Clinical Neuroscience

[Screening of hereditary neuromuscular disorders in the roma population living in Hungary]


DECEMBER 20, 2008

Clinical Neuroscience - 2008;61(11-12)

[Recent medical genetic research has identified a number of novel, or previously known, but rare conditions, caused by private founder mutations. The Finnish and Ashkenazi Jew populations provide the best examples for identifying genes in unique genetic disorders. In these populations, research efforts and high-level medical services resulted in intense improvements of medical care and in organization of population- based screening programs. Hereditary disorders of the Roma populations are known for a long time. The genetic background of these diseases has been established by extensive molecular genetic studies. The Romas represent 6% of the Hungarian population and live under extremely bad health conditions. Therefore, our aim was to map the incidence of the hereditary neuromuscular disorders among the Hungarian Roma population. Moreover, we intended to provide proper information, genetic counseling and possible prevention strategies for the families at risk, which should represent a primer task in public health. Because of our experience in neuromuscular disorders, we choose six, frequent, autosomal recessive disorders for these clinical and genetic studies: hereditary motor and sensory neuropathy type Lom (HMSNL), hereditary motor and sensory neuropathy type Russe (HMSNR), congenital cataracts facial dysmorphism syndrome (CCFDN), Limb- Girdle muscular dystrophy 2C (LGMD2C), congenital myasthenic syndrome (CMS) and spinal muscular atrophy (SMA). Following identification of the founder mutations, the possibility of prenatal diagnosis and carrier screening for family members will contribute to the decrease of the recurrence risk for these severe, mostly untreatable disorders.]



Further articles in this publication

Clinical Neuroscience

[Pediatric intraventricular tumors]

MARKIA Balázs, GYORSOK Zsuzsanna, KORDÁS Mariann, BOGNÁR László

[Pediatric intraventricular tumors present a well circumscribed group from surgical point of view. These tumors growing in the ventricular system cause hydrocephalus in most of the cases, the presenting symptoms are the signs of raised intracranial pressure. The mass lesion may remain silent for a long period, especially in infancy due to compensatory mechanisms, and the tumor might reach extreme size making the surgery a real challenge. This group has very specific postoperative problems resulting from the disturbance of CSF circulation. In this study we present the retrospective analysis of 55 patient operated for intraventricular tumor in the National Institute of Neurosurgery between 1991 and 2006. Data were analysed regarding histological type, presenting symptoms, type of surgical approach, radicalitiy of the resection and postoperative complications. In addition to our own results brief presentation of the specific histological groups is given based on the available literature.]

Clinical Neuroscience

[Changes of the immune functions in patients with eating disorders]

PÁLI Anikó Andrea, PÁSZTHY Bea

[Aims - In this study we investigated whether calorie restriction or redundant food intake influences the function of regulatory T cells (Tregs), and their main regulators (dendritic cells and macrophages), or the targets of Tregs, CD4+ lymphocytes. Patients and methods - We investigated 11 white adolescents (10 girls and 1 boy) with anorexia nervosa, 12 obes adolescents and 10 healthy controlls. With flow cytometry we determined the prevalence of Tregs, myeloid and plasmacytoid dendritic cells. We applied intracellular staining to investigate TNF-alpha and IL-12 production of macrophages, moreover IL-2, IL-4, and IFN-gamma production of CD4+ cells. We also determined calcium flux kinetics upon activation in CD4+ cells. Results - We did not find any difference between obese, anorectic and control individuals in the prevalence of Tregs, dendritic cells, TNF-alpha and IL-12 positive macrophages, IL-4 and IFN-gamma positive CD4+ lymphocytes. We found that the prevalence of IL-2 positive lymphocytes after activation was lower in anorectic than in control subjects [median (range): 11.50 (7.60-15.30) vs. 13.50 (12.00-22.00), p=0.023], and in obese patients, too [12.50 (8.50-15.50) vs. 13.50 (12.00-22.00), p=0.028]. IFN-gamma/IL-4 ratio in CD4+ cells was higher in obese patients compared with control (p=0.046). The calcium flux characteristics of lymphocytes upon activation differed markedly in anorectic and healthy subjects as maximal calcium levels developed later in anorectic patients [86 (45- 232) vs. 215 (59-235) second, p<0.05]. We also tested the association between lymphocyte activation parameters and patients' clinical status, but did not find any association between the variables. Discussion - Our results suggest that the antigen presenting cell - regulatory T cell - CD4+ lymphocyte axis might be affected by calorie and nutritional disturbances, further studies are needed to elucidate the underlying processes.]

Clinical Neuroscience

[Pneumococcal meningitis in children - 9 1/2-year-experience at Szent László hospital, Budapest, Hungary ]

IVÁDY Balázs, LIPTAI Zoltán, ÚJHELYI Enikő, BALÁZS György

[Background and objective - No recent publications are available about pneumococcal meningitis in Hungarian children. The aim of this study was to collect data of epidemiological, clinical and prognostic features of pneumococcal meningitis in children treated at Szent László Hospital, Budapest, Hungary. Methods - We conducted a retrospective review of medical charts and follow-up records of patients aged 1 to 18 years admitted to our Pediatric and Pediatric Intensive Care Units due to pneumococcal meningitis between 1st Jan 1998 and 30th Jun 2007. Results - 31 children with 34 cases of pneumococcal meningitis were admitted to our hospital in the study period. Two children developed recurrent illness. The mean age was 6 years, 26% were under 1 year of age. The mean duration of hospital stay was 21 days, 97% required intensive care. Frequent clinical symptoms were fever (100%), nuchal rigidity and vomiting (78%), altered mental status (71%), Kernig's and Brudzinski's signs (58%) and seizures (41%). Otitis media, sinusitis, mastoiditis were present in 44%, 58%, 41%, respectively. Subdural effusion, parenchymal cerebral lesion and sinus thrombosis were documented in 5, 3 and 2 cases, respectively. One third of the patients recieved ceftriaxon, two thirds were administered ceftriaxon and vancomycin. Adjunctive therapy with dexamethason was given to 91% of the children. 70% of patients required mechanical ventillation. 9 patients (25%) required endoscopic sinus surgery. In 13 cases (38%) mastoidectomy, in 5 children (15%) neurosurgery was performed. The case fatality rate was 23.5%. 8 (23.5%) patients had mild or moderate, 1 child (3%) developed severe neurological sequelae. Conclusion - Pneumococcal meningitis in children remains a source of substantial morbidity and mortality in childhood. The long hospital stay, the frequent need for intensive care and severe neurologic sequelae emphasize the importance of early diagnosis, early treatment and prevention with pneumococcal conjugate vaccines.]

Clinical Neuroscience

[Devastating epileptic encephalopathypseudoencephalitis: the new type of catastrophe epilepsy in our department]


[Purpose - Analysis of history of our five patients with intractable epilepsy whose illnes have begun with prolonged status epilepticus (SE) and high-grad fever of unknow cause. Methods - Retrospective study analysis of selected five intractable epileptic patients at a median age of 11.5 (8-14) years. Results - All children had normal development before epilepsy begun. Intractable SE lasted 3-10 (median seven) days by four patients and three months by one patient. The cause of illness was unknow at the beginning and the MRI were normal. Intractable epilepsy followed the SE in all cases without any latent period. Follow-up of the children was 3-15 (median 9.5) years. The seizures came continually with few-day-long breaks, antiepileptic drugs were ineffective. Semiology of seizures, EEG, and functional imaging examinations (PET, SPECT) referred to temporal and frontal lobe damages. Later on, the MR images showed hippocampal sclerosis in one patient and mild generalized brain atrophy in the others. During the years, cognitive deterioration and behavioral problems have been realized. The most severe patient developed tetraparesis, fell in vigil coma and died after five years. Conclusions - The symptoms of our patients fulfilled the criteria of devastating epileptic encephalopathy in schoolaged children.]

Clinical Neuroscience

[How do temporal lobe seizures changeby age?]


[Seizure semiology describes different - motor, sensory, autonomic, etc. - aspects of epileptic seizures. Several semiological studies showed already that different epilepsies - especially temporal lobe epilepsy - contain age-dependent features. In our researches, we tried to assess these subjective aspects with as objective methods as possible. We gave a comprehensive (preictal, ictal, and postictal) description of seizure semiology in patients fulfilling the gold standard criteria of semiological studies: being seizure free after temporal lobe resections. Our studies based on a large population, assess epileptic features at different levels of brain maturation. They help to understand why certain semiological axes show special characteristics at different ages. In this review, I summarize the most important results of our seizure semiology studies in temporal lobe epilepsy.]

All articles in the issue

Related contents

Clinical Neuroscience

[Consensus statement of the Hungarian Clinical Neurogenic Society about the therapy of adult SMA patients]

BOCZÁN Judit, KLIVÉNYI Péter, KÁLMÁN Bernadette, SZÉLL Márta, KARCAGI Veronika, ZÁDORI Dénes, MOLNÁR Mária Judit

[Background – Spinal muscular atrophy (SMA) is an autosomal recessive, progressive neuromuscular disorder resulting in a loss of lower motoneurons. Recently, new disease-modifying treatments (two drugs for splicing modification of SMN2 and one for SMN1 gene replacement) have become available. Purpose – The new drugs change the progression of SMA with neonatal and childhood onset. Increasing amount of data are available about the effects of these drugs in adult patients with SMA. In this article, we summarize the available data of new SMA therapies in adult patients. Methods – Members of the Executive Committee of the Hungarian Clinical Neurogenetic Society surveyed the literature for palliative treatments, randomized controlled trials, and retrospective and prospective studies using disease modifying therapies in adult patients with SMA. Patients – We evaluated the outcomes of studies focused on treatments of adult patients mainly with SMA II and III. In this paper, we present our consensus statement in nine points covering palliative care, technical, medical and safety considerations, patient selection, and long-term monitoring of adult patients with SMA. This consensus statement aims to support the most efficient management of adult patients with SMA, and provides information about treatment efficacy and safety to be considered during personalized therapy. It also highlights open questions needed to be answered in future. Using this recommendation in clinical practice can result in optimization of therapy.]

Clinical Neuroscience

[Genetically determined neuromuscular disorders of some roma families living in Hungary (in English language)]


[The authors discuss the clinical and molecular genetic aspects of genetically determined neuromuscular disorders of some Roma families living in Hungary. Among the autosomal recessively inherited spinal muscular atrophic (SMA) group, 8 Caucasian children had the typical 7-8 exonal deletions of the SMA gene, but only 2 patients belonged to the Roma population. There was no difference in the molecular genetic findings among the Caucasian and the Roma SMA patients. All of them had 7- 8 exonal deletions of the SMA gene. We wanted to call attention to the founder mutation of the Roma population in 7 patients suffering from congenital myasthenia (CMS) from 3 Roma families. The 1267G deletion for CMS was detected by molecular genetic method. Clinical onset was pubertal and relatively slow progression of specific and phenotypic features for this founder mutation of acetyl-cholin receptor epsylon gene. In 2 patients (sister and brother) the sarcoglycanopathy 2C type C283Q mutation was proven in one Roma family suffering from limb-girdle muscular dystrophy (LGMD). Two out of the three facioscapular-humeral dystrophy (FSHD) Roma families carried 21.8 kb and 18.5 kb alleles in FSHD A1 gene (D4S139). In one family together with prenatal diagnosis founder mutation in FSHD A1 gene was detected, according to the autosomal dominant (AD) inheritence. In (F2) prenatal diagnosis was carried out, 18.5 kb/18.5 kb homozygosity was proven in the fetus, so the pregnancy was interrupted. In the CMS, LGMD and FSHD Roma patients ancient typical Roma founder mutations were found.]

Clinical Neuroscience

[Advances in the diagnostics of spinal muscular atrophy]


[The three most common types of childhood spinal muscular atrophy (SMA) are type I or Werdnig Hoffmann disease, type II or intermediate form, and type III or Kugelberg-Welander disease. The clinical features of these three types are characteristic, profound limb hypotonia, wasting of muscles and areflexia. All three forms of SMA reveal an autosomal recessive mode of inheritance. The gene responsible for all three types of SMA is located on the long arm of chromosome 5 in the region of 5q11.2-913.3. Starting from 1993 blood samples were collected from 87 Hungarian families with all 3 types of SMA. DNA samples of all family members were analysed with the currently available highly informative microsatellite DNA markers in the locus 5q11.2 q13.3. Moreover, affected persons and their family members have been analysed for deletions of the survival of motor neuron gen (SMN). Prenatal diagnoses were performed in 28 cases at the request of the affected families. The possibility of prenatal diagnosis is a major step forward in helping these families, as the risk of recurrence of this devasting, untreatable disease is 25% in affected families.]