Longitudinal changes of metabolites in frontal lobes after hemorrhagic stroke of basal ganglia: a proton magnetic resonance spectroscopy study.

BACKGROUND AND PURPOSE: We investigated serial metabolic changes in frontal lobes of patients with deep intracerebral hemorrhage (ICH) to examine the correlation between N-acetylaspartate (NAA) and degree of motor impairment or clinical outcome. METHODS: - Twenty patients with deep ICH were examined with proton magnetic resonance spectroscopy with the application of a multivoxel method (1 voxel=10x10x20 mm; 64 voxels). NAA/creatine ratios in the white matter of the primary motor and premotor areas on both sides were measured sequentially: within 48 hours, at 2 weeks, and 1 month after onset. The National Institutes of Health Stroke Scale and Barthel Index for disability were measured for each patient. RESULTS: - In the primary motor area on the affected side, where the hematoma did not extend, the NAA/creatine ratio decreased sequentially. At 48 hours and 2 weeks after onset, a negative correlation was detected between NAA/creatine and hematoma volume, but there was no correlation 1 month later. At 2 weeks, NAA/creatine correlated negatively with motor impairment (r=-0.750), and there was a significant correlation with clinical outcome as early as 2 weeks after onset (r=0.954). These sequential changes of NAA/creatine varied according to patients' long-term clinical outcome. Patients with poor outcome demonstrated notable reduction of NAA/creatine over the bilateral frontal lobes. CONCLUSIONS: - The delayed gradual reduction of NAA/creatine ratio in the frontal lobes correlates with motor deficit and clinical outcome after deep ICH, suggesting that the neural networks in the frontal lobe could be important for recovery.

[A case of slowly progressive "pharyngeal-cervical-brachial variant of Guillain-Barré syndrome (PCB)"].

A 69-year-old woman was admitted to our hospital because of slowly progressive weakness in the neck, shoulders, proximal arms, oropharyngeal muscles. From a viewpoint of clinical course and signs, it was suspected that the patient was suffered from motor neuron disease. However, serial electrophysiological studies showed the existence of local demyelination of the motor nerves. The immunoadsorption was then performed and marked recovery of symptoms was obtained. In this case, we could not detect any established anti-ganglioside antibodies which was related to pharyngeal-cervical-brachial variant of Guillain-Barré syndrome(PCB) or Guillain-Barré syndrome (GBS). It is suggested that unknown anti-ganglioside antibody may play an important role in cases of PCB. Despite of atypical slowliness of clinical progression and negative results of immunological studies, this patient is considered to be suffered from PCB, because of the results of electrophysiological studies and effectiveness of immunoadsorption therapy. Accordingly it may be important to take the possibility of PCB into diagnostic consideration, whenever the patient shows slowly progressive weakness in proximal arms, oropharyngeal muscles.

[A case with cerebral subcortical hemorrhage following the administration of phenylpropanolamine].

A 21-year-old woman experienced severe headache and nausea one hour after taking pills containing 160 mg of phenylpropanolamine for common cold. She had no previous history of drug abuse or hypertension. Physical examination revealed slight left-sided hemiparesis. Her blood pressure was 100/52 mmHg. Subcortical hemorrhage was noted in the right frontal lobe with a cranial computed tomography. On the seventh hospital day, cerebral angiography demonstrated with segmental narrowing of a branch of the right anterior cerebral artery, indicating the presence of focal angitis. This finding disappeared on the 35th hospital day. In the majority of the reported cases of the intracerebal hemorrhage associated with the ingestion of phenylpropanolamine, focal angitis rather than induced hypertension is considered to be a causative factor for hemorrhage. Thus, we would like to emphasize that the administration of phenylpropanolamine should be avoided, even to the patients without hypertention or past history of intracerebral hemorrhage.

[Usefulness of diffusion-weighted MRI in the diagnosis of transient ischemic attacks].

Diffusion-weighted imaging(DWI) has been demonstrated to be valuable for assessment of ischemic stroke patients. The aim of this study is to evaluate clinical usefulness of DWI in the diagnosis of transient ischemic attack(TIA). Nineteen patients with symptoms of TIA were studied. DWI was taken with 1.5 Tesla MRI system using spin echo EPI sequence. Seven patients revealed areas of hyperintensity (brightness) on DWI and of hypointensity on apparent diffusion coefficient(ADC) maps relative to normal brain. As the duration of TIA symptom elongated, the percentage of patients with DWI abnormalities became higher. DWI enabled to detect areas of hyperintense lesion in all three patients as early as 3 hours after the onset, while conventional T2 weighted imaging showed in one. All the DWI abnormalities were irreversible in spite of the complete recovery from TIA. DWI is an useful technique for the detection of responsible lesions in TIA. However, TIA cannot be ruled out even if DWI does not demonstrate any abnormal signals.

Diffusion-weighted imaging demonstrates transient cytotoxic edema involving the corpus callosum in a patient with diffuse brain injury.

Reversible T2 hyperintense signal abnormality in the corpus callosum, although frequently seen after diffuse brain injury, has not been well clarified. With some accumulated evidence, we report a case of diffuse brain injury in a 24-year-old man. Magnetic resonance imaging (MRI) demonstrated T2 hyperintense signals in the trunk and the splenium of the corpus callosum 12 days postinjury. Echo-planar diffusion-weighted imaging was also performed on the same day, which revealed decreased diffusion (hyperintense signals) in the same site and almost the same size as T2 hyperintense signals. T1-weighted images were normal. Neuropsychological examination of the patient did not show callosal syndrome, namely hemialexia, unilateral agraphia and unilateral apraxia. Repeat MRI on day 20 demonstrated a signal decrease of both T2-weighted images and diffusion-weighted images (DWI) in the lesion. Follow-up MRI at 6 months showed complete resolution of the T2 signal abnormalities and of the corresponding decreased diffusion. Considering that diffusion-weighted imaging showed transient decreased diffusion, the lesion in the corpus callosum indicated the existence of cytotoxic edema. Also, transient DWI hyperintensity, namely cytotoxic edema, in the trunk and the splenium of the corpus callosum does not necessarily reveal callosal deficits.

[Changes in proton magnetic resonance spectroscopy and Wechsler adult intelligence scale revised after clipping of unruptured aneurysms].

The purpose of this study is to evaluate the influence of surgery for unruptured aneurysms on neuropsychological status and cerebral metabolism. We studied 21 patients with unruptured aneurysms treated with direct surgery accompanied by craniotomy, rather than by the endovascular method. Patients were evaluated before and after surgery, using the Wechsler adult intelligence scale revised (WAIS-R) and proton magnetic resonance spectroscopy which measured the ratio of N-acetyl-aspartate to creatine (NAA/Cr). Although the results of WAIS-R (total IQ, verbal IQ and performance IQ) was not significantly different after surgery in any of the patients, the total IQ of the patients with anterior communicating artery aneurysms (AcoA) showed a significant decline compared with patients with other aneurysms after surgery. Five of eight AcoA patients showed a specific reduction in verbal IQ, suggesting deterioration of recent memory. The NAA/Cr remained within the normal range and was not significantly different before and after surgery. However, the NAA/Cr in the white matter of the frontal lobe of AcoA patients showed a significant reduction compared with that of non-AcoA patients. All three elderly patients older than 70 showed a reduction in NAA/Cr of more than one standard deviation from normal subjects in their frontal or parietal lobes. These results indicated that operation for unruptured aneurysms is reliable and well established but they also show that careful consideration should be given to possible deterioration in neuropsychological status and cerebral metabolism after operation in AcoA and elderly patients.

[Evaluation of cerebral metabolism by multi-voxel proton magnetic resonance spectroscopy imaging in chronic unilateral internal carotid artery occlusion].

Proton magnetic resonance spectroscopy(1H-MRS) has less been used to analyze cerebral metabolism in ischemic lesions compared to single photon emission computed tomography or positron emission computed tomography. Recent advances in magnetic resonance imaging apparatus and the related software have made possible obtaining multi-voxel 1H-MRS in a single study. We examined multi-voxel 1H-MRS in patients with unilateral internal carotid artery(ICA) occlusion to study the relationship between cerebral metabolism and cerebral blood flow. Fifteen patients(male 11; female 4, 47-76; average 67.1 year-old) with chronic unilateral ICA occlusion and without any marked infarction were studied. 1H-MRS was obtained using a 1.5 T Siemens Magnetom Vision scanner. Multi-voxel spectra were recorded using a SE-2 D-CSI sequence(TR/TE = 1500/135 ms). The volume of interest was 90 x 90 x 20 mm3, placed axially above the lateral ventricle. The single voxel size was 10 x 10 x 20 mm3. N-acetyl aspartate/creatine ratios(NAA/Cr) were calculated on each voxel and were averaged in view of the cortex and the white matter. The regional cerebral blood flow(CBF) was measured by Xenon-CT method. Eight patients were also examined by acetazolamide challenge to evaluate the cerebrovascular reserve capacity. NAA/Cr ratios in normal subjects were 1.905 +/- 0.090(mean +/- standard deviation) in the cortex and 2.183 +/- 0.258 in the white matter in 40's(n = 6), 2.046 +/- 0.166 in the cortex and 2.039 +/- 0.288 in the white matter in 60's(n = 5). The study revealed 7 patients with normal NAA/Cr ratio and CBF, 5 with reduced NAA/Cr ratio and normal CBF, and 3 with reduced NAA/Cr ratio and CBF in the affected cortex. A low correlation coefficient of 0.46 was noted between NAA/Cr ratio and the cerebrovascular reserve capacity calculated by acetazolamide challenge in the affected cortex. In the range of less than +10%(lower limit) in percentile change of regional CBF after acetazolamide injection, NAA/Cr ratio was distributed between 1.600 and 2.044, which were normal or slightly under the lower limit(mean-2 x standard deviation). Multi-voxel 1H-MRS is useful for the evaluation of cerebral metabolism, because it enables to quantify different chemicals in many fields at one time and to compare its distribution with regional CBF. In patients with unilateral ICA occlusion, NAA/Cr ratio of the affected cortex varies depending on the collateral circulation and the contralateral ICA lesions. The Extracranial-Intracranial Bypass should be considered if the case with unilateral ICA occlusion reveals reduced CBF and normal or slightly decreased NAA/Cr ratio in the affected cortex.

Partial seizure with aphasic speech arrest caused by watching a popular animated TV program.

On the evening of December 16, 1997, about 700 children across Japan were hospitalized because of convulsive seizures or vomiting experienced while watching a popular animated TV program that included blue and red stimuli that alternated at 12 flashes per second. In one case, an 11-year-old girl developed a hallucination in the right visual field and a subsequent cramp on the right side of her face, with aphasic speech arrest. She had no history of seizures. Her electroencephalogram (EEG) showed normal background activity and no epileptiform discharges. Intermittent photic stimulation provoked a photoparoxysmal response. Her main clinical manifestation was a TV-induced left occipital lobe seizure spreading toward the left inferior frontal lobe. This suggested a functional link from the occipital lobe to the frontal operculum.

Transcranial magnetic stimulation of the central and peripheral motor pathways to the lingual muscles in cats.

OBJECTIVE: We have assessed a technique to stimulate the intracranial hypoglossal nerve with ease and reproducibility by using magnetic coils (MCs) and to detect a reliable site of excitation in animal experiments in order to establish a method to evaluate the motor pathway to lingual muscles. METHODS: We recorded the motor responses from the lingual muscles of 5 adult cats under general anesthesia by magnetic and electrical stimulation of the intracranial hypoglossal nerves. Figure of 8 and round MCs were used to investigate the optimal position and direction to evoke the motor responses. RESULTS: The round MC was useful for cortical stimulation. The figure of 8 coil, positioned in the back of the head of the examined side, parallel to the cervical spine, was essential for stimulation of the intracranial hypoglossal nerve. Analysis of the latencies, and the observation that the motor responses disappeared after transection of the nerves at the exit of the hypoglossal canal, demonstrated that the site of the excitation is at the exit of the hypoglossal canal. CONCLUSION: Magnetic stimulation using a figure of 8 coil can elicit tongue motor responses with ease and reliable reproducibility, stimulating the hypoglossal nerve at the exit of the hypoglossal canal.

Role of the ryanodine receptor in ischemic brain damage--localized reduction of ryanodine receptor binding during ischemia in hippocampus CA1.

1. The ryanodine receptor has recently been shown to play a pivotal role in the regulation of intracellular Ca2+ concentration via Ca(2+)-induced Ca2+ release (CICR). Effects of ischemia on CICR in the brain tissue, however, remain largely unknown since only a few reports have been published on this subject. In this paper we report on work in this area by our group and review related progress in this field. 2. We examined alterations of ryanodine receptor binding and local cerebral blood flow (LCBF) at 15 min, 30 min, and 2 hr after occlusion of the right common carotid artery in the gerbil brain. A quantitative autoradiographic method permitted simultaneous measurement of these parameters in the same brain. The LCBF was significantly reduced in most of the cerebral regions on the occluded side during each time period of ischemia. In contrast, only in the hippocampus CA1 on the occluded side was a significant reduction in ryanodine binding found at 15 min, 30 min and 2 hr after the occlusion. 3. These findings suggest that suppression of ryanodine binding in the hippocampus CA1 may be attributable to a regionally specific perturbation of CICR and that this perturbation may be closely associated with the pathophysiological mechanism that leads to be selective ischemic vulnerability of this region. 4. Other recent studies have also reported an important role for ryanodine receptors in neuronal injury such as the delayed neuronal death in the hippocampus CA1. These data suggest that derangement of CICR is likely to be involved in acute neuronal necrosis as well as in delayed neuronal death in ischemia. 5. Further studies on clarifying the role of CICR in ischemic brain damage are needed in order to develop new therapeutic strategies for stroke patients.

Alteration of ryanodine receptor in the hippocampus CA1 after hemispheric cerebral ischemia.

Alterations in ryanodine binding and local cerebral blood flow (LCBF) were examined at 30 minutes and 2 hours post-ischemia in the gerbil brain in order to evaluate the influence of cerebral ischemia on the intracellular channels of Ca2+-induced Ca2+ release (CICR). Severe hemispheric cerebral ischemia was induced by occluding the right common carotid artery. LCBF was measured at the end of the experiment using [14C]iodoantipyrine method, and the ryanodine binding was evaluated in vitro using [3H]ryanodine as a specific ligand for CICR channels. An autoradiographic method developed in our laboratory enabled us to determine both parameters within the same brain. A group of gerbils who underwent a sham procedure served as controls. LCBF was found to be significantly reduced in most of the cerebral regions on the occluded side at both 30 minutes as well as 2 hours post-ischemia. In contrast, a significant reduction in ryanodine binding was noted only in the hippocampus CA1 on the occluded side at 30 minutes and 2 hours after the occlusion. These findings suggest that regionally specific changes of CICR may be the cause of decreased ryanodine binding in the hippocampus CA1, and that these changes may be related to the pathophysiological mechanisms that cause this region to be particularly vulnerable to ischemia.

Flow threshold for reduction of cyclic AMP binding in the hippocampus CA1 and other brain regions during stroke development in gerbils.

The flow threshold for alterations of the in vitro [3H]cyclic AMP (cAMP) binding, an indicator of the total amount of particulate cAMP-dependent protein kinase, was evaluated in the gerbil brain after 30 min, 2 h, and 6 h of unilateral common carotid artery occlusion, respectively. The autoradiographic method developed in our laboratory enabled us to measure the [3H]cAMP binding and local CBF in each region of the same brain. The ischemic flow thresholds for reduction of the cAMP binding in the hippocampus CA1 were 18, 34, and 49 ml 100 g-1 min-1 after 30-min, 2-h, and 6-h ischemia, respectively. These values were higher than those in other regions such as the hippocampus CA, and temporal cerebral cortex in each duration of ischemia. These findings indicate that (a) the ischemic flow threshold for perturbation of the cAMP system may be higher in the hippocampus CA1 than in other brain regions, suggesting that the hippocampus CA1 could be especially vulnerable to acute ischemic stress; and (b) the level of the aforementioned threshold may increase progressively during the time course of ischemia in particular regions such as the hippocampus CA1 and CA3, suggesting that the duration of ischemia exerts a definite influence on the viability of the ischemic neuronal cells in these regions.

Flow threshold for enhanced phorbol ester binding in the ischemic gerbil brain.

The correlation between regional phorbol ester binding and cerebral blood flow (CBF) was evaluated in the gerbil brain after 2-hour unilateral common carotid artery occlusion. [3H]phorbol 12,13-dibutyrate (PDBu) was used as a specific ligand for estimating the translocation of protein kinase C (PKC), and CBF was determined by the [14C]iodoantipyrine method. A quantitative autoradiographic method permitted concurrent measurement of these two parameters in the same brain. In the ischemia group of the animals, statistically significant, inverse correlations were noted between the CBF and PDBu binding in the hippocampus (CA1 and CA3 regions and dentate gyrus), the caudate-putamen and lateral nuclei of the thalamus. In these regions, the PDBu binding increased progressively as CBF fell below 35-40 ml/100 g/min. On the other hand, the PDBu binding in the cerebral cortices did not show any significant changes even when CBF was decreased to below 35 ml/100 g/min. The above data suggest that (1) the translocation of PKC to the cell membrane may be regionally specific in response to ischemia, and may remain in the regions particularly vulnerable to ischemia such as the hippocampus, caudate-putamen and lateral nuclei of the thalamus in the early ischemic phase; (2) the threshold of CBF below which PKC begins to translocate to the cell membrane in the above regions, may be 35-40 ml/100 g/min in 2-hour ischemia.

Three-dimensional analysis of human carotid atherosclerotic ulcer associated with recent thrombotic occlusion.

To clarify the mechanism of ulcer formation of atherosclerotic plaques in human carotid arteries, autopsy investigations were performed on eight patients who had died of cerebral infarction due to recent carotid thrombosis. Eleven control patients who had carotid atherosclerosis without thrombosis were also investigated. Histological changes of the arteries in serial sections were reconstructed three-dimensionally. Each artery with occlusive thrombosis was found to have an intimal ulcer at the head of the thrombus on the proximal slope near the base of the thickened atheromatous plaque at the carotid sinus. Most ulcers formed obliquely or longitudinally, were parallel to the vessel axis, had a fusiform shape, and measured 7 +/- 2 x 3 +/- 1 mm (mean +/- s.d.). The ulcers arose by marginal separation of the innermost layer from the underlying layer of the stratified intima. An underlying atheroma developed along the borders of these intimal layers reaching the subendothelium, with thinning of the intimal cap to less than 150 microns. The process of ulceration may be generated by vessel injury induced by hemodynamic forces, such as tensile forces and shear stress. The ulcer may extend along the fragile region where the wall may exhibit uneven compliance due to differences in the tissue structures of each intimal layer. Furthermore, macrophages may play a key role in ulcer formation.

Alteration of inositol 1,4,5-trisphosphate receptor after six-hour hemispheric ischemia in the gerbil brain.

In order to evaluate the influence of cerebral ischemia on the inositol 1,4,5-trisphosphate receptor, the alterations of inositol 1,4,5-trisphosphate receptor binding sites and local cerebral blood flow were examined 6 h after occlusion of the right common carotid artery in the gerbil brain. The autoradiographic method developed in our laboratory enabled us to measure both parameters within the same brain. Animals attaining ischemic scores of more than 5, as assessed 1 h after occlusion, were utilized. The local cerebral blood flow was measured 6 h after occlusion by the [14C]iodoantipyrine method. The inositol 1,4,5-trisphosphate binding sites were evaluated in vitro using [3H]inositol 1,4,5-trisphosphate as a specific ligand. The local cerebral blood flow fell below 15 ml/100 g per min in most of the cerebral regions on the occluded side. In contrast, a significant reduction in inositol 1,4,5-trisphosphate binding sites was noted only in the hippocampus CA1 on the occluded side. Inositol 1,4,5-trisphosphate binding tended to decrease when the values of local cerebral blood flow were below 20 ml/100 g per min in this region. On the other hand, the inositol 1,4,5-trisphosphate receptor immunoreactivity in the brain examined with a monoclonal antibody against inositol 1,4,5-trisphosphate receptor protein did not reveal any differences between the ischemia and sham groups on both sides, suggesting that the inositol 1,4,5-trisphosphate receptors may not undergo significant morphological degradation. These findings indicate that the suppression of inositol 1,4,5-trisphosphate binding in the hippocampus CA1 may be attributable to a regionally specific perturbation of the inositol 1,4,5-trisphosphate metabolism in this region.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced maximal binding capacity (Bmax) of second messenger ligand in the acute phase of cerebral ischemia--direct visualization by digital image analysis.

Autoradiographic visualization of the Bmax (maximal binding capacity) and Kd (dissociation constant) of [3H]phorbol 12,13-dibutyrate (PDBu) and [3H]forskolin (FK) was performed after 30-min unilateral carotid artery occlusion in the gerbil brain. These parameters and the local cerebral blood flow (CBF) were measured at the level of the caudate-putamen in the same brain using a digital image processing technique developed in our laboratory. The local CBF was measured at the end of the experiment. [3H]PDBu and [3H]FK were utilized as specific ligands to assess the activities of protein kinase C (PKC) and adenylate cyclase (AC), respectively. The local CBF on the occluded side was severely reduced and ranged from 0.2 to 9.0 ml/100 g/min, whereas the local CBF on the non-occluded side exhibited a moderate reduction except in the midline regions. The Bmax values of PDBu and FK were significantly increased not only on the occluded side but also on the non-occluded side in the ischemia group as compared to the corresponding values in the sham group. In contrast, the Kd value of each ligand remained unchanged in the ischemia group. These findings suggest that both the adenylate cyclase and protein kinase C systems may be significantly and diffusely activated in the initial stage of brain ischemia. Thus, severe hemispheric cerebral ischemia in the acute phase may induce severe perturbation of the second messenger systems in extensive bilateral regions.

Effect of barrier opening on brain edema in human brain tumors.

Blood-brain barrier (BBB) opening was carried out in 10 patients with cerebral lesions, and the MRI findings were evaluated following the barrier opening. An intra-arterial injection of 10% glycerol (4 ml/kg, 1 approximately 2 ml/s) was given as a hyperosmotic solution. T2-weighted MRI was undertaken using a TOSHIBA 22A at 30 minutes after BBB opening. Barrier-opening MRI was performed 10 times in 10 patients, including 5 cases of glioblastoma multiforme, 2 cases of astrocytoma, 1 case of malignant lymphoma, 1 case of cerebral contusion and 1 case of neurinoma. The high-intensity area (HIA) was compared with that in MRI without barrier opening. Three types of changes of HIA in MRI were observed after BBB opening as follows. Type 1: Expansion of the HIA was noted in 4 of 5 cases of glioblastoma multiforme, the 1 case of malignant lymphoma and the 1 case of cerebral contusion. Type 2: Almost no change was observed in the 1 case of neuronoma. Type 3: A decrease in HIA was noted in the 2 cases of astrocytoma and in 1 case of glioblastoma multiforme. The MRI following BBB opening evidently showed 3 types of changes according to the degree of BBB disruption. Glioblastoma multiforme or contusion with a severely disrupted BBB revealed an increase in HIA following barrier opening. Benign posterior fossa neurinoma showed no change in HIA after barrier opening. Moderate malignant tumors exhibited a decrease in HIA on barrier-opening MRI. It was concluded that malignant tumors have a severely damaged BBB, which is readily disrupted by osmotic barrier opening.

Sequential change of brain edema by semiquantitative measurement on MRI in patients with hypertensive intracerebral hemorrhage.

The progression of brain edema in seven patients with hypertensive intracerebral hemorrhage (ICH) was evaluated. Five were of putaminal and two were of thalamic hemorrhage. The hematoma volume in the patients was 4 approximately 40 ml (18.9 +/- 8.0 ml). Sequential MRI (SE: 2000/40) was performed at one, two and four weeks after onset. The edema volume (EV) was calculated as 1/2.(long diameter).(short diameter).(thickness) of the high intensity area (HIA) on MRI. In comparison with the EV at one week after onset, the EV at two weeks was increased and the EV at four weeks returned to the same level of that at one week (132.3 +/- 26.1%, 100 +/- 10.6%, respectively). In contrast, the consciousness level and motor weakness of the patients had already improved at two weeks after onset. Our results demonstrate that progression of brain edema after small or medium size ICH may not bring about a deterioration of the clinical course. Moreover, progression of brain edema to the cerebral cortex and ventricle as indicated by MRI suggested an absorption pathway for the edema fluid, and implying that brain edema following ICH could play a part in the healing process after ICH.

Morphometry of structural preservation of tunica media in aged and hypertensive human intracerebral arteries.

BACKGROUND AND PURPOSE: Medial smooth muscle cell necrosis has been reported as a lesion that may precede angionecrosis, which is a major cause of not only hypertensive brain hemorrhage but also lacunar infarct. We morphometrically studied a loss of smooth muscle cells in the media of cerebral arteries in relation to clinical risk factors. METHODS: The lateral striate, ie, perforating arteries and the medullary arteries in the subcortical white matter of the temporal lobe (100 to 400 microns in diameter) were histologically investigated in 121 autopsied brains. Medial area was measured quantitatively, and the number of nuclei of smooth muscle cells in the area was calculated in 1210 cross-sectional arteries of histological sections. The influence on the structural (ie, smooth muscle cell) preservation of the tunica media (ratio of number of smooth muscle cell nuclei to medial area [N-MA ratio]) of age, blood pressure, serum lipids, and presence of absence of extracerebral severe atherosclerosis was investigated. RESULTS: The N-MA ratio decreased slightly with age in both arteries. A reverse correlation between N-MA ratio and age was seen in groups both with and without hypertension. The mean N-MA ratio in the hypertensive group was significantly lower than that of the nonhypertensive group (P < .001) in all decades of life. The mean N-MA ratio of the perforating arteries was slightly lower than that of the medullary arteries in both groups. Severe atherosclerosis of the internal carotid arteries, even with hypertension, mitigated a decrease of the N-MA ratio, which was as slight as that in the nonhypertensive group. Serum cholesterol in this group was higher than in both the conventional hypertensive group (P < .005) and the nonhypertensive group (P < .001). CONCLUSIONS: Although both hypertension and age were significant risk factors for medial smooth muscle cell necrosis, hypertension was relatively more significant. Medial smooth muscle cells of the perforating arteries in the basal ganglia were more vulnerable than those of the medullary arteries. Cerebral small arteries in subjects with severe atherosclerosis of the carotid and major cerebral arteries (hypertension in eight of nine subjects) may have been protected from extensive loss of medial smooth muscles presumably because of both high serum cholesterol and decreased wall tensile stress associated with reduced blood perfusion due to severe atherosclerotic stenosis.