14 research outputs found
GBA-associated Parkinson’s disease in Hungary: clinical features and genetic insights
Introduction: Parkinson’s disease (PD) has a complex genetic background involving both rare and common genetic variants. Although a small percentage of cases show a clear Mendelian inheritance pattern, it is much more relevant to identify patients who present with a complex genetic profile of risk variants with different severity. The ß-glucocerebrosidase coding gene (GBA1) is recognized as the most frequent genetic risk factor for PD and Lewy body dementia, irrespective of reduction of the enzyme activity due to genetic variants. Methods: In a selected cohort of 190 Hungarian patients with clinical signs of PD and suspected genetic risk, we performed the genetic testing of the GBA1 gene. As other genetic hits can modify clinical features, we also screened for additional rare variants in other neurodegenerative genes and assessed the APOE-ε genotype of the patients. Results: In our cohort, we identified 29 GBA1 rare variant (RV) carriers. Out of the six different detected RVs, the highly debated E365K and T408M variants are composed of the majority of them (22 out of 32). Three patients carried two GBA1 variants, and an additional three patients carried rare variants in other neurodegenerative genes (SMPD1, SPG11, and SNCA). We did not observe differences in age at onset or other clinical features of the patients carrying two GBA1 variants or patients carrying heterozygous APOE-ε4 allele. Conclusion: We need further studies to better understand the drivers of clinical differences in these patients, as this could have important therapeutic implications. © 2023, The Author(s)
Target Identification for Stereotactic Thalamotomy Using Diffusion Tractography
BACKGROUND: Stereotactic targets for thalamotomy are usually derived from population-based coordinates. Individual anatomy is used only to scale the coordinates based on the location of some internal guide points. While on conventional MR imaging the thalamic nuclei are indistinguishable, recently it has become possible to identify individual thalamic nuclei using different connectivity profiles, as defined by MR diffusion tractography. METHODOLOGY AND PRINCIPAL FINDINGS: Here we investigated the inter-individual variation of the location of target nuclei for thalamotomy: the putative ventralis oralis posterior (Vop) and the ventral intermedius (Vim) nucleus as defined by probabilistic tractography. We showed that the mean inter-individual distance of the peak Vop location is 7.33 mm and 7.42 mm for Vim. The mean overlap between individual Vop nuclei was 40.2% and it was 31.8% for Vim nuclei. As a proof of concept, we also present a patient who underwent Vop thalamotomy for untreatable tremor caused by traumatic brain injury and another patient who underwent Vim thalamotomy for essential tremor. The probabilistic tractography indicated that the successful tremor control was achieved with lesions in the Vop and Vim respectively. CONCLUSIONS: Our data call attention to the need for a better appreciation of the individual anatomy when planning stereotactic functional neurosurgery
Using global team science to identify genetic parkinson's disease worldwide.
No abstract available
A Magyar Klinikai Neurogenetikai Társaság konszenzusajánlása a felnôttkori spinalis izomatrophia (SMA) kezeléséhez
CĂ©lkitűzĂ©s – A spinalis izomatrophia (SMA) az alsĂł motoneuronok pusztulásával járĂł progresszĂv, autoÂszomális recesszĂv betegsĂ©g. Az elmĂşlt Ă©vekben fordulat következett be az SMA oki kezelĂ©sĂ©ben, kĂ©t SMN2 splicing mĂłdosĂtĂł Ă©s egy gĂ©nterápiás gyĂłgyszer vált elĂ©rhetĹ‘vĂ©. KĂ©rdĂ©sfelvetĂ©s – Az Ăşj gyĂłgyszerek az SMA gyermekkori lefolyását Ă©rdemben mĂłdosĂtják, Ă©s egyes gyĂłgyszerek felnĹ‘ttkori hatásárĂłl is egyre több adat Ă©rhetĹ‘ el. Nem áll azonban rendelkezĂ©sre olyan szakirodalom, ami a legĂşjabb eredmĂ©nyek alapján segĂtsĂ©get nyĂşjtana a felnĹ‘tt SMA-betegek kezelĂ©sĂ©hez szĂĽksĂ©ges döntĂ©sek meghozatalában. A Magyar Klinikai Neurogenetikai Társaság vezetĹ‘sĂ©ge áttekintette az SMA palliatĂv kezelĂ©sĂ©nek irányelveit, a randomizált, kontrollált gyĂłgyszervizsgálatokat, a felnĹ‘tt SMA-betegek retrospektĂv Ă©s prospektĂv gyĂłgyszeres vizsgálatainak eredmĂ©nyeit. A vizsgálat alanyai – A konszenzusajánlás megalkotása szempontjábĂłl azokat a közlemĂ©nyeket Ă©rtĂ©keltĂĽk, amelyek a felnĹ‘ttkort elĂ©rĹ‘, fĹ‘kĂ©nt SMA II- Ă©s III-csoportba tartozĂł betegek gyĂłgyszeres kezelĂ©sĂ©nek eredmĂ©nyeirĹ‘l szolgáltatnak adatokat. A konszenzusajánlást a felnĹ‘tt SMA-betegek kezelĂ©sĂ©rĹ‘l kilenc pontban fogalmaztuk meg, ami kitĂ©r a gyĂłgyszeres kezelĂ©s technikai, szakmai feltĂ©teleire, biztonságossági szempontjaira, a betegek kiválasztására, Ă©s hosszĂş távĂş monitorizálására. Ajánlásunk a legĂşjabb informáciĂłkra alapozva segĂti a felnĹ‘tt SMA-betegek palliatĂv ellátását Ă©s gyĂłgyszeres kezelĂ©sĂ©t, a szemĂ©lyre szabott kezelĂ©s során figyelembe veendĹ‘ hatĂ©konysági Ă©s biztonságossági szempontokat nyĂşjt. RávilágĂt a kĂ©sĹ‘bbiekben megválaszoÂlanÂdĂł, egyelĹ‘re nyitott kĂ©rdĂ©sekre is. Az ajánlás mindennapi gyakorlatban valĂł használata a kezelĂ©s optimalizáciĂłját eredmĂ©nyezheti