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Neural recordings using invasive devices in humans can elucidate the circuits underlying brain disorders, but have so far been limited to short recordings from externalized brain leads in a hospital setting or from implanted sensing devices that provide only intermittent, brief streaming of time series data. Here, we report the use of an implantable two-way neural interface for wireless, multichannel streaming of field potentials in five individuals with Parkinson’s disease (PD) for up to 15 months after implantation. Bilateral four-channel motor cortex and basal ganglia field potentials streamed at home for over 2,600 h were paired with behavioral data from wearable monitors for the neural decoding of states of inadequate or excessive movement. We validated individual-specific neurophysiological biomarkers during normal daily activities and used those patterns for adaptive deep brain stimulation (DBS). This technological approach may be widely applicable to brain disorders treatable by invasive neuromodulation. An implanted device in the brain enables wireless neural monitoring and stimulation for up to 15 months following implantation.

In 2016, the American Academy of Neurology (AAN) published practice guidelines for botulinum toxin (BoNT) in the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache. This article, focusing on dystonia, provides context for these guidelines through literature review. Studies that led to Food and Drug Administration (FDA) approval of each toxin for dystonia indications are reviewed, in addition to several studies highlighted by the AAN guidelines. The AAN guidelines for the use of BoNT in dystonia are compared with those of the European Federation of the Neurological Societies (EFNS), and common off-label uses for BoNT in dystonia are discussed. Toxins not currently FDA-approved for the treatment of dystonia are additionally reviewed. In the future, additional toxins may become FDA-approved for the treatment of dystonia given expanding research in this area.

Brain-stem and cerebellar encephalitis without the conventional anti-Ma2 autoantibody developed in a man with a history of seminoma. Phage display was used to discover IgG antibody directed at kelch-like protein 11. The same antibody was detected in 12 other men included in an archival series.

Dystonia is a complex disorder with numerous presentations occurring in isolation or in combination with other neurologic symptoms. Its treatment has been significantly improved with the advent of botulinum toxin and deep brain stimulation in recent years, though additional investigation is needed to further refine these interventions. Medications are of critical importance in forms of dopa-responsive dystonia but can be beneficial in other forms of dystonia as well. Many different rehabilitative paradigms have been studied with variable benefit. There is growing interest in noninvasive stimulation as a potential treatment, but with limited long-term benefit shown to date, and additional research is needed. This article reviews existing evidence for treatments from each of these categories. To date, there are many examples of incomplete response to available treatments, and improved therapies are needed.

While deep brain stimulation (DBS) remains an effective therapy for Parkinson’s disease (PD), sources of variance in patient outcomes are still not fully understood, underscoring a need for better prognostic criteria. Here, we leveraged routinely collected T1-weighted (T1-w) magnetic resonance imaging (MRI) data to derive patient-specific measures of brain structure and evaluate their usefulness in predicting changes in PD medications in response to DBS. Preoperative T1-w MRI data from 231 patients with PD were used to extract regional measures of fractal dimension (FD), sensitive to the structural complexities of cortical and subcortical brain. FD was validated as a biomarker of PD progression through comparison of patients with PD and healthy controls (HCs). This analysis revealed significant group differences in FD across nine brain regions, including frontal, occipital, insular, and basal ganglia areas, which supports its utility as a marker of PD. We evaluated the impact of adding imaging features (FD) to a clinical model that included demographics and clinical parameters (age, sex, total number and location of DBS electrodes), and preoperative motor response to levodopa. This model aimed to explain variance and predict changes in medication following DBS. Regression analysis revealed that inclusion of the FD of distributed brain areas correlated with post-DBS reductions in medication burden, explaining an additional 13.6% of outcome variance (R 2  = 0.388) compared to clinical features alone (R 2  = 0.252). Hypergraph-based classification learning tasks achieved an area under the receiver operating characteristic curve of 0.64 when predicting with clinical features alone, versus 0.76 when combining clinical and imaging features. These findings demonstrate that PD effects on brain morphology linked to disease progression influence DBS outcomes. The work also highlights FD as a potentially useful imaging biomarker to enhance DBS candidate selection criteria for optimized treatment planning. This study shows that structural complexity of cortical and subcortical areas, measured from standard anatomical MRI, can predict Parkinson’s patient response to deep brain stimulation using advanced hypergraph modeling techniques.

Objective: Anxiety and depression are prominent non-motor symptoms of Parkinson’s disease (PD), but their pathophysiology remains unclear. We sought to understand their neurophysiological correlates from chronic invasive recordings of the prefrontal cortex (PFC). Methods: We studied four patients undergoing deep brain stimulation (DBS) for their motor signs, who had comorbid mild to moderate anxiety and/or depressive symptoms. In addition to their basal ganglia leads, we placed a permanent prefrontal subdural 4-contact lead. These electrodes were attached to an investigational pulse generator with the capability to sense and store field potential signals, as well as deliver therapeutic neurostimulation. At regular intervals over 3–5 months, participants paired brief invasive neural recordings with self-ratings of symptoms related to depression and anxiety. Results: Mean age was 61 ± 7 years, mean disease duration was 11 ± 8 years and a mean Unified Parkinson’s Disease Rating Scale, with part III (UPDRS-III) off medication score of 37 ± 13. Mean Beck Depression Inventory (BDI) score was 14 ± 5 and Beck Anxiety Index was 16.5 ± 5. Prefrontal cortex spectral power in the beta band correlated with patient self-ratings of symptoms of depression and anxiety, with r -values between 0.31 and 0.48. Mood scores showed negative correlation with beta spectral power in lateral locations, and positive correlation with beta spectral power in a mesial recording location, consistent with the dichotomous organization of reward networks in PFC. Interpretation: These findings suggest a physiological basis for anxiety and depression in PD, which may be useful in the development of neurostimulation paradigms for these non-motor disease features.

People with Parkinson disease (PD) have a variety of complex medical problems that require detailed review at each clinical encounter for appropriate management. Care of other complex conditions has benefited from digital health solutions that efficiently integrate disparate clinical information. Although various digital approaches have been developed for research and care in PD, no digital solution to personalize and improve communication in a clinical encounter is readily available. We intend to improve the efficacy and efficiency of clinical encounters with people with PD through the development of a platform (PD-BRIDGE) with personalized clinical information from the electronic health record (EHR) and patient-reported outcome (PRO) data. Using human-centered design (HCD) processes, we engaged clinician and patient stakeholders in developing PD-BRIDGE through three phases: an inspiration phase involving focus groups and discussions with people having PD, an ideation phase generating preliminary mock-ups for feedback, and an implementation phase testing the platform. To qualitatively evaluate the platform, movement disorders neurologists and people with PD were sent questionnaires asking about the technical validity, usability, and clinical relevance of PD-BRIDGE after their encounter. The HCD process led to a platform with 4 modules. Among these, 3 modules that pulled data from the EHR include a longitudinal module showing motor ratings over time, a display module showing the most recently collected clinical rating scales, and another display module showing relevant laboratory values and diagnoses; the fourth module displays motor symptom fluctuation based on an at-home diary. In the implementation phase, PD-BRIDGE was used in 17 clinical encounters for patients cared for by 1 of 11 movement disorders neurologists. Most patients felt that PD-BRIDGE facilitated communication with their clinician (n=14, 83%) and helped them understand their disease trajectory (n=11, 65%) and their clinician's recommendations (n=11, 65%). Neurologists felt that PD-BRIDGE improved their ability to understand the patients' disease course (n=13, 75% of encounters), supported clinical care recommendations (n=15, 87%), and helped them communicate with their patients (n=14, 81%). In terms of improvements, neurologists noted that data in PD-BRIDGE were not exhaustive in 62% (n=11) of the encounters. Integrating clinically relevant information from EHR and PRO data into a visually efficient platform (PD-BRIDGE) can facilitate clinical encounters with people with PD. Developing new modules with more disparate information could improve these complex encounters even further.

Reports of drummers' dystonia are rare, particularly compared to the literature on dystonia in string, piano and brass players. Several cases of drummers' dystonia have been included in large series of multiple instrumentalists, but there are few reports comprised exclusively of drummers with musicians' dystonia. We present here a series of 12 drummers with task-specific, focal dystonia affecting their upper limbs while drumming and spanning multiple playing techniques and musical styles. We conducted a retrospective chart review of drummers with dystonia seen at academic Movement Disorders centers. All 12 patients were male, and the majority eventually developed spread of dystonia to tasks other than drumming. Ten of the 12 had dystonia affecting their fingers, while 8/12 had dystonia affecting the wrist. Only 1/12 had involvement proximal to the wrist. Pharmacologic interventions were largely ineffective; 3 had some benefit from botulinum toxin injections, but this was limited by problematic weakness in one drummer. The phenomenology in our series is concordant with prior reported cases, demonstrating frequent wrist involvement, though we also found that a greater proportion of patients had dystonia affecting the fingers. It could be hypothesized that different drumming techniques or musical styles modulate the relative risk of dystonic involvement of the different anatomical regions of the upper limb. Drummers' dystonia is one of the least common forms of musicians' dystonia, though this may reflect fewer numbers of these instrumentalists. We present the largest series of drummers' dystonia and review previously published cases. Our cohort, representing diverse drumming styles, showed frequent involvement of dystonia in the wrists and fingers.

In 2016, the American Academy of Neurology (AAN) published practice guidelines for botulinum toxin (BoNT) in the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache. This article, focusing on dystonia, provides context for these guidelines through literature review. Studies that led to Food and Drug Administration (FDA) approval of each toxin for dystonia indications are reviewed, in addition to several studies highlighted by the AAN guidelines. The AAN guidelines for the use of BoNT in dystonia are compared with those of the European Federation of the Neurological Societies (EFNS), and common of f-label uses for BoNT in dystonia are discussed. Toxins not currently FDA-approved for the treatment of dystonia are additionally reviewed. In the future, additional toxins may become FDA-approved for the treatment of dystonia given expanding research in this area.

Neural recordings in humans using invasive devices can elucidate the circuits underlying brain disorders, but have so far been limited to short recordings from externalized brain leads in a hospital setting or from implanted sensing devices that provide only intermittent, brief streaming of time series data. Here we report the use of an implantable two-way neural interface for wireless, multichannel streaming of field potentials in five patients with Parkinson’s disease for up to 15 months after implantation. Bilateral 4-channel motor cortex and basal ganglia field potentials streamed at home for over 2,600 hours were paired with behavioral data from wearable monitors for the neural decoding of states of inadequate or excessive movement. We validated patient-specific neurophysiological biomarkers during normal daily activities and used those patterns for adaptive deep brain stimulation. This technological approach may be widely applicable to brain disorders treatable by invasive neuromodulation.