Pradeep P. Nair

Role of aspirin in tuberculous meningitis: A randomized open label placebo controlled trial

OBJECTIVE To evaluate the efficacy and safety of aspirin in preventing stroke and mortality in tuberculous meningitis (TBM). METHODS Patients with TBM diagnosed on the basis of clinical, MRI and cerebrospinal fluid (CSF) criteria were randomized into aspirin 150 mg daily or placebo. All the patients received four drug antitubercular treatment- RHZE (rifampicin, isoniazide, pyrazinamide and ethambutol) with or without corticosteroid. The primary endpoint was MRI proven stroke at 3 months and secondary end points were mortality and functional outcome assessed by Barthel Index score at 3 months. The adverse drug reactions were also analyzed. RESULTS 118 TBM patients were randomized into aspirin and placebo groups. The baseline demographic, clinical (severity of meningitis, MRI and CSF changes) were not significantly different between the two groups. 19 (16.1%) patients lost from follow up. 21 (33.3%) patients developed stroke after randomization which was insignificantly lesser in aspirin (24.2%) compared to the placebo group (43.3%; OR 0.42, 95%CI 0.12-1.39). Aspirin resulted in absolute risk reduction of stroke in 19.1% and significant reduction in mortality compared to placebo (21.7% Vs 43.4%, P=0.02). On binary logistic regression analysis, the age (OR 1.09, CI 1.03-1.14, P=0.001) was the only independent risk factor of stroke and aspirin was significantly related to survival (OR 3.17, 95% CI 1.21-8.31). Aspirin was well tolerated and was not withdrawn in any patient because of side effects. INTERPRETATION Aspirin resulted in insignificantly lesser strokes and significantly reduced 3 month mortality in patients with TBM.

Predictors of Stroke and Its Significance in the Outcome of Tuberculous Meningitis

BACKGROUND AND AIM We sought to study the frequency and predictors of stroke in tuberculous meningitis (TBM) and its prognostic significance. DESIGN This was an observational study in a tertiary care teaching hospital. METHODS In all, 122 patients with TBM aged 4 to 82 years diagnosed on the basis of clinical, cerebrospinal fluid, and magnetic resonance imaging criteria were prospectively evaluated. Severity of meningitis was graded into stage I to III. Magnetic resonance imaging was done at admission and 3 months after treatment. Outcome was defined at 3 and 6 months as complete, partial, or poor. Predictors of stroke and its significance in long- and short-term outcome were evaluated. FINDINGS A total of 55 patients had stroke; 42 at admission and 13 developed within 3 months of 4 drug antitubercular treatment. Strokes were ischemic in 54 (hemorrhagic transformation in 7) and hemorrhagic in one. Basal ganglia infarctions were present in 30, thalamic in 9, brainstem in 10, cortical in 27, and cerebellar in 4 patients. Stoke was multiple in 29 patients. In all, 38 patients had infarctions in anterior circulation, 7 in posterior, and 10 in both. Stroke was significantly related to stage of meningitis, hydrocephalus, exudate, and hypertension. No difference was found in clinical or laboratory parameters in early and late strokes. At 6 months, 28 patients died. At 3 months there were 21 patients lost to follow up and at 6 months there were 30 patients lost to followup. Outcome is based on the rest of the patients, ie. 101 patients at 3 months and 92 patients at 6 months. CONCLUSION Stroke occurs in 45% of patients with TBM both in early and later stage, mostly in basal ganglia region, and predicts poor outcome at 3 months.

Status Epilepticus in Central Nervous System Infections: An Experience From a Developing Country

OBJECTIVE There is a paucity of comprehensive study in status epilepticus in central nervous system infections. This observational study evaluated the response to antiepileptic drugs in patients with status epilepticus and central nervous system infection. METHODS The study took place at a tertiary care teaching hospital in India. A total of 37 of 93 adult patients (39.8%) with status epilepticus had central nervous system infection, and they underwent clinical evaluation, including status type and duration. Magnetic resonance imaging and cerebrospinal fluid analyses were performed. Patients were categorized into encephalitis, meningitis, and granuloma groups. The response to antiepileptic drugs was noted, and the status was considered refractory if seizures continued after the second antiepileptic drug. Refractory status epilepticus and mortality were correlated with the type of infection and various clinical and magnetic resonance imaging findings. RESULTS The median age of the patients was 37 years (16-78 years), and 17 patients were female; 35 patients had convulsive status epilepticus, and 2 patients had nonconvulsive status epilepticus. Twenty patients had encephalitis (Japanese 4, herpes simplex 3, nonspecific 12), including 1 patient with malaria, 9 patients with meningitis (tubercular 5, pyogenic 3, fungal 1), and 7 patients with granuloma (tubercular 5, neurocysticercosis 2). The mean duration of status epilepticus was 19.6 hours (0.25-72 hours). Magnetic resonance imaging results were abnormal in 66.7% of patients. In 67.6% of patients, status epilepticus was controlled after the first antiepileptic drug. Some 24.3% of patients were refractory to the second antiepileptic drug, and 10.8% of patients did not respond to the third antiepileptic drug. Patients with encephalitis had an insignificantly poor response. Eleven patients (29.7%) died, and mortality was higher in patients with refractory status epilepticus. CONCLUSION Of patients with status epilepticus and central nervous system infection, 24.3% had a refractory status that was associated with a high mortality. Their response to an antiepileptic drug in encephalitis was insignificantly poorer.

A study of cytokines in tuberculous meningitis: clinical and MRI correlation.

There is paucity of studies on cytokines in tuberculous meningitis (TBM) and their relation with clinical and radiological changes; therefore this study was undertaken. 16 TBM patients diagnosed on the basis of clinical, CSF and radiological criteria were included. They were subjected to TNF-alpha, IL-6, IL-8, IL-10, IL-1beta, and IL-12p70 estimation in CSF. The cytokine levels were also estimated in 10 controls. Initial clinical examination, stage of TBM and MRI findings (infarct, hydrocephalus, tuberculoma and exudates) were recorded. The patients were treated with 4 drugs antitubercular (RHZE) therapy and after 3 months clinical examination, cytokine levels, and radiological studies were repeated. Outcome was defined by Barthel index score at 3 months into poor, partial and complete recovery. The patients age ranged between 10 and 50 years, 5 were females. At 3 months, all the patients were clinically followed up and 14 underwent repeat MRI. 10 patients improved, 1 remained stable and 5 deteriorated. There was worsening with respect to tuberculoma in 3, infarction in 2 and exudate in 1 patient. TNF-alpha was expressed in 32% patients, IL-6, IL-10, IL-1beta and IL-8 were significantly expressed in patients and declined after 3 months following treatment. The cytokine levels did not correlate with stage of meningitis, outcome and radiological deterioration or improvement.

A clinical, radiological and outcome study of status epilepticus from India

The objective of this study is to evaluate the clinical and radiological characteristics and the outcome of status epilepticus (SE). 117 consecutive patients with SE were evaluated including their demographics, history of epilepsy, antiepileptic drug (AED) default, comorbidities, SE type and duration. The study included 22 children, 77 adults and 18 elderly patients with SE. Blood counts, serum chemistry, ECG, cranial MRI, cerebrospinal fluid and EEG were done. Patients were treated with IV phenytoin, valproate, lorazepam or diazepam as per a fixed protocol and responses to first and second drugs were noted. Death during hospital was recorded. The etiology of SE was infection in 53.8%, drug default in 7.9%, metabolic in 14.5%, stroke in 12.8% and miscellaneous in 11% of patients. 92.3% of patients had convulsive and 7.7% nonconvulsive SE. Cranial MRI was abnormal in 62%. Infection as an etiology was more common in children, drug default and metabolic causes in adults and stroke in adults and elderly. Following first AED, SE was controlled in 50%. 30% of patients remained refractory to second AED which was related to duration of SE and mortality. 29% patients died and death was higher in elderly (44%) compared to children (14%). Acute symptomatic SE is more common in developing countries. Refractory SE is associated with SE duration and mortality.

Diagnostic approach to peripheral neuropathy

Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx) tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG). EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block) and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG). Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF) examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them.

Status epilepticus in encephalitis: a study of clinical findings, magnetic resonance imaging, and response to antiepileptic drugs

This study evaluates clinical findings, magnetic resonance imaging (MRI), and response to antiepileptic drugs (AEDs) in encephalitis patients with status epilepticus (SE). Encephalitis patients with SE were included and they were grouped into herpes (HSE), Japanese (JE), dengue, and nonspecific encephalitis on the basis of virological studies. The demographic and clinical details, including SE type and duration, were noted. Cranial MRI and cerebrospinal fluid (CSF) were carried out. Response to first, second, and third AEDs were noted and the patients not responding to the second AED were considered refractory SE. The relationships of the mortality and the refractoriness of SE with various clinical findings, MRI, CSF, and the type of encephalitis were evaluated. Thirty SE patients with encephalitis aged 1 to 64 years were included. Nine patients had JE, 4 HSE, 1 dengue, and 16 nonspecific encephalitis. Generalized convulsive SE was present in 26 and nonconvulsive SE in 4 patients. The mean duration of SE was 21 (0.83 to 72) h. MRI was abnormal in 20 patients. A 46.7% of patients responded to the first AED and 36.7% remained refractory to the second AED. In 26.7% patients, the seizure continued even after the third AED. The response to AED was not related to the clinical, MRI, and laboratory variables. Nine patients died and the mortality was related to gender and Glasgow Coma Scale (GCS) score. In encephalitis with SE, 46.7% patients responded to the fist AED and 36.7% remained refractory to the second AED. One third of patients died, which was related to the depth of coma.

Role of cranial imaging in epileptic status

INTRODUCTION There is paucity of studies evaluating the role of cranial imaging in the management of status epilepticus (SE); therefore this study evaluates the role of imaging in predicting the outcome of SE. METHODS Consecutive patients with SE were prospectively evaluated. Clinical evaluation, blood counts, serum chemistry and cerebrospinal fluid (CSF) were carried out. Cranial CT scan was performed on a spiral CT and MRI on a 1.5 T scanner. Patients were treated with IV sodium valproate, phenytoin and benzodiazepines as per fixed protocol. Outcome was defined as seizure control at 1h and mortality. Various clinical and radiological parameters were correlated. RESULTS There were 99 patients with SE whose mean age was 35 (1-78) years, 40 females and 17 were below 12 years of age. Fifty six patients had central nervous system (CNS) infections, 15 strokes, 13 metabolic encephalopathy, 5 drug default and in the remaining 10 patients various acute symptomatic causes were present. Cranial imaging was abnormal in 59% patients. CT was abnormal in 21 (47.7%) out of 44 patients whereas MRI was abnormal in 26 (63.4%) out of 41 patients. Both MRI and CT were carried out in 14 patients and 12 revealed abnormalities; 2 had abnormality only on MRI. Imaging revealed cortical lesions in 10, subcortical in 19 and both cortical as well as subcortical in 30 patients. One hour seizure control was achieved in 60, seizures recurred within 24h in 38 and 27 patients died during hospital stay. Seizure type, duration of SE, seizure control at 1h and mortality did not correlate with radiological abnormalities. CONCLUSION Cranial imaging reveals structural abnormality in 59% patients with SE and was not related to SE control and mortality.

Endoscopic third ventriculostomy in tuberculous meningitis needs more evidence

Sir, We thank the authors for their interest in “cerebral malaria and bacterial meningitis” by Misra et al.[1] The authors highlight the importance of endoscopic third ventriculostomy (ETV) in the management of tuberculous meningitis (TBM) associated hydrocephalus. They suggest that ventriculoperitoneal (VP) shunt is no longer the treatment of choice; instead ETV should be preferred for the management of hydrocephalus even in the early stage of TBM as it precludes many shunt related problems such as infection and block.

Cerebral malaria and bacterial meningitis.

Malaria is one of the most common treatable and preventable infectious diseases in the world; and 300–500 million malaria cases occur annually, leading to 1.5–2.7 million deaths in tropical countries. About one-third of these cases occur in Asia. In hyperendemic area, most of the children acquire infection by the age of 5 years. Children younger than 6 months enjoy immunity from their mothers. In India the disease occurs in all the agegroups. Most clinicians would consider any manifestation of cerebral dysfunction in a patient with malaria as cerebral malaria. These manifestations include impairment of consciousness (confusion, delirium, obtundation, stupor, or coma), convulsions, focal neurologic deficit, and psychosis. These abnormalities can as well be due to hypoglycemia or high fever only. Hence a precise definition has been recommended, which has been summarized in Box 1. Box 1 Definition of cerebral malaria Practical definition