Jae Kyu Roh

Cerebral microbleeds are regionally associated with intracerebral hemorrhage

Background: Cerebral microbleeds (CMB) may be indicative of a hemorrhage-prone microangiopathy. Objective: To determine if increased numbers of these lesions are predictive of intracerebral hemorrhage (ICH), especially in terms of a distributional association. Methods: The authors examined consecutively 227 patients with acute stroke. CMB were counted using T2*-weighted gradient echo MRI data, and old lacunes and leukoaraiosis were also evaluated. The associations between the vascular risk factors and ICH were analyzed. With use of multivariate logistic regression analysis, the locations of the CMB or the old lacunes, which were categorized as being in the corticosubcortical area, the deep gray matter area, or the infratentorial area, were examined with regard to their relationships to the locations of the ICH. Results: The degrees of the CMB (r = 0.43, p < 0.01) and leukoaraiosis (r = 0.20, p < 0.01) were well correlated with the presence of ICH. Multivariate analysis revealed that the grades of the CMB were associated with the presence of ICH (p < 0.01, odds ratio [OR] = 2.67). CMB in the corticosubcortical area (p < 0.01, OR = 5.50) or deep gray matter (p < 0.01, OR = 2.55) were strongly associated with the presence of ICH in the same area, but no such association was observed in the case of CMB in the infratentorial area or in the case of old lacunes in any area. Conclusions: Cerebral microbleeds are strongly associated with the presence of intracerebral hemorrhage, and the distributional associations are also quite strong.

Decreased number and function of endothelial progenitor cells in patients with migraine

Objective: Migraine carries an increased risk for cardiovascular and cerebrovascular diseases that cannot be explained by traditional cardiovascular risk factors. The circulating endothelial progenitor cell (EPC) number is a surrogate biologic marker of vascular function, and diminished EPC counts are associated with higher cardiovascular risk. We investigated whether abnormalities in EPC levels and functions are present in migraine patients. Methods: Consecutive headache patients (n =166) were enrolled, including those with tensiontype headache (TTH; n = 74), migraine without aura (MO; n = 67), and migraine with aura (MA; n = 25). EPC colony-forming units in peripheral blood samples and migratory capacity to chemoattractants (stromal cell-derived factor 1 and vascular endothelial growth factor) and cellular senescence levels were assayed in risk factor-matched subjects (n = 6 per group). Results: The TTH group had more cardiovascular risk factors, more headache days, and higher Framingham risk scores than the other two groups. Mean numbers of EPC colony-forming units were 47.8 ± 24.3 in TTH, 20.4 ±22.2 in MO, and 8.6 ± 10.1 in MA patients (p < 0.001 in TTH vs MO; p = 0.001 in MO vs MA). EPC colony counts of normal subjects (n = 37) were not significantly different from those with TTH. Multiple linear regression models identified only MO, MA, and the presence of migraine (MO + MA) as significant predictors of EPC levels. In addition, EPCs from migraine patients (MO and MA) showed reduced migratory capacity and increased cellular senescence compared with EPCs from TTH or normal subjects. Conclusion: Circulating endothelial progenitor cell (EPC) numbers and functions are reduced in migraine patients, suggesting that EPCs can be an underlying link between migraine and cardiovascular risk. GLOSSARY: ACE= angiotensin-converting enzyme;ATR= angiotensin receptor;β-gal= β-galactosidase; BMI= body mass index; CAD= coronary artery disease; CADASIL= cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CFU= colony-forming unit; EBM= endothelial basal medium; EPC= endothelial progenitor cell; HDL= high-density lipoprotein; HPF= high-power field; IL= interleukin; KDR= kinase-insert domain receptor; LDL= low-density lipoprotein; MA= migraine with aura; MO= migraine without aura; PBS= phosphate-buffered saline; SA-β-gal= senescence-associated β-galactosidase; SDF-1= stromal cell–derived factor 1; TNF= tumor necrosis factor; TTH= tension-type headache; VEGF= vascular endothelial growth factor.

Initial and follow‐up brain MRI findings and correlation with the clinical course in Wilson's disease

We performed pretreatment brain MRIs in 25 patients with neurologically symptomatic Wilsons disease (WD) and clinical and MRI follow-up in 16 of them. All 25 pretreatment MRIs revealed abnormalities, with abnormal high-signal intensity (HSI) in bilateral thalami being the most common (92%). HSI lesions in the brainstem (84%) and the basal ganglia (72%) were also common. Brain atrophy was present in 88% of the 25 patients. In the follow-up period of 5 to 24 months, during which the patients were treated with D-penicillamine, both HSI lesions and neurologic symptoms improved in 88% of the 16 patients, but the brain atrophy did not change.

Comparative analysis of the spatial distribution and severity of cerebral microbleeds and old lacunes

Background: Cerebral microbleeds, which result from microangiopathic changes following chronic hypertension, may reflect bleeding-prone microangiopathy. However, the distribution of these lesions has not been compared with that of lacunes, which represent occlusive type microangiopathy. Objectives: To compare the cerebral distribution of microbleeds and lacunes and correlate their severity. Methods: The study population comprised 129 hypertensive patients who underwent brain magnetic resonance imaging (MRI), including gradient echo (GE) sequences. Cerebral microbleeds were counted using GE-MRI data, and lacunes were also counted by comparing T1 and T2 weighted MRI. To investigate the distributions, the number of patients with each type of lesion was compared, and the occurrence index (the total number of the specific lesions divided by the total number of patients) was examined statistically. Correlation analyses were done on the relations between the different grades of microbleeds, lacunes, and leukoaraiosis. Results: Cerebral microbleeds and lacunes were found at various foci in the brain, with a preference for the cortico-subcortical region and the deep grey matter. The occurrence index of microbleeds, but not of lacunes, was significantly higher in the cortico-subcortical region than in the deep grey matter. The severity of the microbleeds was positively correlated with the severity of lacunes, and both types of lesion were closely correlated with the degree of leukoaraiosis. Conclusions: These data suggest that microbleeds and lacunes tend to occur to a similar extent in long standing hypertension, but not necessarily in the same locations.

Left ventricular hypertrophy is associated with cerebral microbleeds in hypertensive patients.

Background: Cerebral microbleeds (CMBs) are indicative of hemorrhage-prone microangiopathy and known to be closely associated with chronic hypertension. However, no studies have been undertaken on the association between left ventricular (LV) hypertrophy and the severity of CMB. Methods: One hundred two consecutive stroke patients with hypertension were examined. CMBs were counted using T2*-weighted gradient echo MRI data. With use of ordinal logistic regression analysis, the associations between LV mass index and other vascular risk factors and CMBs were analyzed. Results: Hypertensive patients with CMBs showed a higher LV mass index than patients without. The grades of LV mass index were significantly correlated with the grades of CMB in the whole brain (p = 0.02), in the central gray matter (p < 0.01), and in the infratentorial area (p < 0.01), but not with those in the subcortical white matter. Ordinal regression analysis revealed that the LV mass index was independently associated with increased CMB severity (p = 0.01), regionally in the central gray matter (p < 0.01) and in the infratentorial area (p < 0.01), but not in the subcortical white matter (p = 0.63). After excluding patients with cerebral amyloid angiopathy, the association between the LV mass index and the CMB severity in the subcortical white matter became significant (p < 0.01). Conclusions: There is a close relationship between CMBs and LV hypertrophy in hypertensive patients with stroke. Thus, CMBs should be understood as one type of cerebral target organ damage by chronic hypertension.

Rotational vertebral artery syndrome: Oculographic analysis of nystagmus

In four patients with rotational vertebral artery syndrome (RVAS), the initial nystagmus was mostly downbeat, with the horizontal and torsional components beating toward the compressed vertebral artery side (n = 3) or directed away (n = 1). Three patients showed spontaneous reversal of the nystagmus and two exhibited no or markedly diminished responses on immediate retrial of head rotation (habituation). The patterns of nystagmus suggest that RVAS may result from differing mechanisms.

Reduced circulating angiogenic cells in Alzheimer disease

1. Pradhan S. Bilaterally symmetric form of Hirayama disease. Neurology 2009;72:2083–2089. 2. Tashiro K, Kikuchi S, Itoyama Y, et al. Nationwide survey of juvenile atrophy of distal upper extremity (Hirayama disease) in Japan. Amyotroph Lateral Scler 2006;7:38–45. 3. Tataroglu C, Bagdatoglu C, Apaydin FD, Celikbas H, Koksel T. Hirayama’s disease: a case report. Amyotroph Lateral Scler Other Motor Neuron Disord 2003;4:264– 265. 4. Gaio JM, Lechevalier B, Hommel M, Viader F, Chapon F, Perret J. Chronic spinal amyotrophy involving the upper limbs in young adults (O’Sullivan and McLeod syndrome): MRI study of the cervical spinal cord. Rev Neurol 1989;145:163–168. 5. Gamez J, Also E, Alias L, et al. Investigation of the role of SMN1 and SMN2 haploinsufficiency as a risk factor for Hirayama’s disease: clinical, neurophysiological and genetic characteristics in a Spanish series of 13 patients. Clin Neurol Neurosurg 2007;109:844–848. 6. Gouri-Devi M, Suresh TG, Shankar SK. Monomelic amyotrophy. Arch Neurol 1984;41:388–394. 7. Prabhakar S, Chopra JS, Banerjee AK, Rana PV. Wasted leg syndrome: a clinical, electrophysiological and histopathological study. Clin Neurol Neurosurg 1981;83: 19–28. 8. Pradhan S, Gupta RK. Magnetic resonance imaging in juvenile asymmetric segmental spinal muscular atrophy. J Neurol Sci 1997;146:133–138. 9. Gourie-Devi M, Nalani A. Long-term follow-up of 44 patients with brachial monomelic amyotrophy. Acta Neurol Scand 2003;107:215–220. 10. Khandelwal D, Bhatia M, Singh S, et al. Widespread electromyographic abnormalities in patients with monomelic amyotrophy: a detailed EMG study. Electromyogr Clin Neurophysiol 2005;45:63–67.

Correlation of Coronary and Cerebral Atherosclerosis: Difference between Extracranial and Intracranial Arteries

Background: A difference with regard to the correlation with coronary atherosclerosis (CAS) between extracranial carotid atherosclerosis (ECAS) and intracranial cerebral atherosclerosis (ICAS) has been assumed but not proven clearly by direct comparison within the same population. Methods: A consecutive series of 246 patients undergoing coronary artery bypass graft surgery were reviewed. The severity of CAS was estimated as a CAS score based on coronary angiography. The presence of ECAS and ICAS was screened by transcranial Doppler and carotid duplex sonography, and confirmed by magnetic resonance angiography. Results: The CAS scores in patients with ECAS were observed to be higher than those in patients without ECAS (10.62 ± 4.80 vs. 9.45 ± 4.25; p = 0.054 on the Mann-Whitney U test). The difference in CAS scores was smaller between patients with and without ICAS (10.41 ± 4.44 vs. 9.66 ± 4.49; p = 0.201). Similar patterns were observed on comparing the correlation of ECAS and ICAS with a quartile of the CAS score. An advanced CAS, which was generated by collapsing the quartiles of the CAS score into 75th percentile or less and more than the 75th percentile, was significantly associated with ECAS, but not with ICAS. These associations remained unchanged after adjustments had been made for age, sex, hypertension, diabetes mellitus, hyperlipidemia, smoking and a history of stroke or transient ischemic attack. Conclusions: This study suggests that the correlation of CAS with ECAS is stronger than that of CAS with ICAS, and this difference is independent of the classic risk factors for atherosclerosis.

Acute bilateral cerebellar infarcts in the territory of posterior inferior cerebellar artery.

Article abstract The authors report 12 patients with acute bilateral cerebellar infarcts in posterior inferior cerebellar artery (PICA) territory. They found three topographic patterns: A) bilateral medial PICA in six patients; B) unilateral whole + contralateral medial PICA in four; and C) bilateral small multiple in two. Nine patients in Groups A and B had unilateral PICA or vertebral artery disease, and both patients in Group C had bilateral vertebral artery disease. These findings support that unilateral supply to both medial PICA territories may be the most relevant pathogenesis of this syndrome.

High-resolution MR technique can distinguish moyamoya disease from atherosclerotic occlusion

Moyamoya disease (MMD) is an idiopathic progressive narrowing of distal internal carotid arteries and secondary development of small collaterals.1 The distinction between MMD and intracranial atherosclerosis is not easy when a patient has concomitant vascular risk factors. We attempted to differentiate the 2 disease conditions by applying high-resolution plaque MRI in the occluded segment.2 High-resolution MRI of MMD disclosed blunted obliteration of the vessel lumen without eccentric plaque, and black-blood image delineated the occlusion site with homogeneous material and multiple spring-like vascular structures (figure, A). Intracranial atherosclerosis showed eccentric plaque with heterogeneous signals and enhancement (figure, B).