Loss of Efficacy in Ventral Intermediate Nucleus Stimulation for Essential Tremor.

OBJECTIVE: The primary aim of this study is to report long-term outcomes associated with deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) performed at our institution. We further aimed to elicit the factors associated with loss of efficacy and to discuss the need for exploring and establishing reliable rescue targets. METHODS: To study long-term outcomes, we performed a retrospective chart review and extracted tremor scores of 43 patients who underwent VIM DBS lead implantation for essential tremor at our center. We further evaluated factors that could influence outcomes over time, including demographics, body mass index, duration of follow-up, degree of parenchymal atrophy indexed by the global cortical atrophy scale, and third ventricular width. RESULTS: In this cohort, tremor scores on the latest follow-up (median 52.7 months) were noted to be worse than initial postoperative scores in 56% of DBS leads. Furthermore, 14% of leads were associated with clinically significant loss of benefit. Factors including the length of time since the lead implantation, age at the time of surgery, sex, body mass index, preoperative atrophy, and third ventricular width were not predictive of long-term outcomes. CONCLUSIONS: Our study identified a substantial subgroup of VIM-DBS patient who experienced a gradual decline in treatment efficacy over time. We propose that this phenomenon can be attributed primarily to habituation and disease progression. Furthermore, we discuss the need to establish reliable and effective rescue targets for this subpopulation of patients, with ventral-oralis complex and dentate nucleus emerging as potential candidates.

Optimization of inpatient medication administration among persons with Parkinson's disease: recommendations on pharmacy technology and workflow.

Individuals with Parkinson's disease (PD) are vulnerable during hospitalizations due to the underlying complexities o1f symptoms, and acute illness or medication changes often lead to decompensation. Complications during hospitalizations are often due to worsening motor and nonmotor symptoms and commonly result from inaccurate medication regimens. Although the accuracy of medication administration relies on an interplay of factors, including patient status, transitions of care, coordination between the hospital prescriber and outpatient neurologist, etc., hospital pharmacists play an integral role in pharmacotherapy. The main aspects of pharmacy strategies aim to achieve timely administration of levodopa-containing medications, reduction of substitution and omissions of antiparkinsonian medications, and avoidance of antidopaminergic medications. This paper highlights critical areas for improvement and recommendations to minimize the impact of other factors from the pharmacy standpoint.

End of life care of hospitalized patients with Parkinson disease: a retrospective analysis and brief review.

Background: Towards the end of life (EOL), persons with parkinsonism (PwP) have complex needs and can present with unique palliative care (PC) challenges. There are no widely accepted guidelines to aid neurologists, hospitalists, or PC clinicians in managing the symptoms of PwP at EOL. We examined a population of PwP at EOL, aiming to describe trends of in-hospital management and utilization of PC services. Methods: All PwP admitted to two hospitals during 2018 (N = 727) were examined retrospectively, assessing those who died in hospital or were discharged with hospice (EOL group, N = 35) and comparing them to the main cohort. Their demographics, clinical data, engagement of multidisciplinary and palliative services, code status changes, invasive care, frequency of admissions, and medication administration were assessed. Results: Among the EOL group, 8 expired in hospital, and 27 were discharged to hospice. Forty-six percent of EOL patients received a PC consultation during their admission. The median interval from admission to death was 37 days. Seventy-seven percent had a full code status on admission. Compared to hospice patients, those who expired in hospital had higher rates of invasive procedures and intensive care unit transfers (41% vs. 75%, in both variables), and lower rates of PC involvement (52% vs. 25%). The transition of code status change for the EOL group from Full code to Do Not Resuscitate (DNR) occurred at a median 4-5 days from admission. For patients that passed in the hospital, the median days from transition of code status to death was 0(IQR 0-1). Levodopa dose deviations were frequent in both EOL and non-EOL group, but contraindicated medications were infrequently administered (11% in EOL group vs. 9% in non-EOL group). Conclusion: Our data suggest a low utilization of PC services and delayed discussions of goals of care. More work is needed to raise awareness of inpatient teams managing PwP regarding the unique but common challenges facing PwP with advanced disease. A brief narrative review summarizing the suggested management of symptoms common to hospitalized PwP near EOL is provided.

Establishing a framework for quality of inpatient care for Parkinson's disease: A study on inpatient medication administration.

BACKGROUND: The complexity of antiparkinsonian medications makes patients vulnerable to medication deviations. This study examines the frequency and outcomes of deviations between outpatient and inpatient medication administrations in patients with Parkinson's disease (PD). METHODS: We included hospital admissions of patients with PD during a 12-month period at the Cleveland Clinic Main and Fairview campuses. Outpatient regimens were compared with hospital medication administration records to establish rates of deviations in terms of levodopa equivalent daily dose (LEDD) difference, timing deviations/omissions of time-critical medications, substitution of levodopa compounds, and administration of antidopaminergic medications. Logistic regression analyses were used to investigate associations with length of stay (LOS), readmission rates, and mortality. RESULTS: The study included 492 patients with 725 admissions. Of those on time-critical medications, 43% had a LEDD deviation and 19% had levodopa formulation substitutions. Of the admission days with known outpatient timing regimens, 47% had an average deviation of more than 30 min and 22% had at least one missed levodopa dose. LOS was longer with each additional day of over-dose (4%), under-dose (14%), missed dose (21%), timing deviation (15%) and substitution (19%), (all p < 0.0001). Administration of antidopaminergic medications (9.9% of admissions) was associated with increased 30-day readmission/death (OR 1.85, p = 0.041), 90-day mortality (OR 2.2, p = 0.018), and LOS (7.6 vs. 3.8 days, p < 0.0001). LEDD underdose was associated with 30-day readmission/death (OR 1.78, p = 0.025) and 90-day mortality (OR 1.14, CI 1.05-1.24, p = 0.002). CONCLUSIONS: Deviations between outpatient and hospital regimens, and administration of antidopaminergic medications, were associated with poor outcomes.

Identifying misconceptions and knowledge gaps in functional neurological disorders among emergency care providers.

BACKGROUND: Functional Neurologic Disorders (FND) are a common but heterogeneous group of disabling conditions. The Emergency Department (ED) is an important venue for care and referral as it is often the first point of contact when patients with FND are faced with a crisis or exacerbation of symptoms. METHODS: ED providers (n = 273) practicing in the Cleveland Clinic Foundation Northeast Ohio network were invited to participate through secure web application electronic surveys. Data were collected on practice profiles, knowledge, attitudes, management of FND, and awareness of available resources for FND. RESULTS: Sixty providers completed the survey (22% response rate; n = 50 ED physicians, 10 advanced care providers) with 95.0% (n = 57) reporting a lack of understanding about FND. The terms Psychogenic Nonepileptic Seizures and stress induced/stress related disease were used by 60.0% (n = 36) and 58.3% (n = 35) respectively. Ninety percent (n = 53) rated their experience with managing FND patients as at least more difficult. Eighty- five percent (n = 51) agreed with "rule out others" and 60% (n = 36) agreed with "caused by psych stress". Eighty six percent (n = 50) believe that there is a difference between FND from malingering. Only one respondent was familiar with any FND resources and 79% (n = 47) reported the need for FND specific educational materials. CONCLUSION: This survey revealed major gaps in knowledge, inaccurate perceptions, and management that differs from the current standard of care among ED providers caring for patients with FND. Educational opportunities are needed to guide diagnosis and evidence-based treatment to optimize management of patients with FND.

Genetic screening of Filipinos suspected with familial Parkinson's disease: A pilot study.

INTRODUCTION: Although genetic factors are known to play a role in the pathogenesis of Parkinson's disease (PD), true prevalence of familial PD is unknown. We conducted this pilot study to identify genes implicated in familial Parkinson's disease among Filipinos. METHODS: Eighteen Filipino patients belonging to 11 families with personal and family history of PD underwent thorough evaluation by movement disorders specialists. Samples were analyzed in Juntendo University, Tokyo, Japan. Sanger sequencing of polymerase chain reaction products was performed. Each sample was screened for 23 genes (SNCA, PARK 2, UCHL1, PINK 1, DJ-1, LRRK2, ATP13A2, GIGYF2, HTRA2, PLA266, FBX07, VPS35, EIF461, DNAJC13, CHCHD2, GCH1, MAPT, NR4A2, VPS13c, PSEN1, and GRN). RESULTS: Out of 18 patients, six harbored Parkinson-related gene mutations. Five individuals from three families were positive for PINK1 c.10140T > C(p.L347P) mutation while one had heterozygous variant PRKN c.136G>T(p.A465) gene mutation. Three families displayed autosomal recessive pattern while one family with PINK1 mutation showed autosomal dominant mode of inheritance. Bradykinesia and tremor were predominant symptoms. Mean age at onset of symptoms was 40.4 years among those with PINK1 mutations. CONCLUSION: In this study, we presented the clinical profiles and identified two genetic mutations among a small group of Filipino patients with familial PD. They were congruent with most studies showing these mutations as the most common causes of autosomal recessive early-onset PD. Preliminary data from this pilot study will guide planning for larger scale studies, such as collaborative projects including The Global Parkinson's Genetics Program (GP2).

Acute Thyroiditis in a Patient with Neck Trauma.

The management of patients with major depressive disorder who present with self-injurious behavior is best optimized through a collaborative interprofessional approach. We describe a case of a 27-year-old woman without personal or family history of thyroid pathology who presented at the emergency department due to a suicide attempt by hanging. On examination, she was tachycardic with palpitations which persisted despite administration of analgesics and anxiolytics. Left temporal area swelling, left otorrhagia, and neck contusion were noted, involving consults with the Trauma, Neurosurgery, and Otorhinolaryngology teams. She was admitted to the psychiatric ward on account of persistent suicidal ideations. As part of the workup, thyroid function tests were done to rule out hypothyroidism as a cause of depressive symptoms. Results instead showed suppressed thyroid stimulating hormone and elevated free T4. Endocrinology service was consulted, and further workup showed absence of avid uptake of both thyroid glands on thyroid scan and undetectable thyrotropin receptor antibody level, supportive of a diagnosis of trauma-induced thyroiditis. This case increases awareness that trauma-induced thyroid dysfunction should be considered in patients with symptoms including, but not limited to, tachycardia and palpitations after a traumatic neck injury such as hanging.

Multimer Detection System-Oligomerized Amyloid Beta (MDS-OAß): A Plasma-Based Biomarker Differentiates Alzheimer's Disease from Other Etiologies of Dementia.

With emerging amyloid therapies, documentation of the patient's amyloid status to confirm the etiology of a clinical diagnosis is warranted prior to instituting amyloid-based therapy. The Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) is a noninvasive blood-based biomarker utilized to measure Aß oligomerization tendency. We determined the difference in MDS-OAß ratio across the groups: (a) no cognitive impairment or subjective cognitive impairment (NCI/SCI), (b) Alzheimer's disease (AD), (c) non-AD, and (d) mixed Alzheimer's disease-Vascular dementia (AD-VaD). MDS-OAß level was not significantly different between AD and mixed AD-VaD, but both groups were significantly different from the NCI/SCI and from the non-AD group. An MDS-OAß level of >1 could potentially indicate clinical variants of AD or mixed pathology (AD-VaD).

Spectrum of Movement Disorders in two Movement Disorders Centers in the Philippines.

OBJECTIVE: Presently, there are no epidemiologic data on the prevalence of movement disorders in the Philippines. We aim to describe the most common phenomenologies and movement disorders in two specialty centers in Metro Manila dedicated to movement disorders. METHODS: We investigated the clinical spectrum and etiologies of movement disorders referred to our centers from January 2007-December 2019 using a standardized collection form. RESULTS: A total of 1438 patients presenting with complaints relating to movement disorders were evaluated between 2007 to 2019. There were 770 (53.5%) men. The mean age was 57.1 ± 17.9 years. The most common movement disorders were parkinsonism (n=677, 47.1%), myoclonus (n=212, 14.7%) and tremor (n=208, 14.5%). The least common was restless legs syndrome (n=4, 0.3%). There were 78 (37.7% of total dystonia cases) X-linked dystonia-parkinsonism patients referred to our clinic. Majority of the botulinum toxin injections were for hemifacial spasms (n=206). A small number of patients (n=41) were also seen at the center for deep brain stimulation programming. CONCLUSION: The most common movement disorders managed were parkinsonism, myoclonus and tremor. The most common diagnoses were Parkinson's disease, hemifacial spasm and essential tremor. This study highlights the spectrum of movement disorders encountered in two specialty clinics in two Philippine tertiary hospitals. Given these varied cases, there is also a need for more movement specialists and centers dedicated to movement disorders to manage these cases.

Dementia Incidence, Burden and Cost of Care: A Filipino Community-Based Study.

Background: In the midst of competing priorities and limited resources in low-middle-income countries (LMIC), convincing epidemiological evidence is critical for urging governments to develop national dementia plans. The majority of primary epidemiological studies on dementia are from high income countries (HIC). Implications for developing countries are typically extrapolated from these outcomes through modeling, meta-analyses, and systematic reviews. In this study, we directly assessed the incidence of dementia, disability adjusted life years (DALYs), and cost of care among community-dwelling Filipino elderly. Methods: This was a follow-up study of the prospective cohort Marikina Memory Ageing Project (MMAP). Baseline assessment was performed in 2011-2012, and follow-up was done in 2015-2016 (N = 748 at follow-up). Incident dementia was determined. Disease burden was computed using the incidence rates and DALYs. Both indirect and direct (medical and non-medical) costs of dementia care were computed. Results: The crude incidence rate was 16 (CI: 13-20) cases per 1,000 person-years (pyr) with 17 (CI: 12-21) per 1,000 pyr for females and 14 (CI: 9-21) per 1,000 pyr for males. Based on this incidence, we project an estimation of 220,632 new cases in 2030, 295,066 in 2040, and 378,461 in 2050. Disease burden was at 2,876 DALYsper 100,000 persons. The economic burden per patient was around Php 196,000 annually (i.e., ~4,070 USD, or 36.7% of average family annual income in the Philippines). The majority (86.29%) of this care expense was indirect cost attributed to estimated lost potential earning of unpaid family caregivers whereas direct medical cost accounted for only 13.48%. Conclusions: We provide the first Filipino community-based data on the incidence of dementia, DALYs, and cost of care to reflect the epidemiologic and economic impact of disease. The findings of this study serve to guide the development of a national dementia plan.

Real-world experience with botulinum toxin A for the treatment of hemifacial spasm: A study of 1138 injections.

BACKGROUND: Hemifacial spasm (HFS) is a chronic, potentially disabling disorder that often requires long-term management with botulinum toxin (BoNT). In a country where healthcare costs limit compliance to medical follow-up and treatment, the study aims to provide a real-world experience on the use of BoNT for HFS among Filipinos. METHODS: We retrospectively collected data from 162 HFS patients who received 1138 botulinum toxin (BoNT) injections from 2006 to 2019 in our movement disorders center in the Philippines. We described their clinical profile and treatment response. RESULTS: The mean age at onset of disease was 47.7 ± 10.72 years. Majority of the patients reported a baseline moderate disease severity and disease frequency of >75% of waking time (59.8% and 46.9%, respectively). Most patients (61.73%) received 5 or less injections during the follow-up period. The mean duration of follow-up was 2.96 ± 4.28 years. The overall duration of treatment effect per injection was 3.6 ± 1.3 months while the mean interval between injections was 6 ± 5 months. There was no difference in the symptom improvement and duration between onabotulinumtoxinA and abobotulinumtoxinA. Side effects were infrequent. CONCLUSION: This study supports existing evidence on the efficacy and safety of BoNT for the symptomatic relief of HFS. In the Philippines, long-term treatment with BoNT may be limited by the cost of the procedure as majority of our patients had a few injections with long treatment intervals.

Primary headache research output and association with socioeconomic factors in Southeast Asia: a bibliometric analysis.

BACKGROUND: Although headache is one of the most common neurologic conditions with a high disease burden, primary data on headache research from Southeast Asia (SEA) was hypothesized to be inadequate. This study aimed to evaluate research productivity among the different countries in SEA and to determine the association between specific bibliometric indices and socioeconomic factors. METHODS: A systematic search was conducted until June 10, 2020 in Scopus, PubMed, Embase, Cochrane Central Register of Controlled Trials, and Index Medicus for South-East Asia Region to include all primary headache studies on migraine, tension-type headache, and trigeminal autonomic cephalalgia, with at least one author affiliated with a SEA country. Bibliometric indices, such as the number of publications and PlumX metrics, were obtained and correlated with the country-specific socioeconomic factors. RESULTS: We identified 153 articles. Most of the publications (n = 43, 28.1%) were epidemiologic studies and case reports/series (n = 25, 16.3%). Migraine was the most studied primary headache subtype. Malaysia, Singapore, and Thailand were the major contributors to primary headache research in SEA. Only the percent gross domestic product for research and development correlated significantly with research productivity. CONCLUSION: Despite the high global burden of disease, research productivity on primary headache was low in SEA. The move towards a knowledge-based economy may drive research productivity in SEA.

Involuntary Movements Following Administration of Hydroxychloroquine for COVID-19 Pneumonia.

Hydroxychloroquine (HCQ) has been used as an investigational drug for patients with moderate to severe coronavirus disease 2019 (COVID-19). There have been concerns of potential harms from side effects of the drug. We present a case of a 38-year-old male who was started on HCQ for COVID-19 pneumonia. He was referred for evaluation of myoclonus of all extremities, which resolved after discontinuation of HCQ. The involuntary movements were first reported after the initiation of HCQ, persisted despite improvement in inflammatory and radiologic parameters and eventually resolved after HCQ discontinuation. This supports a possible causality related to adverse drug reactions from HCQ that have not been commonly reported.

Dabigatran Reversal With Idarucizumab Preceding Thrombolysis in an Octogenarian Patient with Chronic Kidney Disease and Acute Stroke: A Case Report.

BACKGROUND AND PURPOSE: Reversing the effect of dabigatran among patients with atrial fibrillation is important to normalize coagulation profile among patients who develop serious hemorrhage from any source. However, such intervention always has the potential to cause a prothrombotic state. Among patients suspected of ischemic stroke, Idarucizumab, may be administered preceding thrombolysis. This is a considerable option when given during the critical phase of revascularization. METHODS: We report the case of an 84-year old, male, banker, known hypertensive with chronic renal disease. He has non valvular atrial fibrillation receiving Dabigatran at 75 mg twice daily and presented with symptoms of right-sided weakness, right hemisensory loss, facial asymmetry, and slurring of speech equating to National Institute of Health Stroke Scale (NIHSS) of 5. After coming into the hospital for a suspected stroke, 3 hours and 25 minutes after symptoms, complete reversal of Dabigatran with Idarucizumab was administered and intravenous thrombolysis was initiated 271 minutes post ictus. There was immediate improvement of the right upper extremity weakness and dysarthria 30 minutes post infusion. At 13 days post ictus, the patient was discharged with minimal right central facial palsy and right arm drift (NIHSS 2). Brain CT scan post revascularization did not reveal any hemorrhage and anticoagulant Apixaban 2.5 mg twice daily was started and maintained thereafter. Brain Magnetic Resonance Angiogram (MRA) showed complete recanalization of the left proximal MCA after 52 days. CONCLUSION: Our case showed the effectiveness and safety of giving Idarucizumab followed by thrombolysis in Dabigatran-treated atrial fibrillation with ischemic stroke. Based on this case, the procedure can be performed in an elderly population with chronic kidney disease when administered close to the limit of threshold for thrombolysis.

Acute stroke care algorithm in a private tertiary hospital in the Philippines during the COVID-19 pandemic: A third world country experience.

BACKGROUND AND PURPOSE: Since the declaration of the Novel Coronavirus Disease (COVID-19) pandemic, ensuring the safety of our medical team while delivering timely management has been a challenge. Acute stroke patients continue to present to the emergency department and they may not have the usual symptoms of COVID-19 infection. Stroke team response and management must be done within the shortest possible time to minimize worsening of the functional outcome without compromising safety of the medical team. METHODS: Infection control recommendations, emergency department protocols and stroke response pathways utilized prior to the COVID 19 pandemic within our institution were evaluated by our stroke team in collaboration with the multidisciplinary healthcare services. Challenges during the COVID-19 scenario were identified, from which a revised acute stroke care algorithm was formulated to adapt to this pandemic. RESULTS: We formulated an algorithm that incorporates practices from internationally devised protocols while tailoring certain aspects to suit the available resources in our system locally. We highlighted the significance of the following: team role designation, coordination among different subspecialties and departments, proper use of personal protective equipment and resources, and telemedicine use during this pandemic. CONCLUSIONS: This pandemic has shaped the stroke team's approach in the management of acute stroke patients. Our algorithm ensures proper resource management while optimizing acute stroke care during the COVID-19 pandemic in our local setting. This algorithm may be utilized and adapted for local practice and other third world countries who face similar constraints.

Intravenous Thrombolysis for Stroke in a COVID-19 Positive Filipino Patient, a Case Report.

The 2019 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which was first reported in Wuhan, China last December 2019, has been declared an emergency by the World Health Organization but eventually progressed to become a Pandemic. To date, Coronavirus Disease 2019 (COVID-19) has affected at least 100,000 individuals worldwide, reaching thousands of mortalities (Zhou et al., 2020; World Health Organization, 2020). In the Philippines, the number of COVID-19 confirmed positive cases is over 636 and is expected to rise (Department of Health, 2020). Respiratory infections alongside their comorbidities can induce acute myocardial infarction and acute ischemic stroke (Warren-Gash et al., 2018) [3]. These may further bring challenges in the management and administration of Intravenous (IV) Alteplase in eligible patients. Currently, there are no case reports in the administration IV Altepase in ischemic stroke patients who are COVID-19 positive. We present a case of a 62-year old female who was admitted due to cough, colds and shortness of breath of 2 weeks duration and was tested to be COVD-19 positive. She suffered from an ischemic stroke while in the Medical Intensive Care Unit and was given Intravenous thrombolysis.