A Cysteinyl-tRNA Synthetase Mutation Causes Novel Autosomal-Dominant Inheritance of a Parkinsonism/Spinocerebellar-Ataxia Complex.

This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes, which has not been depicted by the known neurodegenerative disease. We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia, Parkinsonism, and cognitive function, as well as brain magnetic resonance imaging scans with seven sequences. We searched for co-segregations of abnormal repeat-expansion loci, pathogenic variants in known spinocerebellar ataxia-related genes, and novel rare mutations via whole-genome sequencing and linkage analysis. A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay. This pedigree presented novel late-onset core characteristics including cerebellar ataxia, Parkinsonism, and pyramidal signs in all nine affected members. Brain magnetic resonance imaging showed cerebellar/pons atrophy, pontine-midline linear hyperintensity, decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus, and hypo-intensities of the cerebellar dentate nuclei, basal ganglia, mesencephalic red nuclei, and substantia nigra, all of which suggested neurodegeneration. Whole-genome sequencing identified a novel pathogenic heterozygous mutation (E795V) in the CARS gene, meanwhile, exhibited none of the known repeat-expansions or point mutations in pathogenic genes. Remarkably, this CARS mutation causes a 20% decrease in aminoacylation activity to charge tRNACys with L-cysteine in protein synthesis compared with that of the wild type. All family members carrying a heterozygous mutation CARS (E795V) had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia. These findings identify novel pathogenesis of Parkinsonism-spinocerebellar ataxia and provide insights into its genetic architecture.

[Clinical Characteristics of Autoimmune Disease with Dual Seropositive Antibodies of Leucine-rich Glioma Inactivated 1 and Contactin-associated Protein 2].

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.

Cranial and lumbosacral hypertrophic pachymeningitis associated with systemic lupus erythematosus: A case report.

BACKGROUND: Hypertrophic pachymeningitis (HP) is a chronic disease characterized by inflammatory hypertrophy and fibrosis of dura mater. It can be divided into cranial and spinal forms depending on the location of the lesion. HP involving 2 separate sites simultaneously is quite uncommon. CASE SUMMARY: This study presents a case of a 49-year-old woman with pathologically confirmed cranial and lumbosacral hypertrophic pachymeningitis associated with systemic lupus erythematosus (SLE), which is a rare etiology of HP. She experienced persistent numbness and pain of the left lower limb, followed by headache and seizures. In laboratory tests, levels of erythrocyte sedimentation rate and C-reactive protein were elevated, and antinuclear antibodies and anti-double-strand deoxyribonucleic acid (DNA) antibodies were detected. Magnetic resonance imaging revealed dural thickening with homogenous gadolinium enhancement both at lumbosacral level and over cerebral convexities. Histology suggested chronic inflammation in spinal dura mater with extensive fibrosis, dense lymphoplasmacytic infiltrate, and focal vasculitis. Treatment with corticosteroids and cyclophosphamide was started with significant clinical and radiological improvement. CONCLUSION: HP is etiologically heterogeneous. Despite its rarity, SLE should be considered in the differential diagnosis of HP. Early recognition and therapy may provide an optimal outcome.

The clinical and radiological spectrum of posterior reversible encephalopathy syndrome: a retrospective series of 24 patients.

BACKGROUND AND PURPOSE: Some patients with posterior reversible encephalopathy syndrome (PRES) present with atypical clinical and neuroimaging findings. The purpose of this study is to review the clinical and neuroimaging findings in patients diagnosed with PRES. METHODS: We retrospectively included all patients diagnosed with PRES between January 2005 and March 2009. We reviewed demographic, clinical and laboratory data, neuroimaging findings, and prognosis. RESULTS: Twenty-four patients were included with a median age of 19 years. The clinical presentations included seizures (91.7%), headache (83.3%), visual disturbance (62.5%), encephalophathy (29.2%), and paralysis (8.3%). Co-morbidities included systemic lupus erythematous (29.2%), kidney disease (20.8%), eclampsia (20.8%), renal artery stenosis (12.5%), Takayasu arteritis (4.2%), Sheehan's syndrome (4.2%), allergic purpura (4.2%), and acute intermittent porphyria (4.2%). Acute elevation of blood pressure was found in 22 patients (91.7%). Ten patients (41.7%) used steroids or immunosuppressants, three (12.5%) had acute renal failure before the symptoms. Atypical neuroimaging features included involvement of the frontal lobe (54.2%), basal ganglia (4.2%) or cortex (8.3%), and irreversible lesions (3/18, 16.7%). CONCLUSIONS: A large proportion of patients with PRES may present with atypical neuroimaging findings. Apart from the known risk factors, such as hypertension, immunosuppressants, and renal failure of various etiologies may be the precipitants of PRES.

[Etiological, clinical and imaging characters of reversible posterior encephalopathy syndrome].

OBJECTIVE: To elucidate the clinical and imaging characters of reversible posterior encephalopathy syndrome (PRES) and to discuss the etiological factors and the probable pathogenesis. METHOD: Retrospective analysis of basal diseases, clinical manifestations and imaging characters of 13 PRES patients was conducted with follow-ups. RESULTS: The common associated diseases are various kinds of kidney disease and renal inadequacy, eclampsia of gravidity and postpartum, connective tissue disease and immunosuppressives, et al. The main clinical manifestations are headache, convulsion, poor vision, changes of psychology or consciousness. The radiological findings are multifocal, symmetrical and posteriorly distributed in the cerebral hemispheres involving bilateral grey and white matter abnormalities in occipital, parietal and frontal regions. The majority of patients with PRES have an excellent prognosis. CONCLUSION: The etiological factors and pathogenesis of PRES are different and not all of them are reversible. Thus it is decisive to take specific and appropriate measures.