Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis.

Neurologists have a difficult time identifying sporadic cerebellar ataxia. Multiple system atrophy of the cerebellar type (MSA-C), spontaneous late cortical cerebellar atrophy, and prolonged alcohol use are a few possible causes. In a group of people with sporadic cerebellar ataxia that was not MSA-C, an autosomal-dominant spinocerebellar ataxia (SCA) mutation was recently discovered. Chinese single-hospital cohort will be used in this study to genetic screen for SCA-related genes. One hundred forty individuals with CA were monitored over 8 years. Thirty-one individuals had familial CA, 109 patients had sporadic CA, 73 had MSA-C, and 36 had non-MSA-C sporadic CA. In 28 of the 31 non-MSA-C sporadic patients who requested the test, we carried out gene analysis, including SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17, SCA31, and dentatorubro-pallidoluysian atrophy (DRPLA). The control group consisted of family members of the patients. In 57% of the instances with spontaneous CA that were not MSA-C, gene abnormalities were discovered. The most frequent exception among individuals with sporadic CA was SCA6 (36%), followed by monsters in SCA1, 2, 3, 8, and DRPLA. In contrast, 75% of the patients with familial CA had gene abnormalities, the most frequent of which was SCA6 abnormality. The age of 69 vs 59 was higher, and the CAG repeat length was a minor age of 23 vs 25 in the former instances compared to the last one among individuals with SCA6 anomalies that were sporadic as opposed to familial cases. In sporadic CA, autosomal-dominant mutations in SCA genes, notably in SCA6, are common. Although the cause of the increased incidence of SCA6 mutations is unknown, it may be related to a greater age of onset and varied penetrance of SCA6 mutations.

Knockout of Rnf213 Ameliorates Cerebral Ischemic-reperfusion Injury by Inhibiting Neuronal Apoptosis Through the Akt/GSK-3ß/ß-catenin/Bcl-2 Pathway.

Previous studies by us and others have shown that RING finger protein 213 (RNF213) is associated with cerebrovascular disease and systemic vasculopathy. Indeed, Rnf213 mRNA expression is increased in cerebral ischemia reperfusion injury (CIRI). The purpose of the present study was to investigate the role of Rnf213 in CIRI. Using the middle cerebral artery occlusion (MCAO) model, we confirmed that the expression of RNF213 protein was significantly upregulated in neurons in the ischemic penumbra. Rnf213 knockout mice were successfully generated using CRISPR/Cas9 technology. According to TTC staining and Bederson neurological scale, removal of Rnf213 decreased brain infarct volume and improved neurological deficit score, although the restoration of cerebral blood flow after MCAO was similar in WT and Rnf213-/- mice. In addition, the levels of p-Akt, p-GSK-3ß, ß-catenin and Bcl-2 were significantly increased 24 h after MCAO in the ischemic penumbra of the Rnf213-/- mice compared to WT mice, indicating that Rnf213 removal may ameliorate neuronal apoptosis by regulating the Akt/GSK-3ß/ß-catenin/Bcl-2 signaling pathway. Taken together, our study reveals that Rnf213 regulates neuronal apoptosis in CIRI, therefore impacting on brain infarct volume in brain ischemia.

Visual oculomotor abnormalities and vestibulo­ocular reflex dynamics in polyglutamine spinocerebellar ataxias (Review).

Spinocerebellar ataxias (SCAs) are a group of autosomal dominant neurodegenerative diseases that are characterized by cerebellar ataxia. The most common types of SCAs are caused by polyglutamine (polyQ)-encoding cytosine-adenine-guanine repeat expansions. Autosomal dominant SCAs share similar pathophysiological mechanisms. The cerebellum plays an important role in the generation and control of eye movement, and neuropathological findings indicate that cerebellar degeneration is commonly present in polyQ-SCAs. As a result, various patterns of oculomotor impairment are present in most SCA subtypes. The present review summarizes the visual oculomotor abnormalities and vestibulo-ocular reflex dynamics of the most common polyQ-SCAs, as well as their genetic, clinical and neuropathological features. In conclusion, the systemic evaluation of eye movement features is useful in the differential diagnosis of polyQ-SCAs.

Urinary Metabolite Signatures for Predicting Elderly Stroke Survivors with Depression.

BACKGROUND: Post-stroke depression (PSD) is a major complication in stroke survivors, especially in elderly stroke survivors. But there are still no objective methods to diagnose depression in elderly stroke survivors. Thus, this study was conducted to identify potential biomarkers for diagnosing elderly PSD subjects. METHODS: Elderly (60 years or older) stroke survivors with depression were assigned into the PSD group, and elderly stroke survivors without depression and elderly healthy controls (HCs) were assigned into the non-depressed group. Urinary metabolite signatures obtained from gas chromatography-mass spectrometry (GC-MS)-based metabolomic platform were collected. Both univariate and multivariate statistical analysis were used to find the differential urinary metabolites between the two groups. RESULTS: The 78 elderly HCs, 122 elderly stroke survivors without depression and 124 elderly PSD subjects were included. A set of 13 differential urinary metabolites responsible for distinguishing PSD subjects from non-depressed subjects were found. The Phenylalanine, tyrosine and tryptophan biosynthesis, Phenylalanine metabolism and Galactose metabolism were found to be significantly changed in elderly PSD subjects. The phenylalanine was significantly negatively correlated with age and depressive symptoms. Meanwhile, a biomarker panel consisting of 3-hydroxyphenylacetic acid, tyrosine, phenylalanine, sucrose, palmitic acid, glyceric acid, azelaic acid and α-aminobutyric acid was identified. CONCLUSION: These results provided candidate molecules for developing objective methods to diagnose depression in elderly stroke survivors, suggested that taking supplements of phenylalanine might be an effective method to prevent depression in elderly stroke survivors, and would be helpful for future revealing the pathophysiological mechanism of PSD.

Adult-onset SMALED2 due to a novel BICD2 mutation presenting with asymmetrical lower limb involvement.

Heterozygous variants in the bicaudal D homolog 2 gene (BICD2) are associated with autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED2). This disease is usually characterized by congenital or early-onset muscle weakness and atrophy of the lower extremities with benign or slow progression. We herein described an autosomal dominant inherited pedigree with SMALED2 in which the affected individuals presented with late adult-onset muscle weakness and wasting in the lower extremities. Obviously asymmetrical involvement of the lower limbs was observed in 3 individuals. Muscle magnetic resonance imaging revealed considerable fatty infiltrations in the middle compartment of the lower legs, including the soleus and tibialis posterior muscles. Muscle biopsy samples displayed a neurogenic pattern, but some chronic myopathy-like features were also observed. A novel heterozygous missense mutation (c.361C>G) was identified in a highly-conserved motif of BICD2. Patients with SMALED2 can present with late adult-onset and asymmetrical involvement of the lower limbs. The present study expands the clinical and mutational spectrum of SMALED2.