Novel Variants in the FIG4 Gene Associated With Chinese Sporadic Amyotrophic Lateral Sclerosis With Slow Progression

Background@#and Purpose Mutations in the FIG4 gene have been linked to amyotrophic lateral sclerosis (ALS) type 11 in Caucasian populations. The purpose of this study was to identify FIG4 variants in a cohort of 15 familial ALS (FALS) indexes and 275 sporadic ALS (SALS) patients of Han Chinese origin. @*Methods@#All 23 exons of FIG4 were sequenced using targeted next-generation sequencing.An extensive literature review was performed to detect genotype-phenotype associations of FIG4 mutations. @*Results@#No FIG4 variants were identified in the FALS patients. One novel heterozygous missense variant (c.352G>T [p.D118Y]) and one novel heterozygous nonsense variant (c.2158G>T [p.E720X]) in FIG4 were identified in two SALS patients. The p.E720X variant is interpreted as likely pathogenic while the p.D118Y variant is a variant of uncertain significance. The patient carrying the p.E720X mutation developed lower-limb-onset slowly progressive ALS, and survived for 11.5 years. The patient harboring the FIG4 p.D118Y variant also presented with progressive ALS, with the score on the ALS Functional Rating Scale–Revised (ALSFRS-R) decreasing by 0.4 per month. The rate of decrease in the ALSFRS-R scores from symptom onset to diagnosis seemed to be lower in the patients carrying FIG4 variants than the no-FIG4-mutation ALS patients in this study. @*Conclusions@#Our findings suggest that ALS patients carrying FIG4 mutations are not common in the Chinese population and are more likely to exhibit slow progression.

Changes of left ventricular remodeling in hypertension patients with carotid atherosclerosis of phlegm-dampness syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study changes of left ventricular remodeling (LVR) in hypertension patients with carotid atherosclerosis (CAS) of phlegm-dampness syndrome (PDS).</p><p><b>METHODS</b>Doppler ultrasonography data of CAS were observed in 223 hypertension patients with CAS (as the hypertension group, including 119 patients of the PDS group and 104 of the non-PDS group), 81 CAS patients with non-hypertension, and 19 non-hypertension non-CAS patients (as the control group). The difference in the degree of LVR was compared among the above groups.</p><p><b>RESULTS</b>The left ventricular posterior wall thickness (LVPWT), inter ventricular septum thickness (IVS), E/A were higher in the hypertension group than in the non-hypertension group (P < 0.05). The left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), stroke volume (SV) were higher in the soft plaque hypertension group and the soft plaque non-hypertension group than in the hard plaque group, the thickening intimal group, and the normal intimal group (P < 0.01 , P < 0.05). The LVEDD, LVESD, and SV were higher, and the ejection fraction (EF) was lower in the PDS hypertension group than in the non-PDS hypertension group (all P < 0.05). Of them, LVEDD, LVESD, and SV were higher in the soft plaque group than in the hard plaque group (P < 0.01), the thickening intimal group (P < 0.01) and the normal intimal group (P < 0.05). There was no statistical difference in PDS hypertension between the soft plaque group and the hard plaque group (P > 0.05).</p><p><b>CONCLUSION</b>The hypertension patients with CAS of PDS might be correlated to LVR, and LVR was more obviously in the soft plaque patients.</p>

Effect of serotonin depletion on seizures learning-memory in pilocarpine-induced epileptic rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between serotonin (5-HT) and epilepsy and the mechanism of learning-memory in pilocarpine (PILO)-induced epileptic rats after 5,7-dihydroxytryptamine (5,7-DHT) microinjection in median raphe nucleus.</p><p><b>METHODS</b>Adult S D rats were randomly divided into 3 groups: PILO group, PILO+ 5,7-DHT group, vehicle control group; PILO group was divided into two groups by status epilepticus (SE): PILO + SE group and PILO - SE group. The rats' seizures and cortex electroencephalography (EEG) were observed by video EEG. The rats' spatial learning-memory was evaluated by Morris water maze. Finally, serotonergic neuron in raphe nuclei was observed by immunohistochemistry.</p><p><b>RESULTS</b>After treatment of 5,7-DHT (PILO + 5,7-DHT group), the success rate, the mortality and the frequency of chronic spontaneous seizures in pilocarpine-induced epilepsy model were all improved. Compared with the control group, the number of serotonergic neuron in raphe nuclei was decrease in PILO + SE group (P < 0.05). Moreover, it's extremely decrease in PILO + 5,7-DHT group (P < 0.01). Compared with control group, the mean escape latency was prolonged, the times of crossing target was decreased and the retention time in target zone was shortened in PILO + SE group (P < 0.05), but there was no significant difference between PILO + SE group and PILO + 5,7-DHT group.</p><p><b>CONCLUSION</b>Depletion of serotonin may facility the rats' epileptic seizures, but we could not interpret which may cause epileptic rats' cognitive deficit.</p>

Analysis of CLCN1 gene mutations in 2 patients with myotonia congenita / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate chloride channel 1 (CLCN1) gene mutation and clinical features of 2 Chinese patients with myotonia congenita.</p><p><b>METHODS</b>Clinical data of a patient from a family affected with myotonia congenita in addition with a sporadic patient from Fujian province were analyzed. Exons of CLCN1 gene were amplified and sequenced.</p><p><b>RESULTS</b>The proband from the affected family was found to carry a c.1024G>A heterozygous missense mutation in exon 8, whilst the sporadic patient has carried a c.1292C>T heterozygous missense mutation in exon 11.</p><p><b>CONCLUSION</b>Detection of CLCN1 gene mutation is an effective method for the diagnosis of myotonia congenita. Exon 8 of CLCN1 gene may be a mutational hotspot in Chinese patients with myotonia congenita.</p>

The effect of high frequency stimulation of epileptic foci on the release of glutamate and gamma-aminobutyric acid in hippocampus of the kainic acid-kindled rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the dynamics of hippocampal release of glutamate (Glu) and gamma-aminobutyric acid (GABA) in epilepsy (TLE) after administration with high frequency stimulation (HFS).</p><p><b>METHODS</b>The SD were divided into four groups (n =10): (1) Control group (KB) the rats were injected intraperitoneally with saline 0.9%. (2) Kainic acid (KA) group: the rats were injected with KA. (3) Pseudo-deep brain stimulation (DBS) group: the KA-induced rats were implanted with rheophores alone. (4) DBS group: KA induced-rats with DBS in hippocampal epileptic foci. We then collected hippocampal extracellular fluid by microdialysis and the levels of Glu and GABA were measured by high-performance liquid chromatography (HPLC) and fluorescence detection.</p><p><b>RESULTS</b>There was no difference in the baseline of Glu and GABA in the four groups. In contrast, a significant increase in the content of Glu and GABA was shown in the three periods of KA-kindled seizures. Electrical stimulation of hippocampus resulted in a decrease of hippocampal Glu contents, while there was no change in GABA contents. Additionally, HFS of hippocampus normalized the Glu/GABA ratio in the chronic period of seizures.</p><p><b>CONCLUSION</b>The high frequency stimulation of epileptic foci may protect against seizures by modulating the extracellular release of hippocampal Glu.</p>

Correlation analysis of cognitive function and changes in proton magnetic resonance spectroscopy of the hippocampus in patients with complex partial seizures / 中华神经医学杂志

Objective To investigate the features of cognitive impairment in patients with complex partial seizures (CPS) and the correlation between the cognitive function and proton magnetic resonance spectroscopy (~1H-MRS). Methods Forty-five patients with CPS and 16 healthy controls were examined by the following means: memory function examination by the clinical memory scale, intelligence function examination by Ravin's standard progressive Matrices (R'SPM) and ~1H-MRS scan in the bilateral hippocampus. Memory quotient (MQ), Intelligence quotient (IQ), the levels ofNAA, Cho, Cr and the ratio of NAA/Cr+Cho were compared between the two groups. Meanwhile, the correlation coefficients were calculated. Results The scores of pointing memory, associational learning, image free memory, association memory of portrait and MQ except insignificant figure recognition were significantly lower in patients with CPS than those in the control group (P<0.05); the scores of Ravin's standard progressive matrices and IQ were noticeably lower in patients with CPS than those in the controls. The levels of NAA, Cho, Cr and the ratio of NAA/Cr+Cho in patients with CPS were significantly lower than those in the controls (P<0.05). Patients with CPS showed positive correlation between MQ and the level ofNAA, MQ and the ratio ofNAA/Cr+Cho, IQ and the level of NAA, as well as IQ and the ratio ofNAA/Cr+Cho (P<0.05); while level of Cho and both MQ and IQ were in inverse proportion (P<0.05) and no correlation between the lever of Cr and both MQ and IQ was found in patients with CPS (P>0.05). Conclusions The patients with CPS do have the cognitive impairment including short-term memory deficit and the decreased ability of abstraction, maturity judgment and reasoning. The correlation between cognitive function and the levels ofNAA, Cho, Cr and the ratio of NAA/Cr+Cho indicated that ~1H-MRS can check the cognitive function of patients with CPS in early stage objectively. Together with neuropsychology examination, ~1H-MRS can detect the disturbance of cognitive function in the patients with CPS precisely in early stage.

Evaluation of brain dysfunction in chronic anoxic encephalopathy with evoked potentials / 中国应用生理学杂志

<p><b>AIM</b>To explore the relationship between evoked potentials (EPs) and chronic anoxic brain damage by chronic intermittent hypoxia (CIH), and provide theory evidence for diagnosis and treatment of anoxic encephalopathy.</p><p><b>METHODS</b>BAEP and SLSEP were recorded in rat model with CIH (hypoxia group) and rat with normoxia (normal group). Morris water maze was used to observe learning and memory ability. Immunohistochemical method was used to investigate the expression levels of caspase-3 in brain tissue.</p><p><b>RESULTS</b>The peak latency (PL) of wave I, III, V and the interpeak latency (IPL) of wave III - V, I - V in BAEP in hypoxia group were much longer than that of in normal group (P < 0.05). The PL of wave N1, P1 of SEP in hypoxia group were much longer than that of in normal group (P < 0.05). In the water mase test, the escape latency (EL) of hypoxia group was much longer than normal group (P < 0.01). The number of caspase-3 positive cells in hypoxia group was much larger than that of in normal group (P < 0.05). There was a positive correlation among BAEP, SLSEP, the number of caspase-3 positive neuron and EL of water mase.</p><p><b>CONCLUSION</b>The alteration of BAEP and SLSEP has an apparent correlation with chronic anoxic brain damage. This provides theory evidence for diagnosis and treatment of anoxic encephalopathy.</p>