Jayantee Kalita

Overview: Japanese encephalitis.

Japanese encephalitis (JE) is one of the most important endemic encephalitis in the world especially in Eastern and Southeastern Asia. JE affects over 50,000 patients and results in 15,000 deaths annually. JE virus is a single stranded positive sense RNA virus belonging to family flaviviridae. JE virus is transmitted through a zoonotic cycle between mosquitoes, pigs and water birds. Humans are accidentally infected and are a dead end host because of low level and transient viremia. In the northern region, large epidemics occur during summers whereas in the southern region JE tends to be endemic: cases occur throughout the year with a peak in the rainy season. Occurrence of JE is more closely related to temperature than to humidity. JE is regarded as a disease of children in the endemic areas but in the newly invaded areas, it affects both the adults and children because of the absence of protective antibodies. For every patient of JE, there are large numbers of subclinical cases (25-1000). Symptomatic JEV infection manifests with nonspecific febrile illness, aseptic meningitis or encephalitis. Encephalitis manifests with altered sensorium, seizures and focal neurological deficit. Acute flaccid paralysis may occur due to anterior horn cell involvement. A wide variety of movement disorders especially transient Parkinsonian features and dystonia (limb, axial, orofacial) are reported in 20-60% patients. JE mainly affects thalamus, corpus striatum, brainstem and spinal cord as revealed by MRI and on autopsy studies. Coinfection of JE and cysticercosis occurs because of the important role of pigs in the life cycle of both JEV and cysticercosis. Laboratory diagnosis of JE is by IgM capture ELISA, which has high sensitivity and specificity. In the absence of specific antiviral therapy, JE is managed by symptomatic and supportive therapies and preventive measures. Purified formalin inactivated mouse brain derived vaccine and live attenuated vaccine (SA 14-14-2) are available; the latter is reported to be safe, effective and cheap. The role of Chimeric recombinant attenuated JE vaccine is under investigation. Control of JE is related to the wider issues of hygiene, environment, education and economy.

Sodium valproate vs phenytoin in status epilepticus: A pilot study

Sixty-eight patients with convulsive status epilepticus (SE) were randomly assigned to two groups to study the efficacy of sodium valproate (VPA) and phenytoin (PHT). Seizures were aborted in 66% in the VPA group and 42% in the PHT group. As a second choice in refractory patients, VPA was effective in 79% and PHT was effective in 25%. The side effects in the two groups did not differ. Sodium valproate may be preferred in convulsive SE because of its higher efficacy.

Neurological manifestations of dengue virus infection

AIM Paucity of studies on neurological manifestations in dengue virus infection prompted this study. We aim to correlate clinical, radiological and neurophysiological changes in dengue patients with neurological manifestations. METHOD Consecutive IgM seropositive dengue patients admitted in neurology ward during 2003-2005 have been prospectively evaluated. They were subjected to detailed clinical evaluation, blood counts, coagulation profile, serum chemistry including creatine kinase (CK), cerebrospinal fluid (CSF), cranial CT and/or MRI, electroencephalogram (EEG), nerve conduction and needle electromyography (EMG). RESULTS There were 17 patients, aged 5 to 56 years; 11 presented with encephalopathy and 6 with acute motor weakness. In the patients with encephalopathy, seizures were present in 3, myoclonus in 1, CSF pleocytosis and EEG slowing in 8 each and globus pallidus and thoracic spinal cord involvement on MRI in 1 patient each. In the pure motor weakness group, CK was elevated in 5 and EMG and muscle biopsy were consistent with myositis in 1 patient each. The patients with pure motor weakness improved completely but in the encephalopathy group 3 died, 2 had partial, 1 poor and 5 complete recovery by 1 month. CONCLUSION Dengue patients presenting with encephalopathy had more severe illness and worse outcome compared to acute pure motor weakness.

Viral encephalitis and epilepsy.

Viral encephalitis presents with seizures not only in the acute stage but also increases the risk of late unprovoked seizures and epilepsy. Acute symptomatic and late unprovoked seizures in different viral encephalitides are reviewed here. Among the sporadic viral encephalitides, Herpes simplex encephalitis (HSE) is perhaps most frequently associated with epilepsy, which may often be severe. Seizures may be the presenting feature in 50% patients with HSE because of involvement of the highly epileptogenic frontotemporal cortex. The occurrence of seizures in HSE is associated with poor prognosis. In addition, chronic and relapsing forms of HSE have been described and these may be associated with antiepileptic drug‐resistant seizures. Among the epidemic (usually due to flaviviruses) viral encephalitides, Japanese encephalitis (JE) is most common and is associated with acute symptomatic seizures, especially in children. The reported frequency of acute symptomatic seizures in JE is 7–46%. Encephalitis due to other flaviviruses such as equine, St. Louis, and West Nile viruses may also manifest with acute symptomatic seizures. In Nipah virus encephalitis, seizures are more common in relapsed and late‐onset encephalitis in comparison to acute encephalitis (4% vs. 1.8%). Other viruses like measles, varicella, mumps, influenza, and entero‐viruses may cause seizures depending on the area of brain involved. There is no comprehensive data regarding late unprovoked seizures in different viral encephalitides. Prospective studies are required to document the risk of late unprovoked seizures and epilepsy following viral encephalitis due to different viruses as well as to determine the clinical characteristics, course, and outcome of post‐encephalitic epilepsy.

Intravenous Autologous Bone Marrow Mononuclear Stem Cell Therapy for Ischemic Stroke: A Multicentric, Randomized Trial

Background and Purpose— Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke. Methods— This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National Institute of Health Stroke Scale (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area of 18fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days. Results— Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset. There was no significant difference between BMSCs arm and control arm in the Barthel Index score (63.1 versus 63.6; P=0.92), modified Rankin scale shift analysis (P=0.53) or score >3 (47.5% versus 49.2%; P=0.85), NIHSS score (6.3 versus 7.0; P=0.53), change in infarct volume (−11.1 versus −7.36; P=0.63) at day 180. Adverse events were also similar in the 2 arms, and no patient showed any new area of 18fluorodeoxyglucose uptake. Conclusions— With the methods used, results of this hitherto first randomized controlled trial indicate that intravenous infusion of BMSCs is safe, but there is no beneficial effect of treatment on stroke outcome. Clinical Trial Registration— URLs: http://ctri.nic.in/Clinicaltrials and http://www.clinicaltrials.gov. Unique identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177.

Central Poststroke Pain : A Review of Pathophysiology and Treatment

BACKGROUND: Central poststroke pain (CPSP) is a disabling morbidity occurring in 8%–14% of patients with stroke. It is infrequently recognized and difficult to manage. OBJECTIVE: We systematically reviewed the pathophysiology and treatment of CPSP. METHODS: We conducted a Medline search using the key words “central post-stroke pain,” “post-stroke pain,” “CPSP and basic studies,” “CPSP and clinical features,” “CPSP and pharmacological treatment,” “CPSP and nonpharmacological treatment” and “CPSP and treatment guideline.” The articles related to CPSP were categorized into clinical features, pathophysiology and treatment, and then systematically reviewed. RESULTS: Stroke along the spinothalamocortical pathway may result in CPSP after a variable period, usually after 1–2 mo. CPSP may be spontaneous or evoked, variable in intensity and quality. It tends to improve with time. CPSP is associated with mild motor symptoms with relative sparing of joint position and vibration sensations. The pathophysiology of CPSP is not well understood, but central disinhibition, imbalance of stimuli and central sensitization have been suggested. There are few class I and class II studies regarding its management. Amitriptyline and lamotrigine (class IIB) are recommended as first-line and mexiletine, fluvoxamine and gabapentin as second-line drugs. In pharmacoresistant patients, repetitive transcranial magnetic stimulation and deep brain stimulation have been beneficial. CONCLUSIONS: CPSP patients present with diverse sensory symptoms and its pathophysiology is still poorly understood. Amitriptyline and lamotrigine are effective treatments. Further studies are needed to understand the pathophysiology and investigate newer therapeutic modalities.

MRI in Japanese encephalitis

Abstract We document the MRI features in seven patients with Japanese encephalitis. MRI was carried out on a 1.5 T system within 10–60 days of onset. In all the patients MRI revealed bilateral thalamic lesions, haemorrhagic in five. Signal changes were present in the cerebrum in four patients, the midbrain and cerebellum in three each, the pons in two and the basal ganglia in one. The lesions were haemorrhagic in three of the four patients with lesions in the cortex, two of the three with lesions in the midbrain and cerebellum, but the pontine lesions were haemorrhagic in both patients. Spinal cord involvement was seen in one of the three patients who underwent MRI. In two patients MRI was repeated 3 years after the onset, showing marked reduction in abnormal signal; and all the lesions gave low signal on both T1- and T2-weighted images. Bilateral thalamic involvement, especially haemorrhagic, may be considered characteristic of Japanese encephalitis, especially in endemic areas.

Mannitol in intracerebral hemorrhage: a randomized controlled study

OBJECTIVE To study the usefulness of mannitol in spontaneous intracerebral hemorrhage (ICH) patients. METHOD 128 CT proven supratentorial ICH patients within 6 days of ictus were randomized into study and control groups. The study group received mannitol 20%, 100 ml every 4 h for 5 days, tapered in the next 2 days. The control group received sham infusion. Primary endpoint was 1-month mortality and secondary endpoint functional disability at 3 months assessed by Barthel index score. RESULTS There were 65 patients in study and 63 in control groups. The study and control groups were evenly matched regarding age, Glasgow coma scale (GCS) score, Canadian Neurological Scale (CNS) score, pupillary asymmetry, pyramidal signs on non-hemiplegic side, and location, midline shift and ventricular extension of hematoma. At 1 month, 16 patients died in each group. The primary and secondary endpoints were not significantly different between the two groups. CONCLUSION Low dose mannitol does not seem to be beneficial in patients with ICH.

Movement disorders in Japanese encephalitis

Abstract Movement disorders in Japanese encephalitis (JE), although reported, have not been analyzed systematically. In this study, we report an analysis of movement disorders in 14 out of 17 JE patients, correlated with the radiological findings. All patients had at least a four fold rise of IgG antibodies against JE in a haemagglutination inhibition test. The patients’ ages ranged between 2 and 54 years and 4 of them were women. Extrapyramidal signs, such as hypokinesia, hypophonia and masking of the face, were present in all patients by the first month as the patients came out of the coma – except for 1 patient. Eight patients had axial and 3 tongue dyskinesia; rigidity was present in 6 and tremor in 2 patients. At 3 months, these symptoms improved considerably in 6 patients. Cranial CT scan revealed thalamic involvement in 10, which was bilateral in 9 patients. Two patients had brain stem and one had cerebellar involvement. Cranial MRI was carried out in 9 patients and revealed additional findings in lentiform nucleus, midbrain and pons in 3 each and cerebellum in 4 patients. Bilateral thalamic involvement on MRI was seen in all the patients, including two patients whose CT scans were normal. SPECT studies using 99mTc-ECD revealed bilateral thalamic hypoperfusion in all (n = 7) and frontal hypoperfusion in 3 patients. In JE, movement disorders are common and may be due to thalamic involvement in isolation or in combination with basal ganglia or midbrain or both.

Predictors of long-term neurological sequelae of tuberculous meningitis: a multivariate analysis.

There is paucity of studies on predictors of long‐term sequelae of tuberculous meningitis (TBM). We report the neurological sequelae of TBM at 1 year and their predictors. Patients with TBM who were followed up for 1 year were included. The diagnosis of TBM was based on clinical, cerebrospinal fluid (CSF) and computed tomography (CT) scan findings. Detailed neurological examinations at admission and at 1 year were carried out. All the patients received four‐drug antitubercular therapy. The frequency of sequelae at 1 year were noted and the role of various demographic (age, sex, duration of illness, BCG vaccination), clinical (weakness, seizure, extra central nervous system tuberculosis, Glasgow Coma Scale (GCS) score, cranial nerve palsy, stage, corticosteroid, drug‐induced hepatitis, shunt surgery), and laboratory findings (erythrocyte sedimentation rate (ESR), CSF cell and protein, CT scan evidences of hydrocephalus, basal exudates, infarctions and tuberculoma) at presentation were evaluated employing logistic regression analysis. Sixty‐five patients with TBM were included in this study whose age ranged between 13 and 80 years (mean 33.2), 27 of whom were females. Complete neurological recovery at 1 year occurred in 21.5% patients only although about 50% were independent for activities of daily living. Neurological sequelae were observed in 78.5% patients, which included cognitive impairment in 55%, motor deficit in 40%, optic atrophy in 37% and other cranial nerve palsy in 23%. On logistic regression analysis, focal motor deficit at admission was the most important predictor of neurologic deficits at 1 year. GCS score predicted the cognitive and motor sequelae. Neurological sequelae at year occurred in 78.5% patients with TBM in the form of cognitive impairment, motor deficit and optic atrophy. Sequelae were common in patients who had focal motor deficit and altered sensorium at admission.