Study The Clinical Characteristics Of Hereditary Diffuse Leukoencephalopathy With Spheroids

Objective We study clinical presentation and neuroimaging features of hereditary diffuse leukoencephalopathy with axonal spheroids(HDLS),aiming to increase the awareness of clinicians and increase the rate of diagnostic.Methods One case of HDLS was reported in Department of Neurology,Affiliated Hospital of Qingdao University.Inputting the key words "hereditary diffuse leukoencephalopathy with axonal spheroids/HDLS" or "colony stimulating factor1/CSF1R" in WANFANG MED ONLINE and Pub Med.According to our statistics of the clinical manifestations and MRI manifestations of patients with HDLS,analysis the clinical and imaging features of HDLS.Results 1.The patients with HDLS who were middle-aged men in Department of Neurology,Affiliated Hospital of Qingdao University.He presented the rapidly progressive motor dysfunction,behavioral and cognitive changes.The T2 FLAIR of brain MRI showed bilateral frontal lobe white matter Lesions,and bilateral periventricular white matter showed multiple punctate high signal on DWI and persisting on it.CSF1 R gene mutation was detected in patient.2.(1)In this study,46 cases of HDLS(including one case of HDLS patients we reported),of which there were 5 kindred.There are 22 case of female patients(47.83%),23 males(50%).(2)The mean age of onset was 43.26±12.43 years old.The minimum age of onset was 15 years old and the maximum age was 78.The average course of disease was 8.75±8.47.(3)19 cases of patients(41.3%)with cognitive decline as initial symptom,10 cases of patients(21.7%)with personality changes and behavioral abnormalities,10 cases of patients(21.7%)with Parkinsonism,4 cases of patients(8.7%)with dysphagia,2 cases of patients(4%)with epilepsy,and initial symptom with hemiplegia and sensory disturbances is 1 case(2.1%)respectively.41 cases of patients(97.8%)presented cognitive decline in all case.28(60.8%)patients with personality changes and behavioral abnormalities,which of 12 patients with depressive symptoms.14(30.4%)patients presented with Parkinsonism.14(30.4%)patients presented with pyramidal signs and 13(28.3%)patients with epilepsy.In some patients,they had the symptoms of urinary incontinence,sensory dysfunction,cerebellar symptom,dysphagia,extrapyramidal syndrome,hallucitions and othersymptoms.(4)40 patients were performed brain MRI,of all patients with brain MRI showed T2WI/T2 FLAIR white matter high signal,accompanied by brain atrophy in 37 cases.34 patients(85%)periventricular white matter were abnormalities,22(55%)patients' fron-parietal lobe white matter were abnormalities,11 patients' corpus callosum are involvement,6(15%)patients' pyramidal tract are involvement,and 9 cases of patients showed restrict diffusion on DWI.36 patients(90%)showed frontal lobe atrophy,27 patients(67%)showed parietal lobe atrophy,19 patients(47.5%)showed corpus callosum atrophy.10 patients(25%)showed temporal lobe atrophy.3 patients(7.5%)showed occipital lobe atrophy.There was1 patients(2.5%)with pyramidal and cerebellum atrophy respectively.29(72.5%)patients showed periventricular dilatation.2 cases of patients showed calcification in cerebral.(5)Loss of myelin sheaths and axons,axonal spheroids were observed in the 23 patients,who underwent histopathological examination.In some case,pigmented macrophage were observed.Mutational CSF1 R gene was detected in 34 patients.19 patients with HDLS were diagnosed with genetic testing and histopathological examination were not done.Conclusion HDLS had no significant difference in the incidence of male and female.The onset of average age was 43 years.HDLS patients' clinical presentation are cognitive decline,behavioral and personality changes,and motor dysfunction.There are obvious heterogeneity in intra-and inter-family.Cerebral MRI showed bilateral periventriclar white matter high signal on T2 WI or T2 FLAIR.Some cases had restrict diffusion on DWI,this seems to a typical imaging pattern in patients with active disease progression in HDLS.HDLS is easy to be misdiagnosed.Gene detection can avoid the potential risk of invasive operation and improve the mortem diagnosis rate.