Quality of anticoagulation therapy in neurological patients in a tertiary care hospital in north India.

Background & objectives: There is paucity of studies on the quality of anticoagulation in neurological patients from India. This study evaluates the quality of oral anticoagulation therapy in neurology patients. Methods: Consecutive patients attending a tertiary care neurology service in north India who were prescribed oral anticoagulant (OAC), were included. Their international normalized ratio (INR) values were prospectively monitored and the earlier INR values of the patients who were already on OAC were retrospectively analyzed. The patients with multi-organ dysfunction, pregnancy and those below 18 yr of age were excluded. The therapeutic INR range was defined as per standard recommendations. The level of anticoagulation, factors interfering with OAC and complications were noted. Results: The results were based on 77 patients with median age 40 yr. Fifty one patients received OAC for secondary stroke prevention, 23 for cerebral venous sinus thrombosis (CVST) and three for deep vein thrombosis (DVT). A total 167.9 person-years of follow up was done with a median of 1.2 (0.3-9.3) years. Of the 1287 INR reports, 505 (39.3%) reports were in the therapeutic range, 496 (38.5%) were below and 282 (21.91%) were above the therapeutic level. Stable INR was obtained in 33 (42.86%) patients only. INR level was improved by dose adjustment in 20 (26%), drug modification in two (2.6%), and dietary adjustment in six (7.8%) patients. Three patients were sensitive and five were resistant to OAC. Complications were noted in 28 instances; thromboembolic in 16 and haemorrhagic stroke in 12. The overall complication rate was 16.7 per 100 person-years. Interpretation & conclusions: It may be concluded that stable therapeutic INR is difficult to maintain in neurological patients. Optimal modification of diet, drug and dose of oral anticoagulant may help in stabilization of INR.

Pharmacogenomic association study on the role of drug metabolizing, drug transporters and drug target gene polymorphisms in drug-resistant epilepsy in a north Indian population.

BACKGROUND: In epilepsy, in spite of the best possible medications and treatment protocols, approximately one-third of the patients do not respond adequately to anti-epileptic drugs. Such interindividual variations in drug response are believed to result from genetic variations in candidate genes belonging to multiple pathways. MATERIALS AND METHODS: In the present pharmacogenetic analysis, a total of 402 epilepsy patients were enrolled. Of them, 128 were diagnosed as multiple drug-resistant epilepsy and 274 patients were diagnosed as having drug-responsive epilepsy. We selected a total of 10 candidate gene polymorphisms belonging to three major classes, namely drug transporters, drug metabolizers and drug targets. These genetic polymorphism included CYP2C9 c.430C>T (*2 variant), CYP2C9 c.1075 A>C (*3 variant), ABCB1 c.3435C>T, ABCB1c.1236C>T, ABCB1c.2677G>T/A, SCN1A c.3184 A> G, SCN2A c.56G>A (p.R19K), GABRA1c.IVS11 + 15 A>G and GABRG2 c.588C>T. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods, and each genotype was confirmed via direct DNA sequencing. The relationship between various genetic polymorphisms and responsiveness was examined using binary logistic regression by SPSS statistical analysis software. RESULTS: CYP2C9 c.1075 A>C polymorphism showed a marginal significant difference between drug resistance and drug-responsive patients for the AC genotype (Odds ratio [OR] = 0.57, 95% confidence interval [CI] = 0.32–1.00; P = 0.05). In drug transporter, ABCB1c.2677G>T/A polymorphism, allele A was associated with drug-resistant phenotype in epilepsy patients (P = 0.03, OR = 0.31, 95% CI = 0.10-0.93). Similarly, the variant allele frequency of SCN2A c.56 G>A single nucleotide polymorphism was significantly higher in drug-resistant patients (P = 0.03; OR = 1.62, 95% CI = 1.03, 2.56). We also observed a significant difference at the genotype as well as allele frequencies of GABRA1c.IVS11 + 15 A > G polymorphism in drug-resistant patients for homozygous GG genotype (P = 0.03, OR = 1.84, 95% CI = 1.05–3.23) and G allele (P = 0.02, OR = 1.43, 95% CI = 1.05–1.95). CONCLUSIONS: Our results showed that pharmacogenetic variants have important roles in epilepsy at different levels. It may be noted that multi-factorial diseases like epilepsy are also regulated by various other factors that may also be considered in the future.

Methylenetetrahydrofolate reductase gene polymorphism in Indian stroke patients.

BACKGROUND AND AIMS: In view of the prevailing controversy about the role of Methylenetetrahydrofolate reductase (MTHFR) C677T mutation in stroke and paucity of studies from India, this study has been undertaken to evaluate MTHFR C677T gene polymorphism in consecutive ischemic stroke patients and correlate these with folic acid, homocysteine (Hcy) and conventional risk factors. SETTINGS AND DESIGN: Ischemic stroke patients prospectively evaluated in a tertiary care teaching hospital. MATERIALS AND METHODS: Computerized tomography proven ischemic stroke patients were prospectively evaluated including clinical, family history of stroke, dietary habits and addictions. Their fasting and postprandial blood sugar, lipid profile, vitamin B12, folic acid and MTHFR gene analysis were done. STATISTICAL ANALYSIS: MTHFR gene polymorphism was correlated with serum folic acid, Vitamin B12 and Hcy levels; family history of stroke in first-degree relatives; and dietary habits; employing Chi-square test. RESULTS: There were 58 patients with ischemic stroke, whose mean age was 50 (4-79) years; among them, 10 were females. MTHFR gene polymorphism was present in 19 (32.8%) patients, 3 were homozygous and 16 were heterozygous. Both serum folate and B12 levels were low in 29 (50%) patients and Hcy in 48 (83%). Hypertension was present in 28 (48%) patients, diabetes in 12 (21%), hyperlipidemia in 52 (90%), smoking in 17 (29%), obesity in 1 (1.7%) and family history of stroke in first-degree relatives in 13 (22.4%). There was no significant relationship of MTHFR gene polymorphism with folic acid, B12, Hcy levels, dietary habits and number of risk factors. Vitamin B12 level was low in vegetarians (P<0.003). In 3 patients with MTHFR TT alleles, Hcy was elevated in all 3, low folic acid in 2 and family history of stroke in 1 patient. CONCLUSION: MTHFR gene polymorphism was found in one-third of patients with ischemic stroke and was insignificantly associated with higher frequency of elevated Hcy.

Telemedicine in neurology: underutilized potential.

Advances in telecommunication which started with telephone lines, FAX, integrated service digital network (ISDN) lines and now internet have provided an unprecedented opportunity for transfer of knowledge and sharing of information. The information can be used for overlapping applications in patient care, teaching and research. In medicine there is increasing utilization of telemedicine; radiology and pathology being regarded as mature specialties and emergency medicine as maturing specialties compared to other evolving specialties which include psychiatry, dermatology, cardiology and ophthalmology. Of the emergencies, status epilepticus and stroke have high potential for improving patient management. Administration of tPA was more frequent when carried out under telemedicine guidance. Telemedicine has great potential for medical education. The principles of education are in congruence with those of telemedicine and can be closely integrated in the existing medical education system. Our experience of telemedicine as a medical education tool is based on video conferencing with SCB Medical College, Cuttack. We had 30 sessions during 2001 to 2004 in which 2-3 cases were discussed in each session. The patients' details, radiological and neurophysiological findings could be successfully transmitted. These conferences improved the knowledge of participants, provided an opportunity for a second opinion as well as modified the treatment decisions in some cases. The advances in telemedicine should be utilized more extensively in neurology, especially in emergency management, epilepsy and stroke patients as well, as it may have a role in neurophysiology and movement disorders.

Prescribing pattern of antiedema therapy in stroke by neurologists and general physicians.

BACKGROUND: In acute stroke, a number of drugs are used to reduce the raised intracranial pressure (ICP) although their scientific basis has not been established or shown in randomized controlled trials. AIMS: In this communication, we report the pattern of use of antiedema therapy in acute stroke by general physicians (GPs) and neurophysicians (NPs) in India. MATERIAL AND METHODS: A questionnaire was developed regarding the use of various antiedema measures in stroke and responses were collected either through post or when the responders were attending a national conference. The use of antiedema therapy by NPs and GPs was analyzed employing the Chi-square test. RESULTS: We could collect responses from 102 physicians, of whom 48 were NPs and 54 GPs. More than two-thirds of the physicians managed more than three strokes per week and all used antiedema therapy at some time or the other. Thirteen used it in all the patients and the remaining used it in patients with large and moderate strokes or in patients with herniation. Twelve used only one drug, while the remaining physicians used various combinations in different doses and frequency. The prescribing pattern was significantly different between GPs and NPs with respect to the frequency of the antiedema drugs used, type of stroke where these were used, combination of drugs, timing and dose of mannitol. CONCLUSION: This study highlights that antiedema therapy in acute stroke is practiced without any uniformity.

Tuberculous meningitis with pulmonary miliary tuberculosis: a clinicoradiological study.

BACKGROUND AND AIMS: This study aims at evaluating the clinical and radiological outcome of tuberculous meningitis (TBM) patients with pulmonary miliary tuberculosis. MATERIAL AND METHODS: Diagnosis of TBM was based on clinical, CT scan or MRI and CSF criteria, and that of miliary tuberculosis on chest radiograph. Detailed clinical evaluation was done in all. Severity of meningitis was graded into Grades I, II and III. Complete hemogram, serum chemistry and Montaux tests were performed. The recovery was defined on the basis of 6 months Barthel index score as poor, partial or complete. RESULTS: 20 out of 165 patients with TBM had pulmonary miliary tuberculosis. Their mean age was 30 years; there was one child and 13 patients were females. The mean duration of symptoms was 6.3 months. Montoux test was negative in 9 patients. Six patients were in stage I, 3 in stage II, and 11 in stage III meningitis. Hemoglobin was below 12 gm% in 13 and liver dysfunction and hypocalcaemia was present in 8 and 18 patients respectively. CT scan was abnormal in 16 patients and revealed hydrocephalus (10), granuloma (7), exudates (3) and infarction (1). MRI was abnormal in 7 out of 8 patients and 3 of these patients had normal CT scan. MRI revealed multiple granuloma in 7 patients and exudates in 2. At 6 months, 2 patients died, 10 had complete, 2 had partial and 4 had poor recovery. CONCLUSION: TBM with pulmonary miliary tuberculosis was commoner amongst females who were anemic and hypocalcaemic. MRI revealed multiple granuloma and the majority of the patients improved.

Sporadic variety of pallido-pyramidal syndrome.

A rare case of a 40-year-old lady with a sporadic variety of the pallido-pyramidal syndrome (PPS) is reported. She had marked parkinsonian features on the left side. Her single photon emission computed tomography showed left frontoparietal and basal ganglia hypoperfusion. CT scan and central motor conduction time were normal. She responded partially to a combination of trihexyphenydil and L dopa/C dopa therapy. In view of the diversity in the genetic, clinical and laboratory features, it is possible that PPS may be a heterogeneous condition.

Clinical, radiological and neurophysiological spectrum of JEV encephalitis and other non-specific encephalitis during post-monsoon period in India.

AIMS: To study the spectrum of encephalitis during the post-monsoon period in a tertiary care centre of India. METHODS: Clinical, neurophysiological and radiological features of patients with encephalitis are reported in this communication. The patients were subjected to clinical examination, CT or MRI scan, EEG, motor and somatosensory evoked potentials in both upper and lower limbs bilaterally and concentric needle electromyography. The laboratory studies for Japanese encephalitis (JE) comprised virus isolated, IgM capture ELISA, mercaptoethanol test and hemagglutination inhibition titre in paired sera against JE virus. Patients were classified into JEV encephalitis and non-specific encephalitis. On the basis of radiological features, they were classified into group I (thalamic or basal ganglia involvement), group II (brainstem involvement only) and group III (normal MRI). The outcome was defined into poor (bedridden), partial (dependent for daily activities) and complete (independent) recovery at the end of 3 months. RESULTS: Out of 26 patients (Age 7-70 years, mean 24.8 years), laboratory evidences of JEV infection was present in 14 patients and one patient had herpes simplex encephalitis. The patients with JEV encephalitis had more severe illness as evidenced by lower GCS score, higher frequency of anterior horn cell involvement, movement disorders and more extensive MRI changes. The EEG and MEP changes were also more frequently abnormal in the JEV group. On radiology, 15 patients had thalamic or basal ganglia involvement (group I), 3 isolated midbrain involvement (group II) and 8 had normal MRI (group III). Laboratory evidence consistent with JE were present in 11 out of 12 patients in group I and 3 out of 8 in group III, however, there was no laboratory evidence of JE virus infection in patients with isolated brainstem involvement. There was overlap in the neurologic and systemic manifestations in all the 3 radiological groups as well as in the groups with and without laboratory evidences of JEV infection. CONCLUSION: The observed overlap in neurological and systemic involvement in different subgroups of encephalitis may be due to JE or JE-like viral infection. The possibility of strain variation, change in virulence of organism or immunity of host needs further studies.

Landau Kleffner syndrome: electroclinical and etiopathogenic heterogeneity.

Landau - Kleffner syndrome is a rare, functional, age-related epilepsy with aphasia and epileptiform discharges on EEG. The heterogenity of clinical presentations, course, long-term outcome and response to treatment suggests multiple underlying etiologies. Normal children abruptly develop deterioration of language functions along with spike and wave discharges on EEG. Clinical seizures may or may not be present. The aphasia responds poorly to most drugs. Valproic acid and benzodiazepines are most effective. Steroids and intravenous immunoglobulins have shown a variable response. Long-term outcome of aphasia is variable, many patients persist with residual impairment. Important questions regarding etiopathogenesis are unanswered.

Neurophysiological changes in Japanese encephalitis.

Japanese encephalitis (JE) is an encephalomyelitis involving cortex, subcortex, brainstem and spinal cord. There is paucity of studies on the neurophysiological evaluation in JE. This study aims at comprehensive evaluation of EEG, sensory and motor evoked potentials, nerve conduction and electromyography; and correlate these with clinical findings. Sixty five patients with JE diagnosed on the basis of clinical, radiological and virological criteria were subjected to a detailed clinical evaluation during the acute stage of illness. Cranial CT scan or MRI was carried out in all the patients. All the patients underwent 10 or 18 channel EEG, motor and sensory evoked potentials to both upper and lower limbs bilaterally as well as peroneal and sural nerve conductions and concentric needle EMG. Outcome, was defined at the end of 3 months into poor, partial and complete recovery. The patient's age ranged between 2-65 years. There were 40 males and 25 female patients. Fifteen patients were less than 12 years of age. History of seizure was present in 31 patients. Quadriplegia was seen in 39 and hemiplegia in 8 patients. Muscle wasting was present in 16 patients and tendon reflexes were reduced in 12 and of mixed pattern in 14 patients. Cranial MRI revealed thalamic lesion in 38, basal ganglia in 21, substantia nigra in 30, pons in 5, cerebellum in 3 and cerebral cortex in 7 patients out of 57 patients. EEG revealed nonspecific theta to delta slowing in 45, alpha pattern coma in 5 and epileptiform discharges in 8 patients. EMG revealed fibrillations in 23 patients. Motor evoked potentials were abnormal in 34 out of 46 patients and revealed patchy and focal abnormalities comprising of unrecordable, prolonged and normal pattern. Somatosensory evoked potentials were abnormal in 8 patients only. At 3 month, 26 patients had complete, 13 partial and 15 had poor outcome. Eight patients died in acute stage and 3 were lost to followup. MEP correlated with weakness and 3 month outcome whereas EEG, SEP and EMG did not have any correlation. MEP changes were more frequent in JE and had prognostic significance.

Effect of methyl prednisolone on sensory motor functions in tuberculous meningitis.

A prospective hospital based study was undertaken to study the effect of methyl prednisolone therapy on sensory and motor functions in tuberculous meningitis (TBM). The patients with TB meningitis seen during 1994-1998 were studied. CT scan, motor evoked potential (MEP) to upper and lower limbs; and median and tibial somatosensory evoked potentials (SEP) were carried out in all the patients. Outcome was defined at the end of 3 months into poor, partial or complete recovery on the basis of Barthel index score. Inj methyl prednisolone (MPS) 500 mg IV was given to 21 patients followed by oral tapering dose of prednisolone over one month in addition to 4 drug anti-tubercular treatment. The control group comprised of 16 patients who received 4 drugs anti-tubercular therapy without any corticosteroid. These groups were comparable with respect to their age, stage of meningitis, Glasgow coma scale score and radiological findings. In MPS group, CMCT was abnormal in 9 and SEPs in 7 patients. In the control group, these were abnormal in 9 and 5 patients respectively. Three months after the therapy the frequency of improvement, deterioration and stationary evoked potential (EP) changes were also noted in both the groups. Diversity of evoked potential changes were also noted. Evoked potential changes were neither significantly different between the groups nor there was any beneficial effect shown in MPS group at 3 months. On the contrary, the control group fared significantly better than the MPS group. Initial MEP and SEP abnormalities were however related to 3 months outcome (p<0.01).

Seizures after stroke : a prospective clinical study.

Stroke is one of the most common causes of epilepsy in elderly. However, there have been very few prospective studies to define the incidence, pattern and outcome of seizures in stroke. Most studies are based on retrospective analysis of hospital records. Hence, we planned this prospective study to see the clinical, radiological and electroencephalographic characteristics of seizures in stroke and their outcome, from a north Indian tertiary care centre. Over a span of approximately 6 years, 269 consecutive patients with stroke were studied and followed up. Thirty-five (13%) of these developed seizures, primarily related to stroke, during mean follow up period of 15.9 months. Twenty of these had infarctions while 15 had haemorrhages. Involvement of the cortical region was seen in most of the patients with seizures. In these patients, 86% of the lesions involved cortical areas exclusively or in addition to subcortical areas on CT scan of the brain. Twenty-seven (77%) developed early seizures, two third of them had immediate post-stroke seizures. None of the patients with early onset seizures developed recurrent seizures or epilepsy, while 50% of late onset seizures developed epilepsy. No specific EEG pattern was found in those who later developed epilepsy. In the present study, early onset seizures after stroke were rather common and did not affect outcome and did not recur even when not treated with anti-epileptics. Late onset seizures were less common but were associated with recurrent seizures.

Brainstem auditory evoked potentials in tubercular meningitis and their correlation with radiological findings.

The present study has been undertaken to describe brainstem auditory evoked potential (BAEP) changes in tubercular meningitis (TBM) and correlate these with CT scan and MRI findings. 24 patients with TBM were subjected to clinical evaluation and CT scan or MRI study. Outcome was defined by 3 month Barthel index score (BI) into poor (BI<12) and good (BI>or=12). The mean age of patients was 26.4+/-14.9 (range 10-62) years, 8 of them were females. Sixteen patients were in stage III, 5 in stage II and 3 in stage I meningitis. CT scan revealed hydrocephalus in 16, exudate in 9, infarction in 12 and tuberculoma in 3 patients. Brainstem was involved in 3 patients (2 infarction and 1 granuloma). BAEPs were unrecordable in one patient and abnormal in 15. The absolute latencies and inter peak latency (IPL) however were not significantly affected. The wave V/I amplitude ratio was abnormal on 12 sides. The BAEP abnormalities were not related to the stage of meningitis, level of consciousness, any specific CT or MRI changes or outcome at 3 months.

A study of myasthenia gravis in patients with and without thymoma.

This study was undertaken to compare the clinical, neurophysiological, radiological and prognostic features of myasthenia gravis with and without thymoma. 37 patients with myasthenia gravis (27 males, 10 females), with age range of 4.5 to 72 (mean 39) years, were managed at a tertiary care centre in India. Four patients were below 15 years of age and 6 above 55 years. Most of the patients were in stage II (34). There were 2 patients in stage III and 1 in stage I. 27 patients underwent thymectomy. Thymoma was detected in 10 cases. The decrement in patients with thymoma ranged between 11 and 62% (mean 27.9%) and nonthymoma group 10-75% (mean 28%). CT scan of thorax revealed mediastinal mass in 5 out of 10 cases of thymoma and 2 out of 27 patients without thymoma. Outcome of myasthenia gravis with thymoma was worse than without thymoma at 1 year followup. Severity of illness, extent of decrement, lack of facilitation, duration of illness and age of the patients were not related to the outcome. It is concluded the clinical and neurophysiological changes in myasthenia gravis with and without thymoma do not differ. However, patients with thymoma have a worse outcome.

Motor dysfunction on the nonhemiplegic side in patients with intracerebral haemorrhage.

This study was undertaken to evaluate the motor dysfunction on the nonhemiplegic side in patients with acute intracerebral haemorrhage (ICH) and correlate these with radiological and motor evoked potentials findings. 28 patients (23 males, 5 females), with CT proven ICH within 10 days of ictus were subjected to clinical evaluation and central motor conduction studies (CMCT) of upper limbs. The patient's age ranged between 28 and 84 years. Motor signs on the nonhemiplegic side were present in 17 patients in the form of increased tone (10), hyperreflexia (13) and extensor plantar response (10). Sixteen of these patients had severe weakness on the hemiplegic side. Most of the patients had putaminal haemorrhage (13) and thalamic and lobar haemorrhage was seen in 2 patients each. The motor dysfunction on the nonhemiplegic side correlated with midline shift but not with the size of haematoma. CMCT findings correlated with motor signs on the nonhemiplegic side in 6 patients. In the patients without any signs on the nonhemiplegic side, CMCT was normal. Out of 17 patients with motor dysfunction on the nonhemiplegic side 9 revealed improvement in CMCT at 1 month followup. The patients with CMCT abnormalities on the nonhemiplegic side either died (2) or had poor outcome (9). Motor dysfunction on the nonhemiplegic side may be due to tentorial herniation and suggests a poor outcome.