Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in a Chinese pedigree A case report using brain magnetic resonance imaging and biospy

The present study enrolled a Chinese family that comprised 34 members and spanned three generations. Eight members were diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and disease diagnoses corresponded with autosomal incomplete dominance inheritance. The primary clinical manifestations included paralysis, dysarthria, and mild cognitive deficits. Magnetic resonance imaging revealed diffuse leukoencephalopathy with involvement of bilateral anterior temporal lobes, in particular the pons. In addition, multiple cerebral infarction was identified in the proband. Sural nerve biopsy findings of the proband revealed granular osmophilic material deposits in the extracellular matrix, which were adjacent to smooth muscle cells of dermal arterioles. Screening exons 2-4 for NOTCH 3 mutations by direct sequencing did not reveal any abnormalities.

Development, and validation of non-speech dichotic listening test

Background:Classic dichotic listening tests using speech stimuli result in right ear advantage,due to the dominant crossed pathway for speech and language.It is presumed that similar crossed dominance could exist for non-speech stimuli too.Hence,this is an attempt to develop and validate the dichotic nonspeech test using environmental stimuli and explore the effect of focused attention on this test.Materials and method:Three lists of dichotic stimuli were created using these sounds with fifteen tokens in each list.Four professionals and non-professionals validated these materials.Normative estimation was obtained by administering the newly developed test on 70 adults and 70 children using a free-recall and forced-recall condition.Result:The results showed a significant difference between the left ear and right scores where the left ear score was better than the right,depicting left ear advantage(LEA)for free recall condition in both groups.In the forced recall condition,LEA was not seen;rather the mean score was significantly higher in the attended ear,irrespective of the stimuli presented to the right or left ear.The test-retest reliability in free recall was good in both the ears and moderate for forced right ear conditions.Conclusion:The novel test consistently showed LEA with good reliability and can be used to assess the hemispheric asymmetry in normal subjects and also in test batteries for the clinical population.

NOTCH3 Mutations and CADASIL Phenotype in Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Background:The etiology of pulmonary arterial hypertension associated with congenital heart disease(PAHCHD)is complicated and the phenotype is heterogeneous.Genetic defects of NOTCH3 were associated withcerebral disease and pulmonary hypertension.However,the relationship between NOTCH3 mutations and theclinical phenotype has not been reported in CHD-PAH.Methods:We eventually enrolled 142 PAH-CHD patientsfrom Fuwai Hospital.Whole exome sequencing(WES)was performed to screen the rare deleterious variants ofNOTCH3 gene.Results:This PAH-CHD cohort included 43(30.3%)men and 99(69.7%)women with the meanage 29.8±10.9 years old.The pathogenic or likely pathogenic mutations of NOTCH3 were identified in five cases.Patients 2,5,8 and 11 carried the same NOTCH3 mutation c.1630C>T(pArg544Cys),which is the hot-spotmutation for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL).Patient 3 carried the NOTCH3 mutation p.Arg75Gln that has also been reported to be associatedwith the CADASIL.Patients 2,5,8,11 took the examination of the cerebral magnetic resonance imaging(MRI)and confirmed the phenotype of CADASIL.Conclusions:We first reported the NOTCH3 rare mutationsand CADASIL phenotypes in CHD-PAH patients.The NOTCH3 rare variants were with a relatively high positiverate and CADASIL phenotypes were likely enriched in PAH-CHD patients.The preoperative neurological examinationmight be recommended for PAH-CHD patients to determine the surgical contraindications and reduceintraoperative neurological complications.

A case of hereditary multi-infarct dementia Mutation in exon 11 of the Notch3 gene on chromosome 19

This study is a report on one 59-year-old male patient with hereditary multi-infarct dementia who came from a family with a positive family history of this disease. The patient primarily presented with dizziness accompanied by vertigo and a positive Romberg＇s sign. Skull magnetic resonance images showed lacunar infarction in bilateral temporal lobes, bilateral basal ganglias, periventricular white matter and semioval center, and ischemic focus accompanied by white matter degeneration, exhibiting senile morphological brain changes. No abnormalities were observed by skull magnetic resonance angiography. Gene detection further confirmed that there was Arg607Cys heterozygous mutation in exon 11 of the Notch3gene. No other mutations in exons were detected.

Study of Enhanced Depth Imaging Optical Coherence Tomography in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Background： Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy （CADASIL） is a hereditar5 small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imaging optical coherence tomography （EDI-OCT） to evaluate the retinal vessel changes in CADASIL patients and assessed their consonance with brain magnetic resonance imaging （MPRI） findings. Methods： Of 27 genetically confirmed patients and an equal number of controls were recruited at the Peking University First ttospital from January 2015 to August 2016. All patients underwent 7T-MRI of the brain. Fazekas score, number of small infarcts and microblecds were evaluated. All patients and controls underwent EDI-OCT to measure subtbveal choroidal thickness （SFCT）, inner and outer diameters as well as arterial and venous wall thickness, and arterial venous ratio of the inner （AVRin） and outer diameters （AVRout）. The relation between retinal vessel changes and Fazekas scores, numbers of small infarcts, or microbleeds was analyzed. Paired t-test was used to compare the SFCT and retinal vessel measurement data between patients and controls. Spearman＇s correlation was used to investigmc the correlation between retinal vessel changes and MRI lesions. Results： In CADASI L patients, mean SFCT （268.37 ± 46.50 μm） and mean arterial inner diameter （93.46 ± 9.70 gin） were signilicantly lower than that in controls （P 〈 0.00 ）, P = 0.048, respectively）. Mean arterial outer diameter （ 131.74 ± 10.87 μm）, venous inner （ 128.99 ± 13.62 μm） and outer diameter （ 164.82 ±14.77 μm）, and mean arterial （ 19.13 ±1.85 μm） and venous （ 17.91 ±2.76 μm） wall thickness were significantly higher than that in controls （P = 0.023, P 0.004, P 〈 0.001, P 〈 0.001, respectively）. Arterial inner diameter （r= - 0.39, P 0.044）] AVRin （r -0.65, P 〈 0.001）, and AVR,, （r =0.56, P - 0.002） showed a negative correlation with the number of small infarcts. Venous inner diameter （rs=0.46, P= 0.016） showed a positive correlation with the number of small infarcts. Venous inner diameter （r 0.59, P = 0.002）, outer diameter （rs=0.47, P= 0.017）, showed a positive correlation with the number of cerebral microbleeds （CM Bs）. AVRin （r =0.52, P = 0.007） and AVRout （r = -0.40, P =0.048） showed a negative correlation with the number of CMBs. Conclusions： Measurement of retinal vessels using EDI-OCT correlates moderately well with MRI parameters. EDI-OCT might bc a useful evaluation tool for CADASIL patients.

Mapping cortical areas associated with Chinese word processing using functional magnetic resonance imaging

s To identify the cortical areas engaged during Chinese word processing using func tional magnetic resonance imaging (fMRI) and to examine the reliability and repr oducibility of fMRI for localization of functional areas in the human brain Methods FMRI data were collected on 8 young, right handed, native Chinese speakers duri ng performance of Chinese synonym and homophone judgment tasks on two different clinical MRI systems (1 5 T GE Signa Horizon and 1 5 T Siemens Vision) A cro ss correlation analysis was used to statistically generate the activation map Results Broca's area, Wernicke's area, bilateral extrastriate, and ventral tempo ral cortex were significantly activated during both the synonym and homophone ac tivities There was essentially no difference between results acquired on two d ifferent MRI systems Conclusions FMRI can be used for localizing cortical areas critical to Chinese language proc essing in the human brain The results are reliable and well reproducible acros s different clinical MRI systems

Localization of the human language cortex by magnetic source imaging

Objective To localize the language cortex associated with Chinese word processing by magnetic source imaging (MSI) Methods Eight right handed and one left handed healthy native Chinese subjects were examined by magnetoencephalography (MEG) and a 1 5T magnetic resonance imaging (MRI) unit All subjects were given pure tone stimuli 50 times, 150 pairs of Chinese words (meaning related or unrelated) auditory stimuli, and pure tone stimuli subsequently 50 times Evoked response fields time locked to the pure tone and Chinese words were recorded using a whole head neuromagnetometer in real time The acquired data were averaged by the acquisition computer according to the response to the pure tone, related pairs of words and unrelated pairs of words The data obtained by MEG were superimposed on MRI, using a GE Signa 1 5T system Results MEG, showed there were two obviously higher magnetic waves named M50 and M100, which were localized in the bilateral transverse temporal gyri in all subjects The responses to the pairs of Chinese words (meaning related or unrelated) were similar in the same hemisphere of the same subjects There was a higher peak during 300-600 ms in the right hemisphere of one left handed subject, but no peak in the left hemisphere, indicating that the language dominant hemisphere was localized in the right hemisphere Superimposing the MEG data on MRI, the language area was localized in the Wernicke's areas A 300-600 ms response peak was obsarved in each hemisphere (the amplitude of the 300-600 ms response peak in each hemisphere was almost the same) in two right handed subjects, showing that the language area was localized in the 2 hemispheres in the two subjects There was one peak in each hemisphere (300-600 ms response) in 6 subjects, but the amplitude of the wave in the left hemisphere in the 6 subjects was much higher than that in the right hemisphere By choosing randomly from the later component (300-600 ms response) several time points and superimposing them on MRI, all time points were localized in the posterior part of the superior temporal gyri, which is the Wernicke's areas Conclusions Comparing with the later component of the bilateral hemispheres, the wave amplitude in the language dominant hemisphere was much higher than that in the non language dominant hemisphere The language areas could be identified by judging whether meanings of pairs of Chinese words were related or not