Mentor: Erin Smith Program: Neurological Sciences – Movement Disorders Type: Original Research Background: Orthostatic tremor (OT) is a rare neurological disorder characterized by a sensation of instability while standing. Very few clinical signs have been described for OT to date. Finding other symptoms and signs could prove valuable for this hard-to-recognize disease. Methods: This protocol is part of the University of Nebraska Medical Center Orthostatic Tremor longitudinal study. It was noted that OT patients flex their toes and sometimes the foot arch while standing (Plantar Grasp). They reported doing this to “grab” the floor and improve stability. This paper analyses the diagnostic test characteristics of the patient’s self-reported Plantar Grasp, a new sign in OT. Results: There were 34 OT patients (88% females) and 20 control patients (65% females). Eighty-eight percent of patients with OT reported the plantar grasp sign and none of the controls. The Plantar Grasp Sign was found to be very sensitive (88%) and extremely specific (100%) in our cohort. Non-weighted Negative Likelihood Ratio (NLR) was 0.12. And the 3% prevalence weighted NLR was so low that the negative post-test probability was close to zero ( Table 1). Table 1 Plantar Grasp Sign Test Characteristics Plantar Grasp Sign EMG Positive (OT) EMG Negative (No OT) Total Positive Plantar Grasp Sign TP (30) FP (0) 30 PPV (100%) Negative Plantar Grasp Sign FN (04) TN (20) 24 NPV (83%) Total 34 20 54 NLR (0.12) Sensitivity (88%) Specificity (100%) PLR: to infinity Accuracy (92%) EMG-Electromyography, TP-True Positive, FN-False Negative, FP-False Positive, TN-True Negative, PPV-Positive Predictive Value, NPV-Negative Predictive Value, NLR-Negative Likelihood Ratio PLR-Positive Likelihood Ratio Conclusion: Due to its high sensitivity, specificity, and ideal likelihood ratio, we propose that the Plantar Grasp sign could be considered to screen patients with possible OT. Further studies are needed to determine the specificity of this sign in OT versus other balance disorders.

Quantify circadian rest-activity rhythms in persons taking dopaminergic medications for Parkinson's Disease (PD), using real-world (RW) outputs from personal devices (actigraphy) as actionable clinical data for PD clinical management.

Objective: Parkinson's disease (PD) impairs motor and non-motor functions. Driver strategies to compensate for impairments, like avoiding driving in risky environments, may reduce on-road risk at the cost of decreasing driver mobility, independence, and quality of life (QoL). It is unclear how PD symptoms link to driving risk exposure, strategies, and QoL. We assessed associations between PD symptoms and driving exposure (1) overall, (2) in risky driving environments, and (3) in relationship to QoL.Methods: Twenty-eight drivers with idiopathic PD were assessed using the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and RAND 36-Item Short Form Health Survey (SF-36). Real-world driving was monitored for 1 month. Overall driving exposure (miles driven) and risky driving exposure (miles driven in higher risk driving environments) were assessed across PD symptom severity. High traffic, night, and interstate roads were considered risky environments.Results: 18,642 miles (30,001 km) driven were collected. Drivers with PD with worse motor symptoms (MDS-UPDRS Part III) drove more overall (b = 0.17, P < .001) but less in risky environments (night: b = -0.35, P < .001; interstate roads: b = -0.23, P < .001; high traffic: b = -0.14, P < .001). Worse non-motor daily activities symptoms (MDS-UPDRS Part I) did not affect overall driving exposure (b = -0.05, P = .43) but did affect risky driving exposure. Worse non-motor daily activities increased risk exposure to interstate (b = 0.36, P < .001) and high traffic (b = 0.09, P = .03) roads while reducing nighttime risk exposure (b = -0.15, P = .01). Daily activity impacts from motor symptoms (MDS-UPDRS Part II) did not affect distance driven. Reduced driving exposure (number of drives per day) was associated with worse physical health-related QoL (b = 2.87, P = .04).Conclusions: Results provide pilot data revealing specific PD symptom impacts on driving risk exposure and QoL. Drivers with worse non-motor impairments may have greater risk exposure. In contrast, drivers with worse motor impairments may have reduced driver risk exposure. Reduced driving exposure may worsen physical health-related QoL. Results show promise for using driving to inform clinical care.

Introduction: Orthostatic tremor (OT) is a rare neurological disorder characterized by a sensation of instability while standing. Very few clinical signs have been described for OT to date. Finding other symptoms and signs could prove valuable for this hard-to-recognized disease. Methods: This protocol is part of the University of Nebraska Medical Center Orthostatic Tremor longitudinal study. It was noted that OT patients flex their toes and sometimes the foot arch while standing (Plantar Grasp). They reported doing this to “grab” the floor and improve stability. This paper analyses the diagnostic test characteristics of the patient-self-reported Plantar Grasp, a new sign in OT. Results: There were 34 OT patients (88% females), and 20 controls (65% females). Eighty-eight percent of patients with OT reported the plantar grasp sign and none of the controls. The Plantar Grasp Sign was found to be very sensitive (88%), and extremely specific (100%) in our cohort. Non-weighted Negative Likelihood Ratio (NLR) was 0.12. And the 3% prevalence-weighted NLR was so low that the negative post-test probability was close to zero. Conclusion: Due to its high sensitivity, specificity, and ideal likelihood ratio, we propose that the Plantar Grasp sign could be considered to screen patients with possible OT. Further studies are needed to determine the specificity of this sign in OT versus other balance disorders.

Background:Driving is a complex, everyday task that impacts patient agency, safety, mobility, social connections, and quality of life. Digital tools can provide comprehensive real-world (RW) data on driver behavior in patients with Parkinson's disease (PD), providing critical data on disease status and treatment efficacy in the patient's own environment. Objective:This pilot study examined the use of driving data as a RW digital biomarker of PD symptom severity and dopaminergic therapy effectiveness. Methods:Naturalistic driving data (3974 drives) were collected for 1 month from 30 idiopathic PD drivers treated with dopaminergic medications. Prescriptions data were used to calculate levodopa equivalent daily dose (LEDD). The association between LEDD and driver mobility (number of drives) was assessed across PD severity, measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Results:PD drivers with worse motor symptoms based on self-report (Part II: P = 0.02) and clinical examination (Part III: P < 0.001) showed greater decrements in driver mobility. LEDD levels >400 mg/day were associated with higher driver mobility than those with worse PD symptoms (Part I: P = 0.02, Part II: P < 0.001, Part III: P < 0.001). Conclusions:Results suggest that comprehensive RW driving data on PD patients may index disease status and treatment effectiveness to improve patient symptoms, safety, mobility, and independence. Higher dopaminergic treatment may enhance safe driver mobility in PD patients with worse symptom severity.

Artificial Intelligence (AI) is a branch of computer sciences that uses learning algorithms to calculate probability of outcome by using Bayes theorem and other statistical methods for a given certain input (Fig.1). When the chance of an event occurring is calculated over and over again after adding new data or evidence at each step, the probability can reach the level of near certainty for given inputs. Thousands, even millions of data points are incorporated in calculating posterior probability for predictive analytics. The analytics are input neutral as programs predict the future events irrespective of the type of the data. AI has, thus, blurred the boundaries between the physical, digital, and biological worlds. The initial learning process is considered training where inputs are given to the program already marked for the expected outcome. This training information can either be highly precise or very vague allowing different degrees of freedom to the program but also increasing the burden of training. Once trained an AI algorithm is able to predict or analyze given input to suggest the required outcome with some certainty. This improves with continued training through feedback.

Medical education faces a difficult challenge today; an exponential increase in knowledge and the rise and rise of disruptive technologies are making traditional education obsolete. As the world nears the era of Industry and Healthcare 4.0, the medical community needs to keep up and prepare physicians for a hyper-connected digital world. Virtual neurological care is poised to be at the forefront of care delivery claims, yet the virtual communication of neurological knowledge is still in its infancy. This increasing digitalization of care and education is both an opportunity and a challenge. With this paper, the authors aim to bridge the gap between technology and neurological education. After a thorough review of recent literature and assessing current trends, the authors propose that contemporary medical education must adhere to the following tenets: Hybrid, Mobile, Mixed-reality, Open Access, Collaborative, Peer-reviewed, Intelligent, Game-based, and Global. We identify and align education objectives with the needs of future digital neurologists. The authors also discuss real-world advances that are aligned to serve the next generation of patients and providers.

Background:Deep brain stimulation (DBS) is used as a treatment option for patients diagnosed with a form of obsessive-compulsive disorder (OCD) that is highly resistant to conventional treatment methods. In 2009, DBS was granted a humanitarian device exemption-approval by the Food and Drug Administration after promising preliminary data. Monitoring of long-term safety data through post market surveillance of adverse events has not yet been conducted for DBS in OCD patients. This study aims to address this critical knowledge gap.Methods:All patient- and device-related (PR; DR) reports from January 1, 2012, to December 31, 2021, were downloaded and compiled from the manufacturer and user facility device experience (MAUDE) database pertaining to DBS for OCD using the product class name "Deep Brain Stimulator For OCD." Data in this study were examined using descriptive statistics to evaluate for frequency of reporting.Results:The most frequently reported PR adverse event categories included psychiatric (40%), neurological (19%), other (14%), decreased therapeutic response (10%), and infections (10%). The most frequent DR reports were high impedance (14%), energy output problem (7%), battery problem (7%), malposition of device (7%), and improper/incorrect procedure or method (7%).Conclusion:The PR and DR adverse events in our study align with the previous findings of adverse events. They also further solidify that DBS for refractory OCD may be a viable option for the right patient population. However, further studies are essential given the limitations of the MAUDE database.

Abstract Background Age-related neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease (PD), progressively reduce mobility and quality of life (QoL). Real-world mobility from actigraphy predicts PD disease severity. This pilot analysis assessed utility of actigraphy to screen early physical function-related QoL decline in PD. Method: Mobility was monitored for 4 weeks using wrist-worn ActiGraph recordings in 27 participants with idiopathic PD (age = 67.78 ± 5.64, 19 males). Days with >600 mins of wear time during non-sleep times were analyzed (µ = 29.78 days ± 3.78). Typical activity was quantified as average steps per hour. Participants completed demographic and health assessments. Disease severity and physical function QoL were measured using the clinically-validated Unified PD Rating Scale (MDS-UPDRS) and Short Form-36 (SF-36), respectively. Disease severity, QoL, and typical activity were compared using Spearman correlations. Results Lower typical activity from actigraphy was associated with more severe motor symptoms (MDS-UPDRS; r = -0.40, p = 0.04) and with increased impairment in physical function QoL (r = 0.50, p < 0.01). Daily activity from actigraphy did not predict symptom severity of non-motor and motor-related complications. Discussion: Pilot results show utility of actigraphic metrics for indexing real-world mobility and QoL declines in neurodegenerative disorders, in line with broader efforts to turn real-world data into actionable evidence for healthcare interventions. Ongoing discovery in larger populations should yield robust, clinically-relevant indices of daily activity in aging and neurodegenerative impairment.

Sleep dysfunction is signature of Alzheimer’s disease and Parkinson’s disease (PD), and can signify incipient disease, disease risk, and worsen symptoms over time. How real-world sleep dysfunction relates to patient self-report of sleep and clinical cognitive dysfunction is poorly understood, partly because self -report is impaired in patients with cognitive decline. We monitored real-world sleep with wearable actigraphy devices in patients with PD to test the hypothesis that objective patterns of sleep dysfunction are associated with worse cognitive performance. Twenty-nine participants with idiopathic PD (age = 67.44 ± 5.79, 20 males) completed the Montreal Cognitive Assessment (MoCA) and Epworth Sleepiness Scale (ESS) to capture clinical cognitive decline and self-reported daytime sleepiness. Sleep was monitored for 4-weeks using wrist-worn ActiGraphs. Sub-scores and total scores of MoCA were compared with Total Sleep Time (TST), Sleep Efficiency (SE), Wakefulness After Sleep Onset (WASO), and Sleep Fragmentation Index (SFI) measured by actigraphy, as well as ESS total using a Pearson correlation. Worse sleep fragmentation (SFI), the percentage of awakenings and movements during sleep, predicted worse cognitive impairment overall (MoCA score: r  = -0.38, p < .05) and delayed recall ( r  = -0.44, p < .05). Reduced sleep time (TST) and worse sleep quality (SE, WASO) did not worsen patient cognitive impairment. Patient self-report of sleepiness (ESS) did not associate with worse cognitive outcomes. This pilot analysis identifies sleep fragmentation as a key risk factor for cognitive dysfunction in PD. Patient self-report of sleep may not reliably reflect chronic sleep disruption and related cognitive dysfunction. Results underscore that objective measures of real-world dysfunction can help inform clinical care and intervention for patients at risk for cognitive decline and dementia.

Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative disorders that affect millions of individuals worldwide. As incidence of these conditions increases with age, there will undoubtedly be an increased prevalence of cases in the near future. Neuroinflammation is a hallmark in the development and progression of neurodegenerative diseases and prevention or resolution of chronic neuroinflammation may represent a novel approach to treatment. The present review highlights the potential of the anti-inflammatory and pro-resolving effects of polyunsaturated fatty acid (PUFA)-derived mediators (Specialized Pro-resolving Mediators-SPM) in neurodegenerative disorders. PUFA-derived SPM are biosynthesized in response to chemicals produced from acute inflammatory responses. Preclinical studies from both AD and PD models suggest a dysregulation of SPM and their receptors in neurological disorders. Decreased SPM may be due to inadequate substrate, an imbalance between SPM and pro-inflammatory mediators or a disruption in SPM synthesis. SPMs hold great promise for neuroprotection in AD by altering expression of pro-inflammatory genes, modulating macrophage function, serving as a biomarker for AD status, and promoting resolution of neuroinflammation. In PD, data suggest SPM are able to cross the blood-brain barrier, inhibit microglial activation and decrease induced markers of inflammation, possibly as a result of their ability to downregulate NFκB signaling pathways. Several in vivo and in vitro studies suggest a benefit from administration of SPMs in both neurodegenerative disorders. However, extrapolation of these outcomes to humans is difficult as no models are able to replicate all features of AD or PD. Minimal data evaluating these PUFA-derived metabolites in humans with neurodegenerative disorders are available and a gap in knowledge exists regarding behavior of SPM and their receptors in patients with these conditions. There is also large gap in our knowledge regarding which lipid mediator would be most effective in which model of AD or PD and how dietary intake or supplementation can impact SPM levels. Future direction should include focused, translational efforts to investigate SPM as an add-on (in addition to standard treatment) or as standalone agents in patients with neurodegenerative disorders.

Vitamin deficiencies impact neurological conditions and may present as progression of Parkinson's Disease (PD). We have previously shown 6.1% of a cohort of subjects with PD were deficient in Vitamin B1 and that dietary intake of vitamin B1 was significantly lower in those with deficiency (p = 0.02). Here, we aim to assess the prevalence of serum vitamin B1 deficiency in subjects with advanced PD symptoms.

Quality of life (QoL) in Parkinson's Disease (PD) worsens as bradykinesia, rigidity, rest tremor, gait disturbance, and cognitive changes progress over time. We searched for treatable conditions that masquerade as worsening PD. Vitamin deficiencies are common in PD patients, and many can cause neuropathies that worsen gait and cause falls. Deficiencies in B1 and B12 cause cognitive decline, and deficiencies in D increase the risk of fractures with falls. The goal of this research is to improve QoL in patients with PD by identifying and treating vitamin deficiencies.

Objective: To review experience of Botulinum Toxin (BoNT) injections for Oromandibular Dystonia (OMD). Background: OMD causes sustained or repetitive, forceful contractions of the muscles involving jaw and tongue causing jaw opening, jaw closing, lingual and mixed dystonias. When oral pharmacologic agents are inadequate, BoNT is standard of care. Design/Methods: A single center, retrospective chart review (July 2013 – June 2018) of BoNT injections for OMD. Wastage was defined as leftover drug from the vial; prepared but not injected. Patient not receiving injections within last 6 months was considered a ‘dropout’. Results: We had 43 patients (21 females), median age 58 years (range 21–88) with 231 encounters (avg. 5.4/patient, range 1–16). Most commonly used toxin was OnabotulinumToxinA (OnaBoNT, 88%), and very few patients with IncobotulinumToxinA (IncoBoNT, n=3) and RimabotulinumToxinB (RimaBoNT, n=2). Jaw closing dystonia was more common (70%, 60% females) then jaw-opening (21%) and lingual dystonia (21%) with overlap. Isolated Lingual dystonia injections were rare (11%), commonly associated with jaw opening (56%); while Jaw opening injections were never solitary. Isolated Jaw closing injections were also uncommon (23%) and frequently associated with cervical (40%) and facial (40%) injections. Average total dose (in Units, with range) of OnaBoNT was 66 (10–180) for Jaw closing; 54 (30–100) for Jaw opening and 16 (5–30) for Lingual dystonia. RimaBoNT (1000–2000) and IncoBoNT (45–50) were only used for Jaw closing dystonia. Average wastage of Botox was 25 units/patient. Dropout rate over 5 years was 37% after average 4 sessions (range 1–11). Most common reason was lost to follow up (22%) and deceased (22%), while lack of benefits (17%) and side effects (dysphagia 17% and weakness 11%) were uncommon reasons. Conclusions: In our series, jaw-closing dystonia was the most frequent and most OMD were segmental in nature. Although side effects and lack of benefit are infrequently reported, dropout was common. Disclosure: Dr. Ameer has nothing to disclose. Dr. Syed has nothing to disclose. Dr. Bertoni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with KYOWA. Dr. Hellman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceuticals. Dr. Torres-Russotto has nothing to disclose. Dr. Bhatti has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie, Accadia, Merz, Allergan Pakistan, Medtronic, Adamas and Teva Neurosciences.

Medium-chain saturated fatty acids (Octanoic acid (C8:0) and Decanoic acid (C10:0)) are found in high levels in coconut oil and palm kernel oil, commonly used in processed foods in the United States. They have reportedly positive effects on neuronal function in epilepsy and on cognition in Alzheimer's Disease. However, negative effects have been described in vascular diseases (such as stroke). Less is known about the impact of these fatty acids in Parkinson's Disease (PD). This study explored the association between their dietary intake and motor function in PD.

Oromandibular dystonia (OMD) is a chronic focal dystonia that involves the mouth, jaw, and tongue. It may cause repetitive or sustained dystonic movements, which can be very disabling for patients. It is usually a life-long disorder with numerous treatment options that are, most often, partially curative. In our experience, the best modality to treat OMD is botulinum toxin (BoNT) injections, which not only provide long-term relief but also have fewer adverse effects compared to other medications. Although multiple small- and large-scale studies support this fact, there is still a need for evidence from large randomized clinical trials. Jaw-closing dystonia responds very well to BoNT injections compared to other subtypes of OMD. This review discusses in detail the evidence, injection technique, and typical starting doses for botulinum injection.

Background:Orthostatic tremor (OT) is characterized by a sensation of instability while standing, associated with high frequency (1318 Hz) tremor in the legs. Small retrospective series have reported electroencephalography (EEG) findings in OT with discordant results.Methods:We prospectively enrolled 30 OT subjects. Mean age = 68.3 (range 5487) with mean disease duration 16.3 years (range 444). A modified 1020 system EEG recording with additional midline electrodes was obtained. EMG electrodes were placed on quadricep muscles. EEG recording was performed at rest, during sleep and while standing unassisted.Results:In all subjects, EEG showed normal background, normal drowsiness and/or stage 2 sleep, and normal responses to hyperventilation and photic stimulation. These normal results persisted during stance. EEG abnormalities were found in 3 subjects (anterior-mid temporal slow activity), but were not position-dependent and were judged unlikely to be related to OT. Tremor artifact while standing was noted in all subjects, however it was measurable in 26 with frequency in the OT range in 25. When compared with EMG, the average difference in frequency was small at 1.2 Hz (range 0.52.5, p 0.46). Visual EEG analysis in OT patients did not reveal electrographic abnormalities even upon standing unassisted.Discussion:EEG was normal on this prospective, relatively large OT series. Clinicians interpreting video-EEGs should be aware of the OT artifact that can be seen in EEG and EKG leads mostly while standing.

Tuesday, April 28April 14, 2020Free AccessAre balance scales affected by fear of falling? – a Delphi methodology study (1583)Diego Torres-Russotto, James Shou, Nabeel Syed, Venkata Bendi, Lori Schmaderer, Jennifer McKune, Amy Hellman, … Show All … , Luis Zayas, Rebecca Thompson, Pamela May, Ryan Brennan, John Bertoni, Dawn Venema, Joseph Siu, Vivien Marmelat, and Danish Bhatti Show FewerAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.1583 Letters to the Editor