MTSS1/Src family kinase Dysregulation Underlies Multiple Inherited Ataxias

The genetically heterogeneous spinocerebellar ataxias (SCAs) are caused by Purkinje neuron dysfunction and degeneration, but their underlying pathological mechanisms remain elusive. The Src family of nonreceptor tyrosine kinases (SFK) are essential for nervous system homeostasis and are increasingly implicated in degenerative disease. Here we reveal that the SFK suppressor Missing-in-metastasis (MTSS1) is an ataxia locus that links multiple SCAs. MTSS1 loss results in increased SFK activity, reduced Purkinje neuron arborization, and low basal firing rates, followed by cell death. Surprisingly, mouse models for SCA1, SCA2, and SCA5 show elevated SFK activity, with SCA1 and SCA2 displaying dramatically reduced MTSS1 protein levels through reduced gene expression and protein translation, respectively. Treatment of each SCA model with a clinically approved Src inhibitor corrects Purkinje neuron basal firing and delays ataxia progression in MTSS1 mutants. Our results identify a common SCA therapeutic target and demonstrate a key role for MTSS1/SFK in Purkinje neuron survival and ataxia progression

Peri-ictal Water Drinking: An Interesting Phenomenon With Unknown Reason

Background: Peri-ictal water drinking is a rare vegetative symptom reported in temporal lobe epilepsy. Our aim was to investigate the clinical, EEG, MRI findings and psychiatric comorbidities of the patients reporting peri-ictal water drinking in their seizures

Which swallowing difficulty of food consistency is best predictor for oropharyngeal dysphagia risk in older person?

WOS: 000476771900010Key summary pointsAimOur aim was to investigate which swallowing difficulty of food consistency in older people who did not have any disease that might affect swallowing functions, and which symptoms were most likely related to oropharyngeal dysphagia (OD) risk.FindingsWe have found that the eating/drinking difficulty of thick liquids was the highest predictive value with respect to OD risk and the eating difficulty of mixed content food had the highest diagnostic ratio.MessageThe present study reports that even in older person who do not go to the hospital with the complaints of swallowing difficulty, the difficulty of swallowing thick liquids and especially the mixed content food should be questioned. AbstractPurposeThe present study aimed to investigate which swallowing difficulty of food consistency in participants over 65years of age who did not have any disease that might affect swallowing functions, and which symptoms were most likely related to oropharyngeal dysphagia (OD).MethodsThe cross-sectional and multicenter study was conducted at 12 hospitals including 883 participants aged >= 65years who were fed orally and who were admitted to the physical medicine and rehabilitation outpatient clinics between September 2017 and December 2018. Demographic characteristics were recorded. Katz Daily Living Activities Index (KDLAI), swallowing-related quality of life scale (Swal-QoL) and 10-item Eating Assessment Tool (EAT-10) were used. The participants were asked the yes or no questions including swallowing difficulty of various types of food consistency with the face-to-face interview.ResultsParticipants were divided into two groups as normal swallowing (EAT-10= 3 group) (n=244) according to the EAT-10 scores. While there was no difference related to number of teeth and KDLAI scores between groups (p=0.327 and p=0.221, respectively), the significant difference was found between groups in terms of yes/no questions and Swal-QoL scores (p<0.05). Receiver operating characteristic analysis revealed that eating difficulty of mixed content food provided maximum sensitivity (99%) and eating/drinking difficulty of thick liquid had maximum specificity (77%). The higher area under curve was in eating/drinking difficulty of thick liquid (0.891), and higher positive likelihood ratio (LR) was eating/drinking difficulty of thick liquid (4.26) as well as lower negative LR was eating difficulty of mixed content food (0.01). The higher diagnostic odds ratio was eating difficulty of mixed content food (367.0), and the higher posttest probability was eating/drinking difficulty of thick liquid (0.211).ConclusionWhile eating difficulty of hard solid food is the most common symptom in healthy participants over 65years of age, the eating difficulty of thick liquids is the highest predictive value related to oropharyngeal dysphagia risk. Also, the eating difficulty of mixed content food had the highest diagnostic ratio

Which swallowing difficulty of food consistency is best predictor for oropharyngeal dysphagia risk in older person?

© 2019, European Geriatric Medicine Society.Aim: Our aim was to investigate which swallowing difficulty of food consistency in older people who did not have any disease that might affect swallowing functions, and which symptoms were most likely related to oropharyngeal dysphagia (OD) risk. Findings: We have found that the eating/drinking difficulty of thick liquids was the highest predictive value with respect to OD risk and the eating difficulty of mixed content food had the highest diagnostic ratio. Message: The present study reports that even in older person who do not go to the hospital with the complaints of swallowing difficulty, the difficulty of swallowing thick liquids and especially the mixed content food should be questioned. Purpose: The present study aimed to investigate which swallowing difficulty of food consistency in participants over 65 years of age who did not have any disease that might affect swallowing functions, and which symptoms were most likely related to oropharyngeal dysphagia (OD). Methods: The cross-sectional and multicenter study was conducted at 12 hospitals including 883 participants aged ≥65 years who were fed orally and who were admitted to the physical medicine and rehabilitation outpatient clinics between September 2017 and December 2018. Demographic characteristics were recorded. Katz Daily Living Activities Index (KDLAI), swallowing-related quality of life scale (Swal-QoL) and 10-item Eating Assessment Tool (EAT-10) were used. The participants were asked the “yes” or “no” questions including swallowing difficulty of various types of food consistency with the face-to-face interview. Results: Participants were divided into two groups as normal swallowing (EAT-10 < 3 group) (n = 639) and OD risk groups (EAT-10 ≥ 3 group) (n = 244) according to the EAT-10 scores. While there was no difference related to number of teeth and KDLAI scores between groups (p = 0.327 and p = 0.221, respectively), the significant difference was found between groups in terms of yes/no questions and Swal-QoL scores (p < 0.05). Receiver operating characteristic analysis revealed that eating difficulty of mixed content food provided maximum sensitivity (99%) and eating/drinking difficulty of thick liquid had maximum specificity (77%). The higher area under curve was in eating/drinking difficulty of thick liquid (0.891), and higher positive likelihood ratio (LR) was eating/drinking difficulty of thick liquid (4.26) as well as lower negative LR was eating difficulty of mixed content food (0.01). The higher diagnostic odds ratio was eating difficulty of mixed content food (367.0), and the higher posttest probability was eating/drinking difficulty of thick liquid (0.211). Conclusion: While eating difficulty of hard solid food is the most common symptom in healthy participants over 65 years of age, the eating difficulty of thick liquids is the highest predictive value related to oropharyngeal dysphagia risk. Also, the eating difficulty of mixed content food had the highest diagnostic ratio

The GUSS test as a good indicator to evaluate dysphagia in healthy older people: a multicenter reliability and validity study

Purpose Dysphagia is known to be a disorder of the swallowing function, and is a growing health problem in aging populations. Swallowing screening tests have mostly been studied in comorbidities such as stroke associated with old age. There is no simple, quick and easy screening test to best determine the risk of oropharyngeal dysphagia in geriatric guidelines. We aimed to evaluate whether the Gugging Swallowing Screen (GUSS) test is an effective method for evaluating swallowing difficulty in healthy older people. Methods This cross-sectional and multicenter study was conducted at 13 hospitals between September 2017 and February 2019. The study included 1163 participants aged >= 65 years and who had no secondary dysphagia. Reliability was evaluated for data quality, scaling assumptions, acceptability, reliability, and validity as well as cutoff points, specificity and sensitivity. Results The age distribution of 773 (66.5%) patients was between 65 and 74 years and 347 (29.8%) of them were male and 767 (66%) patients were female. The average total GUSS score was 18.57 +/- 1.41. The Cronbach's alpha was 0.968. There was a moderate statistically significant negative correlation between the total GUSS and 10-item Eating Assessment Tool scores as well as between the total GUSS score and quality of life. The cutoff point of the total GUSS score was 18.50, sensitivity was 95.5% and specificity was 94.4%. Conclusions The GUSS test is a valid and reliable test to identify possible oropharyngeal dysphagia risk in healthy older people who had no secondary dysphagia. It is suitable as a screen test for clinical practice