Objective:To analyze the clinical characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS).Methods:A retrospective analysis was performed. The clinical data of 2 patients with genetically conformed HDLS, admitted to our hospital in August 2020 and October 2021, were collected; and a literature search was conducted in domestic and foreign databases from January 2012 to January 2022 (enrolling a total of 48 patients with HDLS caused by colony-stimulating factor-1 receptor [ CSF1R] gene mutation). The population, clinical, imaging and gene mutation characteristics of these patients were summarized and analyzed. Results:(1) In these 50 patients, 20 were male and 30 were female, with onset age of (40.72±11.27) years; 40 patients (80.0%) had been misdiagnosed. (2) The most common first symptom and sign were progressive cognitive impairment (74.0%) and progressive dementia (80.0%). The patients in the middle and old aged group (≥40 years old, n=31) had significantly higher incidences of progressive cognitive impairment and Parkinson's-like symptom, and statistically lower incidence of muscle weakness as compared with those in the youth group (<40 years old, n=19, P<0.05). (3) The highest incidence of abnormal imaging findings was white matter lesions (100.0%), followed by cerebral atrophy (84.0%), ventricular enlargement (84.0%) and corpus callosum atrophy (60.0%). DWI examination was completed in 28 patients, and all patients showed persistent limitation of diffusion (100.0%). The most affected areas of white matter lesions were around the lateral ventricles, followed by the frontal-parietal occipital lobe, and corpus callosum. The incidence of abnormal signal of central semiovale in youth group was statistically higher than that in middle and old aged group ( P<0.05). (4) A total of 36 CSF1R gene mutations or possibly pathogenic mutations were identified in 50 patients, 21 of which were novel mutations reported for the first time. Of the 47 patients whose mutations were described in detail, 8 (17.0%) and 5 (10.6%) probands carried c. 2381T>C/p. I794T and c.2345G>A/p.R782H, respectively. Conclusions:The clinical manifestations of HDLS are diverse and lack of specificity. The most common first symptom and sign are progressive cognitive impairment and progressive dementia; however, the symptom spectrum and MRI imaging changes of white matter damage are related to age. MRI follow-up and targeted gene testing help reduce misdiagnosis and missed diagnosis of HDLS.

Objective:To analyze the clinical characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS).Methods:A retrospective analysis was performed. The clinical data of 2 patients with genetically conformed HDLS, admitted to our hospital in August 2020 and October 2021, were collected; and a literature search was conducted in domestic and foreign databases from January 2012 to January 2022 (enrolling a total of 48 patients with HDLS caused by colony-stimulating factor-1 receptor [ CSF1R] gene mutation). The population, clinical, imaging and gene mutation characteristics of these patients were summarized and analyzed. Results:(1) In these 50 patients, 20 were male and 30 were female, with onset age of (40.72±11.27) years; 40 patients (80.0%) had been misdiagnosed. (2) The most common first symptom and sign were progressive cognitive impairment (74.0%) and progressive dementia (80.0%). The patients in the middle and old aged group (≥40 years old, n=31) had significantly higher incidences of progressive cognitive impairment and Parkinson's-like symptom, and statistically lower incidence of muscle weakness as compared with those in the youth group (<40 years old, n=19, P<0.05). (3) The highest incidence of abnormal imaging findings was white matter lesions (100.0%), followed by cerebral atrophy (84.0%), ventricular enlargement (84.0%) and corpus callosum atrophy (60.0%). DWI examination was completed in 28 patients, and all patients showed persistent limitation of diffusion (100.0%). The most affected areas of white matter lesions were around the lateral ventricles, followed by the frontal-parietal occipital lobe, and corpus callosum. The incidence of abnormal signal of central semiovale in youth group was statistically higher than that in middle and old aged group ( P<0.05). (4) A total of 36 CSF1R gene mutations or possibly pathogenic mutations were identified in 50 patients, 21 of which were novel mutations reported for the first time. Of the 47 patients whose mutations were described in detail, 8 (17.0%) and 5 (10.6%) probands carried c. 2381T>C/p. I794T and c.2345G>A/p.R782H, respectively. Conclusions:The clinical manifestations of HDLS are diverse and lack of specificity. The most common first symptom and sign are progressive cognitive impairment and progressive dementia; however, the symptom spectrum and MRI imaging changes of white matter damage are related to age. MRI follow-up and targeted gene testing help reduce misdiagnosis and missed diagnosis of HDLS.

Objective:To explore the clinical characteristics and prognoses of severe autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).Methods:A retrospective analysis was performed. The clinical data of 12 patients with severe GFAP-A admitted to Department of Neurology, Guangdong 999 Brain Hospital from January 2018 to June 2023 were collected, including demography, clinical manifestations, MRI features, laboratory examination results (such as antibodies), treatments and prognoses.Results:Among the 12 patients, 9 were male and 3 were female, with an average onset age of (46.58±17.53) years. Primary symptoms included headache, limb weakness, limb numbness, mental disorder, epileptic seizure, and urinary and defecation disorder; 9 patients had fever before onset. With aggravated severe GFAP-A, 12 patients had impaired consciousness, 12 had respiratory failure, 6 had unstable blood pressure and heart rate, and 2 had status epilepticus. Cranial MRI indicated abnormal lesions in all 12 patients, including 10 with brainstem involvement (7 had involved medulla oblongata); 10 showed soft meningeal enhancement. In 8 patients received MRI of the whole spinal cord, 7 had abnormal spinal cord lesions; point-like enhancement of the whole spinal meninges was observed in 6 of the 7 patients. All 12 patients had positive cerebrospinal fluid GFAP-IgG, and 3 patients also had positive serum GFAP-IgG. All patients accepted glucocorticoids and immunoglobulin immunotherapy, and 1 patient was supplemented with mycophenolate mofetil; 8 patients had good prognosis, and 4 patients died. Pulmonary infection, hyponatremia, hypoproteinemia, and deep vein thrombosis were the common complications.Conclusion:Patients with severe GFAP-A mainly manifest as meningoencephalitis and meningoencephalomyelitis, and are likely involved medulla oblongata, enjoying rapid clinical progression; even with early immunotherapy, high mortality rate is still noted.