Biomedical subjects

Sumeet Singhal

Publications and source records attributed to Sumeet Singhal.

6 recordsLinked to original sources

PubMed2005

Cerebrovascular reactivity and dynamic autoregulation in nondemented patients with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy).

Reduced cerebrovascular reactivity has been reported in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and the measurement has been suggested as a useful surrogate marker of disease progression. Previous studies have not determined whether cerebral autoregulation is also impaired. We measured dynamic cerebral autoregulation and carbon dioxide reactivity in 24 nondemented CADASIL patients and 20 controls, using transcranial Doppler ultrasound (TCD). No impairment in either measure was found in the CADASIL group. We conclude that either cerebrovascular reactivity and autoregulation are not impaired in early disease, or that TCD may not be a sufficiently sensitive tool to detect haemodynamic changes in early disease. TCD is unlikely to be useful for disease monitoring in patients without advanced disease.

Adult↗

PubMed2004

The influence of genetic and cardiovascular risk factors on the CADASIL phenotype.

The clinical phenotype in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), an autosomal dominant cerebral arteriopathy, is variable, but the reasons for this remain uncertain. Possible factors include the mutation site and the influence of additional modulating factors, which could include both epistatic interactions and interactions with cardiovascular risk factors known to cause sporadic small vessel disease. In a large prospectively recruited cohort of CADASIL subjects we determined relationships between phenotype and mutation site, the apoE genotype and cardiovascular risk factors. In addition to clinical features, disease severity was assessed by MRI lesion volume, measured both semiquantitatively (Scheltens scale) and quantitatively. One hundred and twenty-seven CADASIL cases from 65 families with 17 different mutations were studied. Site of mutation was not associated with the presence or age of onset of stroke, migraine, dementia, dependency or MRI lesion load. There was no evidence of intrafamilial clustering of particular phenotypes. Amongst subjects with stroke/transient ischaemic attack, smoking at the time of the event was independently associated with earlier age of onset (P = 0.01). There were no associations between age of onset or presence of stroke and other cardiovascular risk factors, including homocysteine. Homocysteine levels were higher in migraineurs [mean (SD) 12.8 (5.6) versus 9.8 (3.4) micromol/l, P = 0.02)] and elevated homocysteine was independently associated with an earlier age of onset of migraine (P = 0.01). No relationship was found between MRI lesion volume and risk factors, or between apoE genotype and phenotype. Our results show no notch 3 genotype-phenotype correlations. This implies that modulating factors influence phenotype. Smoking appears to increase the risk of stroke, while high homocysteine levels are associated with an increased risk of migraine.

Adult↗

PubMed2004

Diffusion tensor imaging of thalamus correlates with cognition in CADASIL without dementia.

BACKGROUND: Executive dysfunction is an early feature in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and may progress to a subcortical dementia. The mechanism of cognitive impairment is incompletely understood, and correlations with T2 lesion volumes are not strong. Diffusion tensor imaging (DTI) may provide a better index of white matter tract damage. Previous DTI studies in CADASIL demonstrated abnormalities in normal-appearing white matter, thalamus, and putamen and correlations with the Mini-Mental State Examination (MMSE). OBJECTIVE: S: To determine whether DTI abnormalities could be identified in nondemented patients with CADASIL and whether these correlated particularly strongly with executive function. METHODS: Eighteen CADASIL subjects underwent DTI and cognitive assessment, including tests of several aspects of executive function. DTI was also performed on 12 age-matched control subjects. RESULTS: Mean diffusivity was increased in white matter lesions, normal-appearing white matter, and normal-appearing gray matter (thalamus, putamen, and globus pallidus). A composite score of executive function correlated with diffusivity in both normal-appearing gray matter (r = -0.73, p = 0.002) and white matter (r = -0.68, p = 0.004). The strongest correlation for gray matter was for the thalamus (r = -0.66, p = 0.004); this remained after controlling for age, gender, and T2 lesion volumes. Correlations with MMSE were much weaker, and there was no correlation between T2 lesion volume and the executive function score (r = -0.29, p = 0.27). CONCLUSIONS: Abnormalities of normal-appearing white and deep gray matter are present in nondemented CADASIL patients, and these DTI measurements correlate particularly strongly with executive function.

Adult↗

PubMed2004

Abnormal vasoconstrictor responses to angiotensin II and noradrenaline in isolated small arteries from patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by ultrastructural abnormalities in small cerebral and systemic vessels. We assessed vasomotor function in systemic small arteries in CADASIL. METHODS: We studied 10 CADASIL patients and 10 control subjects. Resistance arteries isolated from gluteal biopsies were mounted on small-vessel myographs, and concentration responses were determined for vasoconstrictors (noradrenaline, angiotensin II, and endothelin-I) and vasodilators (acetylcholine, bradykinin, spermine-NONOate, and nifedipine). Maximum data are shown as percent potassium contraction. RESULTS: There was reduced potency for noradrenaline in CADASIL (CADASIL [38 arteries]: EC50, 240 nmol/L; control subjects [27 arteries]: EC50, 100 nmol/L; 2-way analysis of variance, F=9.76, P=0.002). Maximum response to angiotensin II was greater in CADASIL (120+/-8% versus 97+/-5% in control subjects; F=4.28, P=0.043). Tachyphylaxis to angiotensin II occurred in all control subjects studied but in only 3 of 9 CADASIL subjects (P=0.011, Fisher's exact test). Vasodilation was similar in CADASIL patients compared with control subjects for endothelium-dependent dilators (acetylcholine and bradykinin) and endothelium-independent dilators (spermine-NONOate and nifedipine). CONCLUSIONS: These results suggest a selective systemic microvascular vasoconstrictor abnormality in CADASIL in noradrenaline and angiotensin II pathways that is not explained by vasodilator impairment in endothelium or vascular smooth muscle. This could have important implications for prophylaxis and treatment of CADASIL.

Angiotensin II↗

PubMed2002

Palindromic rheumatism.

A 27-year-old male presented with the complaints of recurring attacks of painful inflammation affecting finger joints of both hands for last one year. There were no constitutional features of weight loss, fever, anaemia, itching or burning sensation over the joints. It was diagnosed to be a case of palindromic rheumatism clinically and treated with hydroxychloroquine. The case is discussed in detail with reference to similar cases reported by others.

Adult↗

PubMedDate not supplied

The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship to age and clinical features.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a condition causing recurrent subcortical strokes. MR imaging, which shows focal lacunar infarcts and leukoaraiosis, plays a central role in the diagnosis and evaluation. We studied MR imaging abnormalities in a large prospectively recruited cohort of CADASIL patients to describe the spatial distribution of abnormalities, determine how this distribution alters with age, and identify any correlations with the clinical features of the disease. METHODS: In this study, 112 CADASIL subjects from 64 families were prospectively recruited. MR imaging scans were graded by a single neuroradiologist, by using the modified Scheltens scale, to quantify the severity of high-signal-intensity changes in different brain regions. RESULTS: Lesion load increased progressively with age. Scores were maximal in the frontal, parietal, and anterior temporal cortex, and the external capsule; intermediate in the pons; and relatively low in the corpus callosum, caudate, globus pallidus, cerebellum, midbrain, and medulla. Anterior temporal pole involvement was common at all ages and, when present, usually confluent, but this was absent in 33% of patients 20-29 years of age. A history of stroke correlated with total Scheltens score and internal capsule and pontine scores. Dementia correlated with total Scheltens score and subcortical white matter score, whereas depression correlated with subcortical white matter score but not total Scheltens score. CONCLUSIONS: There is a characteristic pattern of MR imaging abnormalities in CADASIL that aids in differential diagnosis; however, some characteristic features, such as anterior temporal pole involvement, can be absent. MR imaging lesion load correlated with some clinical features including stroke and dementia, whereas depression is more common in individuals with deep white matter changes.

Adult↗