Wilkinson. Essential Neurology 2005

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Pyogenic bacterial infections

Cerebral abscess and spinal extradural abscess are the consequences of localized pyogenic bacterial infection. Cerebral abscess is the more common of the two. Figure 15.1 shows the common clinical features of these two conditions.

Cerebral abscess

In the case of cerebral abscess, the continuing mortality from this condition is due to delay in diagnosis. The presence of a cerebral abscess must be anticipated whenever some of the features depicted in the left part of Fig. 15.1 occur. In particular, the presence of one of the local infective conditions which can give rise to cerebral abscess must put one ‘on guard’.

The non-specific features of an infection, i.e. fever, elevated white cell count and ESR, may not be very marked in patients with cerebral abscess. Epilepsy, often with focal features, is common in patients with a brain abscess. The diagnosis should be established before the focal neurological deficit (the nature of which will depend upon the site of the abscess) and evidence of raised intracranial pressure are too severe.

Urgent CT brain scan and referral to the local neurosurgical centre are the correct lines of management of patients with suspected cerebral abscess. Lumbar puncture is contra-indicated and potentially dangerous. Neurosurgical drainage, bacteriological diagnosis and intensive antibiotic treatment are required for a successful outcome.

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CT brain scan showing a large cerebral abscess, with surrounding cerebral oedema and shift of midline structures to the opposite side.

MR brain scan showing changes in both temporal lobes due to oedema and haemorrhage in herpes simplex encephalitis.

In the case of acute viral infections, the clinical picture may be of acute meningitis, acute meningo-encephalitis or acute encephalitis. A mild degree of acute meningo-encephalitis probably occurs in many acute viral infections, certainly in the common exanthematous infections of childhood, especially mumps. In adults with the clinical picture of acute viral meningo-encephalitis, the particular virus may not be identified, though ECHO and coxsackie viruses are those most frequently responsible. Meningo-encephalitis occurs at the time of seroconversion in HIV infection.

Herpes simplex encephalitis, caused by herpesvirus type 1, is the most potentially lethal acute viral infection of the CNS. It can occur at any age, and produces a largely encephalitic clinical picture with or without features of raised intracranial pressure. Brain swelling, especially in the temporal regions, is common, and reflects a highly damaging and necrotic process occurring in the brain tissue. Death, or survival with a significant neurological deficit (intellectual, physical and/or epileptic), are common sequels to this infection. Fortunately, the outcome is significantly improved if the antiviral agent, aciclovir, is given early in the course of the disease. Identification of herpes simplex antigen in the cerebrospinal fluid using the polymerase chain reaction is helpful in early diagnosis, but there is no certain way of knowing early enough in the course of the illness which cases of acute encephalitis are due to herpes simplex virus and which are due to other viruses. For this reason, any patient with acute encephalitis should receive aciclovir immediately, especially where the infection is fulminant and producing brain swelling on CT scan.

Japanese encephalitis is a similar illness caused by a mos- quito-borne flavivirus, endemic in India and Asia. There is no specific treatment but the infection can be prevented by vaccination. A related virus causes West Nile viral encephalitis in North America.

Bacterial infections

Acute bacterial infections of the CNS generally give rise to the clinical picture of acute meningitis (also known as bacterial meningitis, purulent meningitis and septic meningitis). It is helpful to remember, however, that these infections are meningo-encephalitic, since confusion or some alteration of the mental state, epilepsy and drowsiness are common features of bacterial meningitis. Furthermore, it is the brain involvement that is so worrying in fulminating infections, e.g. meningococcal meningitis, which may progress to coma within hours. Persistent purulent meningitis is very likely to give rise to CSF

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absorption problems, so that the clinical features of raised intracranial pressure appear, along with CT scan confirmation of hydrocephalus.

Bacterial meningitis is pre-eminently a disease of neonates and infants. It is a medical emergency. Delay in diagnosis and treatment increases both morbidity and mortality. In neonates, the common organisms tend to be Escherichia coli and Group B streptococci, but thereafter the common bacteria are Haemophilus influenzae, meningococcus and pneumococcus. The speed with which meningococcal meningitis can evolve requires stressing. Fulminating septicaemia and meningitis, with fever, shock, petechial or purpuric rash, rapid deterioration in conscious level, neck stiffness and a positive Kernig’s sign, may evolve with startling rapidity. Doctors should give penicillin to patients with suspected bacterial meningitis before transferring them to hospital. Once in hospital, intravenous treatment with a broad-spectrum antibiotic such as ceftriaxone should be started immediately, without being delayed for tests such as scans or lumbar puncture, and should be continued until there is good evidence that the causative organism is likely to be sensitive to a more specific antibiotic, or the diagnosis of bacterial meningitis has been refuted or the treatment is complete.

In all case of bacterial meningitis, perhaps more so in adults, and especially in any case of recurrent infection, a reason for the infection must be sought. The predisposition to infection may be:

1.local, for example:

•head trauma involving the floor of the anterior cranial fossa, possibly with CSF rhinorrhoea,

•head trauma involving the temporal bone, with access of bacteria to the CSF from the ear,

•shunt devices in situ for relief of hydrocephalus.

2.general, for example:

•diabetes mellitus,

•immunodeficiency or immunosuppression.

Other infective agents

Apart from viruses and bacteria, other infective agents causing acute meningo-encephalitis are not common in the UK. Two treponemal infections, leptospirosis and Lyme disease, are occasional causes of meningitis. Meningitis may occur at the height of Weil’s disease (infection with Leptospira icterohaemorrhagica), and the meningitis of Lyme disease (infection with Borrelia burgdorferi) is often associated with facial nerve palsy. An infection with M. pneumoniae in the lungs may be complicated by a meningo-encephalitis, which is usually not too severe.

CHAPTER 15

Viruses AIDS Rabies

Subacute sclerosing panencephalitis Progressive rubella panencephalitis Progressive multifocal

leucoencephalopathy

Bacteria Tuberculous meningitis Tetanus

Leprosy

Spirochaete Syphilis

Fig. 15.3 Subacute and chronic generalized CNS infections.

Subacute and chronic generalized CNS infections

None of these infections is common in the UK currently. This is because of comprehensive immunization of the population (tetanus, tuberculosis), widespread frequent use of antibiotics (syphilis), or because the condition, though common elsewhere in the world, has not yet reached the UK in significant numbers (rabies). None of the infections will be described in great detail therefore, though some awareness of each of them is certainly justified (Fig. 15.3).

AIDS

AIDS patients are predisposed to three groups of problems from the neurological point of view, as shown in Fig. 15.4. The direct effects of HIV and the secondary effects of immunosuppression are both considerably reduced by highly active retroviral therapy regimens, where these are available. In the UK therefore they tend to occur mainly in people who do not realize that they are infected with HIV. Such patients typically present with headache, focal deficit and epilepsy, with a low lymphocyte count and muted evidence of an inflammatory response to infection. Because the immune system is suppressed, microbiological diagnosis relies more on detecting antigens and DNA from the offending organisms than on identifying antibody responses from the patient. Initially it is often necessary to treat the infection that is most likely on clinical and radiological grounds, considering alternative diagnoses (such as lymphoma) if the response to treatment is poor.

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Progressive multifocal leucoencephalopathy

This is a rare condition, occurring in immunocompromised patients, characterized by the subacute accumulation of neurological deficits due to multiple areas of demyelination in the brain, mainly in the cerebral hemispheres. It is caused by opportunistic activation of a human papovavirus (the JC virus) infecting oligodendrocytes.

Rabies

This viral illness is usually contracted because the patient is bitten by an infected dog, which has the virus in its saliva. After a variable incubation period (usually 2–8 weeks, but sometimes much longer), a progressive encephalomyelitis occurs (hallucinations, apprehension, hydrophobia, flaccid paralysis with sensory and sphincter involvement), leading to bulbar and respiratory paralysis. Treatment is difficult, not very specific, prolonged and often unsuccessful. Post-exposure prophylaxis with immunoglobulin may be helpful.

Subacute sclerosing panencephalitis and progressive rubella panencephalitis

After a latency of some years following measles in early childhood or congenital rubella, a slowly progressive, fatal syndrome characterized by personality change, dementia, myoclonic seizures, and ataxia occasionally occurs.

Specific anti-measles or anti-rubella antibodies become increasingly evident in the CSF during the illness, indicating the presence of viral antigen within the CNS.

Tuberculous meningitis

Tuberculosis is increasing in incidence and becoming more resistant to treatment. Tuberculous meningitis causes the same symptoms as other forms of meningo-encephalitis (shown in Fig. 15.2) but evolves more slowly, over days or weeks. The meningitis is often concentrated around the base of the brain, causing cranial nerve palsies, and interfering with the circulation of CSF. Elevated intracranial pressure and hydrocephalus are common in tuberculous meningitis. It can also cause inflammation of the blood vessels as they leave the meninges to enter the brain, causing strokes.

CHAPTER 15

•Subacute accumulation of neurological deficits

•Dog bite abroad

•Incubation period

•Progressive encephalomyelitis

•Dementia

•Myoclonus

•Ataxia

•Subacute meningoencephalitis

•Cranial nerve palsies

•Hydrocephalus

•Evidence of infection

•Severe sensory loss

•Painless sores

•Muscle weakness and wasting

Leprosy is caused by Mycobacterium leprae infection of skin, nerves and mucous membranes. It affects about 600000 new patients each year, mainly in the Indian subcontinent and parts of Africa and South America. The incidence is falling in response to an international eradication programme, but there are still between 1 and 2 million people worldwide who are disabled by the chronic sequelae of the disease.

The milder, paucibacillary form causes hypopigmented skin macules. The macules have reduced pain and light touch sensation. The more severe, multibacillary form causes larger symmetrical skin lesions, nodules and plaques. Patients with this form of the disease are more likely to get a slowly progressive multifocal neuropathy (Chapter 9, see p. 146). Individual peripheral nerves become thickened and there is wasting, weakness and anaesthesia in the distribution of these nerves.

Treatment requires combination antibacterial therapy, with rifampicin and dapsone, combined with clofazimine in multibacillary cases.

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Syphilis

The CNS is involved in the tertiary phase of infection by the spirochaete, Treponema pallidum. Neurosyphilis is mainly encountered in patients with AIDS in the UK nowadays. The manifestations of neurosyphilis are:

•optic atrophy;

•Argyll–Robertson pupils, which are small, unequal, irregular, react to accommodation but do not react to light;

•general paralysis of the insane, in which meningoencephalitic involvement of the cerebral cortex (especially the frontal lobes, including the motor cortex) occurs. It gives rise to a combination of dementia and upper motor neurone paralysis of the limbs;

•tabes dorsalis, in which the proximal axons of the dorsal root ganglion cells, destined to travel in the posterior columns of the spinal cord, become atrophied. The clinical picture is one of proprioceptive sensory loss, especially in the legs. An unsteady, wide-based, stamping gait, and a tendency to fall in the dark, typify patients with tabes dorsalis;

•meningovascular syphilis is perhaps the most frequent clinical expression of neurosyphilis these days. The small arteries perforating the surface of the brain become inflamed and obliterated in the subacute syphilitic meningitis. Acute hemiplegia and sudden individual cranial nerve palsies are the most common clinical events in this form of the disease.

Malignant meningitis

This is a relentlessly progressive meningitis, often with cranial nerve and spinal nerve root lesions, and often associated with headache, pain in the spine or root pain. It is due to infiltration of the meninges by neoplastic cells rather than infection. The neoplastic cells may be leukaemic or lymphomatous, or may be derived from a solid tumour elsewhere. Such patients are often immunosuppressed, so the differentiation of malignant meningitis from an opportunistic infection of the meninges may be difficult. Cytological examination of the CSF may be very helpful, the malignant cells showing themselves in centrifuged CSF samples.

CHAPTER 15

•Optic disc pallor

•Abnormal pupils

•Cranial nerve palsy

•Dementia

•Upper motor neurone signs

•Posterior column sensory loss

•Abnormal gait

•Stroke

•Remorseless progression

•Painful

•Cranial nerve palsies

•Spinal nerve root lesions