A family with mental disorder as the first symptom finally confirmed with Gerstmann-Sträussler-Scheinker disease with P102L mutation in PRNP gene - case report.

Gerstmann-Sträussler-Scheinker (GSS) disease is an autosomal dominant neurodegenerative disease, and it is characterized by progressive cerebellar ataxia. Up to now, GSS cases with the p.P102L mutation have mainly been reported in Caucasian, but rarely in Asian populations. A 54-year-old female patient presented with an unstable gait in the hospital. Last year, she was unable to walk steadily and occasionally choked, could not even walk independently gradually. After taking her medical history, we found that she was misdiagnosed with schizophrenia before the gait problems. The patient's father showed similar symptoms and was diagnosed with brain atrophy at the age of 56, but her daughter showed no similar symptoms at present. On arrival at the Neurology Department, the patient's vital signs and laboratory examinations showed no abnormality. As the proband presented with cerebellar ataxia and had an obvious family history, we were sure that she had hereditary cerebellar ataxia. Then, patient's brain MRI showed an abnormal signal in the right parietal cortex and bilateral small ischaemic lesions in the frontal lobe. A gene panel (including 142 ataxia-related genes) was performed, and a heterozygous mutation PRNP Exon2 c.305C>T p. (Pro102Leu) was identified. Her daughter had the same heterozygous mutation. The patient was diagnosed with GSS with mental disorders as initial symptoms. After 2 months of TCM treatment, the patient's walking instability decreased, and her emotional fluctuations were less than before. In conclusion, we have reported a rare case of GSS in Sichuan, China, and the family with mental disorder as the first symptom was finally confirmed with GSS PRNP P102L mutation.

Monomethyl lithospermate alleviates ischemic stroke injury in middle cerebral artery occlusion mice in vivo and protects oxygen glucose deprivation/reoxygenation induced SHSY-5Y cells in vitro via activation of PI3K/Akt signaling.

Stroke is a fatal neurological disease, which seriously threatens human health and life. Ischemic stroke (IS) is the most common type of stroke in clinic. Its pathogenesis is very complex, mainly caused by nerve damage caused by brain blood supply disorder. Previous studies have confirmed that natural products play important roles in improving neurological disorders. Furthermore, our previous results also suggested that Shenxiong Tongmai granule, a clinically used herbal medicines' prescription, has a good ameliorating effect on IS. In the present study, we found that Monomethyl lithospermate (MOL), a constituent of Shenxiong Tongmai granule, significantly improved the neurological damage in middle cerebral artery occlusion (MCAO) rats. MOL can significantly improve the neurological deficit score of MCAO rats, and improve the damage of hippocampal neurons caused by ischemia-reperfusion (IR). At the same time, we also found that MOL could reduce the level of oxidative stress in the brain tissues of MCAO rats. Furthermore, the oxygen and glucose deprivation/Reoxygenation (OGD/R)-induced SHSY-5Y cell model was established in vitro to investigate the pharmacological activity and molecular mechanisms of MOL in improving the nerve injury of IS rats. The results showed that MOL could increase the cell viability of SHSY-5Y cells, inhibit the mitochondrial membrane potential (MMOP) collapse and suppress apoptosis. In addition, MOL also ameliorated the elevated oxidative stress level caused by OGR/R treatment in SHSY-5Y cells. Further mechanistic studies showed that MOL could activate the PI3K/AKT pathway via promoting the phosphorylation of PI3K and AKT in MCAO rats and OGR/R-induced SHSY-5Y cells, which could be partially blocked by addition of PI3K/AKT pathway inhibitor of LY294002. Taken together, our current study suggested that MOL exerts a protective effect against neural damage caused by IS in vivo and in vitro by activating the PI3K/AKT pathway.

Case Report: DARS Mutations Responsible for Hypomyelination With Brain Stem and Spinal Cord Involvement and Leg Spasticity.

Objective: Hypomyelination with brain stem and spinal cord involvement and leg spasticity (HBSL) is a rare form of leukodystrophy presenting with varying clinical and imaging features. We report a case of HBSL to investigate the clinical and radiological characteristics of HBSL resulting from cytoplasmic aspartyl-tRNA synthetase gene (DARS) mutations. Subjects: We report a patient of HBSL with compound heterozygous mutations in DARS1. To study the potential genetic variations of the patient, targeted next-generation sequencing, whole-exome sequencing, and Sanger sequencing were used. We reviewed the clinical and radiological features of the patient. The literature was thoroughly evaluated. Results: The patient suffered from developmental regression associated with lower limbs spasticity, developmental delay, and paralysis of the lower limbs since childhood. Decreased T1 and increased T2 signals were observed on the bilateral basal, centrum ovale, frontal lobe, parietal lobe, and ganglia in cervical cord magnetic resonance imaging (MRI). The patient had two compound heterozygous mutations (NM_001349:c.1363T > C and NM_001349:c.821C > G) in the DARS1 gene. Conclusion: Two mutations in DARS1 were found to be associated with HBSL, one of them being reported for the first time. These findings can be valuable for diagnosing and providing genetic counseling to HBSL patients in the future.

Leukoencephalopathy hypomyelination with brainstem and spinal cord involvement and leg spasticity caused by DARS1 mutations.

Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL), caused by aspartyl-tRNA synthetase (DARS1) gene mutations, is extremely rare, with only a few cases reported worldwide; thus, reports on HBSL treatment are few. In this review, we summarized the clinical manifestations, imaging features, treatment methods, and gene mutations responsible for HBSL based on relevant studies and cases.