Previous work has established that compound mutations and homozygous loss of function of the parkin gene cause early-onset, autosomal recessive parkinsonism. Classically, this disease has been associated with loss of dopaminergic neurons in the substantia nigra pars compacta and locus ceruleus, without Lewy body pathology. We have sequenced the parkin gene of 38 patients with early-onset Parkinson's disease (<41 years). Two probands with mutations were followed up. Clinical evaluation of their families was performed, blinded to both genetic and pathological findings. Chromosome 6q25.2-27 haplotype analysis was carried out independently of the trait; parkin gene expression was examined at both the RNA and protein levels. Haplotype analysis of these families revealed a common chromosome 6, with a novel 40 bp exon 3 deletion that cosegregated with disease. In the proband of the smaller kindred, an exon 7 R275W substitution was identified in addition to the exon 3 deletion; RNA analysis demonstrated that the mutations were on alternate transcripts. However, Lewy body pathology typical of idiopathic Parkinson's disease was found at autopsy in the proband from the smaller kindred. These data suggest that compound heterozygous parkin mutations and loss of parkin protein may lead to early-onset parkinsonism with Lewy body pathology, while a hemizygous mutation may confer increased susceptibility to typical Parkinson's disease.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the

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Objective:To summarize the clinical presentation, pathogenesis, neuroimaging, treatment, and outcome of stroke-like migraine attacks after radiation therapy (SMART) syndrome, and to propose diagnostic criteria for this disorder.Data Sources:We searched the PubMed database for articles in English published from 1995 to 2015 using the terms of “stroke-like AND migraine AND radiation.” Reference lists of the identified articles and reviews were used to retrieve additional articles.Study Selection:Data and articles related to late-onset effects of cerebral radiation were selected and reviewed.Results:SMART is a rare condition that involves complex migraines with focal neurologic deficits following cranial irradiation for central nervous system malignancies. The recovery, which ranges from hours to days to weeks, can be partial or complete. We propose the following diagnostic criteria for SMART: (1) Remote history of therapeutic external beam cranial irradiation for malignancy; (2) prolonged, reversible clinical manifestations mostly years after irradiation, which may include migraine, seizures, hemiparesis, hemisensory deficits, visuospatial defect, aphasia, confusion and so on; (3) reversible, transient, unilateral cortical gadolinium enhancement correlative abnormal T2 and fluid-attenuated inversion recovery signal of the affected cerebral region; (4) eventual complete or partial recovery, the length of duration of recovery ranging from hours to days to weeks; (5) no evidence of residual or recurrent tumor; (6) not attributable to another disease. To date, no specific treatment has been identified for this syndrome.Conclusions:SMART is an extremely rare delayed complication of brain irradiation. However, improvements in cancer survival rates have resulted in a rise in its frequency. Hence, awareness and recognition of the syndrome is important to make a rapid diagnosis and avoid aggressive interventions such as brain biopsy and cerebral angiography.