Chunkui Zhou

Clinical and histopathological features of familial amyloidotic polyneuropathy with transthyretin Val30Ala in a Chinese family

Familial amyloidotic polyneuropathy (FAP) is characterized by extracellular deposition of amyloid fibrils caused by a point mutation in the transthyretin (TTR) gene. TTR amyloidosis is linked to a vast number of mutations with varying phenotype and tissue distribution. Several Chinese kindred with FAP type 1 have been reported in Beijing, Hong Kong, Taiwan, and elsewhere. Here, histopathological features and TTR gene polymorphism were analyzed by using autopsy and blood specimens from a Chinese proband of a family with FAP. This proband is a 34-year old man with FAP type 1 who developed motor, sensory and autonomic impairments with neuropathy, gastrointestinal dysfunction, and orthostatic hypotension. Genetic findings of TTR revealed a T to C transition in codon 30 causing the mutation TTR Ala30. This patient died of respiratory and circulatory failure 7 years after onset. Autopsy showed heavy amyloid deposition in the peripheral nerves, liver, testes, thyroid, pancreas and muscles. There was moderate deposition in the heart, kidneys, bladder, gastrointestinal tract, tongue, lung, blood vessels, and gall bladder. The spleen showed only slight deposition, and none was observed in the central nervous system. TTR amyloidosis was confirmed by immunochemical staining with a specific TTR antibody. These results indicate that the distribution of amyloid deposition, (i.e., heavy in the liver, testes and slight in the spleen), is a characteristic feature and reflects the severity of FAP with TTR Val30Ala.

Familial Cerebral Cavernous Angiomas: Clinical and Genetic Features in a Chinese Family with a Frame-Shift Mutation in the CCM1 Gene (krit1)

A few cases of cerebral cavernous malformation (CCM) have been reported in Chinese families with different mutations during the past decade. Herein, we report a case of CCM in a proband in a Chinese family, for whom the mutation type of the CCM remains to be identified. The proband of the family presented a range of clinical symptoms and features that included paralysis, aphasia, multiple lesions in the brain, and cutaneous capillary–venous malformations. PCR was performed to amplify all of the coding exons of the three CCM genes (CCM1, CCM2, and CCM3) in the proband and revealed a heterozygous T deletion in exon 15 (c.1542delT) of CCM1 gene. Targeted mutation analysis in family members demonstrated that this mutation segregated with the disease in the family. This is the first report of a heterozygous CCM1 deletion mutation. Our findings provide a new CCM gene mutation profile in a Chinese family which will be of significance in genetic counseling for CCM.

Magnetic resonance diffusion tensor imaging for occult lesion detection in multiple sclerosis

It remains challenging to locate occult lesions in patients with multiple sclerosis (MS). Diffusion tensor imaging (DTI) has been demonstrated to have the potential to identify occult changes in MS lesions. The present study used 3.0T magnetic resonance DTI to investigate the characteristics of different stages of MS lesions. DTI parameters, fractional anisotropy (FA), mean diffusivity (MD), λ// and λ┴ values of lesions were compared at the different stages of 10 patients with MS with 10 normal controls. The results demonstrated that FA and λ// values of MS silent and subacute lesions are decreased and MD and λ┴ values are increased, as compared with those of normal appearing white matter (NAWM) and normal controls. NAWM FA values were lower, and MD, λ//, and λ┴ values were higher than those of normal controls. It was also indicated that MS lesions had reduced color signals compared with the controls, and the lesion area appeared larger using DTI as compared with diffusion-weighted imaging. Furthermore, fiber abnormalities were detected in MS lesions using DTT, with fewer fibers connected to the lesion side, as compared with the contralateral side. FA, MD, λ// and λ┴ values in the thalamus were increased, as compared with those of normal controls (P<0.05); whereas MD, λ// and λ┴ values were significantly increased and FA values significantly decreased in the caudate nucleus and deep brain gray matter (DBGM) of patients with MS, as compared with the controls (P<0.05). λ// and λ┴ values were also significantly increased in the DBGM of patients with MS as compared with normal controls (P<0.05). The present findings demonstrate that DTI may be useful in the characterization of MS lesions.

Evaluate the Efficacy and Safety of Anti-epileptic Medications for Partial Seizures of Epilepsy: A Network Meta-analysis†

Epilepsy is a brain and neurological disorder with high prevalence. It was reported that more than 70% of epileptic seizures were controlled by anti‐epileptic medications, whereas the lack of evidence with respect to head‐to‐head comparisons motivated researchers to seek alternative approaches that are able to provide deep insights into the profile of anti‐epileptic medications. In this study, we performed a network meta‐analysis (NMA) to evaluate the efficacy and safety of anti‐epileptic medications for partial seizures of epilepsy. Publications were retrieved from PubMed, Embase, and Cochrane Library. Then, studies were screened and selected based on the inclusion criteria. Data were extracted and a NMA was performed to combine both direct and indirect evidence. Surface under the cumulative ranking curve (SUCRA) was obtained for ranking purposes. Consistency between direct and indirect evidence was assessed by using the node‐splitting method. Seventeen anti‐epileptic medications from 90 publications were enrolled. Fifty percent responder and state of seizure freedom were studied as outcomes for efficacy; treatment emergent adverse effect (TEAE), including dizziness, somnolence, headache, fatigue, and nausea were evaluated as safety outcomes. Topiramate, levetiracetam, pregabalin, and oxcarbazepine were recommended for their relatively high efficacy and low‐risk of adverse events for partial seizures. Rufinamide was the least preferable medication due to its low efficacy and high‐risk of adverse effects. J. Cell. Biochem. 118: 2850–2864, 2017.

Efficacy and tolerability of short-term duloxetine treatment in adults with generalized anxiety disorder: A meta-analysis

Objective To investigate the efficacy and tolerability of duloxetine during short-term treatment in adults with generalized anxiety disorder (GAD). Methods We conducted a comprehensive literature review of the PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials databases for randomized controlled trials(RCTs) comparing duloxetine or duloxetine plus other antipsychotics with placebo for the treatment of GAD in adults. Outcome measures were (1) efficacy, assessed by the Hospital Anxiety and Depression Scale(HADS) anxiety subscale score, the Hamilton Rating Scale for Anxiety(HAM-A) psychic and somatic anxiety factor scores, and response and remission rates based on total scores of HAM-A; (2) tolerability, assessed by discontinuation rate due to adverse events, the incidence of treatment emergent adverse events(TEAEs) and serious adverse events(SAEs). Review Manager 5.3 and Stata Version 12.0 software were used for all statistical analyses. Results The meta-analysis included 8 RCTs. Mean changes in the HADS anxiety subscale score [mean difference(MD) = 2.32, 95% confidence interval(CI) 1.77–2.88, P<0.00001] and HAM-A psychic anxiety factor score were significantly greater in patients with GAD that received duloxetine compared to those that received placebo (MD = 2.15, 95%CI 1.61–2.68, P<0.00001). However, there was no difference in mean change in the HAM-A somatic anxiety factor score (MD = 1.13, 95%CI 0.67–1.58, P<0.00001). Discontinuation rate due to AEs in the duloxetine group was significantly higher than the placebo group [odds ratio(OR) = 2.62, 95%CI 1.35–5.06, P = 0.004]. The incidence of any TEAE was significantly increased in patients that received duloxetine (OR = 1.76, 95%CI 1.36–2.28, P<0.0001), but there was no significant difference in the incidence of SAEs (OR = 1.13, 95%CI 0.52–2.47, P = 0.75). Conclusion Duloxetine resulted in a greater improvement in symptoms of psychic anxiety and similar changes in symptoms of somatic anxiety compared to placebo during short-term treatment in adults with GAD and its tolerability was acceptable.

Dystrophia myotonica type 1 presenting with dysarthria: A case report and literature review

Dystrophia myotonica (DM) type 1 is an autosomal dominant disorder, caused by a trinucleotide CTG repeat expansion in the 3′ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene (chromosome 19q13.3). The disorder affects different organ systems, including the skeletal muscles, ocular lens, lungs, heart and gastrointestinal tract, as well as the endocrine and central nervous systems. The skeletal muscles are most frequently involved, whereby the disorder manifests as myotonia, muscle weakness and amyotrophy. However, DM type 1 presenting with dysarthria is rare. The current study presents a case of a 28-year-old male with DM type 1 presenting with dysarthria and associated multifocal hyperintense lesions in the white matter. Although electromyogram measurements identified myotonic discharges in all extremities, a muscle biopsy failed to detect the characteristic pathological features of DM type 1. A lack of a positive family history for DM type 1 also obscured diagnosis. However, genetic analysis detected a single allele in the P12 segment of the DMPK gene that included a CTG expansion of 13 repeats and a three-base gradient fragment in the P134 segment that included a CTG expansion of >600 repeats. According to the characteristics of dysarthria, multifocal hyperintense lesions in the white matter, electromyogram measurement results and genetic testing results, a diagnosis of DM type 1 was confirmed.