The Spectrum of Movement Disorders Associated with Systemic Lupus Erythematosus.

Purpose Of Review: This review seeks to examine the prevalence, pathophysiology, diagnostic challenges, and treatment strategies for movement disorders in patients with systemic lupus erythematosus (SLE).

Recent Findings: In recent years, the spectrum and number of autoimmune movement disorders has rapidly expanded with the identification of neuronal and paraneoplastic antibodies which should be considered in the differential for patients with acute to subacute development of a movement disorder. The identification of SLE in a patient with a new onset movement disorder may lead to earlier treatment with immune therapies especially if other systemic manifestations are present.

Cell biology of Parkinson's disease: Mechanisms of synaptic, lysosomal, and mitochondrial dysfunction.

Parkinson's disease (PD) is a growing cause of disability worldwide and there is a critical need for the development of disease-modifying therapies to slow or stop disease progression. Recent advances in characterizing the genetics of PD have expanded our understanding of the cell biology of this disorder. Mitochondrial oxidative stress, defects in synaptic function, and impaired lysosomal activity have been shown to be linked in PD, resulting in a pathogenic feedback cycle involving the accumulation of toxic oxidized dopamine and alpha-synuclein.

Clinical Problem-Solving: Lower Extremity Weakness & Paresthesia in an Immunocompromised Patient With a Complex Cancer History.

We present a case of new onset bilateral lower extremity weakness, paresthesia, urinary retention and bowel incontinence in a 51-year-old man. He had a complicated history of acute myelogenous leukemia with known central nervous system (CNS) and leptomeningeal involvement status post allogenic stem cell transplant complicated by chronic graft versus host disease (GVHD). We review the differential diagnosis as the physical exam and diagnostic results evolved.

Hippocampal BMP signaling as a common pathway for antidepressant action.

The benefits of current treatments for depression are limited by low response rates, delayed therapeutic effects, and multiple side effects. Antidepressants affect a variety of neurotransmitter systems in different areas of the brain, and the mechanisms underlying their convergent effects on behavior have been unclear. Here we identify hippocampal bone morphogenetic protein (BMP) signaling as a common downstream pathway that mediates the behavioral effects of five different antidepressant classes (fluoxetine, bupropion, duloxetine, vilazodone, trazodone) and of electroconvulsive therapy.

Glucocerebrosidase dysfunction in neurodegenerative disease.

Parkinson's disease (PD) and related neurodegenerative disorders, termed the synucleinopathies, are characterized pathologically by the accumulation of protein aggregates containing α-synuclein (aSyn), resulting in progressive neuronal loss. There is considerable need for the development of neuroprotective strategies to halt or slow disease progression in these disorders. To this end, evaluation of genetic mutations associated with the synucleinopathies has helped to elucidate crucial mechanisms of disease pathogenesis, revealing key roles for lysosomal and mitochondrial dysfunction.

Spinocerebellar ataxia clinical trials: opportunities and challenges.

The spinocerebellar ataxias (SCAs) are a group of dominantly inherited diseases that share the defining feature of progressive cerebellar ataxia. The disease process, however, is not confined to the cerebellum; other areas of the brain, in particular, the brainstem, are also affected, resulting in a high burden of morbidity and mortality. Currently, there are no disease-modifying treatments for the SCAs, but preclinical research has led to the development of therapeutic agents ripe for testing in patients.

Newly diagnosed enhancing lesions: Steroid initiation may impede diagnosis of lymphoma involving the central nervous system.

Establishing the pathologic diagnosis of central nervous system (CNS) lymphoma can be challenging, yet management of this potentially curable disease depends heavily on it. One avoidable impediment to obtaining an accurate and timely diagnosis is the pre-operative administration of steroids, which causes tumor involution and prevents appropriate sampling of viable tissue. We discuss a case of primary CNS lymphoma that highlights the evolution of the disease and the attempts to establish a diagnosis in the setting of prior administration of corticosteroids.

β1-integrin restricts astrocytic differentiation of adult hippocampal neural stem cells.

Integrins are transmembrane receptors that mediate cell-extracellular matrix and cell-cell interactions. The β1-integrin subunit is highly expressed by embryonic neural stem cells (NSCs) and is critical for NSC maintenance in the developing nervous system, but its role in the adult hippocampal niche remains unexplored. We show that β1-integrin expression in the adult mouse dentate gyrus (DG) is localized to radial NSCs and early progenitors, but is lost in more mature progeny.