Objective:To analyze the clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis (CTX) to increase the awareness of the disease among clinicians.Methods:The clinical data, including the age of onset and diagnosis, clinical manifestations, neuroimaging and neuroelectrophysiology and the genetic data of patients diagnosed with CTX in the Department of Neurology, Qilu Hospital of Shandong University from March 2017 to December 2023 were retrospectively collected and analyzed.Results:A total of 18 patients were enrolled in this study, including 12 males and 6 females.The onset age was 10 (6, 29) years, with a minimum onset age of 3 years and a maximum onset age of 32 years; the period from onset to diagnosis was 19.00 (8.75, 24.25) years, with the shortest being 6 months and the longest being 35 years. Among the 18 patients, 16 patients had symptoms and signs of spastic paralysis, 9 patients had cognitive impairment and peripheral neuropathy, 8 patients had cerebellar ataxia, 3 patients had mental disorders, 3 patients had autonomic nervous dysfunction, and only 2 patients had seizures. Among the non-neurological symptoms, 9 patients had Achilles tendon xanthoma, of whom 1 patient was accompanied by patellar tendon xanthoma; 8 patients had adolescent cataracts, 6 patients had chronic diarrhea since childhood. All patients underwent brain MRI examination, among whom 15 patients had cerebellar dentate nucleus involvement, 10 patients had corticospinal tract involvement and 2 patients had normal brain MRI. Fourteen patients underwent nerve conduction and electromyography examinations, among whom 9 patients presented with multiple peripheral neuropathy characterized by motor or motor sensory demyelination. A total of 17 CYP27A1 gene variants were detected in 18 patients. The c.1420C>T and c.1263+1G>A were the hot-spot mutations in this cohort. Conclusions:Spastic paralysis, cerebellar ataxia, tendon xanthoma and adolescent cataracts are typical manifestations of CTX. The cerebellar dentate nucleus and corticospinal tract are mainly involved on the neuroimaging. It should be noted that some patients lack the typical characteristics mentioned above. The c.1420C>T and c.1263+1G>A are the hot-spot mutations in this cohort.

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.

Objective: To investigate the feasibility and efficiency of three-line relaxation-based group intervention on mental stress management among nursing students. Methods: A total of 224 nursing students were randomly divided into the intervention group in which three-line relaxation training for 12 weeks were delivered together with psychological health education (PHE), and the control group which only delivered PHE. The SelfRating Anxiety Scale (SAS) and the Self Rating Depression Scale (SDS) were used before and after intervention. T-test was used to compare inter-group difference. Results: After 4-week intervention, there’s no significant difference in the score of SAS and SDS between the two groups(P>0.05). After 12-week intervention, average SAS and SDS score of intervention group was significantly decreased compared with before intervention (both P<0.01). After 12-week intervention, no significant changes were observed in the score of SAS and SDS in the control group (both P>0.05). After 4-and 12-week intervention, average score in SAS and SDS of intervention group was significantly lower than that of the control group(P<0.05). Conclusion Three-line relaxation is effective in relieving mental stress of nursing students.

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.

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.

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.

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.

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.

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.

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.