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Objective: Mutations in CACNA1A, which encodes the P/Q-type calcium channel subunit, are responsible for at least 3 allelic diseases, namely type 2 episodic ataxia (EA-2), familial hemiplegic migraine?type-1 (FHM1), and spinocerebellar ataxia type-6?(SCA 6). Herein we present a case of ataxia with episodic tremors in a 19-year-old man with a missense mutation of CACNA1A gene and summarize the clinical features, genetic analysis and treatment in this case and in his affected family members., Methods: Physical examinations were conducted for the patient and his affected family members. DNA sample from the proband was analyzed with next-generation sequencing technology to identify the causative mutation. Sanger sequencing was used to confirm the gene mutation in the family members., Results: Physical examinations of the patient revealed signs of ataxia, drunken gait, and tremor of his head and body. Four other members in his family had similar but much milder symptoms. A heterozygous missense mutation in CACNA1A (NM_001127221.1 c.4034G->A, p.R1345Q, exon 25) was identified in the proband, which was confirmed in the affected family members. The proband did not respond to methazolamide treatment, but his tremor symptom was well controlled with flunarizine, a calcium channel blocker., Conclusion: Based on the clinical features, mutation analysis and treatment response, we suggest that this patient with a missense CACNA1A mutation, R1345Q, has a new type of ataxia with episodic tremor other than any of EA2, FHM1, or SCA 6.

Objective: To investigate whether intensive statin therapy during the perioperative period improves outcomes in patients undergoing middle cerebral artery (MCA) stent implantation for ischemic stroke., Methods: Forty patients with ischemic stroke undergoing delayed stent implantation in our department from January, 2010 to November, 2014 were randomized to intensive statin group (atorvastatin, 80 mg/day, 3 days before till 3 days after intervention; n=20) and standard therapy group (atorvastatin, 20 mg/day, n=20). All the patients received long-term atorvastatin treatment thereafter (20 mg/day). Serum levels of C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM-1), and soluble extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) were measured at 24 h before and 24 h after the intervention. The primary end point was procedure-related intra-stent thrombosis, 1-month incidence of major adverse cerebrovascular events (stroke, transient ischemic attack, in-stent restenosis, death or unplanned revascularization)., Results: The basic clinical data were similar between the two groups before the intervention (P>0.05). In the intensive therapy group, the levels of CRP, VCAM-1, and sCD147 were significantly lower at 24 h after the intervention than the levels before intervention (P<0.05) and the postoperative levels in the standard therapy group (P<0.05). The levels of CRP, VCAM-1, and sCD147 were all increased after the intervention in the standard therapy group (P>0.05). The incidence of primary end point was lower in intensive therapy group than in standard therapy group (P<0.05)., Conclusion: In patients undergoing MCA intravascular stent implantation for ischemic stroke, perioperative intensive statin therapy improves the patients' outcomes, reduces the levels of CRP, VCAM-1 and sCD147 molecules, and lowers the incidences of cerebrovascular events.

Objective: To analyze the risk factors of cerebral microbleeds (CMBs)., Methods: A total of 113 patients with cerebrovascular diseases underwent examinations of magnetic resonance imaging (MRI) of the brain (including T1WI, T2WI, FLAIR, and SWI) and blood biochemical tests, and the brain regions, number and grades of the CMBs were analyzed. The association between CMBs and the cardiovascular risk factors were analyzed., Results: A The occurrence and grade of CMBs were associated with the patients' age, hypertension, diabetes, lacunar infarction, diastolic blood pressure, systolic blood pressure and high-density lipoprotein (HDL) levels (P<0.05). CMB occurrence was significantly associated with diabetes, hypertension, and lacunar infarction (P<0.05), and its incidence varied significantly between different brain regions (P<0.05)., Conclusion: Age, hypertension, diabetes, lacunar infarction, diastolic blood pressure, systolic blood pressure, and HDL are all risk factors for CMBs, among which diabetes, hypertension, and lacunar infarction are significant risk factors. CMBs occurs most frequently in the cortex and subcortical region, followed by the basal ganglia, thalamus, and the cerebellum, and most unlikely in the brainstem.

Objective: To evaluate the clinical application of susceptibility-weighted magnetic resonance imaging (SWAN) in lacunar cerebral infarction imaging., Methods: Forty-two cases of lacunar cerebral infarction, including 18 complicated by high blood pressure, 4 by type 2 diabetes and 12 by both high blood pressure and type 2 diabetes, underwent examinations with SWAN and conventional MRI sequences (including GRE sequence T(1) and T(2), T(2) gradient echo, T(2) FLAIR, DWI). The imaging data were analyzed in comparison with the clinical data of the patients., Results: In 23 patients with lacunar cerebral infarction, intracerebral micro-hemorrhage displayed point-like, round and oval low signal on SWAN. A total of 123 lesions were identified, distributing from the cortical, subcortical, basal ganglia, thalamus, brain stem to the cerebellum. The conventional sequences were more sensitive in detecting the majority of lacunar cerebral infarction than SWAN, while the latter showed better performance in displaying cerebral micro-hemorrhage, tiny blood vessels and small vascular malformations as well as other small vascular diseases. SWAN was superior to other sequences in showing lacunar cerebral infarction complicated by cerebral micro-hemorrhages., Conclusion: MRI SWAN can better display lacunar cerebral infarction associated with cerebral micro-hemorrhages and small veins in the infract region. Identification of the micro-hemorrhages in lacunar cerebral infarction can be critical in determining the proper treatments. Patients with lacunar cerebral infarction are likely to have cerebral micro-hemorrhages in close relation to the number of lacunar infarction sites. The cerebral micro-hemorrhages and lacunar cerebral infraction are both signs of micro-vessel damage of the brain.

Objective: To investigate the correlation between the diffusion anisotropy of the white matter fibers and the cognitive function in patients with leukoaraiosis (LA)., Methods: Thirty-one LA patients were enrolled in this study, including 13 with grade LA-1 (mild), 12 with grade LA-2 (moderate) and 6 with grade LA-3 (severe) condition. The control group consisted of 18 subjects who were free of obvious clinical symptoms or had only mild dizziness and headache but with negative history for neural system diseases and in the absence of cognitive dysfunction, brain trauma, positive signs in neurological examinations, or abnormities in MRI examination. The Mini-mental State Examination (MMSE) was applied to evaluate the patients' cognitive function. The LA patients underwent examination with diffusion tensor MR imaging (DTI), and the FA and MD values in the normal-appearing white matter (NAWM) were measured., Results: The cognitive function of the LA patients tended to decline with the decrease of the MMSE scores, and their scores for time orientation, place orientation and calculation were significantly lower than those of the control group (P<0.05). No significant difference was found in memory, language and comprehensive abilities between the LA and control groups. In LA-1, LA-2 and total LA cases, the FA value in the NAWM was positively, and the MD value inversely, correlated to the cognitive function with correlation coefficients ranging from 0.5 to 0.8 (P<0.05)., Conclusion: The DTI parameters of NAWM region are correlated to the cognitive function of LA patients. DTI is far more sensitive than MRI in evaluating cognitive dysfunction in LA patients.

Objective: To explore the value of lower-limb short latency somatosensory evoked potentials (SLSEP) in predicting early death in patients with massive cerebral infarction., Methods: Forty-eight patients of massive cerebral infarction were admitted in the Neurological Intensive Care Unit (NICU) between March 2008 and March 2009, and Glasgow-Pittsburgh coma scale (GPCS) and SLSEP were recorded and graded within 24 h after admission. The patients were divided into survival and death groups (including brain death) according to their short-term prognosis. The correlations of SLSEP and GPCS to the mortality were assessed., Results: A significant correlation was found between SLSEP and the mortality in patients with massive cerebral infarction (r=0.484, P<0.001). The positive predictive value of the SLSEP grade 3 to death was 100%, and the patients with malignant middle cerebral artery infarction (mMCAI) appeared to have a 100% mortality., Conclusion: SLSEP grade 3 can be a highly specificity in predicting early death in patients with massive cerebral infarction, and it is also of value in determining the timing of surgical intervention of mMCAI.

Objective: To study the relationship between cystatin C and cerebral infarction and explore the role of cystatin C in the protection against cerebral infarction., Method: Eighty-three patients with cerebral infarction and 71 randomly selected age- and gender-matched patients in the Department of Neurology (control group) were enrolled in this study. Fasting whole blood (3 ml) was obtained from the patients in both groups and the sera were separated to determine the levels of cystatin C using particle reinforced immunoturbidimetric assay., Results: The serum cystatin C level was significantly lower in the cerebral infarction group than in the control group (1.62-/+0.31 vs 2.23-/+0.22 mg/L, P<0.01)., Conclusions: Cystatin C is closely related to cerebral infarction probably as a protective factor against cerebral infarction.

Objective: To investigate the association of IL-1beta+3953, TNFbeta+252 and IL-10-592 polymorphisms with serum lipoprotein levels in Chinese Han population in Guangdong Province., Methods: A total of 428 individuals of Han nationality from Guangdong Province were enrolled in this study. The genotypes of IL-1beta+3953, TNFbeta+252 and IL-10-592 sites were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The serum concentrations of total cholesterol (TC), TG, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very low density lipoprotein (VLDL) were determined using an automatic biochemistry analyzer., Results: The concentrations of TC and LDL in individuals of TNFbeta+252GA genotype was significantly higher than that in TNFbeta+252AA genotype (t=-2.406, P=0.017; t=-2.516, P=0.012). The concentration of LDL in IL-10+3953CT genotype was significantly higher than that in IL-10+3953CC genotype (2.743-/+0.723 vs 2.502-/+0.699 mmol/L, t=-2.639, P=0.009). No significant differences were found in TG, TC, HDL, LDL and VLDL between the 3 genotypes (P>0.05)., Conclusion: The polymorphisms of proinflammatory cytokines are related to the serum lipoprotein level in these subjects. The T allele in IL-1beta+3953 and the G allele in TNFbeta+252 are positively correlated to dyslipidemia.

Objective: To investigate the feasibility of continuous intraspinal ceftazidime administration for treatment of purulent meningitis due to Achromobacter infection., Methods: A patient with established diagnosis of purulent meningitis due to Achromobacter infection was admitted, who failed to respond favorably to a 3-day ceftazidime treatment administered intravenously. Continuous intraspinal ceftazidime administration at the dose of 0.2 g/d was then attempted through a catheter placed in the cisterna magna in addition to intravenous ceftazidime for 3 days, which resulted in obvious relief of the symptoms. The catheter was subsequently withdrawn, and the patient received further treatment with additional intravenous ceftazidime for a week., Results: The symptoms of purulent meningitis was significantly improved after a 3-day continuous intraspinal ceftazidime administration, and the patient was eventually cured after completion of the treatment course. Intrathecal ceftazidime was also attempted previously but failed due to intolerance of pains in the legs. No relapse was observed in this case 3 months after the discharge., Conclusion: Continuous intraspinal ceftazidime administration can be effective and safe for treatment of purulent meningitis.

Objective: To investigate the pathological characteristics of heroin spongiform leukoencephalopathy (HSLE)., Methods: Cerebral tissue specimens were obtained from 15 patients with HSLE and the histological observations under optical and electron microscopes were carried out by HE, Bielschowsky's, and chromotrope 2R-brilliant green staining., Results: HSLE was characterized primarily by spongiform vacuolar degeneration of the cerebral white matter. Neurons in the gray matter, Purkinje and granular cells in the cerebella remain intact in all the cases. Numerous vacuoles, which merged to form larger cavities, appeared in the damaged white matter, and the axons survived in the deep white matter. The myelin sheath in the cerebellar white matter sustained more severe damages than those in the cerebral white matter. No vacuoles or lymphocyte infiltration occurred in the small peripheral vessels., Conclusion: HSLE is pathologically characterized by vacuolar degeneration due to primary damage of the myelin, and the spongiform vacuolar degeneration is closely associated with the severity of demyelination in the white matter.

Objective: To study the mechanisms of dystrophin gene deletion by cloning and sequencing the junction fragment of dystrophin gene with exons 3 to 5 deletion., Methods: PCR was performed to verify dystrophin gene exons 3 to 5 deletion in a patient with Duchenne muscular dystrophy. A PCR-based genome-walking method was used to localize the breakpoint in introns 2 and 5, and the deletion-junction fragment was directly amplified by PCR approach with forward and reverse primers annealing to a DNA sequence as close as possible to the breakpoint in the introns 2 and 5. The sequencing result of the deletion-junction fragment was compared with the normal intron sequences., Results: A sequence of 2113 bp containing the junction fragment was obtained. The 5' breakpoint was located in SINE/Alu element of intron 2, and the 3' breakpoint was located in the unique sequence near the sequence TTTAAA. The breakpoints were associated with a strong topoisomerase II cleavage site. A 26-bp fragment was inserted into the breakpoint and formed 3 duplications (GGCTTATATTTAA) of 13 bp around the deletion-junction fragment., Conclusion: Repeat sequence and strong topoisomerase II cleavage site around the breakpoint may predispose double-strand DNA breaks and recombination, which, in addition to the nonhomologous end-joining mechanism, may contribute as important factors to the gene deletion.