BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small vessel disease. Although postmortem studies have demonstrated mural thickening in leptomeningeal arteries and lenticulostriate perforating arteries, it is unclear whether this also leads to luminal narrowing. High-field MRI scanners enable in vivo imaging of the lumen of the lenticulostriate arteries. The aim of this study is to examine the luminal diameters of lenticulostriate arteries in living patients with CADASIL and to investigate whether luminal narrowing is correlated with the number of lacunar infarcts in the basal ganglia.

METHODS: Twenty-two NOTCH3 mutation carriers and 11 healthy control subjects were examined using high-resolution 3-dimensional time-of-flight MR angiography imaging on a 7-T MRI scanner. Scans were analyzed for the presence of focal stenotic segments. The total number, length, and total cross-sectional area of lenticulostriate arteries were measured and compared between mutation carriers and control subjects. These measurements were correlated with age, disease duration, and number of lacunar infarcts in the basal ganglia.

RESULTS: No stenotic segments were observed. No differences between mutation carriers and control subjects were found in total number of end branches (mutation carriers: mean, 14.6; control subjects: mean, 12.8), length of the lenticulostriate system, or total cross-sectional area of lenticulostriate artery lumina. Measurements of lenticulostriate artery lumina were not associated with lacunar infarct load in the basal ganglia area or with basal ganglia hyperintensities.

CONCLUSIONS: Three-dimensional time-of-flight MR angiographic on 7 T showed no differences in luminal diameters of lenticulostriate arteries between patients with CADASIL and control subjects.

BACKGROUND: Benign essential blepharospasm (BEB) is a common form of focal dystonia. Besides pathology in the basal ganglia, accumulating evidence suggests pathologic changes in the anterior cingulate cortex (ACC).

METHODS: This is a randomized, sham-controlled, observer-blinded prospective study. In 12 patients with BEB, we evaluated the effects of a 15-minute session of low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) over the ACC with stimulation intensities at 100% active motor threshold with 3 stimulation coils: a conventional circular coil (C-coil), a sham coil (S-coil), and a Hesed coil (H-coil, which allows stimulation of deeper brain regions. Primary outcome was the clinical effects on BEB (blink rate, number of spasms rated by a blinded physician and patient rating before, immediately after, and 1 hour after stimulation); secondary outcome was the blink reflex recovery curve.

RESULTS: Subjective stimulation comfort was similar for each coil with no stimulation-associated adverse events. Stimulation with the H- and C-coils resulted in a significant improvement in all 3 outcome measures and was still detectable in physician rating and patient rating 1 hour after stimulation. S-coil stimulation had no effects. The active motor threshold was significantly lower for the H-coil compared to the other 2 coils.

CONCLUSIONS: rTMS could be used as a therapeutic tool in BEB. Further studies will be necessary to show whether repeated stimulation applications result in lasting clinical effects. Classification of evidence: This study provides Class II evidence that for patients with BEB, H- and C-coil rTMS is safe and improves clinical symptoms of BEB immediately and 1 hour after stimulation.

BACKGROUND AND PURPOSE: Time of ischemia onset is the most critical factor for patient selection for available drug treatment strategies. The purpose of this study was to evaluate the abilities of the absolute longitudinal rotating frame (T(1?)) and transverse (T(2)) MR relaxation times to estimate the onset time of ischemia in rats.

METHODS: Permanent middle cerebral artery occlusion in rats was used to induce focal cerebral ischemia and animals were imaged with multiparametric MRI at several time points up to 7 hours postischemia. Ischemic parenchyma was defined as tissue with apparent diffusion coefficient of water <70% from that in the contralateral nonischemic brain.

RESULTS: The difference in the absolute T(1?) and T(2) between ischemic and contralateral nonischemic striatum increased linearly within the first 6 hours of middle cerebral artery occlusion. The slopes for T(1?) and T(2) fits for both tissue types were similar; however, the time offsets were significantly longer for both MR parameters in the cortex than in the striatum.

CONCLUSIONS: T(1?) and T(2) MRI provide estimates for the onset time of cerebral ischemia requiring regional calibration curves from ischemic brain. Assuming that patients with suspected ischemic stroke are scanned by MRI within this timeframe, these MRI techniques may constitute unbiased tools for stroke onset time evaluation potentially aiding the decision-making for drug treatment strategies.

BACKGROUND AND PURPOSE: Oxidized low-density lipoprotein (oxLDL) induces endothelial dysfunction and antibody formation. Because endothelial dysfunction is involved in cerebral small vessel disease (CSVD) (dilated Virchow Robin spaces, lacunar infarcts, and white matter lesions), oxLDL antibodies could play a role in CSVD pathogenesis. Therefore, we studied oxLDL antibodies in patients with high prevalence of CSVD: lacunar stroke patients and essential hypertensive patients.

METHODS: A total of 158 lacunar stroke patients, 158 hypertensive patients, and 43 healthy controls were included. We determined levels of IgG and IgM against hypochlorite (HOCl) and malondialdehyde (MDA) oxLDL using ELISA (values in optical density).

RESULTS: Patients with CSVD had higher levels of IgG-HOCl-oxLDL (0.77 versus 0.70; P<0.01), as well as lower levels of IgM-MDA-oxLDL (0.55 versus 0.65; P<0.05) than patients without such lesions. Higher IgG-HOCl-oxLDL levels were only independently associated with higher numbers of Virchow Robin spaces at the level of the basal ganglia (?=0.218; P<0.001).

CONCLUSIONS: An autoinflammatory process with lower levels of IgM antibodies and higher levels of IgG antibodies against oxLDL may be involved in CSVD.

BACKGROUND: Neuroimaging may prove useful in identifying cardiac arrest patients destined for a poor recovery, as certain patterns have been associated with a poor outcome. However, MRI changes evolve temporally and spatially, which may lead to misinterpretation and misclassification of patients.

METHODS: Eight comatose patients following cardiac arrest underwent diffusion-weighted imaging (DWI) at two time points, and one patient underwent DWI at three time points. Each of the prespecified areas of each study were read as either “normal” or “abnormal” by two stroke neurologists. Neurological examinations, including GCS scores, were recorded on days 0, 1, 3, and 7. Outcomes were determined by the modified Rankin Scale (mRS), with poor outcome defined as mRS score ?4 at 6 months.

RESULTS: In the acute (<24 h) period, two patients exhibited changes on DWI and FLAIR in the cerebellum and basal ganglia. In the early subacute period (days 1-5), cortical abnormalities predominated, with a shift to more white matter changes in the late subacute period (days 6-12). We observed more widespread imaging abnormalities in patients with poor outcomes, and partial or full resolution of DWI abnormalities in the two patients with good outcomes.

CONCLUSIONS: MRI patterns after global hypoxic-ischemic injury follow a characteristic pattern with variable acute changes in the cortex, basal ganglia, and cerebellum, followed by predominantly cortical and white matter changes in the early and late subacute periods. Diffuse, persistent widespread changes on MRI may help to predict poor outcome.

Hemichorea associated with carotid artery occlusive disease is extremely rare. It has been recently suggested that carotid artery stenosis should be considered in the differential diagnosis of chorea, even in the absence of a preceding stroke or transient ischemic attack. Although the pathophysiology of this condition is still under discussion, some reports suggest that impaired cerebral blood flow in the basal ganglia is a key contributing factor. We herein report a case of hemichorea related to severe stenosis of the left internal carotid artery with no basal ganglia lesions on brain MRI. After carotid revascularization, hemichorea gradually subsided and reversible left thalamic and putaminal hypoperfusion were demonstrated by functional neuroimaging. This case report supports the hypothesis about the central role of hemodynamic ischemia in the pathophysiology of hemichorea associated with carotid artery stenosis, and highlights the importance of vascular imaging studies for the early identification of carotid disease in patients with chorea, even in the absence of other clinical signs.

Copyright © 2010 Elsevier B.V. All rights reserved.

Disabling fatigue is a symptom in a number of neurological diseases, including multiple sclerosis, stroke and Parkinson’s disease. We used (18)F-dopa and (11)C-DASB [N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine] positron emission tomography, markers of dopamine storage capacity and serotonin transporter availability, to investigate whether fatigue in Parkinson’s disease is associated with dopaminergic and serotonergic dysfunction in basal ganglia and limbic circuits. Ten patients with Parkinson’s disease and fatigue and 10 patients without fatigue had a (18)F-dopa scan. Seven patients with and eight patients without fatigue also had a (11)C-DASB scan. The two groups were matched for age, disease duration and severity and daily intake of levodopa equivalent units. None had a history of depression or sleep disturbance. Using a region of interest analytical approach, we found that patients with fatigue had significantly lower serotonin transporter binding than patients without fatigue in the caudate, putamen, ventral striatum and thalamus. Striatal (18)F-dopa uptake was similar in the fatigued and non-fatigued groups. Voxel-based analysis localized further relative serotonin transporter binding reductions in the cingulate and amygdala of the fatigue group, and (18)F-dopa uptake reductions in the caudate and insula. We conclude that fatigue in Parkinson’s disease is associated with reduced serotonergic function in the basal ganglia and limbic structures. Insular dopaminergic dysfunction could also play a role. These findings imply that strategies to increase brain level of serotonin would be a rational approach for relieving fatigue symptoms in Parkinson’s disease and may also be relevant to alleviating fatigue in other clinical conditions.

The high convenience of data collection by helical scanning, such as making multi planner reformat (MPR) and shortening scan time, means that the technique is widely used to diagnose various body parts. However, non-helical scanning is still a main current for plane brain computed tomography. The possibility of diagnosing acute cerebral infarction by helical scanning MPR was examined. It was found that image degradation in helical scanning had little influence on the physical evaluation of the characteristics of modulation transfer function and the noise power spectrum, etc. In the evaluation of the ischemic change occurring at the early stage made by examination of clinical images, the result was almost equal to that obtained by non-helical scanning, as the reported sensitivity was 52% and the specificity was 95%. This suggested that brain helical scanning MPR might be applied clinically. However, a disadvantage was confirmed as helical scanning had a higher exposure dose than non-helical scanning at the start and end of scanning. The results of this study indicated that helical scanning demonstrates sufficient convenience for the assessment of acute cerebral infarction at the basal nucleus level.

BACKGROUND AND PURPOSE: Little is known about the risk factors of dilated Virchow-Robin spaces (dVRS) and their relation with other markers of brain small vessel disease. We investigated both issues in a large population-based sample of elderly individuals.

METHODS: Severity of dVRS was semiquantitatively graded in both white matter and basal ganglia using high-resolution 3-dimensional MRI images taken from 1818 stroke- and dementia-free subjects enrolled in the Three-City Dijon MRI study. Multinomial logistic regression models were used to model the association of cardiovascular risk factors, APOE genotype, brain atrophy, and MRI markers of small vessel disease with the degree of dVRS.

RESULTS: Severity of dVRS was found to be strongly associated with age in both basal ganglia (degree 4 versus 1: OR, 2.1; 95% CI, 1.4 to 3.2) and white matter (OR, 1.5; 95% CI, 1.2 to 1.9). The proportion of hypertensive subjects increased with the degrees of dVRS in both basal ganglia (P=0.02) and white matter (P=0.048). Men presented a higher risk of severe dVRS in basal ganglia than women, particularly degree 4 (OR, 6.0; 95% CI, 1.8 to 19.8). The degree of dVRS was associated with the volume of white matter hyperintensities and the prevalence of lacunes, but not with brain atrophy.

CONCLUSIONS: In this large cohort study of elderly subjects, the degree of dVRS appears independently associated with age, hypertension, volume of white matter hyperintensities, and lacunar infarctions. dVRS should be considered as another MRI marker of cerebral small vessel disease in the elderly with regional variations in their severity.

An adolescent male patient originally presented to a prodromal clinical research program with severe obsessive-compulsive behaviors and subthreshold symptoms of psychosis, which eventually developed into first-rank psychotic symptoms. The patient was followed over a 2-year period. His symptoms did not respond to psychotherapy or pharmacotherapy. However, when a pineal region tumor was discovered and treated with chemotherapy and autologous stem cell rescue, both psychotic symptoms and psychosocial functioning reverted toward baseline. Although subcortical brain structures have been implicated in the pathophysiology of idiopathic psychosis, reports of psychiatric sequelae of treatment of subcortical tumors are rare. Etiological pathways that may have played a role in symptom development are of particular interest, as understanding these mechanisms may shed light on the pathophysiology of psychotic disorders more generally.