Interactive mobile application for Parkinson's disease deep brain stimulation (MAP DBS): An open-label, multicenter, randomized, controlled clinical trial.

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), but its efficacy is tied to DBS programming, which is often time consuming and burdensome for patients, caregivers, and clinicians. Our aim is to test whether the Mobile Application for PD DBS (MAP DBS), a clinical decision support system, can improve programming. METHODS: We conducted an open-label, 1:1 randomized, controlled, multicenter clinical trial comparing six months of SOC standard of care (SOC) to six months of MAP DBS-aided programming. We enrolled patients between 30 and 80 years old who received DBS to treat idiopathic PD at six expert centers across the United States. The primary outcome was time spent DBS programming and secondary outcomes measured changes in motor symptoms, caregiver strain and medication requirements. RESULTS: We found a significant reduction in initial visit time (SOC: 43.8 ± 28.9 min n = 37, MAP DBS: 27.4 ± 13.0 min n = 35, p = 0.001). We did not find a significant difference in total programming time between the groups over the 6-month study duration. MAP DBS-aided patients experienced a significantly larger reduction in UPDRS III on-medication scores (-7.0 ± 7.9) compared to SOC (-2.7 ± 6.9, p = 0.01) at six months. CONCLUSION: MAP DBS was well tolerated and improves key aspects of DBS programming time and clinical efficacy.

The Clinical Value of Patient Home Videos in Movement Disorders.

Background: Numerous studies have shown the value of patient home video recordings within the field of epilepsy. Despite the growing influence of mobile technology and telemedicine, there is a paucity of studies examining the role of home videos in the diagnosis of movement disorders. Objective: To characterize the clinical value of patient home videos in a movement disorders practice. Methods: We performed a retrospective review from our video database over the past 10 years and identified 20 encounters where an in-person, clinic evaluation and studio video were supplemented by a home video. We reviewed these encounters to determine if the home video added additional value to the clinic video. The home videos were screened by 3 movement disorders attendings and 3 movement disorders fellows to assess for quality and to determine whether or not the patient phenomenology could accurately be identified. Results: Of the 20 videos identified, 10 (50%) were determined to be of additional clinical value. In 62.4% of evaluations movement disorders attendings and fellows were able to identify phenomenology from the home videos consistent with the final diagnosis. Videos rated as "poor" quality had significantly lower odds of leading to a correct phenomenology (odd ratio: 0.07, 95% confidence interval [0.01-0.72]) than those rated as "excellent" quality. Conclusions: Patients should be encouraged to produce good quality home videos, particularly in paroxysmal or fluctuating movement disorders, as they may add value to the eventual diagnosis and management.

Pilot Study to Evaluate Pimavanserin for the Treatment of Motor and Behavioral Symptoms of Tourette Syndrome.

BACKGROUND: Pimavanserin is a serotonin 2A receptor inverse agonist and antagonist used for the treatment of hallucinations and delusions in Parkinson's disease psychosis. Numerous studies support a modulatory role of serotonin in Tourette syndrome (TS). OBJECTIVES: To determine whether or not pimavanserin affects TS symptoms. METHODS: In this open-label study of TS adult patients, pimavanserin was titrated to 34 mg/day over 1 week and continued for an additional 7 weeks followed by a 2-week washout. Tic severity, the primary outcome measure, was assessed by the Yale Global Tic Severity Scale Total Tic Severity score (YGTSS-TTS). Secondary outcome measures included changes in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Tourette Syndrome Clinical Global Impression of Change (TS-CGIC), the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII), and the Gilles de la Tourette Syndrome - Quality of Life scale (GTS-QOL). RESULTS: We enrolled 12 patients, but 2 dropped out after week 2 due to non-serious side effects. In the 10 patients, mean (standard deviation (SD)) age 34 (12.9) who completed the study the mean (SD) baseline YGTSS-TTS was 34 (9.3). This decreased by 3.6 (4.9) points at week 8, a 12% reduction in tic severity (P = 0.03). This improvement is small and may not be clinically important. Significant improvement was noted in the TS-CGIC, TS-PGII and GTS-QO. No serious adverse events were reported. CONCLUSIONS: The results of this study suggest that pimavanserin is safe and associated with improvement in motor and non-motor TS symptoms. These findings warrant further study by a larger, placebo-controlled, trial.

Generalized Periodic Discharges With Triphasic Morphology in the Setting of Aztreonam Neurotoxicity.

Generalized periodic discharges with triphasic morphology (GPDs + TWm) have been reported with multiple metabolic and drug toxicities. Beta-lactam antibiotics in some cases can cause neurotoxicity with GPDs + TWm on EEG. There are no reports in the literature of aztreonam causing neurotoxicity and GPDs + TWm. Here we describe GPDs + TWm and encephalopathy developing in a patient with underlying dementia and acute kidney injury who was started on aztreonam for cystitis. Neurotoxic effects of beta-lactam antibiotics have been well studied at this point, likely related to GABA receptor antagonism by the beta lactam ring. Risk factors for toxicity include, advanced age, prior neurological injury and decreased renal clearance. This patient carried multiple risk factors for beta-lactam neurotoxicity. Discontinuation of aztreonam led to a resolution of GPDs + TWm on EEG, and regression of encephalopathy.

Parkinson's disease and skin.

Parkinson's disease is associated with a variety of dermatologic disorders and the study of skin may provide insights into pathophysiological mechanisms underlying this common neurodegenerative disorder. Skin disorders in patients with Parkinson's disease can be divided into two major groups: 1) non-iatrogenic disorders, including melanoma, seborrheic dermatitis, sweating disorders, bullous pemphigoid, and rosacea, and 2) iatrogenic disorders related either to systemic side effects of antiparkinsonian medications or to the delivery system of antiparkinsonian therapy, including primarily carbidopa/levodopa, rotigotine and other dopamine agonists, amantadine, catechol-O-methyl transferase inhibitors, subcutaneous apomorphine, levodopa/carbidopa intestinal gel, and deep brain stimulation. Recent advances in our understanding of the role of α-synuclein in peripheral tissues, including the skin, and research based on induced pluripotent stem cells derived from skin fibroblasts have made skin an important target for the study of Parkinson's disease pathogenesis, drug discovery, novel stem cell therapies, and diagnostics.

Current Management of Tics and Tourette Syndrome: Behavioral, Pharmacologic, and Surgical Treatments.

Tourette syndrome is a heterogeneous neurobehavioral disorder manifested by childhood-onset motor and phonic tics, often accompanied by a variety of behavioral comorbidities, including attention deficit and obsessive compulsive disorder. Treatment must be tailored to the needs and goals of the individual patients and their families. All patients should receive education on the condition and, if possible, engage behavioral therapy targeted towards tics and/or comorbidities. Pharmacological therapies, such as alpha agonists, topiramate, and vesicular monoamine transport type 2 inhibitors, are generally used as first-line therapies in patients with troublesome tics that are not controlled by behavioral therapy or when the latter is not available or accessible. Botulinum toxin injections can be used in patients with bothersome focal tics. Second-line therapy includes antipsychotics, such as fluphenazine, aripiprazole, risperidone, and ziprasidone. These medications are generally efficacious but carry the risk of metabolic syndrome, tardive dyskinesia, and other side effects. Much more research is needed before novel therapies such as cannabis-derived products or transcranial magnetic stimulation can be recommended. There is promise in ongoing clinical trials with D1 receptor antagonist ecopipam and other experimental therapeutics. Patients with tics that are refractory to conventional treatments may be candidates for deep brain stimulation, but further studies are needed to determine the optimal target selection.

Subacute Encephalopathy With Seizures in Alcoholics (SESA) Presenting as Focal Nonconvulsive Status Epilepticus.

PURPOSE: To acquaint readers with the underrecognized subacute encephalopathy with seizures in chronic alcoholics (SESA) that has more recently been associated with different types of status epilepticus. METHODS: Case reports and review of the literature on SESA and nonconvulsive status epilepticus (NCSE). RESULTS: Two cases: one with alternating bifrontoparietal NCSE, and one with focal, confusional NCSE, with imaging and EEG correlates. CONCLUSION: Underrecognized SESA may present as NCSE with focal clinical, EEG and reversible diffusion-weighted MRI abnormalities, warranting expedited diagnosis and antiseizure treatment to minimize morbidity.

APP independent and dependent effects on neurite outgrowth are modulated by the receptor associated protein (RAP).

Amyloid precursor protein (APP) and its secreted form, sAPP, contribute to the development of neurons in hippocampus, a brain region critical for learning and memory. Full-length APP binds the low-density lipoprotein receptor-related protein (LRP), which stimulates APP endocytosis. LRP also contributes to neurite growth. Furthermore, the receptor associated protein (RAP) binds LRP in a manner that blocks APP-LRP interactions. To elucidate APP contributions to neurite growth for full-length APP and sAPP, we cultured wild type (WT) and APP knockout (KO) neurons in sAPPα and/or RAP and measured neurite outgrowth at 1 day in vitro. Our data reveal that WT neurons had less axonal outgrowth including less axon branching. RAP treatment potentiated the inhibitory effects of APP. KO neurons had significantly more outgrowth and branching, especially in response to RAP, effects which were also associated with ERK2 activation. Our results affirm a major inhibitory role by full-length APP on all aspects of axonal and dendritic outgrowth, and show that RAP-LRP binding stimulated axon growth independently of APP. These findings support a major role for APP as an inhibitor of neurite growth and reveal novel signaling functions for LRP that may be disrupted by Alzheimer's pathology or therapies aimed at APP processing.