Brain : a journal of neurology
-
Multicenter Study Comparative Study
Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies.
Idiopathic generalized epilepsies account for 30% of all epilepsies. Despite a predominant genetic aetiology, the genetic factors predisposing to idiopathic generalized epilepsies remain elusive. Studies of structural genomic variations have revealed a significant excess of recurrent microdeletions at 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 in various neuropsychiatric disorders including autism, intellectual disability and schizophrenia. ⋯ Eight of the transmitting parents were clinically unaffected, suggesting that the microdeletion itself is not sufficient to cause the epilepsy phenotype. Although the microdeletions investigated are individually rare (<1%) in patients with idiopathic generalized epilepsy, they collectively seem to account for a significant fraction of the genetic variance in common idiopathic generalized epilepsy syndromes. The present results indicate an involvement of microdeletions at 15q11.2 and 16p13.11 in epileptogenesis and strengthen the evidence that recurrent microdeletions at 15q11.2, 15q13.3 and 16p13.11 confer a pleiotropic susceptibility effect to a broad range of neuropsychiatric disorders.
-
Multicenter Study
Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage.
The term cortical spreading depolarization (CSD) describes a wave of mass neuronal depolarization associated with net influx of cations and water. Clusters of prolonged CSDs were measured time-locked to progressive ischaemic damage in human cortex. CSD induces tone alterations in resistance vessels, causing either transient hyperperfusion (physiological haemodynamic response) in healthy tissue; or hypoperfusion [inverse haemodynamic response = cortical spreading ischaemia (CSI)] in tissue at risk for progressive damage, which has so far only been shown experimentally. ⋯ Accordingly, we observed a spreading suppression of LF-VF, which accompanied spreading depression of high-frequency-electrocorticography activity, independently of whether CSD was associated with a physiological, absent or inverse haemodynamic response. Spreading suppressions of LF-VF thus allow the differentiation of progressive ischaemia and repair phases in a fashion similar to that shown previously for spreading depressions of high-frequency-electrocorticography activity. In conclusion, it is suggested that (i) CSI is a novel human disease mechanism associated with lesion development and a potential target for therapeutic intervention in stroke; and that (ii) prolonged spreading suppressions of LF-VF are a novel 'functional marker' for progressive ischaemia.
-
Multicenter Study
MRI of hippocampal volume loss in early Alzheimer's disease in relation to ApoE genotype and biomarkers.
Hippocampal volume change over time, measured with MRI, has huge potential as a marker for Alzheimer's disease. The objectives of this study were: (i) to test if constant and accelerated hippocampal loss can be detected in Alzheimer's disease, mild cognitive impairment and normal ageing over short periods, e.g. 6-12 months, with MRI in the large multicentre setting of the Alzheimer's Disease Neuroimaging Initiative (ADNI); (ii) to determine the extent to which the polymorphism of the apolipoprotein E (ApoE) gene modulates hippocampal change; and (iii) to determine if rates of hippocampal loss correlate with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, such as the beta-amyloid (Abeta(1-42)) and tau proteins (tau). The MRI multicentre study included 112 cognitive normal elderly individuals, 226 mild cognitive impairment and 96 Alzheimer's disease patients who all had at least three successive MRI scans, involving 47 different imaging centres. ⋯ The power to measure hippocampal change was improved by exploiting correlations statistically between successive MRI observations. The demonstration of considerable hippocampal loss in mild cognitive impairment and Alzheimer's disease patients over only 6 months and accelerated loss over 12 months illustrates the power of MRI to track morphological brain changes over time in a large multisite setting. Furthermore, the relations between faster hippocampal loss in the presence of ApoE allele epsilon4 and decreased CSF Abeta(1-42) supports the concept that increased hippocampal loss is an indicator of Alzheimer's disease pathology and a potential marker for the efficacy of therapeutic interventions in Alzheimer's disease.
-
Multicenter Study
Incidence and prognosis of > or = 50% symptomatic vertebral or basilar artery stenosis: prospective population-based study.
The higher risk of early recurrent stroke after posterior circulation transient ischaemic attack or minor stroke versus after carotid territory events could be due to a greater prevalence of large artery stenosis, but there have been few imaging studies, and the prognostic significance of such stenoses is uncertain. Reliable data are necessary to determine the feasibility of trials of angioplasty and stenting and to inform imaging strategies. In the first-ever population-based study, we determined the prevalence of > or = 50% apparently symptomatic vertebral and basilar stenosis using contrast-enhanced MRA in consecutive patients, irrespective of age, presenting with posterior circulation transient ischaemic attack or minor ischaemic stroke in the Oxford Vascular Study and related this to the 90-day risk of recurrent transient ischaemic attack and stroke. ⋯ In patients with posterior circulation events, > or = 50% vertebral and basilar stenosis was associated multiple transient ischaemic attacks at presentation (22% versus 3%; OR = 9.29; 95% CI = 2.31-37.27; P < 0.001) and with a significantly higher 90-day risk of recurrent events (OR = 3.2; 95% CI = 1.4-7.0; P = 0.006), reaching 22% for stroke and 46% for transient ischaemic attack and stroke. The prevalence of > or = 50% vertebral and basilar stenosis in posterior circulation transient ischaemic attack or minor stroke is greater than the prevalence of > or = 50% carotid stenosis in carotid territory events, and is associated with multiple transient ischaemic attacks at presentation and a high early risk of recurrent stroke. Trials of interventional treatment are therefore likely to be feasible, but more data are required on the long-term risk of stroke on best medical treatment.
-
Multicenter Study
Structural changes in the somatosensory system correlate with tic severity in Gilles de la Tourette syndrome.
Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. Previous structural MRI studies have identified regional abnormalities in grey matter, especially in the basal ganglia. These findings are consistent with the assumption of alterations in cortico-striato-thalamo-cortical circuits and dopaminergic neurotransmission playing a major role in the pathophysiology of GTS. ⋯ These findings demonstrate, for the first time, structural alterations in somatosensory pathways in GTS. Changes of water diffusion characteristics point towards reduced branching in somatosensory pathways in GTS patients. The negative correlation between higher regional FA values and fewer tics suggests that these alterations of white matter microstructure represent adaptive reorganization of somatosensory processing in GTS.