Measurement of GCase Activity in Cultured Cells.

Glucocerebrosidase (GCase), which is encoded by the GBA1 gene, has lysosomal glycoside hydrolase activity that hydrolyzes glucosylceramide. Defects in GCase lead to the accumulation of glucosylceramide, which causes the development of the lysosomal storage disease known as Gaucher's disease. Loss-of-function mutations in the GBA1 gene are the most important genetic risk factor for synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies. Recent studies on PD genes associated with lysosomal function suggest that GCase activity is decreased in cell models of PD and in neurons derived from PD patients. In this chapter, we describe a protocol to measure GCase activity in cultured cells.

Eicosapentaenoic-to-Arachidonic Acid Ratio Predicts Mortality and Recurrent Vascular Events in Ischemic Stroke Patients.

AIMS: The ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) is related to major adverse events and death in cardiovascular diseases. The association between long-term prognosis of ischemic stroke and EPA/AA ratio has not been clarified. METHODS: Acute ischemic stroke patients who had undergone blood examinations for polyunsaturated fatty acids were enrolled. Major cardiovascular events, including recurrence of ischemic stroke, occurrence of cardiovascular and peripheral artery diseases and hemorrhagic stroke, and death, were analyzed, retrospectively. Cox proportional hazards regression analysis was used to explore factors, including clinical characteristics, laboratory data including EPA/AA ratio, and treatments associated with major cardiovascular events and death. RESULTS: A total of 269 patients (mean age, 70±13 years; 179 men) were enrolled. During follow-up (mean, 2.3 ±1.0 years), 64 patients exhibited major cardiovascular events and death (annualized rate, 10.5% per person-year). Multivariate Cox analysis revealed that EPA/AA ratio (hazard ratio, 0.26; 95% confidence interval, 0.07- 0.99; p=0.048) and statin therapy (hazard ratio, 0.43; 95% confidence interval, 0.25-0.73; p=0.002) correlated inversely with major cardiovascular events and death. In the Kaplan-Meier analysis, cumulative event-free rates were significantly lower among patients with EPA/AA ratio ＜0.33 and patients without statin therapy (p=0.006). CONCLUSIONS: Low EPA/AA ratio at baseline and treatment without statins could predict mortality, recurrent ischemic stroke, cardiovascular and peripheral artery diseases, and hemorrhagic stroke among patients with acute ischemic stroke. The combination of baseline EPA/AA ratio and statin therapy could be critical in predicting the long-term prognosis of ischemic stroke patients.

Clinical Characterization of Definite Autoimmune Limbic Encephalitis: A 30-case Series.

Objective Limbic encephalitis (LE) is an inflammatory condition of the limbic system that has an acute or subacute onset. Several types of antibodies are related to the onset of LE, including anti-N-methyl D-aspartate receptor (NMDAR) antibodies and voltage-gated potassium channel (VGKC)-complex antibodies. However, the characteristics and prevalence of LE remain unclear, especially in Asian cohorts, due to the rarity. We aimed to survey their characteristics. Materials and Methods Data of 30 cases clinically defined as "definite autoimmune LE" (based on the standard criteria) were retrospectively collected. These patients were categorized into four subtypes: NMDAR (+) (n=8), VGKC (+) (n=2), antibodies related to paraneoplastic syndrome (n=2), and an antibody-negative group (uncategorized) (n=18). Results LE is rare in Japan, and affected only 30 of 16,759 hospital patients (0.2%) over a ten-year period. The NMDAR (+) group showed distinctive symptoms, while the other three groups had similar indications. Brain MRI indicated significant medial temporal lobe atrophy at one year follow up after discharge. The prevalence of cognitive dysfunction as a complication was 64% (9/14). First-line immunotherapy resulted in a good outcome. A drastic improvement was seen from 4.0±1.1 to 1.1+ on the modified Rankin Scale. A good treatment outcome was observed in all groups (NMDAR, VGKC, and uncategorized), suggesting the importance of an early clinical diagnosis and the early initiation of treatment. Furthermore, we reviewed 26 cases that were clinically diagnosed as definitive autoimmune LE in previous case reports. Conclusion Our findings show that the establishment of a clinical diagnosis based on the clinical criteria of definitive autoimmune LE is important for the initiation of immunotherapy.

Cervico-shoulder dystonia following lateral medullary infarction: a case report and review of the literature.

BACKGROUND: Secondary cervical dystonia is induced by organic brain lesions involving the basal ganglia, thalamus, cerebellum, and brain stem. It is extremely rare to see cervical dystonia induced by a medullary lesion. CASE PRESENTATION: We report a case of an 86-year-old Japanese woman who developed cervical dystonia following lateral medullary infarction. She developed sudden-onset left upper and lower extremity weakness, right-side numbness, and dysarthria. Brain magnetic resonance imaging revealed an acute ischemic lesion involving the left lateral and dorsal medullae. A few days after her stroke, she complained of a taut sensation in her left neck and body, and cervico-shoulder dystonia toward the contralateral side subsequently appeared. Within a few weeks, it disappeared spontaneously, but her hemiplegia remained residual. CONCLUSIONS: To date, to the best of our knowledge, there has been only one reported case of cervical dystonia associated with a single medullary lesion. It is interesting to note the similarities in the clinical characteristics of the previously reported case and our patient: the involvement of the dorsal and caudal parts of the medullary and associated ipsilateral hemiplegia. The present case may support the speculation that the lateral and caudal regions of the medulla may be the anatomical sites responsible for inducing cervical dystonia.

Anti-NMDA receptor encephalitis due to large-cell neuroendocrine carcinoma of the uterus.

A 44-year-old woman presented with a large-cell neuroendocrine carcinoma and uterine endometrioid carcinoma with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Following the diagnosis of uterine cancer, the patient suddenly developed psychosis with abnormal behaviors, delusions, irritability, and forgetfulness. The cerebrospinal fluid tested positive for anti-NMDAR antibodies (encoding the NR1 subunit). The patient was diagnosed with paraneoplastic limbic encephalitis due to uterine cancer. Histology of multiple abdominal metastatic samples revealed a neuroendocrine tumor. Her consciousness improved temporarily after tumor resection and comprehensive immunomodulatory therapy. On day 104 after admission, the patient died of multiple organ failure. The autopsy revealed a perivascular infiltration of inflammatory cells in the amygdala and NMDAR-positive cells in the primary uterine cancer. Our findings demonstrated that neuroendocrine tumors can induce anti-NMDAR encephalitis, which is consistent with three previous reports. A comprehensive treatment with resection of the carcinoma, immunoglobulins, and plasma exchange can induce a partial improvement of the symptoms.