Cerebrospinal fluid transcripts may predict shunt surgery responses in normal pressure hydrocephalus.

Molecular biomarkers for neurodegenerative diseases are critical for advancing diagnosis and therapy. Normal pressure hydrocephalus (NPH) is a neurological disorder characterized by progressive neurodegeneration, gait impairment, urinary incontinence and cognitive decline. In contrast to most other neurodegenerative disorders, NPH symptoms can be improved by the placement of a ventricular shunt that drains excess CSF. A major challenge in NPH management is the identification of patients who benefit from shunt surgery. Here, we perform genome-wide RNA sequencing of extracellular vesicles in CSF of 42 NPH patients, and we identify genes and pathways whose expression levels correlate with gait, urinary or cognitive symptom improvement after shunt surgery. We describe a machine learning algorithm trained on these gene expression profiles to predict shunt surgery response with high accuracy. The transcriptomic signatures we identified may have important implications for improving NPH diagnosis and treatment and for understanding disease aetiology.

iTex Gloves: Design and In-Home Evaluation of an E-Textile Glove System for Tele-Assessment of Parkinson's Disease.

Parkinson's disease (PD) is a neurological progressive movement disorder, affecting more than 10 million people globally. PD demands a longitudinal assessment of symptoms to monitor the disease progression and manage the treatments. Existing assessment methods require patients with PD (PwPD) to visit a clinic every 3-6 months to perform movement assessments conducted by trained clinicians. However, periodic visits pose barriers as PwPDs have limited mobility, and healthcare cost increases. Hence, there is a strong demand for using telemedicine technologies for assessing PwPDs in remote settings. In this work, we present an in-home telemedicine kit, named iTex (intelligent Textile), which is a patient-centered design to carry out accessible tele-assessments of movement symptoms in people with PD. iTex is composed of a pair of smart textile gloves connected to a customized embedded tablet. iTex gloves are integrated with flex sensors on the fingers and inertial measurement unit (IMU) and have an onboard microcontroller unit with IoT (Internet of Things) capabilities including data storage and wireless communication. The gloves acquire the sensor data wirelessly to monitor various hand movements such as finger tapping, hand opening and closing, and other movement tasks. The gloves are connected to a customized tablet computer acting as an IoT device, configured to host a wireless access point, and host an MQTT broker and a time-series database server. The tablet also employs a patient-centered interface to guide PwPDs through the movement exam protocol. The system was deployed in four PwPDs who used iTex at home independently for a week. They performed the test independently before and after medication intake. Later, we performed data analysis of the in-home study and created a feature set. The study findings reported that the iTex gloves were capable to collect movement-related data and distinguish between pre-medication and post-medication cases in a majority of the participants. The IoT infrastructure demonstrated robust performance in home settings and offered minimum barriers for the assessment exams and the data communication with a remote server. In the post-study survey, all four participants expressed that the system was easy to use and poses a minimum barrier to performing the test independently. The present findings indicate that the iTex glove system has the potential for periodic and objective assessment of PD motor symptoms in remote settings.

Subthalamic-Cortical Network Reorganization during Parkinson's Tremor.

Tremor, a common and often primary symptom of Parkinson's disease, has been modeled with distinct onset and maintenance dynamics. To identify the neurophysiologic correlates of each state, we acquired intraoperative cortical and subthalamic nucleus recordings from 10 patients (9 male, 1 female) performing a naturalistic visual-motor task. From this task, we isolated short epochs of tremor onset and sustained tremor. Comparing these epochs, we found that the subthalamic nucleus was central to tremor onset, as it drove both motor cortical activity and tremor output. Once tremor became sustained, control of tremor shifted to cortex. At the same time, changes in directed functional connectivity across sensorimotor cortex further distinguished the sustained tremor state.SIGNIFICANCE STATEMENT Tremor is a common symptom of Parkinson's disease (PD). While tremor pathophysiology is thought to involve both basal ganglia and cerebello-thalamic-cortical circuits, it is unknown how these structures functionally interact to produce tremor. In this article, we analyzed intracranial recordings from the subthalamic nucleus and sensorimotor cortex in patients with PD undergoing deep brain stimulation surgery. Using an intraoperative task, we examined tremor in two separate dynamic contexts: when tremor first emerged, and when tremor was sustained. We believe that these findings reconcile several models of Parkinson's tremor, while describing the short-timescale dynamics of subcortical-cortical interactions during tremor for the first time. These findings may describe a framework for developing proactive and responsive neurostimulation models for specifically treating tremor.

Prognostic predictors relevant to end-of-life palliative care in Parkinson's disease and related disorders: a systematic review.

Parkinson's disease and related disorders (PDRD) are the second most common neurodegenerative disease and a leading cause of death. However, patients with PDRD receive less end-of-life palliative care (hospice) than other illnesses, including other neurologic illnesses. Identification of predictors of PDRD mortality may aid in increasing appropriate and timely referrals. To systematically review the literature for causes of death and predictors of mortality in PDRD to provide guidance regarding hospice/end-of-life palliative care referrals. We searched MEDLINE, PubMed, EMBASE and CINAHL databases (1970-2020) of original quantitative research using patient-level, provider-level or caregiver-level data from medical records, administrative data or survey responses associated with mortality, prognosis or cause of death in PDRD. Findings were reviewed by an International Working Group on PD and Palliative Care supported by the Parkinson's Foundation. Of 1183 research articles, 42 studies met our inclusion criteria. We found four main domains of factors associated with mortality in PDRD: (1) demographic and clinical markers (age, sex, body mass index and comorbid illnesses), (2) motor dysfunction and global disability, (3) falls and infections and (4) non-motor symptoms. We provide suggestions for consideration of timing of hospice/end-of-life palliative care referrals. Several clinical features of advancing disease may be useful in triggering end-of-life palliative/hospice referral. Prognostic studies focused on identifying when people with PDRD are nearing their final months of life are limited. There is further need for research in this area as well as policies that support need-based palliative care for the duration of PDRD.

A pilot trial of square biphasic pulse deep brain stimulation for dystonia: The BIP dystonia study.

BACKGROUND: Dystonia often has inconsistent benefits and requires more energy-demanding DBS settings. Studies suggest that squared biphasic pulses could provide significant clinical benefit; however, dystonia patients have not been explored. OBJECTIVES: To assess safety and tolerability of square biphasic DBS in dystonia patients. METHODS: This study included primary generalized or cervical dystonia patients with bilateral GPi DBS. Square biphasic pulses were implemented and patients were assessed at baseline, immediately postwashout, post-30-minute washout, 1 hour post- and 2 hours postinitiation of investigational settings. RESULTS: Ten participants completed the study. There were no patient-reported or clinician-observed side effects. There was improvement across time on the Toronto Western Spasmodic Torticollis Rating Scale (χ2 = 10.7; P = 0.031). Similar improvement was detected in objective gait measurements. CONCLUSIONS: Square biphasic stimulation appears safe and feasible in dystonia patients with GPi DBS. Further studies are needed to evaluate possible effectiveness particularly in cervical and gait features. © 2016 International Parkinson and Movement Disorder Society.

Nonmotor Symptoms in Parkinson's Disease.

Nonmotor symptoms (NMSs) in Parkinson's disease (PD) have become increasingly recognized as major determinants of quality of life across cultures worldwide. Behavioral symptoms include dementia, depression, anxiety, apathy, and fatigue. Somatic symptoms include hypotension, constipation, diaphoresis, and pain. However, somatic symptoms may also be intrinsic, such as dementia, and iatrogenic, such as compulsive disorders. The authors address some of the more common disorders, yet few have been the target of clinical trials.

Randomized, Blinded Pilot Testing of Nonconventional Stimulation Patterns and Shapes in Parkinson's Disease and Essential Tremor: Evidence for Further Evaluating Narrow and Biphasic Pulses.

OBJECTIVES: Evidence suggests that nonconventional programming may improve deep brain stimulation (DBS) therapy for movement disorders. The primary objective was to assess feasibility of testing the tolerability of several nonconventional settings in Parkinson's disease (PD) and essential tremor (ET) subjects in a single office visit. Secondary objectives were to explore for potential efficacy signals and to assess the energy demand on the implantable pulse-generators (IPGs). MATERIALS AND METHODS: A custom firmware (FW) application was developed and acutely uploaded to the IPGs of eight PD and three ET subjects, allowing delivery of several nonconventional DBS settings, including narrow pulse widths, square biphasic pulses, and irregular pulse patterns. Standard clinical rating scales and several objective measures were used to compare motor outcomes with sham, clinically-optimal and nonconventional settings. Blinded and randomized testing was conducted in a traditional office setting. RESULTS: Overall, the nonconventional settings were well tolerated. Under these conditions it was also possible to detect clinically-relevant differences in DBS responses using clinical rating scales but not objective measures. Compared to the clinically-optimal settings, some nonconventional settings appeared to offer similar benefit (e.g., narrow pulse widths) and others lesser benefit. Moreover, the results suggest that square biphasic pulses may deliver greater benefit. No unexpected IPG efficiency disadvantages were associated with delivering nonconventional settings. CONCLUSIONS: It is feasible to acutely screen nonconventional DBS settings using controlled study designs in traditional office settings. Simple IPG FW upgrades may provide more DBS programming options for optimizing therapy. Potential advantages of narrow and biphasic pulses deserve follow up.

Updates in medical and surgical therapies for Tourette syndrome.

Tourette syndrome is a complex neurobehavioral disorder defined by multiple motor and at least 1 vocal tic, persisting over 1 year, waxing and waning in severity, and not explained by another condition. The condition may range from mild nuisance to debilitating and disabling in severity. Management includes counseling and reassurance, behavioral interventions, pharmacologic, and rarely, surgical interventions. Traditionally, alpha-2 agonists and dopamine receptor antagonists have been utilized. In addition, a number of different pharmacotherapies have been implemented in the search for improved management of tics with better tolerability. In rare, severely disabling cases, neuromodulation with deep brain stimulation may be indicated. Optimal brain targets and candidate selection are still in evolution. This article will review the evidence for current medical and surgical therapies with a focus on recent updates.

Current Status of Integrated Palliative Care Among Parkinson Foundation Centers of Excellence in the United States.

Background and Objectives: To assess the current structures, knowledge, and readiness to integrate palliative care (PC) into Parkinson disease (PD) care at Parkinson's Foundation Centers of Excellence (COE) in the United States. Methods: Three unique surveys were administered to health care professionals/staff at COEs to assess PC (1) resources, (2) knowledge and comfort, (3) clinical experience and processes, (4) barriers, and (5) readiness for implementation. Results: Response rates for the 3 surveys were 97%, 98%, and 56%. In total, 41% of COEs have access to outpatient PC specialists, 71% have mental health counseling, 82% have support groups, and 9% had very limited PC resources. Overall, 74% of providers believed persons with advanced PD should receive PC, and knowledge of PC fundamentals was good across providers. For high-needs persons with PD (PWP), only 16% of physicians and 24% of advanced practice providers made referrals to PC specialists ≥75% of the time, while 9% and 16% never made such referrals. Limited time, space, financing, and staffing were seen as major barriers to PC implementation. In total, 37% of providers were satisfied with their COE's ability to provide PC services. Most COEs report a culture open to change and appear well-positioned to implement PC in a more comprehensive fashion. Discussion: These results demonstrate the emergence of structures and processes to provide PC to persons with PD at COEs. They also identify concrete opportunities to strengthen integration of PC through educational, quality improvement, and advocacy efforts.

The evolving role of diffusion magnetic resonance imaging in movement disorders.

Significant advances have allowed diffusion magnetic resonance imaging (MRI) to evolve into a powerful tool in the field of movement disorders that can be used to study disease states and connectivity between brain regions. Diffusion MRI is a promising potential biomarker for Parkinson's disease and other forms of parkinsonism, and may allow the distinction of different forms of parkinsonism. Techniques such as tractography have contributed to our current thinking regarding the pathophysiology of dystonia and possible mechanisms of penetrance. Diffusion MRI measures could potentially assist in monitoring disease progression in Huntington's disease, and in uncovering the nature of the processes and structures involved the development of essential tremor. The ability to represent structural connectivity in vivo also makes diffusion MRI an ideal adjunctive tool for the surgical treatment of movement disorders. We review recent studies using diffusion MRI in movement disorders research and present the current state of the science as well as future directions.

Improvement in Parkinson Disease Symptoms After Treatment for COVID-19 with Monoclonal Antibodies.

BACKGROUND: Parkinson disease (PD) is a neurodegenerative disease characterized by motor symptoms, such as bradykinesia, and non-motor symptoms, such as fatigue, which can be a particularly disabling feature of the disease. METHODS: We conducted a retrospective chart review on a patient who reported improvement in baseline PD symptoms after COVID-19 treatment. RESULTS: The patient is a 76-year-old male with a six-year history of PD who developed a COVID-19 infection, underwent treatment with COVID-19 monoclonal antibodies, and experienced a remarkable improvement in his pre-COVID PD symptoms, most notably his gait and fatigue. Prior to COVID, he rated his fatigue as '9 out of 10,' which worsened to 10 out of 10 during his COVID infection, and post-COVID treatment, his fatigue improved to '3 out of 10'. PRINCIPAL CONCLUSIONS: We described an unexpected improvement in baseline PD symptoms for a patient treated with COVID-19 monoclonal antibodies. Further investigation will be essential to understand the mechanisms underlying this phenomenon.

Concurrent decoding of distinct neurophysiological fingerprints of tremor and bradykinesia in Parkinson's disease.

Parkinson's disease (PD) is characterized by distinct motor phenomena that are expressed asynchronously. Understanding the neurophysiological correlates of these motor states could facilitate monitoring of disease progression and allow improved assessments of therapeutic efficacy, as well as enable optimal closed-loop neuromodulation. We examined neural activity in the basal ganglia and cortex of 31 subjects with PD during a quantitative motor task to decode tremor and bradykinesia - two cardinal motor signs of PD - and relatively asymptomatic periods of behavior. Support vector regression analysis of microelectrode and electrocorticography recordings revealed that tremor and bradykinesia had nearly opposite neural signatures, while effective motor control displayed unique, differentiating features. The neurophysiological signatures of these motor states depended on the signal type and location. Cortical decoding generally outperformed subcortical decoding. Within the subthalamic nucleus (STN), tremor and bradykinesia were better decoded from distinct subregions. These results demonstrate how to leverage neurophysiology to more precisely treat PD.

Inpatient Mortality in Parkinson's Disease.

Introduction: Although a majority of the American public prefer to die at home, a large percentage of Parkinson's disease patients die in acute care hospitals. We examine trends in the clinical and demographic characteristics of Parkinson's disease patients who die in a hospital to identify populations potentially vulnerable to unwanted inpatient mortality. Methods: Patients with Parkinson's disease admitted to a hospital from 2002-2016 were identified from the National Inpatient Sample (n = 710,013) along with their associated clinical and demographic characteristics. The main outcome examined was mortality during inpatient admission. From these data, logistic regression models were estimated to obtain the odds ratios of inpatient mortality among clinical and demographic attributes, and their change over time. Results: Characteristics significantly associated with increased odds of inpatient mortality included increased age (OR = 1.70 for 55-65, 2.52 for 66-75, 3.99 for 76-85, 5.72 for 86+, all P < 0.001), length of stay ≤5 days (reference; 6 + days OR = 0.37, P < 0.001), white race or ethnicity (reference; Black OR = .84 P < .001, Hispanic OR = 0.91 P = 0.01), male (reference; female OR = 0.93 P < 0.001), hospitalization in Northeast (reference; Midwest OR = 0.78, South 0.84, West OR = 0.82; all P < 0.001), higher severity of illness (moderate OR = 1.50, major OR = 2.32, extreme OR = 5.57; all P < 0.001), and mortality risk (moderate OR = 2.88, major OR = 10.92, extreme OR = 52.30; all P < 0.001). Fitted probabilities overall declined over time. Conclusion: Differences exist among PD patient populations regarding likelihood of in-hospital mortality that are changing with time. Insight into which PD patients are most at risk for inpatient mortality may enable clinicians to better meet end-of-life care needs.

Increased rate of aspiration pneumonia and poor discharge outcome among acute ischemic stroke patients following intubation for endovascular treatment.

BACKGROUND: An increased risk of aspiration pneumonia among acute ischemic stroke patients following intubation for endovascular treatment may explain the higher rates of poor outcomes among patients requiring general anesthesia compared with those performed under local sedation. METHODS: Rates of aspiration pneumonia and its contribution to poor outcome at discharge (modified Rankin score ≥ 3), and in-hospital mortality were analyzed among endovascularly treated acute ischemic stroke patients at two university-affiliated comprehensive stroke centers. Logistic regression model was used to assess the contribution of intubation and aspiration pneumonia on poor outcome after adjusting for potential confounders. RESULTS: There were 136 acute ischemic stroke patients who received endovascular treatment: 83 patients received local sedation without intubation and 53 patients were intubated. The rates of aspiration pneumonia were 12 (14%) in endovascularly treated patients not intubated, and 12 (23%) in endovascularly treated intubated patients. Rates of poor outcomes were 46 (55%) in the non-intubated endovascularly treated patients, and 44 (83%) in intubated endovascularly treated patients. After adjusting for age, gender, National Institutes of Health Stroke Scale (NIHSS) score strata, poor outcome at discharge (OR 2.9, 95% CI 1.2-7.4) (P = 0.0243) and in-hospital mortality (OR 4.5, 95% CI 1.5-12.5) (P = 0. 0.0046) were significantly higher among intubated patients. After adjusting for pneumonia, the effect of intubation on poor outcome at discharge (OR 2.7, CI 1.1-7.1) (P = 0.0006) and in-hospital mortality (OR 4.4, CI 1.6-12.5) (P = 0.00051) remained significant in the multivariate model. CONCLUSIONS: Careful consideration should be exercised when emergently intubating acute ischemic stroke patients for endovascular treatment, because the rate of death and disability appears to be high. This increased rate is not explained by higher rates of subsequent aspiration pneumonia.

Long-term outcomes with pimavanserin for psychosis in clinical practice.

Introduction: Pimavanserin is the only medication FDA-approved for the treatment of Parkinson disease (PD) psychosis (PDP), but reports of long-term, real-world clinical experience are lacking. Methods: A retrospective chart review of all patients treated with pimavanserin was conducted at our large Movement Disorders practice in Providence, Rhode Island, USA. Demographic and clinical data for each patient were collected and descriptive analyses were performed. Results: We identified 54 patients (23 female) who initiated pimavanserin, whose median age was 70 years (range 44-87 years) and the median duration of pimavanserin therapy was 26 weeks. Initial improvement was seen in 47% of the entire group, and 50% of the DLB patients. Additional antipsychotic medication was needed concomitantly with pimavanserin to maintain a positive response for 40% of patients. Only 15% of the entire group had effective treatment of their condition with pimavanserin monotherapy over a median of 52 weeks. Among the initial responders, 32% continued on pimavanserin monotherapy. Among the non-responders, the mean trial period for patients who did not improve was 27 weeks, for patients who worsened was 16 weeks, and for those who experienced adverse effects was 1-2 weeks. Reported sex was similar across responders (60%), non-responders (56%), and the overall cohort (57%). Conclusion: Our real-world experience shows that pimavanserin is safe and tolerable, with a lower response rate than reported in other publications. While it has been proven to be effective in short-duration clinical trials, our clinical experiences, however, demonstrate less promising results in the long term.

The evaluation of the swallow tail sign in patients with parkinsonism and gait disorders.

BACKGROUND: Swallow tail sign (STS), which represents nigrosome-1 in the substantia nigra on 3 Tesla (T) susceptibility-weighted imaging (SWI), has attracted attention as a promising magnetic resonance imaging (MRI) biomarker for idiopathic Parkinson's disease (iPD). Some reports have shown high sensitivity and specificity-both above 94%-for distinguishing iPD from healthy controls. However, abnormal STS has been observed in many neurodegenerative parkinsonisms and even in multiple sclerosis. METHODS: All patients with parkinsonism who had 3 T MRI were included in a retrospective chart review from a single movement disorders clinic. All subjects were evaluated by a single movement disorder specialist, using Movement Disorders Society diagnostic criteria and American Academy of Neurology consensus guidelines for diagnoses. All MRIs were interpreted by a single neuroradiologist who was blinded to the diagnosis. RESULTS: Twenty patients were included in the study. Twelve had abnormal STS: iPD (n = 2), probable multiple system atrophy (n = 3), vascular parkinsonism (n = 1), psychogenic gait disorder (n = 1), neuroleptic parkinsonism (n = 2), cervical dystonia (n = 1), static encephalopathy (n = 1) and gait disorder of unknown etiology (n = 1). Eight had normal STS: iPD (n = 1), probable progressive supranuclear palsy (n = 1), vascular parkinsonism (n = 2), transient parkinsonism of unknown etiology (n = 2), valproic acid induced parkinsonism (n = 1), and essential tremor with parkinsonism (n = 1). 123I-Ioflupane SPECT dopamine transporter (DaT) scan results were available on seven subjects; four subjects had incongruency between DaT and MRI. CONCLUSION: Our results suggest that the abnormal STS is not, in isolation, a reliable biomarker of idiopathic Parkinson's disease.

Racial and geographic disparities with gastrostomy tube placement in dementia and parkinsonian disorders.

INTRODUCTION: Many patients with advanced dementia and Parkinson's disease and related disorders (PDRD) are receiving gastrostomy tube (GT) placement annually, despite its lack of proven benefit for preventing aspiration, enhancing nutrition, or prolonging survival. Given clinical practice variability in the care of people with neurodegenerative disorders, we sought to examine racial and geographic disparities in GT placement for these populations in the United States. METHOD: Data were extracted from a publicly-available national database using diagnostic and procedural codes from 2006 to 2010. GT placement rates and odds ratios were calculated for two groups: PDRD and non-parkinsonian dementia (NPD). RESULTS: In the PDRD group, odds of GT placement were higher among patients coded as Black (OR 1.69, CI 0.80-3.56, p = 0.17) and Asian (OR 2.17, CI 0.70-6.78, p = 0.18) than Whites; although these tendencies did not reach statistical significance. In the NPD group, GT placement among Black patients was significantly more likely (OR 2.88, CI 1.90-4.36, p < 0.001) than their white counterparts, while Asian patients were significantly less likely (OR 0.12, CI 0.02-0.91, p = 0.04). Compared to the Northeast region, there were significantly lower odds of GT placement in the Midwest region (OR 0.37, CI 0.24-0.58, p < 0.001) in the NPD group only. No difference in odds was observed between the sexes in both groups. CONCLUSION: This study showed geographic and racial disparities in GT placement among PDRD and NPD patients. Further studies should aim to clarify best practices for GT placement in PDRD and causes of practice differences within and between PDRD and NPD groups.

Trends and outcomes associated with gastrostomy tube placement in common neurodegenerative disorders.

INTRODUCTION: Dysphagia causing aspiration pneumonia is a common complication in the advanced stages of neurodegenerative disorders. Historically, physicians attempted to prevent this complication with gastrostomy tube (GT) placement. Its use is supported in amyotrophic lateral sclerosis (ALS), not supported in Alzheimer's disease (AD), and without disease-specific guidelines in Parkinson's disease (PD). METHOD: The rate of GT placement in these three populations over two decades, from 1990 to 2010, was calculated using a binomial regression model with the data extracted using diagnosis and procedural codes from a national database. The median length-of-stay (LOS) and discharge destinations were compared. RESULTS: The rate of GT placement was 6.0% lower annually in AD, 3.4% in PD, and 0.2% in ALS (all p ≤ 0.007). The analysis of hospital LOS and discharge destination showed 3.2 to 5.5 days longer LOS with GT placement in all groups (all p ≤ 0.01), and three to four times lower odds of going home with GT placement in AD and PD groups (OR 0.28, 95% CI 0.14-0.55, and OR 0.22, CI 0.11-0.42 respectively), while unchanged in ALS group (OR 1.1, 95% CI 0.6-1.9). CONCLUSION: Despite the downward trend of GT placement over two decades, thousands of AD and PD patients still underwent GT placement annually, and this was associated with longer LOS in all groups and increased likelihood of being discharged to a nursing facility in AD and PD. Further research is necessary to understand the effects of GT on physician practices and patient expectations in advanced AD and PD.

Rapid motor fluctuations reveal short-timescale neurophysiological biomarkers of Parkinson's disease.

OBJECTIVE: Identifying neural activity biomarkers of brain disease is essential to provide objective estimates of disease burden, obtain reliable feedback regarding therapeutic efficacy, and potentially to serve as a source of control for closed-loop neuromodulation. In Parkinson's disease (PD), microelectrode recordings (MER) are routinely performed in the basal ganglia to guide electrode implantation for deep brain stimulation (DBS). While pathologically-excessive oscillatory activity has been observed and linked to PD motor dysfunction broadly, the extent to which these signals provide quantitative information about disease expression and fluctuations, particularly at short timescales, is unknown. Furthermore, the degree to which informative signal features are similar or different across patients has not been rigorously investigated. We sought to determine the extent to which motor error in PD across patients can be decoded on a rapid timescale using spectral features of neural activity. APPROACH: Here, we recorded neural activity from the subthalamic nucleus (STN) of subjects with PD undergoing awake DBS surgery while they performed an objective, continuous behavioral assessment that synthesized heterogenous PD motor manifestations to generate a scalar measure of motor dysfunction at short timescales. We then leveraged natural motor performance variations as a 'ground truth' to identify corresponding neurophysiological biomarkers. MAIN RESULTS: Support vector machines using multi-spectral decoding of neural signals from the STN succeeded in tracking the degree of motor impairment at short timescales (as short as one second). Spectral power across a wide range of frequencies, beyond the classic 'ß' oscillations, contributed to this decoding, and multi-spectral models consistently outperformed those generated using more isolated frequency bands. While generalized decoding models derived across subjects were able to estimate motor impairment, patient-specific models typically performed better. SIGNIFICANCE: These results demonstrate that quantitative information about short-timescale PD motor dysfunction is available in STN neural activity, distributed across various patient-specific spectral components, such that an individualized approach will be critical to fully harness this information for optimal disease tracking and closed-loop neuromodulation.