Telemedicine in Neurological Disorders: Opportunities and Challenges.

Introduction: Telemedicine represents an emerging model for the assessment and management of various neurological disorders. Methods: We sought to discuss opportunities and challenges for the integration of telemedicine in the management of common and uncommon neurological disorders by reviewing and appraising studies that evaluate telemedicine as a means to facilitate the access to care, deliver highly specialized visits, diagnostic consultations, rehabilitation, and remote monitoring of neurological disorders. Results: Opportunities for telemedicine in neurological disorders include the replacement of or complement to in-office evaluations, decreased time between follow-up visits, reduction in disparities in access to healthcare, and promotion of education and training through interactions between primary care physicians and tertiary referral centers. Critical challenges include the integration of the systems for data monitoring with an easy-to-use, secure, and cost-effective platform that is both widely adopted by patients and healthcare systems and embraced by international scientific societies. Conclusions: Multiple applications may spawn from a model based on digitalized healthcare services. Integrated efforts from multiple stakeholders will be required to develop an interoperable software platform capable of providing not only a holistic approach to care but also one that reduces disparities in the access to care.

Factors Associated With the Place of Death in Huntington Disease: Analysis of Enroll-HD.

Background: Most people prefer to die at home. Hospice is the standard in end-of-life care for people with Huntington disease (HD), a neurodegenerative genetic disorder that affects people in middle adulthood. Yet, we have little knowledge regarding the place of death for people with HD. Therefore, the current state of knowledge limits HD clinicians' ability to conduct high-quality goals of care conversations. Objectives: We sought to determine the factors associated with the place of death in people with HD. Design: We obtained cross-sectional data from Enroll-HD and included participants with a positive HD mutation of 36 or more CAG repeats. Results: Out of 16,120 participants in the Enroll-HD study, 536 were reported as deceased. The mean age at death was 60. The leading place of death was home (29%), followed by the hospital (23%). The adjusted odds ratio (aOR) of dying at a skilled nursing facility was significantly lower for those partnered (aOR: 0.48, confidence interval [95% CI]: 0.26-0.86). The aOR for dying on hospice compared to home was increased in a person with some college and above (aOR: 2.40, 95% CI: 1.21-4.75). Conclusions: Our data further suggest that models that predict the place of death for serious illnesses do not appear to generalize to HD. The distribution in the places of death within HD was not uniform. Our findings may assist HD clinicians in communication during goals of care conversations.

Advance Care Planning and Health-Related Quality of Life in Huntington Disease: Results from a Multicenter National Study.

Objective: With Huntington disease (HD), a fatal neurodegenerative disease where the prevalence of suicidal thoughts and behavior (STB) remains elevated as compared to other neurological disorders, it is unknown whether STB and health-related quality of life (HRQoL) affect plans for the end of life or more broadly, advance care planning (ACP). Conversely, it is unknown whether ACP would provoke future changes to STB and HRQoL. Therefore, we sought to evaluate whether STB and HRQoL patient-reported outcomes (PROs) contribute to ACP and whether ACP relates to changes in STB and HRQoL at 24 months. Methods: HD-validated clinician- and patient-assessments (i.e., HRQoL PROs) were obtained at baseline enrollment, 12 and 24 months through our multi-center study (HDQLIFE™) throughout the United States among people with premanifest, early-stage, and late-stage manifest HD. We used linear mixed-effects models to determine the relationships between STB and HRQoL at baseline and HDQLIFE End of Life Planning at follow-up. Separate linear mixed-effects models were used to assess the relationship between HDQLIFE End of Life Planning at baseline, and HRQoL and STB at 12 and 24 months. False discovery rate adjustments were used to account for multiple comparisons. Results: At baseline enrollment, STB and HRQoL were not related to HDQLIFE End of Life Planning at 12 or 24 months. Similarly, at baseline, HDQLIFE End of Life Planning demonstrated no association with STB or HRQoL at 12 or 24 months. Interpretation: STB and HRQoL PROs do not significantly affect patient engagement with ACP. Most importantly, engaging in ACP does not cause untoward effects on HRQoL or STB for this rare neurodegenerative disease where the lifetime prevalence of STB approaches 30%.

Death Anxiety in Huntington Disease: Longitudinal Heath-Related Quality-of-Life Outcomes.

Objective: Death anxiety, represented by the HDQLIFE™ Concern with Death and Dying (CwDD) patient-reported outcome (PRO) questionnaire, captures a person's worry about the death and dying process. Previous work suggests that death anxiety remains an unremitting burden throughout all stages of Huntington disease (HD). Although palliative interventions have lessened death anxiety among people with advanced cancer, none has yet to undergo testing in the HD population. An account of how death anxiety is associated with longitudinal changes to aspects of health-related quality of life (HRQoL) would help optimize neuropalliative interventions for people with HD. Methods: HDQLIFE collected PROs concerning physical, mental, social, and cognitive HRQoL domains and clinician-rated assessments from people with HD at baseline and 12 and 24 months. Linear mixed-effects models were created to determine how baseline death anxiety was associated with follow-up changes in HRQoL PROs after controlling for baseline death anxiety and other disease and sociodemographic covariates. Results: Higher baseline HDQLIFE CwDD is associated with 12- and 24-month declines in HDQLIFE Speech Difficulties, neurology quality of life (NeuroQoL) Depression, Suicidality, HDQLIFE Meaning and Purpose, and NeuroQoL Positive Affect and Well-being. Interpretation: Death anxiety may be a risk factor for worsening mental health and speech difficulty. A further prospective study is required to evaluate whether interventions on death anxiety or mental health generally can reduce declines in HRQoL for people with HD over time.

Clinical Reasoning: A 77-Year-Old Man With Involuntary Movements, Sleep Changes, Falls, Bulbar Symptoms, and Cognitive Complaints.

A 77 year-old-man presents with chorea, parasomnias, dysarthria and dysphagia, and cognitive issues. A broad work-up reveals positive anti-IgLON5 antibody. This case report represents a "textbook" example of anti-IgLON5 syndrome.

Disparities in Palliative Care Utilization Among Hospitalized People With Huntington Disease: A National Cross-Sectional Study.

BACKGROUND: People with Huntington's disease (HD) often become institutionalized and more frequently die away from the home setting. The reasons behind differences in end-of-life care are poorly understood. Less than 5% of people with HD report utilization of palliative care (PC) or hospice services, regardless of the lack of curative therapies for this neurodegenerative disease. It is unknown what factors are associated with in-patient specialty PC consultation in this population and how PC might be related to discharge disposition. OBJECTIVES: To determine what HD-specific (e.g., psychosis) and serious illness-specific factors (e.g., resuscitation preferences) are associated with PC encounters in people with HD and explore how PC encounters are associated with discharge disposition. DESIGN: We analyzed factors associated with PC consultation for people with HD using discharge data from the National Inpatient Sample and the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality. An anonymized, cross-sectional, and stratified sample of 20% of United States hospitalizations from 2007 through 2014 were included using ICD-9 codes. RESULTS: 8521 patients with HD were admitted to the hospital. Of those, 321 (3.8%) received specialty PC. Payer type, (specifically private insurer or other insurer as compared to Medicare), income, (specifically the top quartile as compared to the bottom quartile), mortality risk, D.N.R., aspiration pneumonia, and depression were significantly associated with PC in a multivariate model. Among those who received PC, the odds ratio (OR) of discharge to a facility was 0.43 (95% CI, 0.32-0.58), whereas the OR of discharge to home with services was 2.25 (95% CI 1.57-3.23), even after adjusting for possible confounders. CONCLUSIONS: Among patients with HD, economic factors, depression, and serious illness-specific factors were associated with PC, and PC was associated with discharge disposition. These findings have implications for the adaptation of inpatient PC models to meet the needs of persons with HD.

When Should Neuroendovascular Care for Patients With Acute Stroke Be Palliative?

Noncurative surgeries intended to relieve suffering during serious illness or near end of life have been analyzed across palliative settings. Yet sparse guidance is available to inform clinical management decisions about whether, when, and which interventions should be offered when ischemic stroke and other neurological complications occur in patients whose survival is extended by other novel disease-modifying interventions. This case commentary examines key ethical and clinical considerations in palliative neuroendovascular care of patients with acute stroke.

Goal-Concordant Care in the Era of Advanced Stroke Therapies.

Stroke is a leading cause of disability and mortality worldwide. Recent advances in stroke care now enable patients with severe ischemic stroke owing to large vessel occlusion to safely undergo endovascular thrombectomy (EVT) up to 24 hours since their time of last known well, with the goal of improving functional outcomes by recanalization of the occluded vessel and reperfusion of downstream ischemic brain tissue. The objective of this analysis is to highlight clinical and ethical challenges related to ensuring goal-concordant care in this era of unprecedented advances in acute stroke care. Specifically, there is a salient challenge of whether advanced therapies such as EVT may be justifiably considered comfort focused, given their potential to preempt accumulated neurologic disability and suffering at the end of life. Through the lens of a patient case, we discuss key challenges, lessons learned, and suggestions for future care and research endeavors at the intersection of acute stroke care and palliative care principles. Although therapies such as thrombolysis and EVT may be considered aggressive prima facie, their potential to ameliorate additional disability and potential suffering at the end of life prompt close consideration of the proper role of these therapies on a case-by-case basis in the context of comfort-focused care. Modification to the workflow for EVT evaluations may facilitate goal-concordant care and timely resource allocation, especially for cases that involve hospital-to-hospital transfers for advanced stroke care.

Meaning and purpose in Huntington's disease: a longitudinal study of its impact on quality of life.

OBJECTIVE: Previous work in Huntington's disease (HD) has shown that a sense of meaning and purpose (M&P) is positively associated with positive affect and well-being (PAW); however, it was unknown whether HD-validated patient-reported outcomes (PROs) influence this association and how M&P impacts PROs in the future. Our study was designed to examine if HD-validated PROs moderate the relationship between M&P and PAW and to evaluate if baseline M&P predicts 12- and 24-month changes in HD-validated PROs. METHODS: This was a longitudinal, multicenter study to develop several PROs (e.g., specific for the physical, emotional, cognitive, and social domains) for people with HD (HDQLIFE). The sample consisted of 322 people with HD (n = 50 prodromal, n = 171 early-stage manifest, and n = 101 late-stage manifest HD). A single, multivariate linear mixed-effects model was performed with PAW as the outcome predicted by main effects for M&P and several moderators (i.e., an HD-validated PRO) and interactions between M&P and a given PRO. Linear-mixed models were also used to assess if baseline M&P predicted HD-validated PROs at 12 and 24 months. RESULTS: Higher M&P was positively associated with higher PAW regardless of the magnitude of symptom burden, as represented by HD-validated PROs, and independent of disease stage. In our primary analysis, baseline M&P predicted increased PAW and decreased depression, anxiety, anger, emotional/behavioral disruptions, and cognitive decline at 12 and 24 months across all disease stages. INTERPRETATION: These findings parallel those seen in the oncology population and have implications for adapting and developing psychotherapeutic and palliative HD interventions.

Best Practices in the Clinical Management of Progressive Supranuclear Palsy and Corticobasal Syndrome: A Consensus Statement of the CurePSP Centers of Care.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS; the most common phenotype of corticobasal degeneration) are tauopathies with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years. There is as yet no specific or disease-modifying treatment. Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes. They center on rigidity, bradykinesia, postural instability, gait freezing, supranuclear ocular motor impairment, dysarthria, dysphagia, incontinence, sleep disorders, frontal cognitive dysfunction, and a variety of behavioral changes. CBS presents with prominent and usually asymmetric dystonia, apraxia, myoclonus, pyramidal signs, and cortical sensory loss. The symptoms and deficits of PSP and CBS are amenable to a variety of treatment strategies but most physicians, including many neurologists, are reluctant to care for patients with these conditions because of unfamiliarity with their multiplicity of interacting symptoms and deficits. CurePSP, the organization devoted to support, research, and education for PSP and CBS, created its CurePSP Centers of Care network in North America in 2017 to improve patient access to clinical expertise and develop collaborations. The directors of the 25 centers have created this consensus document outlining best practices in the management of PSP and CBS. They formed a writing committee for each of 12 sub-topics. A 4-member Steering Committee collated and edited the contributions. The result was returned to the entire cohort of authors for further comments, which were considered for incorporation by the Steering Committee. The authors hope that this publication will serve as a convenient guide for all clinicians caring for patients with PSP and CBS and that it will improve care for patients with these devastating but manageable disorders.

The case of a 30-year-old man with subacute gait instability, weakness, and muscle spasms.

A 30-year-old healthy man presents after a fall with diffuse weakness and pain and recent onset left eye ptosis in the setting of three weeks of progressive bilateral leg weakness, gait instability, and difficulty washing his hair due to upper extremity weakness. He had also developed stiffness in his neck and shoulders and uncontrollable muscle spasms. Exam was notable for ptosis, fatiguing weakness in extremities, increased tone, hyperreflexia with clonus, and spastic gait. A mediastinal mass was found on chest CT (Fig. 1), and biopsy confirmed an invasive thymoma with positive nodes. Serum testing was positive for antibodies to acetylcholine receptors as well as glutamic acid decarboxylase.

Social Media Perceptions of Legacy-Making: A Qualitative Analysis.

Background: Individuals with life-limiting illnesses experience psychotherapeutic benefits of transmitting their life's history to loved ones; however, the scope and depth of what warrants preservation and who ought to undertake such activity remains less clear. Furthermore, individuals with conditions that afflict the brain face barriers regarding the timing and structure of such interventions. We analyzed data from an online social media forum to understand perceptions of legacy-making. Methods: This is a qualitative descriptive study of Slashdot, a social media website with a focus on science, technology, and politics. In August 2010, a Slashdot user inquired about a loved one with a life-limiting illness and asked for opinions on how to preserve the individual's memories. We conducted a content analysis of the individual comments related to digital legacy-making to identify common themes. Results: Slashdot users contributed 527 replies to the initial inquiry. Users often included bereaved individuals who offered input on the need to preserve information about a loved one, the modalities in which to preserve, and what type of content to preserve. Three key themes emerged related to legacy-making: (1) capture the individual's essence and avoid the minutia, (2) live for now to avoid prolonged suffering, and (3) recognize the equal benefits to all who memorialize. Conclusions: Users in a social media forum articulated the value of capturing their loved ones' essence for posterity, which many believed would help them to avoid prolonged grief. These findings have implications for the development and timing of personalized psychosocial interventions as well as informing application development of evidence-based digital legacy systems.

Advance care planning in Parkinson's disease: ethical challenges and future directions.

Recent discoveries support the principle that palliative care may improve the quality of life of patients with Parkinson's disease and those who care for them. Advance care planning, a component of palliative care, provides a vehicle through which patients, families, and clinicians can collaborate to identify values, goals, and preferences early, as well as throughout the disease trajectory, to facilitate care concordant with patient wishes. While research on this topic is abundant in other life-limiting disorders, particularly in oncology, there is a paucity of data in Parkinson's disease and related neurological disorders. We review and critically evaluate current practices on advance care planning through the analyses of three bioethical challenges pertinent to Parkinson's disease and propose recommendations for each.

Deep brain stimulation in uncommon tremor disorders: indications, targets, and programming.

BACKGROUND: In uncommon tremor disorders, clinical efficacy and optimal anatomical targets for deep brain stimulation (DBS) remain inadequately studied and insufficiently quantified. METHODS: We performed a systematic review of PubMed.gov and ClinicalTrials.gov. Relevant articles were identified using the following keywords: "tremor", "Holmes tremor", "orthostatic tremor", "multiple sclerosis", "multiple sclerosis tremor", "neuropathy", "neuropathic tremor", "fragile X-associated tremor/ataxia syndrome", and "fragile X." RESULTS: We identified a total of 263 cases treated with DBS for uncommon tremor disorders. Of these, 44 had Holmes tremor (HT), 18 orthostatic tremor (OT), 177 multiple sclerosis (MS)-associated tremor, 14 neuropathy-associated tremor, and 10 fragile X-associated tremor/ataxia syndrome (FXTAS). DBS resulted in favorable, albeit partial, clinical improvements in HT cases receiving Vim-DBS alone or in combination with additional targets. A sustained improvement was reported in OT cases treated with bilateral Vim-DBS, while the two cases treated with unilateral Vim-DBS demonstrated only a transient effect. MS-associated tremor responded to dual-target Vim-/VO-DBS, but the inability to account for the progression of MS-associated disability impeded the assessment of its long-term clinical efficacy. Neuropathy-associated tremor substantially improved with Vim-DBS. In FXTAS patients, while Vim-DBS was effective in improving tremor, equivocal results were observed in those with ataxia. CONCLUSIONS: DBS of select targets may represent an effective therapeutic strategy for uncommon tremor disorders, although the level of evidence is currently in its incipient form and based on single cases or limited case series. An international registry is, therefore, warranted to clarify selection criteria, long-term results, and optimal surgical targets.

Clinical signs in functional (psychogenic) gait disorders: a brief survey.

Clinical signs are critical in ascertaining the functional nature of a gait disorder. Four signs of gait impairment have been documented in the course of examining patients with clinically definite functional (psychogenic) movement disorders: "huffing and puffing" during standing and walking, manipulation-resistance dorsiflexion of the first toe, fixed plantar flexion and inversion, and marked discrepancy between ambulation with and without swivel chair assistance. While large studies are needed to ascertain their prevalence, sensitivity, and specificity, the identification of these signs may help elevate the diagnostic certainty of functional gait disorders.

Cautionary optimism: caffeine and Parkinson's disease risk.

Most Parkinson's disease (PD) patients present without known family history and without a diagnosed prodromal phase, underscoring the difficulty of employing primary (neuroprevention) and secondary (neuroprotection) preventions. In cases of monogenic forms, however, potential gene-carrying family members of a proband could engage in neuroprevention, such as exercise or diet modifications, to attenuate the risk of, or delay, disease development. However, a historical lack of recognized disease-modifying interventions has limited clinicians' ability to recommend reliable preventive measures in caring for at-risk populations. We briefly analyze the first retrospective study to examine caffeine consumption and PD risk in a LRRK2 R1628P cohort.