Meredith Spindler

The past, present, and future of telemedicine for Parkinson's disease

Travel distance, growing disability, and uneven distribution of doctors limit access to care for most Parkinsons disease (PD) patients worldwide. Telemedicine, the use of telecommunications technology to deliver care at a distance, can help overcome these barriers. In this report, we describe the past, present, and likely future applications of telemedicine to PD. Historically, telemedicine has relied on expensive equipment to connect single patients to a specialist in pilot programs in wealthy nations. As the cost of video conferencing has plummeted, these efforts have expanded in scale and scope, now reaching larger parts of the world and extending the focus from care to training of remote providers. Policy, especially limited reimbursement, currently hinders the growth and adoption of these new care models. As these policies change and technology advances and spreads, the following will likely develop: integrated care networks that connect patients to a wide range of providers; education programs that support patients and health care providers; and new research applications that include remote monitoring and remote visits. Together, these developments will enable more individuals with PD to connect to care, increase access to expertise for patients and providers, and allow more‐extensive, less‐expensive participation in research.

Multimodal evaluation demonstrates in vivo 18 F-AV-1451 uptake in autopsy-confirmed corticobasal degeneration

in vivo evaluations of F-AV-1451 in patients with pathological confirmation. We report a multimodal evaluation of a 58-year-old male with autopsy-confirmed CBD. He participated in in vivo baseline (15 months pre-death) clinical, F-AV-1451 PET, F-florbetapir PET, MRI, and DTI and longitudinal (5 months pre-death) F-AV-1451 PET research studies (Online Resource 1). When enrolled in research, the patient met clinical criteria for progressive supranuclear palsy (Online Resource 2). Baseline F-AV-1451 (Fig. 1a) revealed the highest retention in deep grey matter areas commonly associated with CBD pathology [1], including bilateral substantia nigra, globus pallidus, and midbrain. Follow-up F-AV1451 revealed more visible retention in bilateral frontal and posterior temporal cortical regions along with midbrain and pons (Fig. 1b). A direct assessment of annualized change revealed a 1–9 % increase in F-AV-1451 retention, which was highest in the pons, medulla, and midbrain along with bilateral frontal and right temporo-parietal cortices (Fig. 1c). Baseline MRI (Fig. 2a) revealed predominantly reduced cortical grey matter in bilateral frontal cortex and right angular gyrus along with deep grey structures, including the midbrain, putamen, right globus pallidus, right caudate, and left hippocampus. White matter revealed increased mean diffusivity (a measure of white matter integrity) in the corpus callosum, bilateral tapetum, pontine crossing fibres, and right lateralized corticospinal tract, and posterior corona radiata. These observations are consistent with previously reported distributions of disease in CBD [6]. Spearman correlations revealed inverse associations between baseline F-AV-1451 and grey matter volume (rs = −0.209; p = 0.016; Fig. 2b) and mean diffusivity (rs = −0.329; p = 0.032; Fig. 2c). Furthermore, we Corticobasal degeneration (CBD) is characterized by 4-repeat misfolded tau (4Rtau) including astrocytic plaques, threads, and neuronal tangles [1]. F-AV-1451 is a PET radioligand that achieves in vivo binding in Alzheimer’s disease (AD) [8] and autoradiographic evidence of binding to paired helical filaments (PHFs) composed of 3-repeat misfolded tau (3Rtau) and 4Rtau characteristic of AD histopathology [4, 5, 7]. However, autoradiographic studies of F-AV-1451 on CBD postmortem tissue failed to demonstrate binding in cortical regions [5, 7], though there was minimal pathology in one study (<1.1 % tau-load) [7]. Another study suggests minimal, but present, autoradiographic binding of F-AV-1451 for 4Rtau [4]. Given mixed autoradiographic evidence in CBD, there is a need for

Globus pallidus interna deep brain stimulation for tardive dyskinesia: Case report and review of the literature

Tardive dyskinesia (TD) can be a disabling condition and is frequently refractory to medical therapy. Over the past decade there have been many reports of TD patients experiencing significant benefit with deep brain stimulation (DBS) of the globus pallidus interna (GPi). The growing literature on this treatment option for TD consists predominantly of case reports and series. The reported benefit ranges widely, but the majority of cases experienced at least a 50% improvement in symptoms. The anatomical distribution of dyskinesias has not clearly influenced outcome, though fixed postures appear less likely to improve than phasic movements. Onset of benefit can be immediate or take months, and benefit is sustained in most cases, for at least 6 months and up to several years. A wide variety of voltages, frequencies, and pulse widths have demonstrated efficacy. A small number of reports which examined psychiatric symptoms before and after surgery did not find any decline, and in some cases revealed improvement in mood. However, these overall positive results should be interpreted with caution, as the majority of reports lacked blinded assessments, control groups, or standardized therapy parameters. Finally, we present an illustrative case of refractory tardive dyskinesia treated with GPi-DBS with 5 years of follow-up and 4 accompanying video segments.

Laser light visual cueing for freezing of gait in Parkinson disease: A pilot study with male participants

Freezing of gait (FOG) is a debilitating feature of Parkinson disease (PD). In this pilot study, we sought to assess the efficacy of a rolling walker with a laser beam visual cue to treat FOG in PD patients. We recruited 22 subjects with idiopathic PD who experienced on- and off-medication FOG. Subjects performed three walking tasks both with and without the laser beam while on medications. Outcome measures included time to complete tasks, number of steps, and number of FOG episodes. A crossover design allowed within-group comparisons between the two conditions. No significant differences were observed between the two walking conditions across the three tasks. The laser beam, when applied as a visual cue on a rolling walker, did not diminish FOG in this study.

High patient satisfaction with telehealth in Parkinson disease: A randomized controlled study

Background:Parkinson disease (PD) is a complex neurodegenerative disorder that benefits from specialty care. Telehealth is an innovative resource that can enhance access to this care within a patient-centered framework. Research suggests that telehealth can lead to increased patient satisfaction, equal or better clinical outcomes, and cost savings, but these outcomes have not been well-studied in PD. Methods:We conducted a dual active-arm 12-month randomized controlled trial to assess patient satisfaction, clinical outcomes, travel burden, and health care utilization in PD using video telehealth for follow-up care with specialty providers. Telehealth visits took place either at a facility nearer to the patient (satellite clinic arm) or in the patients home (home arm). Each control group received usual in-person care. Patient satisfaction, assessed by quantitative questionnaires, was the primary outcome. Results:Eighty-six men were enrolled (home arm: 18 active, 18 control; satellite clinic arm: 26 active, 24 control) with a mean age of 73 years (range 42–87). There were no differences in baseline characteristics between the active group and the controls in each arm (p > 0.05). A significant difference in overall patient satisfaction was not found; however, high levels of patient satisfaction were found in all groups. Greater satisfaction for the telehealth modality was found in assessments of convenience and accessibility/distance. Clinical outcomes were similar between groups, travel burden was reduced using telehealth, and health care utilization was largely similar in both groups. Conclusions:As the need for PD subspecialty care increases, innovative patient-centered solutions to overcoming barriers to access, such as video telehealth, will be invaluable to patients and may provide high patient satisfaction.

National Randomized Controlled Trial of Virtual House Calls for People with Parkinson's Disease: Interest and Barriers

BACKGROUND Delivering specialty care remotely directly into peoples homes can enhance access for and improve the healthcare of individuals with chronic conditions. However, evidence supporting this approach is limited. MATERIALS AND METHODS Connect.Parkinson is a randomized comparative effectiveness study that compares usual care of individuals with Parkinsons disease in the community with usual care augmented by virtual house calls with a Parkinsons disease specialist from 1 of 18 centers nationally. Individuals in the intervention arm receive four virtual visits from a Parkinsons disease specialist over 1 year via secure, Web-based videoconferencing directly into their homes. All study activities, including recruitment, enrollment, and assessments, are conducted remotely. Here we report on interest, feasibility, and barriers to enrollment in this ongoing study. RESULTS During recruitment, 11,734 individuals visited the studys Web site, and 927 unique individuals submitted electronic interest forms. Two hundred ten individuals from 18 states enrolled in the study from March 2014 to June 2015, and 195 were randomized. Most participants were white (96%) and college educated (73%). Of the randomized participants, 73% had seen a Parkinsons disease specialist within the previous year. CONCLUSIONS Among individuals with Parkinsons disease, national interest in receiving remote specialty care directly into the home is high. Remote enrollment in this care model is feasible but is likely affected by differential access to the Internet.

Uncommon applications of deep brain stimulation in hyperkinetic movement disorders.

Background In addition to the established indications of tremor and dystonia, deep brain stimulation (DBS) has been utilized less commonly for several hyperkinetic movement disorders, including medication-refractory myoclonus, ballism, chorea, and Gilles de la Tourette (GTS) and tardive syndromes. Given the lack of adequate controlled trials, it is difficult to translate published reports into clinical use. We summarize the literature, draw conclusions regarding efficacy when possible, and highlight concerns and areas for future study. Methods A Pubmed search was performed for English-language articles between January 1980 and June 2014. Studies were selected if they focused primarily on DBS to treat the conditions of focus. Results We identified 49 cases of DBS for myoclonus-dystonia, 21 for Huntingtons disease, 15 for choreacanthocytosis, 129 for GTS, and 73 for tardive syndromes. Bilateral globus pallidus interna (GPi) DBS was the most frequently utilized procedure for all conditions except GTS, in which medial thalamic DBS was more common. While the majority of cases demonstrate some improvement, there are also reports of no improvement or even worsening of symptoms in each condition. The few studies including functional or quality of life outcomes suggest benefit. A limited number of studies included blinded on/off testing. There have been two double-blind controlled trials performed in GTS and a single prospective double-blind, uncontrolled trial in tardive syndromes. Patient characteristics, surgical target, stimulation parameters, and duration of follow-up varied among studies. Discussion Despite these extensive limitations, the literature overall supports the efficacy of DBS in these conditions, in particular GTS and tardive syndromes. For other conditions, the preliminary evidence from small studies is promising and encourages further study.

Daytime Sleepiness is Associated with Falls in Parkinson's Disease

Falls are frequent in Parkinsons disease (PD), and may be influenced by daytime sleepiness. We reviewed the records of 120 men with PD. Mean Epworth Sleepiness Scale (ESS) values were significantly different between non-fallers and fallers (6.0 vs. 9.7, p < 0.01). In multivariate analysis, ESS remained significantly associated with falls (OR 1.2, 95% CI 1.1-1.4, p = 0.02), along with cognitive impairment (OR 4.4 95% CI 1.0-18.7, p = 0.04) and postural instability/gait dysfunction (OR 1.6 95% CI 1.0-2.4, p = 0.03) in non-depressed patients. In conclusion, non-depressed PD patients are 20% more likely to fall for every one unit increase in the ESS measure of sleepiness.

CSF tau and amyloid-beta predict cerebral synucleinopathy in autopsied Lewy body disorders

Objective To test the association of antemortem CSF biomarkers with postmortem pathology in Lewy body disorders (LBD). Methods Patients with autopsy-confirmed LBD (n = 24) and autopsy-confirmed Alzheimer disease (AD) (n = 23) and cognitively normal (n = 36) controls were studied. In LBD, neuropathologic criteria defined Lewy body α-synuclein (SYN) stages with medium/high AD copathology (SYN + AD = 10) and low/no AD copathology (SYN − AD = 14). Ordinal pathology scores for tau, β-amyloid (Aβ), and SYN pathology were averaged across 7 cortical regions to obtain a global cerebral score for each pathology. CSF total tau (t-tau), phosphorylated tau at threonine181, and Aβ1-42 levels were compared between LBD and control groups and correlated with global cerebral pathology scores in LBD with linear regression. Diagnostic accuracy for postmortem categorization of LBD into SYN + AD vs SYN − AD or neocortical vs brainstem/limbic SYN stage was tested with receiver operating curves. Results SYN + AD had higher CSF t-tau (mean difference 27.0 ± 8.6 pg/mL) and lower Aβ1-42 (mean difference −84.0 ± 22.9 g/mL) compared to SYN − AD (p < 0.01, both). Increasing global cerebral tau and plaque scores were associated with higher CSF t-tau (R2 = 0.15–0.16, p < 0.05, both) and lower Aβ1-42 (R2 = 0.43–0.49, p < 0.001, both), while increasing cerebral SYN scores were associated with lower CSF Aβ1-42 (R2 = 0.31, p < 0.001) and higher CSF t-tau/Aβ1-42 ratio (R2 = 0.27, p = 0.01). CSF t-tau/Aβ1-42 ratio had 100% specificity and 90% sensitivity for SYN + AD, and CSF Aβ1-42 had 77% specificity and 82% sensitivity for neocortical SYN stage. Conclusions Higher antemortem CSF t-tau/Aβ1-42 and lower Aβ1-42 levels are predictive of increasing cerebral AD and SYN pathology. These biomarkers may identify patients with LBD vulnerable to cortical SYN pathology who may benefit from both SYN and AD-targeted disease-modifying therapies.

Longitudinal decline in speech production in Parkinson's disease spectrum disorders

&NA; We examined narrative speech production longitudinally in non‐demented (n = 15) and mildly demented (n = 8) patients with Parkinsons disease spectrum disorder (PDSD), and we related increasing impairment to structural brain changes in specific language and motor regions. Patients provided semi‐structured speech samples, describing a standardized picture at two time points (mean ± SD interval = 38 ± 24 months). The recorded speech samples were analyzed for fluency, grammar, and informativeness. PDSD patients with dementia exhibited significant decline in their speech, unrelated to changes in overall cognitive or motor functioning. Regression analysis in a subset of patients with MRI scans (n = 11) revealed that impaired language performance at Time 2 was associated with reduced gray matter (GM) volume at Time 1 in regions of interest important for language functioning but not with reduced GM volume in motor brain areas. These results dissociate language and motor systems and highlight the importance of non‐motor brain regions for declining language in PDSD. HighlightsSpeech was studied longitudinally in Parkinsons disease spectrum disorder (PDSD).Gray matter (GM) volume was assessed in motor and language‐related brain regions.Demented PDSD patients declined over time in fluency, grammar, and informativeness.Reduced GM volume in language‐associated brain regions predicted decline in speech.There was no association of language variables with reduced GMP in any motor areas.