Infections of the nervous system I

Meningitis

Bacterial meningitis

This occurs in 5–10 per 100 000 per year in the developed world. The most common organisms are Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae. N. meningitidis tends to occur in epidemics. Neonatal meningitis is usually due to Escherichia coli or group B streptococcus. In developing countries, tuberculous meningitis is also common but usually clinically distinct (see below).

Overcrowding and poverty have been shown to be risk factors.

Meningitis can occur with organisms crossing the blood–brain barrier during systemic infection or as a result of a breakdown in the barrier, for example after skull fracture or a neurosurgical procedure. In the latter cases, a wider range of organisms is seen.

The clinical features of meningitis are:

headache

fever

neck stiffness.

There may also be altered consciousness, seizures and focal signs in about 15% of patients. Patients may have a positive Kernig’s sign (Fig. 1), another sign of meningism. Meningococcal meningitis may be associated with a purpuric rash (Fig. 2).

Fig. 1 Kernig’s sign. Flex the leg at the hip and knee and try to extend the knee. Low back pain with this procedure indicates meningeal irritation.

Fig. 2 Meningococcal rash.

Bacterial meningitis is a medical emergency. Treatment should begin as soon as the diagnosis is suspected and should not await investigation results or on occasion investigation. Acute treatment is usually with systemic penicillin and a third generation cephalosporin, though alternatively ampicillin and chloramphenicol may be used.

Blood cultures should be taken immediately. Lumbar puncture is important to confirm the diagnosis and determine the organism. However, if the patient has focal signs, altered consciousness or has had a seizure, then a CT brain scan or MRI needs to be done prior to the lumbar puncture. In severely ill children, lumbar puncture may lead to deterioration and should be avoided. The CSF findings are indicated in Table 1. The Gram stain and culture are usually diagnostic, and can be helped by newer tests for specific bacterial antigens.

Table 1 Typical changes in the CSF in different types of meningitis

The main differential diagnoses are subarachnoid haemorrhage and other meningitic illnesses.

There is a 10% mortality; 20% of patients have some sequelae, most commonly hearing loss, but also higher-function deficits and epilepsy.

Encephalitis

Infectious encephalopathies, either alone or with an associated meningitis (meningoencephalitis) present with altered behaviour, seizures, confusion or coma (p. 50). These patients often have a history of a prodromal infection and are febrile. Their CSF shows some abnormalities: a slightly lymphocytic pleocytosis (50–150 cells/µl) and an elevated protein level, usually with a normal glucose level. Brain imaging is usually normal. The EEG is slow, and cannot distinguish between infective and other encephalopathies.

Viral encephalitis occurs in about 10–15 per 100 000 per year. The syndrome can be caused by a range of different viruses: some are sporadic, such as herpes simplex virus (HSV), Epstein–Barr virus and adenovirus; others are epidemic, such as arbovirus infections (e.g. eastern equine encephalitis); and others such as rabies, are transmitted by animals. Virological diagnosis is often made after the acute illness, serologically or from viral culture. PCR is showing promise in the earlier diagnosis.

Outside epidemics, the major concern is whether the encephalitis is due to HSV, which is the proven cause in less than 10% of cases of viral encephalitis. The diagnosis is considered more frequently because specific antiviral therapy is available. The virus demonstrates a predilection to affect the temporal lobes. Clinically this is manifest as behavioural changes, speech disturbances, hemiplegia and seizures. The most common and disabling sequela, short-term memory loss, results from this. If the diagnosis is considered, the patient should be treated with aciclovir intravenously. Without treatment, the mortality rises to 80%, but falls to 30% with antiviral treatment. Patients with other sporadic viral encephalitis usually have a more benign course, resolving spontaneously. Most of these patients now receive aciclovir to cover the possibility of HSV.

Cerebral abscess

Cerebral abscesses are now rare. They result from:

direct spread into the brain from adjacent tissues (75%), such as paranasal sinus infection, or middle ear and mastoid infection

haematogenous spread (25%), particularly from a proximal source of infection such as endocarditis.

The presentation is with progressive headache (75%), focal neurological symptoms or signs (50%), fever (50%) and seizures (30%). The brain scan shows one or more usually ring enhancing lesions with associated oedema. There may be features of the primary infection, ear or sinus, and markers of systemic infection. The main differential diagnosis is cerebral tumours (p. 94). Management is with a combination of antibiotics and surgical drainage. There is a high incidence of epilepsy following cerebral abscess.

Non-bacterial intracerebral abscesses can occur. They are seen in toxoplasmosis, fungal infections, cerebral amoebiasis, cysticercosis or echinococcus in restricted geographical areas or in the immunocompromised (see below).

Slow infections

There are several infections that present in a chronic or subacute manner and can simulate degenerative disease. Subacute sclerosing panencephalitis, a progressive intellectual deterioration with seizures, myoclonus and progressive tetraparesis, occurs in late childhood and adolescence as the sequela to measles. Whipple’s disease is a rare infection with Tropheryma whippelii that can affect the bowel and, occasionally, the CNS. It is usually associated with supranuclear gaze disorder and sometimes with a bizarre rhythmical movement of the eyes and mouth. It is variable in its clinical manifestations.

The spongiform encephalopathies, Creutzfeldt–Jakob disease (CJD) and new-variant CJD, are rare but have been intensively studied recently. CJD occurs in about 1 per million per year; new-variant CJD had about 100 cases reported by 2004. They are caused by abnormalities in prion proteins. Some cases of CJD occur from transmission from using infected dural transplants or human pituitary extracted growth hormone. Most CJD is sporadic, but 5% of cases are familial and due to mutation of endogenous prion protein (chromsome 20), referred to as the Gerstmann–Straussler syndrome. The onset of the sporadic disease is usually between 50 and 70 years of age with dementia and subsequently myoclonus and typical EEG changes (Fig. 3); median survival is less than 1 year.

Fig. 3 EEG in classical CJD.

New-variant CJD presents in young adults with psychiatric disturbance, followed by dementia, ataxia and dystonia progressing over months. Myoclonus and typical EEG changes of classical CJD are absent. New-variant CJD is caused by transmission of bovine spongiform encephalopathy (BSE) from cattle to humans.

Infections of the nervous system I

Bacterial meningitis is a medical emergency.

Bacterial meningitis presents with headache, fever and neck stiffness.

Encephalitis can present with headaches, confusion, behavioural changes and seizures.