Clinical Neuroscience

[Quantitative analysis of the genes determining spinal muscular atrophy]


NOVEMBER 30, 2009

Clinical Neuroscience - 2009;62(11-12)

[Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases, affecting approximately one in 10.000 live births and with a carrier frequency of approximately one in 35. The disease is caused by a deficiency of the ubiquitous protein survival of motor neuron (SMN), which is encoded by the SMN1 and SMN2 genes. Due to a single nucleotide polymorphism in exon 7, SMN2 produces less full-length transcript than SMN1 and cannot prevent neuronal cell death at physiologic gene dosages. On the other hand, the copy number of SMN2 affects the amount of SMN protein produced and the severity of the SMA phenotype. SMN gene dosage analysis can determine the copy number of SMN1 to detect carriers and patients heterozygous for the absence of SMN1 exon 7. This study provides copy number estimation of SMN1 gene by real-time PCR technique in 56 SMA type I., II., III. patients, 159 parents and healthy relatives and in 152 undefined SMA patients. Among the family members, 91 carriers have been detected and in 56 patients homozygous deletion of SMN1 exon 7 has been confirmed. Moreover, in 12 patients compound heterozygosity of SMN1 exon 7 mutation has been detected, thus providing the possible diagnosis of SMA. In 94 patients, copy number of SMN2 has also been evaluated and a good correlation has been found with the phenotype of the disease. Due to the genetic complexity and the high carrier frequency, accurate risk assessment and genetic counselling are particularly important for the families. These new results provide improvement of the diagnostic service in SMA in Hungary with focus on proper genetic counselling and possible enrolment of the patients in future therapeutic interventions.]



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[New vistas and views in the concept of generalized epilepsies]


[The aim of this work is to show explicitly why the “idiopathic generalized epilepsy” concept becomes outfashioned and untenable. As the concept of “generalized epilepsies” is from long ago closely related to the thalamo-cortical system, we briefly summarize the functional anatomy, the double working mode of the thalamo-cortical system in different vigilance states and it’s role in development of the spike - wave pattern. The next part shows weaknesses of this concept from the EEG, seizure semiology, and neuroimaging point of view. Further experimental and clinical arguments are accumulated from the reflex epileptic features in IGE, indicating local/regional cortical hyperexcitability. A separate part is devoted to genetic aspects of the question. Lastly implications to epilepsy classification are shown and an outlook toward a unified epilepsy concept is provided. The epileptic disorder of the thalamo-cortical system is responsible for the development of “generalized", synchronous spike-wave paroxysms as the common neurophysiological background in “primary” - idiopathic and in “secondary” generalized epilepsies. This disorder is specifically related to the burstfiring working mode of the thalamo-cortical system during NREM sleep (is an epileptic exageration of it). The “generalized” epilepsy category should be abandoned, being misleading. Epilepsies are proposed to be classified according to their network properties and relations to different physiological systems of the brain. The different phenotypes, named earlier idiopathic (primary) generalized, or symptomatic (secondary) generalized (with encephalopathic features), should be delineated depending on the following factors: 1. speed and extent of syncronization within the thalamo-cortical system, 2. the way how the thalamo-cortical system is involved, 3. which kind of cortical triggers play role, 4. the degree and level of the disorder (restricted to the molecular level or extended to the level of structural alterations - in the cortex or more diffusely, 5. genetic targets and features.]

Clinical Neuroscience

[Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]


[On the basis of six randomized controlled trials, zonisamide (ZNS) can be prescribed as add-on treatment in focal adulthood epilepsy in USA and Europe. In Japan, it can be prescribed as first-line monotherapy drug - independent of age. ZNS may also be effective in idiopathic generalized epilepsy and some difficult-to-treat epilepsies including West, Lennox-Gastaut, or Dravet syndromes. The most frequent side effects of ZNS are related to central nervous system occurring in 19%. Kidney stones and oligohidrosis are ZNS-specific side effects. Loss of appetite and weight are usually “beneficial” effects. ZNS is not recommended in pregnancy. ZNS can be taken once daily, which may be beneficial in non-compliance. The pathomechanism of ZNS is different from other antiepileptic drugs. ZNS has an effect on the voltage-gated Na+- and T-type Ca2+ channels as well as on the dopaminerg, glutamaterg, cholinerg, and GABAerg systems. The multiple way of action may be the reason why ZNS seems to be a broad-spectrum drug and beneficial in various neurological disorders. ZNS reduces production of free radicals according to in vitro and in vivo studies. Animal experiments suggest that ZNS may be a neuroprotective agent. Based on an adequate randomized controlled trial, ZNS is effective in adjuctive treatment of Parkinson disorder. A peculiar benefit of the ZNS is that parallel to its positive effect on motor impairment it also reduces severity of dyskinesias. ZNS may be effective in bipolar disorder, obesity, eating disorders, and migraine prophylaxis.]

Clinical Neuroscience

[Guillain–Barré syndrome in childhood]

KOLLÁR Katalin, LIPTAI Zoltán, ROSDY Beáta, MÓSER Judit

[Background - Guillain-Barré syndrome (GBS) is clinically well known since 1916. It can occur at any age. Its main characteristic is acute rapidly ascending flaccid paresis. It is a neuro-immunologic disorder with heterogeneous background. In Hungary we could not find reports about big paediatric population with GBS. Patient and method - We analysed retrospectively the data of 38 children diagnosed and treated with GBS at the Neurological Department of Paul Heim Children’s Hospital or at the Paediatric Department of St. László Hospital from January 2000 till April 2008. We analysed the clinical characteristics, seriousness of clinical signs, laboratory results, and electrophysiological features of them as well documented the preceding illness. We observed the effectiveness of our treatment; we measured the speed and time of the healing process and documented the residual clinical signs. Results - 35 children could be classified as having acute inflammatory demyelinating polyneuropathy (AIDP), 2 as having acute motor axonal neuropathy (AMAN) and 1 as Miller-Fisher syndrome. By those patients who at the very beginning did not show the characteristic clinical signs, electrophysiology helped in establishing the diagnosis. By one child spinal MRI with gadolinium supported our diagnosis. Those children, who lost their ambulation, got immunotherapy: intravenous immunoglobulin (IVIG) or plasmapheresis (PEX). Both method seemed to be effective. None of our patients died. All were cured. By five patients residual clinical symptoms could be found. Conclusion - The disease process, the relative incidence of each subtype of GBS is nearly similar to that in Western Europe and North America according to the literature. By the currently used immune therapy most of the pediatric patients recover fully within a short time.]

Clinical Neuroscience

[Myelination disturbance in a patient with hyperuricemia and hyperserotoninemia combined with 18q deletion syndrome]

LÁSZLÓ Aranka, VÖRÖS Erika, BUGA Klára, HORVÁTH Katalin, MAYER Péter, OSZTOVICS Magda†, PÁVICS László, SVEKUS András, PATTERSON C. Marc

[We previously reported a male patient with an 18q21.3 deletion, hyperuricemia and typical symptoms of the Lesch- Nyhan syndrome who lacked hypoxanthine-guanine-phosphoribosyl- transferase (HGPRT) deficiency. The patient developed progressive peripheral neuropathy in additon to his profound mental retardation and self-injurious behavior. At the age of 23 years MR imaging revealed globally delayed myelination with relative sparing of the corpus callosum and frontal lobes. They were focal hyperintensities suggestive of gliosis. Multimodality evoked potentials found evidence of impaired central and peripheral conduction. Single photon emission computed tomographic (SPECT) imaging demonstrated left frontal hyperperfusion and under it a temporoparietal hypoperfusion.]

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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

[Nusinersen in the treatment of spinal muscular atrophy]

SINKÓ Gabriella, KISS Zsuzsanna, BERNADETTE Kalman

[Until recently, the diagnosis of spinal muscular atrophy (SMA) has been associated with severe life-long motor disability in adults and with early death in infants. The new experimental therapeutic approaches of the last few years have become more and more promising, while nusinersen was approved for the treatment of SMA in December 2016 in the USA, and in May 2017 in Hungary. Our paper presents mechanisms and clinical benefits of this new medication, and highlights some of the other therapeutic strategies still in experimental stages.]

Clinical Neuroscience


KAREN Eskesen, TAJTI János, HORTOBÁGYI Tibor, SZOK Délia, VÉCSEI László, LARS Edvinsson

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