Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC gene on 9q21 were recently found to cause chorea-acanthocytosis. CHAC encodes a large, novel protein with a yeast homologue implicated in protein sorting. In this study, all 73 exons plus flanking intronic sequence in CHAC were screened for mutations by denaturing high-performance liquid chromatography in 43 probands with ChAc. We identified 57 different mutations, 54 of which have not previously been reported, in 39 probands. The novel mutations comprise 15 nonsense, 22 insertion/deletion, 15 splice-site and two missense mutations and are distributed throughout the CHAC gene. Three mutations were found in multiple families within this or our previous study. The preponderance of mutations that are predicted to cause absence of gene product is consistent with the recessive inheritance of this disease. The high proportion of splice-site mutations found is probably a reflection of the large number of exons that comprise the CHAC gene. The CHAC protein product, chorein, appears to have a certain tolerance to amino-acid substitutions since only two out of nine substitutions described here appear to be pathogenic.

Nifedipine as an add-on drug in the management of refractory epilepsy.

We report the effects of the addition of nifedipine, a calcium channel antagonist, to the antiepileptic therapy of 20 patients with severe medically refractory epilepsy. Six patients developed side effects and in two the drug had to be discontinued because of these. The commonest side effects were headaches, dizziness and lethargy. Two patients experienced deterioration in seizure control and only 2 patients showed improved seizure control. One of these patients subsequently developed tolerance at 5 months. In 16 patients there was no change.

The efficacy and long-term tolerability of lamotrigine in the treatment of severe epilepsy.

We report the effects of the addition of lamotrigine, a novel antiepileptic drug, to the therapy of 125 patients with severe refractory epilepsy. Forty-five patients (36%) reported adverse experiences and in 19 (15%), the drug was withdrawn. The commonest adverse experiences were diplopia, headache, ataxia, drowsiness, skin rash and deterioration in seizure control. Two patients were withdrawn for other reasons. The remaining 104 patients were followed for a mean of 11 months (range 3-27): 26 (25%) of these showed a marked improvement in seizure frequency (a 50% or more reduction when compared with the pre-trial period), but no patient was rendered seizure-free. Tolerance to the effects of the drug was not seen.

Cognitive Performance of Patients with Epilepsy and Calcified Neurocysticercotic Lesions: A Case-Control Study.

Neuropsychological tests were applied to 20 patients with focal epilepsy related to calcified neurocysticercosis (NCC) (mean: three lesions/patient; NCC group), 22 patients with focal epilepsy without NCC (EPI group), and 29 healthy controls matched for age, sex, and educational level. The EPI and NCC groups were matched for age at onset of epilepsy, epilepsy duration, frequency of attacks, seizure semiology, interictal EEG findings, and antiepileptic drugs used. There were no differences in the digit span, word span, calculus, and Mini-Mental State examination among the three groups studied. The NCC and EPI groups showed lower scores than controls in immediate and delayed verbal memory, famous faces test, spatial recognition span, abstractions and judgment, and visuoconstructional abilities. The EPI group, but not the NCC group, also had lower scores in a praxis tests. There were no differences between the NCC and EPI groups in any of the tests applied (P > 15), except for the spatial recognition span, which was lower in the former. Cognitive impairment is a prevalent neuropsychological feature of patients with epilepsy and NCC.

[Progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of a case and review of the literature]. / Paralisia supranuclear progressiva. (Sindrome de Steele-Richardson-Olszewski) apresentação de caso e revisão da literatura.

Progressive supranuclear palsy (PSP) was first recognized as a distinct syndrome by Richardson, Steele and Olszewski roughly a quarter century ago. Subsequent clinical experience has corroborated and enlarged their original observations. PSP has become familiar as a chronic progressive disorder with extrapyramidal rigity, bradykinesia, gait impairment, bulbar palsy, dementia and a characteristic supranuclear ophthalmoplegia. It is a significant cause of parkinsonism and its etiology remains obscure. The case of a patient from Santa Catarina who presented definite clinical evidences of this syndrome is reported. This is the first description in this southern Brazilian State, where at least 50 more patients should exist, if we may extrapolate the prevalence rate of this condition in developed countries to this well developed area of Brazil. A review of the literature was undertaken with emphasis on recent clinical and therapeutic aspects of PSP.

[Causes of late-onset epilepsy in an epilepsy clinic of Santa Catarina--Southern Brazil]. / Causas de epilepsia tardia em uma clínica de epilepsia do estado de Santa Catarina.

OBJECTIVE: To identify the most common etiologies of late-onset epilepsy in our society. METHOD: Retrospective and descriptive study in the CME/SUS of Florianópolis from 1990 to 1998, evaluating 120 handbooks of patients with late-onset epilepsy, that is, those that had initiated epileptic seizures of the 18 years in ahead. The collected variables were: age of the first seizure, etiologies and morbid familial history. RESULTS: The prevalence rate found for late-onset epilepsy was 29.48%. Most of the sample had partial symptomatic epilepsy and the most frequent and important were: cysticercosis with 20%, head trauma with 15%, febrile convulsions in infancy with 5% and 35% were classified as idiopatic. CONCLUSION: Prevalence of late-onset epilepsy in our society is 29.48%, value slightly upper to the told one in developed countries (25%). Very probably, this difference is consequence of the epidemic character of cysticercosis among us. Moreover, head trauma and febrile convulsions are common etiologies. Prophylaxis of epilepsy is viable and urgently necessary in our society.

[Interictal personality syndrome in non-dominant temporal lobe epilepsy: case report]. / Síndrome de personalidade interictal na epilepsia do lobo temporal não-dominante: relato de caso.

The syndrome of interictal personality in non-dominant temporal lobe epilepsy consists of hyposexuality, hyperreligiosity, humorlessness and hypergraphia. Its notification, in 1974, was followed by an extensive search for these traits in broad epileptic populations. Nevertheless, these statistical studies failed to match this syndrome in general temporal lobe epileptics, and its existence became then target of doubt. We report the case of a 35 year-old man presenting partial complex epilepsy, whose singularity lies in his sophisticated drawing abilities. The large amount of buildings and houses he paints expresses his hypergraphia. He also presents hyposexuality and hyperreligiosity. MRI shows right mesial temporal sclerosis. Temporal hyperconnection, caused by a basal temporal irritative focus, is the most probable pathophysiological mechanism. Epileptic fits can be controlled in the majority of cases. However, behavioural symptoms usually do not respond to pharmacological approach or psychotherapy.

[Neuroacanthocytosis. A case report]. / Neuroacantocitose. Relato de caso.

We present a 45 years old man with neuroacanthocytosis. This gentleman has complex partial seizures and generalized tonic-clonic seizures, as well as movement disorders characterized by chorea and orofacial diskinesia. Complementary examination shows acanthocytosis of 11% on peripheral blood, irritative focus on right temporal lobe on EEG, serum creatinokinase of 101 U/l and volume reduction and hypersignal on caudate nucleus and putamen bilaterally on MRI.

[Lennox-Gastaut syndrome of late onset? Report of a case]. / Síndrome de Lennox-Gastaut com início na vida adulta? A respeito de um caso.

The Lennox-Gastaut syndrome (LGS), although described earlier, was first accepted in 1966 as a form of severe childhood epileptic encephalopathy, characterized by refractory epileptic seizures of diverse types, typical EEG abnormalities and slow mental development. This condition, however, is surrounded by controversy as the clinical criteria used by various authors to define it are quite different. It is very likely that this eponym has been used to harbour distinct epileptic conditions, all of which have in common a slow spike and wave complex in their EEG recording. Despite the fact that one of the hallmarks of LGS is an onset in early childhood, to add to the confusion, some cases of a LGS-like condition with onset in adulthood have been described. We report here one such case: a 28 year old man whose LGS-like condition started after severe head trauma at the age of 20. In addition we briefly review the difficulties in making this diagnosis, using this case to illustrate these aspects.

[Epilepsy and Turner's syndrome: report of a case and review of the literature]. / Epilepsia e síndrome de Turner: apresentação de um caso e revisão da literatura.

Fifty years ago Henry Turner identified the association of sexual infantilism, webbed neck and cubitus valgus to be a separate entity and subsequently gonadal dysgenesis was appended to the definition. Twenty years after the original report it was demonstrated that in typical patients with Turner's syndrome the chromosomal composition was 45.XO and in addition cases of mosaicism were described. Although much general information is now available about Turner's syndrome the neurological complications are largely neglected. In this paper we review the case of a patient with Turner's syndrome who at age of 16 years developed severe epilepsy. In addition, a survey of the literature concerning neurological abnormalities associated with this syndrome is presented. It seems clear that neurological symptoms in patients with Turner's syndrome deserves consideration for many reasons; may be the most significant is the evidence that patients with this syndrome have a high incidence of vascular abnormalities, which may also affect the CNS. Empirically patients with Turner's syndrome are at risk of developing cerebral vascular diseases. Also the relatively high frequency of cognitive abnormalities in these patients seems to justify the hypothesis that in a certain percentage of cases a CNS dysfunction or malformation, not necessarily of a vascular nature, may be a component of the syndrome still nor described.

[Machado-Joseph disease: description of 5 members of a family]. / Doença de Machado-Joseph: descrição de cinco membros de uma família.

The authors report the clinical and laboratorial findings of 5 affected members (all males) of a family with Machado-Joseph disease. The mode a inheritance was autosomal dominant. The mean onset age was 38 years (range 30-50 years). The clinical picture was pleomorphic and included cerebellar ataxia, external ophthalmoplegia with bulging eyes, extrapyramidal/pyramidal syndromes, amyotrophy with fasciculations and peripheral neuropathy, in variable degrees of severity. In one patient parkinsonian rigidity was greatly improved with the use of trihexaphenidyl and L-dopa. CT scan examinations disclosed a variable degree of cerebellar atrophy, with mild cerebral atrophy in one patient. Brainstem evoked potentials were normal in two patients. EMG showed denervation in three patients. Muscle biopsy (gastrocnemium) with histochemical studies revealed chronic muscle denervation in four cases. Sural nerve biopsy with conventional pathological study was normal in four cases. This family was living in Florianopolis, Santa Catarina, where there is a great number of Portuguese descendants from the Azores Islands. The worldwide presence of the disease seems to result from the genic diffusion of the disease with the Portuguese emigration during the Great Navigations Era and with some later emigratory settlement.

[Clinical-epidemiological study of patients with juvenile myoclonic epilepsy in Santa Catarina State, Brazil]. / Estudo clínico-epidemiológico de pacientes com epilepsia mioclônica juvenil em Santa Catarina.

We aimed to characterize the clinical profile and to establish the prevalence of juvenile myoclonic epilepsy (JME) among 939 consecutive patients referred to our epilepsy clinic. Inclusion criteria in the study were: a) myoclonic jerks, preferably on awakening; b) beginning of the symptoms between 8 and 26 year-of-age; c) typical pattern of electroencephalographic discharges; and d) good response to sodium valproate (VPA). In a retrospective design, 26 cases of JME were identified (prevalence 2.8%). Most of these patients were female (73.1%). Mean age at onset of symptoms was 13 (range 7-18). Tonic-clonic seizures were reported in 92.3% and absence seizures in 19.2%. Besides, 92.3% of the patients had typical EEG epileptiform activity and 76.9% had good response to VPA with daily dose ranging from 500 mg to 1500 mg.

[Prevalence of neurocysticercosis among epileptic in-patients in the west of Santa Catarina--southern Brazil]. / Neurocisticercose em pacientes internados por epilepsia no hospital regional de Chapecó região oeste do estado de Santa Catarina.

Neurocysticercosis (NC) is an endemic condition in several areas of Brazil. It is most likely the major responsible for the high prevalence of epilepsy in our country, estimated in 1-2% of general population. We performed a study to evaluate NC as aetiology of epilepsy in the west of Santa Catarina. This state belong to southern Brazil and it has a very developed economy. However, due the widespread swine farming in the west district, many of them without any sanitary control, the national health authorities have considered all this area at risk to NC. The study was carried out in Chapecó, the main town in that region, where CT Scan service was started in 1995. All patients put on hospital care due epileptic seizures in 1995-96 were considered. Febrile convulsions were excluded of the sample. We found a very expressive prevalence rate of NC among patients suffering from epilepsy. Roughly 24% of these patients, showed unequivocal tomography evidences for the diagnosis of NC. Our data suggest cysticercosis as a real endemic trouble in the area and, overdosis of information in proper language, diffuse to the whole population, seems to be the only remedy to fight against it. Moreover, we should pay special attention to everyone related to swine farming, does not matter how this activity has been classified.

Ketoconazole in the treatment of cryptococcosis of the central nervous system.

Two patients with cryptococcosis of the CNS were treated with ketoconazole (KTZ), an imidazole derivative with fungistatic properties: they had either failed standard therapy (Amphotericin-B + 5-Fluorocytosine) or suffered intolerable side-effects to it. Both patients were administered KTZ 800 mg/day as monotherapy for six months without interruption and both responded. One month after KTZ therapy was withdrawn, however, a relapse of the infection was seen in one case. Side-effects were minimal during the trial of treatment. KTZ could be a useful drug in some cases of neurocryptococcosis.

Phenytoin as the first option in female epileptic patients?

OBJECTIVE: Phenytoin (PHT) is one of the first-choice drugs in several epileptic syndromes, mostly in partial epilepsies, in which case it is effective as carbamazepine and phenobarbital. However, like any other anti-epileptic drug (AED), unpleasant side-effects are not rare. The aim of this study is the evaluation of dermatological troubles related to chronic PHT usage in female patients. METHOD: Between 1990-93, 731 new patients underwent investigation for epilepsy at the Multidisciplinary Clinic for Epilepsy in our State. In this sample 283 were AED users at the time of the first assessment. Sixty one female patients taking PHT were identified. They were taking PHT in a dosage ranging from 100 to 300 mg daily, in mono or polytherapy regimen, during 1-5 previous years. RESULTS: More than 50% of the sample showed coarse facial features made by the combination of several degrees of acne, hirsutism and gingival hyperplasia. CONCLUSION: Except in emergency situations, PHT should not be prescribed as the first option to the treatment of female epileptic patients, because not uncommonly the cosmetic side-effects are more socially handicapping than the epileptic syndrome by itself.

[Epilepsy at a psychiatric hospital]. / Epilepsia em um hospital psiquiátrico.

Epilepsy was surveyed in the largest psychiatric hospital in the Santa Catarina State, southern Brazil. This establishment was designed for one thousand long-term beds but at the time of the survey there were 1126 inpatients. Diagnosis ranged from anxiety neurosis to schizophrenia although patients with epilepsy, with or without psychiatric symptoms were also admitted. The following aspects were analyzed: prevalence of epilepsy, seizure types, antiepileptic drug treatment and psychiatric diagnosis. 171 patients with epilepsy were identified (prevalence 152/1000), generalized tonic clonic attacks were the commonest seizure type and polytherapy was the standard treatment. In at least 85 of the epileptic patients there was no reason for prolonged institutionalization in a psychiatric environment. Moreover, most of the sample were prescribed large amounts of sedative drugs. A multidisciplinary approach and outpatients services are urgently required to improve the prognosis and well-being of patients with epilepsy who are referred to psychiatric care.

[The most common conditions in a neurology specialty clinic]. / Condições mais frequentes em um ambulatório de perícia neurológica.

OBJECTIVE: To present the most frequent diagnosis among patients referred for neurological evaluation to estimate their labour capacities at the unit of National Institute of Social Security (INSS), Florianópolis-SC, southern Brazil. METHOD: Review of all medical records of 108 patients evaluated between October 97 and May 98. The sample was submitted to judicious medico-legal assessment to define their final diagnosis. RESULTS: Neurological evaluation disclosed as the commonest disorders, in decreasing order of frequency: epilepsy, rheumatic diseases, psychiatric illnesses, neurological disorders related to chronic alcoholism, head trauma syndrome and cerebrovascular diseases. CONCLUSION: Neurological disorders may be responsible for important disability among workers in our society. However, the potential for social rehabilitation, often underestimated, must be considered. Moreover, diverse non-neurological conditions used to be sent for neurological evaluation.

Frequency of the different mutations causing spinocerebellar ataxia (SCA1, SCA2, MJD/SCA3 and DRPLA) in a large group of Brazilian patients.

Spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2) and Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) are three distinctive forms of autosomal dominant spinocerebellar ataxia (SCA) caused by expansions of an unstable CAG repeat localized in the coding region of the causative genes. Another related disease, dentatorubropallidoluysian atrophy (DRPLA) is also caused by an unstable triplet repeat and can present as SCA in late onset patients. We investigated the frequency of the SCA1, SCA2, MJD/SCA3 and DRPLA mutations in 328 Brazilian patients with SCA, belonging to 90 unrelated families with various patterns of inheritance and originating in different geographic regions of Brazil. We found mutations in 35 families (39%), 32 of them with a clear autosomal dominant inheritance. The frequency of the SCA1 mutation was 3% of all patients; and 6% in the dominantly inherited SCAs. We identified the SCA2 mutation in 6% of all families and in 9% of the families with autosomal dominant inheritance. The MJD/SCA3 mutation was detected in 30% of all patients; and in the 44% of the dominantly inherited cases. We found no DRPLA mutation. In addition, we observed variability in the frequency of the different mutations according to geographic origin of the patients, which is probably related to the distinct colonization of different parts of Brazil. These results suggest that SCA may be occasionally caused by the SCA1 and SCA2 mutations in the Brazilian population, and that the MJD/SCA3 mutation is the most common cause of dominantly inherited SCA in Brazil.

Evaluation of vigabatrin as an add-on drug in the management of severe epilepsy.

The effects of the addition of Vigabatrin, a new anti-epileptic drug, to the therapy of 128 patients with severe medically refractory epilepsy is reported. Forty two (33%) of patients experienced side effects, which were predominantly neurotropic. In 28 (22%), the drug was withdrawn because of these side effects. The commonest side effects were drowsiness and behavioural change. The remaining 100 patients were followed for a mean of 30 weeks (range 12-75). Forty one of these patients showed a marked improvement in seizure frequency (a 50% or more reduction when compared with the pre-trial period), and nine (7%) were rendered seizure free. Apparent tolerance to the effects of the drug were noted in five patients. An exacerbation of seizures may occur if the drug is withdrawn too quickly. Vigabatrin appears to be a promising new anti-epileptic drug.