Videoconferencing Software Options for Telemedicine: A Review for Movement Disorder Neurologists.

Background: The use of telemedicine has increased to address the ongoing healthcare needs of patients with movement disorders. Objective: We aimed to describe the technical and basic security features of the most popular telemedicine videoconferencing software. Methods: We conducted a systematic review of articles/websites about "Telemedicine," "Cybersecurity," and "Videoconferencing software." Technical capabilities and basic security features were determined for each videoconferencing software. Results: Twenty-six videoconferencing software programs were reviewed, 13 (50.0%) were specifically designed for general healthcare, and 6/26 (23.0%) were compliant with European and US regulations. Overall technical and security information were found in 5/26 software (19.2%), including Microsoft Teams, Google Hangout, Coviu, Doxy.me, and Thera platforms. Conclusions: Detailed information about technical capabilities and data security of videoconferencing tools is not easily and openly retrievable. Our data serves as a guide for practitioners seeking to understand what features should be examined when choosing software and what options are available.

Global Survey on Telemedicine Utilization for Movement Disorders During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic restricted usual healthcare management for movement-disorders patients, with a consequent upsurge in telemedicine to bridge the gap. OBJECTIVE: To assess global telemedicine usage in the context of the pandemic. METHODS: The Movement Disorder Society (MDS) Telemedicine Study Group surveyed telemedicine experts from 40 countries across all continents in March-April 2020. Four domains of telemedicine were assessed: legal regulations, reimbursement, clinical use, and barriers; comparing emerging responses to the pandemic versus the baseline scenario. RESULTS: All forms of telemedicine for movement disorders increased globally, irrespective of country income categorization, as an immediate response to the pandemic. This was aided by widespread availability of technology and updated government regulations. However, privacy concerns, lack of reimbursement, limited access, and lack of telemedicine training were barriers highlighted worldwide. CONCLUSIONS: Questions remain about the longevity and extent of changes in regulations and reimbursement regarding telemedicine in the aftermath of the pandemic. © 2020 International Parkinson and Movement Disorder Society.

Historias de la niñez enferma. El caso del primer hospital marítimo de América Latina. Buenos Aires 1893-1945 / Histories of a sick childhood. The case of the first maritime hospital in Latin America. Buenos Aires 1893-1945

El objetivo de este artículo es reflexionar sobre los "niños tuberculosos", "débiles" o "pre-tuberculosos" que fueron derivados e internados en el Hospital Marítimo de la provincia de Buenos Aires (Argentina) entre fines del siglo XIX y mediados del XX. Se analiza el universo individual de la enfermedad, mostrando que la infancia que padeció anomalías y discapacidades en sus cuerpos no fue objeto de las mismas atenciones y protecciones de las que gozaron el resto de las infancias durante el período estudiado

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Transdermal Rotigotine Improves Sleep Fragmentation in Parkinson's Disease: Results of the Multicenter, Prospective SLEEP-FRAM Study.

Sleep disturbances occur frequently in patients with Parkinson's disease (PD). The aim of this study was to investigate the effects of rotigotine on sleep fluctuations in a sample of PD patients with self-reported complaints of nocturnal awakenings. This prospective, open-label, observational, and multicenter study enrolled consecutive outpatients with PD and administered rotigotine (mean dose 8.9 mg/day) for 3 months. The primary endpoint was the change from baseline in sleep fragmentation, assessed using the sleep maintenance subscale score of the Parkinson's Disease Sleep Scale (PDSS). The newly designed Parkinson's Disease Sleep Fragmentation Questionnaire (PD-SFQ) was used to measure other sleep parameters. A total of 62 patients were enrolled (mean age 70.2 years; 66% male). At 3 months, rotigotine significantly improved sleep fragmentation from baseline on the PDSS-2 sleep maintenance subscale (from 3.4 ± 0.9 to 1.9 ± 1.4; P < 0.0001). Rotigotine also significantly improved nocturnal motor symptoms (P < 0.0001), restless legs-like symptoms (P < 0.005), and nocturia (P = 0.004). Rotigotine significantly improved self-reported complaints of sleep fragmentation in PD patients and could be a useful treatment to improve this specific sleep problem in PD. However, these results are based on a small and clinically heterogeneous sample so they must be taken cautiously.

The natural history of multiple system atrophy: a prospective European cohort study.

BACKGROUND: Multiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA. METHODS: Patients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test. FINDINGS: 141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56·2 (SD 8·4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9·8 years (95% CI 8·1-11·4). The parkinsonian variant of MSA (hazard ratio [HR] 2·08, 95% CI 1·09-3·97; p=0·026) and incomplete bladder emptying (HR 2·10, 1·02-4·30; p=0·044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74% (12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0·68, 0·5-0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1-10·2; p=0·03) predicted rapid UMSARS progression. Sample size estimation showed that an interventional trial with 258 patients (129 per group) would be able to detect a 30% effect size in 1-year UMSARS motor examination decline rates at 80% power. INTERPRETATION: Our prospective dataset provides new insights into the evolution of MSA based on a follow-up period that exceeds that of previous studies. It also represents a useful resource for patient counselling and planning of multicentre trials.

G2019S LRRK2 mutation causing Parkinson's disease without Lewy bodies.

The G2019S leucine-rich repeat kinase 2 gene (LRRK2) mutation has been identified in a significant proportion of familial and sporadic cases of Parkinson's disease (PD). Until now, information on the neuropathological changes associated with the G2019S LRRK2 mutation has been sparse. We report a 77-year-old patient who presented with a 14 year history of PD but, unexpectedly, histopathological examination disclosed mild neuronal loss in the substantia nigra without α-synuclein, tau or ubiquitin cytoplasmic inclusions. A G2019S LRRK2 mutation was eventually detected. The present case confirms that clinical PD caused by G2019S mutations can be associated with non-specific nigral degeneration without Lewy.

Red flags for multiple system atrophy.

The clinical diagnosis of multiple system atrophy (MSA) is fraught with difficulty and there are no pathognomonic features to discriminate the parkinsonian variant (MSA-P) from Parkinson's disease (PD). Besides the poor response to levodopa, and the additional presence of pyramidal or cerebellar signs (ataxia) or autonomic failure as major diagnostic criteria, certain other clinical features known as "red flags" or warning signs may raise the clinical suspicion of MSA. To study the diagnostic role of these features in MSA-P versus PD patients, a standardized red flag check list (RFCL) developed by the European MSA Study Group (EMSA-SG) was administered to 57 patients with probable MSA-P and 116 patients with probable PD diagnosed according to established criteria. Those red flags with a specifity over 95% were selected for further analysis. Factor analysis was applied to reduce the number of red flags. The resulting set was then applied to 17 patients with possible MSA-P who on follow-up fulfilled criteria of probable MSA-P. Red flags were grouped into related categories. With two or more of six red flag categories present specificity was 98.3% and sensitivity was 84.2% in our cohort. When applying these criteria to patients with possible MSA-P, 76.5% of them would have been correctly diagnosed as probable MSA-P 15.9 (+/-7.0) months earlier than with the Consensus criteria alone. We propose a combination of two out of six red flag categories as additional diagnostic criteria for probable MSA-P.

Screening for the LRRK2 G2019S and codon-1441 mutations in a pathological series of parkinsonian syndromes and frontotemporal lobar degeneration.

BACKGROUND: The neuropathology associated with LRRK2 mutations is heterogeneous but Lewy body (LB) type pathology is the most common substrate encountered. While the prevalence of LRRK2 mutations has been extensively studied in Parkinson's disease (PD), limited information is available on the frequency of LRRK2 mutations in dementia with Lewy bodies (DLB) and in other pathological conditions associated with these mutations, such as non-specific nigral degeneration without LB, tau-immunopositive neurofibrillary tangle pathology, and ubiquitin-positive neuronal inclusions resembling those observed in a subtype of frontotemporal lobar degeneration (FTLD-U). OBJECTIVE: To further investigate the neuropathology associated with LRRK2 mutations. METHODS: We have screened for the LRRK2 G2019S and codon-1441 (R1441G/C/H) mutations in 110 cases from a Spanish Brain Bank, which include: 66 synucleinopathies (33 PD, 25 DLB and 8 multiple system atrophy cases), 29 tauopathies (21 progressive supranuclear palsy, 3 corticobasal degeneration and 5 tau-positive FTLD cases), 3 cases of non-specific nigral degeneration and 12 tau-negative FTLD (9 FTLD-U and 3 dementia lacking distinctive histology cases). RESULTS: The G2019S mutation was found in two cases: One case had a clinical and pathological diagnosis of PD and the other suffered from typical PD and on neuropathological examination had non-specific nigral degeneration without LB. A synonymous variant (R1441R; c.4323C>T) was detected in another PD case. CONCLUSIONS: In this brain bank-based series, LRRK2 G2019S mutation occurred in patients with parkinsonism associated with either typical brainstem LB pathology or non-specific nigral degeneration. LRRK2 mutations were not encountered in other neurodegenerative disorders associated with synuclein and tau deposition.

Relevance of COX-2 gene expression in dementia with lewy bodies associated with Alzheimer pathology.

The aim of the present study was to investigate whether cyclooxygenase-2 (COX-2) expression is involved in the pathogenesis of neurodegeneration in dementia with Lewy bodies (DLB) by measuring COX-2 mRNA and protein expression in frontal cortex and substantia nigra pars compacta of DLB and control human brains. DLB cases were classified as pure form or common form according to the absence or the presence of Alzheimer pathology including neurofibrillary tangles and amyloid deposits by Braak staging. Using Western Blot and Real-time Polymerase chain reaction (PCR) analysis, we have shown that cortical COX-2 protein levels were decreased in DLB cases (P < 0.01). However, no differences in nigral COX-2 mRNA expression were observed between control and DLB cases. In conclusion, the present results suggest that in DLB nigral COX-2 mRNA expression does not correlate with dopaminergic neurodegeneration and that the slight changes observed in the common type are probably due to the concomitant AD pathology.

Cerebrospinal fluid hypocretin-1 levels in multiple system atrophy.

Hypocretin (orexin) cerebrospinal fluid (CSF) levels have been previously found normal or decreased in Dementia with Lewy bodies and Parkinson disease, two synucleinopathies commonly associated with excessive daytime sleepiness (EDS). We evaluated CSF hypocretin-1 levels in 15 patients with moderately severe multiple system atrophy (MSA), another synucleinopathy where sleep disorders occur frequently and EDS has been reported, performing additional electrophysiological studies in 5 of them to assess the presence of EDS and sleep onset REM (SOREM) periods. Despite relatively low sleep efficiencies in nocturnal sleep, mean sleep latencies in the Multiple Sleep Latency Test were normal with no SOREM periods. All patients had CSF hypocretin-1 levels in the normal range (>200 pg/mL) suggesting that the hypocretin system is not altered in MSA, at least in patients with a moderately severe disease.

Safety and tolerability of growth hormone therapy in multiple system atrophy: a double-blind, placebo-controlled study.

The objective of this study was to investigate tolerability and possible neurotrophic effects of growth hormone (GH) in treatment of multiple system atrophy (MSA). In this double-blind pilot study, MSA patients were randomized to recombinant human growth hormone (r-hGH, n = 22), 1 mg every second day (6 months) followed by alternating daily injections of 1 mg and 0.5 mg (6 months), or matched placebo (n = 21). Safety analysis demonstrated no obvious between-group differences. In both groups, there was progressive worsening of Unified Parkinson's Disease Rating Scale total score, which tended to be less in r-hGH-treated patients (12.9% at 6 months, 25.3% at 12 months) than in placebo (17.0% and 35.7%). Similarly, there was a trend to less worsening in Unified MSA Rating Scale total score with r-hGH (13.2% and 21.2%) than with placebo (21.1% and 36.5%). Cardiovascular reflex autonomic testing also tended to show less deterioration with r-hGH than with placebo at 12 months. However, 95% CI did not indicate treatment differences for any efficacy measures. In conclusion, r-hGH administration in MSA patients for up to 1 year appears safe and might influence disease symptoms, signs and, possibly, progression. The results support further studies utilizing higher doses in more patients.

G2019S LRRK2 mutation causing Parkinson's disease without Lewy bodies.

The G2019S leucine-rich repeat kinase 2 gene (LRRK2) mutation has been identified in a significant proportion of familial and sporadic cases of Parkinson's disease (PD). Until now, information on the neuropathological changes associated with the G2019S LRRK2 mutation has been sparse. We report a 77-year-old patient who presented with a 14 year history of PD but, unexpectedly, histopathological examination disclosed mild neuronal loss in the substantia nigra without alpha-synuclein, tau or ubiquitin cytoplasmic inclusions. A G2019S LRRK2 mutation was eventually detected. The present case confirms that clinical PD caused by G2019S mutations can be associated with non-specific nigral degeneration without Lewy bodies.

Health-related quality of life in multiple system atrophy.

Although multiple system atrophy (MSA) is a neurodegenerative disorder leading to progressive disability and decreased life expectancy, little is known about patients' own evaluation of their illness and factors associated with poor health-related quality of life (Hr-QoL). We, therefore, assessed Hr-QoL and its determinants in MSA. The following scales were applied to 115 patients in the European MSA-Study Group (EMSA-SG) Natural History Study: Medical Outcome Study Short Form (SF-36), EQ-5D, Beck Depression Inventory (BDI), Mini-Mental state examination (MMSE), Unified MSA Rating Scale (UMSARS), Hoehn & Yahr (H&Y) Parkinson's disease staging scale, Composite Autonomic Symptom Scale (COMPASS), and Parkinson's Disease Sleep Scale (PDSS). Forty-six percent of patients had moderate to severe depression (BDI > or = 17); Hr-QoL scores on the SF-36 and EQ-5D were significantly impaired. Pain, the only domain with similar scores in MSA and published PD patients, was reported more frequently in patients with MSA-P (predominantly parkinsonian motor subtype) than MSA-C (predominantly cerebellar motor subtype; 76% vs. 50%; P = 0.005). Hr-QoL scores correlated most strongly with UMSARS motor, COMPASS, and BDI scores but not with MMSE scores, age at onset, or disease duration. The COMPASS and UMSARS activities of daily living scores were moderate-to-strong predictors for the SF-36 physical summary score and the BDI and UMSARS motor scores for the SF-36 mental summary score. This report is the first study to show that Hr-QoL is significantly impaired in MSA. Although not all possible factors related to impaired Hr-QoL in MSA could be assessed, autonomic dysfunction, motor impairment, and depression were most closely associated with poor Hr-QoL, and therapeutic management, therefore, should concentrate upon these aspects of the disease.

Progression of multiple system atrophy (MSA): a prospective natural history study by the European MSA Study Group (EMSA SG).

The disease-specific Unified Multiple System Atrophy Rating Scale (UMSARS) has been developed recently and validated for assessing disease severity in multiple system atrophy (MSA). Here, we aimed at (1) assessing rates of disease progression in MSA and (2) validating UMSARS for sensitivity to change over time. Impairment was assessed at two time points 12 months apart using UMSARS Part I (historical review), UMSARS Part II (motor examination), as well as measures of global disease severity, including UMSARS Part IV, Hoehn and Yahr (HY) Parkinson's disease staging, Schwab England Activities of Daily Living (SE ADL), and a three-point global Severity Scale (SS3). Fifty patients (male:female ratio, 1:0.9; possible MSA, 16%; probable MSA, 84%; MSA-parkinsonian, 58%; MSA-cerebellar, 42%) were assessed twice with an interval of 12.3 months. UMSARS II scores progressed by 57.3% (P<0.0001) and UMSARS I scores by 35.6% (P<0.0001) in relation to the respective baseline scores with no differences between motor subtypes, diagnostic categories and gender. Significant inverse correlations between (1) UMSARS I or UMSARS II progression and (2) baseline disability measures (i.e., the respective UMSARS or SS3 scores) and disease duration were found. Furthermore, the increases in HY staging, SE ADL and SS3 correlated significantly with UMSARS I, UMSARS II, and UMSARS IV progression. This report is the first prospective study showing rapid annual UMSARS rates of decline in MSA. Our data contribute to the ongoing validation process of UMSARS, and they facilitate the planning and implementation of future neuroprotective intervention trials.

Severe cerebral white matter involvement in a case of dentatorubropallidoluysian atrophy studied at autopsy.

BACKGROUND: The pathophysiology of white matter involvement in dentatorubropallidoluysian atrophy (DRPLA) is controversial. Moreover, the clinical repercussions and evolution of these lesions have not been well documented. OBJECTIVE: To describe a case of DRPLA with severe cerebellar white matter involvement. DESIGN: Case report. Patient A 62-year-old woman with DRPLA. RESULTS: When the genetic diagnosis was made, the patient manifested severe ataxia, slight dysarthria, and subcortical cognitive impairment. Cranial magnetic resonance imaging showed atrophy of the cerebellum and brainstem and moderate high-intensity signal alterations in the periventricular cerebral white matter in T2-weighted sequences. In the following 5 years, she developed uncontrolled head movements associated with severe bruxism and tetraparesis, and became deeply demented. New magnetic resonance imaging showed severe diffuse cerebral white matter alterations in T2 sequences with only slight progression of brainstem and cerebellar atrophy. After her death at 67 years of age, the autopsy study showed diffuse myelin pallor, axonal preservation, and reactive astrogliosis in the cerebral white matter, with only mild atherosclerotic changes, and moderate neuronal loss in the cerebellum and brainstem. CONCLUSIONS: Leukoencephalopathy could be a prominent finding in some patients with DRPLA, explaining, at least in part, their clinical evolution. In our case, the disproportion between the severity of white matter damage and vascular changes does not support a cardinal role for ischemic mechanisms in leukoencephalopathy.

Unclassifiable parkinsonism in two European tertiary referral centres for movement disorders.

In view of reports on high frequencies of atypical parkinsonism from different parts of the world and in non-white communities in the United Kingdom, we have prospectively surveyed 1,000 consecutive patients with parkinsonism presenting to two European tertiary referral centres for movement disorders (London, UK, and Barcelona, Spain). The aims of our study were to assess in a cross-sectional, prospective manner the proportion of patients who could not be classified diagnostically, to identify the factors precluding classification, and to determine which diagnostic measures would increase the rate of classifiable cases. Diagnoses were established using published clinical diagnostic criteria for Parkinson's disease (PD) and for other conditions associated with parkinsonism. Twenty-nine patients in London and 25 in Barcelona were initially considered unclassifiable; nine could be classified after further investigations. Levodopa (L-dopa) responsiveness was found to have a pivotal role in establishing a clinical diagnosis in previously unclassifiable patients: In those 45 patients who remained unclassifiable, failure to respond to L-dopa without other exclusion criteria for PD was the most common finding in each centre. Our results show that 4.0 to 5.0% of parkinsonian patients presenting to specialist clinics in Western Europe cannot be categorised using currently available clinical diagnostic criteria for parkinsonian syndromes. Prolonged follow-up and neuropathological diagnosis will be needed to determine whether all these cases represent atypical presentations of established clinico-pathological entities or whether some represent unrecognised new disorders.

El papel de un banco de tejidos neurológicos en la investigación de las demencias / The role of a bank of neurological tissue in dementia research

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