Preliminary evaluation of Rivotril in epilepsy

Treatment with Rivotril in doses of 2-10 mg daily was given to 26 patients with various forms of epilepsy, mostly refractory to previous treatment. In 2 cases the drug was withdrawn on account of intolerance, in 4 cases treatment was stopped after several days in view of greatly increased frequency of seizures. In the remaining cases the drug was administered during 2 to 27 months, (mean 7 months) in 3 cases as the only medication and in 17 with other anticonvulsants. The best therapeutic results were obtained in patients with partial seizures of complex symptomatology and in generalized non-convulsive seizures, the worst results in generalized seizures. Electroencephalographic findings included particularly disappearance of seizure activity, while focal changes persisted and even grew worse in some cases. Apart from 2 cases of acute intolerance in another 4 cases side effects were observed with somnolence, dizziness, equilibrium disturbances, and in one case granulocytopenia developed. Allergic changes and liver or renal damage were never observed. The authors suggest introduction of the drug in treatment of epilepsy in view of its favourable clinical effect even in cases refractory to previous treatment, especially since the drug is relatively well tolerated.     

Treatment of warts with topical pyruvic acid: with and without added 5-fluorouracil

Numerous studies have suggested that epilepsy and asthma may be related conditions. There has, however, been little epidemiologic data published to support this association. We conducted a retrospective study to determine whether the prevalence of epilepsy is increased among children with asthma, and the prevalence of asthma is increased among children with epilepsy, in comparison with the general pediatric population. We reviewed the medical records, at a large city hospital, of two groups of pediatric outpatients: (1) 400 consecutive patients with asthma followed regularly at the asthma and allergy clinic; and (2) 201 consecutive patients with idiopathic epilepsy followed regularly at the pediatric neurology clinic. Patients with a history of birth prior to 36 weeks' gestational age were excluded. Among the 400 cases of asthma, there were three patients with idiopathic epilepsy (prevalence of 0.75%). The prevalence of epilepsy was similar in mild (0.79%) and moderate-to-severe (0.73%) asthma. Among the 201 cases of idiopathic epilepsy, there were 12 patients with asthma (prevalence of 5.97%). Similar percentages of epilepsy patients with and without asthma reported generalized tonic-clonic, complex partial, simple partial, and myoclonic seizures as their predominant type. The prevalence values in this study are consistent with the prevalence of epilepsy and asthma in the general pediatric population. Our findings therefore suggest that idiopathic epilepsy and asthma are not etiologically related or mutually predisposing conditions. Small samples, failure to exclude patients born prematurely, and the equation of electroencephalographic (EEG) abnormalities with epilepsy may account for the results of previous studies.     

Refined mapping of the epilepsy susceptibility locus EJM1 on chromosome 6

Juvenile myoclonic epilepsy (JME) is a genetically determined common subtype of idiopathic generalized epilepsy. Linkage to the HLA complex on chromosome 6p21.3 and an allelic association with HLA-DR13 and -DQB1 alleles suggest that a susceptibility locus for JME, designated as "EJM1," is located within or near the HLA region. However, further studies revealed controversial results, and genetic heterogeneity has been suspected. The present study was designed to evaluate the validity of the association and linkage findings and to refine the map position of EJM1. Our association analysis showed no significant difference of the frequency of HLA-DR13 carriers in 62 German JME patients compared with that in 77 German controls (X2 = 0.98, df = 1, p = 0.161, one-tailed). Multipoint linkage analysis with use of microsatellite markers from the chromosomal region 6p25-q13 in 29 German families of JME patients provided significant evidence that an epilepsy locus (EJM1) close to the HLA locus confers susceptibility to "idiopathic" generalized seizures (Zmax = 3.27 at theta max = 0.033 centromeric to the HLA-DQ locus), assuming an autosomal dominant mode of inheritance with 70% penetrance. Haplotype analyses revealed key recombinations in five families, which locate EJM1 to the centromeric side of the HLA-DQ locus. This study confirms a causative role of EJM1 in the pathogenesis of idiopathic generalized seizures in the majority of German families of JME patients and refines a candidate region of 10.1 cM in the chromosomal region 6p21 between the flanking loci HLA-DQ and D6S1019. A possible explanation for the current controversial results in families of different populations might be ethnic variation of interfering polygenic effects that could be permissive for heterogeneous susceptibility alleles.     

The immunopathology and immunogenetics of some forms of pediatric epilepsy

52 patients with primary and 42 with secondary generalized epilepsy at the age of 2-16 years were examined. In all the patients blood content of T- and B-lymphocytes as well as of their subpopulations (T-helpers, T-suppressors) was estimated with the use of monoclonal antibodies. Immunogenetic studies of allogenic lymphocytes were also performed in mixed lymphocyte cultures for proband and mother. There was an increase of CD4/CD8 ratio (T-helper/T-suppressor) as well as elevation of B-lymphocytes level in patients with secondary generalized form of epilepsy. A positive reaction of allogenic lymphocytes from mother and child in mixed cultures was observed in 46 patients with primary generalized epilepsy (88.5%), in 16 cases with progredient disease. In secondary generalized form of epilepsy it occurred in 7 cases only (16.7%). In 28 cases of epilepsy with progredient course not only antiepileptic drugs but also immunomodulators were used with positive effect in 14 patients.     

Etiological factors of epilepsy

INTRODUCTION: The epilepsies are one of the main reasons for consultation and hospital admission in neurology. They may be caused by multiple factors. OBJECTIVES: To determine the types of epilepsy, their aetiology and the value of a clinical history in diagnosis of their cause. PATIENTS AND METHODS: We studied 96 epileptic patients aged over 15 years in the epilepsy clinic of the Hospital Dr. Carlos J. Finlay in La Habana, Cuba. On a questionnaire we recorded: family history, pre-, peri- and postnatal histories, clinical features of the crises and physical exploration. All had inter-ictal electroencephalograms, 62 had cranial CTs, 36 had MR studies and 8 had both types of imaging studies. We excluded acute metabolic disorders and cerebral tumours. RESULTS: There was a predominance of persons aged between 26 and 35 (78%) and 59.37% were men. Symptomatic epilepsy was seen in 51.4%, in 38.54% this was cryptogenic and in 10.41% idiopathic. Perinatal damage was present in 20.8%, head injury in 11.4%, febrile convulsion in 10.4%, meningoencephalitis in 8.3% and cardiovascular disease in 4.1%. CONCLUSIONS: The international classification of epilepsy permits our patients to be divided into groups. In most of them aetiological factors were detected after an interview and medical exploration.     

Magnetic stimulation of the brain in generalized epilepsy: reversal of cortical hyperexcitability by anticonvulsants

Observations on experimental models suggest that diffuse cortical hyperexcitability is an important abnormality in the generalized epilepsies. We used the threshold for transcranial magnetic stimulation as an index of motor cortical excitability in 89 neurologically normal control subjects and 56 patients with idiopathic generalized epilepsy (20 untreated and 36 chronically treated with anticonvulsants). Magnetic stimulation was repeated in 10 patients after valproate monotherapy had been commenced and in 23 control subjects. The threshold intensity was significantly lower in the untreated patients (46 +/- 5% [mean +/- 95% confidence interval]) than in the control subjects (56 +/- 2%). Treated patients had significantly higher thresholds (64 +/- 4%) than did untreated patients and control subjects. A significant increase in threshold intensity (8 +/- 2%) occurred in patients retested after starting valproate; there was no significant change in retested control subjects (-1 +/- 2%). Threshold intensity was positively correlated with plasma valproate levels (rs = 0.37). The findings suggest that cortical excitability is increased in idiopathic generalized epilepsy and is reduced following anticonvulsant treatment. Transcranial magnetic stimulation is of use in examining the pathophysiology of generalized epilepsy. Furthermore, changes in threshold intensity in response to anticonvulsant treatment may prove useful in guiding therapy.     

Ciprofloxacin in the treatment of chronic bacterial prostatitis

17 exacerbation and 13 latent CBP cases received ciprofloxacin in a dose 500 mg twice a day orally for 6-34 days. At pretreatment microbiological investigation of the prostatic juice 49 cultures of 7 microorganism species were isolated (12 cases of monoculture, 18 cases of 2-component associations). S. epidermidis and E. faecalis occurred more frequently (in 29.4 and 25%, respectively). Ciprofloxacin was highly active against all the isolated agents and by the number of sensitive to it strains proved superior to control antimicrobial drugs. Good and satisfactory treatment outcomes were achieved in 76.8% of patients. Side effects recorded in 8 patients (26.6%) caused the drug undue discontinuation in 1 patient only.     

A study of apoptosis in human glomerulonephritis as determined by in situ non-radioactive labelling of DNA strand breaks

With a morbidity of 0.8%, epilepsy in childhood is one of the most frequent chronic diseases of the CNS. Improved diagnostic and therapeutical options of the last two decades made it possible that today 60-70% of the patients are without attacks for a long period and are fully socially integrated. Epilepsy is clinically classified into generalized epilepsies; which are of symptomatic origin in 50% of the cases, and focal epilepsies, which are even more frequent caused by CNS-injuries. The diagnosis of epilepsy results from the synopsis of the clinical picture of the attack and the electro-encephalogram (EEG), in case of doubts from the analysis of the video-EEG. The anti-convulsive drug therapy is undertaken as long-term treatment when free of attacks for 3-5 years and has to be monitored clinically as well as biochemically. The option of epilepsy-surgical procedures in a center of epilepsy should be considered in cases of a resistance to drug therapy. The tight cooperation with the family physician is of great importance for the ambulant epileptic care, others like social service, careers guidance and psychologic service have to be integrated.     

Long-term effects of selective decontamination on antimicrobial resistance

OBJECTIVE: To determine whether selective decontamination of the digestive tract exerts any long-term effects on antimicrobial resistance patterns. DESIGN: A surveillance and interventional study comparing the antimicrobial sensitivity patterns of clinically important bacterial isolates the year before a 2-yr, double-blind, randomized, controlled study of selective decontamination of the digestive tract, and for the year thereafter when no use of the regimen was made. SETTING: A ten-bed respiratory intensive care unit (ICU) in a 1,200-bed teaching hospital. PATIENTS: All 1,528 patients admitted to the ICU over the 4-yr study period were included. There were 406 patients admitted in the year before the study of decontamination of the digestive tract (65% medical, 23% surgical, and 12% trauma), of whom 76% required mechanical ventilation. There were 719 patients admitted during the 2-yr study of selective decontamination (55% medical, 28% surgical, and 17% trauma), of whom 79.6% required mechanical ventilation. There were 403 patients admitted in the subsequent year (61% medical, 25% surgical, and 14% trauma), of whom 76.9% required mechanical ventilation. INTERVENTIONS: We performed daily clinical monitoring to detect nosocomial infection, with microbiological investigation when clinically indicated, as well as twice-weekly routine microbiological surveillance sampling. Antimicrobial susceptibility testing using standard laboratory methods was also performed. Selective decontamination of the digestive tract included parenteral cefotaxime and oral and enteral polymyxin E, amphotericin B, and tobramycin. MEASUREMENTS AND MAIN RESULTS: The occurrence rate of nosocomial infection was 20.6%, 16.6%, and 25.3%, respectively, in the three study periods. In the year after selective decontamination, there was an increase in the occurrence rate of infection (p = .005), with an-associated increase in infections caused by the Enterobacteriaceae, while a reduction in the level of resistance to the third-generation cephalosporins were found (p = .07). There was a progressive increase in the occurrence rate of infections caused by Acinetobacter species (p = .05). Only 11 infections over the 4 yrs were caused by Enterococcus species. Staphylococcal infections were uncommon (5.7% of admissions), and the level of methicillin resistance did not change. No increase in aminoglycoside resistance occurred. CONCLUSION: No long-term effects on antimicrobial resistance or the spectrum of nosocomial pathogens could be attributed to the use of selective decontamination of the digestive tract over a 2-yr period in a respiratory ICU admitting all categories of patients.     

Upper digestive hemorrhage. Comparison of terlipressin and octreotide

The efficacy and tolerability of both Terlipressin and Octreotide in the treatment of upper digestive haemorrhage (oesophagus, stomach and duodenum) have been compared, at random, on 30 adult patients. Terlipressin dosage was 2 mg/4 hours i.v. during the first 24 hours, 2 mg/6 hours during the following 24 hours. Octreotide dosage was 50 micrograms i.v. and infusional therapy, 25 micrograms/hours, followed. Haemostasis was obtained in 100% of patients treated with Terlipressin and in 73% of patients treated with Octreotide. Rebleeding occurred in 3 patients treated with Terlipressin and 4 patients treated with Octreotide. Side effects occurred in 4 patients treated with Terlipressin and 8 patients treated with Octreotide. Terlipressin proved to have a better efficacy in comparison with Octreotide, and had less side effects.     

Technetium-99m-HMPAO brain SPECT in Beh?et's disease

Beh?et's disease (BD) is an idiopathic multisystem disorder. Involvement of the central nervous system (CNS) occurs in 4%-48% of cases. The aim of this study was to evaluate 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT findings in BD patients and eventually to detect CNS involvement by depicting cerebral blood flow disturbances. METHODS: Technetium-99m-HMPAO brain SPECT was performed on 33 consecutive BD patients. Qualitative and quantitative evaluation of the cortical uptake was done using an automatic program that generated 32 regions of interest (ROIs). An uptake index for each ROI was obtained. Reference values were obtained from a healthy control group (n = 20). Twenty-five patients also had an MRI study. RESULTS: Twelve of 32 patients (36%) presented with a clinical neurological disorder. SPECT and visual evaluation revealed that 17 patients (51.5%) had abnormalities; 9 of 25 MRI studies (36%) were abnormal. Using the quantitative approach for SPECT, 23 patients (69.7%) had abnormally low values. Six of 12 patients with neurological symptoms had a visually abnormal SPECT scan, whereas quantitative analysis showed abnormalities in 11 patients. Of the 21 patients with no neurological findings, 9 had abnormal SPECT results, and 12 had low uptake indexes. CONCLUSION: HMPAO brain SPECT shows high rates of cerebral blood flow abnormalities in BD patients presenting with neuropsychiatric symptoms, and it also is frequently abnormal in asymptomatic BD patients who have no abnormalities on MR scans. Compared with visual analysis, quantitative analysis detects an even higher rate of SPECT changes in BD patients.     

Therapeutic failure, treatment and non-treatment of childhood epilepsy

INTRODUCTION: The classification of epileptic syndromes defines the prognosis and offers some orientation about treatment in childhood epilepsy. OBJECTIVE: To study the medical therapy according to epileptic syndromes in the everyday practice of a hospital based outpatient neuropediatric clinic. METHODS: Survey of the database using an algorithm to define therapeutic failure, treatment and spontaneous evolution, according to syndrome and drug, of all epileptic patients attended at the clinic during 1966. RESULTS: 465 patients with: monotherapy 38%, politherapy 20%, therapeutic success (follow-up after drug discontinuation) 21%, spontaneous evolution 22% (54% of partial idiopathic epilepsies). Most used antiepileptic drugs (VPA > CBZ > VGB > CLB > PB > PHT > LTG > ESM > PRM > GBT) are those with lowest failure rate and highest percentage of patients on monotherapy. Percentages of monotherapy in treated patients and of previous failure out of total number of patients are: idiopathic partial epilepsies: 85% and 10%; remote symptomatic partial: 58% and 43%; cryptogenic partial: 53% and 50%; idiopathic generalized: 83% and 25%; symptomatic-cryptogenic generalized: 34% and 63%; undetermined: 45% and 43%. CONCLUSIONS: Screening of the database serves as a quality control but the use of an algorithm offers only an approximation to reality. In idiopathic partial epilepsy treatment can be avoided in half of the patients and failure is lowest for VPA and CBZ. In idiopathic generalized epilepsies VPA predominance is almost absolute with a very low failure rate. In all other epileptic syndromes the therapeutic failure rate is about 50% regardless of drug, except for VPA which shows a moderately better outcome.     

Ectopic cerebral tissue in the middle ear. A case report

Most idiopathic generalized epilepsies have an onset in childhood or adolescence, with a moderate second incidence peak in the presenium predominantly in women. This study addressed the question of a later onset. The available literature and the records of four personal data sets (two prospective incidence surveys of epileptic seizures, one prevalence study of epilepsy, and one clinical series of individuals with epilepsy) were screened for patients who had experienced a first generalized convulsive seizure with bilateral spike-wave complexes on EEG after 60 years of age. Reports of first idiopathic generalized tonic-clonic seizures occurring after age 60 were extremely rare and none was found in our four cohorts regardless of the methodology involved. Only five case reports were found, all involving a woman. Two had a family history of seizure disorders and two had had at least one seizure earlier in life. Idiopathic generalized epilepsy of late onset, if this condition actually exists, is likely to be the consequence of a genetic predisposition triggered by acquired epileptogenic factors.     

Ischemic stroke in children

OBJECTIVE: Ischemic stroke in children and infants is a rare condition. We present a series of 23 pediatric patients of ischemic stroke. PATIENTS AND METHODS: A retrospective series of 23 patients, aged between 1 month and 13 years, diagnosed by anamnesis, clinical examination and neuroimaging. The clinical picture, neuroimaging findings, etiology, evolution and sequelae are evaluated. RESULTS: Eighteen of the patients had an ischemic stroke in the carotid territory (78.3%) and 5 in the vertebro-basilar (21.7%). Idiopathic (30.4%), cardiopathy (21.7%) and migraine (17.4%) were the most frequent etiologies. The recovery was complete in 9 patients (39.1%). There was a death as a result of systemic complications caused by dehydration (4.3%), and 13 patients (56.6%) were disabled: 6 with hemiparesis of diverse grades, 5 with epilepsy and hemiparesis, one with epilepsy, and one with mental retardation. CONCLUSIONS: Ischemic stroke in children and infants is an unusual entity. The causes are multiple, although there is an elevated percentage of idiopathic cases. In our series, we highlight the significative percentage of vertebro-basilar strokes and the finding of three unusual etiologies in ischemic stroke in childhood, such as migraine, Mycoplasma pneumoniae infection and smallpox.     

Identification of neuropsychological deficits in epilepsy using the Luria-Nebraska Neuropsychological Battery.

80 hospitalized patients, 22 diagnosed as having idiopathic seizures, 18 who developed epilepsy secondary to brain trauma or another CNS disorder, and 40 who demonstrated no evidence of CNS involvement, were given the Luria-Nebraska Neuropsychological Battery. Mean ages of Ss were 38.3, 35.2, and 41.1 yrs, respectively. Results demonstrate that the standardized Luria test may be useful in the evaluation of neuropsychological deficits in adult epileptics. (6 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid arrest of seizures with an inhalation aerosol containing diazepam

Diazepam (DZP) and a mixture of Chinese herbs customarily used to treat epilepsy were prepared as an aerosol under the trade name Aerosolum Diaiepami Compositae or Flvalscop (FVS). FVS was studied in a single-blind trial in 101 patients with seizures preceded by an aura and in 19 without an aura to whom was administered by another person. FVS or a control preparation was administered. In 16-22 s, (average 18.5 s), the aura was interrupted and no seizure ensued in 90% of the cases treated with FVS and in 26% of cases treated with the control preparation. Of the 120 patients, 8 had elementary partial seizures with Jacksonian march, 18 had complex partial seizures (CPS), 7 had simple partial seizures with autonomic symptoms, and 87 had secondarily generalized tonic-clonic seizures. Eleven patients have now received FVS for 2 years (400 ml each). Forty patients for 1 year (150-200 ml each); none of these patients have shown any side effects or abnormal laboratory findings. An aerosol-administered drug may be a valuable adjunct to the antiepileptic drug (AED) arsenal and merits more extensive evaluation.     

Hydrophobic proteins which bind cholinergic agonists from brains of lethargic mutant mice

An investigation of hydrophobic proteins of synaptosomes isolated from the CNS tissue of the lethargic mutant mouse, which exhibits a behavioral epilepsy as the major visible effect of the mutant gene (lh), has revealed that the binding affinity of these proteolipid components for acetylcholine was higher than that observed in control (+/+) animals, a finding that may be directly related to the behavioral epilepsy.     

Effect of thyroid hormone deficiency on RC3/neurogranin mRNA expression in the prenatal and adult caprine brain

We describe a new syndrome of familial temporal lobe epilepsy in 38 individuals from 13 unrelated white families. The disorder was first identified in 5 concordant monozygotic twin pairs as part of a large-scale twin study of epilepsy. When idiopathic partial epilepsy syndromes were excluded, the 5 pairs accounted for 23% of monozygotic pairs with partial epilepsies, and 38% of monozygotic pairs with partial epilepsy and no known etiology. Seizure onset for twin and nontwin subjects usually occurred during adolescence or early adult life. Seizure types were simple partial seizures with psychic or autonomic symptoms, infrequent complex partial seizures, and rare secondarily generalized seizures. Electroencephalograms revealed sparse focal temporal interictal epileptiform discharges in 22% of subjects. Magnetic resonance images appeared normal. Nine affected family members (24%) had not been diagnosed prior to the study. Pedigree analysis suggested autosomal dominant inheritance with age-dependent penetrance. The estimated segregation ratio was 0.3, indicating an overall penetrance of 60% assuming autosomal dominant inheritance. The mild and often subtle nature of the symptoms in some family members may account for lack of prior recognition of this common familial partial epilepsy. This disorder has similarities to the El mouse, a genetic model of temporal lobe epilepsy with a major gene on mouse chromosome 9, which is homologous with a region on human chromosome 3.     

Serum levels of cytokeratin 19 fragments in cervical cancer

The objective of this study was to compare the efficacy and tolerability of two new antiepileptic drugs, lamotrigine (LTG) and vigabatrin (GVG) in everyday clinical practice. A comprehensive retrospective survey of a computerized data base and hospital case notes was carried out at the Mersey Regional Epilepsy Clinic (MREC), Liverpool, which services a population of 3 million in the North West of England. The study comprised 333 out-patients with refractory epilepsy exposed to LTG and GVG forming a subset in a total population of 2250 patients with epilepsy held on a comprehensive database. The main outcome measures were duration of treatment with each drug described by a Kaplan-Meier survival curve, seizure control determined by a 50% decrease in seizure frequency and freedom from seizures, and incidence of adverse drug effects leading to discontinuation. The Kaplan-Meier curve indicated a 57% probability of patients continuing to take LTG and 43% GVG after 40 months. A 50% improvement in seizure control followed the addition of LTG in 45% of patients, with 10% seizure free, compared with 32% and 6%, respectively after the addition of GVG. LTG was discontinued because of adverse events (most frequently skin rash) in 15% of patients compared to GVG in 25% (particularly because of personality disturbance and psychiatric disorder). Both LTG and GVG are effective new AEDs in patients with refractory epilepsy, treated in a tertiary referral out-patient setting. LTG has a broader spectrum of antiepileptic efficacy for patients with both partial and idiopathic generalized seizures, whereas GVG should be reserved for patients with partial seizures at low risk of psychiatric disorder.     

ILAE-defined epilepsy syndromes in children: correlation with quantitative MRI

PURPOSE: The role of quantitative magnetic resonance imaging (MRI) in evaluation of childhood epilepsy remains poorly defined, with minimal published data. Previous work from our center questioned the specificity of hippocampal asymmetry (HA) in an outpatient group whose epilepsy was defined by using clinical and interictal data only. By using childhood volunteer controls and defining epilepsy syndromes using video-EEG monitoring, we readdressed the utility of HA in differentiating mesial temporal lobe epilepsy (MTLE) from other partial and generalized epileptic syndromes in children. METHODS: Seventy children were enrolled; entry criteria were age younger than 18 years with predominant seizure type recorded on video-EEG telemetry with volumetric MRI in all cases. Thirty healthy child volunteers had volumetric MRI. Epilepsy syndrome classification was according to ILAE. RESULTS: Control data revealed symmetric hippocampi, mean smaller/larger ratio of 0.96 (0.95-0.97, 95% CI) with no gender or right/left predominance. Overall 23% of patients had significant HA. Mean hippocampal ratio for MTLE was 0.78 (95% CI, 0.70-0.86), significantly lower than controls and from all other epilepsy syndromes. HA was highly specific (85%) to the syndrome of MTLE. Other potential epileptogenic lesions were found in 27 (39%) patients, lowest yield in frontal and mesial temporal syndromes. Dual pathology was present in 10% of patients. There was no significant association between HA and risk factors. CONCLUSIONS: In this study, we found that HA in children with a well-defined epilepsy syndrome is highly sensitive and specific for MTLE. Whether this will correlate with surgical outcome, as in adults, is the subject of ongoing study.