The phenotypic and genetic spectrum of colony-stimulating factor 1 receptor gene-related leukoencephalopathy in China / 中华神经科杂志

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Characteristics of clinical manifestations and molecular genetics of late-onset cobalamin C deficiency / 中华神经科杂志

Objective To investigate the characteristics of clinical manifestations and genetics of late-onset cobalamin (cbl) C deficiency,also named as combined methylmalonic acidemia and homocystinemia, cblC type. Methods We reviewed 26 late-onset cblC deficiency patients diagnosed in Qilu Hospital, Shandong University from 2012 to 2017 and analysed the clinical, biochemistry, neuroimaging, follow-up and MMACHC gene data. Results Among the 26 patients, male:female ratio is 11:15, with the age of diagnosis from 4 to 39 years and sibling comorbidity in 4 families. The clinical manifestaions of nervous system included spastic paraplegia,mental and behavior disorder,intelectual decline,epilepsy,ataxia,dystonia and peripheral neuropathy. There were four cases with proteinuria at onset. At first visit, the levels of serum total homocystinuria of all patients were elevated, from 61.4 to 193.4μmol/Lwith methylmalonic acidemia. The neuroimaging data of the 26 cases showed 11 with cerebral atrophy, 10 with thoracic spinal cord atrophy, five with brain parenchymal lesions, three with longitudinal myelopathy which were reversible in follow-up, one with syringomyelia, one with multiple cerebral artery stenosis. In all the cases, cobalamins were supplied parenterally and folate, betaine, L-carnitine, vitamin B6 were supplied orally during acute metabolic crisis, and the symptoms of acute encephalopathy disappeared but symptoms of spastic paraplegia had little improvement. In chronic stage, frequency of intramuscular injection of hydroxocobalamine could be decreased while the index can still be improved. All the 26 cases had definite mutations in MMACHC gene, the most common mutations of which were found to be c.482G>A(15/52) and c. 609G>A(13/52). Conclusions Homocystine is the important biomarker for cblC deficiency. Once diagnosed, parenteral hydroxocobalamin and oral betaine should be supplied for a lifetime with good prognosis. The most common mutations of MMACHC gene in our cases are c. 482G>A and c. 609G>A missense mutations.

Clinical and neuroimaging features of dyssynergia cerebellaris myocionica in a Chinese family / 中华神经科杂志

Objective To investigate the clinical,genetic and neuroimaging features by reporting a family with dyssynergia cerebellaris myoclonica. Methods The proband was examined clinically by neuroimaging,electromyography ( EEG),skin and muscles pathology and hematology.The patients with the illness in the family were followed up and the pedigree was drawn.Results There were 6 patients with dyssynergia cerebellaris myoclonica of the 27 family members in the family.All patients had disproportionate myoclonus,epilepsy,progressive cerebellar ataxia performance. Proband brain MRI showed cerebral atrophy.Cerebellar and cortical atrophy were more serious than other parts.There were long T,and long T2 signals in the white matter,high signal in T2FLAIR.EEG showed bursts of spike-low wave,polyspilke-low waves and polyspike waves distributing in the whole brain.Pathology of the skin and muscles was normal.Conclusions Dyssynergia cerebellaris myoclonica is an autosomal dominant disease,characterised by myoclonus,progressive cerebellar ataxia and epilepsy.Brain MRI shows cerebral cortical and cerebellar atrophy,abnormal signal in white matter.EEG showes spike and ware wave.The diagnosis is mainly based on family history,typical clinical manifestations,brain MRI and EEG changes.

Vogt-Koyanagi-Harada syndrome: 5 cases report with clinical and neuroimaging features / 中华神经科杂志

Objective To investigate the clinical and neuroimaging features of Vogt-KoyanagiHarada syndrome ( VKH ).Methods Cerebrospinal fluid ( CSF ), neuroimaging examination, clinical manifestation and pharmacotherapy features were investigated in 5 patients diagnosed as VKH. ResultsAll 5 patients were diagnosed as uveitis in the early stage of disease.All patients suffered “ headache”.Meningeal irritation sign was appeared in 3 cases. The MRI enhanced scan of all 5 cases showed abnormal enhancement of meninges. CSF examination showed increased leukocyte number ((4--196) × 106/L). All patients were alleviatedwith combination therapyof high dose of steroid with cyclophosphamide.ConclusionsVKH is a systemic disease that usually involving the uvea, central nervous system, internal ear and the skin. MRI and CSF examination are valuable for diagnosis. High dose of steroid combined with cyclophosphamide is an effective therapeutic strategy.

Poly adenosine diphosphate-ribose polymerase regulates the expression of nuclear factor-κB and related inflammatory factors in rat hippocampus after epilepsy / 中国病理生理杂志

AIM:To investigate the time course of nuclear factor-κB (NF-κB) and the effects of 3-aminobenzamide (3-AB) on the expressions of NF-κB,interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) in hippocampus after seizures. METHODS:Epilepsy were induced by kainic acid through cerebral ventricular injection. Western blotting was used to detect NF-κB p65 expression in nucleus at various experiment groups. Moreover,mRNA and protein expressions of IL-1β and COX-2 in different experiment groups were determined by RT-PCR and Western blotting analysis. RESULTS:NF-κB p65 immunoreactivity began to increase in the nuclear fraction at 2 h (P<0.05),kept rising at 12 h (P<0.05) and returned to control level at 24 h after epilepsy seizures. Furthermore,3-AB sharply decreased the accumulation of NF-κB p65 in nucleus (P<0.05). In addition,3-AB significantly decreased the mRNA and protein expressions of IL-1β and COX-2 which obviously increased in hippocampus at 6 h after epilepsy seizures (P<0.05). CONCLUSION:Seizures triggers NF-κB nucleus translocation and promotes the expressions of IL-1β and COX-2 in hippocampus. In addition,poly (adenosine diphosphate-ribose) polymerase inhibition by 3-AB suppresses NF-κB associated inflammatory pathway in epileptic rat hippocampus.

Study on the long-term change of calcium homeostasis and kinetics in chronic epilepsy model / 中华神经科杂志

Objective To study the role of calcium homeostatic and kinetics in the epileptogenesis activity. Methods Hippocampal neurons were acutely isolated from controls and status epilepticus (SE) models induced by lithium-pilocarpine at different time point. The [Ca2+]i levels were detected by laser scanning confocal microscope. And the ability to restore resting [Ca2+]i levels after a brief exposure to 5 μmol/L glutamate in control and epileptic neurons were evaluated. Results The [Ca2+]i level of acute separated hippocampal neurons in the control rats was (95.4±22. 1) nmol/L After injection of lithium pilocarpine, the [Ca2+]i level in hippecampal neurons increased dramatically to (867.6±35.2) nmol/L, and decreased to (292.8 ± 18.3) nmol/L on the 7th day, lasting for about 30 days ((220. 8± 17.6) nmol/L), it is higher than that in the control group (t = 12. 55, P < 0.01). The distribution of neuronal [Ca22+]i showed that 92% of control neurons were in the normal range of [Ca2+]i level (25-150 nmol/L) ; After 6 hours, however [Ca2+]i levels of all SE neurons increased, and 85% of which were higher than 500 nmol/L; After 7, 14 and 30 days, there were 75%, 60% and 52% of SE neurons still manifested an elevated [Ca22+]i level, but less than 500 nmol/L. After the exposure to 5 μmol/L glutamate treatment for 2 minutes, [Ca2+]i of the control neurons restored to baseline values in (9. 5±3.4) minutes, whereas the SE rats of acute, latent and chronic phases did not (t = 5.08, 4. 56, 4. 21, all P < 0. 01). Conclusion Lithium-pilocarpine induced epilepsy causes a long-term alteration of calcium homeostatic mechanisms of hippocampus neurons, which may play an important role in the development and maintenance of spontaneous recurrent seizures.

Clinical and neuroimaging features of hypoglycemia encephalopathy in the elderly / 中华神经科杂志

Objective To investigate the clinical and neuroimaging features of hypoglycemia encephalopathy in the elderly. Methods The history and clinical features of 36 patients who had undergone brain CT and MRI were analyzed retrospectively. Results Twenty-seven patients had infections and fevers as a trigger, presenting all kinds of symptoms. Eleven cases were found to have abnormal signals in bilateral caudate nucleus and lenticular nucleus in MRL But CT examination showed no new lesions in corresponding position. Hypoglycemia encephalopathy were commanly found in the elderly who had diabetes mellitus and treated with drugs. After being followed up for 6 months, their neuroimaging did not change. Conclusions Because the patients often present unconsciousness and weakness with a sudden onset, hypoglycemia is easily mistaken for other disorders, especially in the elderly. For those with consciousness, we should pay more attations to hypoglycemia. Brain CT has no value of diagnosing hypoglycemia encephalopathy, while MRI plays an impotant role in diagnosing the disease. The characteristic MRI features predicts a bad prognosis.

Clinical and neuroimaging futures of chorea due to nonketotic hyperglycemia:7 cases report / 中华神经科杂志

Objective To investigate the clinical and neuroimaging futures of chorea due to nonketotic hyperglycemia.Methods Seven cases of chorea due to nonketotic hyperglycemia were clinically examined and underwent brain CT and MRI as well.Results Investigations revealed uncontrolled diabetes with absent ketones of 7 cases.They all presented with sudden onset hemiachorea or bilateral chorea or generalized chorea.The CT scan of brain could find abnormal lesions in our cases.Hyperintense lesions in the basal ganglia,on T1 WI of MRI were demonstrated in our study.Pure drugs was unable to control chorea.The symptoms of chorea and neuroimaging lesions were normal after the hyperglycemia being controlled.Conclusions Chorea caused by nonketotic hyperglycemia is mainly found in aged people with diabetes mellitus in a mechanism of causing striatal neuronal dysfunction,presenting charicristic CT scan or MRI of brain.Chorea should be considered potentially reversible when associated with nonketotic hyperglycemia,for rapid detection and early correction of hyperglycemia could lead to complete recovery of these involuntary movements.

Meningeal malignant melanosis:3 cases report with clinicopathological and neuroimaging / 中华神经科杂志

Objective To investigate clinicopathological and neuroimaging features of meninheal malignant melanosis.Methods The cytologic study of cerebrospinal fluid(CSF)and neuroimaging examination and meningeal histochemistry were performed in 3 cases of meningeal malignant melanosis. Results Three patients were found to have initial onsets of headache.followed by meningeal irritation.One case had huge malignant melanoma on skin.The second patient had diabrotic malignant melanoma on her face,which did not healed for a long time.The third patient had no malignant melanoma on skin and viscera.The MRI enhanced scanning of all 3 cases showed abnormal enhancement of meninge.There were a large number of abnormal shape cells in CSF.The meninxes were blackbrown or brown.The tumor cells were in various shapes with big and round irregular nucleus and rich cytoplasm.There were a great quantitv of melanosomes.The tumor cells were disarranged. Immunohistochemistry analyses found S-100 protein and Vim and HMB-45 were positive reaction. Conclusions The patients with meningeal malignant melanosis have an initial onset of headache,followed by meningeal irritation,and MRI enhanced scanning plays a valueble role in the diagnosis.A lage number of tumor cells in abnormal shape have been found in CSF.Thetumour cells of meninx presents different shapes with big and round or irregular nucleus.There are a great quantity of mellanosomes,and the tumour cells are arranged in a state of chaos.

The value of gradient echo T2*-weighted imaging for detection of familial cerebral cavernous malformation / 中华神经科杂志

Objective To investigate the value of gradient echo T2'* -weighted imaging for detection of familial cerebral cavernous malformation (FCCM). Methods Twenty-six members in 2 families of FCCM were examined at 3.0 T by using CT, conventional MRI and GRE T2'*2'-WI sequences to detect numbers of FCCM. Results Twelve cases of FCCM were found by GRE T2'*-WI sequences. These patients all had multiple lesions(average of 23). The lesions were mainly located in ganglia area, followed by cortico-subcortical, thalamus, cerebellar and brain stem. These lesions appeared as special reticulated core of mixed signal intensity with a surrounding rim of decreased signal intensity representing bemosiderin from previous hemorrhages. The numbers of lesions (average of 5-17) and cases of FCCM (average of 3-9) examined by the conventional MRI were decreasing in the order of SE, DWI, T2FLAIR, T1WI and T2WI, each less than GRE T2'*-WI. CT only identified 3 cases with big lesions combined with hemorrhage and calcification.Conclusions GRE T2'*-WI could be a better choice of MRI sequence in diagnosing FCCM compared with CT and conventional MRI.

Primary culture of hippocampal neurons of new-born rats / 基础医学与临床

Objective To establish a primary culture method of hippocampal neurons of new-born rats,and to observe the morphological characteristics at different developmental and differential stages.Methods The hippocampus was digested and the cells were seeded in a flask.The neurons were then transferred and re-seeded on cover glasses coated with poly-L-lysine.The neurons were identified by polyclonal antibody against neuron specific enolase(NSE).The morphology was observed under phase-contrast microscope.Results A large number of hippocampal neurons began to adhere to the cover glasses after 12～24 hours.They showed different shapes-shuttle,triangle,pyramidal,or nonregular after clinging to the plate.Their processes connected into nets and different in length and thickness.They were well developed on the 7th～10th day and survived as long as 28 days after seeding.Immunocytochemistry of NSE proved high purity.Conclusion The culture method of new-born rat hippocampal neurons in vitro is successful and can be used as an in vitro model of research.

Expression of gap junction connexin 32 and connexin 43 and inhibition of carbenoxolone in cultured hippocampal neurons of rats after epileptiform discharges / 中华神经科杂志

Objective To study the role of gap junctions in epileptiform activity. Methods The epileptiform activity was induced by zero-Mg 2+ medium in cultured hippocampal neurons of newborn rats. Immunocytochemistry and real time RT-PCR were introduced to evaluate the expression of gap junction Cx32 and Cx43. Results The level of Cx32 mRNA increased quickly one hour after the neurons were treated with zero-Mg 2+ medium and was raised by 10 times 5 hours later, while Cx32 protein began to develop at the 2nd hour (21.80?1.74) and was raised by 5 times at the 8th hour (47.30?5.75). The expression of Cx43 mRNA went up obviously 5 hours later, and Cx43 protein developed visibly 8 hours later. Carbenoxolone depressed the expressions of Cx32 and Cx43. Conclusions The expression of Cx32 and Cx43 increases dramatically after epileptic discharges and carbenoxolone inhibits both the discharges and the expression of gap junctions, which indicates that gap junction could contribute to epileptogenesis.

Poly adenosine diphosphate-ribose polymerase regulates the expression of nuclear factor-?B and related inflammatory factors in rat hippocampus after epilepsy / 中国病理生理杂志

AIM:To investigate the time course of nuclear factor-?B (NF-?B) and the effects of 3-aminobenzamide (3-AB) on the expressions of NF-?B,interleukin-1? (IL-1?) and cyclooxygenase-2 (COX-2) in hippocampus after seizures. METHODS:Epilepsy were induced by kainic acid through cerebral ventricular injection. Western blotting was used to detect NF-?B p65 expression in nucleus at various experiment groups. Moreover,mRNA and protein expressions of IL-1? and COX-2 in different experiment groups were determined by RT-PCR and Western blotting analysis. RESULTS:NF-?B p65 immunoreactivity began to increase in the nuclear fraction at 2 h (P