Beyond neuropathy in hereditary sensory and autonomic neuropathy type V: cognitive evaluation.

BACKGROUND AND PURPOSE: Hereditary sensory and autonomic neuropathy (HSAN) type V is a very rare disorder. It is characterized by the absence of thermal and mechanical pain perception caused by decreased number of small diameter neurons in peripheral nerves. Recent genetic studies have pointed out the aetiological role of nerve growth factor beta, which is also involved in the development of the autonomic nervous system and cholinergic pathways in the brain. HSAN type V is usually reported not to cause mental retardation or cognitive decline. However, a structured assessment of the cognitive profile of these patients has never been made. METHODS AND RESULTS: We performed a throughout evaluation of four HSAN type V patients and compared their performance with 37 normal individuals. Our patients showed no cognitive deficits, not even mild ones. DISCUSSION AND CONCLUSIONS: Although newer mutations on this and related disorders are continuously described, their clinical characterization has been restricted to the peripheral aspects of these conditions. A broader characterization of this rare disorder may contribute to better understand the mechanisms of the nociceptive and cognitive aspects of pain.

Association of TP53 mutation, p53 overexpression, and p53 codon 72 polymorphism with susceptibility to apoptosis in adult patients with diffuse astrocytomas.

Clarification of TP53 alterations is important to understand the mechanisms underlying the development of diffuse astrocytomas. It has been suggested that the alleles of TP53 at codon 72 differ in their ability to induce apoptosis in human cancers. The aim of this study was to analyze the possible association of TP53 mutation, p53 overexpression, and p53 codon 72 polymorphism with susceptibility to apoptosis in adult Brazilian patients with diffuse astrocytomas. We analyzed 56 surgical specimens of diffuse astrocytomas for alterations of TP53, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) direct sequencing. p53 and cleaved caspase 3 protein expression were assessed by immunohistochemistry. We found TP53 mutations in 19.6% (11 out of 56) of tumors tested, with the lowest mutation rate found in the cases of glioblastomas (8.8%) (p = 0.03). Only 16.1% of tumors tested showed cleaved caspase 3-positive staining, demonstrating that apoptosis is very inhibited in these tumors. All tumors having TP53 mutation and p53 accumulation had no expression of cleaved caspase 3. Additionally, no association was observed in tumors having proline and arginine alleles and expression of cleaved caspase 3. We concluded that clarification of the TP53 alterations allows a better understanding of the mechanisms involved in the progression of diffuse astrocytomas, and the allele status at codon 72 was not associated with apoptosis in these tumors.

Dystrophin-glycoproteins associated in congenital muscular dystrophy: immunohistochemical analysis of 59 Brazilian cases

The congenital muscular dystrophies (CMD) are heterogeneous muscular diseases with early and dystrophic pattern on muscle biopsy. Many different subtypes have been genetically identified and most phenotypes not yet identified belong to the merosin-positive (MP) CMD subgroup. OBJECTIVE: To analyze the immunohistochemical expression of the main proteins of the dystrophin-glycoproteins associated complex in muscle biopsy of patients with different CMD phenotypes, for investigating a possible correlation with clinical and histopathological data. METHOD: Fifty-nine patients with CMD had clinical, histopathological and immunohistochemical data evaluated: 32 had MP-CMD, 23 CMD with merosin deficiency (MD-CMD), one Ullrich phenotype and three Walker-Warburg disease. RESULTS: Dystrophin and dysferlin were normal in all; among the patients with MD-CMD, merosin deficiency was partial in nine who showed the same clinical severity as those with total deficiency; the reduced expression of alpha-sarcoglycan (SG) and alpha-dystroglycan (DG) showed statistically significant correlation with severe MD-CMD phenotype. CONCLUSION: There is a greater relationship between merosin and the former proteins; among MP-CMD patients, no remarkable immunohistochemical/phenotypical correlations were found, although the reduced expression of beta-DG had showed statistically significant correlation with severe phenotype and marked fibrosis on muscular biopsy.

A distrofia muscular congênita (DMC) é doença muscular heterogênea, de início precoce e padrão histopatológico de distrofia. Diversos subtipos foram geneticamente identificados e os fenótipos ainda não identificados pertencem em geral ao subgrupo de DMC merosina-positiva (MP). OBJETIVO: Analisar a expressão imuno-histoquímica das principais proteínas do complexo distrofina-glicoproteínas associadas na biópsia muscular de pacientes com diferentes fenótipos de DMC, a fim de investigar uma eventual correlação com o quadro clínico e histopatológico. MÉTODO: Cinqüenta e nove pacientes com DMC foram avaliados clinicamente e sua biópsia muscular, histopatologica e imuno-histoquimicamente: 32 eram MP, 23 merosina-deficiente (MD), um mostrava fenótipo Ullrich e três síndrome de Walker-Warburg. RESULTADOS: Distrofina e disferlina foram normais em todos; nove pacientes MD apresentavam déficit parcial de merosina, porém com a mesma gravidade clínica daqueles com deficiência total. CONCLUSÃO: A hipoexpressão de a-sarcoglicana (SG) and a-distroglycan (DG) se correlacionou estatisticamente com o grave fenótipo MD, assim indicando maior correlação entre a merosina e as referidas proteínas; entre os pacientes MP, apesar da hipoexpressão de b-DG ter se correlacionado significativamente com fenótipo e histopatologia mais grave, não houve correlação clínica/imuno-histoquímica valorizável.

Ullrich congenital muscular dystrophy and Bethlem myopathy: clinical and genetic heterogeneity

Ullrich congenital muscular dystrophy (UCMD), due to mutations in the collagen VI genes, is an autosomal recessive form of CMD, commonly associated with distal joints hyperlaxity and severe course. A mild or moderate involvement can be occasionally observed. OBJECTIVE: To evaluate the clinical picture of CMD patients with Ullrich phenotype who presented decreased or absent collagen VI immunoreactivity on muscular biopsy. RESULTS: Among 60 patients with CMD, two had no expression of collagen V and their clinical involvement was essentially different: the first (3 years of follow-up) has mild motor difficulty; the second (8 years of follow-up) never acquired walking and depends on ventilatory support. A molecular study, performed by Pan et al. at the Thomas Jefferson University, demonstrated in the first a known mutation of Bethlem myopathy in COL6A1 and in the second the first dominantly acting mutation in UCMD and the first in COL6A1, previously associated only to Bethlem myopathy, with benign course and dominant inheritance. CONCLUSION: Bethlem myopathy should be considered in the differential diagnosis of UCMD, even in patients without fingers contractures; overlap between Ullrich and Bethlem phenotypes can be supposed.

A distrofia muscular congênita (DMC) com hiperextensibilidade articular distal (fenótipo Ullrich) associa-se a mutações nos genes do colágeno VI e corresponde a um grave quadro congênito de herança autossômica recessiva e curso progressivo, ocasionalmente mostrando menor gravidade. OBJETIVO: Avaliar o quadro clínico dos pacientes com DMC tipo Ullrich que apresentam imunoexpressão baixa ou ausente do colágeno VI na biópsia muscular. RESULTADOS: Entre 60 pacientes com DMC, dois mostravam imunomarcação negativa do colágeno VI. Mostravam-se clinicamente essencialmente diferentes: o primeiro, com 8 anos de idade e três de seguimento mostra leve dificuldade motora; o segundo, com 14 anos de idade e 8 de seguimento, não deambula e apresenta insuficiência respiratória. O estudo molecular, realizado na Thomas Jefferson University por Pan et al., revelou no primeiro, no gene COL6A1, mutação típica da miopatia de Bethlem, que tem curso benigno e herança autossômica dominante; e no segundo a primeira mutação de efeito dominante e do gene COL6A1, previamente associado apenas à miopatia de Bethlem. CONCLUSÃO: A miopatia de Bethlem deve constar no diagnóstico diferencial da DMC tipo Ullrich, mesmo na ausência das típicas contraturas dos dedos; pode existir sobreposição dos fenótipos Ullrich e Bethlem.

Normative data for the Brazilian population in the Boston Diagnostic Aphasia Examination: influence of schooling.

In Neurolinguistics, the use of diagnostic tests developed in other countries can create difficulties in the interpretation of results due to cultural, demographic and linguistic differences. In a country such as Brazil, with great social contrasts, schooling exerts a powerful influence on the abilities of normal individuals. The objective of the present study was to identify the influence of schooling on the performance of normal Brazilian individuals in the Boston Diagnostic Aphasia Examination (BDAE), in order to obtain reference values for the Brazilian population. We studied 107 normal subjects ranging in age from 15 to 84 years (mean +/- SD = 47.2 +/- 17.6 years), with educational level ranging from 1 to 24 years (9.9 +/- 4.8 years). Subjects were compared for scores obtained in the 28 subtests of the BDAE after being divided into groups according to age (15 to 30, N = 24, 31 to 50, N = 33 and 51 years or more, N = 50) and education (1 to 4, N = 26, 5 to 8, N = 17 and 9 years or more, N = 61). Subjects with 4 years or less of education performed poorer in Word Discrimination, Visual Confrontation Naming, Reading of Sentences and Paragraphs, and Primer-Level Dictation (P < 0.05). When breakdown by schooling was 8 years or less, subjects performed poorer in all subtests (P < 0.05), except Responsive Naming, Word Recognition and Word-Picture Matching. The elderly performed poorer (P < 0.05) in Complex Ideational Material, Visual Confrontation Naming, Comprehension of Oral Spelling, Written Confrontation Naming, and Sentences to Dictation. We present the reference values for the cut-off scores according to educational level.

Normative data for the Brazilian population in the Boston Diagnostic Aphasia Examination: influence of schooling

In Neurolinguistics, the use of diagnostic tests developed in other countries can create difficulties in the interpretation of results due to cultural, demographic and linguistic differences. In a country such as Brazil, with great social contrasts, schooling exerts a powerful influence on the abilities of normal individuals. The objective of the present study was to identify the influence of schooling on the performance of normal Brazilian individuals in the Boston Diagnostic Aphasia Examination (BDAE), in order to obtain reference values for the Brazilian population. We studied 107 normal subjects ranging in age from 15 to 84 years (mean ± SD = 47.2 ± 17.6 years), with educational level ranging from 1 to 24 years (9.9 ± 4.8 years). Subjects were compared for scores obtained in the 28 subtests of the BDAE after being divided into groups according to age (15 to 30, N = 24, 31 to 50, N = 33 and 51 years or more, N = 50) and education (1 to 4, N = 26, 5 to 8, N = 17 and 9 years or more, N = 61). Subjects with 4 years or less of education performed poorer in Word Discrimination, Visual Confrontation Naming, Reading of Sentences and Paragraphs, and Primer-Level Dictation (P < 0.05). When breakdown by schooling was 8 years or less, subjects performed poorer in all subtests (P < 0.05), except Responsive Naming, Word Recognition and Word-Picture Matching. The elderly performed poorer (P < 0.05) in Complex Ideational Material, Visual Confrontation Naming, Comprehension of Oral Spelling, Written Confrontation Naming, and Sentences to Dictation. We present the reference values for the cut-off scores according to educational level.

Superior orbital 'petrositis' and late ischaemic monocular blindness induced by intense UV radiation exposure.

Many physical agents cause neuropathies. The most common are chronic pressure, vibration and temperature. In general, these lesions occur at work, as a result of accidents or through chronic exposure to the physical agent. Radiation leading to peripheral neuropathy is also related to radiotherapy in cancer treatment, as an undesirable side-effect. We present here a case report of short, intense UV radiation exposure at work, leading to delayed-onset ocular neuropathy. A clear cause-effect relationship is shown, demonstrated using magnetic resonance imaging scans. We suggest that the mechanism was thermal and ischaemic.

The prevalence of multiple sclerosis in the city of São Paulo, Brazil, 1997.

July 1, 1997 was stipulated as the day for estimating the prevalence of multiple sclerosis within the city of São Paulo. The patients were identified via various sources, including associated universities and magnetic resonance services of the city of São Paulo. The area covered by the study has a population of 9,380,000, mainly white and of European origin, with a large number of immigrants from Spain and Portugal. The patients were classified in accordance with the criteria of Poser et al. (1983), and only those with defined multiple sclerosis were registered. The study gave a prevalence of 15.0/10(5) inhabitants, or three times the value obtained in a similar study in 1990. This increase reveals the larger number of cases encompassed by the study, and is attributed to the use of more detailed recording methods, improvements in diagnosis, and better conditions for treatment.

[Benign paroxysmal positioning vertigo]. / Vertigem de posicionamento paroxística benigna.

Benign paroxysmal positioning vertigo is a frequent vestibular disorder. With a simple maneuver one can easily diagnose this condition and treatment is based on liberatory maneuvers. On this review the pathogenesis, the clinical features and different maneuvers are briefly discussed.

Parkinsonism after glycine-derivate exposure.

This 54-year-old man accidentally sprayed himself with the chemical agent glyphosate, a herbicide derived from the amino acid glycine. He developed disseminated skin lesions 6 hours after the accident. One month later, he developed a symmetrical parkinsonian syndrome. Two years after the initial exposure to glyphosate, magnetic resonance imaging revealed hyperintense signal in the globus pallidus and substantia nigra, bilaterally, on T2-weighted images. Levodopa/benserazide 500/125 mg daily provided satisfactory clinical outcome.

[Use of transcranial Doppler in monitoring cerebral vasospasm secondary to subarachnoid hemorrhage]. / Uso do Doppler transcraniano para monitorização do vasoespasmo cerebral secundário à hemorragia subaracnóide.

UNLABELLED: Cerebral vasospasm accounts for an increased morbidity and mortality in patients with spontaneous subarachnoid hemorrhage (SAH). Its early and non invasive detection by transcranial Doppler (TCD) may contribute to a better prognosis in such cases. PURPOSE: To discuss the use of transcranial Doppler (TCD) in the detection of cerebral vasospasm secondary cerebral to spontaneous subarachnoid hemorrhage (SAH). METHODS: We analyzed the flow velocities registered by TCD in intracranial arteries in 31 patients with SAH, performed sequentially, associated with neurological examinations. All patients (except one) had intracranial aneurysms. RESULTS: Clinical vasospasm was found in 11 patients (36,6% from the total), with correspondent sonographic vasospasm present in 9 cases (82%). In 3 cases (33.3%) the flow velocity alterations preceded the clinical symptoms. Between the 20 asymptomatic patients, 15 (75%) had normal flow velocity, with evidence of sonographic vasospasm without clinical repercussion in 5 (25%). The index of false negatives in the correlation between clinical examination and TCD (symptomatic vasospasm with normal flow velocity records) was 18%. However, there was correspondence between clinical and ultrasonographic findings in 26 of the 31 patients (83.8%). The average flow velocity values in the various arteries and its interpretation for each subgroup are discussed with further details. CONCLUSION: TCD is a valuable auxiliary method in the detection of cerebral vasospasm (even pre-symptomatic) secondary to SAH, allowing a more precocious therapeutic intervention. Our results are similar to those described in the literature.

Uso do Doppler transcraniano para monitorizaçäo do vasoespasmo cerebral secundário à hemorragia subaracnóide / Use of transcranial Doppler in the monitoration of cerebral vasospasm secondary to subarachnoid hemorrhage

O vasoespasmo cerebral é responsável por aumento de morbidade e mortalidade em pacientes acometidos por hemorragia subaracnóide (HSA). Sua detecçäo de forma precoce e näo-invasiva pelo método de Doppler transcraniano (DTC) pode contribuir para um melhor prognóstico destes doentes. OBJETIVO: Discutir o uso do método de DTC para diagnóstico do vasoespasmo cerebral secundário à HSA espontânea. METODOS: Foram analisados os registros de velocidade de fluxo em artérias intracranianas por DTC em 31 pacientes com diagnóstico tomográfico de HSA, realizados sequencialmente em conjunto com exame neurológico. Todos os pacientes (à exceçäo de um) eram portadores de aneurismas intracranianos. RESULTADOS: Vasoespasmo clínico foi constatado em 11 pacientes (36,6 por cento do total), com correspondente vasoespasmo ultra-sonográfico presente em nove casos (82 por cento). Em três casos (33,3 por cento) as alteraçöes de velocidade de fluxo precederam os sinais clínicos. Entre os 20 pacientes assintomáticos, 15 (75 por cento) apresentaram medidas de velocidade normais, havendo evidência de vasoespasmo sonográfico sem repercussäo clínica em cinco (25 por cento). O índice de falso negativo na correlaçäo entre exame clínico e DTC (sinais clínicos de vasoespasmo presentes, com velocidades de fluxo normais) foi de 18 por cento. No entanto, houve correspondência entre os achados clínicos e ultra-sonográficos em 26 dos 31 pacientes (83,8 por cento). Os valores de velocidades médias nas várias artérias e sua interpretaçäo para cada subgrupo säo discutidos com maiores detalhes. CONCLUSAO: O método de DTC Ú um auxiliar valioso na detecçäo pré-sintomática do vasoespasmo secundário à HSA, permitindo uma intervençäo terapêutica mais precoce. Os dados obtidos neste trabalho coadunam-se com os diversos estudos publicados na literatura

Intracranial vertebral artery dissection presenting as subarachnoid hemorrhage: successful endovascular treatment.

INTRODUCTION: Intracranial vertebral artery dissection is a rare condition which may present as subarachnoid hemorrhage. In this situation, treatment is controversial. CASE REPORT: A case of intracranial right vertebral artery dissection in a 55-year-old woman presenting with subarachnoid hemorrhage is reported. The patient underwent therapeutic occlusion of the dissected artery through microcatheterization using pushing detachable platinum microcoils and had a good outcome. At this moment, the patient has a normal neurologic examination and a control digital subtraction angiography 1 year after the procedure showed an occluded right vertebral artery at V3; there was retrograde flow in the right intracranial vertebral artery up to the origin of a meningeal branch; the artery was thin and had mural irregularities, without any evidence of aneurismatic dilatation. DISCUSSION: We review the literature and discuss the role of endovascular therapy and other therapeutic options in the treatment of this condition.

Stroke as the first manifestation of calcific aortic stenosis.

Heart valve calcifications are rarely recognized as a potential source for cerebral embolism. Previous studies have identified mitral, but not aortic, valve calcifications to be risk factors for stroke. Based on these studies, heart surgery is unlikely to be indicated in patients who present with a stroke and an 'incidental' aortic valve calcification. We report a case of a 46-year-old man presenting with acute onset of left-sided weakness and numbness. A previous smoking history was the only cardiovascular risk factor found. Head CT scan revealed a right middle cerebral artery territory infarct and an adjacent high-density lesion. CT angiography demonstrated the presence of calcific embolic material in the middle cerebral artery. A search for embolic sources revealed a calcific aortic stenosis (CAS). Initially placed on coumadin, the patient developed silent myocardial infarction 2 months later, presumed to be also embolic in origin from the CAS. After aortic valve replacement, the patient has been symptom-free during a 2-year follow-up. In conclusion, CT angiography may be the method of choice for detecting calcific cerebral emboli, and demonstration of a causal relationship between CAS and an embolic stroke by CT angiography may be an important adjunct in surgical decision-making.

[Malignant hyperthermia susceptibility in 3 patients with malignant neuroleptic syndrome]. / Susceptibilidade à hipertermia maligna em três pacientes com síndrome maligna por neurolépticos.

Hyperthermia, skeletal muscle rigidity, rhabdomyolysis, acidosis and multiple system insufficiency characterize malignant hyperthermia. Anaesthetic malignant hyperthermia follows halogenated volatile agents and/or depolarizing muscle relaxants utilization. Diagnosis is based on in vitro muscle contracture in response to halothane and/or caffeine exposure. Neuroleptic malignant syndrome affects patients taking neuroleptic drugs; clinical findings include hyperthermia, extrapyramidal rigidity, acidosis, neurovegetative instability and neurological signs. We report three neuroleptic malignant syndrome patients with positive muscle contracture tests which shows that muscle from neuroleptic malignant syndrome patients may in some instances show alterations similar to those of anaesthetic malignant hyperthermia.

Inherited thrombophilia as a risk factor for the development of ischemic stroke in young adults.

INTRODUCTION: Several recent studies have analyzed a possible effect of thrombophilia risk factors such as factor V Leiden, the prothrombin variant (allele 20210 A), and homozygosity for thermolabile methylenetetrahydrofolate reductase (MTHFR-T) on the development of ischemic stroke (IS). In the present study, we determined the role of these prothrombotic polymorphisms in the early onset of arterial IS or cerebral venous thrombosis (CVT) in a group of young Brazilian adults of Caucasian and African descent. MATERIALS AND METHODS: We conducted a cross-sectional study of 167 survivors of IS (153 patients with arterial IS and 14 cases of CVT; 66 men: 101 women; 124 of Caucasian and 43 of African origin; median age: 32.6 years; range: 15 to 45 years) and compared the prevalence of inherited thrombophilia risk factors with a control group of 225 sex and age matched individuals of the same ethnic background. To determine the interaction with atherogenic risk factors, the following diagnoses were considered: hypertension, hyperlipoproteinemia, diabetes mellitus, smoking status and use of oral contraceptives. RESULTS: In the arterial IS group, no significant variation was found between patients and controls of Caucasian origin regarding the prevalence of factor V Leiden (P = 0.92), the prothrombin variant (P = 0.13) or homozygosity for MTHFR-T (P = 0.61). Among Brazilians of African descent, 10.3% were homozygous for MTHFR-T, which was significantly elevated, odds ratio of 5.9 (95% CI: 0.88 to 49.15). In the CVT group, two Caucasian patients (20%) were heterozygous for the prothrombin variant, odds ratio of 9.7 (95% CI: 0.95 to 89.71) and one patient was carrier of factor V Leiden (P = 0.49). No prothrombotic polymorphism was identified in patients with CVT of African descent. All women in the CVT group were in use of oral contraceptives or in the post-partum state. DISCUSSION: Inherited thrombophilia risk factors were not found to increase the risk of arterial IS among young patients of Caucasian descent. However, a potential role of homozygosity for MTHFR-T was observed in a small group of patients of African origin. The analysis of patients with CVT revealed an increased risk due to the prothrombin gene variant or oral contraceptive use. Further studies including all incoming patients with IS are necessary to evaluate the impact of inherited thrombophilia risk factors on early mortality.

Magnetic resonance imaging in five patients with a tumefactive demyelinating lesion in the central nervous system.

Five patients with a tumefactive lesion were clinically followed from 1992 to 1993. Four patients were female; age ranged from 32 to 57 years, the duration of symptoms varied from 3 days to 3 years. Neurological examination disclosed dementia in two patients, aphasia in three, hemiparesis in four, hemihypoaesthesia in three, optical neuritis in two, tetraparesis with sensitive level and neurogenic bladder in one. MRI disclosed lesions with a hypersignal on images assessed at T2 and hyposignal at T1, and gadolinium heterogeneous enhancement; these lesions were located in the: a) temporooccipital region bilaterally and brain stem, b) frontoparietal white matter, c) basal ganglia, bilateral white matter and brain stem, d) left parietal region, e) cervical spinal cord, with enlargement of this region. Cerebral biopsy was performed in three patients; acute and subacute demyelinating disease was diagnosed by histological examination. Two patients had an evolutive diagnosis; exclusion of other pathologies and clinical and radiological improvement after corticotherapy, pointed to an inflammatory disease.

Kearns-Sayre syndrome "plus". Classical clinical findings and dystonia.

We present a boy of eight years of age with symptoms of Kearns-Sayre syndrome (KSS) characterised by ophthalmoparesis, palpebral ptosis, mitochondrial myopathy, pigmentous retinitis, associated to short stature, cerebellar signs, cardiac blockade, diabetes mellitus, elevated cerebrospinal fluid protein concentration, and focal hand and foot dystonia. The skeletal muscle biopsy demonstrated ragged red fibers, cytochrome C oxidase-negative and succinate dehydrogenase-positive fibers. The magnetic resonance imaging showed symmetrical signal alteration in tegmentum of brain stem, pallidum and thalamus. Mitochondrial DNA analysis from skeletal muscle showed a deletion in heteroplasmic condition. The association of dystonia to KSS, confirmed by molecular analysis, is first described in this case, and the importance of oxidative phosphorylation defects in the physiopathogenesis of this type of movement disorder is stressed.