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Frontotemporal dementia (FTD) is a clinical, genetic, and pathologic heterogeneous group of neurodegenerative diseases. In this study, we investigated the role of APOƐ4, rs5848 in GRN, and rs1042522 in TP53 gene as disease risk factors and/or phenotype modifiers in 440 FTD patients, including 175 C9orf72 expansion carriers. We found that the C9orf72 expansion carriers showing an earlier age at onset (p < 0.001). Among the clinical groups, the FTD-MND (motoneuron disease) showed the lowest survival (hazard ratio [HR] = 4.12), and the progressive nonfluent aphasia group showed the highest onset age (p = 0.03). In our cohort, the rs1042522 in TP53 was associated with disease onset (p = 0.02) and survival (HR = 1.73) and rs5848 GRN with a significantly shorter survival in CC homozygous patients (HR = 1.98). The frequency of APOƐ4 carriers was significantly increased in the C9orf72 noncarriers (p = 0.022). Although validation of our findings is necessary, our results suggest that TP53, GRN, and APOE genes may act as phenotype modifiers in FTD and should be considered in future clinical trials., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To describe the clinical and electromyographic characteristics of blepharospasm caused by selective involvement of the pars pretarsalis of the orbicularis oculi muscle., Methods: Clinical assessment and simultaneous electromyographic recordings from levator palpebrae superioris and pars orbitaria and pretarsalis of orbicularis oculi muscles were performed in patients with blepharospasm and primary failure to botulinum toxin injections. Patients with selective abnormal electromyographic activity of the pars pretarsalis of the orbicularis oculi muscle were identified and treated with selective pretarsal injections of botulinum toxin., Results: We found 24 patients with pretarsal blepharospasm confirmed by the electromyographic assessment. All of them were functionally blind. Three clinical-electromyographic patterns were identified: (a) Impairment of eyelid opening; (b) Increased blinking; (c) Spasms of eye closure combined with varying degrees of excessive blinking and impairment of eye-opening. Pretarsal injections of botulinum toxin induced a significant improvement in all patients and 50 % regained normal or near-normal vision. The clinical improvement was sustained after repeated pretarsal injections., Conclusions: Pretarsal blepharospasm can be suspected on clinical grounds and it can be confirmed by electromyographic recordings., Significance: Recognition of this type of blepharospasm is important because of its excellent response to botulinum toxin injections applied into the pretarsal part of the orbicularis oculi muscle., Competing Interests: Declaration of Competing Interest F. Grandas received honoraria for lecturing from Allergan S.A. The other authors: none., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

We analyzed the frequency of intermediate alleles (IAs) in the ATXN1, ATXN2, and HTT genes in several neurodegenerative diseases. The study included 1126 patients with Alzheimer's disease (AD), 440 patients with frontotemporal dementia (FTD), and 610 patients with Parkinson's disease. In all cohorts, we genotyped ATXN1 and ATXN2 CAG repeats. In addition, in the FTD cohort, we determined the number of HTT CAG repeats. The frequency of HTT IAs was higher in patients with FTD (6.9%) versus controls (2.9%) and in the C9orf72 expansion noncarriers (7.2%) versus controls (2.9%), although the difference was nonsignificant after correction for multiple testing. Compared with controls, progressive nonfluent aphasia (PNFA) groups showed a significantly higher frequency of HTT IAs (13.6% vs. 2.9% controls). For the ATXN2 gene, we observed an increase in IA frequency in AD cases (AD 4.1% vs. controls 1.8%) and in the behavioral FTD group (4.8% vs. 1.8%). For the ATXN1 gene, we found a significant increase of IAs in patients with PNFA (18.6%) versus controls (6.7%). In conclusion, our work suggests that the HTT and ATXN1 IAS may contribute to PNFA pathogenesis and point to a link between ATXN2 IAS and AD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Histological image analysis plays a key role in understanding the effects of disease and treatment responses at the cellular level. However, evaluating histology images by hand is time-consuming and subjective. While semi-automatic and automatic approaches for image segmentation give acceptable results in some branches of histological image analysis, until now this has not been the case when applied to skeletal muscle histology images. We introduce Charisma, a new top-down cell segmentation framework for histology images which combines image processing techniques, a supervised trained classifier and a novel robust clump splitting algorithm. We evaluate our framework on real-world data from intensive care unit patients. Considering both segmentation and cell property distributions, the results obtained by our method correspond well to the ground truth, outperforming other examined methods., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Freezing of gait is an episodic gait disorder that may occur in patients with Parkinson's disease. The risk factors for this disorder are poorly understood. To determine the relevant risk factors for this condition, we screened 160 consecutive patients with Parkinson's disease for freezing of gait and assessed 36 potentially related variables. Freezers and non-freezers were compared using statistical univariate analysis, followed by bivariate and multivariate logistic regression, receiver operating characteristics curves and Kaplan-Meier estimates. Seventy-one patients (44.4%) reported freezing of gait. At onset, the mean disease duration was 8.1±6.3years. Freezers experienced falls more frequently than non-freezers (57.7% vs 23.6%, p<0.001). Disease duration was the independent variable most associated with freezing of gait (OR=1.10, 95% CI=1.01-1.19, p=0.020). Its specificity was 77%, but its sensitivity was low, and Hoehn and Yahr staging and the UPDRS (part III) score showed similar accuracy to that of disease duration in predicting freezers. Previous antiparkinsonian treatments and predominant motor signs (tremor/akinesia-rigidity subtypes) at the onset of Parkinson's disease were not related to freezing of gait. Patients who developed Parkinson's disease before the age of 60years experienced freezing of gait earlier than older patients (log-rank, p<0.005). Freezing of gait is a common and disabling motor complication of Parkinson's disease that is related to the progression of the disease. It is not primarily associated with dopamine replacement therapy and may occur early in young patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Dopamine dysregulation syndrome is a complication of the dopaminergic treatment for Parkinson's disease, probably related to sensitization of the mesolimbic dopamine system. The relationship between dopamine dysregulation syndrome and deep brain stimulation of the subthalamic nucleus remains unclear. We report three patients with Parkinson's disease who developed de novo dopamine dysregulation syndrome after deep brain stimulation of the subthalamic nucleus. We hypothesized that the combined effect of dopaminergic replacement therapy and deep brain stimulation on the limbic territory of the subthalamic nucleus could have precipitated the dopamine dysregulation syndrome in these patients, by inducing hyperstimulation of the mesolimbic dopamine system. The outcome of postoperative dopamine dysregulation syndrome is poor despite deep brain stimulation adjustments, attempts to reduce the dose of dopaminergic drugs and the addition of quetiapine or antidepressants., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Hemiballism is a relatively rare hyperkinetic movement disorder characterized by involuntary, violent, coarse and wide-amplitude movements involving ipsilateral arm and leg. Although classically related to lesions in the subthalamic nucleus, in clinical-radiological series of hemiballism most patients had lesions outside this nucleus, involving mainly other basal ganglia structures. It has been suggested that abnormal neuronal firing patterns in the internal segment of the globus pallidus may be related to the pathogenesis of hemiballism. Stroke is the most common cause, but in recent years an increasing number of patients with hemiballism associated with nonketotic hyperglycemia or with complications of human immunodeficiency virus (HIV) infection have been reported. Contrarily to what was stated in older literature, hemiballism has, in general, a relatively good prognosis. Depending on the underlying causes, many patients may experience spontaneous improvements or remissions. Treatment should be directed to the cause of hemiballism. Symptomatic treatment includes the use of drugs, particularly blockers of striatal D2 dopamine receptors and tetrabenazine. Surgical treatment, especially pallidotomy, is a therapeutic option for the minority of patients with severe persistent disabling hemiballism., (Copyright © 2011 Elsevier B.V. All rights reserved.)