Characteristics of CADASIL in Chinese mainland patients.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has been reported in many geographical regions. However, relatively few reports about CADASIL in Chinese were reported. MATERIALS AND METHODS: We retrospectively collected and analyzed clinical characteristics, magnetic resonance (MRI) features and genetic data of 52 Chinese mainland CADASIL patients. RESULTS: Mean age of onset was 42.43 years. The primary clinical manifestations included: Ischemic stroke/transient ischemic attack (62.5%), primary intracerebral hemorrhage (25%), vertigo (25%), migraine (39.58%), dementia (18.75%) and emotional disturbance (20.83%). The most frequently observed MRI abnormalities were hyperintensity in the cerebral white matter on T2-weighted images and multiple infarcts, high-signal lesions on T2 images in anterior temporal lobes and external capsule were uncommon. The highest mutation frequency was in exon regions, 4 and 3, followed by exon 11. Granular osmiophilic material (GOM) was identified in 66.67% of the cases examined with biopsy. CONCLUSIONS: Most characteristics of Chinese mainland CADASIL patients are similar to those of CADASIL patients living in other regions. However, the prevalence of primary intracerebral hemorrhage and vertigo is much higher in Chinese mainland CADASIL patients. Significant leukoaraiosis in anterior temporal poles on T2-weighted image are uncommon. Exons 3 and 4 are the mutation hotspots.

Leber's hereditary optic neuropathy companied with multiple-related diseases.

Objective: To elucidate the clinical, radiologic characteristics of Leber's hereditary optic neuropathy (LHON) associated with the other diseases. Materials and methods: Clinical data were retrospectively collected from hospitalized patients with LHON associated with the other diseases at the Neuro-Ophthalmology Department at the Chinese People's Liberation Army General Hospital (PLAGH) from December 2014 to October 2018. Results: A total of 13 patients, 24 eyes (10 men and 3 women; mean age, 30.69 ± 12.76 years) with LHON mitochondrial DNA (mtDNA) mutations, were included in the cohort. 14502(5)11778(4)11778 &11696(1)12811(1)11696(1)3460(1). One patient was positive for aquaporin-4 antibody (AQP4-Ab), and two were positive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab). Three patients were associated with idiopathic optic neuritis (ON). Two patients were with compression optic neuropathy. Three patients were with the central nervous system (CNS) diseases. One patient was with proliferative diabetic retinopathy (PDR) and one with idiopathic orbital inflammatory syndrome (IOIS). At the onset, visual acuity (VA) in eighteen eyes was below 0.1, one eye was 0.5, five eyes were above 0.5, while VA in sixteen eyes was below a 0.1 outcome, three eyes experienced moderate vision loss. MRI images showed T2 lesions and enhancement in nine patients who received corticosteroids treatment; additional immune modulators treatment was performed on two patients. None of the patients had relapse during the follow-up time. Conclusion: Leber's hereditary optic neuropathy can be accompanied with multiple-related diseases, especially different subtypes of ON, which were also exhibited with IOIS and compression optic neuropathy for the first time in this cohort. This condition may be a distinct entity with an unusual clinical and therapeutic profile.

Structural-visual functional relationships detected by optical coherence tomography in varying age-cohorts' patients with optic neuritis.

AIM: To assess the relationships of final best-corrected visual acuity (BCVA) and the optic nerve structural loss in varying age-cohorts of optic neuritis (ON) patients. METHODS: This is a retrospective, cross-sectional study. Totally 130 ON subjects (200 eyes) without ON onset within 6mo were included, who underwent BCVA assessment, peripapillary retinal nerve fibre layer (pRNFL) and macular segmented layers evaluation by optical coherence tomography (OCT). RESULTS: For the 0-18y cohort, the final BCVA (logMAR) was significantly better and less frequent recurrences than adult cohorts (P=0.000). The final BCVA (logMAR) in all age-cohorts of the ON patients had negative and linear correlations to the pRNFL thicknesses and macular retinal ganglion cell layer (mRGCL) volumes, when the pRNFL thicknesses were reduced to the thresholds of 57.2-67.5 µm or 0.691-0.737 mm3 in mRGCL volumes, respectively, with the strongest interdependence in the 19-40y cohort. The ON patients from varying age cohorts would be threatened by blindness when their pRNFL thicknesses dropped 36.7-48.3 µm or the mRGCL volumes dropped to 0.495-0.613 mm3. CONCLUSION: The paediatric ON has best prognosis and young adult ON exhibits perfectly linear correlations of final vision and structural loss. The pRNFL and the mRGCL could be potential structural markers to predict the vision prognosis for varying-age ON patients.

Mitochondrial Mutations in Ethambutol-Induced Optic Neuropathy.

Background: Ethambutol-induced optic neuropathy (EON) is a well-recognized ocular complication in patients who take ethambutol as a tuberculosis treatment. The aim of the current study was to investigate the presence of mitochondrial mutations, including OPA1 and Leber's hereditary optic neuropathy (LHON)-mitochondrial DNA (mtDNA), in patients with EON and to determine their effect on clinical features of these patients. Methods: All 47 patients underwent clinical evaluations, including best-corrected visual acuity, fundus examination, and color fundus photography; 37 patients were then followed up over time. Molecular screening methods, including PCR-based sequencing of the OPA1 gene and LHON-mtDNA mutations, together with targeted exome sequencing, were used to detect mutations. Results: We detected 15 OPA1 mutations in 18 patients and two LHON-mtDNA mutations in four patients, for an overall mutation detection rate of 46.8%. The mean presentation age was significantly younger in the patients with the mitochondrial mutations (27.5 years) than in those without mutations (48 years). Fundus examination revealed a greater prevalence of optic disc hyperemia in the patients with mutations (70.5%) than without mutations (48%). Half of the patients with mutations and 91% of the patients without mutations had improved vision. After adjusting for confounders, the logistic regression revealed that the patients with optic disc pallor on the first visit (p = 0.004) or the patients with the mitochondrial mutations (p < 0.001) had a poorer vision prognosis. Conclusion: Our results indicated that carriers with OPA1 mutations might be more vulnerable for the toxicity of EMB to develop EON.

[Change of CCR7 and CD45RA after blocking of Kv1.3 potassium channel of CD4+ T lymphocytes in multiple sclerosis].

OBJECTIVE: To investigate the changes of CCR7 and CD45RA expression after blocking of the potassium channel Kv1.3 in myelin specific CD4 T lymphocytes and the relation thereof with multiple sclerosis(MS). METHODS: Peripheral blood mononuclear cells were isolated from 15 activated MS patients, 15 INF-beta-1b treated MS patients, and 15 normal controls, CD4+ T lymphocytes were isolated using positive selection method with anti-CD4-coated magnetic beads. To establish culturing MBP special CD4+ T lymphocyte lines, the different groups of T cell were labeled with CD3, CD4, CCR7, and CD45RA fluorescence-antibody or homotype controls and analyzed by four-color flow cytometer. RESULTS: The most part of phenotype in the activated MS patients was CD4+ CCR7- CD45RA- T cells and the percentage was increased after myelin antigen stimulation (P < 0.05), whereas the percentage of CCR7+ CD45RA+ T cells was decreased (P < 0.05). SHK greatly inhibited CCR7- CD45RA- in activated MS (P < 0.05). CCR7-CD45RA- and CCR7+ CD45RA- were in correlation with expanded disability status scale (EDSS) score (r = 0.73, r = 0.705, P < 0.05) in the peripheral blood of activated MS. CONCLUSION: There is a strong correlation between T(EM) phenotype and severity of MS, which may suggest Tem phenotype as the marker to estimate the state of illness. Kv1.3 potassium channel may be the new target in treatment of MS.

Retinal segmented layers with strong aquaporin-4 expression suffered more injuries in neuromyelitis optica spectrum disorders compared with optic neuritis with aquaporin-4 antibody seronegativity detected by optical coherence tomography.

PURPOSE: To evaluate retinal segmented layer alterations in optic neuritis (ON) in an AQP4-Ab seropositive (AQP4-Ab+/ON) cohort and in neuromyelitis optica (NMO) with ON eyes (NMO-ON) compared with an AQP4-Ab seronegative ON (AQP4-Ab-/ON) cohort using optical coherence tomography (OCT). METHODS: We recruited 109 patients with ON (161 eyes) and 47 healthy controls. All patients with ON were subdivided into three subcohorts: 37 patients (54 eyes) with AQP4-Ab+/ON, 45 patients (65 eyes) with AQP4-Ab-/ON and 27 patients (42 eyes) with NMO-ON. All subjects were evaluated for their peripapillary retinal nerve fibre layer (pRNFL) and inner macular segmented layer using OCT. RESULTS: AQP4-Ab+/patients with ON had the same structural injury patterns as patients with NMO-ON, and the injury patterns were distinct from those of AQP4-Ab-/patients with ON. NMO-ON and AQP4-Ab+/ON preferentially damaged the pRNFL (all p=0.000), the macular retinal nerve fibre layer (mRNFL; p=0.000 and 0.032, respectively), and the inner plexiform layer (IPL; p=0.000 and 0.006, respectively) without differences in the retinal ganglion cell layer (p=0.106 and 0.374, respectively) compared with AQP4-Ab-/patients with ON. The thickness of the inner nuclear layer (INL) increased in NMO-ON (p=0.043) compared with that of AQP4-Ab-/ON without a significant difference in AQP4-Ab+/ON versus AQP4-Ab-/ON (p=0.353). When the thickness of the inferior nasal quadrant (NI) of the pRNFL was reduced to ≤46.5 µm (area under the curve 0.772, sensitivity 89.2% and specificity 57.5%) 6 months after ON onset, NMO was considered. CONCLUSIONS: AQP4-Ab+/ON produced similar structural injury patterns as NMO-ON. The pRNFL, mRNFL and IPL in the two types of ON and the INL in NMO-ON suffered more damage than those in AQP4-Ab-/ON, which could be associated with strong aquaporin-4 expression. The thickness of the NI of the pRNFL could be a potential clue for predicting ON progression to definite NMO.

[R1239H mutation of CACNA1S gene in a Chinese family with hypokalaemic periodic paralysis].

OBJECTIVE: Mutation screening was performed to a Chinese family with hypokalaemic periodic paraiysis(HOKPP) for locating the corresponding mutations of gene and for specifying the clinical features associated with mutations. METHODS: The cilnical features of patients from HOKPP family were summurized. Techniques of target exon PCR and direct sequencing were used to screen the mutation in CACNA1S and SCN4A genes in all numbers of the family. RESULTS: Two patients of the family showed the typical features of HOKPP: the age of disease onset is during the childhood, acetazolamide is effective to patients treated. A heterozygous point mutation 3716 (G>A) causing R1239H was found in exon 30 of CACNA1S gene of the patients, but not found in normal members of the family. CONCLUSION: The mutant R1239H in CACNA1S gene exists in Chinese patients with familial hypokalaemic periodic paralysis.

[The mutation R672H in SCN4A gene exists in Chinese patients with hypokalaemic periodic paralysis].

OBJECTIVE: Mutation screening was performed on two Chinese families with HOKPP to locat the corresponding mutations and to specify the clinical features associated with the mutation. METHODS: Target-exon PCR and direct sequencing were used to screen mutation in the CACNA1S and SCN4A gene of all numbers of the two families. The clinical features of patients were summary. RESULTS: A heterozygous point mutation 2015G-->A causing R672H in the SCN4A was found in five patients and five normal relatives of the two families. Features of R672H mutation are incomplete penetrance, especially non-penetrance of phenotype in women and potassium is effective, but acetazolamide is not. CONCLUSION: The SCN4A R672H mutation exists in the Chinese family with HOKPP.