| 1. |
- Fatima, Ambrin, et al.
(författare)
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Monoallelic and bi-allelic variants in NCDN cause neurodevelopmental delay, intellectual disability, and epilepsy
- 2021
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Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 108:4, s. 739-748
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Tidskriftsartikel (refereegranskat)abstract
- Neurochondrin (NCDN) is a cytoplasmatic neural protein of importance for neural growth, glutamate receptor (mGluR) signaling, and synaptic plasticity. Conditional loss of Ncdn in mice neural tissue causes depressive-like behaviors, impaired spatial learning, and epileptic seizures. We report on NCDN missense variants in six affected individuals with variable degrees of developmental delay, intellectual disability (ID), and seizures. Three siblings were found homozygous for a NCDN missense variant, whereas another three unrelated individuals carried different de novo missense variants in NCDN. We assayed the missense variants for their capability to rescue impaired neurite formation in human neuroblastoma (SH-SY5Y) cells depleted of NCDN. Overexpression of wild-type NCDN rescued the neurite-phenotype in contrast to expression of NCDN containing the variants of affected individuals. Two missense variants, associated with severe neurodevelopmental features and epilepsy, were unable to restore mGluR5-induced ERK phosphorylation. Electrophysiological analysis of SH-SY5Y cells depleted of NCDN exhibited altered membrane potential and impaired action potentials at repolarization, suggesting NCDN to be required for normal biophysical properties. Using available transcriptome data from human fetal cortex, we show that NCDN is highly expressed in maturing excitatory neurons. In combination, our data provide evidence that bi-allelic and de novo variants in NCDN cause a clinically variable form of neurodevelopmental delay and epilepsy, highlighting a critical role for NCDN in human brain development.
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| 2. |
- Liik, Maarika, et al.
(författare)
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Repetitive nerve stimulation often fails to detect abnormal decrement in acute severe generalized Myasthenia Gravis
- 2016
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457 .- 1872-8952. ; 127:11, s. 3480-3484
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We assessed the diagnostic pattern of repetitive nerve stimulation (RNS) test and concentric electrode (CNE) jitter analysis between patients with generalized myasthenia gravis (GMG) with acute versus slow onset. Methods: All examinations that established the diagnosis of GMG at the department of Clinical Neurophysiology, Uppsala University Hospital, were retrospectively analyzed from January 2012 to December 2014. Patients were grouped according to disease duration at neurophysiological evaluation: acute onset (< 4 weeks) or slow onset (>= 4 weeks). Results: We identified 41 patients diagnosed with GMG. Of the nine patients with acute onset GMG (5 women) only one patient had abnormal decrement, whereas of the 32 patients with slow onset (13 women) 26 patients (84%) had abnormal decrement. CNE jitter was abnormal in all. AChR antibody status was comparable (78% versus 84%) whereas the MGFA class was higher in the acute onset group (range: 3A-5) compared to the slow onset group (range: 2A-3B). Conclusions: RNS test is frequently normal in cases of acute severe GMG, including myasthenic crisis. Performing CNE jitter analysis is therefore of crucial importance for a correct early diagnosis. Significance: MG patients with acute severe onset of bulbar or generalized fatigue often have normal findings on RNS test in proximal muscles. (C) 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
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| 3. |
- Rostedt Punga, Anna, et al.
(författare)
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Botulinum toxin injections associated with suspected myasthenia gravis : An underappreciated cause of MG-like clinical presentation
- 2020
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Ingår i: Clinical Neurophysiology Practice. - : Elsevier BV. - 2467-981X. ; 5, s. 46-49
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe application of botulinum toxin type A (BoNTA) is accelerating, and this includes the uncontrolled cosmetic use of the BoNTA. Diffusion of BoNTA can disturb neuromuscular transmission in several surrounding and distant muscles and result in clinical manifestations similar to myasthenia gravis (MG).Case presentationsWe report two cases of patients referred for neurophysiological evaluation of suspected MG. A 55-year-old female who experienced dysphagia, dysarthria, right-sided ptosis, and neck extensor muscle weakness; and a 46-year-old male who presented with episodic double vision and right-sided ptosis. Both had the history of previous BoNTA use for cosmetic purposes and for the treatment of migraine before the presentation of their symptoms. In both cases examination revealed normal RNS, quite remarkably increased jitter, and signs of denervation and reinnervation in muscles surrounding the injection sites. After extensive neurophysiological evaluations, the primary cause of their symptoms was found to be related to previous BoNTA injections rather than a primary neuromuscular transmission disorder. It could also be concluded that patients do not automatically inform their physicians about cosmetic BoNTA use and they may not be aware of the potential risks associated with BoNTA therapy.ConclusionsThe presented cases illustrate the neurophysiological findings in two patients with suspected MG after the use of BoNTA and emphasize the importance of inquiring about previous BoNTA injections and highlight that it is essential that patients are informed about possible side effects of BoNTA therapy.
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| 4. |
- Rostedt Punga, Anna, et al.
(författare)
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Keeping up appearances : Don't frown upon the effects of botulinum toxin injections in facial muscles
- 2023
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Ingår i: Clinical Neurophysiology Practice. - : Elsevier. - 2467-981X. ; 8, s. 169-173
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Forskningsöversikt (refereegranskat)abstract
- Aesthetic use of low doses of Botulinum toxin (BoNT) injections into the facial muscles has become a leading non-surgical aesthetic treatment worldwide to reduce facial wrinkles, including glabellar lines, forehead lines, and periorbital wrinkles. Within these aesthetic applications, BoNT injections intend to reduce and prevent wrinkles, and the recommended usage of 2 years is often exceeded, which may result in atrophy of the injected muscles. The long-term effects of BoNT injections in the facial muscles and the evidence of diffusion of BoNT to surrounding muscles are obvious pitfalls and challenges for clinical neurophysiologists in differential diagnosing neuromuscular transmission failures. Also, this is further complicated by the risk of developing side effects upon permanent chemical denervation of facial muscles, with less possibility for reinnervation.This review summarizes the known long-term effects of BoNT over time in different facial muscles and the use of objective electrophysiological measures to evaluate these. A better understanding of the longterm effects of BoNT is essential to avoid misdiagnosing other neuromuscular disorders.
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| 6. |
- Sabre, Liis, et al.
(författare)
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Diversity in mental fatigue and social profile of patients with myasthenia gravis in two different Northern European countries
- 2017
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Ingår i: Brain and Behavior. - : WILEY. - 2162-3279 .- 2162-3279. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Tntroduction: Self-estimated health can be used for comparison of different diseases between countries. It is important to elaborate on whether disparities in self-estimated health are due to disease-specific parameters or socioeconomic differences. In this study, we aimed at evaluating clinical and social similarities and differences in myasthenia gravis (MG) patients between comparable regions in two Baltic Sea countries, Estonia and Sweden. Methods: This cross-sectional study included southern counties in Sweden and Estonia of comparable size. All patients with a confirmed MG diagnosis were asked to answer two questionnaires including demographic and disease-specific data, lifestyle issues, and mental fatigue (Fatigue Severity Scale [FSS]). Clinical fatigue was assessed objectively through the Quantitative Myasthenia Gravis Score (QMG). Results: Thirty-six of 92 identified patients in Estonia and 40 of 70 identified MG patients in Sweden chose to participate in the study. The demographic characteristics and symptoms reported by the patients were similar. QMG score did not differ; however, the Estonian patients scored their current subjective disease severity significantly higher (5.6 +/- 2.8) compared to the Swedish patients (3.4 +/- 2.3, p=.0005). Estonian patients also had significantly higher FSS scores (5.0 +/- 1.7) than Swedish patients (3.5 +/- 1.6; p=.001). Swedish patients were more active and performed physical activity more regularly (29.1% in Estonia and 74.2% in Sweden, p=.004). Conclusions: Although, the patients had comparable clinical fatigue, Estonian patients evaluated their health state as being more severe and reported more mental fatigue than Swedish patients. These data indicate large regional differences in disease perception of MG, which is important to consider in international studies.
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