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Abstract Background The Freezing of Gait Questionnaire (FOGQ) was developed in response to the difficulties of observing and quantifying freezing of gait (FOG) clinically as well as in laboratory settings. However, as the FOGQ is a clinician-administered patient-reported rating scale it cannot be used in postal surveys. Here we report the development and measurement properties of a self-administered version of the FOGQ (FOGQsa). Methods A clinical sample and a postal survey sample of non-demented people with Parkinson's disease (PD; total n = 225) completed the FOGQsa and questionnaires concerning physical functioning (PF) and fall-related self efficacy (FES). Additional questions (No/Yes) regarded previous falls and whether they were afraid of falling. The clinical sample was also assessed with the Unified PD Rating Scale (UPDRS). Thirty-five participants completed FOGQsa and were also assessed with the original version (FOGQ) in a clinical interview. Results There were no differences (P = 0.12) between FOGQ (median, 10; q1-q3, 2-14) and FOGQsa (median, 8; 2-14) scores. The Spearman (rs) and intra-class correlations between the two were 0.92 and 0.91 (95% CI, 0.82-0.95), respectively. For FOGQsa, corrected item-total correlations ranged between 0.68-0.89. Reliability was 0.93 (95% CI, 0.91-0.94). FOGQsa scores correlated strongest with UPDRS Item 14 (Freezing; rs, 0.76) and with FES (rs, -0.74). The weakest correlation was found with age (rs, 0.14). Fallers scored significantly (p < 0.001) higher on FOGQsa compared to non-fallers, median scores 8 (q1-q3, 4-14) versus 2 (0-7). Those expressing a fear of falling scored higher (p < 0.001) than those who did not, median scores 2 (0-7) versus 6 (2-14). Conclusions The present findings indicate that the FOGQsa is as reliable and valid as the original interview administered FOGQ version. This has important clinical implications when investigating FOG in large scale studies.

Hereditary ataxia is a heterogeneous group of complex neurological disorders. Next-generation sequencing methods have become a great help in clinical diagnostics, but it may remain challenging to determine if a genetic variant is the cause of the patient's disease. We compiled a consecutive single-center series of 87 patients from 76 families with progressive ataxia of known or unknown etiology. We investigated them clinically and genetically using whole exome or whole genome sequencing. Test methods were selected depending on family history, clinical phenotype, and availability. Genetic results were interpreted based on the American College of Medical Genetics criteria. For high-suspicion variants of uncertain significance, renewed bioinformatical and clinical evaluation was performed to assess the level of pathogenicity. Thirty (39.5%) of the 76 families had received a genetic diagnosis at the end of our study. We present the predominant etiologies of hereditary ataxia in a Swedish patient series. In two families, we established a clinical diagnosis, although the genetic variant was classified as "of uncertain significance" only, and in an additional three families, results are pending. We found a pathogenic variant in one family, but we suspect that it does not explain the complete clinical picture. We conclude that correctly interpreting genetic variants in complex neurogenetic diseases requires genetics and clinical expertise. The neurologist's careful phenotyping remains essential to confirm or reject a diagnosis, also by reassessing clinical findings after a candidate genetic variant is suggested. Collaboration between neurology and clinical genetics and combining clinical and research approaches optimizes diagnostic yield., (© 2023. The Author(s).)

Background: The Scale for Outcomes in Parkinson's disease for Autonomic symptoms (SCOPA-AUT) is an instrument intended to assess overall and domain-specific autonomic symptom burden. In this study the SCOPA-AUT is translated into Swedish and its measurement properties are assessed., Methods: Following translation the SCOPA-AUT was field-tested regarding comprehensibility, relevance, and respondent burden (n = 20). It was then tested according to Rasch measurement theory using data from 242 persons with PD, of whom 162 completed SCOPA-AUT at baseline and 1-2 years later, giving a total of 404 data points for analysis., Results: The Swedish SCOPA-AUT took a mean of 6 min to complete and was considered easy to use and relevant by respondents. SCOPA-AUT exhibited acceptable Rasch model fit, represents more severe levels of dysautonomia than that reported by the sample, and response categories were not working as expected for 17 items. Local dependency was identified and followed a pattern resembling the suggested subscales. Accounting for the subscale structure eliminated local dependency and reduced the initially inflated reliability from 0.81 to 0.68., Conclusions: The SCOPA-AUT is useful as a clinical check-list but requires further developmental work in order to meet more rigorous standards as an outcome measurement instrument., (© 2022. The Author(s).)

Background: Orthostatic hypotension (OH) is common among older people and in particular in conditions like Parkinson's disease (PD). The OH Questionnaire (OHQ) has been proposed as a useful patient-reported assessment tool consisting of the OH Symptom Assessment (OHSA), OH Daily Activity Scale (OHDAS), and a composite score., Aims of the Study: To translate the OHQ into Swedish and assess its psychometric properties., Methods: Following forward-backward translation, the Swedish OHQ was field-tested (n = 6) for relevance, comprehensibility, and respondent burden. It was then tested regarding scaling assumptions, targeting, reliability, and construct validity in persons with PD (n = 27) and multiple system atrophy (n = 2)., Results: The Swedish OHQ was considered relevant and easy to use, with a mean completion time of 5.3 min. Scaling assumptions were acceptable for OHSA and OHDAS (corrected item-total correlations, .30-.67) but not for the total score (.12-.69). Floor/ceiling effects were ≤3.4% and reliability was >.64. Construct validity was supported by expected correlations with the SCOPA-AUT, RAND-36, and blood pressure measurements., Conclusions: The Swedish OHQ was well received, and psychometric results suggest that the OHQ (particularly the OHDAS) is a useful tool for OH assessment in parkinsonian disorders. Further testing in larger samples is needed., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: IRL752 is a novel small-molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex., Objective: The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia., Methods: Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients' regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days., Results: A total of 32 patients were randomized to treatment, and 29 patients completed the 4-week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2-hour postdose plasma concentration of about 4 μM on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa., Conclusions: IRL752 appears to be safe and well tolerated for a 4-week treatment in patients with Parkinson's disease and dementia. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Introduction: Kaczyńska et al. reported a family with myoclonus-dystonia (M-D) caused by a truncating SGCE mutation, in which two members had epilepsy. Further, patients had mild psychiatric and developmental deficits., Clinical Reflections: Characteristic motor features of M-D include myoclonus, dystonia and tremor. A wide range of additional disease manifestations are known. A few patients with M-D have seizures., Clinical Implications: Altered neuronal excitability has been found in the pathogenesis of M-D. This may explain the partial effectiveness of antiepileptics and a lower seizure threshold, and could encourage trials of other membrane stabilisers. Careful clinical observations of seemingly well-known diseases remain important.

In advanced stages of Parkinson's disease, serotonergic terminals take up L-DOPA and convert it to dopamine. Abnormally released dopamine may participate in the development of L-DOPA-induced dyskinesias. Simultaneous activation of 5-HT1A and 5-HT1B receptors effectively blocks L-DOPA-induced dyskinesias in animal models of dopamine depletion, justifying a clinical study with eltoprazine, a 5-HT1A/B receptor agonist, against L-DOPA-induced dyskinesias in patients with Parkinson's disease. A double-blind, randomized, placebo-controlled and dose-finding phase I/IIa study was conducted. Single oral treatment with placebo or eltoprazine, at 2.5, 5 and 7.5 mg, was tested in combination with a suprathreshold dose of L-DOPA (Sinemet®) in 22 patients with Parkinson's disease (16 male/six female; 66.6 ± 8.8 years old) with L-DOPA-induced dyskinesias. A Wilcoxon Signed Ranked Test was used to compare each eltoprazine dose level to paired randomized placebo on the prespecified primary efficacy variables; area under the curve scores on Clinical Dyskinesia Rating Scale for 3 h post-dose and maximum change of Unified Parkinson's Disease Rating Scale part III for 3 h post-dose. Secondary objectives included effects on maximum Clinical Dyskinesia Rating Scale score, area under the curve of Rush Dyskinesia Rating Scale score for 3 h post-dose, mood parameters measured by Hospital Anxiety Depression Scale and Montgomery Asberg Depression Rating Scale along with the pharmacokinetics, safety and tolerability profile of eltoprazine. A mixed model repeated measures was used for post hoc analyses of the area under the curve and peak Clinical Dyskinesia Rating Scale scores. It was found that serum concentrations of eltoprazine increased in a dose-proportional manner. Following levodopa challenge, 5 mg eltoprazine caused a significant reduction of L-DOPA-induced dyskinesias on area under the curves of Clinical Dyskinesia Rating Scale [-1.02(1.49); P = 0.004] and Rush Dyskinesia Rating Scale [-0.15(0.23); P = 0.003]; and maximum Clinical Dyskinesia Rating Scale score [-1.14(1.59); P = 0.005]. The post hoc analysis confirmed these results and also showed an antidyskinetic effect of 7.5 mg eltoprazine. Unified Parkinson's Disease Rating Scale part III scores did not differ between the placebo and eltoprazine treatments. The most frequent adverse effects after eltoprazine were nausea and dizziness. It can be concluded that a single dose, oral treatment with eltoprazine has beneficial antidyskinetic effects without altering normal motor responses to L-DOPA. All doses of eltoprazine were well tolerated, with no major adverse effects. Eltoprazine has a favourable risk-benefit and pharmacokinetic profile in patients with Parkinson's disease. The data support further clinical studies with chronic oral eltoprazine to treat l-DOPA-induced-dyskinesias., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: We describe the clinical characteristics of a Swedish family with autosomal dominant cerebellar ataxia, sensory and autonomic neuropathy, additional neurological features and unknown genetic cause., Methods: Fourteen affected family members were identified. Their disorder was characterized by neurological examination, MRI, electroneurography, electromyography, MIBG-scintigraphy, and tilt-testing., Results: The disorder presented as a balance and gait disturbance starting between 16 and 47 years of age. Cerebellar ataxia progressed slowly over the course of decades, and MRI showed mild to moderate cerebellar atrophy. Sensory axonal polyneuropathy was the most prominent additional feature and occurred in all patients examined. Autonomic neuropathy caused pronounced orthostatic dysregulation in at least four patients. Several affected members showed muscle wasting, and mild upper or lower motor neuron signs were documented. Patients had no nystagmus but slow or hypometric horizontal saccades and ocular motor apraxia. Cognition remained unimpaired, and there were no non-neurological disease manifestations. The disorder affected men and women in successive generations in a pattern compatible with autosomal dominant inheritance without evidence of anticipation. A second family where 7 members had very similar symptoms was identified and its origin traced back to the same village in southern Sweden as that of the first family's ancestors. All relevant known genetic causes of cerebellar ataxia were excluded by a novel next-generation sequencing approach., Conclusion: We present two probably related Swedish families with a characteristic and novel clinical syndrome of cerebellar ataxia and sensory polyneuropathy. The study serves as a basis for the mapping of the underlying genetic cause., (Copyright © 2014 Elsevier Ltd. All rights reserved.)