Category Archives: Neurological Diseases and Diseases of Voluntary Muscle

Congenital and inherited diseases

CEREBRAL PALSY

This term describes disorders apparent at birth or in childhood due to brain damage in the neonatal period leading to non-progressive deficits.
Mental retardation, varying from severe intellectual impairment to mild learning disorders, is common in all forms of cerebral palsy, but severe physical disability is not necessarily associated with a severe defect in higher erebral function.

CAUSES

The precise cause of brain damage in an individual child may be difficult to determine. The following may be responsible:
HYPOXIA in utero and/or during parturition TRAUMA, during parturition or in the neonatal period PROLONGED CONVULSIONS OR COMA (e.g. febrile convulsions, hypoglycaemia) in infancy

Infantile hemiparesis
Hemiparesis may be noted at birth or during childhood. Hemiatrophy of the limbs (and atrophy of the contralateral  emisphere) is usual. Seizures are common.

Congenital ataxia
This is incoordination and hypotonia of the trunk and limbs.
DYSRAPHISM
Failure of normal fusion of the fetal neural tube leads to this group of congenital anomalies.

Anencephaly

Anencephaly is absence of the brain and cranial vault, and is incompatible with life. Meningo-encephalocele This is an extrusion of brain and meninges through a midline skull defect that varies from a minor protrusion to a massive defect.
Spina bifida
In spina bifida there is failure of fusion of the neural tube, usually in the lumbosacral region. Several varieties occur. SPINA BIFIDA OCCULTA. This is failure of fusion of the vertebral arch only. There are rarely neurological abnormalities and a bony anomaly is seen on X-ray. It occurs in 3% of the population. A dimple or a tuft of hair may overlie the lesion.
MENINGOMYELOCELE AND MYELOCELEWITH SPINA BIFIDA. Meningomyelocele consists of elements of the cord and lumbosacral roots contained within a meningeal sac that herniates through a defect in the vertebrae. In severe cases the lower limbs and sphincters are paralysed. The defect is visible at birth.Meningocele is a meningeal defect alone.  Hydrocephalus is commonly associated with theseabnormalities  Meningitis may follow if a sinus connects the s pinal canal with the overlying skin.

BASILAR IMPRESSION OF THE SKULL (PLATYBASIA) This is usually a congenital anomaly in which there is invagination of the foramen magnum and skull base upwards. The lower cranial nerves, medulla, upper cervical cord and roots are affected. It is often complicatedby the Arnold-Chiari malformation, in which aberrant cerebellar tissue extends through the foramen magnum. The condition also occurs in Paget’s disease and rarely in osteomalacia.

NEUROECTODERMAL SYNDROMES

These are disorders in which organs derived from ectoderm show a tendency to form tumours and hamartomas, with lesions in the skin, eye and nervous system. Neurofibromatosis (von Recklinghausen’s disease)
This is characterized by multiple skin neurofibromas and pigmentation. The neurofibromas arise from the neurilemmal sheath. One new case occurs in every 3000 live births. The mode of inheritance is autosomal dominant.

CLINICAL FEATURES (see p. 1025)

Clinically neurofibromatosis can be divided into type 1 (or peripheral) and type 2 (bilateral acoustic or central). The predisposing gene for type 1 has been localized to chromosome 17 and for type 2 to the long arm of chromosome 22. The main application for these genetic markerswill be for antenatal diagnosis and genetic counselling,  although the severity of the disease itself will not be predictable.

Skin tumours

Subcutaneous, soft, sometimes pedunculated, tumours appear. They may be multiple. Skin pigmentation Multiple caje-au-lait patches-pale brown macules 1- 20 em in diameter-are found. These are common in
the normal population, but more than five patches is abnormal.

TREATMENT

Surgery may be necessary for cosmetic reasons. Tumours causing pressure within the nervous system require excision, if this is feasible.
Tuberose sclerosis (epiloia) This is a rare autosomal dominant condition whose principal features are adenoma sebaceum, epilepsy and mental retardation (often severe). Adenoma sebaceum These are reddish nodules (angiofibromas) that develop on the cheeks in childhood. Other lesions Other lesions include shagreen patches, amelanotic naevi, retinal phakomas (glial masses), renal tumours, glial overgrowth in brain and gliomas. Cardiac rhabdomyomas, hamartomas of lung and kidney, and polycystic kidneys may also occur. Sturge-Weber syndrome (encephalofacial angiomatosis) There is an extensive port-wine naevus on one side of the face (usually in the distribution of a division of the fifth nerve) and a leptomeningeal angioma.Epilepsy is common. Familial occurrence is exceptional.  Von Hippel-Lindau syndrome (retinocerebellar angiomatosis)This is the occurrence in families (dominant inheritance  with variable penetrance) of retinal and cerebellar haem angioblastomas or, less commonly, aemangioblastomas
of the cord and cerebrum. Renal, adrenal and pancreatic cysts (and haemangioblastomas) may also be found. Polycythaemia sometimes occurs. There are numerous other disorders related to these conditions,for example ataxia telangiectasia and Osler-Web er-Rendu syndrome.

SPINOCEREBELLAR DEGENERATIONS

The classification of this large group of rare inherited disorders is complex. Three conditions will be mentioned here.

Hereditary spastic paraparesis Isolated progressive paraparesis runs in some families. The inheritance is variable. Additional features includingcerebellar signs, pes cavus, wasted hands and optic atrophy are somet  mes seen. The conditions are usually mild and progress slowly over many years. Ataxia telangiectasia (see p. 147) This is a rare, autosomal recessive condition that produces a progressive ataxic syndrome in childhood and early adult life.
There is striking telangiectasia of the conjunctiva, nose, ears and skin creases. There are also defects in cellmediated immunity and antibody production. A defect in DNA repair has been demonstrated. Death is usual by the third decade, either from infection or from the development
of lymphoreticular malignancy. PERONEAL MUSCULAR ATROPHY AND OTHER INHERITED NEUROPATHIES These disorders are classified within a large and complex group-the hereditary motor and sensory neuropathies (HMSN).
Peroneal muscular atrophy Peroneal muscular atrophy (Charcot-Marie-Tooth disease) is a common clinical syndrome in which there isdistal limb wasting and weakness that slowly progresses  over many years, mostly in the legs, with variable loss of sensation and reflexes. In advanced cases the distal wasting below the knees is so marked that the legs resemble ‘inverted champagne bottles’. Mild cases have only pes cavus and clawing of the toes and may pass unnoticed. Three forms are recognized:

1 HMSN type I-a demyelinating neuropathy
2 HMSN type II-an axonal neuropathy
3 Distal spinal muscular atrophy
Both autosomal dominant and recessive inheritance is seen in different families. In HMSN type I with dominant inheritance (the commonest form), linkage has been demonstrated for the locus on the long arm of chromosome
1.Optic atrophy, deafness, retinitis pigmentosa and spastic paraparesis are sometimes seen in variants of theseconditions. HMSN type III This was formerly known as the ‘hypertrophic neuropathy of Dejerine-Sottas’. It is an autosomal recessive demyelinating sensory neuropathy of childhood leading to severe incapacity during adolescence. It is notable because the CSF protein may be greatly elevated to g litre-lor more, and the CSF pathways are obstructed by greatly hypertrophied nerve roots.

Headache, migraine and facial pain

Tension headache’

The vast majority of chronic and recurrent headaches are believed, on no good evidence, to be due to ‘tension’ within the scalp muscles. What is certain is that they are, in terms of pathology, innocent. ‘Tight band’ sensations, pressure behind the eyes, and throbbing and bursting sensations are common.

depressed skull fracture or meningeal tear may be necessary.
Polyvalent vaccines are available against recurrent pneumococcal meningitis (e.g. when there is a CSF leak following skull fracture) and against some strains of meningococci (see p.23). In meningococcal outbreaks rifampicin prophylaxis should be given to contacts and family members as well as to the patient. Differential diagnosis of (SF pleocytosis Difficulties occur in meningitis when a raised, often mixed (lymphocyte and polymorph, i.e. pleocytic) picture is found but no infecting organism. This is sometimes called ‘aseptic meningitis’. The conditions should be considered.

ENCEPHALITIS

Encephalitis is inflammation of brain parenchyma. It is caused by a wide variety of viruses and may also occur in bacterial and other infections. Acute viral encephalitis In many cases a viral aetiology is presumed but not confirmed serologically or by culture. The usual organisms cultured from cases of viral encephalitis in adults in the UK are Echo, Coxsackie, mumps and herpes simplex viruses.
Adenovirus, varicella zoster, influenza, measles and other viruses are rarer causes.

CLINICAL FEATURES

Many of these infections cause a mild self-limiting illnesswith headache and drowsiness. In a minority there is a  more serious illness accompanied by focal signs, seizures and coma. Herpes simplex virus (HSV-1) accounts for many of these severe infections in Britain and has a mortality of around 20% even with treatment. In the Far East the Japanese B arbovirus is a more usual, and epidemic, cause of severe encephalitis, with a high mortality.

Partially treated bacterial meningitis

Viral meningitis
Tuberculosis or fungi
Neoplastic meningitis
Parameningeal foci (e.g. paranasal sinus)
Syphilis
Intracranial abscess
Cerebral venous or arterial infection
Following subarachnoid haemorrhage
Encephalitis, including AIDS
Rare causes (e.g. cerebral malaria, sarcoidosis, Behcet’s syndrome, Lyme disease)

DIFFERENTAL DIAGNOSIS
This includes:
• Bacterial meningitis complicated by cerebral oedema and/or cerebral venous thrombosis
• Cerebral abscess
• Acute disseminated encephalomyelitis
• Toxic confusional states in febrile illnesses and In septicaemia

INVESTIGATION

Investigation in severe cases includes CT scanning (which characteristically shows areas of oedema), EEG (which shows slow-wave changes and/or ‘periodic complexes’) and viral serology of blood and CSF. Brain biopsy is now seldom performed in the UK.

TREATMENT

Suspected herpes simplex encephalitis is immediatelytreated with intravenous acyclovir, the active form of  which inhibits DNA synthesis. Phosphorylation of. this drug is dependent upon the presence of viral thymidine kinase; thus the drug is specific for herpesvirus infections. If the patient is in coma the outlook is poor whether or  not drugs are given.Supportive measures are required for comatose patients. Seizures are treated with anticonvulsants. Prophylactic immunization is possible against Japanese B encephalitis and sometmes advised particularly for travellers to the Far East in endemic areas.
Acute disseminated
encephalomyelitis (AD E)
This follows many common viral infections (e.g. measles, varicella zoster, mumps and rubella) and rarely after immunization against rabies, influenza or pertussis. The clinical syndrome is often similar to acute viral encephalitis, with added focal brain stem and/or spinal cord lesions due to demyelination, but in which viral particlesare not usually present. The prognosis is variable. Mild  cases recover completely but in severe cases (those in coma) mortality is around 25% and the survivors often have permanent brain damage. Treatment is supportive, with steroids and anticonvulsants.

MYELITIS

Myelitis means inflammation of the spinal cord causing paraparesis or tetraparesis. It occurs with varicella zoster or as part of a postinfective encephalomyelitis. Poliomyelitis is a specific enterovirus infection of anterior horn cells.
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HERPES ZOSTER (SHINGLES)
This is a recrudescence of infection with varicella zoster virus within the dorsal root ganglia, the original infection having been acquired in an attack of chickenpox many There may be obvious precipitating factors such as worry, noise, concentrated visual effort or fumes. Depression is also a frequent underlying cause. Tension headaches are often attributed to cervical spondylosis, refractive errors or high blood pressure; the evidence for these is poor. Similar headaches also follow head injuries,which may be minor.
There ar e no abnormal physical signs other than tenderness and tension in the nuchal and scalp muscles.

MANAGEMENT

This involves:
• Firm reassurance
• Avoiding the causes
• Analgesics
• Physical treatments-massage, relaxation
• Antidepressants-when indicated
Investigation may be needed to confirm the benign nature of the problem.

Migraine

Migraine means recurrent headaches associated with visual and gastrointestinal disturbance; despite the origin of the word, it does not invariably mean unilateral headache.

INCIDENCE

About 10% of any population sampled admit to these symptoms.

MECHANISMS

The cause of migraine is unknown. The headache, oftenthrobbing, is believed to be due to vasodilatation or oedema  of blood vessels, with stimulation of nerve endings near affected extracranial and meningeal arteries. The release of vasoactive substances such as nitric oxide are thought to playa role. In addition, the serum level of 5- hydroxytryptamine rises at the onset of the prodromal symptoms and falls during the headache. Cerebral symptoms and signs (e.g. tingling of limbs, aphasia, weakness) are caused by ischaemia and/ordepression of cortical function.  Definite precipitating factors are unusual. Somepatients complain of symptoms at times of relaxation(e.g.  weekend migraine). Others find that chocolate (high  in phenylethylamine) and cheese (high in tyramine) precipitate attacks. Migraine is common around puberty, at he menopause and premenstrually, and sometimes increases in severity or frequency with the contraceptivepill, in pregnancy and with the development of hypertension. There is no reason to suppose that migraine is associated with any major intracranial lesion. However, since migraine is such a common symptom complex, an intracranial mass lesion and migraine sometimes both occur in the same patient by coincidence. Rarely, migraine follows head injuries.

CLINICAL PATTERNS

There are several types of migraine, the attacks varyingfrom intermittent headaches barely distinguishable from tension head aches to discrete episodes that mimic thromboembolic cerebral ischaemia. The distinction between the variants is somewhat artificial.
The attack itself may be divided into:
• Prodromal symptoms
• Headache and associated symptoms
Prior to the attack some patients experience a feeling of well-being.

Migraine with aura (classical)
Prodromal symptoms are usually visual and are related to ischaemia in the distribution of the intracranial arteries. There are unilateral patchy scotomata (when the retinal vessels are involved), unilateral blindness (involvement of the ophthalmic artery) and sometimes hemianopic field loss (involvement of the posterior cerebral artery). Teichopsia (flashes) and fortification spectra (jagged lines resembling battlements) are common. Transient aphasia sometimes occurs, together with tingling, numbness or vague weakness of one side. The patient feels nauseated.
The prodrome lasts for 15 min to 1 hour or more. Headache follows. This is occasionally hemicranial (‘splitting the head’) but often begins locally and becomes generalized. Nausea increases and vomiting follows. The patient is irritable and prefers to be in a darkened room. The superficial temporal artery (either or both) is engorged and pulsating.
After several hours the attack ceases. There is sometimes a diuresis towards the end of an attack. Sleep often follows.
Migraine without aura (common) This is the usual variety of migraine. Prodromal visual symptoms are vague. There is recurrent headache accompanied by nausea and malaise. Distinction from tension headache may be impossible.

Basilar migraine

The prodromal symptoms are due to ischaemia in theposterior cerebral circulation. Circumoral tingling,  numbness of the tongue, vertigo, diplopia, transient blindness, syncope, dysarthria and ataxia occur.

Hemiplegic migraine

This is a rarity in which classical migraine is accompanied by hemiparesis. Recovery occurs within 24 hours. Exceptionally, cerebral infarction follows.

Ophthalmoplegic migraine

This is a third (or exceptionally a sixth) nerve palsy occurring in a migraine attack. The condition is rare and is difficult to distinguish from other causes of a third nerve palsy (see p. 886) without investigation.
Facioplegic migraine This rarity is unilateral facial weakness occurring during a migraine attack.

DIFFERENTIAL DIAGNOSIS

The sudden onset of headache may be similar to meningitis or SAH.
The hemiplegic, visual and hemisensory symptoms must be distinguished from thromboembolic TIAs (see p. 906). In TIAs the maximum deficit is present immediately and headache is unusual.
Unilateral tingling or numbness should be distinguished from sensory epilepsy (partial seizures). In the latter a distinct ‘march’ of symptoms is usual.

MANAGEMENT

General measures
These include:
REASSURANCE and relief of anxiety.
AVOIDANCE OF PRECIPITATING DIETARY FACTORS (rarely helpful).
PATIENTS ON ORAL CONTRACEPTIVEs-a change in brand or stopping of the drug may help. Severe hemiplegic symptoms are an indication for stopping these drugs.
During the attack

Paracetamol or other simple analgesics should be given, with antiemetics (e.g. metocloprarnide) if necessary. The 5-hydroxytryptamine (5HT1) agonist sumatiptan is of considerable value either by self-administered subcutaneous injection or orally in recurrent severe attacks. Itshould not be taken until 24 hours after ergotamine.  Ergotamine tartrate (1-2 mg orally or rectally, 360 ILg by aerosol or 0.25-0.5 mg by injection) is sometimes, though not often, helpful if given early in attack. Ergotamine
should not be used in patients with a history of vascular disease.

Prophylaxis

It is particularly difficult to discern the true (as opposedto placebo) effects of prophylactic drugs in migraine.  When drugs are necessary, the following are used: PIZOTIFEN (a 5-hydroxytryptamine antagonist) 0.5 mg at night for several days, increasing to 1.5 mg at night.Common side-effects are slight weight gain and  drowsiness.
PROPRANOLOL 10 mg three times daily, increasing to 40-80 mg three times daily. METHYSERGIDE (a 5-hydroxytryptamine antagonist) 2- 6 mg daily. An occasional side-effect is retroperitoneal fibrosis, which precludes its use for longer than 6 months.

CLINICAL FEATURES

In the cranial nerves, herpes zoster has a predilection for the fifth and seventh nerve. ‘Ophthalmic herpes’ is infection of the first division of the fifth nerve and may lead to corneal scarring and secondary panophthalmitis. ‘Geniculate herpes’ (the Ramsay Hunt syndrome, seep. 889) leads to facial palsy accompanied by vesicles on  the pinna, external auditory meatus and fauces. The local complications of shingles are secondary bacterial infection, very rarely purpura and necrosis in the affected segment (‘purpura fulminans’), generalized herpes zoster, and postherpetic neuralgia.
A myelitis, meningo-encephalitis or motor radiculopathy may be caused by varicella zoster. Treatment with acyclovir is given (see p. 1015).
Postherpetic neuralgia Postherpetic neuralgia is pain in the zone of the previous eruption; it occurs in some 10% of patients (often elderly). It is a burning, continuous pain responding poorly to all analgesics. Depression is almost universal. Treatment is unsatisfactory but there is a trend towards gradual recovery over 2 years.

NEUROSYPHILIS

Tertiary neurological disease is now rare but a wide variety of syndromes still occur, particularly in those who may have had many sexual partners.
For practical purposes, negative sero ogical tests for syphilis in blood exclude the disease. The main syphilitic syndrome are described below. Asymptomatic neurosyphilis This is the term used to describe positive CSF serology without signs.
MeningovascuIar syphilis
This presents as:
SUBACUTE MENINGITIS often with cranial nerve palsies and papilloedema
A FOCAL FORM (a gumma), is an expanding intracranial mass which causes epilepsy, raised pressure and focal deficits, e.g. hemiplegia
PARAPARESIS caused by a spinal meningovasculitis Tabes dorsalis
This is a complex syndrome in which demyelination occurs in the dorsal roots. Many of the features are due to ‘de-afferentation’. The elements of the syndrome are:
• Lightning pains
• Ataxia, loss of reflexes, widespread sensory loss andsome muscle wasting
• Neuropathic joints (Charcot’s joints)
• Argyll Robertson pupils
• Ptosis and optic atrophy

General paralysis of the insane (GPI)

The grandiose title indicates that this is a syndrome of madness and weakness. The dementia is often similar to that associated with Alzheimer’s disease (see p. 965). Progressive dementia, brisk reflexes, extensor plantar reflexes and tremor occur. Death follows within 3 years of the onset.
Argyll Robertson pupils are usually present. Seizures may occur.
Other forms
Mixtures of the syndromes described above occur. In congenital neurosyphilis (acquired in utero), there are features of both tabes dorsalis and GPI in childhood; this is known as taboparesis.
In secondary syphilis, a self-limiting meningeal reaction occurs that may be symptomless or may cause a subacute meningitis.

TREATMENT

Benzylpenicillin 1 g daily by injection for 10 days in primaryinfection eliminates the risk of future tertiary syphilis.  Established neurological disease can be arrested but ot usually reversed with penicillin. Parenteral penicillin for 2-3 weeks is given for all forms of neurosyphilis. Allergic reactions (Jarisch-Herxheimer reactions) may occur; high-dose steroid cover is usually given with penicillin to reduce their severity.

AIDS AND THE NERVOUS SYSTEM

Individuals with HIV infection frequently present with ordevelop neurological disease. In addition, HIV-infected  patients have a high rate of cerebrovascular disease. There is a variety of clinical neurological pictures, which may  e confusing.

Meningitis

ACUTE ASEPTIC MENINGITIS. This is believed to be a  primary HIV meningitis. Spontaneous recovery is usual. CHRONIC MENINGITIS. This may occur with HIV itself, fungi (e.g. Cryptococcus neoformans or Aspergillus), tuberculosis, Listeria monocytogenes, Escherichia coli or other organisms. Treatment is typically difficult and unsuccessful.

Diffuse encephalopathies

AIDS-DEMENTIA COMPLEX. This is a diffuse, progressive,usually fatal HIV -related dementia, sometimes associated with a cerebellar syndrome, thought to be due  to a primary cerebral HIV infection.
ENCEPHALITIS. Cytomegalovirus, herpes simplex, Toxoplasma and other organisms cause a severe and often fatal encephalitis.

CNS LYMPHOMA AND PROGRESSIVE MULTIFOCAL LEUCOENCEPHALOPATHY. These are progressive late complications of HIV infection. They are usually fatal.

Paraparesis

This occurs in AIDS in the following patterns.
ACUTE HIV TRANSVERSE MYELITIS. This is believed to be a primary HIV myelitis. Spontaneous recovery is usual.
MYELOPATHY DUE TO INFECTION, e.g. with herpes simplex or zoster, cytomegalovirus.
CNS LYMPHOMA. Lymphomatous masses cause cord compression or malignant meningitis.

AIDS-related neuropathy

Three patterns occur:
1 Mononeuropathy, e.g. a common peroneal nerve lesion
2 Mononeuritis multiplex
3 Polyneuropathy
MANAGEMENT OF AIDS OTHER INFECTIONS
The nervous system is involved in many infective diseases. Rabies Rabies is transmitted to humans from infected animals via penetrating wounds. The rabies virus multiplies in the wound and migrates via the peripheral nerves and dorsal root ganglia to the eNS. A fatal encephalitis follows in
which, at autopsy, characteristic neuronal inclusion bodies (Negri bodies) are observed.

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Tetanus

Tetanus may follow even a trivial wound. There is liberation of a powerful toxin that travels within motor nerves to reach the eNS, where it binds irreversibly with certain sialic acid-containing gangliosides. The toxin blocks inhibition of spinal reflexes, resulting in spasms.
Botulism. The paralytic symptoms of botulism are caused by a presynaptic block in neuromuscular transmission.

Lyme disease

This produces a chronic radiculopathy. A paraparesis can occur.
Leprosy

In tuberculoid leprosy a mononeuritis multiplex is seen. The infected nerves become large and palpable as hard cords. The peripheral nerves are also affected in lepromatous leprosy.
Poliomyelitis (see p. 50)
In this condition there is invasion of the anterior horn cells by the pathogenic virus. Many infections are subclinical but in a minority there is serious paralytic disease involving the respiratory muscles and sometimes causing a bulbar palsy.
Other examples of infection involving the eNS are summarized in Table 18.45. See also individual viral infections.
MISCELLANEOUS CONDITIONS
Progressive rubella encephalitis Some 10 years after the primary infection there is rarely a progressive syndrome of mental impairment, fits, optic atrophy, cerebellar and pyramidal signs. There is evidence of local antibody production against rubella viral antigen within the CNS.
Subacute sclerosing panencephalitis (SSPE) The persistence of measles antigen in the CNS is believed to be the cause of this rare late sequel to measles infection. Progressive mental deterioration, fits, myoclonus
and pyramidal signs occur, usually in a child. Diagnosis is confirmd by demonstrating a high titre of measles antibody in the blood and CSF.

Creutzfeld-Iakob disease (CJD)

This is a slowly progressive dementia characterized pathologically by ‘spongiform encephalopathy’. It occurs worldwide and is transmitted by an agent resistant to many of the usual sterilization processes. This is an
example of a ‘prion’ (proteinaceous infectious particles) or ‘slow’ virus disease. Infection has been transmitted from post-mortem and surgical specimens and corneal grafts, and to the recipients of human growth hormone (which was obtained from human pituitary glandsremoved at autopsy). The pathology of CJD is very   imilar to bovine spongiform encephalopathy of cattle. The condition has a long incubation period, sometimes up to several years. Death is almost invariable within 2years from the onset of symptoms.

Kuru

This is a dementia and cerebellar ataxia occurring in thehighlands of New Guinea. It is believed to have been  spread by ritual cannibalism. Spongiform change occursin the brain (very similar to that in CJD). This obscure condition is also believed to be transmitted by a slowVIrus.
Progressive multifocal leucoencephalopathy  This is an opportunistic infection with the papovaviruses JC and SV-40 (and others) in patients who are immunocompromised. Multifocal demyelinating hemisphere lesions develop that contain virus particles. Death is usual
after several years.

Reye’s syndrome

This is a severe encephalitic illness, usually of children, accompanied by fatty infiltration of the liver and hypoglycaemia. A viral cause has been postulated but other factors, including aspirin therapy, have also been implicated. Mollaret’s meningitis
This term is used to describe recurrent episodes of ‘aseptic meningitis’ over many years. A viral cause is postulated. Some of these patients are helped by treatment with he mitotic poison colchicine. Vogt-Koyanagi-Harada syndrome This is a recurrent inflammatory disease of cells of neural crest origin, causing uveitis, meningo-encephalitis, vitiligo, deafness and alopecia.

ME: myalgic encephalomyelitis (epidemic neuromyasthenia) (see p. 963)
Headache, fever, lassitude, torpor, myalgia and depression sometimes follow viral infection (e.g. hepatitis, infectious mononucleosis, Coxsackie infections). It is paticularly difficult to distinguish between organic and psychological elements in these cases and there is wide variation of opinion about causation.

Sarcoidosis

This condition may cause a chronic meningo-encephalitiswith sarcoid lesions within the brain and spinal cord, a  peripheral neuropathy, cranial nerve palsies (particularly bilateral seventh nerve palsies) or, rarely, a myopathy.

Behcet’s syndrome

The three principal features are recurrent oral and genital ulceration, inflammatory ocular disease and neurological syndromes. Brain stem and cord lesions, aseptic meningitis, encephalitis and cerebral venous thrombosis also occur.
ABSCESSES WITHIN THE NERVOUS SYSTEM
Brain abscess
A focal area of infection within the cerebrum or cerebellum presents as an expanding mass lesion (see p. 932). The usual organisms are streptococci (aerobic, anaerobic and microaerophilic species), Bacteroides spp., staphylococci nd enterobacteria. Mixed infections are common. Fungi can also cause brain abscesses. Multiple abscesses may develop. A parameningeal (e.g. ear, nose, paranasal  inus, skull fracture) or distant (e.g. lung, heart, abdomen) focus of infection may be present. Frequently no cause is found.
Tuberculoma
Tubercle bacilli cause chronic caseating intracranial granulomas-tuberculomas-which are the commonest single intracranial masses in areas such as India where tuberculosis is common. Tuberculomas either present as mass lesions or occur in the course of tuberculous meningitis.
They may also be symptomless and appear on skull X-rays as areas of intracranial calcification.

CLINICAL FEATURES

Headache, focal signs (e.g. hemiparesis, aphasia, hemianopia), epilepsy and raised intracranial pressure occur. Fever, leucocytosis and a raised ESR are usual in cerebral abscess but are not always present. The presentation may thus be remarkably similar to many cerebralneoplasms. The symptoms may be indolent, developing over we ks, particularly in the cerebral hemispheres. Cerebellar abscesses tend to develop more acutely.

MANAGEMENT

Urgent CT or MRI scanning is essential. The search fora focus of infection should include a detailed examination of the skul l, ears and paranasal sinuses. Lumbar puncture is contraindicated in suspected brain abscess prior to scanning.
Treatment should be carried out with liaison between neurosurgeon and microbiologist. Surgical decompression may be necessary if antibiotics are unsuccessful. Despite treatment, the mortality of abscess remains high, at around 25%, and epilepsy is common in survivors.

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Subdural empyema

This is usually secondary to local infection. The featuresare similar to those of a cerebral abscess.  Intracranial epidural abscess
Rarely, a collection of pus tracks along the intracranial epidural space, causing sequential cranial nerve lesions, typically without evidence of raised pressure. There is usually evidence of local infection. Drainage is necessary Spinal epidural abscess Staphylococcus aureus is the usual organism responsible. It reaches the spine via the bloodstream, e.g. from a boil. There is fever and usually back pain followed by paraparesisor root lesions. Emergency myelography, decompression  and antibiotics are indicated.

Hydrocephalus

Hydrocephalus means that there is an excessive amountof CSF within the cranium. Although this also occurs in  cerebral atrophy, in practice the term hydrocephalus is used to describe different syndromes in which there is, or has been, obstruction to CSF outflow with consequent high pressure and dilatation of the cerebral ventricles. Exceptionally an increase in CSF production occurs.
• Infantile hydrocephalus
Enlargement of the head in infancy is diagnosed in about 1 in 2000 live births. There are several causes: ARNOLD-CHIARI MALFORMATION. There is elongation of the medulla and abnormal cerebellar tissue
(the tonsils) in the cervical canal. Associated spina bifida is common. Syringomyelia may develop. DANDy-WALKER SYNDROME. There is cerebellar hypoplasia and obstruction to the outflow foramina of the fourth ventricle.
STENOSIS OF THE AQUEDUCT OF SYLVIUS (Fig. 18.21). This may be either congenital or acquired following neonatal meningitis or haemorrhage.

Hydrocephalus in adult life

Infantile hydrocephalus not infrequently becomes symptomaticonly in adult life. The features are of headache, vomiting, papilloedema , ataxia and bilateral pyramidal signs.
Hydrocephalus in adults also occurs with:
TUMOURS OF THE POSTERIOR FOSSA AND BRAIN STEM. These obstruct the aqueduct or fourth ventricular outflow.
SUBARACHNOID HAEMORRHAGE, HEAD INJURY OR MENINGITIS (PARTICULARLY TUBERCULOUS). The  ydrocephalus is often a transient phenomenon.
TUMOURS OF THE THIRD VENTRICLE. A colloid cyst of the third ventricle causes enlargement of the lateral entricles, headache and papilloedema.
NORMAL-PRESSURE HYDROCEPHALUS. In this syndrome enlarged cerebral ventricles occur without cortical atrophy. It presents with dementia, urinary incontinence and apraxia, usually in the elderly. The
CSF pressure is characteristically normal. It is currently thought that this syndrome is the late result of previous episodes of high pressure, though usually of unknown cause.
PAPILLOMA OF THE CHOROID PLEXUS. This is an extremely rare neoplasm that secretes CSF. Ventriculo-atrial or ventriculo-peritoneal shunting may be necessary when hydrocephalus is diagnosed.

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Idiopathic (or benign) intracranial hypertension
This syndrome consists of marked papilloedema without other signs in patients who are subsequently shown to have neither a mass lesion nor an increase in ventricular size. It occurs mainly in obese young women with vague menstrual irregularities. Steroid therapy is sometimes thought to be a cause and many other drugs have seen occasionally implicated. Other causes of papilloedema should be excluded. The condition is benign only in that it is not fatal. Infarction of the optic nerve occurs (with consequent blindness) when the papilloedema is severe and longstanding. Surgical decompression or shunting may be necessary. Thiazide diuretics appear to reduce the intracranial pressure in this condition. Weight reduction is important.

Intracranial turnours

Primary intracranial tumours account for approximately 10% of all neoplasms. The commoner varieties of tumours are outlined in Table 18.46; around one-quarter are metastases (see Fig. 18.20e).
Differences between overall annual incidence rates (see Table 18.1) and presentation as clinical problems (Table 18.46) are accounted for by the fact that small meningiomas and cerebral metastases are commonly found unexpectedly at post mortem.

Gliomas
These are malignant, intrinsic turnours that originate in neuroglia, usually within the cerebral hemispheres. Their cause is unknown. They are occasionally associated with neurofibromatosis. Primary intracranial malignant turnours virtually never metastasize outside the eNS and spread only by direct extension.
ASTROCYTOMAS. These gliomas arise from astrocytes. They are classified into grades I-N, depending on malignancy. Grade I astrocytomas grow slowly over many years while grade N turnours cause death within several months.
Cystic astrocytomas occur in childhood, usually within the cerebellum. They are relatively benign.
OLIGODENDROGLIOMAS. These arise from oligodendroglia and grow slowly, usually over several decades. Calcification is common.
Meningiomas (see Fig. IS.2Od) These benign turnours arise from the arachnoid membrane and may grow to a large size, usually over years. When close to the skull they erode bone. They often occur along the intracranial venous sinuses, which they may invade. They are rare below the tentorium. Neurofibromas
These arise from Schwann cells and occur principally in the cerebellopontine angle, where they arise from the eighth nerve sheath (see p. S90).

Other less common neoplasms include:
• Cerebellar haemangioblastoma
• Ependymoma of the fourth ventricle
• Colloid cyst of the third ventricle
• Pinealoma
• Chordoma of the skull base
• Glomus turnour-a vascular neoplasm of the jugular bulb
• Medulloblastoma-a cerebellar tumour of childhood
• Craniopharyngioma

Pituitary turnours

CLINICAL FEATURES

Mass lesions within the cranium produce symptoms and signs in three coexisting ways: 1 By the direct effects of the mass on surrounding structures, which are either destroyed or suffer impairment of function from infiltration, pressure or cerebral oedema
2 By the effects of raised intracranial pressure and the shift of intracranial contents 3 By provoking either generalized or partial seizures Although neoplasms, either secondary or primary, are the
commonest lesions to cause these effects, cerebral abscess, tuberculoma, subdural and intracranial haematoma may also produce symptoms and signs that may be clinically indistinguishable.
Direct effects of mass lesions
These will depend upon the site of the mass and its speed of growth. The hallmark of a mass lesion is a progressive deterioration of function.
Three examples of possible effects are given below:
1 A left frontal meningioma (see Fig. IS.20d) will cause a vague disturbance of personality, apathy and impairment of intellectual function over several months. When the frontal speech area becomes affected, an expressive aphasia will develop. As the corticospinal pathways become involved, a right hemiparesis will follow.2 A right parietal glioma involving the fibres of the optic radiation will cause a left homonymous field defect. Cortial sensory loss and a left hemiparesis may follow. Partial seizures causing episodes of numbness of the left limbs may develop.
3 A left eighth nerve sheath neurofibroma (an ‘acoustic neuroma’) (see Fig. IS.20t) growing in the cerebellopontine angle will cause progressive perceptive deafness (VIII), vertigo (VIII), numbness of the left side of the
face (V) and facial weakness (VII), followed by cerebellar ataxia as the cerebellar connections are compressed. The direct effects are commonly those that first bring the patient to seek medical attention. The rate of progression will vary greatly from a few days or weeks to several yearsin the case of a slowly enlarging mass. Since cerebral oedema  surrounds many mass lesions it is often difficult on clinical grounds to distinguish its effect from that of the mass itself.
Raised intracranial pressure
The triad of headache, vomiting and papilloedema is an important, though relatively unusual, presentation of a mass lesion. These symptoms usually imply that obstruction to CSF pathways has occurred. Typically this picture is produced early by masses within the posterior fossa and as a later event with lesions above the tentorium. Shift of the intracranial contents produces symptoms and signs that coexist with the direct effects of an expanding mass:
DISTORTION OF THE UPPER BRAIN STEM, as midline
structures are displaced either caudally or laterally by a hemisphere mass (see Fig. 18.20), leads to impairment of consciousness (drowsiness progressing to stupor and coma).
COMPRESSION OF THE MEDULLA by herniation of the cerebellar tonsils caudally through the foramen magnum (an example of ‘coning’) causes impairment of consciousness, respiratory depression, bradycardia, decerebrate posturing and death.FALSE LOCALIZING SIGNS APPEAR (‘false’ only  because they are not related directly to the site of the mass).
Three examples of false localizing signs are: 1 A sixth nerve lesion, first on the side of a mass and later bilaterally, is caused as the nerve is compressed during its long intracranial course.
2 A third nerve lesion develops as the uncus of the temporal lobe herniates caudally, compressing the third nerve against the petroclinoid ligament and stretching it by downward displacement of the posterior communicating artery. The first sign of this is dilatation of
the pupil as the parasympathetic fibres in the nerve are compressed.
3 Hemiparesis on the same side (i.e. ‘the one you don’t expect’) as a hemisphere tumour is caused by compression of the brain stem (the contralateral cerebral peduncle) on the free edge of the tentorium.
These false localizing signs ‘lfe of importance in clinical neurology because their development indicates that a shift of the brain is taking place. Urgent surgical intervention may be necessary.
Seizures
Partial seizures, simple or complex, which may evolve to generalized tonic-clonic seizures, are characteristic features of many hemisphere masses, whether malignant or benign. The site of origin of a partial seizure is frequently of localizing value (se p. 913). Generalized tonic-clonic seizures with EEG (but not clinical) evidence of a focal onset also occur.

INVESTIGATION
CT scan is the investigation of choice when the diagnosis of a turnour is suspected. cr scan
It is important to emphasize that CT indicates only the site of a mass and not its nature. Cerebral abscess, cerebral infarction, benign and malignant tumours have characteristic, but not entirely diagnostic, appearances. Contrast enhancement adds to the discriminating ability
of CT and should be used when a mass is suspected.

MRI

MRI is often more discriminating than other noninvasive tests, particularly for posterior fossa turnours.

 EEG

The EEG may show electrical abnormalities in the regionof a mass (but it may be normal): it is rarely of major  value in management. The main exception is with cerebral abscess, where the EEG shows characteristic marked slow wave changes.
Technetium brain scan
This is sometimes useful to confirm the site of a lesion shown on CT, but the test discriminates poorly and misses many tumours. Very occasionally this test shows a lesion that has been missed by CT.
Skull films Plain X-rays of the skull are discussed on p. 874. In pituitary and parasellar lesions they do give important information about changes in the dorsum sellae and clinoid processes. In hemisphere lesions, plain films are frequently abnormal but the test has little value as a screening process.
‘Routine’ tests
Since the proportion of cerebral turnours that prove to be metastases is high, ‘routine’ tests such as a chest X-ray are of great importance.
Specialized neuroradiology Angiography, ventriculography and other contrast studies may sometimes be necessary to define the site or the blood supply of a mass.

Lumar puncture

Lumbar puncture is contraindicated when the differential diagnosis includes any mass lesion. Examination of CSF rarely yields diagn stically useful information in this situation, and the procedure may be followed by immediate herniation of the cerebellar tonsils.
If there are pressing reasons for the procedure it  should be carried out after careful assessment of the consequences and after a CT scan has been performed.

TREATMENT

Surgical exploration and either biopsy or removal of the mass is usually carried out to ascertain its nature. Some benign turnours can be removed in their entirety.  adiotherapy is usually recommended for gliomas and for radiosensitive metastases. Chemotherapy is of little value in the majority of primary brain turnours.
Cere ral oedema surrounding a turnour is rapidly reduced by corticosteroids; dexamethasone or betamethasone are used by injection in an emergency. Intravenous mannitol may also be used as an osmotic diuretic. Epilepsy is treated with anticonvulsants. With all malignant brain turnours the overall outlook is poor, with less than 50% survival at I year. Meningiomas are, however, often removed in their entirety and
thus cured.

Infective and inflammatory disease

MENINGITIS

Meningitis (inflammation of the meninges) may becaused by:
• Bacteria
• Viruses
• Fungi
• Other organisms
• Malignant cells
• Drugs and contrast media
• Blood (following SAH)
The term is usually restricted to inflammation due to infective agents (Table 18.41). Microorganisms reach the

Bacteria
Neisseria meningitidis”
Haemophilus irdluenzse:
Streptococcus pneumoniee”
Staphylococcus aureus
Listeria monocytogenes
Gram·negative bacilli
Mycobacterium tuberculosis
Treponema pallidum
Viruses
Enteroviruses
Echo
Coxsackie
Polio
Mumps
Herpes simplex
HIV
Epstein-Barr virus
Fungi
Cryptococcus neoformans
Candida
(Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis in USA)

PATHOLOGY
In acute bacterial meningitis the pia-arachnoid is congested with polymorphs. A layer of pus forms that may organize to form adhesions, causing cranial nerve palsies and hydrocephalus. In tuberculous infection the brain is covered in a viscous grey-green exudate; numerous
tubercles are found on the meninges. Cerebral oedema is common in bacterial meningitis. In viral meningitis there is a predominantly lymphocytic inflammatory reaction in the CSF without the formation of pus or adhesions. There is no cerebral oedema unless viral encephalitis develops.

CLINICAL FEATURES

Meningitic syndrome
There is intense malaise, fever, rigors, severe headache, photophobia and vomiting. The patient is irritable and often prefers to lie still.
Neck stiffness and a positive Kernig’s sign appear within a few hours. In milder cases (and many viral meningitides) there are few other signs, but it is most  unreliable to rely on the clinical impression alone whenassessing the severity of the infection. In uncomplicated meni ngitis, consciousness is not impaired, although the patient may be delirious with a high fever. Papilloedema may occur. The appearance of drowsiness, lateralizing signs and cranial nerve lesionsindicate a complication such as a venous sinus thrombosis  (see p. 912), severe cerebral oedema or hydrocephalus, or an alternative diagnosis such as a cerebral abscess (see p. 930) or encephalitis

Specific varieties of meningitis Particular attention should be paid to rashes and associated clinical features (see Table 18.42), and a search
should be made for infected foci.
ACUTE BACTERIAL MENI GITIS. The onset is sudden, with rigors and a high fever. A petechial rash, often sparse, is strong evidence of meningococcal meningitis. Septicaemia may present with acute septicaemic shock.
TUBERCULOUS MENINGITIS. Tuberculosis causes a chronic meningitis commencing with vague headache, lassitude, anorexia and vomiting. Meningitic signs may appear only after some weeks. Drowsiness, focal signs and seizures may occur. A similar picture occurs in cryptococcal meningitis, the commonest fungal meningitis in Europe. MALIGNANT MENINGITIS. Malignant cells sometimescause a subacute or chronic meningitic process. Meningitis,  cranial nerve palsies, paraparesis and root lesions are seen, often in complex patterns. The CSF shows increased cells and protein and often a low glucose. Treatment is with intrathecal cytotoxic agents. The prognosis is poor.

DIFFERENTIAL DIAGNOSIS

Acute meningitis may resemble SAH, severe migraine and  ther causes of a sudden severe headache. Meningitis  hould be considered in all patients who have headache and fever.

MANAGEMENT
Meningitis is an emergency that has a high mortality even in countries with highly developed systems of health care. Although viral meningitis is a self-limiting condition, untreated bacterial meningitis is lethal; in most series the death rate is around 15% even with treatment. f meningococcal (or other acute bacterial) meningitis is diagnosed clinically, particularly in children, immediate treatment with intravenous benzylpenicillin should be started with subsequent urgent investigations. In this acute illness, minutes count.

If there is no suggestion of an intracranial mass lesion (when CT scanning should be performed), immediate lumbar puncture should be carried out. Typical changes in the CSF are shown in Table 18.43. CSF pressure is characteristically elevated. Blood should be taken for culture
and glucose levels as well as for routine tests. Chest and skull films should be taken if possible. Gram-staining of the CSF may demonstrate organisms (e.g. Gram-positive intracellular diplococci-pneumococcus;
Gram-nega tive cocci-meningococcus). Ziehl- Nielsen stain demonstrates acid-fast bacilli (tuberculosis), though these organisms are rarely numerous. Indian ink stains fungi.
Many serological tests are now available for CSF. Syphilitic serology should always be carried out. The clinical picture and CSF examination should allow at least a presumptive diagnosis of the cause of the meningitis to be made within several hours of presentation.
Patients with impaired consciousness should be nursed as described on p. 903. General management includes diazepam for convulsions and analgesics for headache. Treatment of bacterial meningitis
It is often possible to distinguish between viral, pyogenic, tuberculous and other organisms from the clinical setting and immediate examination of the CSF. If bacterial meningitis is suspected, high doses of antibiotics are started immediately. There should be close liaison with   microbiologist. In children, dexamethasone should also be given as this reduces the frequency of complications particularly deafness.
In a pyogenic meningitis in an adult (where the organism is unknown), intravenous benzylpenicillin 2 g 2- hourly and intravenous chloramphenicol 75 mg kg:” have been given. Because of resistant organisms it is now recommended that immediate i.v. cefotaxime is used instead. If the diagnosis of pneumococcal or meningococcal infectionhas been made, penicillin alone or cefotaxime are  used. Chloramphenicol alone or third-generation cephalosporins should be used in Haemophilus infections. Tuberculous meningitis is treated for at least 9 months with antituberculous drugs; rifampicin, isoniazid and pyrazinamide is the usual combination (see p. 686).
It is no longer necessary to use intrathecal antibiotics. Local infection (e.g. an infected paranasal sinus) should also be treated, surgically if necessary. Surgical repair of depressed skull fracture or meningeal tear may be necessary.
Polyvalent vaccines are available against recurrent pneumococcal meningitis (e.g. when there is a CSP leak following skull fracture) and against some strains of meningococci (see p.23). In meningococcal outbreaks rifampicin prophylaxis should be given to contacts and family members as well as to the patient.

Differential diagnosis of (SF pleocytosis Difficulties occur in meningitis when a raised, often mixed (lymphocyte and polymorph, i.e. pleocytic) picture is found but no infecting organism. This is sometimescalled ‘aseptic meningitis’. The conditions listed in Table  18.44 should be considered.

ENCEPHALITIS

Encephalitis’ is inflammation of brain parenchyma. It iscaused by a wide variety of viruses and may also occur  in bacterial and other infections.
Acute viral encephalitis In many cases a viral aetiology is presumed but not confirmed serologically or by culture. The usual organisms cultured from cases of viral encephalitis in adults in the UK are Echo, Coxsackie, mumps and herpes simplex viruses, Adenovirus, varicella zoster, influenza, measles and other viruses are rarer causes.

CLINICAL FEATURES

Many of these infections cause a mild self-limiting illness with headache and drowsiness. In a minority there is a more serious illness accompanied by focal signs, seizures and coma. Herpes simplex virus (HSV-1) accounts for many of these severe infections in Britain and has a mortality of around 20% even with treatment. In the Far East the Japanese B arbovirus is a more usual, and epidemic, cause of severe encephalitis, with a high mortality. depressed skull fracture or meningeal tear may be necessary.

Polyvalent vaccines are available against recurrentpneumococcal meningitis (e.g. when there is a CSP leak  following skull fracture) and against some strains of meningococci (see p.23). In meningococcal outbreaks rifampicin prophylaxis should be given to contacts and family members as well as to the patient. Differential diagnosis of (SF pleocytosis Difficulties occur in meningitis when a raised, oftenmixed (lymphocyte and polymorph, i.e. pleocytic) picture is found but no infecting organism. This is sometimes called ‘aseptic meningitis’. The conditions listed in Table 18.44 should be considered.

ENCEPHALITIS

Encephalitis’ is inflammation of brain parenchyma. It iscaused by a wide variety of viruses and may also occur in bacterial and other infections.
Acute viral encephalitis  In many cases a viral aetiology is presumed but not confirmed serologically or by culture. The usual organismscultured from cases of viral encephalitis in adults in the  UK are Echo, Coxsackie, mumps and herpes simplex viruses,
Adenovirus, varicella zoster, influenza, measles and other viruses are rarer causes.

CLINICAL FEATURES

Many of these infections cause a mild self-limiting illnesswith headache and drowsiness. In a minority there is a  more serious illness accompanied by focal signs, seizures and coma. Herpes simplex virus (HSV-1) accounts for many of these severe infections in Britain and has a mortality of around 20% even with treatment. In the Far East the Japanese B arbovirus is a more usual, and epidemic, cause of severe encephalitis, with a high mortality. Partially treated bacterial meningitis
Viral meningitis

Tuberculosis or fungi
Neoplastic meningitis
Para meningeal foci (e.g. paranasal sinus)
Syphilis
Intracranial abscess
Cerebral venous or arterial infection
Following subarachnoid haemorrhage
Encephalitis, including AIDS
Rare causes (e.g. cerebral malaria, sarcoidosis, Behcet’s
syndrome, Lyme disease

DIFFERENTIAL DIAGNOSIS
This includes:
• Bacterial meningitis complicated by cerebral oedema and/or cerebral venous thrombosis
• Cerebral abscess
• Acute disseminated encephalomyelitis
• Toxic confusional states in febrile illnesses and III septicaemia
INVESTIGATION
Investigation in severe cases includes CT scanning (which characteristically shows areas of oedema), EEG (which shows slow-wave changes and/or ‘periodic complexes’) and viral serology of blood and CSP. Brain biopsy is now seldom performed in the UK.
TREATMENT
Suspected herpes simplex encephalitis is immediately treated with intravenous acyclovir, the active form of which inhibits DNA synthesis. Phosphorylation of. this drug is dependent upon the presence of viral thymidine kinase; thus the drug is specific for herpesvirus infections. If the patient is in coma the outlook is poor whether or not drugs are given.
Supportive measures are required for comatose patients. Seizures are treated with anticonvulsants. Prophylactic immunization is possible against Japanese B encephalitis and sometimes advised particularly for travellers to the Far East in endemic areas.
Acute disseminated
encephalomyelitis (ADE)
This follows many common viral infections (e.g. measles, varicella zoster, mumps and rubella) and rarely after immunization against rabies, influenza or pertussis. The  clinical syndrome is often similar to acute viral encephalitis, with added focal brain stem and/or spinal cord
lesions due to demyelination, but in which viral particles are not usually present. The prognosis is variable. Mild cases recover completely but in severe cases (those in coma) mortality is around 25% and the survivors often have permanent brain damage. Treatment is supportive, with steroids and anticonvulsants.

MYELITIS

Myelitis means inflammation of the spinal cord causing paraparesis or tetra paresis. It occurs with varicella zoster or as part of a postinfective encephalomyelitis. Poliomyelitis is a specific enterovirus infection of anterior horn cells .
.
HERPES ZOSTER (SHINGLES)

This is a recrudescence of infection with varicella zoster virus within the dorsal root ganglia, the original infection having been acquired in an attack of chickenpox many years previously. The viruses causing chickenpox and shingles are identical.

Multiple sclerosis

MS is a common disease of unknown cause in which there are multiple areas of demyelination within the brain and spinal cord. These are ‘disseminated in time and place’ (hence the old name ‘disseminated sclerosis’). An acquired defect in the oligodendroglial cells that produce myelin is responsible. The commonest age of onset is between 20 and 35 years, the disease being commoner in women. In the UK MS causes disability of varying degree in over 50000 people.

PREVALENCE

The disease occurs worldwide, but the prevalence varies widely, being directly proportional to the distance from the equator. At 50-650 N (roughly Land’s End to Iceland) the prevalence is 60-100 per 100000 people; at latitudes less than 300 N the prevalence is less than 10 per 100 000; and at the equator it is a rarity. In the Southern Hemisphere the variation is similar, with progressive increase in prevalence away from the equator.

AETIOLOGY

The cause of the disease is unknown. Familial incidenceand HLA linkage First-degree relatives of a patient have an increased  chance of developing MS, although there is no clear-cut pattern of inheritance. There is an increased concordance amongst monozygotic twins. In Caucasians in northern Europe and the USA, there is a positive association between MS and antigens HLAA3, B7 and DRl. Infection Although efforts to transmit MS experimentally have been uniformly unsuccessful, there is an abnormal immune response in MS patients, with an increase in the titres of serum and CSF antibodies to many common viruses, particularly measles.
Certain epidemic transmissible zoonoses, such as scrapie, a demyelinating disease in sheep, are pathologically similar to MS. Human T-cell leukaemia virus 1 (HTLV- 1) infection in humans (tropical spastic paraparesis) is an example of a viral demyelinating disease. Diet
It has been suggested that MS is related to the consumption of large quantities of animal fats. Surveys in Norway have shown that MS is distinctly uncommon in coastal fishing communities compared with agricultural areas. However, the role of diet is particularly difficult to
evaluate.
PATHOLOGY
The essential features are plaques of demyelination, initially 2-10 mm in size (Fig. 18.19). These lesions ire perivenular and have a predilection for the following sites within the brain and spinal cord:
• Optic nerves
• Brain stem and its cerebellar connections
• Cervical cord
• Periventricular region
Plaques rarely destroy large groups of neighbouring anterior horn cells (so that muscle wasting is unusual) and never occur in the myelin sheaths of peripheral nerves. Remyelination seldom occurs and the mechanism of the remission of symptoms is unclear.

CLINICAL FEATURES

No single group of signs or symptoms is diagnostic ofMS. Despite this, the disease is often recognizable on PREVALENCE  The disease occurs worldwide, but the prevalence varies widely, being directly proportional to the distance from the equator. At 50-650 N (roughly Land’s End to Iceland) the prevalence is 60-100 per 100000 people; at latitudesless than 300 N the prevalence is less than 10 per 100 000;  and at the equator it is a rarity. In the Southern Hemisphere the variation is similar, with progressive increase in prevalence away from the equator.
AETIOLOGY
The cause of the disease is unknown. Familial incidence and HLA linkage First-degree relatives of a patient have an increased chance f developing MS, although there is no clear-cut pattern of inheritance. There is an increased concordance amongst monozygotic twins.In Caucasians in northern Europe and the USA, there  is a positive association between MS and antigens HLAA3, B7 and DRl.
Infection
Although efforts to transmit MS experimentally have been uniformly unsuccessful, there is an abnormal immune response in MS patients, with an increase in the titres of serum and CSF antibodies to many common viruses, particularly measles.
Certain epidemic transmissible zoonoses, such as scrapie, a demyelinating disease in sheep, are pathologically similar to MS. Human T-cell leukaemia virus 1 (HTLV- 1) infection in humans (tropical spastic paraparesis) is an example of a viral demyelinating disease.
Diet It has been suggested that MS is related to the consumption of large quantities of animal fats. Surveys in Norway have shown that MS is distinctly uncommon in coastal fishing communities compared with agricultural areas. However, the role of diet is particularly difficult to
evaluate.
PATHOLOGY

The essential features are plaques of demyelination, initially 2-10 mm in size (Fig. 18.19). These lesions ire perivenular and have a predilection for the following sites
within the brain and spinal cord:
• Optic nerves
• Brain stem and its cerebellar connections
• Cervical cord
• Periventricular region
Plaques rarely destroy large groups of neighbouring anterior horn cells (so that muscle wasting is unusual) and never occur in the myelin sheaths of peripheral nerves. Remyelination seldom occurs and the mechanism of the remission of symptoms is unclear.

CLINICAL FEATURES

No single group of signs or symptoms is diagnostic of MS. Despite this, the disease is often recognizable on clinical grounds. There are two patterns:

1 Relapsing and remitting MS with lesions occurring in different parts of the CNS at different times
2 Chronic progressive MS (approximately 20%) Common presentations of MS are described below.

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ptic neuropathy (ON)

SYMPTOMS. The patient complains of blurring of vision in one eye. Mild ocular pain is usual. The symptoms progress, usually over days, to produce severe visual loss. Recovery occurs, typically within a month. Bilateral ON occasionally occurs. SIGNS. The signs of ON depend upon the site of the plaque. When the lesion is in the optic nerve head there is disc swelling (optic neuritis). If the lesion is several millimetres proximal to the disc there are often no ophthalmoscopic features (‘the doctor sees nothing and the patient sees nothing’); this is known as retrobulbar neuritis.
Optic neuritis is easily distinguished from papilloedema of other causes by the presence of early visual loss. A relative afferent pupillary defect is often present in the early stages. This persists after recovery.
SEQUELAE. There are usually no residual symptoms, but small scotomata and defects in colour vision can be demonstrated. Following the attack, disc pallor appears (optic atrophy), first in the temporal region and then spreading to affect the whole disc. The visual evoked responses (VER) remain abnormal (see below).
Brain stem demyelination
An acute episode affecting the brain stem causes diplopia, vertigo, facial numbness or dysphagia. ‘Pyramidal’ signs in the limbs occur when the corticospinal tracts are involved.
A typical picture is sudden diplopia and vertigo with nystagmus, but without tinnitus or deafness. This lasts for some weeks before recovery. Diplopia in MS may be caused by many different lesions-a sixth nerve lesion and an internuclear ophthalmoplegia (INO) are two examples.
Cord lesion
A spastic paraparesis is caused by demyelination in the cord. There is difficulty in walking and sensory disturbance. Urinary symptoms are common. In the initial episode it may be impossible to decide, even with specialized tests, whether or not a lesion is due to demyelination. The appearance of subsequent lesions confirms the diagnosis. Remissions may last for many years; their length is unpredictable.
Unusual presentations
Epilepsy occurs more commonly in MS patients than in he general population. So, too, does trigeminal neuralgia (see p. 887). Tonic spasms or brief spasms of a limb are other unusual symptoms of this disease.
End-stage multiple sclerosis In the later stages of the disease the patient is severely disabled with a combination of spastic tetraparesis, ataxia,
optic atrophy, nystagmus, brain stem signs, pseudobulbar palsy and incontinence of urine. Dementia is common. Death follows from uraemia and/or bronchopneumonia.

DIFFERENTIAL DIAGNOSIS

Few other neurological diseases of young people follow asimilar relapsing and remitting course. Thromboembolism  causes symptoms that are characteristically more sudden in onset. Other degenerative conditions, such as Friedreich’s ataxia, are gradually progressive, without remissions.
Initially individual plaques (e.g. in the optic nerve, brain stem or cord) may cause diagnostic difficulty; they must be distinguished from compressive, inflammatory, mass or vascular lesions.
CNS sarcoidosis, SLE and Behcet’s syndrome may mimic the relapsing pattern of MS.

INVESTIGATION

MRI of the brain is now the first-line investigation. Multipleplaques are visible, principally in the periventricular  region and brain stem (see Fig. 18.2). The lesions are rarely visible on CT scan. Examination of the peripheral blood and urine is unhelpful and there are no features on plain X-rays. Table 18.40 summarizes the changes seen in the CSF. The appearance and pressure of the fluid and the level of glucose are normal, and serological tests for syphilis are negative. The presence of oligoclonal bands of IgG indicate the production of immunoglobulin (to unknown antigens) within the CNS. This investigation is now being superseded by MR!.

Electrophysiological tests

Delay in the visual-evoked response (VER) follows opticneuropathy. As some attacks are subclinical, a delayed  VER may provide evidence of a second lesion within the CNS in, for example, an undiagnosed cord lesion. Brain stem and somatosensory evoked potentials are also sometimes measured. Peripheral nerve studies are normal. EEG recordings are unhelpful.
MANAGEMENT AND PROGNOSIS Once diagnosed, practical decisions need to be taken about employment, home and plans for the future in the face of a potentially disabling disease for which there is no curative treatment. It is now usual practice to informpatients of the diagnosis. There is no method of predicting the course  of MS but there is wide variation in its severity. Many MS patients live self-sufficient, productive lives while others are ravely disabled.
Wise counsel and honesty, tempeed with reassurance of the benign course of many cases of MS, is important. Many forms of therapy have been suggested for MS, including cryotherapy, pyrotherapy, vaccines, purified protein derivative (PPD), transfer factor, electrical stimulation, gluten-free diets, sunflower seed oil, arsenicals and hyperbaric oxygen. None of these has been shown to benfit patients.
Short courses of ACTH and corticosteroids are usedwidely in exacerbations and do sometimes appear to reduce temporarily the effect of a relapse. They do not influence the outlook in the long term. Immunosuppressants (azathioprine, cyclophosphamide) are also used, but there is no agreement about their value. Recently f3 interferonhas been shown to reduce the attack rate by a third  and reduces the number of lesions seen on MRI. In any chronic neurological disease, treatment of intercurrent infections is important. Urinary infection frequently exacerbates the symptoms.
Muscle relaxants (e.g. baclofen, benzodiazepines and  antrolene) reduce the pain and discomfort of spasticity,  articularly when there are flexor spasms of the lower limbs. Prevention of bed sores is vital.

Other measures

There is much that should be done for a patient with any chronic neurological disease. Practical advice at work, on walking aids, wheelchairs, car conversions, alterations to houses and gardens can be given. Support in a wide range of areas from fear and reactive depression to the sexual difficulties of the disabled is also helpful. Liaison between family practitioner, physiotherapist, occupational therapist and social worker is important.

Chorea

Chorea consists of jerky, quasi-purposive and sometimesexplosive movements, following each other but flitting  from one part of the body to another. The causes of chorea are listed in Table 18.38; the commoner conditions are outlined below.
Huntington’s disease
Relentlessly progressive chorea and dementia in middle life are the hallmarks of this inherited disease. The prevalence of the disease is about 1 in 20000. It occurs worldwide. Inheritance is as an autosomal dominant trait with full penetrance; the children of an affected parent have a 50% chance of inheriting the disease. The family history of the disease in previous generations is often concealed, either by design or default. A mutation has been identified at the distal short arm of chromosome  4 with a sequence of randomly repeated trinucleotides(CAG). The messenger RNA for the gene is expressed in many tissues and its protein product has been termed huntingtin.

Huntington’S diseaseSydenham’s choreaBenign hereditary chorea Abetaiipoproteinaemia and chorea Choreas associated with:
Drugs-phenytoin, levodopa, alcohol Thyrotoxicosis, pregnancy and oral contraceptive pill Systemic lupus erythematosus
Polycythaemia vera
Encephalitis lethargica
Stroke (basal ganglia)
Rarities (tumour, trauma, subdural haematoma, carbon monoxide poisoning)

PATHOLOGY. There is cerebral atrophy with marked loss of small neurones in the caudate nucleus and putamen. Three important changes in neurotransmitters occur:
1 There is reduction in the enzymes synthesizing acetylcholine and GABA in the striatum.
2 There is depletion of GABA, angiotensin-converting enzyme and met-enkephalin in the substantia nigra.
3 Somatostatin levels are high in the corpus striatum. These changes may be secondary to the cell damage. In contrast to Parkinson’s disease, dopamine and tyrosine hydroxylase activity are normal.
MANAGEMENT AND COURSE. There is steady progression, of both the dementia and chorea. No treatment arrests the disease, although phenothiazines may reduce the chorea by causing drug-induced parkinsonism. Tetrabenazine or sulpiride may help to control the chorea.
Death usually occurs between 10 and 20 years after the onset.
Mutation analysis, which is accurate and specific, is ecoming available for presymptomatic testing. This raises ethical problems and centres performing these tests have adopted a common protocol for counselling.
Sydenham’s chorea (St Vitus’ dance) Thomas Sydenham described this transient chorea of adolescence and childhood in 1686. Fewer than half of the cases follow within 3 months of rheumatic fever (se ep. 591). It may recur, or appear, in adult life during pregnancy (chorea gravidarum) or in those taking oral contraceptives. In each case there is a diffuse mild encephalitis. The onset of the chorea is usually gradual. Irritability, insolence and inattentiveness herald the onset of fidgetymovements, which are sometimes predominantly unilateral. A mino rity of patients are confused. Although rheumatic heart disease is sometimes found, the child usually does not have a fever or other features of rheumatic fever. The antistreptolysin-O (ASO) titre and erythrocyte sedimentation rate (ESR) are usually normal. Recovery occurs spontaneously within weeks or months.
Hemiballismus
Hemiballismus (also called hemiballism) describes violent swinging movements of one side of the body caused usually  y infarction or haemorrhage in the contralateral subthalamic nucleus.
Myoclonus
Myoclonus is the sudden, involuntary jerking of a single muscle or a group of muscles. It occurs in a wide range of disorders and is sometimes provoked by a sudden stimulus such as a loud noise.
Benign essential myoclonus
Nocturnal myoclonus, i.e. sudden jerking of a limb or the body on falling asleep, is extremely common and not pathological.

Paramyoclonus multiplex’ is widespread, random muscle jerking usually occurring in adolescence. Fits do not occur.
Myoclonic epilepsy
Muscle jerking is a feature of many different forms of epilepsy.
Progressive myoclonic epilepsy
These very rare conditions include various familial and metabolic disorders where myoclonus accompanies a progressive encephalopathy.
An example is Lafora body disease, a syndrome of myoclonus, epilepsy and dementia, with mucopolysaccharide inclusion bodies in neurones, liver cells and intestinal mucosa.

Static myoclonic encephalopathy

Myoclonus may follow a severe brain insult such as severe erebral anoxia following cardiac arrest. Tics
Repetitive twitching movements of the face, neck or hand are part of our normal motor gestures. Patients or their relatives seek advice about them when they become too frequent or irritating. Simple transient tics, e.g. sniffing or a particular facial grimace, are common in childhood,but may persist into adult life. The rare Gilles de la Tourette syndrome is  the occurrence of multiple tics accompanied by sudden explosive barking and grunting with the utterance of sexuallyrelated obscenities. The condition develops in childhood  or adolescence, in either sex, and is usually lifelong. This is thought to be due to an organic disorder of the basal ganglia. Treatment with haloperidol is sometimes helpful.

Torsion dystonias

Dystonia implies a movement caused by a prolongedmuscular contraction when a part of the body is thrown  into spasm. A classification of these unusual conditions Generalized dystonia Dystonia musculorum deformans Drug-induced dystonia (e.g. metoclopramide)Symptomatic dystonia (e.g. after encephalitis lethargica
or in Wilson’s disease) Paroxysmal dystonia (very rare, familial, with marked fluctuation)
Focal dystonia
Spasmodic torticollis
Writer’s cramp
Oromandibular dystonia
Blepharospasm
Hemiplegic dystonia (e.g. following stroke)

Parkinson’s disease and other movement disorders

Disorders of movement can be classified broadly into akinetic-rigid syndromes, where there is loss of move ment with increase in muscle tone, and dyskinesias, where there are added movements outside voluntary control. Both are due to disorders of neurotransmitters of the extrapyramidal system.
Parkinson’s disease is much the commonest of these conditions. A classification of movement disorders i
given in Table 18.37.
AKINETIC-RIGID SYNDROMES
Idiopathic Parkinson’s disease In 1817, James Parkinson, a physician in Hoxton, London, described the clinical appearance of patients with the ‘shaking palsy’. The disease is common and worldwide,with prevalence increasing sharply with age to about 1 in200 in those over 70 years. The condition is clinically distinct  from other ‘parkinsonian’ syndromes. There are few clues as to its cause:
NICOTINE. Some epidemiological studies suggest the disease is less prevalent in tobacco smokers than in lifelong abstainers.
MINUTE DOSES OF A PYRIDINE COMPOUND (MPTP)
(see p. 920) cause a severe parkinsonian syndrome. The significance of this to idiopathic Parkinson’s disease is not clear.
SURVIVORS OF ENCEPHALITIS LETHARGICA, which is presumed to be a viral disease, develop parkinsonism. However, it is not thought that the idiopathic disease is related to this or to another infective agent. The condition is not inherited.

PATHOLOGY

In the pars compacta of the substantia nigra there is progressive cell degeneration and the appearance of eosinophilic inclusion bodies (Lewy bodies). Degeneration also occurs in other brain stem nuclei. Biochemically there is loss of dopamine (and melanin) in the striatum that correlates  well with the areas of cell loss and also with the degree of akinesia. The underlying cause of these biochemical changes remains obscureAkinetic-rigid syndromes
Idiopathic Parkinson’s disease
Drug-induced parkinsonism, e.g.
phenothiazines MPTP-induced parkinsonism
Postencephalitic parkinsonism ‘Parkinsonism plus’
Childhood akinetic-rigid syndromes
Dyskinesias
Essential tremor
Chorea
Hemiballismus
Myoclonus
Tic or ‘habit spasm

CLINICAL FEATURES

There is a combination of tremor, rigidity and akinesia, together with important changes in posture. Symptoms
The commonest symptoms are tremor and slowness of movement. Patients also complain that the limbs feel stiff and ache and that fine movements are difficult. The slowness of movement causes the characteristic symptoms of difficulty in rising from a chair or getting into or out of bed. Writing becomes small (micrographia) and spidery, with a tendency to tail off at the end of a line. Other evidence of the disease often comes from relatives who have noted slowness and an impassive facial expression. Signs
TREMOR. This is a characteristic 4-7 Hz rest tremor that is usually decreased by action and increased by emotion. ‘Pill-rolling’ movements of the fingers and thumbs may be seen. The shaking is sometimes unilateral or more prominent on one side. .
RIGIDITY. Stiffnes s of the limbs develops that can be felt throughout the range of movement and is equal in opposing groups of muscles (in contrast to the selective increase in tone found in spasticity). This ‘lead-pipe’ rigidity is often more marked on one side and is present in the neck and axial muscles (where it is difficult to examine).
The rigidity is usually more easily felt when a joint is moved slowly and gently. Simultaneous active movement of the opposite limb increases the tone of the side under examination. When combined with tremor, the smooth plasticity of the increase in tone is broken up into a jerky resistance to passive movement, a phenomenon known as ‘cogwheeling’.
AKINESIA. The poverty and slowing of movement (bradykinesia) is an additional handicap, distinct from rigidity. There is difficulty in initiating movement. Rapid finger movements (such as piano-playing movements)
become indistinct,  slow and tremulous. The immobility of the face gives a mask-like facies with the appearance of depression. The frequency of spontaneous blinking is reduced, causing a ‘serpentine stare’.
POSTURAL CHANGES. A stoop is characteristic and the gait is shuffling, festinant and with poor arm swinging. The posture is sometimes called ‘simian’ to describe the forward flexion, immobility of the arms and lack of facial expression. The patient sits with the trunk bent forward and motionless, without gesture or animation, but the limbs are tremulous. Balance is impaired, but despite this the gait remains on a narrow base. Falls are common as the usual corrective righting reflexes fail, the sufferer falling stiffly ‘like a telegraph pole’.
SPEECH. Speech is altered to a monotonous slurring dysarthria, due to the combination of akinesia, tremor and rigidity. Dribbling is frequent, and dysphagia occurs as the disease progresses.
GASTROINTESTINAL SYMPTOMS. These include heartburn, dysphagia, constipation and weight loss.
OTHER FIDINGS. Urinary difficulties are common, especially in men. The skin is greasy and sweating is excessive.
Power remains normal until advanced akinesia makes its assessment difficult. There is no sensory loss, although patients often complain of discomfort in the limbs. The reflexes are normal (though they may be asymmetrical, following an asymmetrical increase in tone). The plantar responses are flexor.
Cognitive function is preserved, at least in the early stages. Dementia sometimes occurs in the late stages.

Natural history

Parkinson’s disease progresses over a period of years, beginning as a mild inconvenience but slowly overtaking the patient. Remissions are unknown except for rare and emarkable short-lived periods of release. These tend to occur at times of great emotion, fear or excitement, when the sufferer is released for seconds or minutes and ableto move quickly.
The rate of progression is very variable, with a benign form running over several decades. Usually the course is over 10-15 years, with death resulting from bronchopneumonia.

DIFFERENTIAL DIAGNOSIS

There is no laboratory test for the disease. The diagnosisis made on clinical grounds alone. The condition must  be distinguished from other akinetic-rigid syndromes. Hypothyroidism and depression also cause slowing of movement.
Certain diffuse or multi focal brain diseases cause some features of ‘parkinsonism’ (i.e. the slowing, rigidity and tremor). Alzheimer’s disease, multi-infarct dementia, and the sequelae of repeated head injury or hypo ia are the commoner examples.

TREATMENT

Older treatments with anticholinergic drugs altered the disease little, and frequently caused mental confusion. Benzhexol is still used in mild cases and as an adjunct to other therapy. Amantadine, originally introduced as an antiviral agent, is also sometimes helpful.
Levodopa
The introduction of levodopa in the late 1960s was a revolutionary therapeutic approach, apparently replacing thelost neurotran mitter dopamine. Today levodopa is usually combined with a peripheral decarboxylase inhibitor- benserazide (co-beneldopa, as Madopar) or carbidopa (co-careldopa, as Sinemet). This combined therapy reduces the periperal side-effects, principally nausea, oflevodopa and its metabolites. Tratment is commenced gradually (co-beneldopa 125 mg or co-careldopa ‘1l0’ one tablet three times daily) and increased until either an adequate improvement has taken place or side-effects limit further increase in dose. The great majority of patients with idiopathic Parkinson’s disease (but not other parkinsonian syndromes)
improve initially with levodopa. The response in severe, previously untreated disease may be dramatic.
UNWANTED EFFECTS OF LEVODOPA THERAPY. Nausea and vomiting within an hour of treatment are the commonest symptoms of the dose being too large. Confusion and visual hallucinations also occur. Chorea occurs in acute overdose.
As there are considerable problems with long-term treatment, levodopa therapy should not be started until necessary. Sometimes the drug appears to become ineffective, even with increasing doses. The disease progresses and the patient suffers from severe episodes of ‘freezing’and falls. Fluctuation in the response to levodopa may  also occur. The duration of action of the drug contracts, and the patient begins to suffer from a ‘chronic levodopa syndrome’, fluctuating between dopa-induced dyskinesias (chorea and dystonic movements) and severe and sometimes
sudden immobility (on-off syndrome).
These are major and often insoluble problems in management. Approaches to treatment of the complications
include the following:
THE INTERVAL BETWEEN LEVODOPA DOSES can be shortened and the individual doses reduced. SELEGILINE-a type B monoamine oxidase inhibitorinhibits the catabolism of dopamine in the brain. This sometimes has the effect of smoothing out the response to levodopa.
BROMOCRIPTINE, a directly acting dopaminergic agonist, is sometimes used.
‘DRUG HOLIDAYS’ -periods of drug withdrawal-are sometimes helpful. They require close supervision since severe rigidity and akinesia follow the withdrawal of levodopa.
Psychiatric aspects
Depression is common in Parkinson’s disease as the symptoms become worse and unresponsive to treatment. It is particularly difficult to treat, since type A monoamine oxidase inhibitor antidepressants (e.g. phenelzine) are absolutely contraindicated with levodopa, and tricyclic antidepressants (e.g. amitriptyline) have extrapyramidal side-effects.
All antiparkinsonian drugs, particularly in high doses, may cause confusion with visual hallucinations, which may exacerbate an associated dementia. Neurosurgery
Stereotactic placement of small lesions in the ventrolateral nucleus of the thalamus was commonly used in the two decades preceding the development of levodopa. The procedure was effective in reducing tremor but poor for relieving akinesia; it is now rarely performed.
Attempts to transplant fetal or autologous dopaminecontaining tissue (adrenal medulla) to the cerebral ventricles or basal ganglia, though technically feasible, have not produced any major clinical improvement in patients with Parkinson’s disease despite some early claims.
Physiotherapy and physical aidsSkilled and determined physiotherapy can improve  he gait and help the patient to overcome particular problems. Sensible guidance should be given about:
CLOTHING-avoiding zips, fiddly buttons and lace-up shoes.
CUTLERy-using built-up handles.
CHAIRS-high, upright chairs are easier to rise fromthan deep, comfortable armchairs. RAI LS-should be fitted near the lavatory and bath. SHOES- should be easy to put on and have smooth soles.FLOORING-patients’ feet sometimes ‘stick’ to carpets and rugs and they prefer to walk on vinyl or linoleum.  ALKING AIDS are often a hindrance in the early stages but later a frame or a tripod may be helpful.
Drug-induced parkinsonism Reserpine, phenothiazines and butyrophenones induce a parkinsonian syndrome, with slowness and rigidity but usually little tremor. Methyldopa and tricyclic ntidepressants also cause some slowing of movement. These syndromes tend not to progress. They respond poorly to levodopa. They disappear when the drug is stopped. Other movement disorders due to neuroleptic drugs Neuroleptic drugs (i.e. phenothiazines and butyrophenones) also produce other varieties of movement disorder.Three are described here.
AKATHIS IA. This is a restless, repetitive and irresistible need to move.
ACUTE DYSTONIC REACTIONS. These sometimes follow, unpredictably, single doses of these drugs, even those used as antiemetics or vestibular sedatives (such as prochlorperazine and metoclopramide). Spasmodic torticollis, trismus and oculogyric crises (i.e. episodes of sustained upward gaze) may occur. These acute dystonias respond promptly to the intravenous injection of an anticholinergic drug (e.g. benztropine 1-2 mg).
CHONIC TARDIVE DYSKINESIAS. These disabling disorders consist of mouthing and smacking of the lips,  rimaces and contortion of the face and neck. They tend to occur some 6 months after commencing neuroleptic therapy and may be made temporarily worse when the offending drug is stopped. Only about half of the cases eventually recover.
Postencephalitic parkinsonism
An epidemic of an encephalitic illness (encephalitis lethargica) occurred in 1918-1930 that left in its wake a severe extrapyramidal syndrome of parkinsonism with added dystonic movement disorders. Many of the survivors were permanently disabled. Occasionally, sporadic cases of the disease have been recorded recently in the UK; a recent epidemic may have occurred in Bulgaria. MPTP-induced parkinsonism MPTP (l-methyl-4-phenyl-,2,3,6-tetrahydropyridine) is an impurity roduced inadvertently when opiate analgesics are synthesized illicitly. A few cases of a severe and largely irreversible parkinsonian syndrome have followed
ingestion of minute quantities of M PTP. The relevance of this to idiopathic Parkinson’s disease is not clear. ‘Parkinsonism plus’
This describes rare disorders in which there is parkinsonism and evidence of a separate pathology. Progressive supranuclear palsy is the commonest disorder and consists of axial rigidity, dementia and signs of
parkinsonism together with a striking inability to move the eyes vertically or laterally.Other examples of ‘Parkinsonism plus’ are the rare
multiple system atrophies, e.g. olivopontocerebellar degeneration and primary autonomic failure (Shy- Drager syndrome).
Akinetic-rigid syndromes in children
A group of extremely rare disorders cause an akineticrigid syndrome in those under 20 years of age. The most important are Wilson’s disease and athetoid cerebral palsy.
Wilson’s disease
This is a rare and treatable disorder of copper metabolism that is inherited as an autosomal recessive disease. There is deposition of copper in the brain (particularly in the basal ganglia), in the cornea and in the liver (see p. 270). It is most important that all young patients with cirrhosis are screened for this condition, as the neurological damage is irreversible unless early treatment is instituted.  Children with the disease have an akinetic-rigid syndrome and/or dyskinesias followed by progressive intellectual impairment.
DIAGNOSIS AND TREATMENT

Athetoid cerebral palsy Writhing movements of the limbs, sometimes with an  increase in tone, are seen in cerebral palsy following kernicterus. This is now much less common following the prophylactic treatment of rhesus haemolytic disease. DYSKINESIAS Benign essential tremor This common condition, often inherited as an autosomal dominant trait, causes tremor at 5-8 Hz that is usually worse in the  pper limbs. The head is often tremulous (titubation) and also the trunk. Pathologically there is patchy neuronal loss in the cerebellum and cerebellar connections. Tremor is seen when the hands adopt a posture, such as holding a glass or a spoon. Oscillations are not usually present at rest nor do they worsen on movement. Essential remor may be seen at any age but occurs most frequently in the elderly. It is slowly progressive but rarely produces a severe disability. Writing is shaky and
untidy but there is no micrographia. Anxiety exacerbatesthe tremor, sometimes dramatically.  Treatment is often unnecessary. Many of those affected are reassured to find they do not have Parkinson’s disease, with which the condition is often confused. Small doses of alcohol and f3-adrenergic blockers such as propranolol often reduce the tremor. The anticonvulsant primidone also helps some patients. Sympathomimetics (e.g. salbutamol) make the tremor worse.Though usually postural, in some cases the tremor may  occur at rest (i.e. like Parkinson’s disease) or be cerebellar (i.e. with past pointing).

OTHER CAUSES OF RECURRENT ATTACKS OF DISTURBED CONSCIOUSNESS AND FALLS

Episodes of transient disturbance of consciousness and falls are common clinical problems. It is usually possible to distinguish between a ‘fit’ (a seizure), a ‘faint’ (syncope) and other types of attack from the history given by the patient and the account of an eye witness.

Syncope (situational or vasovagal)
‘Faint’
Cough
Effort
Micturition
Carotid sinus
Epilepsy
Narcolepsy and cataplexy
Transient ischaemic attacks
Psychogen ic attacks
Panic attacks
Hyperventilation
Night terrors }
Breath holding
Choking
Cardiac arrhythmias
Postural hypotension
Hypoglycaemia
Hypocalcaemia
Vertigo
Drop attacks
Hydrocephalus

Syncope (‘fainting’, vasovagal attacks) and related disorders. Sudden reflex bradycardia and peripheral and splanchnic vasodilatation leading to loss of consciousness occurs commonly in response to prolonged standing, fear, venesection or pain. This is also known as neurocardiogenic syncope. It almost never occurs in the recumbent posture. The subject falls to the ground and is unconscious for less than 2 minutes. Recovery is rapid. A few jerking movements are uncommon, but do occur. Incontinence of urine is exceptional. This is the ‘simple faint’ from which the majority of the population suffer at some time, particularly in childhood, in youth or in pregnancy. Syncope may occur after micturition in men(particularly at night) and when the venous return to  the heart is obstructed by breath-holding and severe coughing.The syndrome of carotid sinus syncope is believed to  be due to excessive sensitivity of the sinus to external pressure. It may occur in elderly patients who lose consciousness on touching of the neck.
Postural hypotension occurs in patients with impaired utonomic reflexes, e.g. in the elderly, in autonomic neuropathy, or with ganglion-blocking drugs used in hypertension, with phenothiazines, levodopa or tricyclic antidepressants. A tilt test will show hypotension as the  patient is raised to the vertical and is useful in diagnosis.Transient cerebral ischaemia in the posterior cerebral circulation is a cause of episodes of loss of consciousness in patients with cervical spondylosis in which vertebral artery compression occurs. Cardiac arrhythmias (cardiac syncope, Stokes-Adams attacks-see p.527) are important causes of recurrent episodes of loss of consciousness, particularly in the elderly. There is sometimes a preceding warning of palpitations (either f ast or slow). The loss of consciousness is sudden and accompanied by pallor. Exceptionally, there are convulsive movements (‘anoxic convulsions’). Flushing may occur when the patient recovers. The usual cardiac arrhythmias that cause loss of consciousness are paroxysmal bradycardias (e.g. in complete heart block) or tachycardias (e.g. ventricular tachycardias, ventricular fibrillation). Supraventricular tachycardias are unusual causes of loss of consciousness.
Effort syncope (syncope on exertion) is of cardiac origin (e.g. aortic stenosis, hypertrophic obstructive cardiomyopathy) .

INVESTIGATION

Syncope and related conditions where cerebral blood flow is impaired can usually be distinguished from epilepsy on the clinical history alone. Cardiac monitoring may sometimes be necessary to detect an arrhythmia. Tilt testing (see p. 541) is useful in neurocardiogenic syncope.

MANAGEMENT

The immediate management of syncope, or impending syncope, is to lie the patient down, to elevate the lower limbs and to record the pulse. In the rare circumstances where cerebral blood flow cannot be restored, e.g. in a dentist’s chair, syncope may be followed by cerebral infarction.

Drop attacks

These sudden episodes of weakness of the lower limbs with falling but without loss of consciousness occur in middle-aged women. They are believed to be due to sudden changes in tone in the lower limbs, presumably of brain stem origin. Previously they have been regarded as forms of TIA, from which they are distinct.Panic attacks. night terrors.  psychogenic attacks and hyperventi lation Panic attacks are usually associated with an autonomic disturbance, e.g. tachycardia, sweating and piloerection.
Consciousness is usually preserved. Hyperventilation (see below) is common. Night terrors are sudden episodes seen in children who awake as if from a dream in a state of terror.
Psychogenic attacks cause considerable difficulty in diagnosis. Attacks resembling grand mal fits may occur but more usually there are bizarre and irregular limb movements.
The alkalosis accompanying hyperventilation leads to a feeling of light-headedness, which may be accompanied by circumoral and peripheral tingling and tetany (e.g. carpopedal spasm) (see p. 430).
Hypoglycaemia (see also p. 852) Hypoglycaemia causes attacks in which the patient either feels unwell or may lose consciousness, sometimes with a convulsion. There is often some warning, with hunger, shaking and sweating. There is prompt relief with intravenous (or oral) glucose.
Hypoglycaemic attacks unrelated to diabetes are rare. ost patients who feel unwell after fasting or in the early morning have no serious organic disease.

Hypocalcaemia

A grand mal fit may accompany hypocalcaemia.
Vertigo Acute episodes of vertigo may cause prostration: consciousness is sometimes lost for a few seconds.
Choking Sudden prostration sometimes follows choking, particularly when a large bolus of meat obstructs the larynx. The patient goes blue, is speechless and may die in the attack if the obstruction is not relieved. Treatment involves immediately grasping the patient around the abdomen and squeezing hard in an effort to eject the food (Heimlich manoeuvre, see p. 656).
SLEEP AND ITS DISTURBANCES
Sleep is required on a regular basis  The reason for this is unclear; it is postulated that the laying down of memory is one important component. Complex pathways between the cortex and reticular formation are involved in the production and maintenance of sleep. During a normal night’s sleep, there are periods of deep sleep associated with rapid eye movement (REM). Dreaming occurs during REM sleep. In insomnia, sleep is fitful. Less time than usual is spent in REM sleep. Sleep requirement falls to as little as 4 hours a night in old age. Insomnia, particularly early morning waking, is a common symptom of depression (see p. 970). In practice, insomnia itself is rarely a feature of serious organic neurological disease but in the elderly nocturnal confusion and/or nightmares are caused by drugs and organic brain disease. In sleep apnoea, the normal short periods of apnoea seen during REM sleep are prolonged. This occurs with brain stem lesions and with upper airways obstruction, when it is accompanied by snoring. The latter is particularly important in patients with chronic bronchitis and emphysema, who may become severely hypoxic.
Narcolepsy and cataplexy Narcoleptic attacks are periods of irresistible sleep in inappropriate circumstances. They may occur when there is little distraction, after meals, while travelling in a vehicle, or without obvious cause. Genetically, narcolepsy is strongly associated with HLA-DR2 and HLA-DQwl antigens
Cataplexy is a sudden loss of tone in the lower limbs with preservation of consciousness. Attacks are set off by sudden surprise or emotion. The two conditions are related and may be accompanied by hypnagogic hallucinations (terrifying hallucinations on falling asleep), hypnopompic hallucinations (on waking) and sleep paralysis (a frightening inability to move whilst drowsy). The EEG is normal in these attacks.
Treatment is with methylphenidate, other amphetamine- ike drugs, or small doses of tricyclic antidepressants.