Fukuyama-type congenital muscular dystrophy: a case report in the Japanese population living in Brazil

INTRODUCTION: We present herein clinical, histological and magnetic resonance imaging (MRI) findings in a patient with Fukuyama-type congenital muscular dystrophy (FCMD). He is the first case report in the Japanese population living in Brazil. CASE REPORT: The child presented with neonatal hypotonia, delayed motor abilities and speech, seizures, cerebral and cerebellar gyrus abnormalities with signal intensity change in the white matter by MRI, high serum level of creatinephosphokinase (CK), and dystrophic skeletal muscle with normal merosin, alpha-sarcoglycan and dystrophin expression. The fukutin gene study showed one founder 3-kb retrotransposal insertion in the 3'-non-coding region, and in the other allele no mutation was detected after screening all exons and flanking introns by sequencing. DISCUSSION: This case report emphasizes the importance to consider FCMD in Japanese people living in other countries.     

Eye-hand preference dissociation in obsessive-compulsive disorder and dyslexia

Dyslexia may be a development disturbance in which there are alterations in visual-spatial and visual-motor processing, while obsessive-compulsive disorder (OCD) is a psychiatric disease in which there are alterations in memory, executive function, and visual-spatial processing. Our hypothesis is that these disturbances may be, at least partially, the result of a crossed eye and hand preference. In the present study 16 controls, 20 OCD (DSM-IV criteria) and 13 dyslexic adults (Brazilian Dyslexia Association criteria) were included. All had a neurological examination, the Yale-Brown scale for obsessive-compulsive symptoms application and the Zazzó evaluation for laterality, abridged by Granjon. Results showed a right hand preference for 100% of controls, 84.6% of dyslexics, and 75% of OCD patients and a right eye preference for 73.3% of controls, 69.2% of dyslexics, and 35% of OCD patients. The left eye preference was significantly higher in OCD when compared with the two other groups (p = 0.01) and the left hand preference of OCD patients (25%) was also significant when compared to Brazilian population (4%) or British population (4.5%). It is possible that this crossed preference may be partially the reason for visual-spatial and constructive disturbances observed in OCD.     

Stereologic study of the cerebellar Purkinje cells submitted to alcoholic intoxication in Wistar rats

BACKGROUND: to analyze the effect of the alcohol on the cells of Purkinje. METHOD: Wistar rats received alcoholic solutions orally in different concentrations 4%, 12% and 24%. The animals were sacrificed with 4, 8 and 12 weeks and the cerebella were randomly cut and embedded in paraffin. Sections of 6 micrometer (H&E) were stereologically analyzed. RESULTS: The differences among the density for area and density of surface of the cells of Purkinje of all of the experimental groups (E) and the respective controls (C) were significant. With 12 weeks the cell of Purkinje volume density decreased among the groups C and E in the concentrations of 4% and 12%, but not for the concentration of 24%, probably due to smaller liquid ingestion by the animals. CONCLUSION: The alcohol has toxic effect on the Purkinje cellular body in the three studied concentrations from 4 weeks.     

Cerebral trypanosomiasis and AIDS

A 36 year-old black female, complaining of headache of one month's duration presented with nausea, vomiting, somnolence, short memory problems, loss of weight, and no fever history. Smoker, intravenous drugs abuser, promiscuous lifestyle. Physical examination: left homonimous hemianopsia, left hemiparesis, no papilledema, diffuse hyperreflexia, slowness of movements. Brain CT scan: tumor-like lesion in the splenium of the corpus calosum, measuring 3.5 x 1.4 cm, with heterogeneous enhancing pattern, suggesting a primary CNS tumor. Due to the possibility of CNS infection, a lumbar puncture disclosed an opening pressure of 380 mmH(2)0; 11 white cells (lymphocytes); glucose 18 mg/dl (serum glucose 73 mg/dl); proteins 139 mg/dl; presence of Trypanosoma parasites. Serum Elisa-HIV tests turned out to be positive. Treatment with benznidazole dramatically improved clinical and radiographic picture, but the patient died 6 weeks later because of respiratory failure. T. cruzi infection of the CNS is a rare disease, but we have an increasing number of cases in HIV immunocompromised patients. Diagnosis by direct observation of CSF is uncommon, and most of the cases are diagnosed by pathological examination. It is a highly lethal disease, even when properly diagnosed and treated. This article intends to include cerebral trypanosomiasis in the differential diagnosis of intracranial space-occupying lesions, especially in immunocompromised patients from endemic regions.     

Clinical,endoscopical and manometric evaluation of swallowing in patients with acquired autoimmune myasthenia gravis

Dysphagia, or difficulty swallowing, is a common problem following myasthenia gravis (MG) and may lead to aspiration of saliva, food or liquids. We herein present 22 MG patients, with complaint of dysphagia, evaluated by phonoaudiological evaluation, nasofibrolaryngoscopical analysis and manometry of upper esophageal sphincter. The main objective was to evaluate the phases of the swallowing process and anatomical and functional aspects of oropharyngeal musculature. The age of patients varied from 19 to 74 years; being 19 female and 3 male. The main data were: (1) statistically significant relation between the phonoaudiological clinical evaluation and nasofibrolaryngoscopical one; (2) stomatognatical system disorders present in 100%; (3) swallowing and chewing disorders present in 100%, when clinically evaluated, and in 81,8% when evaluated by the nasofibrolaryngoscopy; (4) statistically significant relation between penetration/aspiration and antecedents of pneumonia; (5) stomatognatical muscles very altered, difficulty controlling the bolus, collection of food in the pharynx or larynx and presence of penetration and/or aspiration showed significant correlation with weakness of a pharyngeal muscles. These findings justify the necessity to evaluate clinically the swallowing phases in MG patients, with the main purpose to prevent both aspiration and dehidration from inadequate oral intake.     

Neuroprotective action of melatonin on neonatal rat motoneurons after sciatic nerve transection

The neuronal isoform of nitric oxide synthase (nNOS), a NADPH-dependent diaphorase, is considered to play a role in motoneuron death induced by sciatic nerve transection in neonatal rats. Neuronal loss in these circumstances has been correlated with nitric oxide (NO) production and NADPH-diaphorase positivity in motoneurons after axotomy. In the present study we looked for a possible protective effect of melatonin, an antioxidant agent and inhibitor of nNOS, on spinal motoneurons after axonal injury. Neonatal Wistar rats (P2) were submitted to sciatic nerve transection and allowed to survive to P7. Melatonin at doses of 1, 5, 10, 50 and 100 mg/kg was given subcutaneously before and at intervals after the surgery. Controls operated in the same way received dilution vehicle or no treatment. The animals were killed by perfusion of fixative and the spinal cord was examined in serial paraffin sections. The motoneurons of the sciatic pool were counted in the axotomized and contralateral sides. Immunohistochemistry for nNOS and glial fibrillary acidic protein was used to evaluate nNOS expression in the axotomized cells and the astrocytic response. We found that melatonin at doses of 1-50 mg/kg decreased neuronal death. Astrocytic hypertrophy in melatonin treated animals was less intense. There were no differences in nNOS expression between treated and control rats, and surviving motoneurons of the sciatic pool did not express the enzyme, suggesting that nNOS may not be involved in neuronal death or survival in these experimental conditions. Possible mechanisms of melatonin neuroprotection, which was equally effective at doses of 1-50 mg/kg, are discussed. Doses of 50 and 100 mg/kg caused failure to thrive, seizures or death. The fact that neuroprotective doses were far smaller than toxic ones should encourage testing of melatonin in neurologic diseases.     

Guanine and adenine nucleotidase activities in rat cerebrospinal fluid

Adenine and guanine nucleotides have been shown to exert multiple roles in central and peripheral nervous systems, and the sequential breakdown of these nucleotides by enzymatic systems is an important step in the modulation of their extracellular effects. The aim of this study was to investigate whether nucleotide hydrolysis also occurs in the cerebrospinal fluid (CSF) of rats. CSF was able to hydrolyze all guanine and adenine nucleotides investigated (2.0 mM): GDPADP=ATP=GTPAMP=GMP. More detailed studies with the diphosphate nucleotides showed that the hydrolysis of ADP and GDP was linear with incubation time and protein concentration. The apparent K_M (Henry–Michaelis–Menten constant) and V (maximal velocity) values for ADP and GDP were 164.3±54.7 μM and 12.2±3.8 nmol P_i/min per mg protein, and 841.0±90.2 μM and 22.8±8.0 nmol P_i/min per mg protein. The sum of ADP, GDP and UDP hydrolysis (2.0 mM) upon individual incubations with CSF was similar to the hydrolysis observed when all three nucleotides were incubated together. This pattern of hydrolysis strongly suggests the involvement of more than one enzyme activity. The higher maximum activity for GDP and UDP compared to ADP is compatible with presence of a soluble NTDPase5.     

Central serotonergic and adrenergic/imidazoline inhibitory mechanisms on sodium and water intake

Recent studies have shown the existence of two important inhibitory mechanisms for the control of NACL and water intake: one mechanism involves serotonin in the lateral parabrachial nucleus (LPBN) and the other depends on alpha(2)-adrenergic/imidazoline receptors probably in the forebrain areas. In the present study we investigated if alpha(2)-adrenergic/imidazoline and serotonergic inhibitory mechanisms interact to control NaCl and water intake. Male Holtzman rats with cannulas implanted simultaneously into the lateral ventricle (LV) and bilaterally into the LPBN were used. The ingestion of 0.3 M NaCl and water was induced by treatment with the diuretic furosemide (10 mg/kg of body weight)+the angiotensin converting enzyme inhibitor captopril (5 mg/kg) injected subcutaneously 1 h before the access of rats to water and 0.3 M NaCl. Intracerebroventricular (i.c.v.) injection of the alpha(2)-adrenergic/imidazoline agonist clonidine (20 nmol/1 microl) almost abolished water (1.6+/-1.2, vs. vehicle: 7.5+/-2.2 ml/2 h) and 0.3 M NaCl intake (0.5+/-0.3, vs. vehicle: 2.2+/-0.8 ml/2 h). Similar effects were produced by bilateral injections of the 5HT(2a/2c) serotonergic agonist 2,5-dimetoxy-4-iodoamphetamine (DOI, 5 microg/0.2 microl each site) into the LPBN on water (3.6+/-0.9 ml/2 h) and 0.3 M NaCl intake (0.4+/-0.2 ml/2 h). Injection of the alpha(2)-adrenergic/imidazoline antagonist idazoxan (320 nmol) i.c.v. completely blocked the effects of clonidine on water (8.4+/-1.5 ml/2 h) and NaCl intake (4.0+/-1.2 ml/2 h), but did not change the effects of LPBN injections of DOI on water (4.2+/-1.0 ml/2 h) and NaCl intake (0.7+/-0.2 ml/2 h). Bilateral injections of methysergide (4 microg/0.2 microl each site) into the LPBN increased 0.3 M NaCl intake (6.4+/-1.9 ml/2 h), not water intake. The inhibitory effect of i.c.v. clonidine on water and 0.3 M NaCl was still present after injections of methysergide into the LPBN (1.5+/-0.8 and 1.7+/-1.4 ml/2 h, respectively). The results show that the inhibitory effects of the activation of alpha(2)-adrenergic/imidazoline receptors in the forebrain are still present after blockade of the LPBN serotonergic mechanisms and vice versa for the activation of serotonergic mechanisms of the LPBN. Therefore, each system may act independently to inhibit NaCl and water intake.