Baduanjin Qigong Intervention by Telerehabilitation (TeleParkinson): A Proof-of-Concept Study in Parkinson's Disease.

Many people living with Parkinson's Disease (PD) face issues with healthcare services, including delays in diagnosis and treatment, as well as limited access to specialized care, including rehabilitation programs. Non-motor and motor signs and symptoms typically observed in people with PD, such as tremor, rigidity, postural instability, bradykinesia, and freezing are particularly disabling and have been associated with falls, fractures, hospitalizations, and a worse quality of life. Baduanjin Qigong (BDJ) programs have been proven potentially effective in improving physical outcomes and reducing the incidence of falls in PD. The aim of this case report, proof-of-concept, study was to explore the adherence, feasibility, acceptability, and potential efficacy of a BDJ program offered via telerehabilitation in people with PD living in the community. Two participants performed semi-supervised exercise sessions at home, twice a week (over eight weeks) using the TeraPlus platform. Adherence, adverse events, and feasibility (technical implementability), acceptability (patient satisfaction), patient-reported, self-reported, and performance outcomes were measured. Results were based on single-subject descriptive data, minimal detectable change, and anchor-based minimally important difference. Our findings suggest that the intervention seems feasible with no major technical issues or adverse events, and high adherence; acceptable (patient satisfaction); and potentially effective to improve markers of walking performance (gait speed, balance), and quality of life (activities of daily living, mobility).

Deep Brain Stimulation in Rare Inherited Dystonias.

BACKGROUND: Rare causes of inherited movement disorders often present with a debilitating phenotype of dystonia, sometimes combined with parkinsonism and other neurological signs. Since these disorders are often resistant to medications, DBS may be considered as a possible treatment. METHODS: Patients with identified genetic diseases (ataxia-telangiectasia, chorea-achantocytosis, dopa-responsive dystonia, congenital nemaline myopathy, methylmalonic aciduria, neuronal ceroid lipofuscinosis, spinocerebellar ataxia types 2 and 3, Wilson's disease, Woodhouse-Sakati syndrome, methylmalonic aciduria, and X trisomy) and disabling dystonia underwent bilateral GPi DBS (bilateral thalamic Vim nucleus in 1 case). The primary outcome was the difference in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) between baseline, 1 year and last available follow-up. Preoperative factors such as age at surgery, disease duration at surgery, proportion of life lived with dystonia and severity of dystonia were correlated to the primary outcome. RESULTS: Eleven patients were operated between February 2003 and December 2013. Age and duration of disease at time of surgery were 30 ± 19 and 12.5 ± 15.7 years, respectively. DBS effects on dystonia severity were variable but overall marginally effective, with a mean improvement of 7.9% (p = 0.39) at 1-year follow-up and 16.7% (p = 0.46) at last follow-up (mean 47.3 ± 19.9 months after surgery). No preoperative factors were identified to predict the surgical outcome. CONCLUSION: Our findings support the current knowledge that DBS is modestly effective in treating rare inherited dystonias with a combined phenotype. However, the BFMDRS might not be the best tool to measure outcome in these severely affected patients.

What is a clinically important change in the Unified Dyskinesia Rating Scale in Parkinson's disease?

INTRODUCTION: Dyskinesia remain a significant problem in Parkinson Disease (PD). The translation process of novel drug targets for dyskinesia has proven difficult with several failures at phase III level. Determining the 'clinically important change' (CIC) for dyskinesia rating scales in phase II clinical trials may assist in optimizing drug development of new anti-dyskinetic treatments. We used a standard phase IIa acute levodopa infusion paradigm to determine for the first time the CIC for dyskinesia using the new UDysRS. METHODS: We performed a randomized, double-blind, placebo-controlled crossover study with eleven PD patients with stable bothersome dyskinesia. We used the following patient-reported clinically important events as CIC anchors: onset, maximum intensity, remission of dyskinesia. Objective dyskinesia scores using the UDysRS part III Impairment were determined at these same events by blinded video-rating. The CIC was determined using the 'within-patient' score change and a sensitivity- and specificity-based approach. RESULTS: Patients were most aware of 'onset of dyskinesia', followed by 'remission of dyskinesia'. An 11.1-point median change (UDysRS Part III Impairment, p < 0.0001) was the CIC for patient-reported remission of dyskinesia from a practically defined-OFF state. A 2.32-point change (UDysRS Part III Impairment) had the best specificity and sensitivity to distinguish between patient-reported remission and perception of dyskinesia. CONCLUSIONS: In this study, we provide the first report of a CIC for the UDysRS Part III Impairment. Early knowledge of a CIC may help inform the decision to advance into phase III trials and contribute for a higher yield of success in finding new anti-dyskinetic treatments.

Behavioral effects of levodopa.

In recent years, levodopa-induced behavioral changes have received increased attention in the medical literature and in clinical practice. The spectrum of these symptoms includes non-motor fluctuations with neuropsychiatric symptoms, compulsive behaviors such as punding, dopamine dysregulation syndrome, and impulse control disorders, psychosis and hallucinations, as well as hypomania and mania. Despite knowledge of the clinical features associated with these behaviors, many of them are probably underdiagnosed. Although the mechanisms underlying behavioral symptoms are still incompletely understood, recent data from imaging and pathological studies have increased our understanding and guided new treatment strategies. Appropriate management remains challenging, because reduction of levodopa (l-dopa) and dopaminergic treatment is often recommended; however, doses required for control of motor symptoms may still induce behavioral changes. Newer modes of delivery of dopaminergic treatment, deep brain stimulation, and nondopaminergic agents may either provide alternatives for treatment of these behavioral problems or permit treatment of parkinsonism with less risk of these behavioral disorders.

Emerging drugs for levodopa-induced dyskinesia.

INTRODUCTION: Levodopa continues to be the main symptomatic therapy for clinical features of Parkinson's disease. However, prolonged use leads to motor complications, including levodopa-induced dyskinesia (LID). This has debilitating impact on the patients and is a significant challenge for the treating physician. There are currently limited pharmacological options for reducing established LID without causing side effects. Drugs to prevent or delay LID are also an increasing part of the strategy to manage LID, but have yet to show promise. Agents that allow levodopa to be used effectively, without inducing LID, are the goal of current research strategies. AREAS COVERED: LID occurs due to significant modifications in the basal ganglia circuitry, probably related to the chronic, pulsatile stimulation of striatal dopaminergic receptors by levodopa, as well as altered non-dopaminergic neurotransmitter system signaling pathways. Novel treatments that either result in continuous dopaminergic receptor stimulation, levodopa 'sparing strategies' or non-dopaminergic targets, including glutamatergic, serotonergic, adenosine, adrenergic and cholinergic neurotransmission are thus the main treatment options and the focus of this manuscript. Randomized controlled trials in progress (ClinicalTrials.org) or recently published articles are included. EXPERT OPINION: The success of future therapeutic approaches will depend on the potential success of translational research.

Vascular cognitive impairment: most useful subtests of the Montreal Cognitive Assessment in minor stroke and transient ischemic attack.

BACKGROUND/AIMS: Cognitive impairment is frequent in cerebrovascular disease but often remains undetected. The Montreal Cognitive Assessment (MoCA) has been proposed in this context. Our aim was to evaluate the MoCA and its subtests in cerebrovascular disease. METHODS: We assessed 386 consecutive patients with minor stroke (National Institutes of Health Stroke Score <4) or transient ischemic attack at 3 months. The MoCA and the modified Rankin Scale (mRS) were administered. Computed tomography (CT) scans were assessed for stroke and white matter changes. An unfavorable functional outcome was defined as mRS >1. RESULTS: The prevalence of cognitive impairment (cutoff of 26) was 55% using the MoCA and 13% using the MMSE. In a multivariate analysis, MoCA <26 was associated with the outcome (OR 3.00, CI 1.78-5.03), as were remote lacunar stroke on CT and white matter changes of at least moderate severity. Five subtests (5-word recall, word list generation, trail-making, abstract reasoning and cube copy) formed an optimal short MoCA with 6/10 or less showing a sensitivity of 91% and a specificity of 83%. CONCLUSION: This study extends the utility of the MoCA to milder forms of cerebrovascular disease. The MoCA is associated with the 3-month functional outcome. Five subtests may constitute an optimal brief tool in vascular cognitive impairment.

Troponin elevation predicts atrial fibrillation in patients with stroke or transient ischemic attack.

BACKGROUND: Atrial fibrillation (AF) is a major cause of ischemic stroke. Cardiac troponin (cTnI) is a marker of myocardial damage and may predict arrhythmia. We sought to determine if increased cTnI levels were a predictor of new-onset AF in ischemic stroke or patients with transient ischemic attack (TIA). METHODS: Consecutive patients who presented to Charles-Lemoyne Hospital between October 2006 and November 2010 with a diagnosis of acute ischemic stroke or TIA, without a history of AF, with a baseline measurement of cTnI were included in the study. The primary outcome was new-onset AF on 24-hour Holter measurement within 1 week of admission in patients without AF on the baseline electrocardiogram (ECG). Secondary outcomes included AF on Holter measurement, death, myocardial infarction (MI), and stroke within 3 months. RESULTS: A total of 408 patients were included. Forty-six patients (11.3%) had elevated cTnI levels. These patients were older and had a higher prevalence of coronary artery disease and diabetes. AF on baseline ECG or 24-hour Holter measurement was present in 51 patients (12.5%) and was more frequent among patients with increased cTnI levels compared to patients with normal cTnI levels (34.7% vs 9.7%; P = .004 multivariate analysis). Elevated cTnI levels also predicted the composite outcome of stroke, MI, and death at 3 months (50.0% vs 16.1%; P = .0001). CONCLUSIONS: cTnI elevation predicts new-onset AF on 24-hour Holter measurement in patients with acute ischemic stroke or TIA and may indicate a poorer prognosis and a higher risk of stroke, MI, and death at 3 months.

Hemimegalencephaly in an adult with normal intellectual function and mild epilepsy.

Hemimegalencephaly is a rare congenital brain malformation, usually associated with mental retardation, * refractory epilepsy, and progressive neurological deficits. We report the case of a 19-year-old female with de novo diagnosis of right hemimegalencephaly, normal intellectual function, and history of non-refractory epilepsy. She presented with weakness and paraesthesia of the left leg. Extensive evaluation was negative for other causes for the weakness, which was attributed to progressive neurological damage secondary to long-standing subclinical epileptic activity in the hemimegalencephalic hemisphere. This patient underwent a cerebral fluorodeoxyglucose positron emission tomography that demonstrated near-normal cortical metabolism. Formal neuropsychological evaluation revealed mild deficits in the affected hemisphere, but preserved general intellectual function. This case illustrates the wide phenotypic variations in this condition and raises questions about prenatal counselling for hemimegalencephaly.