Protein kinetics of superoxide dismutase-1 in familial and sporadic amyotrophic lateral sclerosis

OBJECTIVE: Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark of SOD1-related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo protein kinetics may clarify how SOD1 influences neurodegeneration and inform optimal dosing for therapies that lower SOD1 transcripts. METHODS: We employed stable isotope labeling paired with mass spectrometry to evaluate in vivo protein kinetics and concentration of soluble SOD1 in cerebrospinal fluid (CSF) of SOD1 mutation carriers, sporadic ALS participants and controls. A deaminated SOD1 peptide, SDGPVKV, that correlates with protein stability was also measured. RESULTS: In participants with heterozygous SOD1 INTERPRETATION: These results highlight the ability of stable isotope labeling approaches and peptide deamidation to discern the influence of disease mutations on protein kinetics and stability and support implementation of this method to optimize clinical trial design of gene and molecular therapies for neurological disorders. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03449212

Spinocerebellar ataxia-10 with paranoid schizophrenia

Spino-cerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder that is characterized by cerebellar ataxia, seizures and nystagmus with a fragmented pursuit. Schizophrenia has been reported with SCAs 1 and 2 yet in SCA 10, psychiatric manifestations are uncommon. We report a Hispanic family involving a father and his four children with SCA10 genetic mutation. Two of his children, a 20-year-old female and a 23-year-old male, presented with gradually progressive spino-cerebellar ataxia and paranoid schizophrenia. Neurological examination revealed ocular dysmetria, dysdiadokinesia, impaired finger-to-nose exam, gait ataxia and hyperreflexia in both the cases. Additionally, they had a history of psychosis with destructive behavior, depression and paranoid delusions with auditory hallucinations. Serology and CSF studies were unremarkable and MRI brain revealed cerebellar volume loss. Ultimately, a test for ATAXIN-10 mutation was positive thus confirming the diagnosis of SCA10 in father and his four children. We now endeavor to investigate the association between schizophrenia and SCA10

Complementary and alternative medicine in chronic neurological pain

Background: There is a growing trend towards opting for complementary and alternative medicine (CAM) in the therapeutic management of various medical disorders. We try to evaluate the current recommendations for CAM therapies in key neurological disorders. Materials and Methods: Sources like PubMed, Embase, UCLA libraries, USC libraries, and National Center for Complementary and Alternative Medicine (NCCAM) books were searched to gather data for this review. Results: We discuss the current recommendations for CAM therapies in headaches, neck pains, lower back pains, neuropathic pains, and cancer-related pains. The CAM therapies discussed include natural therapies, mind and body therapies, and several other modalities. Conclusion: We conclude that in spite of vast literature available on the CAM therapies for neurological disorders; there is little evidence for the most beneficial CAM remedies that target common neurological disorders. Although new CAM modalities are brought to light in addition to those that have existed for centuries, further scientific data from evidence-based studies is needed to accurately compare the CAM therapies amongst each other and allopathic treatments

An unusual case of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy with occipital lobe involvement

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant angiopathy caused by a mutation in the notch 3 gene on chromosome 19. Clinically, patients may be asymptomatic or can present with recurrent ischemic episodes and strokes leading to dementia, depression, pseudobulbar palsy, and hemi- or quadraplegia. Additional manifestations that have been described include migraine (mostly with aura), psychiatric disturbances, and epileptic seizures. Neuroimaging is essential to the diagnosis of CADASIL. On imaging CADASIL is characterized by symmetric involvement by confluent lesions located subcortically in the frontal and temporal lobes as well as in the insula, periventricularly, in the centrum semiovale, in the internal and external capsule, basal ganglia, and brain stem; with relative sparing of the fronto-orbital and the occipital subcortical regions. We describe a 49 year old male with CADASIL with absence of temporal lobe findings on MRI but predominant lesions within the periventricular white matter, occipital lobes with extension into the subcortical frontal lobes, corpus callosum and cerebellar white matter. Although CADASIL characteristically presents with anterior temporal lobe involvement, these findings may be absent and our case addresses the atypical imaging findings in CADASIL

Changes in functional magnetic resonance imaging with

BACKGROUND: The neural substrates of AIMS AND OBJECTIVE: Pilot data of a functional magnetic resonance imaging (fMRI) study is presented to observe and understand the selective activations of designated brain regions during meditation. MATERIAL AND METHODS: Four trained healthy Patanjali Yoga practitioners in their mid-60s participated in this prototype interventional study. A three-part 1-min block design alternating between meditation (test) and relaxation (control) phase with an imaginary visual fixation and auditory stimulation was used. RESULT AND OBSERVATION: The fMRI images revealed strong activation in the right prefrontal regions during the visual and auditory fixation meditation phases compared to no activations during the relaxation phase. A comparison between the visual and auditory fixations revealed shifts within the prefrontal and temporal regions. In addition, activation in occipital and temporal regions was observed during the meditation phase. Occipital lobe activation was more apparent during visual meditation phase. CONCLUSION: It is concluded that specific fMRI brain activations are observed during different forms o

Ischemic Stroke in a Patient with Parry-Romberg Syndrome.

OBJECTIVE: This study aimed to discuss a case of a patient with a known diagnosis of Parry-Romberg syndrome (PRS) presenting with ischemic stroke, the second such reported case. BACKGROUND: PRS is a rare genetic disorder with progressive hemifacial atrophy, which usually presents within the first 2 decades of life. Neurologic manifestations include trigeminal neuralgia with associated deafness, hemifacial pain with associated migraine headaches, seizures, movement disorders, and neuropsychiatric symptoms. Many patients have elevated antinuclear antibody (ANA) titers. However, stroke is uncommon. CASE DESCRIPTION: A 34-year-old right-handed woman, diagnosed with PRS at age 15, presented with right-sided weakness on waking up. Brain magnetic resonance imaging revealed a small infarct of the posterior limb of the left internal capsule. Vessel imaging revealed an aberrant right subclavian artery. Atrophy of the right-sided muscles of mastication is consistent with her known diagnosis of right-sided PRS. Stroke workup revealed a patent foramen ovale; however, no evidence of deep venous thrombosis was found. Hypercoagulability workup revealed an elevated ANA. The cause of stroke in this patient with PRS remains unclear, as she has no known risk factors. CONCLUSION: It is possible that elevated inflammatory markers associated with PRS may cause a proinflammatory state and predispose patients to small-vessel vasculopathy. It is important to note the association between PRS and ischemic stroke