Erasmo Barbante Casella

Griscelli Syndrome: Characterization of a New Mutation and Rescue of T-Cytotoxic Activity by Retroviral Transfer of RAB27A Gene

Griscelli syndrome (GS) is caused by mutations in the MYO5A (GS1), RAB27A (GS2), or MLPH (GS3) genes, all of which lead to a similar pigmentary dilution. In addition, GS1 patients show primary neurological impairment, whereas GS2 patients present immunodeficiency and periods of lymphocyte proliferation and activation, leading to their infiltration in many organs, such as the nervous system, causing secondary neurological damage. We report the diagnosis of GS2 in a 4-year-old child with haemophagocytic syndrome, immunodeficiency, and secondary neurological disorders. Typical melanosome accumulation was found in skin melanocytes and pigment clumps were observed in hair shafts. Two heterozygous mutant alleles of the RAB27A gene were found, a C-T transition (C352T) that leads to Q118stop and a G-C transversion on the exon 5 splicing donor site (G467+1C). Functional assays showed increased cellular activation and decreased cytotoxic activity of NK and CD8+ T cells, associated with defective lytic granules release. Myosin-Va expression and localization in the patient lymphocytes were also analyzed. Most importantly, we show that cytotoxic activity of the patients CD8+ T lymphocytes can be rescued in vitro by RAB27A gene transfer mediated by a recombinant retroviral vector, a first step towards a potential treatment of the acute phase of GS2 by RAB27A transduced lymphocytes.

Attention deficit and hyperactivity disorder in people with epilepsy: diagnosis and implications to the treatment

The association between attention deficit and hyperactivity disorder (ADHD) and epilepsy can cause significant impact on the social life of affected individuals and their families. Clinical studies suggest that 30-40% of people with epilepsy also have ADHD. There are no studies which demonstrate that short or long-term treatment with methylphenidate increases the risk of seizures. Some studies attempt to relate drug interactions between methylphenidate and antiepileptic drugs, but adverse effects of methylphenidate have not been shown clearly. This review presents some neurobiological and physiopathogenic aspects, common to ADHD and epilepsy, from recent research studies, related to pharmacology, neuroimaging and electroencephalography. Possible risk of occurrence of seizures associated with the use of methylphenidate are also discussed.

Efficacy and safety of methylphenidate in treating ADHD symptoms in children and adolescents with uncontrolled seizures: A Brazilian sample study and literature review

OBJECTIVE Attention-deficit/hyperactivity disorder (ADHD) is observed in 30% of children and adolescents with epilepsy. Recent studies have demonstrated the safety of methylphenidate (MPH) in patients with controlled epilepsy. There are few studies of patients with uncontrolled epilepsy. The goal was to study the efficacy and safety of MPH use in children and adolescents diagnosed with ADHD and uncontrolled epilepsy. METHODS We evaluated 24 patients ranging from 7 to 16 years of age who took MPH for 6 months. Inclusion criteria were at least two epileptic seizures in the previous 6 months and a diagnosis of ADHD based on DSM-IV criteria. CONCLUSION Patients were classified according to ADHD subtype as follows: 41.7% inattentive type, 37.5% combined, and 20.8% hyperactive/impulsive type; 58.3% had partial epilepsy and 41.7% generalized epilepsy. There was an overall improvement in ADHD symptoms in 70.8% of patients, and there was no increase in frequency of epileptic seizures in 22 patients (91.6%).

Reaction time assessment in children with ADHD

UNLABELLED Attention deficit, impulsivity and hyperactivity are the cardinal features of attention deficit hyperactivity disorder (ADHD) but executive function (EF) disorders, as problems with inhibitory control, working memory and reaction time, besides others EFs, may underlie many of the disturbs associated with the disorder. OBJECTIVE To examine the reaction time in a computerized test in children with ADHD and normal controls. METHOD Twenty-three boys (aged 9 to 12) with ADHD diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, 2000 (DSM-IV) criteria clinical, without comorbidities, Intelligence Quotient (IQ) > or = 89, never treated with stimulant and fifteen normal controls, age matched were investigated during performance on a voluntary attention psychophysical test. RESULTS Children with ADHD showed reaction time higher than normal controls. CONCLUSION A slower reaction time occurred in our patients with ADHD. This findings may be related to problems with the attentional system, that could not maintain an adequate capacity of perceptual input processes and/or in motor output processes, to respond consistently during continuous or repetitive activity.

Sequelae from meningococcal meningitis in children: a critical analysis of dexamethasone therapy

OBJECTIVE To evaluate the effectiveness of dexamethasone as an adjunctive therapy to antibiotics in children with meningococcal meningitis. METHOD A total of 81 children diagnosed with meningococcal meningitis hospitalized in sequence were studied at the University Hospital of São Paulo University, with the objective of evaluating the presence of sequelae in four different groups of patients, following the administration of dexamethasone: Group I - 25 patients who received the first dose at least 10 minutes before the introduction of the antibiotic therapy; Group II - 19 patients who received the corticosteroid concomitantly; Group III - 14 patients for which the dexamethasone was administered after beginning the antibiotic scheme; Group IV - 23 patients that did not receive dexamethasone. The groups were evaluated for homogeneity through the prognostic indexes and clinical and laboratory characteristics, based on the records obtained at hospitalization. RESULTS Some degree of sequelae occurred in 16 (26.22%) of the survivors and 23 patients (28.39%) coursed with sequelae or died. The mean period of neurological attendance was 36.97 months and neurological alterations were detected in 16.17% of the patients. No significant difference was found between the four groups. There was also no statistical difference in the comparison of the neurological sequelae in the children from group IV with the children of groups I and II or even with groups I, II and III analyzed as a whole. The presence of hearing loss occurred in 11.11% of the patients, again there was no significant difference between the four groups. Psychological evaluation was performed using the WPSSI and WISC tests. A mild mental disability was detected in one patient from group I and another in group III. The overall analysis of the sequelae (neurological, auditory and intellectual level) also did not demonstrate any significant difference between the four groups. Comparing the children from groups I and II together and also groups I, II and III as a whole with the children in group IV also failed to detect a significant difference arising from the use or nonuse of the corticosteroid. CONCLUSION Dexamethasone was not proven to be effective in decreasing the number of sequelae among patients with meningococcal meningitis.

Spinal cord schistosomiasis in children: analysis of seven cases

We describe seven cases of children (ages 2 to 14 years) with myeloradiculopathy caused by infection with S. mansoni. None of them presented hepatosplenic involvement and one presented an intestinal picture. The myeloradicular and pseudotumoral forms were observed in four and three patients, respectively. Comparing the reports in the literature, we found that the pseudotumoral form is more similarly frequent among children than in adults, while the myelitic and myeloradicular forms are the most frequent and distributed across all age groups. Diagnosis is based on clinical and epidemiological findings in association with laboratory tests. The diagnosis was confirmed by the presence of S. mansoni eggs in feces (5 cases) and / or the positivity in specific immunological tests (5 cases) associated with a cerebrospinal fluid inflammatory pattern with presence of eosinophils (between 1 and 24%). Magnetic resonance image, although it does not enable an etiological diagnosis, helped to confirm the form and spinal cord level of the lesion.

Ketogenic diet for the treatment of refractory epilepsy: a 10 year experience in children

A dieta cetogenica (DC) tem alto teor de gordura e baixo de carboidratos e proteinas, sendo usada no tratamento da epilepsia refrataria. Analisamos os efeitos da DC em 54 criancas do Instituto da Crianca da Universidade de Sao Paulo. Eficacia, tolerabilidade e efeitos adversos foram estudados. A DC foi considerada eficaz (E) quando houve reducao de crises >75% e boa (B) quando a reducao foi entre 50-75%. Correlacionamos, quando possivel, esses resultados com a sindrome epileptica e com a idade dos pacientes. Observamos resultados (E) em 57,4%, 63,8%, 71,8% e 62,1% dos pacientes no 2o, 6o, 12o e 24o meses, respectivamente e (B) em 31,4%, 25,5%, 25,6% e 37,9%, respectivamente. Houve reducao significativa das drogas antiepilepticas. A DC foi mais eficaz nas epilepsias generalizadas e nao houve diferencas quanto a idade. Efeitos adversos foram raros. Em conclusao, a DC e um tratamento antiepileptico eficaz em casos refratarios.Ketogenic diet (KD) is a high fat and low carbohydrate diet, which controls refractory epilepsy. We analyzed the KD effects on 54 children of the Childrens Institute of the University of São Paulo. Efficacy, tolerability, and adverse effects were studied. Response to KD was effective (E) if seizure control was >75%, good (G) when 50-75%. When possible, we correlated the results with the epileptic syndrome and patients age. By the second month on diet, 57.4% of the patients had E response and 31.4% G results. At the 6th month, 63.8% had E response and 25.5% G. At the 12th month, 71.8% had E and 25.6% G. At the 24th month, 62.1% had E and 37.9% G. Antiepileptic drugs have been reduced, and generalized epilepsy was the most sensitive. Age-related differences were not observed. Adverse effects were rarely observed. In conclusion, KD proved to be an effective treatment for refractory epilepsy.

Polarized light microscopy of hair shafts aids in the differential diagnosis of Chédiak-Higashi and Griscelli-Prunieras syndromes

PURPOSE To study and compare the appearance of hairs from patients with Chédiak-Higashi and Griscelli-Prunieras syndromes under light and polarized light microscopy. METHOD Hairs from 2 Chédiak-Higashi and 2 Griscelli-Prunieras patients were obtained and examined under normal and polarized light microscopy. RESULTS Under light microscopy, hairs from Chédiak-Higashi patients presented evenly distributed, regular melanin granules, larger than those seen in normal hairs. Under polarized light microscopy, shafts exhibited a bright and polychromatic refringence appearance. In contrast, hair from Griscelli-Prunieras patients, under light microscopy, exhibited bigger and irregular melanin granules, distributed mainly near the medulla. Under polarized light microscopy, shafts appeared monotonously white. CONCLUSION Light microscopic examination of hair shafts of patients with Chédiak-Higashi or Griscelli-Prunieras syndrome reveals subtle differences that are useful in identifying both disorders, but not in distinguishing between them. We provide evidence that polarized light microscopy of hair shafts, an approach that has not been previously described, aids in differentiating between these syndromes. We propose hair study by polarized light microscopy as a helpful complementary diagnostic method for differential diagnosis between CHS and GPS, especially when the more sophisticated molecular studies are not available.

Acute hemorrhagic encephalomyelitis in childhood: Case report and literature review.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory immune-mediated disorder which is more common in pediatric patients. The clinical setting is characterized by a rapid onset of encephalopathy and multifocal neurological features. Acute hemorrhagic encephalomyelitis (AHEM) is considered a rare form of ADEM. This report shows a 2-year-old patient who presented with the classical features of ADEM and after 8 weeks developed severe neurological worsening. The second magnetic resonance image (MRI) showed hemorrhagic lesions. Differences in prognosis between ADEM and AHEM justify the investigation of AHEM whenever a patient has neurological recrudescence in a known patient of ADEM.

Guillain-Barré syndrome in children: clinic, laboratorial and epidemiologic study of 61 patients

The aim of the study was to analyze the epidemiologic, clinical, laboratory and development profile of Guillain-Barré syndrome series studied at the Child Institute, between 1989 and 2000. From the 61 patients that fulfilled the selection criteria, aged between 7 months and 13 years old, no sexual or seasonal variation was observed. Clinical events prior to neurological symptoms (with an average time gap of 20.7 days) were observed in 62.3%, 55% had cranial nerve disturbances, 27.9% dysautonomic symptoms, and 27.9% respiratory dysfunction. Installation time varied from 2-40 days, plateau from 0-28 days and recuperation from 30-480 days; 94% of patients had a complete clinical recuperation. Electrophysiology in 20 patients disclosed an abnormal demyelination pattern in 15, an exclusively motor axonal pattern in 4 and a mixed pattern in 1 patient. The results obtained did not differ from those in the literature but it was observed that boys and older children had a longer recuperation time. It was not possible to correlate electroneurography with clinical abnormalities and evolution due to the reduced number of patients.