Highlights This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients. Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use. Methods: This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey. Results: 205 patients completed the study. The co-primary endpoints were met (p≪0.0001), with 62% (TET-RAS) and 68% (BF-ADL) of 'severe' or 'moderate' patients improving to 'mild' or 'slight'. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced ≥50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported. Discussion: This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients.

Stroke, the sudden onset of brain dysfunction from a vascular cause, is one of the most common causes of long-term disability. Although rare during childbearing years, stroke is even more devastating when it occurs in a young woman trying to start a family. Pregnancy and the postpartum period are associated with an increased risk of ischemic stroke and intracerebral hemorrhage, although the incidence estimates have varied. There are several causes of stroke that are in fact unique to pregnancy and the postpartum period, such as preeclampsia and eclampsia, amniotic fluid embolus, postpartum angiopathy and postpartum cardiomyopathy. Data regarding these individual entities are scant. Most concerning is the lack of data regarding both prevention and acute management of pregnancy-related stroke. The purpose of this article is to summarize existing data regarding incidence, risk factors and potential etiologies, as well as treatment strategies for stroke in pregnancy.

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The evolution of mammalian brain function depends in part on levels of natural, heritable variation in numbers, location, and function of neurons. However, the nature and amount of natural genetic variation in neural traits and their physiological link to variation in function or evolutionary change are unknown. We estimated the level of within-population heritable variation in the number of gonadotropin-releasing hormone (GnRH) neurons, which play a major role in reproductive regulation, in an unselected outbred population recently derived (<10 generations) from a single natural population of white-footed mice (Peromyscus leucopus, Rafinesque). Young adult male mice exhibited an approximately threefold variation in the number of neurons immunoreactive for GnRH in the brain areas surveyed, as detected using SMI-41 antibody with a single-label avidin-biotin complex method. Consistent with earlier findings of selectable variation in GnRH neurons in this population, the level of genetic variation in this neuronal trait within this single population was high, with broadsense heritability using full-sib analysis estimated at 0.72 (P<0.05). Either weak selection on this trait or environmental variation that results in inconsistent selection on this trait might allow a high level of variation in this population.

Objective To highlight the importance of a broad differential and histopathologic confirmation in patients with newly diagnosed cancer with brain lesions atypical for CNS metastasis. MethodsWe report 2 cases of biopsy-proven CNS vasculitis in patients undergoing treatment for a newly diagnosed nonmetastatic cancer. Comprehensive medical record review was performed to identify the clinical presentation, representative neuroimaging, histopathologic features, and response to treatment. ResultsPatient 1 presented 1 month into induction therapy of malignant vaginal squamous cell carcinoma (stage 3, T2N1M0) with acute episodic left-sided hemiparesis due to seizure activity progressing to severe encephalopathy. Imaging revealed a right frontoparietal lesion while systemic workup was unrevealing. Biopsy demonstrated necrotizing vasculitis. Patient 2 presented 6 months after diagnosis of right breast invasive ductal carcinoma (stage IIa, T2N0M0, estrogen receptor-positive, progesterone receptor-positive, human epidermal growth factor receptor-2 positive) with subacute bifrontal headaches with associated phonophobia. Imaging showed hyperintense lesions involving the right temporoparietal region and systemic workup was unrevealing. Brain biopsy showed a necrotizing vasculitis. Patient 1 was treated with methyprednisolone and plasmapheresis and patient 2 was treated with prednisone. Both patients showed complete resolution of symptoms shortly after treatment and improvement on imaging. ConclusionsThese cases highlight the importance of comprehensive evaluation of new brain lesions in patients with nonmetastatic solid tumors. Characteristics of new brain lesions in patients with cancer that should raise suspicion of diagnoses other than brain metastasis include (1) primary malignancy without regional or distant metastasis, (2) imaging without discrete mass-like enhancement, and (3) cortically based location of lesions not at the gray-white matter junction.