Depression, Anxiety, and Quality of Life in Paroxysmal Kinesigenic Dyskinesia Patients

Background：Paroxysmal kinesigenic dyskinesia （PKD） is a rare movement disorder characterized by recurrent dystonic or choreoathetoid attacks triggered by sudden voluntary movements.Under the condition of psychological burden,some patients＆#39; attacks may get worsened with longer duration and higher frequency.This study aimed to assess nonmotor symptoms and quality of life of patients with PKD in a large population.Methods：We performed a cross-sectional survey in 165 primary PKD patients from August 2008 to October 2016 in Rui Jin Hospital,using Symptom Check List-90-Revised （SCL-90-R）,World Health Organization Quality of Life-100 （WHOQoL-100）,Self-Rating Depression Scale,and Self-Rating Anxiety Scale.We evaluated the differences of SCL-90-R and WHOQOL-100 scores in patients and Chinese normative data （taken from literature） by using the unpaired Student＆#39;s t-test.We applied multivariate linear regression to analyze the relationships between motor manifestations,mental health,and quality of life among PKD patients.Results：Compared with Chinese normative data taken from literature,patients with PKD exhibited significantly higher （worse） scores across all SCL-90-R subscales （somatization,obsessive-compulsive,interpersonal sensitivity,depression,anxiety,hostility,phobic anxiety,paranoid ideation,and psychoticism;P =0.000 for all） and significantly lower （worse） scores of five domains in WHOQoL-100 （physical domain,psychological domain,independence domain,social relationship domain,and general quality of life;P =0.000 for all）.Nonremission of dyskinesia episodes （P =0.011） and higher depression score （P =0.000） were significantly associated with lower levels of quality of life.The rates of depression and anxiety in patients with PKD were 41.2% （68/165） and 26.7% （44/165）,respectively.Conclusions：Depression,anxiety,and low levels of quality of life were prevalent in patients with PKD.Co-occurrence of depression and anxiety was common among these patients.Regular mental health interventions could set depression and anxiety as intervention targets.Considering that the motor episodes could be elicited by voluntary movements and sometimes also by emotional stress,and that symptoms may get worsened with longer duration and higher frequency when patients are stressed out,intervention or treatment of depression and anxiety might improve the motor symptoms and overall quality of life in PKD patients.

Clinicopathologic characterization and abnormal autophagy of CSF1R-related leukoencephalopathy

Background:CSF1R-related leukoencephalopathy,also known as hereditary diffuse leukoencephalopathy with spheroids(HDLS),is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor(CSF1R)gene mutation.Few of CSF1R mutations have been functionally testified and the pathogenesis remains unknown.Methods:In order to investigate clinical and pathological characteristics of patients with CSF1R-related leukoencephalopathy and explore the potential impact of CSF1R mutations,we analyzed clinical manifestations of 15 patients from 10 unrelated families and performed brain biopsy in 2 cases.Next generation sequencing was conducted for 10 probands to confirm the diagnosis.Sanger sequencing,segregation analysis and phenotypic reevaluation were utilized to substantiate findings.Functional examination of identified mutations was further explored.Results:Clinical and neuroimaging characteristics were summarized.The average age at onset was 35.9±6.4 years(range 24–46 years old).Younger age of onset was observed in female than male(34.2 vs.39.2 years).The most common initial symptoms were speech dysfunction,cognitive decline and parkinsonian symptoms.One patient also had marked peripheral neuropathy.Brain biopsy of two cases showed typical pathological changes,including myelin loss,axonal spheroids,phosphorylated neurofilament and activated macrophages.Electron microscopy disclosed increased mitochondrial vacuolation and disorganized neurofilaments in ballooned axons.A total of 7 pathogenic variants(4 novel,3 documented)were identified with autophosphorylation deficiency,among which c.2342C>T remained partial function of autophosphorylation.Western blotting disclosed the significantly lower level of c.2026C>T(p.R676*)than wild type.The level of microtubule associated protein 1 light chain 3-II(LC3-II),a classical marker of autophagy,was significantly lower in mutants expressed cells than wild type group by western blotting and immunofluorescence staining.Conclusions:Our findings support the loss-of-function and haploinsufficiency hypothesis in pathogenesis.Autophagy abnormality may play a role in the disease.Repairing or promoting the phosphorylation level of mutant CSF1R may shed light on therapeutic targets in the future.However,whether peripheral polyneuropathy potentially belongs to CSF1R-related spectrum deserves further study with longer follow-up and more patients enrolled.

ovel Mutations in SCN4A Gene Cause Myotonia Congenita with Scoliosis

Myotonia congenita （MC） is a group of genetically and clinically heterogeneous congenital neuromuscular channelopathies, typically characterized by the delayed relaxation of the muscles after voluntary contraction, stifthess, hypertrophy, transient weakness, and cramping.

Novel Mutations in Endoplasmic Reticulum Lipid Raft-associated Protein 2 Gene Cause Pure Hereditary Spastic Paraplegia Type 18

Hereditary spastic paraplegia type 18 （HSP18） is a complicated form ofautosomal recessive HSP characterized by progressive weakness and spasticity of the lower extremities,dysarthria,and cognitive decline. In the year 2011,HSP18,also known as Spastic Paraplegia 18 （SPG18）,was firstly identified due to a candidate gene endoplasmic reticulum lipid raft-associated protein 2 （ERLIN2） on chromosome 8pl 1.2 in one Saudis family.During the past 5 years,another two families with SPG18 due to ERLIN2 mutations have been reported presenting with complicated phenotype. Here,we reported a patient born in a nonconsanguineous family who possessed an autosomal recessive pure form of HSP owing to novel mutations in ERLIN2.Patient was characterized by late-onset spasticity of lower extremities without significant speech involvement or cognitive disability.