Usha Kant Misra

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.

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.

Comparison of CT scan and MRI findings in the diagnosis of Japanese encephalitis.

Japanese encephalitis (JE) is the commonest endemic encephalitis but there are very few studies on the radiological changes and these are based on relatively small number of patients. The present study aims at comparing the CT scan and MRI findings in JE and correlate these with the reported histopathological findings. Forty two patients with JE were subjected to detailed neurological examination. Cranial CT scan was carried out in 38 and MRI scan in 31 patients. Haemagglutination inhibition test was carried out in the acute and convalescent sera. The CT scan and MRI findings have been compared. Both CT scan and MRI were available in 28 patients. In 21 patients, CT scans were abnormal and changes included thalamic hypodensity in 15, midbrain and basal ganglia hypodensity in 1 patient each, cerebral oedema in 4 and cortical atrophy with ventricular dilatation in 2 patients. MRI however was abnormal in all 31 patients including 17 with normal CT scan. Cranial MRI revealed either mixed intensity or hypointense lesion on T(1) and hyperintense or mixed intensity lesion on T(2) in thalami in all except two patients. The MRI lesions were also noted in basal ganglia in 11, midbrain in 18, pons in 8, cerebellum and cerebral cortex in 6 patients each and subcortical white matter in 2 patients. MRI was more sensitive than CT scan in revealing thalamic and extrathalamic abnormalities. Thalamic changes may be helpful in the diagnosis of JE especially in endemic area.

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 intraspinal tuberculosis

We studied 20 patients with intraspinal tuberculosis (TB), to characterise the MRI features of tuberculous meningitis and myelitis. MRI leptomeningitis and intramedullary involvement in 11 patients, intramedullary lesions alone in 5, leptomeningitis alone in 2, and isolated extradural disease in 2. TB leptomeningitis was characterised by loculation of the cerebrospinal fluid (CSF), nerve root thickening and clumping (seen only in the lumbar region) or complete obliteration of the subarachnoid space on unenhanced images. Gd-DTPA-enhanced images proved useful in 6 cases, revealing linear enhancement of the surface of the spinal cord and nerve roots or plaque-like enhancement of the dura-arachnoid mater complex. Intramedullary lesions included tuberculomas (8), cord oedema (5) and cavitation (3). In seven cases of intramedullary tuberculoma multiple lesions with skip areas were seen, without significant cord swelling. One patient had an isolated lesion in the conus medullaris. The lesions were iso- or hypointense on T1-weighted images, iso-, hypo- or hyperintense on T2-weighted images and showed rim or nodular enhancement with contrast medium.

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.

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.

Role of clinical, radiological, and neurophysiological changes in predicting the outcome of tuberculous meningitis: a multivariable analysis

OBJECTIVES The role of EEG and evoked potentials has not been evaluated in predicting the prognosis of tuberculous (TB) meningitis. The present study was aimed at evaluating the prognostic significance of clinical, radiological, and neurophysiological variables using multi-variable analysis. METHODS Patients with TB meningitis diagnosed on the basis of clinical, radiological, and CSF criteria have been prospectively evaluated. All the patients were subjected to a detailed neurological evaluation. The outcome was defined 6 months after starting treatment on the basis of the Barthel index (BI) score into poor (BI <12) and good recovery (BI⩾12). Death was included in the poor recovery group for statistical analysis. Thirteen clinical (age, sex, seizure, focal weakness, stage of meningitis, Glasgow coma scale score, methyl prednisolone therapy), CT (infarction, hydrocephalus, tuberculoma) and neurophysiological (EEG, motor and somatosensory evoked potentials) variables were evaluated employing single variable logistic regression followed by multivariable logistic regression analysis. The best set of predictors were obtained by stepdown logistic regression analysis. RESULTS Fifty four patients were included in the present study. Their age ranged between 5 and 62 years, 11 were children younger than 12 years and 14 were female. Nine patients were in stage I meningitis, 12 in stage II, and 33 in stage III. On single variable logistic regression analysis the significant predictors of 6 months outcome of TB meningitis included focal weakness, Glasgow coma scale (GCS), motor evoked potential (MEP) and somatosensory evoked potential (SEP). On multivariable analysis the best set of predictors comprised focal weakness, GCS, and SEP. CONCLUSIONS In patients with TB meningitis focal weakness, GCS, and SEP are the best predictors of 6 month outcome.