Tuberculous Meningitis Clinical Presentation

Tuberculous meningitis (TBM) is difficult to diagnose, and a high index of suspicion is needed to make an early diagnosis.

Inquire about the patient’s medical and social history, including recent contact with patients with tuberculosis (TB). Elicit any known history of a positive result on the purified protein derivative test, especially a recent conversion. Determine if the patient has a history of immunosuppression from a known disease or from drug therapy.

Check if the patient has a negative history for bacillus Calmette-Guérin (BCG) vaccination. Walker et al reported that BCG vaccination is partially protective against TB meningitis; therefore, a history of BCG vaccination or the presence of a BCG vaccination scar affords some degree of reassurance when considering a diagnosis of TBM (grade C).^[18] In patients in whom TBM is suspected clinically, the diagnosis must be rigorously investigated; a history of BCG vaccination does not rule out the diagnosis (grade C).

In an immunocompetent individual, central nervous system (CNS) TB usually takes the form of meningitis that causes an acute-to-subacute illness characterized by fever, headache, drowsiness, meningism, and confusion over a period of approximately 2-3 weeks.

Usually, during the prodromal period, nonspecific symptoms are present, including fatigue, malaise, myalgia, and fever. In one study, only 2% of patients reported meningitic symptoms. The duration of presenting symptoms may vary from 1 day to 9 months, although 55% presented with symptoms of less than 2 weeks' duration.

Often, in the first stage of meningitis, patients have infection of the upper respiratory tract, a fact that should be remembered when the concurrent fever and irritability or lethargy seem out of proportion to the obvious infection or when general symptoms persist after improvement in the local manifestations. Fever and headache can be absent in 25% of patients, and malaise can be absent in as many as 60% of patients. Headache and mental status changes are much more common in elderly persons.

Visual symptoms include visual impairment or blindness and, occasionally, abrupt onset of painful ophthalmoplegia. Ocular tuberculosis presents a form of granulomatous uveitis. Delayed or wrong diagnosis may be detrimental to the ocular structures and the health of the individual.^[19]

Sudden onset of focal neurologic deficits, including monoplegia, hemiplegia, aphasia, and tetraparesis, has been reported. Tremor and, less commonly, abnormal movements, including choreoathetosis and hemiballismus, have been observed, more so in children than in adults. Myoclonus and cerebellar dysfunction have also occurred.

The syndrome of inappropriate antidiuretic hormone (SIADH) secretion is a common complication and is linked to a poor prognosis.

Less frequent presentations include atypical febrile seizures in children, isolated cranial nerve (CN) palsies, bilateral papilledema, and acute confusional state.

Tuberculous spinal meningitis

Tuberculous spinal meningitis may manifest as an acute, subacute, or chronic form. The clinical picture in primary spinal meningitis is often characterized by myelopathy, with progressive ascending paralysis, eventually resulting in basal meningitis and associated sequelae.

In some cases with acute onset, in addition to variable constitutional symptoms, patients develop acute paraplegia with sensory deficits and urinary retention. The clinical picture often mimics transverse myelitis or Guillain-Barré syndrome.

The subacute form is often dominated by myeloradiculopathy, with radicular pain and progressive paraplegia or tetraplegia. A less virulent chronic form might mimic a very slowly progressive spinal cord compression or a nonspecific arachnoiditis.

The dorsal cord seems to be affected most commonly, followed by the lumbar and the cervical regions.

Tuberculous spondylitis

Tuberculous spondylitis is also known as Pott disease or spinal caries. In regions where the disease is endemic, such as Asia and Africa, this condition still accounts for 30-50% of all cases of compressive myelopathy resulting in paraplegia. Spinal TB also accounts for approximately 50% of all bone and joint TB cases.

In the lumbar region, tuberculous spondylitis may result in a psoas abscess that often calcifies. It usually runs a subacute or a chronic course, with back pain and fever and variable neurological deficits. Spondylitis can also result in various symptoms, including local and radicular pain, limb motor and sensory loss, and sphincter disturbances.

Eventually, complete spinal cord compression with paraplegia, the most dreaded complication, may supervene.

Serous tuberculous meningitis and tuberculous encephalopathy

Two rare forms of TBM are serous TB meningitis and TB encephalopathy. Serous TB meningitis is characterized by signs and symptoms of a mild meningitis with spontaneous recovery.

TB encephalopathy usually occurs in a young child with progressive primary TB; the presentation is that of reduced levels of consciousness with few focal signs and minimal meningism. Diffuse edema and white matter pallor with demyelination are found upon pathologic examination. The pathogenesis is uncertain but is presumed to be immune mediated. Diagnosis is important because anecdotal reports suggest a good response to corticosteroids.

Tuberculous radiculomyelitis

Tuberculous radiculomyelitis (TBRM) is a rare complication of TBM.

Perform careful general, systemic, and neurologic examinations, looking especially for lymphadenopathy, papilledema, and tuberculomas during funduscopy, and meningismus. Look also for a BCG vaccination scar. Because BCG vaccination is partially protective against TB meningitis, the presence of a BCG vaccination scar affords some degree of reassurance when considering a diagnosis of TBM.^[18] Nevertheless, prior BCG vaccination does not rule out the diagnosis.

Visual findings

Apart from papilledema, fundus examination occasionally reveals a retinal tuberculoma or a small grayish-white choroidal nodule, highly suggestive of TB. These lesions are believed to be more common in miliary TB than in other forms of TB. In children, fundus examination may reveal pallor of the disc. Examination may elicit visual impairment.

Neurologic findings

Cranial neuropathies, most often involving CN VI, may be noted. CNs III, IV, VII, and, less commonly, CNs II, VIII, X, XI, and XII, also may be affected. Focal neurological deficits may include monoplegia, hemiplegia, aphasia, and tetraparesis.

Tremor is the most common movement disorder seen in the course of TBM. In a smaller percentage of patients, abnormal movements, including choreoathetosis and hemiballismus, have been observed, more so in children than in adults. In addition, myoclonus and cerebellar dysfunction have been observed. Deep vascular lesions are more common among patients with movement disorders.

TBRM is a complication of TBM that has been reported only rarely in the modern medical literature. It develops at various intervals after TBM, even in adequately treated patients after sterilization of the CSF. The most common symptoms are subacute paraparesis, radicular pain, bladder disturbance, and subsequent paralysis.

In 1948, the British Medical Research Council developed a method for staging the severity of the disease, as follows:

• Stage I describes the early nonspecific symptoms and signs including apathy, irritability, headache, malaise, fever, anorexia, nausea, and vomiting, without any alteration in the level of consciousness
• Stage II describes altered consciousness without coma or delirium but with minor focal neurological signs; symptoms and signs of meningism and meningitis are present, in addition to focal neurological deficits, isolated CN palsies, and abnormal involuntary movements
• Stage III describes an advanced state with stupor or coma, dense neurological deficits, seizures, posturing, and/or abnormal movements

Prognosis is related directly to the clinical stage at diagnosis.