Understanding the Pathophysiology of Spinocerebellar Ataxias through genetics, neurophysiology, structural and functional neuroimaging

Over the past 10 years a large cohort of 656 index patients with clinically suspected degenerative ataxias were clinically evaluated under various research projects. Of these, 625 index patients underwent genetic tests for the clinically suspected most probable diagnosis. A diagnosis could be achieved in 218 patients (34.9%). Among these 218 index patients, 82 each were SCA1 and SCA2, 32 were SCA3, 4 were SCA12, and 18 were Friedreich's Ataxia. Thus among the Autosomal Dominant Ataxias (SCAs) there was equal prevalence of SCA1 and SCA2 (41% each) followed by SCA3 (16%) and SCA12 (2%). This high prevalence of SCA1 is in contrast to the available National and International literature. The rate of clinical disease progression, especially in SCA2, was dependent on the CAG repeat size, and may commence linearly from birth.Apart from cerebellar involvement, a comprehensive evaluation of the neuroaxis in various subsets of this genetically proved cohort showedsubclinicalinvolvement of the cerebral cortex, central motor and sensory pathways, peripheral nervous system and autonomic nervous system. Important findings include: (a)Amixedsensorimotor and pure sensory neuropathy was seen in all the three subtypes of SCAs, while pure motor neuropathy was uncommon; (b) There was reduced cortical excitability and prolonged central motor conduction time, most evident in SCA1 and least in SCA2; (c) Cardiac autonomic dysfunction, predominantly parasympathetic, was seen in SCA, and the severity correlated with the duration of illness in SCA1; (d) In SCA1 there was a global impairment of balance, with greater instability in anterior–posterior than medio–lateral directions; (e) In all the three SCAs there was a significant loss of gray matter in both cerebellar hemispheres and vermis. Vermian atrophy was more pronounced in SCA3, while SCA1 and SCA2 had significant white matter atrophy. Pontine white matter atrophy was more pronounced in SCA2; (f) Cerebellar activity was largely absent with additional activity in contralateral cortices and in thalami in patients with SCA1; increased thalamic function could be one of the causes for disinhibition of the motor cortex contributing to uncoordinated movements.Studies on larger cohort of each subtype of SCAs to validate the above findings, follow-up studies to determine the rate and nature of progression of neurodegeneration and evaluation of pre-symptomatic genetically confirmed SCAs will help understand the pathophysiology of the SCAs

The Non-motor Features of Essential Tremor: A Primary Disease Feature or Just a Secondary Phenomenon?

Essential tremor (ET) is a pathologically heterogeneous neurodegenerative disorder with both motor and increasingly recognized non-motor features. It is debated whether the non-motor manifestations in ET result from widespread neurodegeneration or are merely secondary to impaired motor functions and decreased quality of life due to tremor. It is important to review these features to determine how to best treat the non-motor symptoms of patients and to understand the basic pathophysiology of the disease and develop appropriate pharmacotherapies. In this review, retrospective and prospective clinical studies were critically analyzed to identify possible correlations between the severities of non-motor features and tremor. We speculated that if such a correlation existed, the non-motor features were likely to be secondary to tremor. According to the current literature, the deficits in executive function, attention, concentration, and memory often observed in ET are likely to be a primary manifestation of the disease. It has also been documented that patients with ET often exhibit characteristic personality traits. However, it remains to be determined whether the other non-motor features often seen in ET, such as anxiety, depression, and sleep disturbances are primary or secondary to motor manifestations of ET and subsequent poor quality of life. Finally, there is evidence that patients with ET can also have impaired color vision, disturbances of olfaction, and hearing impairments, though there are few studies in these areas. Further investigations of large cohorts of patients with ET are required to understand the prevalence, nature, and true significance of the non-motor features in ET

Simulation of Brushless DC Motor for Performance Analysis using MATLAB/SIMULINK EnvironmentÂ

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Re-emergent Tongue Tremor in Neuroleptic Induced Parkinsonism

Background: A re-emergent tremor is suggested to be specific to Parkinson’s disease and although a tongue tremor has been reported in levosulpiride-induced parkinsonism (LIP), re-emergence has never been reported. Case Report: A 59-year-old female presented with a 3-month history of bradykinesia, 2-week history of right-leg tremor, and 10-day history of lip and tongue tremor. A review of the medication revealed a 15-month history of levosulpiride consumption. On examination, asymmetric bradykinesia, rigidity, rest tremor of the right leg, and re-emergent tongue tremor were observed. The parkinsonism subsided after levosulpiride was stopped. Discussion: This is the first report of re-emergent tongue tremor in LIP

Total Ionization Cross Sections due to Electron Impact of Ammonia from Threshold to 10 MeV

In the present paper, we have employed modified Khare-BEB method [Atoms, (2019)] to evaluate total ionization cross sections by the electron impact for ammonia in energy range from the ionization threshold to 10 MeV.  The theoretical ionization cross sections have been compared to the available previous theoretical and experimental results. The collision parameters dipole matrix squared  and CRP  also have been calculated. The present calculations were found in remarkable agreement with the available experimental results

Status Dystonicus as an Acute Sequelae Following Anoxic Cerebral Damage

Background: Status dystonicus (SD) is the term used for extreme, continuous, generalized muscle contractions that are poorly responsive to treatment. Here, we report a rare case of acute hypoxic ischemic encephalopathy presenting with SD. Case Report: A young male sustained cerebral hypoxia following a cardiac event and presented with opisthotonic posturing and dystonia refractory to medical therapy. His serum creatine phosphokinase was high and his urine tested positive for myoglobin. Discussion: SD as an acute sequelae following acute brain hypoxia is rare. Management of brain anoxia is challenging, even more so when the presentation is compounded by refractory SD. Keywords: Dystonia, emergency, hypoxia, status, anoxia Citation: Ray S, Sidhu RJS, Pal PK, Yadav R. Status dystonicus as an acute sequelae following anoxic cerebral damage. Tremor Other Hyperkinet Mov. 2019; 9. doi: 10.7916/98r0-743

Large tuneable exchange fields due to purely paramagnetically limited domain wall superconductivity

The ability to locally apply and tune large magnetic fields is a crucial requirement for several devices, most notably for detection and generation of majorana fermions. Such a functionality can be achieved in Superconductor (S) /Ferromagnet (F) bilayers, where superconductivity is strengthened on top of domain walls due to local lowering of the proximity induced effective exchange fields. This is predicted to result in significant superconducting Tc enhancements and possible complete magnetic controlled switching on and off of the superconducting state. By using thin films of superconducting Nb and ferromagnetic insulating (GdN) bilayers, and through detailed magneto-transport measurements, we demonstrate the previously unobserved phenomena of complete switching in and out of the S state in S/F bilayers. In the thinnest of Nb layers, we estimate that the domain wall state induced tunability of proximity induced exchange fields can be as high as 1.3T with application of in plane external fields of only a few mT.Comment: 3 figure

Chemical potential shift and gap-state formation in SrTiO3−δ_{3-\delta} revealed by photoemission spectroscopy

In this study, we report on investigations of the electronic structure of SrTiO$_3$ annealed at temperature ranging between 550 and 840$^\circ$C in an ultrahigh vacuum. Annealing induced oxygen vacancies (O$_{vac}$) impart considerable changes in the electronic structure of SrTiO$_3$. Using core-level photoemission spectroscopy, we have studied the chemical potential shift ($\Delta\mu$) as a function of annealing temperature. The result shows that the chemical potential monotonously increases with electron doping in SrTiO$_{3-\delta}$. The monotonous increase of the chemical potential rules out the existence of electronic phase separation in the sample. Using valence band photoemission, we have demonstrated the formation of a low density of states at the near Fermi level electronic spectrum of SrTiO$_{3-\delta}$. The gap-states were observed by spectral weight transfer over a large energy scale of the stoichiometric band gap of SrTiO$_3$ system leading finally to an insulator - metal transition. We have interpreted our results from the point of structural distortions induced by oxygen vacancies.Comment: 7 pages, 6 figures, 1 tabl