Central nervous system disorders

III./4.6.: Differential diagnosis of meningitises Differentiation is based on the neurological examination and on the patient’s history.

III./4.6.1.: Encephalitis

Encephalitis often lacks the symptoms of meningeal irritation contrary to bacterial meningitis. The probable source of meningitis has to be clarified; previous infections, diseases affecting the immune system, harmful environmental factors (animal contact, etc.) have to be ascertained. In Europe rare viral meningitises are caused by RNA viruses (picorna and enteroviruses: ECHO, Coxsackie, herpes simplex 1 (HS1) and herpes simplex 2 (HS2), arboviruses (arthropod-borne), lymphocytic choriomeningitis virus, mumps virus and poliomyelitis virus. Clinical symptoms: fever, headache, vomiting, agitation or lethargy and confusion, sometimes nuchal rigidity and hypnoid unconsciousness. Symptoms ease in 3-4 days, the illness rarely lasts longer than two weeks. Besides typical symptoms a few hundred lymphocytes in the lumbar liquor are considered as a specific finding as well.

III./4.6.2.: Tuberculous meningitis 

The prevalence of the disease is 1.5:100 000. Around 10% of TB meningitis occurs in patients with AIDS. TB is transmitted via inhalation. Bacteria form a granuloma in the brain. It leads to chronic fibrosis in the basal cisterns (basilar meningitis) and a consequent non-communicative hydrocephalus. Symptom progression is slow. Patients are subfebrile complaining of headaches and malaise. Signs of meningeal irritation can be absent. Later confusion, focal signs and altered consciousness can develop.

Diagnosis: liquor findings include mixed pleocytosis (few hundred lymphocytes and granulocytes), in the liquor sample fibrin can precipitate. Protein level is usually high, while the liquor sugar is low (protein/glucose dissociation).

TB bacteria can be found in 10-20% of all liquor cells. Bacteria can be cultured in vitro and with animal tests. TB skin test reaction is positive in 80-85% of TB meningitises. Treatment: Isoniazid and streptomycin treatment has to be initiated before the results of culture methods are known. Treatment of TB of the central nervous system consists of the ‘triple combination’ (isoniazid, rifampicine and ethambutol), which have to be administered for 3-6 months. Prognosis: mortality is low in case of an effective therapy, but residual symptoms (cranial nerve palsy, hydrocephalus, headache) can remain.

III./4.6.3.: Brain abcesses

Can originate from

• - hematogenous spread and

• - direct contamination from contiguous structures

The source of the hematogenous infection is most often the lung, or a subacute bacterial endocarditis or congenital heart diseases, as well as dental infections, tonsillitis or endometritis. Streptococcus spreading from the paranasal sinuses can cause a brain abscess in the frontal cortex. Temporal lobe and cerebellar abscesses are caused by the anaerob pyogens of otitis media. Staphylococci reach the brain following skull traumas through the sinuses and the ear. Brain abscess is surrounded by a perifocal oedema causing an increased intracranial pressure, which could result in medulla oblongata herniation.

In an early stage CT scan shows a hypodensity with enhancement around the abscess. In later stages the hyperdense capsule can also be seen without contrast material. Symptoms: headache, focal or generalized epileptic seizures, focal signs and signs of an increased intracranial pressure. Treatment: Parenteral antibiotic treatment is necessary (aminoglycosides, penicillin, third-generation cephalosporin, sometimes chloramphenicol). Neurosurgical decompression, drainage to prevent herniation should always be considered. Prognosis: mortality is 30% after a neurosurgical intervention, without that it is 60%.

III./4.6.4.: Syphilitic meningitis

Acute syphilitic meningitis is caused by Treponema pallidum, which is transmitted sexually. Meningitis develops in 6 weeks-1 year after infection. Symptoms: headache, vomiting, agitation, confusion, epileptic seizures and cranial nerve palsy (VII., VIII.). The above described stage can be followed by an asymptomatic period (latent syphilis). Meningovascular syphilis is a chronic meningitis occurring months or years after the infection. During this stage meningeal fibrosis is more pronounced than the inflammatory reaction. Due to vascular deficiencies the illness is accompanied by focal signs corresponding to the cerebral ischemia.

III./4.6.5.: Necrotizing herpes encephalitis

Necrotizing herpes encephalitis has a predilection for the mediobasal parts of the frontal and temporal lobes, the insula, and the frontal cingulate gyrus. The disease is characterised by the necrosis of neurons, glial cells and blood vessels. Clinical symptoms: fever, headache, altered consciousness, epileptic seizures, focal signs. Symptom progression is fast, in most patients a comatose state develops within a few days. Liquor findings include mononuclear pleocytosis (>100/3 cells) and moderately increased proteins. EEG proves the epilepsy in 90% of cases. MR and CT scans show the hemorrhagic necrosis along the temporal lobes.

Treatment: acyclovir administered early is effective, preventing viral reproduction in the infected cells. Prognosis: mortality of patients receiving treatment is 20% depending on age and the stage of altered consciousness. Under 30 in case of a mildly altered consciousness the prognosis is good. Dementia develops in most of the patients. Bilateral damage can result in Klüver-Bucy syndrome.

III./4.6.6.: Toxoplasmosis

In Europe 25-50%, in the USA 3-10% of patients suffering from AIDS develop a subacute Toxoplasma encephalitis (TE) or Toxoplasma abscess. Frequent symptoms include hemiparesis, aphasia, and epileptic seizures. TE occurs mostly in patients already diagnosed with AIDS, but sometimes can be the first manifestation of the illness as well. Neurological symptoms are only preceded by fever in half of the cases. The disease can be diagnosed with MRI, stereotactic brain biopsy and serological tests. It has to be differentiated from cerebral lymphomas and brain tumours. CT scans show the infection as bilateral, multiple lesions with annular contrast enhancement. MRI scans are able to reveal the small and multiple lesions as well.

III./4.6.7.: Fungal meningitis

Fungal meningitis is caused by Cryptococcus neoformans in 12% of patients suffering from AIDS. Clinical symptoms are often atypical, the only symptom is lethargy, signs of meningeal irritation, fever and headache can be missing. Liquor cell number is only rarely elevated. Cryptococcus antigens can be demonstrated from the liquor. Antimycotic treatment is temporarily effective in 60% of patients.

III./4.6.8.: Progressive multifocal leukoencephalopathy (PML)

Progessive multifocal leukoencephalopathy (PML) frequently occurs as a consequence of HIV infections. Histology of PML is characterized by the disseminated distribution in the hemispheres, brain stem, cerebellum and spinal cord of tumorous astroglia proliferation, inclusion bodies, perivascular infiltration and extensive demyelinisation.