azathioprine (and sometimes plasmapheresis) is co bined with prednisolone in steroid-resistant cases.

Myasthenic-myopathic syndrome (Eaton-Lambert syndrome

This is a rare non-metastatic manifestation of small-cell carcinoma of the bronchus. There is defective acetylcholine release at the neuromuscular junction. Proximal muscle weakness, sometimes involving the ocular and bulbar muscles, is found, with absent reflexes. Weakness tends to improve after muscular contraction (unlike myasthenia gravis).
Other myasthenic syndromes Other rare myasthenic syndromes occur, for example congenital myasthenia.

MUSCULAR DYSTROPHIES

These are progressive, genetically determined disorders of skeletal and sometimes cardiac muscle. Duchenne muscular dystrophy (DMD) This is inherited as an X-linked recessive disorder, but one-third of cases arise by spontaneous mutation. It  ccurs in 1 in 3000 male infants. Recently the DMD locus has been localized to the Xp21 regio  of the X chromosome and the disease is characterized by the absence of the gene product-the protein dystrophin, which is a rod-shaped cytoskeletal protein found in muscle. DMD is usually obvious by the fourth year, and causes death by the age of 20 years.

CLINICAL FEATURES

The boy has difficulty in running and in rising to an erect position, when he has to ‘climb up his legs with his hands’ (Cowers’ sign).
There is initially a proximal limb weakness with pseudohypertrophy of the calves. The myocardium is affected. The boy becomes severely disabled by 10 years.

INVESTIGATION

The diagnosis is often made on clinical grounds alone. The creatine phosphokinase is grossly elevated (100- 200 times the normal level). Muscle biopsy shows characteristic variation in fibre size, fibre necrosis, regeneration and replacement by fat, and on immunochemical stainingan absence of dystrophin. The electromyogram shows a myopat ic pattern.

MANAGEMENT

There is no curative treatment. Passive physiotherapy helps to prevent contractures in the later stages of the disease. A trial of prednisolone therapy has shown a short-term improvement in muscle strength and
function.

Carrier detection

A female with an affected brother has a 50% chance of carrying the gene. In carrier females, 70% have a raised creatine phosphokinase level and the remainder usually have electro myographic abnormalities or changes on biopsy. Accurate carrier and prenatal diagnosis can be made using cDNA probes that are co-inherited with the DMD locus.
Genetic advice explaining the inheritance of the condition and counselling about abortion should be given. Determination of the fetal sex by amniocentesis and selective abortion of a male fetus is sometimes carried out. Many proven carrier females choose not to have offspring.
Limb girdle and facio-scapulohumeral dystrophy
These milder dystrophies are summarized in Table 18.58. There are many other varieties of muscular dystrophy.

MYOTONIAS

These conditions are characterized by myotonia, i.e. continued muscle contraction after the cessation of voluntary effort. The electromyogram is characteristic (see p. 951). The myotonias are important because patients tolerate general anaesthetics poorly. The commonest two of theserare conditions are mentioned below.  Dystrophia myotonica Myotonia congenita (Thomsen’s disease)
This is an autosomal dominant disorder. An isolated myotonia, usually mild, occurs in childhood and persists throughout life. The myotonia is accentuated by rest and by cold. Diffuse muscle hypertrophy occurs and the patient appears to have well-developed muscles. PERIODIC PARALYSES These are rare membrane disorders characterized by intermittent flaccid muscle wealcness and alterations in serum potassium.
Hypokalaemic periodic paralysis This condition, usually inherited as an autosomal dominant trait, is characterized by generalized wealcness (including the speech and bulbar muscles) that often starts after a heavy carbohydrate meal or after a period of rest after exertion. Attacks last for several hours. It is often first noted in the teenage years and tends to remit after the age of 35 years. The serum potassium is usually below 3.0 mmol litre ” in an attack. The wealcness responds to the administration of potassium chloride. Similar wealcness also occurs in hypokalaemia due to diuretics, and may occur during thyrotoxicosis.

Hyperkalaemic periodic paralysis

This condition, usually inherited as an autosomal dominant trait, is characterized by sudden attacks of wealcness that are sometimes precipitated by exercise. Attacks start in childhood and tend to remit after the age of 20 years. They last from 30 min to 2 hours. Myotonia may occur. The serum potassium is raised.The attacks are terminated by intravenous calcium  gluconate or chloride.
A very rare normokalaemic, sodium-responsive periodic paralysis also occurs.

SPECIFIC METABOLIC MYOPATHIES
This is a large group of rare, genetically determined muscle diseases. Two of these diseases will be mentioned here.
Myophosphorylase deficiency (McArdle’s syndrome)
This is an autosomal recessive disorder in which there isa lack of skeletal muscle myophosphorylase. The disorder  causes easy fatiguability and severe cram on exercise, with myoglobinuria. There is no rise in venous lactate during ischaemic exercise; this forms the basis of a test for the condition. Malignant hyperpyrexia Widespread skeletal muscle rigidity and hyperpyrexia developing as a sequel to general anaesthesia is due to a genetic defect in the calcium release channel of the sarcoplasmic reticulum. Sudden death during or after anaesthesia may occur in this rare condition, which is some times inherited as an autosomal dominant trait. Dantrolene is useful in controlling the rigidity.

Diseases of the peripheral nerves

The different nerve fibre types within a peripheral nerveare shown in Table 18.49. All are myelinated except the  C fibres, which carry impulses from painful stimuli. Two pathological processes affect peripheral nervesaxonal (the axon itself) degeneration and demyelination(the myelin sheath). Neuropathies are classified broadly  into which of the two processes predominate. Wallerian degeneration refers to the changes seen after section of a nerve.
Axonal degeneration
Axonal degeneration occurs after a nerve has been sectioned or its axon severely damaged. Within 7-10 days the axon and the myelin sheath distal to the injur  degenerate and ar in excitable electrically. When a motor nerve is damaged there is atrophy of the muscle fibres inthe motor units it supplies. Denervation may be detected  by recording fibrillation potentials on electromyography. Regeneration occurs by axonal growth down the nerve sheath and axonal sprouting from the stump. Growth takes place at a rate of up to 1 mm daily. In a chronic neurop athic process (e.g. MND or polyneuropathy), sprouts from the terminal axons of normal motor axons reinnervate the denervated muscle fibres; giant polyphasic units are then seen on electromyography. Demyelination
Here damage to the myelin sheath (the axon itself is  nitially preserved) causes conduction block or marked  lowing of conduction; this can be used to distinguish demyelination from axonal degeneration. Local demyelination is caused by pressure (compression and entrapment neuropathies) or by inflammation (e.g. Guillain-
Barre syndrome).

Definitions

NEUROPATHY means a pathological process affecting a peripheral nerve or nerves.
MONONEUROPATHY is a process affecting a single nerve, and multiple mononeuropathy (or mononeuritis multiplex) is a process affecting several or multiple nerves.
POLYNEUROPATHY is a diffuse, symmetrical disease process, usually progressing proximally. It is either acute, subacute or chronic. Its course may be progressive, relapsing or towards recovery. Polyneuropathy may be motor, sensory, sensorimotor (mixed) or autonomic.RADIe ULOPATHY means a disease process affecting the  nerve roots.

MONONEUROPATHIES
Peripheral nerve compression and
entrapment (Table 18.50)
Damage to a nerve by compression is either acute (e.g. due to a tourniquet or other sustained pressure) or chronic (entrapment neuropathy). In both, demyelination predominates, but some axonal degeneration occurs.

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Acute compression usually affects nerves which are exposed anatomically (e.g. the common peroneal nerve at the head of the fibula).
Entrapment occurs where a nerve passes through relatively tight anatomical passages (e.g. the carpal tunnel). These conditions are diagnosed largely from the clinical features. Diagnosis is confirmed by nerve conduction studies and electromyography. The commoner conditions are mentioned below.
Median nerve compression at the wrist (carpal tunnel syndrome)
This common syndrome is sometimes seen in:
• Hypothyroidism
• Diabetes mellitus
• Pregnancy and obesity
• Rheumatoid arthritis
• Acromegaly
The condition is, however, usually idiopathic. It causes nocturnal tingling and pain in the hand (and sometimes forearm) followed by weakness of the thenar muscles. Wasting of abductor pollicis brevis develops, with sensory loss of the palm and radial three-and-a-half fingers. Tinel’s sign may be positive, i.e. tapping on the carpaltunnel will reproduce the pain.  Treatment with a splint at night or a local steroid injection in the wrist gives temporary relief. When the condition occurs in pregnancy (due to fluid retention) it is often self-limiting. Surgical decompression of the carpel tunnel is a simple and definitive treatment.
Ulnar nerve compression This typically occurs at the elbow, where the nerve is compressed in the cubital tunnel. It follows fracture ofthe ulna or prolonged or recurrent pressure on the nerve  at this site.
Wasting of the ulnar-innervated muscles develops (hypothenar muscles and interossei) together with sensory loss in the ulnar one-and-a-half fingers. Decompression and transposition of the nerve at theelbow may be necessary.  The deep (solely motor) branch of the ulnar nerve maybe damaged in the palm by recurrent pressure from tools  (e.g. screwdrivers), crutches or cycle handlebars. Radial nerve compression
The radial nerve is compressed acutely against the humerus, e.g. when the arm is draped over a hard chair for several hours (‘Saturday night palsy’). Wrist drop and weakness of finger extension and of the brachioradialis muscle follow. Recovery is usual within 1-3 months. Meralgia paraesthetica
Burning, tingling and numbness on the anterolateral aspect of the thigh is caused by entrapment of the lateral cutaneous nerve of the thigh beneath the inguinal ligament.
Many of the patients are obese; weight reduction helps to relieve the symptoms. Division of the inguinal ligament is not usually effective.
Common peroneal nerve palsy When the common peroneal nerve is compressed against the head of the fibula (owing to prolonged squatting,
wearing plaster casts, prolonged bed rest or coma) there is foot drop and weakness of eversion. A patch of numbness on the anterolateral border of the shin or dorsum of the foot may be found. Recovery is usual (but not invariable) within several months. Multiple mononeuropathy
(mononeuritis multiplex) Multiple mononeuropathy occurs in:
• Diabetes mellitus
• Leprosy (still the commonest worldwide)
• Connective tissue disease (polyarteritis nodosa, SLE, giant-cell arteritis, rheumatoid arthritis)
• Sarcoidosis
• Malignancy
• Amyloidosis
• Neurofibromatosis
• AIDS
Diagnosis is largely clinical, supported by electrical studies.

 Treatment is that of the underlying disease.
POLYNEUROPATHIES
Although many toxins and disease processes are known to be associated with polyneuropathy (see below), the cause of the majority of cases remains undetermined. The commonest presentation is a chronic or subacute sensorimotor neuropathy. A classification of polyneuropathy. Idiopathic chronic sensorimotor neu ropath ies
The patient complains of a progressive symmetrical umbness and tingling in the hands and feet, which spreads proximally in a ‘glove and stocking’ distribution. There is distal weakness, which also ascends. Rarely the cranial nerves may be affected. Tendon reflexes involving affected nerves are lost. The symptoms may progress over many months, remain static or remit at any stage. Autonomicfeatures are sometimes seen.
Investigati on (nerve conduction studies, electromyography) of the neuropathy shows either axonal degeneration or demyelination, or features of both of these processes. Some cases of demyelinating (not axonal) chronic sensorimotor neuropathy respond to steroid or immunosuppressive therapy.

Idiopathic chronic sensorimotor neuropathies Postinfective neuropathy (Guillain-Barre syndrome) Drugsltoxic, metabolic and vitamin-deficiency neuropathies

Neoplastic neuropathies

Neuropathies in connective tissue diseases Autonomic neuropathies
Hereditary sensorimotor neuropathies ostinfective polyneu ropathy
(Guillain-Barre syndrome, acute inflammatory neuropathy)

CLINICAL FEATURES

This demyelinating neuropathy, which is the commonestrecognizable acute neuropathy has an autoallergic basis.  It follows 1-3 weeks after a viral infection that is often trivial. The patient complains of weakness of distal limb muscles or distal numbness. This ascends over several days or weeks. In mild cases there is little disability, but in some 20% of cases the respiratory and facial muscles are affected and the patient may become paralysed. Weakness, areflexia and sensory loss are found (i.e. an ascending weakness).
Autonomic features (see below) are sometimes seen. There is a rare proximal form of the condition that initially affects the ocular muscles and in which ataxia is found (Miller-Fisher syndrome).
DIAGNOSIS This is established on clinical grounds and is confirmed  by nerve conduction studies, which show the slowing of conduction or conduction block seen in demyelinating neuropathies. The CSF contains a normal cell count and sugar level but the protein is frequently raised to 1-3 g litre “,
The differential diagnosis includes other paralytic illnesses such as poliomyelitis, botulism or primary muscle disease.

TREATMENT AND COURSE

High dosage intravenous y-globulin reduces the duration and severity and should be given to all patients. Supportive treatment is essential, with particular attention being paid to compensating for weakness of the
respiratory and bulbar muscles. Ventilation may be necessary.
Corticosteroids are sometimes used to treat the Guillain-Barre syndrome but are not of proven value. Plasmapheresis has been shown to be of proven benefit in shortening the period of disability.
Recovery, though gradual over many months, is usual but may be incomplete.

Diphtheria

Demyelinating neuropathy is sometimes caused by the exotoxin of Corynebacterium diphtheriae. Palatal weakness followed by pupillary paralysis and a sensorimotor neuropathy occur several weeks after faucial infection. The condition is now rare in countries where immunization against diphtheria is practised.

Metabolic, toxic and vitamindeficiency neuropathies

The commoner of these neuropathies . All are due to impairment of normal metabolism of the axon, myelin or both.
METABOLIC NEUROPATHIES Diabetes mellitus
Several varieties of neuropathy occur in diabetes mellitus:
1 Symmetrical sensory polyneuropathy
2 Acute painful neuropathy
3 Mononeuropathy and ultiple mononeuropathy
(a) Cranial nerve lesions
(b) Isolated peripheral nerve lesions, e.g. median
4 Diabetic amyotrophy
5 Autonomic neuropathy
.
Uraemia

Progressive sensorimotor neuropathy occurs in chronic uraemia. The response to dialysis is variable but the neuropathy usually improves after renal transplantation. Thyroid disease
A mild chronic sensorimotor neuropathy is sometimes seen in both hyperthyroidism and hypothyroidism. Porphyria
Acute intermittent porphyria is a rare metabolic disorder (see p. 866) in which there are episodes of a severe, mainly proximal, neuropathy, sometimes associated with abdominal pain, confusion and later coma. Alcohol and barbiturates may precipitate attacks.Amyloidosis.

Refsum’s disease

This is a rare condition inherited as an autosomal recessive trait. There is a sensorimotor polyneuropathy with ataxia, retinal damage and deafness. It is due to a defect in the metabolism of phytanic acid.

TOXIC NEUROPATHIES

Alcohol

A polyneuropathy, mainly in the lower limbs, occurs in chronic alcoholics. Calf pain is common. The response to abstention is variable. Thiamine should be given.

Drugs

Many drugs have been reported to be associated with apolyneuropathy. The more important ones.

Industrial toxins

A wide variety of industrial toxins have been shown tocause polyneuropathy:  LEAD POISONING causes a motor neuropathy. ACRYLAMIDE (PLASTICS INDUSTRY), TRICHLORETHYLENE (A SOLVENT), HEXANE AND OTHER FAT-SOLUBLE HYDROCARBONS (e.g. those inhaled in glue-sniffing, see p. 985) cause a progressive polyneuropathy. ARSENIC AND THALLIUM cause a polyneuropathy. VITAMIN-DEFICIENCY NEUROPATHIES Vitamin deficiencies are an important cause of disease of the nervous system because they are potentially reversible if treated early (and progressive if not). They occur in malnutrition, when they are commonly multiple. Thiamine (vitamin B\)
Deficiency causes the clinical syndrome of beri-beri (see p. 162). The principal features are polyneuropathy, an amnesic syndrome (Wernicke-Korsakoff psychosis) and cardiac failure. Alcohol abuse is the commonest cause in Western countries. Other neurological  onsequences of alcohol are summarized.

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WERNICKE-KoRSAKOFF SYNDROME. This important syndrome is an acute or gradual encephalopathy associated with alcohol abuse and other causes of thiamine deficiency. The typical triad comprises ocular signs, ataxia and a confusional state, but the condition occurs in partialforms. It is due to ischaemic damage to the brain stem and its connections. Clinical features include: OCULAR SIGNS. Nystagmus, bilateral lateral rectus palsies, conjugate gaze palsies, fixed pupils and, rarely,papilloedema are found. ATAX IA. There is a broad-based gait, cerebellar signs in the limbs and vestibular paralysis (absent response to
caloric stimulation). CONFUSION. Apathy, decreased awareness or restlessness, amnesia, stupor and coma occur. ypothermia and hypotension due to hypothalamic damage are rare findings.
The condition is underdiagnosed. Erythrocyte transketolase activity is reduced but is of limited practical value because the measurement is rarely available. Thiamine (i.m. or i.v.) should be given immediately if the diagnosis is in question: it is harmless, the condition is not. Untreated Wernicke-Korsakoff syndrome commonly leads to a severe irreversible amnesic syndrome and residual brain stem signs. Pyridoxine (vitamin B6) Deficiency causes a mainly sensory neuropathy (seep. 164). It may be precipitated during isoniazid therapy  for tuberculosis in those who acetylate the drug slowly.

Acute intoxication

Disturbance of balance, gait and speech Coma
Head injury and its sequelae
Alcohol withdrawal
‘Morning shakes’
Tremor of arms and legs
Delirium tremens
Thiamine deficiency
Polyneuropathy
Wernicke-Korsakoff syndrome
Epilepsy
Acute intoxication
Alcohol withdrawal
Hypoglycaemia
Cerebellar degeneration
Cerebral infarction
Cerebra I atrophy
Dementia
Central pontine myelinolysis
Marchiafava-Bignami syndrome (a rare degeneration of the corpus callosum)

Vitamin B12

Deficiency causes disease of the brain, spinal cord and peripheral nerves.
SUBACUTE COMBINED DEGENERATION OF THE CORD. This syndrome of the spinal cord is a sequel of Addisonian pernicious anaemia and rarely other causes of vitamin B12 deficiency (see p. 306). It is frequently associated with a polyneuropathy. The patient complains initially of numbness and tingling of the extremities. The signs are of distal sensory loss (particularly posterior column) with absent ankle jerks (due to the neuropathy) combined with evidence of cord disease (exaggerated knee-jerk reflexes, extensor plantar responses). Optic atrophy and retinal haemorrhage may occur. In the later stages sphincter disturbance, weakness and dementia are seen.
Macrocytosis and megaloblastic changes in the bone arrow are invariable in subacute combined degeneration of the cord. The cause of the B’2 deficiency should be established (see p. 305). Treatment with parenteral B12 reverses the peripheral nerve damage but has little effecton the eN5 (cord and brain) signs.  Neoplastic neuropathy
Polyneuropathy is sometimes seen as a non-metastatic manifestation of malignancy (see p. 950). In myeloma and other dysproteinaemic states polyneuropathy occurs, probably owing to impaired perfusion of nerve trunks or to demyelination associated with allergic reactions within peripheral nerves. P0 EM5 s YN D ROM E is characterized by a chronic
inflammatory demelinating Polyneuropathy, Organomegaly (hepatomegaly 50%), Endocrinopathy (gynaecomastia and atrophic testes), an M protein band on electrophoresis with less than 5% of plasma cells in the bone marrow and Skin hyperpigmentation. Chemotherapy is used.
Neuropathies associated with connective tissue diseases Neuropathy occurs in 5LE, polyarteritis nodosa, rheumatoid disease and giant-cell arteritis owing to microinfarction of peripheral nerves. This presents either as a multiple mononeuropathy or a symmetrical sensorimotor neuropathy.

Autonomic neuropathy

Autonomic neuropathy causes postural hypotension, retention of urine, impotence, diarrhoea (or occasionally constipation), diminished sweating, impaired pupillary responses and cardiac arrhythmia. Many varieties of neuropathy affect autonomic function to a mild, and often subclinical, degree. Occasionally, when there is damage to small myelinated and nonmyelinated B and C fibres, the clinical features of the
autonomic neuropathy predominate. This situation may occur in diabetes mellitus, in amyloidosis and in the Guillain- Barre syndrome.

Cervical rib (thoracic outlet syndrome)

A fibrous band or cervical rib extending from the tip of the transverse process of C7 to the first rib stretches the lower roots of the brachial plexus (C8 and Tl). There is pain along the ulnar border of the forearm, and sensory loss initially in the distribution of Tl with wasting of thethenar muscles, principally the abductor pollicis brevis mu scle. Horner’s syndrome may occur. The rib or band can be excised.
In other patients the rib or band causes subclavan artery or venous occlusion. The neurological and vascular problems rarely occur together.
Neuralgic amyotrophy This is a condition in which severe pain in the muscles of the shoulder is followed by wasting, usually of theinfraspinatus, supraspinatus, deltoid and serratus anterior
mu cles (a ‘brachial plexus neuropathy’). The cause is unknown but, since the condition follows viral infection or immunization in some cases, an allergic basis is postulated.
Recovery of the wasted muscles occurs over some months.

Malignant infiltration

Metastatic disease of nerve roots of the brachial or lumbosacral plexus causes a painful radiculopathy.

Plexus

Trauma
Malignant infiltration
Cervical rib
Neuralgic amyotrophy
Nerve root
Trauma
Herpes zoster
Meningeal inflammation (e.g. syphilis)
Tumours (neurofibroma, metastases)
Cervical and lumbar spondylosis

A common example is an apical bronchial neoplasm (Pancoast’s tumour) that causes a T1 lesion and involves the sympathetic outflow. There is wasting of the small muscles of the hand, pain and sensory loss in areas supplied by Tl and ipsilateral Horner’s syndrome. This condition also occasionally occurs in apical tuberculosis.

Facial pain

The face is richly supplied with pain-sensitive structures the teeth, gums, sinuses, temporomandibular joints, jaw and eyes-disease of which causes facial pain. Facial pain is also caused by some specific neurological conditions; these are mentioned below.

Migrainous neuralgia (cluster headache)

This condition, which is distinct from migraine despite its name, causes recurrent bouts of excruciating pain that wake the patient at night and are centred around one eye. It affects adults in the third and fourth decades and is more common in men. Alcohol sometimes precipitates an attack. The pain lasts for several hours. Vomiting occurs. The face and nostril feel congested. A transient ipsilateral Horner’s syndrome is common during the attack. Despite the pain there are no serious sequelae. Treatment of the attack with analgesics is unhelpful. Prophylactic drugs for migraine are of little value. Lithium carbonate sometimes has a dramatic effect in preventing attacks: the drug level should be monitored carefully. Atypical facial pain
Facial pain for which no cause can be found is seen in the elderly, mainly in women. It is believed to be a somatic equivalent of depression. Tricyclic antidepressants are sometimes helpful.
Other causes
Facial pain occurs in usual variants of migraine and in giant-cell arteritis (see below). Giant-cell arteritis (cranial arteritis,temporal arteritis) (see p. 406)  This important syndrome is a granulomatous arteritis of unknown aetiology occurring chiefly in those over the age of 0 years and affecting in particular the extradural arteries. Other forms of arteritis, e.g. SLE (see p. 400) and polyarteritis nodosa (see p. 406) can present with similar features but with a more generalized arteritis affecting intracranial arteries and vasa nervorum of the cranialnerves. Giant-cell arteritis is closely related to polymyalgia  and these can occur in the same patient.

CLINICAL FEATURES

Headache

Headache is almost invariable. It is felt over the inflamed superficial, temporal or occipital arteries. Touching the kin over the inflamed vessel (e.g. combing the hair) causes pain. The arterial pulsation is soon lost and the artery becomes hard, tortuous and thickened. The skinover the vessels may be red. Rarely, gangrenous patches  appear in the scalp.
Facial pain
Pain in the face, jaw and mouth occurs and is caused by inflammation of the facial, maxillary and lingual branches of the external carotid artery. Pain is characteristically worse on eating (jaw claudication). Opening the mouth and protruding the tongue is difficult. A painful, ischaemic tongue occasionally occurs.

Visual problems

Visual loss due to inflammation and occlusion of the ciliary and/or central retinal artery occurs in 25% of untreated cases. The patient complains of sudden uniocular visual loss, either partial or complete, which is painless. Amaurosis fugax (see p.906) may precede total visual loss, which is usually permanent.
When the ciliary vessels are affected, the optic disc becomes swollen and pale (see p. 882). The retinal branch vessels are usually normal. If the central retinal artery is occluded, there is sudden unilateral blindness, pallor of the disc and retinal ischaemia.Systemic features
Generalized limb pains, proximal limb  girdle pain and tenderness, without joint effusion, i.e. polymyalgia rheumatica (see p. 406), occurs in half the cases. Weight loss, sweating and malaise also occur.

Rare complications

Brain stem ischaemia, cortical blindness, ischaemic neuropathy of peripheral nerves, cranial nerve lesions, and involvement of the aorta, coronary, renal and mesenteric arteries are sometimes seen.

INVESTIGATION

The ESR is greatly elevated, 60-100 rom hour-I being common, although very rarely the ESR is normal. Plasma u2-globulins are raised and the albumin is occasionally reduced. Normochromic normocytic anaemia occurs. The diagnosis is usually confirmed by biopsy of a superficial temporal artery. A 1 em (or greater) segment should be excised because the characteristic granulomatous changes within the walls (lymphocytes, plasma cells, multinucleate giant cells, destruction of the internal elastic lamina) may be patchy.

TREATMENT

The diagnosis should be established without delaybecause of the risk of blindness. High doses of steroids  (prednisolone, initially 60-100 mg daily) should be started immediately in a patient with typical features even before the biopsy. The dose is reduced as the ESR falls. A characteristic of the condition is that the headache subsides within hours of the first large dose of steroid. It is usually possible to stop steroid treatment after some months to several years.

Head injury

There are 200-300 admissions annually for head injuryper 100000 population in most Western countries: 10 people per  100000 die annually and the prevalence of survivors with a major persisting handicap is of the order of a 100 per 100 000. Road traffic accidents and alcohol abuse are the principal aetiological factors in this major cause of morbidity and mortality.

Skull fractures

Linear skull fracture of the vault or base is an indicationof the severity of injury, but is not necessarily associated  with any neurological sequelae. Healing takes place and surgical intervention is usually unnecessary.
Depressed skull fracture of the vault is followed by a high incidence of post-traumatic epilepsy (see p.913). Surgical elevation and debridement are usually necessary. The principal local complications of skull fracture are:
RUPTURE OF A MENINGEAL ARTERY, causing an extradural haematoma (see p. 911).
TEARING OF DURAL VEINS, causing SDH (see p.911) or CSF rhinorrhoea and otorrhoea with its risk of meningitis.

Brain damage

Older classifications attempted to separate ‘concussion’,in which transient coma was followed by complete recovery,  from brain contusion after which there were prolonged coma and focal signs. There is little pathological support for this. The mechanisms of brain damagefollowing trauma are complex and interrelated. They involve:
• Direct axonal and neuronal damage
• Raised intracranial pressure
• Brain oedema
• Brain ischaemia
• Brain hypoxia

CLINICAL COURSE

In a mild injury a patient is first stunned or dazed for afew seconds or minutes. Loss of consciousness is transient  and following this the patient is alert, and there is no amnesia. The period of loss of consciousness indicates severity; over several hours it is regarded as indicating severe brain injury. The Glasgow Coma Scale (see p. 901)can be used to assess the degree of coma and brain damage  as well as indicating prognosis; a low score implies a severe injury and 50% of such patients die or remain in a vegetative state.
Recovery may take a long period of time, depending on the severity of the injury. During early recovery patients are often restless and lethargic and they may have mild focal neurological deficits. Gradually patients become more alert to their surroundings.

LATE SEQUElAE

These are common causes of morbidity and haveimportant social and medicolegal consequences. They  include the following:
PROLONGED AND INCOMPLETE RECOVERY occurs in many patients with severe head injuries. These patients are left with impairment of higher cerebral function, hemiparesis and other deficits.

POST-TRAUMATIC EPILEPSY may occur (see p.913). ‘CHRONIC TRAUMATIC ENCEPHALOPATHY’ follows repeated (and often minor) injuries. This ‘punch drunk’ syndrome is dementia and presents with extrapyramidal and pyramidal signs. It is seen mainly in professional boxers.
THE ‘POST-TRAUMATIC SYNDROME’ describes the vague complaints of headache, dizziness and malaise that follow even minor head injuries. Depression is prominent. Symptoms may be prolonged.
BENIGN POSITIONAL VERTIGO (see p. 891) is a transient sequel of head injury. CHRONIC SUBDURAL HAEMATOMA (see p. 911).
HYDROCEPHALUS (see p.934).
MANAGEMENT
Patients with head injury require skilled, prolonged and energetic supportive therapy. Acute management of the unconscious patient.

REHABILITATION

Patients left with severe neurological deficits will requirerehabilitation in specialized units. Recovery requires not  only intensive physiotherapy but also the overall care of their mental state. Many patients are depressed and have behavioural problems and they and their families need long-term support and counselling.

Diseases of the spinal cord

The cord extends from Cl (its junction with the medulla) to the vertebral body of Ll (the conus medullaris). The blood supply is via the anterior spinal artery and a plexus on the posterior cord. This network is supplied
by the vertebral arteries, the thyrocervical trunk and several branches from the lumbar and intercostal vessels. Spinal cord compression The principal features of cord compression are of radicular pain at the site of compression, spastic paraparesis or tetraparesis and sensory loss which rises to the level of compression.
For example, in compression at the level of T6 a band of pain radiates around the chest wall and is characteristically worse on coughing or straining. A spastic paraparesis develops either over many months, days or hours, depending upon the underlying pathology. Numbness commencing distally in the lower limbs rises to the level of compression (the ‘sensory limb’). Compression of the cord is a potential medical emergency. It is sometimes difficult to distinguish chronic cord compression from other causes of paraparesis and tetra paresis on clinical grounds alone. This is because pain and the sensory level may be absent.

Spinal cord neoplasms
Disc and vertebral lesions
Trauma
Chronic degenerative
Inflammatory
Epidural abscess
Tuberculosis
Granuloma
Vertebral neoplasms
Metastases
Myeloma
Epidural haemorrhage
Rarities
Paget’s disease
Epithelial. endothelial and parasitic cysts
Aneurysmal bone cyst
Vertebral angioma
Haematomyelia, arachnoiditis
Osteoporosis

Spinal cord neoplasms

Extramedullary turnours (extradural and intradural) cause cord compression gradually over weeks to months, with local or referred root pain and a sensory level.
Intramedullary turnours (e.g. glioma) typically have a very slowly progressive course over several years. Sensory disturbances similar to syringomyelia  may appear.

Disc and vertebral lesions

Central cervical disc protrusion and lumbar disc protrusion are considered.

Extradural
Metastases
Bronchus
Breast
Prostate
lymphoma
Thyroid
Melanoma
Extramedullary
Meningioma
Neurofibroma
Ependymoma
Arteriovenous malformation
Intramedullary
Glioma
Ependymoma
Haemangioblastoma
lipoma
Arteriovenous malformation
Teratoma

Epidural haemorrhage and haematoma

These are rare sequelae of anticoagulant therapy, bleedingdisorders and trauma. A rapidly progressive cord lesion  develops.
Tuberculosis
Spinal tuberculosis is a frequent cause of cord compression in countries where tuberculosis is common (e.g. India, Pakistan, Bangladesh and Africa). There is destruction of vertebral bodies and disc spaces, with spread of infection along the extradural space. Cord compressionand paraparesis follow (Pott’s paraplegia).

MANAGEMENT

Early recognition of the syndrome is vital. Surgical exploration is frequently necessary and, if this is not performed  ufficiently early, irreversible paraplegia may follow. Plain spinal films show degenerative bone disease and destruction of vertebrae by infection or neoplasm. Routine tests, e.g. chest X-ray, may indicate a primary neoplasmor infection.  MRI can identify most lesions and is beginning to replace myelography. Investigations should, if possible, be done promptly in a centre equipped to carry out neurosurgical exploration. The signs of cord compression may increase after lumbar puncture. The results following the early removal of benign tumours are excellent.
Transverse myelitis This broad term is used to describe acute inflammation of the cord and paraplegia occurring with viral infection, MS and other inflammatory and vascular disorders (e.g. syphilis, radiation myelopathy, anterior spinal artery occlusion). Myelography or MRI is usually required to exclude a compressive lesion.
Anterior spinal artery occlusion Cord infarction, causing an acute paraparesis or tetra paresis (or tetraplegia) may occur in any thrombotic or embolic vascular disease (e.g. endocarditis, shock, atheroma,diabetes mellitus, syphilis, polyarteritis nodosa). It  sometimes occurs during surgery to the posterior mediastinum, and follows dissection of the aorta and trauma. It occasionally occurs as an isolated event.

Radiation myelopathy

A mild paraparesis and sensory loss sometimes develops within several weeks to a year of radiotherapy if the cord has been damaged. Particular care is usually taken to shield the cord during radiotherapy.Metabolic and toxic cord disease  Subacute combined degeneration of the cord due to vitamin BI2 deficiency (see pp. 948 and 304) is the most important example of metabolic disease causing spinal cord damage.
Cord lesions may also be seen in severe malnutrition, when they are probably due to multiple B-vitamin deficiencies.

Lathyrism

This is an endemic, spastic paraparesis of central India caused by the toxin f3-(N)-oxalylaminoalanine. It occurs when excessive quantities of a drought-resistant pulse, Lathyrus sativa, are consumed.
Syringomyelia and syringobulbia Fluid-filled cavities within the spinal cord (myelia) and brain stem (bulbi a) are the essential features of these
conditions.

AETIOLOGY

A history of birth injury may be obtained and bony anomaliesat the foramen magnum, spina bifida (see p. 942),  Arnold-Chiari malformation (see p. 942) or hydrocephalus (see p. 934) are often seen.
It is believed that in the presence of an anatomical abnormality at the foramen magnum, the normal pulsatile CSF pressure waves are transmitted to the delicate tissues of the cervical cord and brain stem, with secondary cavity formation. The cavity, or syrinx, is in continuity with the central canal of the cord.

PATHOLOGICAL ANATOMY

The expanding cavity gradually destroys:
• Second-order spinothalamic neurones In the cervical  cord
• Anterior horn cells
• Lateral corticospinal tracts
The vestibular system, trigeminal nuclei, sympathetic system and twelfth nerve nuclei may also be affected.

CLINICAL FEATURES

Patients usually present in the third to fourth decade.Pain in the upper limbs is common. This may be  exacerbated by exertion or coughing. Spinothalamic (pain and temperature) sensory loss in the upper limbs leads to painless burns. Difficulty in walking may occur. The signs of a cavity in the cervical region are: AREAS OF DISSOCIATED SENSORY LOSS, i.e. pain and temperature but not touch (posterior column). These
may extend in a bizarre distribution over the trunk and upper limbs.
Loss OF UPPER LIMB REFLEXES.
WASTING of the small muscles of the hand. SPASTIC PARAPARESIS. This may initially be mild and symptomless.Neuropathic joints, trophic skin changes and ulcers  may follow.
When the cavity extends through the foramen magnum into the brain stem (syringobulbia), there is atrophy and fasciculation of the tongue, nystagmus, Horner’s syndrome, hearing loss and impairment of facial sensation.

MANAGEMENT AND COURSE

The condition is intermittently progressive over several decades.
Investigation shows widening of the cervical canal on plain films and, frequently, ventricular enlargement on CT scan. An MRI scan (the investigation of choice) demonstrates the intrinsic cavity. Myelography (which is sometimes followed by deterioration) shows widening of the cord and herniation of the cerebellar tonsils through the foramen magnum. There is no curative treatment. Decompression of the foramen magnum sometimes reduces the rate of deterioration.

Paraplegia

MANAGEMENT
The patient who becomes paraplegic from any cause demands skilled and prolonged nursing care. Particular problems are discussed below.
Bladder Intermittent (or continuous) catheterization is usually necessary initially. A reflex emptying bladder develops in permanent paraplegia, avoiding the need for catheterization and some of the risks of urinary stasis, infection, and renal and bladder calculi.
Bowel Constipation and faecal impaction must be avoided.Manual evacuation is necessary following acute paraplegia,  but reflex emptying later develops. Skin care The risk of pressure sores is great. Meticulous attention must be paid to cleanliness and to turning the patient every 2 hours. The sacrum, iliac crests, greater trochanters, heels and malleoli should be inspected frequently. Ripple mattresses and water beds are useful. If pressure sores develop, plastic surgical repair shouldbe considered.  The lower limbs
Passive physiotherapy is helpful in avoiding contractures. Severe spasticity (with spasms either in flexion or extension) may be helped by dantrolene sodium, baclofen or diazepam.
General considerations
The general health and morale of the patient should be considered carefully and regularly. Any intercurrent infection (urinary or respiratory) is potentially hazardous and should be recognized and treated early, as chronic renal failure is the single most common cause of death in paraplegia.
Rehabilitation Many patients with traumatic paraplegia or tetraplegia return to partial self-sufficiency and a wheelchair existence. Specialist advice from a skilled rehabilitation unit is necessary. Lightweight, specially adapted wheelchairs are often recommended. The patients have demanding practical, psychological and social needs but with guidance and help can often return to an active role in society.
Other causes of cord lesions
• MS
• Motor neurone disease
• Familial or sporadic paraparesis
• Non-metastatic manifestation of malignancy
• Neurosyphilis
Rarities, e.g. sarcoidosis (see p. 687), Behcet’s syndrome

Degenerative diseases

The term ‘degenerative’ underlines a present lack of understanding of the aetiology of this group of progressive diseases of the nervous system.
Motor neurone disease (MND) In this disease there is progressive degeneration of motor neurones in the spinal cord, in the somatic motor nuclei of the cranial nerves and within the cortex. The condition is sporadic and of entirely unknown cause. Though not familial, rece t work has assigned the gene for the condition to chromosome 21. The prevalence is about 6 in 100000, with a slight male predominance. The onset is in middle life. The sensory system is not involved.

CLINICAL FEATURES

There are three patterns:
1 Progressive muscular atrophy
2 Amyotrophic lateral sclerosis
3 Progressive bulbar palsy
Although useful as a means of understanding the disease, these are not distinct aetiological or pathological variants; the three merge later in the course of the condition. Progressive muscular atrophy
Wasting often begins in the small muscles of one hand and spreads inexorably throughout the arm. Although it may begin unilaterally, wasting soon follows on the opposite side.
Fasciculation is common. It is due to the spontaneous firing of abnormally large motor units formed by the branching fibres of surviving axons that are striving to innervate muscle fibres that have lost their nerve supply. Cramps may occur but pain does not. The physical signs are of wasting and weakness, with fasciculation that is often widespread. Tendon reflexes are lost when the reflex arc is interrupted (by anterior horn cell loss) but are often preserved or exaggerated because of the loss of motor neurones in the corticospinal tracts.
Amyotrophic lateral sclerosis (ALS)
‘Lateral sclerosis’ means disease of the lateral corticospinal tracts (i.e. a spastic paraparesis). ‘Amyotrophy’ means atrophy of muscle (which would be unusual in most other forms of spastic tetraparesis or paraparesis). The clinical picture is thus of a progressive spastic etraparesis or paraparesis with added LMN signs and fasciculation. ALS is the term usually given to MND in the USA. Progressive bulbar palsy Here the brunt of the onset of the disease falls upon the lower cranial nerve nuclei and their supranuclear connections.
Dysarthria, dysphagia, nasal regurgitation of fluids and choking are common symptoms. For reasons unknown, this form of the disease is more common in women than in men. The characteristic features are of a bulbar and pseudobulbar palsy, i.e. a mixture of UMN and LMN signs in the lower cranial nerves, e.g. a wasted fibrillating tongue with a spastic weak palate.

COURSE

The ocular movements are not affected. There are never cerebellar or extrapyramidal signs. Awareness is preserved and dementia is unusual. Sphincter disturbance occurs late, if at all. Remission is unknown. The disease progresses, spreading gradually and causes death, often from bronchopneumonia. Survival for more than 3 years is most unusual, although there are rare ‘benign’ forms of the condition in which survival is prolonged.

MANAGEMENT

There are no specific diagnostic tests and the diagnosis can often be made on clinical grounds alone. Cervical radiculopathy and myelopathy and the rare (almost extinct) syphilitic cervical pachymeningitis may sometimes cause diagnostic difficulty. Bulbar myastheniagravis may sometimes appear similar in the early stages.  Denervation may be confirmed by electromyography, which characteristically shows chronic partial denervation with preserved motor conduction velocity. The CSF is usually normal (the protein may be slightly raised).No treatment has been shown to influence the course  of this disease although recently Riluzole, a glutamate antagonist, has been shown to help, particularly in patients with disease of bulbar onset. Management of patientswith MND, who are often well-informed and aware of the outlook, is particularly difficult. Spinal muscular atrophies  These are a group of rare genetically determined disorders of the motor neurone that give rise to slowly progressive, usually symmetrical, muscle wasting and weakness. An acute infantile type (Werdnig-Hoffman disease), a chronic childhood type (Kugelberg-Weilander disease) and adult forms are recognized. Clinically these conditions may be confused with muscular dystrophies, hereditary neuropathies or MND .

Dementia 

This is a diffuse deterioration in mental function producedby a number of pathological processes. The commonest  is Alzheimer’s disease.