Status epilepticus: why, what, and how.

Status epilepticus (SE) is an important neurological emergency with high mortality and morbidity. The first official definition of SE was the product of 10 th Marseilles colloquium held in 1962 which was accepted by International League Against Epilepsy in 1964. There are as many types of SE as of seizures. SE is supposed to result from failure of normal mechanisms that terminate an isolated seizure. In half of the cases, there is no history of epilepsy and SE is precipitated by some intercurrent infection. In children, it is often infection, whereas in adults, the major causes are stroke, hypoxia, metabolic derangements, and alcohol intoxication or drug withdrawal. The treatment of SE aims at termination of SE, prevention of seizure recurrence, management of precipitating causes, and the management of complications. The extent of investigations done should be based on the clinical picture and cost benefit analysis. The first line antiepileptic drugs (AED) for SE include benzodiazepines, phenytoin, phosphenytoin, and sodium valproate. Mortality of SE ranges between 7 and 39% and depends on underlying cause and response to AEDs.

Renal tubular acidosis presenting as respiratory paralysis: report of a case and review of literature.

Respiratory paralysis due to renal tubular acidosis (RTA) is rare. We report a 22-year-old lady who developed severe bulbar, respiratory and limb paralysis following respiratory infection. She had hypokalemia (1.6 meq/L) and hyperchloremic (110 meq/l) acidosis (pH 7.1). She was diagnosed as distal RTA by ammonium chloride test. She improved following sodium bicarbonate and potassium supplementation. RTA should be differentiated from familial periodic paralysis (FPP) because acetazolamide used in FPP aggravates RTA and sodium bicarbonate used in RTA aggravates hypokalemic periodic paralysis.

MRI pattern of infarcts in basal ganglia region in patients with tuberculous meningitis.

INTRODUCTION: This study aimed to evaluate the pattern of infarct in basal ganglia region in tuberculous meningitis (TBM) and ischemic strokes and its sensitivity and specificity in the diagnosis of these disorders. METHODS: Patients with TBM and ischemic strokes in basal ganglia region were retrospectively evaluated from our tuberculous meningitis and ischemic stroke registry. Magnetic resonance imaging findings were grouped into anterior (caudate, genu, anterior limb of internal capsule, anteromedial thalamus) and posterior (lentiform nuclei, posterior limb of internal capsule, posterolateral thalamus). The sensitivity and specificity of these patterns in diagnosing TBM and ischemic stroke were evaluated. RESULTS: There were 24 patients in each group. Infarct in TBM was purely anterior in eight patients and in ischemic stroke purely posterior in 18 patients. The frequency of caudate infarct was significantly higher in TBM compared to ischemic stroke (37.5% vs 8.3%). In TBM patients, purely posterior infarcts were present in seven patients; three had associated risk factors of ischemic stroke. The sensitivity of pure anterior infarct in the diagnosis of TBM was 33%, specificity 91.66%. For ischemic stroke, the sensitivity of posterior infarct was 75% and specificity 70.83%. CONCLUSION: TBM patients having infarcts in posterior region should be looked for associated risk factors of ischemic stroke.

Head to head comparison between neurology residents and a mobile medical application for diagnostic accuracy in cognitive neurology.

BACKGROUND: A novel Mobile Medical Application (App) App was created on iOS platform (Neurology Dx®) to deduce Differential Diagnoses (DDx) from a set of user selected Symptoms, Signs, Imaging data and Lab findings. The DDx generated by the App was compared for diagnostic accuracy with differentials reasoned by participating neurology residents when presented with same clinical vignettes. METHODS: Hundred neurology residents in seven leading Neurology centers across India participated in this study. A panel of experts created 60 clinical vignettes of varying levels of difficulty related to Cognitive neurology. Each neurology resident was instructed to formulate DDx from a set of 15 cognitive neurology vignettes. Experts in Cognitive Neurology made the gold standard DDx answers to all 60 clinical vignettes. The differentials generated by the App and neurology residents were then compared with the Gold standard. RESULTS: Sixty clinical vignettes were tested on 100 neurology residents (15 vignettes each) and also on the App (60 vignettes). The frequency of gold standard high likely answers accurately documented by the residents was 25% compared with 65% by the App (95% CI 33.1-46.3), P < 0.0001. Residents correctly identified the first high likely gold standard answer as their first high likely answer in 35% (95% CI 30.7-36.6) compared with 62% (95% CI 14.1-38.5), P < 0.0001. CONCLUSION: An App with adequate knowledge-base and appropriate algorithm can augment and complement human diagnostic reasoning in drawing a comprehensive list of DDx in the field of Cognitive Neurology (CTRI/2017/06/008838).

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 of died, which was related to the depth of coma.

Paroxysmal nocturnal haemoglobinuria presenting as cerebral venous sinus thrombosis.

Paroxysmal nocturnal haemoglobinuria (PNH) is associated with anaemia, intravascular haemolysis and venous thrombosis. Cerebral venous sinus thrombosis (CVST) is a late but serious complication of PNH. We for the first time report a young man who presented with CVST and was diagnosed to have PNH after 11 months. We highlight the reasons for delay in the diagnosis and discuss the special issues in the management.

Traditional journal club: a continuing problem.

OBJECTIVE: To evaluate the pattern, motivation and facilities for choosing journal club topics by residents in two medical institutions in India. METHOD: A self-appraisal questionnaire was used to compare motivation for choice of topics, availability of infrastructure, sites and type of articles accessed and formal training in computer based literature search in two medical institutions- a postgraduate institute (PGI) and medical college (MC) which provided mainly specialty and superspecialty training respectively. RESULTS: One hundred and fifty five out of two hundred and fifty five residents responded to the questionnaire. Super-specialty training was pursued by 58 and specialty training by 97 residents. The residents in PGI more frequently selected journal articles which they considered good and in MC, faculty guidance determined the choice of journal club topics. The super-specialty residents, however, more frequently selected patient management related topics compared to specialty residents. MEDLINE and MD Consult were more frequently accessed by PGI residents where infrastructure and training in literature search were superior to MC. CONCLUSION: In both the institutions surveyed, journal clubs were of traditional type. Better infrastructure and training at PGI were not reflected in quality of journal club. Successful journal club should focus on current, real patient's problem of most interest to the group.

DNA synthesis and thymidine kinase activity of rat colon epithelial cells fractionated by discontinuous Ficoll gradient.

Epithelial cells from colons of adult Sprague-Dawley rats were fractionated on a discontinuous Ficoll gradient at low centrifugal forces (170 x g) for approximately 60 minutes. Epithelial cells were separated into three distinct zones, whereas cell debris, yeast, and bacteria remained at the top of the gradient. The percentage of cells in each zone was inversely related to the density of the gradient. More than 95% of the cells were morphologically intact and viable (excluded trypan blue). Cells sedimenting at higher densities of Ficoll exhibited higher thymidine kinase activity and DNA synthesis, suggestive of active cell division. The cells sedimenting at lower densities of Ficoll showed the least thymidine kinase activity and DNA synthesis, properties that are compatible with those of mature absorptive cells. Tall columnar cells with vesicular nuclei were predominant in the fraction sedimenting at the lowest density (top fraction). At higher densities (middle and lower fractions), most of the cells were short and columnar with basally located condensed dark-staining nuclei.

Effects of alcohol consumption on plasma and urinary hormone concentrations in premenopausal women.

BACKGROUND: Most epidemiologic studies of the relationship between alcohol consumption and breast cancer risk over the past decade have shown that persons who consume a moderate amount of alcohol are at 40%-100% greater risk of breast cancer than those who do not consume alcohol. Dose-response effects have been observed, but no causal relationship has been established. PURPOSE: This study examines the hypothesis that alcohol consumption affects levels of reproductive hormones. METHODS: A controlled-diet study lasting for six consecutive menstrual cycles was conducted. Participants were randomly assigned to two groups, and a crossover design was used. During the last three menstrual cycles, alcohol consumption of the two groups was reversed. Thirty-four premenopausal women, aged 21-40 years, with a history of regular menstrual cycles, consumed 30 g of ethanol (equivalent to approximately two average drinks) per day for three menstrual cycles and no alcohol for the other three. All food and alcohol consumed were provided by the study. Caloric intake was monitored to ensure that each woman would maintain body weight at approximately the baseline level. Hormone assays were performed on pooled plasma or 24-hour urine specimens collected during the follicular (days 5-7), peri-ovulatory (days 12-15), and mid-luteal (days 21-23) phases of the third menstrual cycle for subjects on each diet. RESULTS: Alcohol consumption was associated with statistically significant increases in levels of several hormones. Plasma dehydroepiandrosterone sulfate levels were 7.0% higher in the follicular phase (P = .05). In the peri-ovulatory phase, there were increases of 21.2% (P = .01) in plasma estrone levels, 27.5% (P = .01) in plasma estradiol levels, and 31.9% (P = .009) in urinary estradiol levels. In the luteal phase, urinary estrone levels rose 15.2% (P = .05), estradiol levels increased 21.6% (P = .02), and estriol levels rose 29.1% (P = .03). No changes were found in the percent of bioavailable estradiol, defined by the sum of percent free estradiol and percent albumin-bound estradiol. However, increased total estradiol levels in the peri-ovulatory phase suggest elevated absolute amounts of bioavailable estradiol. CONCLUSION: This study has shown increases in total estrogen levels and amount of bioavailable estrogens in association with alcohol consumption in premenopausal women. IMPLICATION: This possible explanatory mechanism for a positive association between alcohol consumption and breast cancer risk merits further investigation.

Nature of tissue-bound lithocholic acid and its implications in the role of bile acids in carcinogenesis.

Lithocholic acid, a monohydroxy secondary bile acid, is present in tissues in two forms. One form is extractable with 95% ethanol-0.1% ammonia (soluble lithocholate), and the other form is firmly bound to tissue residues and can be released only by the bile salt-deconjugating enzyme, clostridial cholanoylamino acid hydrolase (tissue-bound lithocholate). Studies on bile salt-protein interactions revealed that lithocholic acid had amino group-modifying activity specifically directed against the basic side group of lysine residues. Degradative procedures yielded N-epsilon-lithocholyllysine, confirmed by comparison with the authentic compound synthesized in our laboratories. Studies on the distribution of tissue-bound lithocholate in tissues have revealed high concentrations of this form of lithocholate in livers of rats treated with the carcinogen, methylazoxymethanol. In light of these observations, the role of bile acids, and specifically lithocholic acid, as promoters of tumorigenesis must be further investigated.

Serum hormones and lipoproteins in benign breast disease.

Seventeen young women with clinically confirmed mammary dysplasia and six age-matched controls were treated with alpha-tocopherol. Serum samples collected during the luteal phase of each woman at monthly intervals for the 4-month duration of the study were analyzed for serum luteinizing hormone, follicle-stimulating hormone, and prolactin concentrations by radioimmunoassay and for lipoprotein levels by a combination of precipitation, ultracentrifugation, and enzymatic techniques. Fifteen patients showed objective and subjective remission from disease. While prolactin levels did not change significantly, elevated levels of luteinizing and follicle-stimulating hormones were decreased to normal levels. Ratios of serum cholesterol to high-density lipoprotein cholesterol decreased; high-density lipoprotein and free cholesterol associated with low-density lipoproteins increased as a result of therapy. The results suggest that alpha-tocopherol may serve as an effective agent not only to treat patients with benign breast disease but also to normalize abnormal hormone and lipid levels in subjects at high risk for breast cancer.

Endocrine parameters and alpha-tocopherol therapy of patients with mammary dysplasia.

Patients with mammary dysplasia (17 patients) and controls (6 patients) were treated in a double-blind study with alpha-tocopherol acetate (600 units/day). Determination of serum alpha-tocopherol, estradiol, estriol., and progesterone were made from blood samples collected on Day 21 of the menstrual cycle before and during therapy. Eight-eight % of patients showed clinical response to therapy. Serum alpha-tocopherol concentrations rose after therapy in patients and controls. Serum estradiol and progesterone concentration were not statistically different in patients or controls after therapy, although patients showed a trend toward increased serum progesterone concentration. However, the ratio of progesterone to estradiol, which is abnormal in mammary dysplasia patients, rose from 30 +/- 7 (S.E.) to 53 +/- 11 in patients after alpha-tocopherol therapy (p less than 0.05). Control patients showed no significant change in progesterone/estradiol ratio. Results of this study indicate that alpha-tocopherol therapy may correct an abnormal progesterone/estradiol ratio in patients with mammary dysplasia, with implications on reducing future risk for malignant breast disease.

Case-control study of colorectal cancer and fecapentaene excretion.

The fecapentaenes are potent mutagens found in high concentrations in the stools of some individuals. These compounds are produced in vivo by common species of the colonic microflora, from precursors of unknown origin. The fecapentaenes have been postulated to increase the risk of colorectal cancer. To test this hypothesis, we measured fecapentaene excretion in 69 patients with adenocarcinoma of the colon or rectum, newly diagnosed at three Washington, DC area hospitals. The cases were compared with 114 surgical controls, frequency matched to the cases on age, sex, and hospital. We attempted to measure fecapentaene excretion 4 times for each subject: before surgery; and at 1 mo; 3 mo; and 6 mo following surgery. Contrary to our study hypothesis, we found fecapentaene excretion during the four study periods to be similar or even lower in cases compared to controls. An indirect measurement of fecapentaene precursors also tended to be lower in cases. The case-control differences could not be explained as effects of bleeding or of the colorectal diagnostic workup, which was assessed in a separate group of 86 patients. We conclude from these data that the excretion of fecapentaenes does not increase the risk of colorectal cancer, at least when measured near the time of diagnosis.

Case-control study of colorectal cancer and fecal mutagenicity.

Fecal mutagenicity was measured in 68 patients with colorectal cancer and in 114 controls, using Salmonella tester strains TA98 and TA100 with and without S9 activation. Samples were also tested for fecapentaenes by high-performance liquid chromatography, to permit the separation of fecapentaene and non-fecapentaene mutagenicity. Overall, no significant case-control differences in fecal mutagenicity were observed. However, when samples containing high concentrations of fecapentaenes were excluded, non-fecapentaene TA98 mutagenicity was observed in eight cases (12%) and only four controls (4%), resulting in an estimated relative risk of 4.4 (95% confidence interval = 1.0-21.1). The association of colorectal cancer risk with non-fecapentaene TA98 mutagenicity could not be explained as an artifact of diagnostic workup or gastrointestinal bleeding among the cases. Smoking could also be excluded as a source of the TA98 mutagenicity seen, but possible dietary origins are still being explored.

Effect of dietary fat on length of the follicular phase of the menstrual cycle in a controlled diet setting.

The length of the follicular phase of the menstrual cycle (defined as the time from the first day of menses until the day of urinary LH peak, inclusive) was examined in 30 healthy, premenopausal women. The women consumed defined, weight maintaining diets, with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of either 0.3 or 1.0. Both P/S groups consumed a high fat diet (40% energy from fat) for 4 menstrual cycles, followed by 4 menstrual cycles of a low fat diet (20% energy from fat). There was a significant increase (P less than 0.006) in the length of the follicular phase of the menstrual cycle during consumption of the low fat diet. Two thirds of the women showed increases in follicular phase length with an average increase of 1.9 days.

Role of bile acids and neutral sterols in carcinogenesis.

Epidemiological evidence regarding cancer causation suggests the existence of a strong link to diet-related lifestyles. Neutral sterols and bile acids constitute a group of metabolic endproducts known to have multiple interactions both from the standpoint of being influenced by diet as well as from the standpoint of their role in cellular and molecular processes relating to carcinogenesis. Epidemiological and experimental studies on the possible role of these steroid metabolites are reviewed.

Effects of different vitamin E-deficient basal diets on hepatic catalase and microsomal cytochromes P-450 and b5 in rats.

Male Sprague-Dawley rats maintained for a period of 6 or 12 weeks on a basal vitamin E-dificient diet consisting of 70% sucrose, 20% vitamin-free casein, 4% tocopherol stripped lard, 4% salt mixture, and 2% tocopherol-free vitamin fortification mixture were used to compare two sets of commonly used salt mixtures (salt mixtures USP XIV versus Briggs' salt mixture) and two sets of vitamin fortification mixtures (NBC vitamin fortification mixture versus that of Weglicki). Among the rats maintained on the deficient diets for 6 weeks, only those that received the combination of salt mixture USP XIV and vitamin fortification mixture of Weglicki showed a significantly lower level of hepatic catalase activity compared to the corresponding control animals. While there were no significant changes in microsomal cytochromes at this time period, after 12 weeks on the deficient diet, a significant depression in these cytochromes was noted in all experimental groups except the one on salt mixture USP XIV and NBC vitamin fortification mixture. A similar decrease in hepatic catalase was observed in deficient animals at 12 weeks. Since the most striking differences in these diets are in their content of iron and menaquinone, it appears that these two dietary constituents may interact in modulating the effect of vitamin E on hepatic hemeproteins.

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. In situ bromination for the separation of the cholesterol-cholestanol pair in human fecal extracts.

Neutral sterols from human feces were fractionated by thin-layer chromatography and by gas-liquid chromatography (GLC). A simple thin-layer chromatography procedure for the separation of cholestanol from cholesterol is described. This technique, involving in situ bromination of sterols on thin-layer chromatography plates, converts cholesterol and other unsaturated sterols to the corresponding dibromides. Under these conditions, the cholestanol-cholesterol pair which is normally indistinguishable on thin-layer chromatography and gas-liquid chromatography, is separated. Final quantification of the sterols was carried out by gas-liquid chromatography.

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Metabolism of bile acids.

High levels of fecal bile acids have been associated with populations at high risk for developing colon cancer. In this study, 168 subjects were drawn from populations that show low and high mortality from colon cancer [pure vegetarians, lacto-ovo vegetarians, and nonvegetarians Seventh-day Adventists (SDA) and demographically comparable group from the general population]. Lyophilized aliquots of 3-day stool samples were examined for levels of primary (cholic and chenodeoxycholic acids) and secondary (deoxycholic and lithocholic acids) bile acids. Total bile acids (mg/g lyophilized stools) were statistically different among dietary groups: SDA pure vegetarians 2.16 +/- 0.32, SDA lacto-ovo vegetarians 3.66 +/- 0.41, SDA nonvegetarians 4.39 +/- 0.44, general population nonvegetarians 6.04 +/- 0.75; but were similar when stool weights, body weights, and fat intake were taken into account. The most striking difference was evident in the ratio of secondary to primary bile acids: when compared to SDA pure vegetarians, both SDA lacto-ovo vegetarians and SDA nonvegetarians had twice the ratio while values for general population nonvegetarians were five to six times. The data indicate that these differences in excretion patterns among dietary groups reveal distinctly characteristic metabolic features associated with diet and lifestyle.

Influence of caloric contribution and saturation of dietary fat on plasma lipids in premenopausal women.

Total cholesterol, HDL cholesterol, and triglycerides were measured in 31 premenopausal women randomized into one of two diet groups: one diet with a P:S ratio of 1.0 and one diet with a P:S ratio of 0.3. Both groups were fed a high-fat diet (40% of energy from fat) for four menstrual cycles per subject followed by a similar interval on a low-fat diet (20% of energy from fat). Changing from the high-fat to the low-fat diet resulted in a nonsignificant mean decrease of 7% in total cholesterol. HDL-cholesterol response to the low-fat regimen was influenced by the P:S ratio. Women in the high P:S group showed no change; mean HDL cholesterol in women in the low P:S group decreased 12%. Plasma triglycerides increased in both groups on the low-fat diet although the increase was greatest in the low P:S group.