Influence of anti-epileptic drugs on hematological and biochemical parameters in patients with epilepsy.

Background: Epilepsy is a chronic neurological condition which may require long-term treatment with antiepileptic drugs (AEDs). The challenge in AED management is to attain freedom from seizures, without side-effects and with good quality-of-life. However, AEDs are reported to induce potential adverse effects, which can remain unnoticed over long time. In this regard, earlier studies report inconsistent results in hematological and biochemical toxicity of AEDs. The objective of the present study was to evaluate the effects of AED monotherapy and polytherapy on hematological and biochemical parameters. Methods: This was a cross-sectional, observational study carried out among patients with epilepsy (PWE) receiving AEDs. The data on baseline demographic characteristics, treatment, adverse drug reactions, hematological, and biochemical investigations were collected. Statistical analysis was performed using the SPSS version 18 and descriptive statistics such as mean and median were used to summarize the data and inferential tests like Chi-square was used to compare categorical variables between groups. Results: There were 255 PWE in mean age range of 28.68±9.29 years, with 56.54% males. A total of 78.04% had focal, 18.04% had generalized seizures and remaining 3.92% were unclassified. Majority of (55.69%) PWE received polytherapy with AEDs. Females had significantly lower levels of hemoglobin (Hb) when compared with males (p=0.000), and patients on AED polytherapy showed significant difference in low Hb (p=0.006) and high alkaline phosphatase (ALP) levels (p=0.001). Conclusions: The results of this study showed significant alterations in the levels of Hb and ALP with the use of AED polytherapy in PWE. Routine hematological and biochemical investigations may be considered during AED treatment in those patients receiving AED polytherapy.

Feasibility study of stroke surveillance: Data from Bangalore, India.

Background & objectives: Stroke is a leading cause of deaths, and disabilities in India. Reliable and good quality data on epidemiological characteristics of stroke are essential to plan, implement and evaluate stroke prevention and control programmes. A feasibility study was undertaken in Bangalore to examine the possibility of establishing stroke surveillance and to develop methodology for a larger programme. Methods: The study adapted WHO STEPs-STROKE methodology to collect data on hospitalized stroke events and fatal stroke events in the city of Bangalore. In STEP I, Information was collected from 1,174 stroke patients in three large hospitals and were followed till discharge and 28 days; outcome was measured as death or disability. Stroke cases fulfilling diagnostic criteria, evaluated by neurologists and CT/MRI confirmed cases were included. Brief information on major risk factors was collected from all stroke patients / family members and from medical records by trained research officers. In STEP II, death records of Bangalore Mahanagara Palike for 2004 (n=23,312) were analyzed to identify stroke related deaths. Results: Using WHO-STEPs approach, a methodology was developed for stroke surveillance in a geographically defined population. By STEP 1 method - 7 per cent of medical and 45 per cent of neurological admissions were due to stroke with a fatality rate of 9 per cent at hospital discharge and 20 per cent at 28 days. With a mean age of 54.5 (± 17.0) yr and male preponderance, nearly half had one or more risk factors. Weakness or paresis (92%) was the commonest presentation and ischaemic stroke was most frequent (73.8%). One third of total stroke patients were dependent at both discharge and 28 day follow up. By STEP II method the proportional mortality rate for Bangalore city was observed to be 6 per cent and more than 50 per cent of total stroke deaths had occurred in 10 major hospitals. Interpretation & conclusions: The present study has shown that stroke surveillance is possible and feasible. Institution based (hospitals and vital registry data) stroke surveillance supplemented with periodical population based information can provide comprehensive information on vital aspects of stroke like mortality, risk factors, disability and outcome. There is a need to develop stroke surveillance in a phased manner along with mechanisms to apply data for prevention and control programmes.

A study of epilepsy-related psychosis.

The association of epilepsy and psychosis is studied. Among the 500 patients of epilepsy evaluated, there were 12 patients, 8 males and 4 females with epilepsy-related psychosis. Their average age was 38 years. The interval between the age of onset of epilepsy and psychotic features was 9 years. Complex partial seizures were present in 7 patients and primary generalized tonic-clonic seizure was present in 1 patient. Four patients had post-ictal psychosis, 7 had acute interictal psychosis and 1 patient had chronic psychosis. The inter-ictal and chronic psychoses were schizophreniform whereas the post-ictal psychoses were not. EEG showed a temporal focus in 7 patients with complex partial seizures and an extra-temporal focus was identified in 4 out of the other 5 patients. Imaging (CT scan/MRI) revealed abnormalities in 10 patients. This study attempts to define the characteristics of psychoses occurring in epileptics.

Post-cardiorespiratory arrest beta-alpha coma: an unusual electroencephalographic phenomenon.

The presence of frontally-dominant alpha pattern in the EEG is common in patients with coma due to trauma, toxic-metabolic causes and following cardiorespiratory arrest. Diffuse beta activity following resuscitation after a cardiac arrest is not well recognized. We report a case of coma in a 3-year-old girl who had a cardiac arrest from which she was revived. Initial EEG showed diffuse beta activity, which later evolved to predominantly alpha activity. The possible mechanisms involved in the generation of such rhythms are discussed. Transition of EEG activity from faster to slower frequencies is suggested as an adverse prognostic factor in post-cardiorespiratory arrest coma.

Relevance of computerized electroencephalographic topography (brain mapping) in ischemic stroke.

BACKGROUND AND AIMS: Computerized electroencephalographic topography (CET) (brain mapping) is a non-invasive, spatially oriented procedure for depicting amplitude and frequency patterns by two-dimensional color-coded frequency and amplitude display of the electroencephalograph (EEG). MATERIAL AND METHODS: We prospectively studied the relationship between CT scan lesions, conventional EEG and brain mapping in 40 patients with ischemic stroke within 1 week of onset. EEG and brain mapping was done within 24 hours of doing CT scan. RESULTS: There were 32 males and 8 females and the mean age was 56 years (range 27-75 years). CET/EEG was normal in 2 patients with capsular infarct. Brain mapping showed abnormalities (most commonly low-frequency high-amplitude changes) in 95% of patients, whereas EEG abnormalities were seen in only 40%. Brain mapping abnormalities were appropriate to the side of the CT scan lesion in 20 (52.63%) patients and were present bilaterally n 18 (47.37%) patients. Brain mapping abnormalities were ipsilateral to the side of the CT lesion when the lesion was < 2 cm in diameter and they were bi-hemispherical when the CT lesion was > 2 cm in diameter. CONCLUSIONS: There was no correlation between motor deficits and brain map abnormalities.

Nadroparin plus aspirin versus aspirin alone in the treatment of acute ischemic stroke.

Low-molecular-weight-heparin (LMWH) has been widely used in the treatment of acute ischemic stroke but controlled trials are few. In this study, 40 patients with acute ischemic stroke of less than 24 hours duration were randomized to receive either aspirin (325 mg/day) alone or aspirin (325 mg/day) plus subcutaneous nadroparin 4100 units/day. At the end of 4 weeks, the morbidity and mortality were significantly less in the nadroparin group as compared to the aspirin group. There was no increased risk of clinically significant intracranial hemorrhage in either group. The combination of aspirin and LMWH deserves to be tested in larger studies.

Exposure to pulsed magnetic fields in the treatment of plantar ulcers in leprosy patients--a pilot, randomized, double-blind, controlled clinical trial.

A pilot, randomized, double-blind, controlled clinical trial to study the effect of exposure to pulsed magnetic fields (PMF) on the rate of healing of plantar ulcers in leprosy patients was undertaken. Twenty patients were randomly allocated to receive standard wound-care treatment (controls) and 20 others received standard treatment plus exposure to PMF (sinusoidal form, 0.95 to 1.05 Hz, amplitude +/- 2400 nano Teslas) (study group) for four weeks. Assessment of the outcome of treatment was based on the volume of ulcers, calculated from the maximal length, breadth and depth of the ulcer recorded on the day of admission, at one and two weeks and at the end of treatment. The analysis of the results was based on 15 control patients and 18 PMF patients after deletion of four patients due to irregularity in attendance and three others on account of suspected malignancy of the ulcers. In the control group, the geometric mean volumes of the ulcers were 2843 and 1478 cu mm on the day of admission and at the end of the treatment (P = 0.03); the corresponding values in the PMF group were 2428 and 337 cu mm, respectively (P < 0.001). A decrease in the volume of 40% or more was observed in 53% of control patients and 89% of PMF patients (P = 0.02); a decrease of 80% or more was observed in none of the controls and in 33% of PMF patients. These findings strongly suggest that exposure to PMF causes a significantly more rapid healing of plantar ulcers in leprosy patients.

Effect of anti-tuberculosis drugs on the iron-sequestration mechanisms of mycobacteria.

The effect of sub-lethal concentrations of isoniazid, ethambutol, rifampicin and pyrazinamide on the growth in vitro and the production of both exochelins and mycobactins by the high virulent and the South Indian low virulent strains of M. tuberculosis was examined under iron-deficient and iron-rich conditions. There was a marked decrease in the growth of both strains in the presence of increasing concentrations of all four drugs, the inhibition being total in the presence of minimal inhibitory concentrations of the drugs. It was also observed that the growth-inhibitory effect of all four drugs was slightly reversed in the presence of high concentration of iron in the medium. A significant increase was observed in the concentrations of both siderophores in the presence of all four drugs, under both iron-deficient (or) iron-rich conditions.

Salivary cortisol in the assessment of adrenocortical function in patients with pulmonary tuberculosis.

Adrenocortical function was assessed on the basis of changes in salivary cortisol in patients with pulmonary tuberculosis and the findings compared with those in healthy subjects. A method of direct radioimmunoassay of salivary cortisol was standardized and the sensitivity was 0.8 nmol/l. Cortisol levels in saliva were significantly higher in the patients than in the healthy subjects (P less than 0.001). The diurnal rhythm of cortisol secretion was disturbed in the patients with a significant increase in salivary cortisol beyond 1800 h. While dexamethasone caused an appreciable suppression (87%), stimulation with ACTH (tetracosactrin) resulted in a marked increase in salivary cortisol, the increase being significantly higher in the healthy subjects than in the patients (P less than 0.001). Attempts to classify subjects as positive or negative responders to tetracosactrin based on increases in salivary cortisol in relation to plasma cortisol changes were however not successful, as the agreement between the two methods ranged from 73 to 80 per cent with various criteria used.

Classification of children as slow or rapid acetylators based on concentrations of isoniazid in saliva following oral administration of body-weight and surface-area-related dosages of the drug.

The acetylator phenotype of 180 children aged 3-11 years was determined on the basis of isoniazid concentrations in saliva collected at 5 hours after oral administration of body-weight and surface-area-related dosages of the drug in a syrup form. Isoniazid 2.5 mg/kg was administered on one occasion and 75 mg/m2 surface-area on another, with an interval of 3 days between the occasions. A cross-over design was employed and the sequence was determined by random allocation. The distribution of the concentrations was bimodal with both procedures, indicating the presence of two groups namely, the slow and rapid acetylators. The criterion for a rapid acetylator was a concentration of 0.3 micrograms/ml or less by body-weight-related dosage and 0.4 micrograms/ml or less by that based on surface-area. Based on these criteria, 62% of the children were classified as slow acetylators and 38% as rapid acetylators by body-weight, and 59 and 41%, respectively by surface-area, and the findings were similar in children in the different age-groups. The agreement between the two procedures was 98%.

Acute phase proteins in tuberculous patients.

The serum concentrations of some acute phase proteins were determined on admission, during treatment, at the end of treatment and at 12 months after stopping treatment in 20 patients with pulmonary tuberculosis. Measurements were also made, on admission and at the end of treatment, in 19 patients with abdominal tuberculosis, and 11 children with tuberculous meningitis. All 20 patients with pulmonary TB had quiescent disease by the end of treatment and none had a bacteriological relapse during the follow-up period of 12 months. The response to treatment was considered favourable in 18 of the 19 patients with abdominal TB, and the CSF findings had returned to normal in 9 of 11 patients with TB meningitis. There was a significant decrease with treatment in the concentrations of C-reactive protein, ceruloplasmin, haptoglobin and alpha-1-acid glycoprotein in all 3 groups of patients. While there was an increase in the concentrations of transferrin in patients with pulmonary and abdominal TB, there was a significant decrease in those with TB meningitis; alpha 2-macroglobulin did not appear to function as an acute phase reactant in any of the 3 groups. Amalgamating the findings in all 3 groups of tuberculous patients, the proportions of patients with abnormal values on admission and at the end of treatment were 62% and 14% for C-reactive protein, 78% and 50% for ceruloplasmin, 86% and 26% for haptoglobin and 92% and 6% for alpha 1-acid glycoprotein, respectively.

Induction of rifampicin metabolism during treatment of tuberculous patients with daily and fully intermittent regimens containing the drug.

Self-induction of rifampicin metabolism during daily and intermittent chemotherapy was studied by monitoring the changes in the serum half-life of the drug over a 4-week period in patients with pulmonary tuberculosis. Rifampicin 450 mg was administered to 8 patients who received treatment daily, 7 on thrice-weekly and 7 others on twice-weekly treatment. Serum half-life was computed from concentrations of the drug determined at 3, 4 1/2 and 6 hours after drug administration, on admission and at 1, 2 and 4 weeks after start of treatment. In the daily series, the mean serum half-life decreased from 4.9 hours on admission to 3.6 hours at 1 week (P = 0.02), and treatment beyond this had no further effect. In the thrice-weekly series, maximal induction was observed at the 2nd week, the mean values on admission and at 2 weeks being 5.8 and 3.7 hours, respectively (P less than 0.01). In the twice-weekly series, maximal induction was observed only at the 4th week, the mean values on admission and at 4 weeks being 4.9 and 3.7 hours, respectively (P less than 0.01). Serum activity of gamma glutamyl transferase was not found to be a suitable in vivo marker to monitor induction of the hepatic microsomal enzymes as no significant changes were observed in the activity of this enzyme in any of the 3 series during the 4-week period.