A family of Niemann-Pick disease type C caused by compound heterozygous mutations in NPC1 gene / 中华神经科杂志

Objective:To report the clinical and genetic characteristics of a family with Niemann-Pick disease type C caused by novel compound heterozygous mutations in the NPC1 gene to improve the clinicians′ recognition of the disease. Methods:Two patients from the family with non-consanguineous marriages admitted to the Department of Neurology of the First Affiliated Hospital of Kunming Medical University in 2020 were examined in detail. Peripheral blood DNA was extracted, and whole exome sequencing was performed on the patients, combined with Sanger sequencing for verification. The mutation and protein function predictor softwares were applied to analyze the mutation sites.Results:The inheritance was autosomal recessive in this family. The onset age of the proband was 9 years, and the main clinical manifestations were dysarthria, dysphagia, cognitive impairment, ataxia, bilateral pyramidal tract impairment, vertical supranuclear gaze palsy and splenomegaly. The clinical phenotype of the proband′s younger brother was similar to that of the proband, but it was more severe than that of the proband. The younger brother of the proband had an earlier age of onset and severe psychomotor retardation. Whole exome sequencing showed that both brothers carried 2 rare variants of NPC1 gene:1 pathogenic, stop gain at c.352_353del, p.Gln119ValfsTer8, and a missense change, c.593A>G, p.Asn198Ser, of suspected pathogenic. Sanger sequencing confirmed that compound heterozygous mutations were derived from the proband′s parents. According to the American College of Medical Genetics and Genomics guidelines, the above variants were rated as pathogenic and suspected pathogenic, respectively. And the c.593A>G, p.Asn198Ser mutation found in this family was a novel one which had not been reported yet. The proband had delayed diagnosis for 7 years from the onset of symptoms. After taking megastat for 1 year, the symptoms of dysphagia, ataxia and vertical eye movement disorder were significantly improved. Conclusions:The clinical phenotype of the pedigree was consistent with the clinical phenotype of Niemann-Pick disease type C. Compound heterozygous mutations of NPC1 gene (c.352_353del; c.593A>G) were found to be the genetic cause of the family.

Anti-contactin associated protein-like 2 antibody encephalitis complicated with reversible posterior encephalopathy syndrome: a case report / 中华神经科杂志

Anti-contactin associated protein-like 2 (CASPR2) antibody encephalitis is a rare autoimmune encephalitis with variable clinical symptoms and atypical imaging manifestations. The prognosis of the patients with severe disease is poor. Reversible posterior leukoencephalopathy syndrome is rarely reported in autoimmune encephalitis. The clinical data, diagnosis and treatment of a patient with anti-CASPR2 antibody encephalitis complicated with reversible posterior encephalopathy syndrome were reported, in order to improve the understanding of clinicians on the rare disease complicated with atypical imaging manifestations.

Research progress of new-onset refractory status epilepticus / 中华神经科杂志

New-onset refractory status epilepticus is a rare and special clinical manifestation with high mortality. About half of the patients have no clear cause. At present, the pathogenesis is unclear, and the treatment plan is controversial. In recent years, it has been found that inflammatory and immune responses of the body may be involved in the pathogenic process, and it is called “inflammatory-immune mediated epileptic encephalopathy” based on the perspective of pathogenesis. There have also been many treatment attempts based on the inflammatory and immunological mechanisms, some of which have achieved satisfactory results. However, most of them are based on the review of small sample cases, and relevant guidelines are still lacking at present. In this paper, the definition, etiology, pathogenesis, clinical manifestations and treatment of persistent status of new-onset refractory status epilepticus are reviewed.

Neuroelectrophysiological Characteristics of Peripheral Neuropathy after Chronic Obstructive Pulmonary Disease / 中国康复理论与实践

@#Objective To analyze the neuroelectrophysiological characteristics of peripheral neuropathy after chronic obstructive pulmonary disease. Methods From January to December, 2016, a total of 60 patients of chronic obstructive pulmonary disease with peripheral neuropathy were reviewed the motor conduction velocity and compound muscle action potential amplitude of median, ulnar, tibial, peroneal nerves; the sensory conduction velocity and sensory nerve action potential amplitude of median, ulnar, tibial, superficial peroneal nerves; and the skin sympathetic response of limbs. Results The incidence of abnormalities was higher in amplitude than in conduction velocity of motor nerve and sensory nerves (χ2=190.026, P<0.001). The incidence of abnormal conduction velocity was similar in motor nerve and sensory nerves (χ2=1.538, P>0.05), as well as the abnormal action potential amplitude (χ2=2.839, P>0.05). The incidence of abnormal conduction was similar with abnormal skin sympathetic response (χ2=0.001, P>0.05). The incidence of abnormalities of nerve conduction study (χ2=81.114, P<0.001) and abnormal skin sympathetic response (χ2=5.689, P<0.05) was more in lower limbs than in upper limbs. Conclusion The peripheral neuropathy after chronic obstructive pulmonary disease characters mainly as motor-sensory multiple neuropathy, involving motor, sensory and autonomic nerve. The axonal damage is significant, with the similar severity between motor and sensory nerves, as well as between the large and small nerves.

Anti-oxidant Effect of Gastrodin in Epilepsy Rats / 昆明医科大学学报

Objective To explo the antioxidant effect and molecular mechanism of gastrodin (Gas) in epilepsy (EP) rats induced by LiCl-pilocarpine (PILO) . Methods Eighty male SD rats were randomly divided into 5 groups: sham group, EP group, therapy groups (pretreated with 60 mg/kg, 90 mg/kg, 120 mg/kg of gastrodin respectively) . The EP model was esteblished by peritoneal injection of LiCl-PILO. Therapy groups were pretreated with various concerntration of Gas. The control group was given the same dosage of normal saline. The alteration of behavior was observed, the concentration of catalase (CAT), glutathion (GSH), superoxide dismutase (SOD), glutathion reductase (GR), total antioxidtion (T-AOC) and malondialdehyde (MDA) in rats brain cortex were detected by chemical colorimetric method, phosphorylation of p38 was determined by western blot. Results There was no EP seizure in sham group,and the EP seizure degree in therapy groups (gas pretreated groups) was significantly decreased,and had statistically significant difference with EP group (P<0.05) . The EP model rats exhibited a significant decrease in the concentration of endogenous antioxidants (CAT, GSH, SOD, GR and T-AOC), while an increase of the concentration of MDA and phosphorylation p38 protein as compared to sham group (P<0.05) . After treatment of the Gas,treatment group rats attenuated the seizure degree,exhibited a significant increase of the concentration of endogenous antioxidants (P<0.05),while a decrease in concentration of MDA and phosphorylation of p38 as compared to model group (P<0.05) . Conclusion Gas may have a neuroprotective role in central nervous system of epileptic rats modle by down-regulateing the seizure degree and the activity of p38 kinase and up-regulateing the content of endogenous antioxidants.

The Activation and Polarization of Microglia in Epileptic Rats Induced by Pilocarpine / 昆明医科大学学报

Objective To explore the activition and polarization of microglia in the epileptic rats induced by lithium chloride-pilocarpine. Methods One hundred male SD rats were randomly divided into five groups: control group and different time points model groups including 1d,3d,7d and 14d. Epilepsy models were established by lithium chloride-pilocarpine intraperitoneal injection. The control group was given the same dosage of normal saline. The morphology change was detected by immunofluorescence,and the expressions of iNOS and Arg-1 were determined by IHC at respective time points. Results Compared the model groups with control group,microglia was activated,synapsis was shorten,volume got bigger,most of them seemed as amoebocyte,the expression of iNOS increased and Arg-1 decreased,especially at 3d.ConclusionThe results from this study indicated that microglia was activated and polarized in epileptic rats induced by pilocarpine.