Effect of motor symptom onset asymmetry on facial expressivity

Objective: Previous studies have shown that the prolonged duration of TIA symptoms or ABCD2 score are associated with DWI abnormality, and the presence of DWI abnormality is associated with an increased early risk of stroke. However, there are few reports that show the relation between TIA clinical etiology and DWI abnormality. Our aim of this study is to clarify the prevalence of positive DWI in relation to characteristics of patients and TIA. Methods: The subjects were enrolled from patients who were admitted to our stroke unit within 7 days after symptom onset from January 2006 to July 2013. The diagnosis of TIA was done by NINDS criteria, and we classified TIA etiology by TOAST classification based on clinical symptoms, ECG monitoring, carotid ultrasound, MR angiography and transesophageal echocardiography. All patients underwent DWI-MRI within 7 days after symptom onset. We examined an association between TIA etiology, symptom, duration of symptoms and DWI abnormality. Results: A total of 141 patients (mean 64 years; 63% men) were admitted with TIA during this period. Those included lacuna TIA (n=17, 12.1%), atherothrombotic TIA (n=32, 22.7%), cardioembolic TIA (n=23, 16.3%), TIA due to other causes (n=35, 24.8%), and TIA with unknown etiology (n=34, 24.1%). Prevalence of positive DWI findings were 47.1% in lacunar TIA, 43.7% in atherothrombotic TIA, 52.1% in cardioembloic TIA, 42.8% in TIA due to other causes, and 23.5% in TIA with unknown etiology. DWI abnormality was the most frequent in cardiogenic TIA. In relation to symptom duration, the prevalence of DWI positive findings were 45.2% in less than 1 hour (N=53), 36.6% in 1-3 hour (N=41), 25.0% in 3-6 hour (N=12) and 42.9% in 6-24 hours (N=35). In relation to motor symptoms, there was no difference in prevalence of DWI abnormality between patient with motor symptoms (39.8%, N=113) and without (42.8%, N=28). There was no relation between DWI abnormalities and age, a history of stroke/TIA episode or vascular risk factors. Conclusion: Prevalence of DWI positive findings was high in cardiogenic TIA, and low in TIA with unclassified etiology. There were no relation between DWI abnormality, duration of symptom, and motor symptom.

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Motor neuron translatome reveals deregulation of SYNGR4 and PLEKHB1 in mutant TDP-43 amyotrophic lateral sclerosis models

Human Molecular Genetics ◽

10.1093/hmg/ddaa140 ◽

2020 ◽

Vol 29 (16) ◽

pp. 2647-2661 ◽

Cited By ~ 1

Author(s):

Rita F Marques ◽

Jan B Engler ◽

Katrin Küchler ◽

Ross A Jones ◽

Thomas Lingner ◽

...

Keyword(s):

Spinal Cord ◽

Amyotrophic Lateral Sclerosis ◽

Motor Neuron ◽

Symptom Onset ◽

Rna Binding ◽

Affinity Purification ◽

Disease Onset ◽

Motor Symptom ◽

Pathological Feature ◽

Lateral Sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is an incurable neurological disease with progressive loss of motor neuron (MN) function in the brain and spinal cord. Mutations in TARDBP, encoding the RNA-binding protein TDP-43, are one cause of ALS, and TDP-43 mislocalization in MNs is a key pathological feature of >95% of ALS cases. While numerous studies support altered RNA regulation by TDP-43 as a major cause of disease, specific changes within MNs that trigger disease onset remain unclear. Here, we combined translating ribosome affinity purification (TRAP) with RNA sequencing to identify molecular changes in spinal MNs of TDP-43–driven ALS at motor symptom onset. By comparing the MN translatome of hTDP-43A315T mice to littermate controls and to mice expressing wild type hTDP-43, we identified hundreds of mRNAs that were selectively up- or downregulated in MNs. We validated the deregulated candidates Tex26, Syngr4, and Plekhb1 mRNAs in an independent TRAP experiment. Moreover, by quantitative immunostaining of spinal cord MNs, we found corresponding protein level changes for SYNGR4 and PLEKHB1. We also observed these changes in spinal MNs of an independent ALS mouse model caused by a different patient mutant allele of TDP-43, suggesting that they are general features of TDP-43-driven ALS. Thus, we identified SYNGR4 and PLEKHB1 to be deregulated in MNs at motor symptom onset in TDP-43-driven ALS models. This spatial and temporal pattern suggests that these proteins could be functionally important for driving the transition to the symptomatic phase of the disease.

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A.01 Parkinson’s disease prognosis by early motor subtypes

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2018.82 ◽

2018 ◽

Vol 45 (s2) ◽

pp. S9-S9

Author(s):

N Hey ◽

ML Rajput ◽

AH Rajput ◽

A Rajput

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Symptom Onset ◽

Primary Outcome ◽

Disease Duration ◽

Motor Symptom ◽

Future Studies ◽

Disease Prognosis ◽

Significant Difference

Background: Studies of autopsy-confirmed cases suggest that Parkinson’s disease (PD) prognosis can be predicted using motor symptom severity at first visit. We evaluated the association between motor symptom subtype at first visit and severity at eight years disease duration among clinically-diagnosed cases at the Saskatchewan Movement Disorder Program. Methods: Retrospective data review identified 374 patients with first visit within three years of symptom onset, a clinical diagnosis of idiopathic PD, and a follow-up visit eight years after symptom onset. Subtypes were grouped as tremor-dominant (TD) if tremor was greater than rigidity and bradykinesia, akinetic-rigid (AR) if rigidity or bradykinesia was greater than tremor, and mixed (MX) if patient was neither TD nor AR based on assessment of all four limbs. Primary outcome was disease severity as measured by Hoehn & Yahr score at eight years after symptom onset. Results: The most common subtype was AR (n=164) followed by MX (n=156). TD was least common (n=54). There was no significant difference between subtypes in H&Y scores at eight years disease duration. Conclusions: These findings suggest that early PD prognosis cannot be predicted based on motor symptoms in all four limbs at first visit. Earlier studies had longer follow-up and future studies will examine progression at longer periods of disease duration.

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Altered CB1 receptor and endocannabinoid levels precede motor symptom onset in a transgenic mouse model of Huntington's disease

Neuroscience ◽

10.1016/j.neuroscience.2009.06.014 ◽

2009 ◽

Vol 163 (1) ◽

pp. 456-465 ◽

Cited By ~ 64

Author(s):

M.J. Dowie ◽

H.B. Bradshaw ◽

M.L. Howard ◽

L.F.B. Nicholson ◽

R.L.M. Faull ◽

...

Keyword(s):

Mouse Model ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Transgenic Mouse ◽

Symptom Onset ◽

Transgenic Mouse Model ◽

Cb1 Receptor ◽

Motor Symptom

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An Exploration of Apathy and Impulsivity in Parkinson Disease

Current Gerontology and Geriatrics Research ◽

10.1155/2012/390701 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 14

Author(s):

David J. Ahearn ◽

Kathryn McDonald ◽

Michelle Barraclough ◽

Iracema Leroi

Keyword(s):

Factor Analysis ◽

Parkinson Disease ◽

Symptom Onset ◽

Regression Models ◽

Future Orientation ◽

Motor Symptom ◽

Disease Stage ◽

Factor Solution ◽

Security Planning ◽

Clinically Significant

Background. Apathy and impulsivity in Parkinson disease (PD) are associated with clinically significant behavioral disorders.Aim. To explore the phenomenology, distribution, and clinical correlates of these two behaviors.Methods. In PD participants (n=99) without dementia we explored the distribution of measures of motivation and impulsivity using univariate methods. We then undertook factor analysis to define specific underlying dimensions of apathy and impulsivity. Regression models were developed to determine the associated demographic and clinical features of the derived dimensions.Results. The factor analysis of apathy (AES-C) revealed a two-factor solution: “cognitive-behavior” and “social indifference”. The factor analysis of impulsivity (BIS-11) revealed a five-factor solution: “inattention”; “impetuosity”; “personal security”; “planning”; and “future orientation”. Apathy was significantly associated with: age, age of motor symptom onset (positive correlation), disease stage, motor symptom severity, and depression. Impulsivity was significantly associated with: age of motor symptom onset (negative correlation), gambling and anxiety scores, and motor complications. We observed an overlap of apathy and impulsivity in some participants.Conclusion. In PD, apathy and impulsivity have specific phenomenological profiles and are associated with particular clinical phenotypes. In spite of this, there is some overlap of behaviors which may suggests common aspects in the pathology underlying motivation and reward processes.

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Body side of motor symptom onset in Parkinson's disease is associated with memory performance

Journal of the International Neuropsychological Society ◽

10.1017/s1355617706060875 ◽

2006 ◽

Vol 12 (5) ◽

pp. 736-740 ◽

Cited By ~ 26

Author(s):

M.M. AMICK ◽

J. GRACE ◽

K.L. CHOU

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Symptom Onset ◽

Verbal Memory ◽

Visual Memory ◽

Right Hemisphere ◽

Verbal Learning ◽

Motor Symptom ◽

Hemispheric Dominance ◽

Body Side

The relation of body side of motor symptom onset in Parkinson's disease (PD) to memory measures associated with hemispheric dominance was examined. Fourteen patients with right body side motor symptom onset (RPD, inferred left hemisphere dysfunction) and 16 patients with left side onset (LPD, right hemisphere dysfunction) were administered measures of verbal (Hopkins Verbal Learning Test-Revised) and visual memory (Brief Visual Memory Test-Revised), that require similar task demands and are associated with left or right hemisphere dominance, respectively. The LPD group demonstrated poorer visual than verbal memory, both within group and in comparison to the RPD group. By contrast, the RPD group showed poorer verbal than visual memory within group. These findings suggest that side of motor symptom onset is associated with asymmetrical memory dysfunction (JINS, 2006, 12, 736–740.)

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Common variation at the LRRK2 locus is associated with survival in the primary tauopathy progressive supranuclear palsy

10.1101/2020.02.04.932335 ◽

2020 ◽

Author(s):

Edwin Jabbari ◽

Manuela M.X. Tan ◽

Regina H. Reynolds ◽

Kin Y. Mok ◽

Raffaele Ferrari ◽

...

Keyword(s):

Gene Expression ◽

Progressive Supranuclear Palsy ◽

Symptom Onset ◽

Genetic Risk ◽

Genetic Basis ◽

Regulation Of Gene Expression ◽

Alpha Synuclein ◽

Motor Symptom ◽

Common Variation ◽

Neuro Inflammation

AbstractThe genetic basis of variation in the rate of disease progression of primary tauopathies has not been determined. In two independent progressive supranuclear palsy cohorts, we show that common variation at the LRRK2 locus determines survival from motor symptom onset to death, possibly through regulation of gene expression. This links together genetic risk in alpha-synuclein and tau disorders, and suggests that modulation of proteostasis and neuro-inflammation by LRRK2 inhibitors may have a therapeutic role across disorders.

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