Multiple sclerosis conference synopsis and discussion: cellular therapy for treatment of autoimmune diseases (October 2005).

At a conference held in October 2005, participants presented studies on high dose immunosuppression with hematopoietic cell transplant (HCT) for multiple sclerosis (MS), including neuroimmunological and magnetic resonance imaging (MRI) mechanistic approaches, clinical registry reports, and ongoing or newly-designed protocols. A discussion panel considered questions on how to define success, timing of controlled clinical trials, difficulty in patient recruitment, and future direction of high dose therapy.

Multiple sclerosis: long-term remission after a high dose of cyclophosphamide.

The objective of this case report is to document the possibility that immunoablative doses of cyclophosphamide may provide a long-term remission of multiple sclerosis (MS). We report the case of a 48-year-old woman with definite MS diagnosed in 1994 who has been in complete remission since a dose of 3800 mg of cyclophosphamide was accidentally given intravenously in early 1997. For 7 years there have been no signs of disease activity on history, physical examination, or on high-quality magnetic resonance imaging (MRI) with appropriate contrast-enhancement methodology. This case includes information on the possibility that less aggressive chemotherapy than that used with stem cell transplantation may be effective in the long-term control of MS.

Simple, cost-effective technique for portable digital eletrocorticography.

We revised 16 patients submitted to epilepsy surgery using a new method of digital, real-time, portable electrocorticography. Patients were operated upon over a period of 28 months. There were no complications. The exam was useful in 13 cases. The low installation and operational costs, the reliability and simplicity of the method, indicate it may be useful for defining the epileptogenic regions in a variety of circumstances, including surgery for tumors, vascular malformations, and other cortical lesions associated with seizure disorders.

A proposal to declare neurocysticercosis an international reportable disease.

Neurocysticercosis is an infection of the nervous system caused by Taenia solium. It is the most important human parasitic neurological disease and a common cause of epilepsy in Africa, Asia, and Latin America, representing enormous costs for anticonvulsants, medical resources and lost production. Neurocysticercosis is a human-to-human infection, acquired by the faecal-enteric route from carriers of intestinal T. solium, most often in areas with deficient sanitation. Intestinal tapeworms cause few symptoms, but adult taeniae carried by humans release large numbers of infective eggs and are extremely contagious. Ingestion of poorly cooked pig meat infested with T. solium larvae results in intestinal taeniosis but not neurocysticercosis. With a view to hastening the control of taeniosis and neurocysticercosis we propose that neurocysticercosis be declared an international reportable disease. New cases of neurocysticercosis should be reported by physicians or hospital administrators to their health ministries. An epidemiological intervention could then be launched to interrupt the chain of transmission by: (1) searching for, treating and reporting the sources of contagion, i.e. human carriers of tapeworms; (2) identifying and treating other exposed contacts; (3) providing health education on parasite transmission and improvement of hygiene and sanitary conditions; and (4) enforcing meat inspection policies and limiting the animal reservoir by treatment of pigs. We believe that the first step required to solve the problem of neurocysticercosis is to implement appropriate surveillance mechanisms under the responsibility of ministries of health. Compulsory notification also has the major advantage of providing accurate quantification of the incidence and prevalence of neurocysticercosis at regional level, thus permitting the rational use of resources in eradication campaigns.

[The clinical relevance of serial determinations of plasma concentrations of carbamazepine and sodium valproate]. / Relevancia clínica de las determinaciones seriadas de concentraciones séricas de carbamacepina y valproato sódico.

INTRODUCTION: Serum concentrations of valproate (VPA) and carbamazepine (CBZ) were monitored in 66 epileptic out patients to determine then pharmacokinetic profiles. PATIENTS AND METHODS: Thirty-eight patients were receiving monotherapy, 17 with CBZ and 28 with VPA, and 28 patients were receiving VPA and CBZ. All were receiving standard (not controlled-release) CBZ or VPA preparations. Blood samples were obtained 2, 4, and 6 hours after the last dose. Serum concentrations were determined by gas chromatography. RESULTS: Mean serum concentrations of patients receiving CBZ were 8.2, 7.3 and 6.4 micrograms/ml for the 2, 4 and 6 hours samples, respectively. Mean serum concentrations of CBZ in the group receiving CBZ + VAP were 7.8, 8.4 and 7.8 micrograms/ml, respectively. Patients receiving VPA had mean serum concentrations of 92.8, 97.8 micrograms/ml, respectively. Those receiving CBZ + VPA had serum concentrations of 69.1, 70.6 and 55.8 micrograms/ml, respectively. Mean variation in the CBZ serum concentrations was 45% (range 7-91%) in patients receiving monotherapy and 31% (range 8-93%) in patients receiving CBZ + VPA. Mean variation in VPA serum levels of the patients receiving CBZ + VPA (56%) was greater than those of patients receiving CPA alone (38%). Subtherapeutic serum levels of either drug were detected in 35% of the patients. CONCLUSIONS: The large inter- and intraindividual variability of serum concentrations showed that a single measurement does not reflect the reality or CBZ and VPA clinical kinetics. The results confirm that three samples collected at 2, 4, and 6 hours after the last dose determine a clinically useful kinetic profile.

[Visual and volumetric analysis with magnetic resonance of hippocampus formations in a group of patients with clinical diagnosis of temporal lobe epilepsy]. / Análises visual e volumétrica por ressonância magnética das formações hipocampais em um grupo de pacientes com diagnóstico clínico de epilepsia do lobo temporal.

The purpose of this study is to test the sensitivity of the volumetric analysis compared to the visual analysis of the hippocampal formations of a group of 153 patients with clinical diagnosis of temporal lobe epilepsy and candidates to temporal lobectomy, evaluated by magnetic resonance (MR), using a 0.5 Tesla machine and inversion-recovery T1-weighted images and 5 mm coronal slices. There was agreement between the prospective visual analysis and another retrospective visual analysis carried out by two independent observers (C = 0.748 and C = 0.720). There was also agreement between the retrospective analysis of the two investigators (C = 0.733). There was genuine agreement (C = 0.788) between the results of the qualitative and quantitative analyses carried out prospectively. Volume measurements showed a nonsignificant tendency to lateralize more cases of clinically presumed hippocampal atrophy. Our results confirm the reliability of a qualitative visual analysis and indicate the utility of hippocampal volumetry as a supplementary, objective and quantitative measure of hippocampal sclerosis.

[Neuroleptic malignant syndrome: case report with recurrence associated with the use of olanzapine]. / Síndrome neuroléptica maligna. Relato de caso com recorrência associada ao uso de olanzapina.

The neuroleptic malignant syndrome (NMS) consists in an idiosyncratic reaction to neuroleptic drugs, probably related to a blockage of dopamine receptors in basal ganglia. Research criteria for diagnosing NMS from DSM-IV require severe rigidity and fever accompanied by 2 of 10 minor features including diaphoresis, dysphagia, tremor, incontinence, altered mentation, mutism, tachycardia, elevated or labile blood pressure, leukocytosis and elevation of creatine phosphokinase. From a clinical point of view, the NMS may range a large spectrum of presentations. Haloperidol is the most frequent drug associated with this syndrome. We report the case of a 30 year-old man who developed NMS at two different occasions, the first related to haloperidol and chlorpromazine and the second related to olanzapine, to our knowledge without previous mention in the indexed literature.

The intracarotid amobarbital procedure (Wada test) with two protocols combined, Montreal and Seattle.

The intracarotid amobarbital procedure was carried out in 8 male and 7 female candidates to temporal lobectomy, and a female candidate to frontal lesionectomy, aged 18-50 (mean 32.5) years. Language and memory were tested after injection in each hemisphere. Both were measured by the Montreal procedure. In 9 patients language and memory were evaluated with the Seattle procedure too. In 12 patients the left hemisphere was dominant for language; three had bilateral dominance. In 1 patient the Seattle procedure demonstrated the dominant hemisphere by relatively slowness of speech during the drug effect in the left hemisphere. Memory was defined to be in the left hemisphere in 12 patients, in the right in 2, bilateral in 1 and in another lateralization was not possible. In 1 patient memory dominance was determined by the Montreal protocol alone because of lack of cooperation. These early results indicate that the methods may be complementary for determination of language and memory dominance in epilepsy surgery candidates.

Epilepsy surgery without invasive EEG. Early results of a new program.

A total of 42 patients were submitted to a clinical, behavioural and neuropsychological evaluation with the objective of eventual surgical treatment of epilepsy refractory to the usual clinical therapies. Prolonged video-EEG monitoring, MRI hippocampal volume measurement, lateralization of speech and memory using the amobarbital (Wada) test were used. Of 18 operated cases, 12 were submitted to temporal lobectomy, with a follow-up of 6-30 months; 8 patients had significant improvement in seizures control; 2 patients had partial improvement in seizure frequency and intensity; 2 patients had no improvement in seizure control. One patient underwent right frontal lobectomy with total remission of seizures and 5 had callosotomy with varying degrees of success. There was no mortality. Morbidity included one subdural hematoma, one transient hemiparesis, one episode of mania, one lobar pneumonia and frequent immediately post-operative muscular tension headaches. These early results indicate good results of temporal lobectomy patients investigated through a non-invasive presurgical evaluation.

[Digital EEG with brain mapping in Alzheimer's dementia and Parkinson's disease. A prospective controlled study]. / Eletrencefalograma digital com mapeamento em demência de Alzheimer e doença de Parkinson: estudo prospectivo controlado.

In order to evaluate the EEG activity during wakefulness in senile dementia of the Alzheimer type (AD) and Parkinson's disease (PD), a prospective controlled study was performed. We compared 6 AD and 11 PD patients with a control group of 12 patients with mild to moderate major chronic depression (DSM-III-R, 1987). The median of the frequencies and the power of the posterior dominant activity was obtained in the three groups using spectral analysis. The posterior activity had a frequency of 8.79 +/- 0.52 (mean +/- sd) in the control group, 6.65 +/- 0.80 (mean +/- sd) in the AD group and 7.69 +/- 1.39 (mean +/- sd) in the PD group. The experimental hypothesis that patients with AD and PD differ from controls in relation to the background activity (defined as abnormal < 8) was confirmed by the chi square test (p = 0.01) and the t test showed that the mean of the frequency of the posterior power was significantly lower in AD (p = 0.01) and PD (p = 0.05) patients, compared with the controls. The results indicate that this abnormality could be correlated with the degree of cortical damage and natural history of these disorders.

[Temporal lobe epilepsy: report of an intact patient 26 years later without treatment]. / Epilepsia do lobo temporal: relato de um paciente intacto após 26 anos de evolução sem tratamento.

We present the case of a 36 years old man with temporal lobe epilepsy since 10 years old without treatment, and daily complex partial seizures and weekly tonic-clonic seizures. The diagnosis was made by clinical aspects and electroencephalographic findings. CT scan was normal. Cognitive functions were tested and showed no alterations. The patient had normal clinic, neurologic and mental exam.

Rationalized polytherapy for epilepsy.

In the past, epilepsy was usually treated with polytherapy, but with little knowledge as to the interactions and side-effects of the combinations of the anti-epileptic drugs used. Adverse events and sparse clinical knowledge led to monotherapy becoming the treatment regime of choice. A new generation of drugs, which are well-tolerated and have few or predictable interactions, have enabled the reassessment of polytherapy for the treatment of epilepsy. Extensive clinical trials of these drugs are allowing the emergence of a new, rationalized approach to polytherapy. In our study, 19 patients with refractory partial epilepsy, and who were 'socially active and integrated into society', received vigabatrin as add-on therapy. Patients were taking a mean of 1.5 drugs, and five patients were taking small doses of drugs which lead to tolerance, such as barbiturates and benzodiazepines. With vigabatrin as add-on therapy, 14 patients (73%) had a greater than 50% reduction in seizure frequency, and 10 (52%) had a greater than 70% reduction in seizure frequency. In one patient, seizure frequency increased, and two patients developed myoclonic jerks. Vigabatrin was not shown to have any harmful effects in extensive laboratory, EEG and cognitive function tests. In fact, a minor improvement occurred in visual memory, which was probably related to the reduction in seizures. Addition of vigabatrin may, therefore, be of benefit to patients with partial epilepsy refractory to monotherapy with standard anti-epilepsy drugs.

[Quantitative clinical and EEG measures of epileptogenesis in temporal lobe epilepsy]. / Medidas quantitativas clínicas e electrencefalográficas de epileptogênese na epilepsia do lobo temporal.

In this controlled, prospective and partially blind study two groups of patients with temporal lobe epilepsy were evaluated, respectively with good and bad prognosis. Measurements of epileptogenesis were based on frequency of seizures, and on epiletogenic electroencephalographic abnormalities obtained from scalp electrodes over the temporal lobes. The results were analysed by non-parametric analysis of variance, comparison of groups and analysis of correlation. The results indicated the temporal lobe groups were similar to at least one of the control groups in age, sex, educational and social level, therapeutic regime, age at onset and length of history of epilepsy. The quantitative measurements showed a global difference between the group of temporal lobe with bad and good prognosis, reaching statistical significance in clinical epileptogenesis, and a trend towards greater epileptogenesis on the electroencephalogram, in the same group of patients. The results indicate the experimental usefulness of some of the original measurements used in the study, but also their problems. A review of the literature is carried out.

[Lateralization of the epileptogenic area by magnetic resonance imaging in temporal lobe epilepsy]. / Lateralização da área epileptogênica através de ressonância magnética na epilepsia do lobo temporal.

We studied 5 patients with medically refractory temporal lobe epilepsy using special methods of MRI, in order to localize the epileptogenic area. Coronal sequences were obtained with 5 mm sections from the posterior margin of the brainstem to the base of the frontal lobe using: "Inversion recovery T1" (TR = 2500 msec, TE = 26 msec, T1 = 600 msec) to analyse loss of internal structure and atrophy of the hippocampus, and morphology of the temporal lobe; and Spin-echo T2w (TR = 250 msec, TE = 120 msec) looking for abnormal high intensity signal. In two cases with left focal EEG the MRI showed atrophy, loss of internal structure and abnormal high intensity signal in the hippocampus, and atrophy of the anterior temporal lobe, ipsilaterally. One case with independent bilateral foci at the EEG showed atrophy, loss of internal structure and abnormal high intensity signal in the right hippocampus. Other case with right focal EEG showed bilateral atrophy of the anterior temporal lobes. Another case was normal. We conclude that this methodology can facilitate the surgical indication in temporal lobe epilepsy.

Vigabatrin: clinical evidence supporting rational polytherapy in management of uncontrolled seizures.

Monotherapy is the policy for management of patients with epilepsy. With increasing knowledge of the biology of epilepsy and of the modes of action of antiepileptic drugs (AEDs), this concept must be reevaluated. When monotherapy fails to control seizures, subsequent treatment should be based on "rational pharmacology," taking into consideration the mode of action of the drugs, to provide improved efficacy with maintained tolerance and ease of administration. Introduction of vigabatrin (VGB) as a new AED calls for just such a reevaluation. VGB is an enzyme-activated irreversible inhibitor of gamma-aminobutyric acid (GABA)-transaminase that increases brain and cerebrospinal (CSF) GABA concentrations in animals and humans. It has limited efficacy in the classic animal seizure screening tests, but in many clinical studies has halved the incidence of seizures in approximately 50% of patients, especially those with partial epilepsies. We evaluated the efficacy of VGB in "socially integrated and active outpatients" as a likely subset to demonstrate any advantage of rational polytherapy. The criteria for this evaluation included the effects on seizure frequency, patient tolerability, and cognitive performance in a battery of psychometric tests. Fourteen of the 19 patients (73%) completing the study had > 50% reduction in seizure frequency, and 10 of 19 (52%) had > 70% reduction in seizure frequency. Tolerability appeared good; somnolence was the most frequent adverse event. Three patients complained of a worsening of their seizures, 1 with an increase in frequency and 2 with development of myoclonic jerks not previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)