Adult diagnosis of Cockayne syndrome

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Manual and semi-automated approaches to MIBG myocardial scintigraphy in patients with Parkinson’s disease

OBJECTIVE: This study investigates the effects of manual and semi-automatic methods for assessing MIBG semi-quantitative indices in a clinical setting. MATERIALS AND METHODS: We included (123)I-MIBG scans obtained in 35 patients with idiopathic Parkinson’s Disease. Early and late heart-to-mediastinum (H/M) ratios were calculated from (123)I-MIBG images using regions of interest (ROIs) placed over the heart and the mediastinum. The ROIs were derived using two approaches: (i) manually drawn and (ii) semi-automatic fixed-size ROIs using anatomical landmarks. Expert, moderate-expert, and not expert raters applied the ROIs procedures and interpreted the (123)I-MIBG images. We evaluated the inter and intra-rater agreements in assessing (123)I-MIBG H/M ratios. RESULTS: A moderate agreement in the raters’ classification of pathological and non-pathological scores emerged regarding early and late H/M ratio values (κ = 0.45 and 0.69 respectively), applying the manual method, while the early and late H/M ratios obtained with the semi-automatic method reached a good agreement among observers (κ = 0.78). Cohen-Kappa values revealed that the semi-automatic method improved the agreement between expert and inexpert raters: the agreement improved from a minimum of 0.29 (fair, for early H/M) and 0.69 (substantial, in late H/M) with the manual method, to 0.90 (perfect, in early H/M) and 0.87 (perfect, in late H/M) with the semi-automatic method. CONCLUSION: The use of the semi-automatic method improves the agreement among raters in classifying’ H/M ratios as pathological or non-pathological, namely for inexpert readers. These results have important implications for semi-quantitative assessment of (123)I-MIBG images in clinical routine

TWNK in Parkinson's Disease: A Movement Disorder and Mitochondrial Disease Center Perspective Study

Background: Parkinsonian features have been described in patients harboring variants in nuclear genes encoding for proteins involved in mitochondrial DNA maintenance, such as TWNK. Objectives: The aim was to screen for TWNK variants in an Italian cohort of Parkinson's disease (PD) patients and to assess the occurrence of parkinsonism in patients presenting with TWNK-related autosomal dominant progressive external ophthalmoplegia (TWNK-adPEO). Methods: Genomic DNA of 263 consecutively collected PD patients who underwent diagnostic genetic testing was analyzed with a targeted custom gene panel including TWNK, as well as genes causative of monogenic PD. Genetic and clinical data of 18 TWNK-adPEO patients with parkinsonism were retrospectively analyzed. Results: Six of 263 PD patients (2%), presenting either with isolated PD (n = 4) or in combination with bilateral ptosis (n = 2), carried TWNK likely pathogenic variants. Among 18 TWNK-adPEO patients, 5 (28%) had parkinsonism. Conclusions: We show candidate TWNK variants occurring in PD without PEO. This finding will require further confirmatory studies. © 2022 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society

Recent developments in clinical trials of botulinum neurotoxins

Botulinum neurotoxins (BoNTs) are increasingly used in clinical practice for several indications. Following the pioneering years of discoveries, the recent years have witnessed an increase of new indications and new toxin brands.We review here the clinical trials on BoNTs performed since 2014 and put them into perspective. We also review the ongoing trials listed by the National Institutes of Health registry (Clinicaltrials.gov). The following indications are reviewed here: blepharospasm, cervical dystonia, spasticity, cerebral palsy, urinary incontinence, headache, topical formulations, postoperative cardiac arrhythmia, keloids and scars. For each of these indications the latest trials are reviewed and commented

Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases

Most neurodegenerative disorders are diseases of protein homeostasis, with misfolded aggregates accumulating. The neurodegenerative process is mediated by numerous metabolic pathways, most of which lead to apoptosis. In recent years, hydrophilic bile acids, particularly tauroursodeoxycholic acid (TUDCA), have shown important anti-apoptotic and neuroprotective activities, with numerous experimental and clinical evidence suggesting their possible therapeutic use as disease-modifiers in neurodegenerative diseases. Experimental evidence on the mechanisms underlying TUDCA's neuroprotective action derives from animal models of Alzheimer's disease, Parkinson's disease, Huntington's diseases, amyotrophic lateral sclerosis (ALS) and cerebral ischemia. Preclinical studies indicate that TUDCA exerts its effects not only by regulating and inhibiting the apoptotic cascade, but also by reducing oxidative stress, protecting the mitochondria, producing an anti-neuroinflammatory action, and acting as a chemical chaperone to maintain the stability and correct folding of proteins. Furthermore, data from phase II clinical trials have shown TUDCA to be safe and a potential disease-modifier in ALS. ALS is the first neurodegenerative disease being treated with hydrophilic bile acids. While further clinical evidence is being accumulated for the other diseases, TUDCA stands as a promising treatment for neurodegenerative diseases

Manual and semi-automated approaches to MIBG myocardial scintigraphy in patients with Parkinson’s disease

Objective: This study investigates the effects of manual and semi-automatic methods for assessing MIBG semi-quantitative indices in a clinical setting. Materials and methods: We included 123I-MIBG scans obtained in 35 patients with idiopathic Parkinson’s Disease. Early and late heart-to-mediastinum (H/M) ratios were calculated from 123I-MIBG images using regions of interest (ROIs) placed over the heart and the mediastinum. The ROIs were derived using two approaches: (i) manually drawn and (ii) semi-automatic fixed-size ROIs using anatomical landmarks. Expert, moderate-expert, and not expert raters applied the ROIs procedures and interpreted the 123I-MIBG images. We evaluated the inter and intra-rater agreements in assessing 123I-MIBG H/M ratios. Results: A moderate agreement in the raters’ classification of pathological and non-pathological scores emerged regarding early and late H/M ratio values (κ = 0.45 and 0.69 respectively), applying the manual method, while the early and late H/M ratios obtained with the semi-automatic method reached a good agreement among observers (κ = 0.78). Cohen-Kappa values revealed that the semi-automatic method improved the agreement between expert and inexpert raters: the agreement improved from a minimum of 0.29 (fair, for early H/M) and 0.69 (substantial, in late H/M) with the manual method, to 0.90 (perfect, in early H/M) and 0.87 (perfect, in late H/M) with the semi-automatic method. Conclusion: The use of the semi-automatic method improves the agreement among raters in classifying’ H/M ratios as pathological or non-pathological, namely for inexpert readers. These results have important implications for semi-quantitative assessment of 123I-MIBG images in clinical routine

Eligibility criteria in clinical trials for cervical dystonia

Introduction: Cervical dystonia (CD) is the most common form of adult-onset focal dystonia. Because of a heterogeneous clinical presentation, the diagnosis rests on clinical opinion. During the last decades, several clinical trials have tested safety and efficacy of medical and surgical treatments for CD. We analyzed all the published CD trials and reviewed the strategies adopted for patient enrollment.Methods: The review included clinical trials in patients with CD published in PubMed. Studies were excluded if reviews, meta-analyses, post-hoc analyses on pooled data, or if not reporting a treatment for CD.Results: A total of 174 articles were identified; 134 studies met inclusion criteria. Diagnosis of CD varied among studies and in most cases was based on clinical judgement, using different descriptors such as "cervical dystonia " (37 studies), "idiopathic or isolated CD " (35), "primary CD " (13), and "torticollis " (40). Clinical judgement was supported by a phenomenological description of dystonia in four studies, and by a specific diagnostic strategy in other four. Finally, one study adopted general diagnostic criteria for dystonia. Inclusion and exclusion criteria proved heterogeneous across trials and were defined only in 108 studies, mainly considering age or the phenomenological pattern of muscle involvement.Conclusion: The review showed lack of consolidated diagnostic criteria and non-uniformity of eligibility criteria for CD across clinical trials. There is need to move beyond clinical judgement as diagnostic criterion for selecting participants. New trials assessing specific CD patient subgroups or comparing medical and surgical procedures will need grounds that are more consistent

Defective Somatosensory Inhibition and Plasticity Are Not Required to Develop Dystonia

Background: Dystonia may have different neuroanatomical substrates and pathophysiology. This is supported by studies on the motor system showing, for instance, that plasticity is abnormal in idiopathic dystonia, but not in dystonia secondary to basal ganglia lesions. Objective: The aim of this study was to test whether somatosensory inhibition and plasticity abnormalities reported in patients with idiopathic dystonia also occur in patients with dystonia caused by basal ganglia damage. Methods: Ten patients with acquired dystonia as a result of basal ganglia lesions and 12 healthy control subjects were recruited. They underwent electrophysiological testing at baseline and after a single 45-minute session of high-frequency repetitive somatosensory stimulation. Electrophysiological testing consisted of somatosensory temporal discrimination, somatosensory-evoked potentials (including measurement of early and late high-frequency oscillations and the spatial inhibition ratio of N20/25 and P14 components), the recovery cycle of paired-pulse somatosensory-evoked potentials, and primary motor cortex short-interval intracortical inhibition. Results: Unlike previous reports of patients with idiopathic dystonia, patients with acquired dystonia did not differ from healthy control subjects in any of the electrophysiological measures either before or after high-frequency repetitive somatosensory stimulation, except for short-interval intracortical inhibition, which was reduced at baseline in patients compared to control subjects. Conclusions: The data show that reduced somatosensory inhibition and enhanced cortical plasticity are not required for the clinical expression of dystonia, and that the abnormalities reported in idiopathic dystonia are not necessarily linked to basal ganglia damage. \ua9 2020 International Parkinson and Movement Disorder Society