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Clinical Neuroscience

JANUARY 30, 2019

[Multiple ischemic stroke in Osler-Rendu-Weber disease]

SALAMON András, FARAGÓ Péter, NÉMETH Viola Luca, SZÉPFALUSI Noémi, HORVÁTH Emese, VASS Andrea, BERECZKY Zsuzsanna, TAJTI János, VÉCSEI László, KLIVÉNYI Péter, ZÁDORI Dénes

[Hereditary hemorrhagic teleangiectasia (HHT, Osler-Rendu-Weber disease) is an autosomal dominantly inherited disorder caused by the mutation of several possible genes and characterized by malformations of the arteriovenous system in multiple organs. The clinical diagnosis is based on the Curaçao criteria ((1) spontaneous, recurrent epistaxis; (2) teleangiectasias in characteristic sites (lips, oral cavity, nose, fingers); (3) visceral lesions (gastrointestinal, pulmonary, cerebral, spinal); (4) affected first degree relative). The aim of this study is to present the first genetically confirmed Hungarian case of hereditary hemorrhagic teleangiectasia with multiple ischemic strokes. Our 70-year-old woman has been suffering from severe epistaxis since her childhood and presented gastrointestinal bleeding during her adulthood as well. The characteristic skin lesions developed in the 5th decade of life. She was admitted to our department with loss of consciousness and fluctuating speech and swallowing problems. MRI of the brain supplemented with angiography revealed multiple arteriovenous malformations and multiple subacute ischemic lesions. The EEG demonstrated slowing of electric activity in the left frontal lobe. The neuropsychological assessment showed deficits in anterograde memory and executive functions. The diagnostic work-up for other characteristic alterations identified an arteriovenous malformation in the left lung. The genetic analysis demonstrated a heterozygous mutation in the 7th exon of the ENG gene at position 834 resulting in a thymine duplication and an early stop codon by a frame shift. The present case is largely similar to those already described in literature and draws the attention to the importance of multidisciplinary collaboration in the care of HHT patients.]

Hypertension and nephrology

OCTOBER 20, 2016

[Dialysis treatment in Hungary: 2010–2015]

KULCSÁR Imre, ILLÉS Melinda, KOVÁCS LÁSZLÓ

[The authors show the data of Hungarian dialysis statistics from 2010 to 2015. The questionnaire - based data collection was made by Dialysis Registry Committee of the Hungarian Society of Nephrology. The number of all patients entered in the dialysis program increased by 8.4% over six years (an average of 1.4/ per year) and the number of new ones increased by 10.5% (1.75% per year). Between 2003 and 2009 the mean annual increasing of new patients was 7.5%! The incidence of new dialyzed patients was 440/1 million population in 2010 and 486/1 million) in 2015. The population point prevalence at the end of the year was 621/1 million in 2010 and 643/1 million in 2015. The penetrance of peritoneal dialysis was 13.5% in 2010, and 13.6% in 2015. The proportion of incident patients with diabetic or hypertensive nephropathies (conditions which lead to end stage renal disease) was about the same in 2010 (27 and 21%) than in 2016 (27 and 22%). The mean age of incident patients entered into dialysis program decreased from 66.9 years (2010) to 62.8 years (2015), surprisingly. The rate of patients on waiting list for renal transplantation was 10.7% in 2009 and increased to 15,8% in 2015. There is also a significant increase in the number of the annual renal transplantations (268 in 2010 and 356 in 2015). The mortality rate of chronically dialyzed patients shows little decrease (14.4-13.1%).]

Clinical Neuroscience

JULY 30, 2016

[Transthyretin familial amyloid polyneuropathy - three Hungarian cases with rare mutations (His88Arg and Phe33Leu)]

CSILLIK Anita, POZSONYI Zoltán, SOÓS Krisztina, BALOGH István, BODÓ Imre, ARÁNYI Zsuzsanna

[Introduction - Transthyretin familial amyloid polyneuropathy is a rare autosomal dominant progressive systemic disesase of adults caused by endoneural amyloid deposition due to point mutations of the transthyretin gene. It is the most severe form among hereditary polyneuropathies, being fatal within 10 years if left untreated. The disease is underdiagnosed, the late onset forms (above the age of 50) being probably more widespread than previously thought. Early diagnosis is essential as the early introduction of causal therapy (tafamidis) slows progression and prolongs survival. Patients - We report here three non-related Hungarian cases of transthyretin familial amyloid polyneuropathy with non- Val30Met mutations (His88Arg in two cases, Phe33Leu in one case). They were all characterized by late-onset, progressive, length-dependent, axonal, sensorimotor polyneuropathy and the simultaneous presentation of severe restrictive cardiomyopathy. In all three cases, clinical and electrophysiological signs of myopathy were also present, suggesting the involvement of skeletal muscles as well. In two cases, high resolution ultrasound of the peripheral nerves was also performed, which showed segmental structural alterations (change or loss of fascicular structure) and some increase of echogenicity of the interfascicular epineurium, without substantial enlargement of the nerves. Conclusion - In Hungary, mainly the rare, non-Val30Met mutation forms of transthyretin familial amyloid polyneuropathy are encountered, as in our cases. As opposed to the Val30Met forms, these mutations are characterized by late onset and simultaneous presentation of severe cardiomyopathy. Our report highlights the importance of considering transthyretin familial amyloid polyneuropathy in the differential diagnosis of late-onset, progressive, axonal polyneuropathies of unknown etiology, particularly if associated with cardiac disease.]

Clinical Neuroscience

NOVEMBER 28, 2014

[The modifying effect a PMP22 deletion in a family with Charcot-Marie-Tooth type 1 neuropathy due to an EGR2 mutation]

REMÉNYI Viktória, INCZÉDY-FARKAS Gabriella, GÁL Anikó, BEREZNAI Benjámin, PÁL Zsuzsanna, KARCAGI Veronika, MECHLER Ferenc, MOLNÁR Mária Judit

[Background - Mutations of both the PMP22 and EGR2 genes cause Charcot-Marie-Tooth (CMT) disease type 1. Deletion of the PMP22 gene, results in hereditary neuropathy with liability to pressure palsies. More publications exist about the interaction of PMP22 duplication and other CMTcausing gene mutations. In these cases the intrafamiliar discordant phenotypes draw the attention to the possible role of modifying genes. The gene-gene interactions between the PMP22 and EGR2 genes are not well understood. Case report - We report two brothers with late onset CMT1 due to a c. 1142 G>A (Arg381His) heterozygous substitution in the EGR2 gene. Additionally, the older brother with the less severe symptoms harbored the PMP22 gene deletion also. Conclusion - The coexistence of the two genetic alterations did not aggravate the clinical symptoms. Moreover, the PMP22 deletion appeared to have a beneficial modifying effect, thus implying potential gene-gene interaction of PMP22 and EGR2. PMP22 deletion may increase Schwann cells proliferation and compensate the dominant-negative effect of the Arg381His substitution in the EGR2 gene.]

Lege Artis Medicinae

JANUARY 20, 2012

[Genetic background of thyroid cancers]

HALÁSZLAKI Csaba, LAKATOS Péter, KÓSA P. János, BALLA Bernadett, JÁRAY Balázs, TAKÁCS István

[Molecular genetics has become an indispensable diagnostic tool in a number of diseases. The most frequent thyroid tumours are associated with genetic alterations that might be used for diagnostic purpose in the future. Somatic mutations and rearrangements in BRAF, RAS family RET/PTC and PAX8/PPAR-gamma genes may occur in papillary and follicular thyroid carcinomas. Other mutations of the RET gene can be found in medullary carcinomas (in sporadic as well as hereditary types), whereas mutations of the genes TP53, RAS, and BRAF are associated with poorly differentiated and anaplastic carcinomas. At present, the most reliable diagnostic tool for the differential diagnosis of thyroid nodules is fine-needle aspiration cytology. However, the existing malignancy cannot be unequivocally proven in up to 10-40% of all samples. On the basis of previous results, genetic examination of fine needle aspiration samples from thyroid nodules can contribute to a more precise diagnosis and the timely removal of potentially malignant nodules.]

Hypertension and nephrology

DECEMBER 20, 2011

[Genetics of isolated steroid-resistant nephrotic syndrome - results of the two decades around the turn of the millennium]

TORY Kálmán, KERTI Andrea, REUSZ György

[Childhood steroid-resistant nephrotic syndrome (SRNS) is a devastating clinical condition which progresses to end-stage renal disease in 30-40% of the cases after a follow up of 10 years. Based on its etiology, two forms can be distinguished, an immune and a genetic form. During the last two decades, mutations of ten genes - encoding mainly podocyte proteins - were identified in the latter group. As the treatment in the immune and genetic forms are different, and only the identification of the causative mutation can reliably distinguish them, it is important to be familiarized with the genotype-phenotype correlations. The aim of the present review is to summarize our current knowledge on the phenotypes linked to the identified genes.]

Hypertension and nephrology

OCTOBER 20, 2010

[Dialysis in Hungary: 2003-2009]

KULCSÁR Imre, SZEGEDI János, LADÁNYI Erzsébet, TÖRÖK Marietta, TÚRI Sándor, KISS István

[The authors show the data of Hungarian dialysis statistics from 2003 to 2009. The questionnaire-based data collection was made by the Dialysis Committee of the Hungarian Society of Nephrology. The number of all patients entered in the dialysis program increased by 45.2% over six years (an average of 7.5% per year) and the number of new ones increased by 51.2% (8.5% per year). The increase in number of patients treated with haemodialysis was 39% (6.5% per year) in this period. The increase in the number of patients in the peritoneal dialysis program was extremely high: 80.6% (an average of 13.4% per year). The population incidence of new dialysed patients was 332/1 million in 2003 and 483/1 million in 2009. The population point prevalence at the end of the year was 437/1 million in 2003, but 607/1 million in 2009. The penetrance of peritoneal dialysis was 12.8% in 2009. Differences exist among the regions of Hungary in the number of patients, the penetrance of peritoneal dialysis and the prevalence of renal replacement therapies. Among patients suffering in conditions which lead to end stage renal disease the proportion of patients with diabetic or hypertensive nephropathies is increasing and the proprtion of patients with glomerular or tubulointerstitial damage is decreasing. The number (and rate) of the elderly people is growing continuously year by year. The rate of patients on waiting list for renal transplantation is decreasing (the rate was 20% in 2003, but only 10.7% in 2009). There is also a slow decrease in the number of the annual renal transplantations. The mortality rate of chronically dialysed patients shows a little increase. Five dialysis centres for paediatric patients and 58 for adults have been functioning in Hungary by the end of 2009. In average 106 patients have been treated by each Hungarian dialysis centre in contrast to the optimal of 60 persons. The number of nephrologists increased between 2003 and 2007, but slightly decreased since then. The case is similar regarding nephrological nurses.]

Clinical Neuroscience

JANUARY 20, 2005

[CALPAIN-3 GENE DEFECT CAUSING LIMB GIRD MUSCULAR DYSTROPHY IN A HUNGARIAN FAMILY]

HORVÁTH Rita, WALTER C. Maggie, LOCHMÜLLER Hanns, HÜBNER Angela, KARCAGI Veronika, PIKÓ Henriett, TÍMÁR László, KOMOLY Sámuel

[Limb gird muscular dystrophies (LGMD2) are a clinically and genetically heterogeneous group of hereditary diseases with autosomal recessive trait, characterized by progressive atrophy and weakness predominantly in the proximal limb muscles. The authors present clinical, histological, immunohistochemical and immunoblot results of two sisters suffering from so far unclassified autosomal recessive limb girdle muscular dystrophy. Haplotype analysis for genes possibly involved in autosomal recessive limb girdle muscular dystrophies was performed in the genetically informative family. All of the results pointed to a molecular genetic defect of the calpain-3 (CAPN3) gene. Direct sequencing of the CAPN3 gene revealed compound hetereozygous state for two mutations previously described in association with limb girdle muscular dystrophy, proving pathogenity. The authors would like to emphasize the importance of the above described combined strategy in diagnosing limb girdle muscular dystrophies.]

Clinical Neuroscience

MARCH 20, 2011

[CADASIL and other hereditary small vessel diseases of the brain - Increasingly diagnosed conditions underlying familial ischaemic stroke and dementia]

GUNDA Bence, HUGUES Chabriat, BERECZKI Dániel

[CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) has recently gained great interest in vascular neurology as the most common heritable cause of stroke and vascular dementia in adults. This autosomal dominant small vessel disease of the brain - unlike the sporadic, hypertensive form - appears already in adult midlife in the absence of vascular risk factors with ischemic episodes and progressive dementia, its first manifestation can be migraine with aura, and is often associated with psychiatric disturbances. The magnetic resonance imaging (MRI) changes showing a characteristic pattern may precede symptoms by more than a decade. The identification of the mautation of the NOTCH 3 gene responsible for the disorder encoding a transmembrane receptor of vascular smooth muscle cells - has given great impetus on research to understand the molecular and vascular pathogenesis of the disease. The special importance of this latter lies in the fact that CADASIL provides a pure genetic model for subcortical cerebral ischemia and vascular dementia without the confounding factors of comorbidities and advanced age. Thus insights into CADASIL may help us better understand the more common sporadic forms as well. Moreover CADASIL is one of the best studied examples of secondary migraine. Currently we have far less knowledge on other forms of hereditary small vessel disease of the brain such as CARASIL, HERNS, CRV, HVR, PXE etc. Neurologists are becoming more and more familiar with CADASIL, and with the wider availability of MRI it is increasingly diagnosed. However the disorder is still probably underrecognised. This review aims to summarize our current knowledge on CADASIL with special emphasis on diagnostic and diffrential diagnostic points for the practising neurologist.]