Detection of spinal muscular atrophy carriers in a sample of the Brazilian population.

BACKGROUND: Spinal muscular atrophy is a common autosomal recessive neuromuscular disorder caused by mutations in the SMN1 gene. Identification of spinal muscular atrophy carriers has important implications for individuals with a family history of the disorder and for genetic counseling. The aim of this study was to determine the frequency of carriers in a sample of the nonconsanguineous Brazilian population by denaturing high-performance liquid chromatography (DHPLC). METHODS: To validate the method, we initially determined the relative quantification of DHPLC in 28 affected patients (DHPLC values: 0.00) and 65 parents (DHPLC values: 0.49-0.69). Following quantification, we studied 150 unrelated nonconsanguineous healthy individuals from the general population. RESULTS: Four of the 150 healthy individuals tested (with no family history of a neuromuscular disorder) presented a DHPLC value in the range of heterozygous carriers (0.6-0.68). CONCLUSIONS: Based on these results, we estimated there is a carrier frequency of 2.7% in the nonconsanguineous Brazilian population, which is very similar to other areas of the world where consanguineous marriage is not common. This should be considered in the process of genetic counseling and risk calculations.

Symptom onset of spinocerebellar ataxia type 10 in pregnancy and puerperium.

Spinocerebellar ataxia type 10 is an autosomal dominant neurodegenerative disorder. It was initially described in Mexican families presenting with ataxia and epilepsy, with or without polyneuropathy, pyramidal signs and cognitive symptoms. The authors report three patients from the same family who were asymptomatic until gestation and puerperium, when they developed symptoms and signs suggestive of the syndrome. Genetic diagnosis was made in the three patients. The authors hypothesize that hormonal changes are likely to influence the manifestation of the condition.

Coexistence of primary sclerosing cholangitis in a patient with myasthenia gravis.

Myasthenia gravis (MG) is an immune-mediated disease that compromises the postsynaptic membrane of the neuromuscular junction. Primary sclerosing cholangitis (PSC) is considered an immune-mediated cholestatic liver disease. Both MG and PSC include an autoimmune pathogenesis, so there is some evidence that patients with MG or PSC have a higher risk of developing autoantibodies and other immune disorders than normal controls, but the coexistence of these two disorders has never been documented. We report a 40-year-old woman who presented with MG when she was 20 years old and developed PSC 20 years after a thymectomy. Liver biochemistry revealed cholestasis. Magnetic resonance imaging showed multifocal strictures and beads involving the intrahepatic bile ducts. A liver biopsy confirmed sclerosing cholangitis. Serological analysis demonstrated positive autoantibodies (Anti-nuclear antibodies, anti-smooth muscle antibodies). Repetitive stimulation had a decremental response, and antibodies to acetylcholine receptors were detectable. To our knowledge, this is the first case of PSC in a patient with MG. The main characteristics of both MG and PSC combination are discussed.

Molecular characterisation of congenital myasthenic syndromes in Southern Brazil.

OBJECTIVE: To perform genetic testing of patients with congenital myasthenic syndromes (CMS) from the Southern Brazilian state of Parana. PATIENTS AND METHODS: Twenty-five CMS patients from 18 independent families were included in the study. Known CMS genes were sequenced and restriction digest for the mutation RAPSN p.N88K was performed in all patients. RESULTS: We identified recessive mutations of CHRNE in ten families, mutations in DOK7 in three families and mutations in COLQ, CHRNA1 and CHRNB1 in one family each. The mutation CHRNE c.70insG was found in six families. We have repeatedly identified this mutation in patients from Spain and Portugal and haplotype studies indicate that CHRNE c.70insG derives from a common ancestor. CONCLUSIONS: Recessive mutations in CHRNE are the major cause of CMS in Southern Brazil with a common mutation introduced by Hispanic settlers. The second most common cause is mutations in DOK7. The minimum prevalence of CMS in Parana is 0.18/100 000.

Fungal encephalitis following bone marrow transplantation: clinical findings and prognosis.

BACKGROUND: Central nervous system fungal infections (FI) are important complications and a cause of mortality in patients who receive hematopoietic stem cell transplantation (HSCT). AIMS: To study the clinical aspects of fungal encephalitis (FE). SETTINGS AND DESIGN: The study was carried out at the HSCT Center of the Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil. MATERIALS AND METHODS: Clinical records and autopsy reports from patients submitted to HSCT with a diagnosis of FE. RESULTS: Twelve patients were diagnosed with FE presenting with lowered level of consciousness, hemiparesis and seizures. We were able to identify two subgroups regarding susceptibility to FE: (1) patients with early onset FI and severe leucopenia, and (2) patients with later onset FI with graft-versus-host disease using immunosuppressive drugs. Eleven of the patients died directly due to the neurological complication, all had post-mortem confirmation of the diagnosis of FI. CONCLUSIONS: These clinical, paraclinical and temporal patterns may provide the opportunity for earlier diagnosis and interventions.

Prevalence of migraine in Noonan syndrome.

A randomized double-controlled trial involving 22 patients with Noonan syndrome (NS) and 22 normal individuals (control group) was carried out to determine the prevalence of migraine in patients with NS. The NS group consisted of 11 males aged 19.55 +/- 6.11 years and 11 females aged 18.81 +/- 5.47 years. The control group consisted of 11 males aged 19.55 +/- 6.6 years and 11 females aged 18.81 +/- 5.47 years. Seven NS-group patients reported migraine without aura (MO), and three reported probable MO (PMO). Taken together, these represent a prevalence of migraine in the NS group of 45.5%. Two control-group patients reported MO, a prevalence of 9.09%. The prevalence of migraine was significantly higher in the NS-group patients than in the controls (P < 0.005), suggesting a positive association between NS and migraine. Nevertheless, further studies are needed to confirm our findings.

Leao's cortical spreading depression: from experimental "artifact" to physiological principle.

Cortical spreading depression was described in 1943 by Aristides Leão, a Brazilian neurophysiologist. Initially considered to be a mysterious event as it was discovered serendipitously, its nature has become progressively better known. Cortical spreading depression is now accepted as the mechanism underlying migraine aura and has became known as either Leão's spreading depression or cortical spreading depression. Recent studies have suggested a role for Leão's cortical spreading depression in the pathogenesis and symptomatology of neurologic disorders such as transient global amnesia, head injury, and cerebrovascular diseases.

An open study of botulinum-A toxin treatment of trigeminal neuralgia.

Thirteen subjects with trigeminal neuralgia were treated with botulinum-A neurotoxin (BoNT/A) in an open-label pilot study. After BoNT/A, visual analog scale score, surface area of pain, and therapeutic coefficient were reduced in all patients and for all branch trigeminal nerves studied. Therefore, BoNT/A is an efficient treatment. There were no major side effects. A placebo-controlled clinical trial is needed to confirm these findings.

Hamartoma fibrolipomatoso de nervo mediano: relato de caso / Fibrolipomatous hamartoma of the median nerve: case report

Fibrolipomatous hamartoma is a rare benign neoplasm that in some cases is associated with macrodactylia. We describe a 31-year-old man who had a tissue enlargement in the wrist, second and third fingers of the left hand since infancy. At 23-years-old he began with continuous, progressive and high intensity pain that occurred more frequently at night, localized in the left hand. It was associated with paraesthesias and hypostesias predominantly at the fingers described above. Investigation with X-ray, ultrasonography, electrodiagnosis, magnetic resonance image of the left wrist and hand showed carpal tunnel syndrome with macrodactylia by fibrolipomatous hamartoma of the median nerve. The patient did not a have good response to clinical therapy, so he was submitted to a surgical decompression of the left carpal tunnel, and after three months of follow up is asymptomatic.

O hamartoma fibrolipomatoso é neoplasia benigna rara que em alguns casos esta associada com macrodactilia. Descrevemos o caso de homem de 31 anos que apresentava desde o nascimento aumento de volume em região de punho, segundo e terceiro quirodáctilos da mão esquerda. Aos 23 anos iniciou dor contínua, de forte intensidade, predominante no período noturno e de evolução progressiva em mão esquerda. Associada à dor havia hipoestesia e parestesias de predomínio nos segundo e terceiro quirodáctilos esquerdos. A investigação complementar com radiografia, ultrassonografia, estudo eletrofisiológico e ressonância magnética de mão e punho esquerdos confirmaram a suspeita de síndrome do túnel do carpo secundária a macrodactilia com hamartoma fibrolipomatoso do nervo mediano. O paciente foi submetido à descompressão cirúrgica do túnel do carpo esquerdo devido a ausência de resposta ao tratamento clínico e evoluiu com melhora dos sintomas em avaliação após três meses do procedimento.

Estudo da condução nervosa motora na doença de McArdle: relato de caso / Motor nerve conduction study in McArdle disease: case report

McArdle disease (glycogenosis type V) is a metabolic myopathy with symptoms of exercise intolerance caused by deficiency of the enzyme myophosphorylase. In these patients, the motor nerve conduction studies after a short period of maximal voluntary muscle contraction or repetitive stimulation reveals characteristic findings of the disease. A 37-year-old man presented symptoms of exercise intolerance, muscular fatigue and cramps in the beginning of the physical activity with [quot ]second wind[quot ] phenomenon. The motor nerve conduction studies after a voluntary contraction of 30 and 90 seconds presented decrease in the amplitude of the compound muscle action potential in median, ulnar and deep peroneal nerves; and decrement after 200 stimulation at the 40 Hz in deep peroneal nerve. The electromyography presented myopathic pattern and during the ischemic exercise electric silence was not proven. The characteristic of electrophysiological studies are discussed with emphasis at the importance of the motor nerve conduction studies in the patients with suspicion of metabolic myopathy.

A doença de McArdle (glicogenose tipo V) é miopatia metabólica com sintomas de intolerância ao exercício, causados pela deficiência da enzima miofosforilase. Nesses pacientes, o estudo da condução nervosa motora após período de esforço muscular máximo ou ao estímulo repetitivo pode revelar achados característicos da doença. Descrevemos o caso de um homem de 37 anos com sintomas de intolerância aos exercícios, fadiga muscular e cãibras no início da atividade física com a presença do fenômeno de "second wind". O estudo da condução nervosa motora apresentava redução na amplitude do potencial de ação muscular composto após esforço de 30 e 90 segundos em nervos mediano, ulnar e fibular profundo e decremento após 200 estímulos a 40 Hz em nervo fibular profundo. A eletromiografia de agulha apresentava padrão miopático e durante o exercício isquêmico não se evidenciou silêncio elétrico. Discutimos as características eletrofisiológicas enfatizando a importância do estudo da condução nervosa motora e teste de estimulação repetitiva nos pacientes com suspeita de miopatia metabólica.

Critical flicker frequency in migraine. A controlled study in patients without prophylactic therapy.

The critical flicker frequencies (CFF) of individuals with migraine with and without aura were determined and compared to those of normal controls. Twenty-six migraine patients, 12 with aura and 14 without aura and 30 healthy controls were included. Migraineurs were tested during a migraine-free period, through both the continuous flicker method (CFM) and the forced choice method (FCM). Migraineurs presented a mean flickering fusion threshold lower than healthy controls with the CFM (40.45 vs. 44.33, respectively; P = 0.019) and with the FCM (34.16 Hz vs. 38.5 Hz, respectively, P = 0.019). Both groups of migraineurs had significantly lower thresholds as compared to controls, migraineurs with aura presenting the lowest thresholds for the fusion of flickering (P = 0.008 and P = 0.0001 with the CFM and the FCM, respectively). Results confirmed and extended previous observations of abnormal flicker fusion thresholds in migraineurs. We hypothesize that this finding might be related to a shorter cortical stimulation silent period.

Generalized dystonia and striatal calcifications with lipoid proteinosis.

Lipoid proteinosis (LP) is an autosomal recessive disease that typically presents with papular, verrucous, poxlike, or acneiform scars and lesions and hoarseness. LP was recently mapped to the 1q21 locus and shown to result from mutations in the extracellular matrix protein 1 gene (ECM1). Epilepsy, mental retardation, and hippocampal calcifications can occur. The authors describe a patient with generalized dystonia caused by striatal calcifications.

Clinical phenotype of Brazilian families with spinocerebellar ataxia 10.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant ataxia caused by an ATTCT repeat expansion in an intron of the SCA10 gene. SCA10 has been reported only in Mexican families, in which the disease showed a combination of cerebellar ataxia and epilepsy. The authors report 28 SCA10 patients from five new Brazilian families. All 28 patients showed cerebellar ataxia without epilepsy, suggesting that the phenotypic expression of the SCA10 mutation differs between Brazilian and Mexican families.

Headache related to a specific screen flickering frequency band.

The case of a 25-year-old white male, who had migrainous headaches each time he sat in front of his personal computer screen, is described. Changing the screen frequency from 60 to 75 Hz through a Windows command could abolish the headaches. In several surveys, computer screens have been reported to be a migraine trigger. We hypothesize that this environmental trigger may be related to the abnormal flicker fusion thresholds that have been described in migraineurs. It may be that modifying the frequencies of light sources, such as computer screens, could become a non-pharmacological approach to prevent migraine attacks.

Central nervous system paracoccidioidomycosis: clinical features and laboratorial findings.

OBJECTIVE: To study prospectively the clinical features and laboratorial characteristics of 24 patients with central nervous system (CNS) involvement with paracoccidioidomycosis (PCM). PCM is an infectious disease caused by the dimorphic fungus Paracoccidioides brasiliensis, endemic in subtropical areas of Central and South America. METHODS: From 173 cases of PCM, 24 (13.9%) had CNS involvement (NPCM) and were studied prospectively from 1993 to 1997. In all the patients, the diagnosis of systemic PCM was made by the demonstration of the P. brasiliensis organisms or positive serology, DID (double immunodiffusion). In seven cases the diagnosis was made by means of a CNS biopsy. CNS clinical manifestations, neuroimaging (CT or MRI) and CSF cytochemical characteristics were reported. RESULTS: The mean age was 44 years (range 25-72 years); 23 patients were male, only one was female. Neurological symptoms began before systemic symptoms in 21%; simultaneously in 33%, and after systemic symptoms in 46%. Epilepsy was the more frequent neurological presentation (44%). Twenty-three cases had parenchymatous involvement and in two of these cases there was an association with meningitis and one case had spinal cord involvement. Lesions were more frequent in the brain hemispheres (69%), in 65% there were multiple granuloma characterized by hypodense images with annular or nodular enhancing. All cases were treated with sulphamethoxazole-trimethoprin. Four patients died, while 20 patients showed a good therapeutic response. CONCLUSION: NPCM should always be considered in the differential diagnosis of expanding lesions of the CNS and meningoencephalitis. Being alert to this diagnosis depends on knowledge of epidemiology. There was good response to sulphamethoxazole-trimethoprin treatment.

Central nervous system Aspergillus fumigatus infection after near drowning.

AIMS: To report the case of a 26 year old white man, who developed chronic meningitis and intracerebral granulomata 15 days after an episode of near drowning in a swamp. METHODS: Aspergillus fumigatus was isolated from cerebrospinal fluid cultures. RESULTS: The patient died 70 days after the symptoms were first noticed, and seven days after a subarachnoid haemorrhage. Aspergillus has never been reported before as a cause of intracranial infection after near drowning. CONCLUSIONS: Physicians must be aware of this possibility when confronted with such a situation, because there are now effective therapeutic options for systemic aspergillosis.

Infection of the CNS by Scedosporium apiospermum after near drowning. Report of a fatal case and analysis of its confounding factors.

This report describes a fatal case of central nervous system pseudallescheriasis. A 32 year old white man presented with headache and meningismus 15 days after nearly drowning in a swine sewage reservoir. Computerised tomography and magnetic resonance imaging of the head revealed multiple brain granulomata, which vanished when steroid and broad spectrum antimicrobial and antifungal agents, in addition to dexamethasone, were started. Cerebrospinal fluid analysis disclosed a neutrophilic meningitis. Treatment with antibiotics and amphotericin B, together with fluconazole and later itraconazole, was ineffective. Miconazole was added through an Ommaya reservoir, but was insufficient to halt the infection. Pseudallescheria boydii was finally isolated and identified in cerebrospinal fluid cultures, a few days before death, three and a half months after the symptoms began. Diagnosis was delayed because of a reduction in the lesions after partial treatment, which prevented a stereotactic biopsy. Physicians should be aware of this condition, and provide prompt stereotactic biopsy. Confirmed cases should perhaps be treated with voriconazole, probably the most effective, currently available treatment for this agent.