Recent experimental evidence showed that cerebral ischemia induces stress response in the brain. A number of specific genes are expressed in the brain following ischemia, such as early inducible genes including c-fos and zinc finger gene, heat shock proteins, and amyloid precursor protein. Neurotrophic factors such as nerve and fibroblast growth factors are also induced. A variety of harmful stresses, including ischemia, elicit a stereotyped stress response in order to repair the injury. Because the so-called stress proteins are ubiquitously seen in various stress responses and in Alzheimer disease, it may be possible to assume that the accumulation of such abnormal proteins in Alzheimer disease brains may occur secondary to some pathological stress which has not yet been identified.

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We examined platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid (AA), and platelet activating factor (PAF) in 74 patients suffering cerebral ischemia and taking oral antiplatelet agents (ticlopidine and/or aspirin) during mean period of 34 months. In 65 non-recurrent patients, platelet aggregation induced by all 3 agonists was suppressed after antiplatelet therapy (p<0.001). By contrast, in 9 recurrent patients, platelet aggregation induced by any agents did not significantly suppressed after the therapy. In the recurrent group of patients, incidence of atrial fibrillation (Af) (33%) was much higher than in the non-recurrent group of patients (4%) (p<0.05) despite platelet aggregation in Af patients was well suppressed compared to that in non-Af patients after antiplatelet therapy. Above results suggest that the recurrence in Af patients is hard to be prevented by antiplatelet therapy even when it is effective in the inhibition of platelet aggregation. This may reflect that the stroke recurrence in Af patients is attributable to fibrin-rich thrombi formed in cardiac chambers. In 68 non-Af patients, we examined the relationship between recurrence and platelet aggregation after antiplatelet therapy. The rate of recurrence (2.4%) in the patients whose platelet aggregation was suppressed in responce to 2 or 3 agonists is lower than that (18.5%) in the patients whose platelet aggregation was suppressed in responce to 1 or neither agonist (p<0.05). Therefore, inhibition of multiple pathways leading to platelet aggregation might be potentially valuable in preventing recurrent stroke among non-Af patients.

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We allocated 19 aged patients with acute non-cardioembolic stroke to two therapy groups. They were admitted within 24 hours from the first neurological symptoms. A cranial computed tomography revealed no hypodensity. Finally we excluded patients with atrial fibrillation, myocardial infarction, congestive heart failure, renal dysfunction, respirtory failure and disseminated intravascular coagulation. 10 patients underwent administration of low-molecular weight dextran until hematocrit was reduced to 33% during the first 3 days (hypervolemic hemodilution group) and 9 patients (standard group) recieved only glycerol. In the hemodilution group, all patients improved neurological scoring with a hematocrit reduction over the first 3 days. On the other hand, no improvement of scoring and hematocrit reduction occurred in the standard group. Thus, hypervolemic hemodilution therapy improves early neurologic outcome in acute non-cardioembolic stroke and it is important to rule out cardioembolic stroke and continue hypervolemic hemodilution only for 3 days.

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To clarify the pathophysiology of recurrent cerebral thrombosis, 22 patients with cerebral thrombosis who suffered a second attack under stable conditions more than 22 days after the initial stroke were studied by neuroradiological techniques. Hypertension, diabetes, and hypercholesterolemia was seen in 20, 8, and 12 out of the 22 patients, respectively. Neither antiplatelet therapy nor antihypertensive therapy with good control was carried out before recurrence in aproximately half of them. The patients were divided into three groups according to their symptoms. The co-existent group had symptoms that differed between the first and second attacks, the progressive group showed abrupt deterioration of their original symptoms, and the combined group had mixed symptoms. The majority of the 12 patients in the co-existent group had an initial hemiparesis followed by either contralateral hemiparesis or suprabulbar palsy. The interval until recurrence varied from 4 months to 9 years. As causative lesions in this group, CT/MRI findings indicated not only lacunae in both hemispheres, but also deep white-matter ischemia of the centrum semi-ovale. In two cases, supratentorial lesions were combined with infratentorial infarcts. In the 6 patients of the progressive group, hemiparesis or visual field defects deteriorated during a short interval of a few months. The recurrent interval was usually so short as a few months. Neuroimaging revealed not lacunae, but cortical infarction (superficial type due to thrombotic obstruction of middle or posterior cerebral artery branches) in the left hemisphere or deep white-matter ischemia (watershed infarction due to main trunk obstruction) in the right hemisphere. Two patients with cortical infarction had polycythemia. The 4 patients in the mixed group had deterioration of hemiparesis associated with aphasia. CT/MRI, SPECT and angiography indicated mainly deep white-matter ischemia caused by main trunk lesions in the left hemisphere. Regarding the pathophysiological aspects, the mixed type seemed to be equivalent to the progressive type except for the laterality of the lesion. The mechanism of recurrence could be hemodynamic changes, because the patients had uncontroled hypertension with fluctuating blood pressures.
In conclusion, recurrent lacunar thrombosis tended to produce infarcts at another site (co-existent symptoms), while cortical infarcts and watershed infarcts tended to expand with progressive or mixed symptoms. It is suggested that neuroradiological assessment of the initial stroke may help to predict the mode of recurrence to some extent, although the pathopysiology of cerebral thrombosis is complicated and varies case by case.

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We studied 33 patients with subarachnoid hemorrhage of unknown etiology despite from repeated angiography last 18 years. The incidence was 4.9% among the aneurysmal subarachnoid hemorrhage. Male predominance revealed (male : female=1 : 0.89) and mean age was 51.2 years which showed slightly younger than the patients with aneurysmal subarachnoid hemorrhage. Ten of 21 patients obtained CT examination showed perimesencephalic hemorrhage. In these patients, one patient showed normal pressure hydrocephalus, however, 2 out of 4 patients who had subarachnoid hemorrhage in not only basal cistern but also Sylvian cistern showed normal pressure hydrocephalus. 23 patients had good prognosis and returned previous activity. No patients showed re-bleeding. One patient died of hypertensive intracerebral hemorrhage, one died of malignancy and 3 died of repiratory failure or cardiac failure.
These results show that the subarachnoid hemorrhage especialy localized in peri-mesencephalic cistern is a distinct pathology from aneurysmal subarachnoid hemorrhage.

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The purpose of the present study was to compare the outcome of medical treatment with that of surgical treatment in patients with cerebellar hemorrhage. The subjects comprised 118 patients (77 males and 41 females; 64 ± 10 years of age (mean ± SD)) admitted to the Department of Neurology, Keio University Hospital and its 10 affiliated neurological institutes and hospital in the past 5 years (from 1984 to 1988). Every patient was diagnosed by brain CT scan within 24 hours after onset. Among the 118 patients with cerebellar hemorrhage, 87 were treated by conservative treatment and the remaining 31 patients were treated surgically. The surgical treatment consisted of evacuation of hematoma in 12 cases, evacuation of the hematoma with ventricular drainage in 13 cases, aspiration of the hematoma in 1 cases, and ventricular drainage in 5 case. The mean age of the surgical group (59 ± 13 years) was significantly (p<0.01) younger than that of the conservative group (65 ±9 years). The patients were classified on the basis of the neurological grading (NG) on admission and brain CT findings (maximal diameter of the hematoma, volume of the hematoma, ventricular rupture, and hydrocephalus). The outcome of the patients was evaluated by ADL on discharge. For the classification of the neurological grading and ADL, the criteria of the Japan Society for Research on Surgical Treatment for Stroke were employed.
The results obtained were as follows :
1) In mild or moderate cases with cerebellar hemorrhage (NG, 1, 2, 3; maximal diameter of the hematoma, 3 cm or less; volume of the hematoma, 10 ml or less; no ventricular rupture; no obstructive hydrocephalus), the overall prognosis was significantly better in the conservative group.
2) In severe cases (NG, 4, 5; maximal diameter of the hematoma, 3.1-5.0 cm; volume of the hematoma, 11 ml or more; ventricular rupture; obstructive hydrocephalus), the mortality rate was significantly higher in the conservative group. Some of the patients survived after surgical treatment in severe cases showed good functional prognosis.
It is suggested that surgical treatment for cerebellar hemorrhage should be considered in severe cases.

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We report a case of left thalamic hemorrhage presenting pure ataxia. A 71-year-old male was admitted because of the sudden onset of gait distrubance and right-sided ataxia on October 13, 1988. Neurological examination revealed slight truncal ataxia, right-sided cerbellar ataxia, and very mild dysarthria. Muscle strength of the extremities was normal. Plain CT scans revealed a small high density area in the left frontal region as well as the left thalamus. Pure cerebellar ataxia caused by thalamic hemorrhage is rare. In this case, ataxia may have been caused by hemorrhage localized in the lateral thalamus (VL) where the dentate-rubro-thalamic pathway terminated.
This case suggests that it is necessary to consider the possibility of thalamic hemorrhage even when the patient presents pure cerebellar ataxia.

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We reported a case of hypoglycemic hemiplegia (HH). A 28-year-old diabetic woman, who had been taken insulin therapy, since 13 year of age, experienced two episodes of transient left hemiparesis. On admission, deep tendon reflexes in lower extremities were decreased but other neurological deficits were not detected. Brain CT, MRI and cerebral angiography were negative. No hematological abnormalities nor cardioembolic sources were detected. When another left hemiparetic attack occurred after hospitalization, she was fully consciouss and the blood sugar level was 54 mg/dl. She took sugar orally, then her hemiparesis was gradually solved. We diagnosed as HH, and diminished the insulin dosage. Afterwards, no hemiparesis occurred. During hospitalization, when HbAlc was 6.3%, cerebral blood flow measured by 99mTc-HMPAO SPECT was decreased in the right basal ganglia to the internal capsule, while four months later, when HbAlc was 7.7%, cerebral blood flow in that area was improved.
HH had been regarded as a rare manifestation, but it may have been misdiagnosed as cerebrovascular disease.HH should be considered as a possible cause when a diabetic patient presents transient hemiparesis.

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A number of conditions have been linked to the etiology of cerebral venous sinus thrombosis (CVST). Adding to this information, we report an unusual case of CVST occurring after excision of a hydatidiform mole.
Five days after undergoing evacuation of a hydatidiform mole, a 47-year-old female developed headache, monoparesis of the right upper extremity, restriction of voluntary eye-movement, conscious disturbance and convulsion. Laboratory findings showed an increase in platelet activation, intrinsic coagulation factors, and fibrinolysis. There was a marked change in human chroionic gonadotropin from 200, 000 IU/L before the evacuation to 20, 000 IU/L after the procedure. MRI revealed thrombosis in the anterior portion of the superior sagittal and left transverese sinuses, and showed edematous changes in bilateral frontal convexities. The immediate use of an anticoagulant (heparin), a thrombolytic agent (urokinase) and a hyperosmotic solution (glycerol) improved her neurologic signs and symptoms, along with her abnormally hyperactive hemostatic system.
It is well known that CVST may occur during pregnancy, after delivery, or during medication with oral contraceptives. However, there has been no report of CVST associated with hydatidiform mole. This case suggests that the removal of a hydatidiform mole, often considered analogous to pregnancy, may cause the onset of CVST.

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The temporal changes of a thrombotic aneurysm of the posterior cerebral artery by MR angiography (MRA) in a 58-year-old man were reported. On October 4, 1990, the patient was admitted with chief complaints of headache and vertigo. Plain brain CT scanning revealed a round lesion which appeared as an area of slightly high absorption in the right cisterna ambiens. On brain T1-weighted MRI, almost the entire lesion showed homogeneous intensity, but some portions of the lesion showed a high signal intensity. The lesion showed a low signal intensity on T2-weighted MRI. A portion of the lesion was slightly enhanced in contrast MRI studies using GD-DTPA. Angiography revealed obstruction of the posterior cerebral artery distal to the origin of the posterolateral choroidal artery. On rephase MRA, the lesion was seen to be adjacent to the vessel at the site of obstruction seen in angiography, however this finding was not confirmed by subtraction MRA. This lesion was diagnosed as a thrombotic aneurysm at the bifurcation of the right posterior cerebral artery and the posterolateral choroidal artery. On rephase MRA performed 2 months later, the image of the thrombotic cerebral aneurysm was less clear. On rephase MRA performed 4 months later, it was not visualized at all. It appears likely that the temporal changes in this case seen using rephase MRA were due to the conversion of methemoglobin to hemosiderin, which resulted in blurring of the image.

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A 61-year-old hypertensive man developed conjugate upgaze palsy and the right monocular downgaze paresis with slight lateral and downward deviation. In the horizontal eye movement, he also had the right monocular paresis to the leftward gaze. Both near reflex and doll's eye phenomenon were positive, whereas convergence was disturbed. Brain CT and MRI revealed multiple infarctions limited to the right internal thalamo-mesencephalic junction, the right oculomotor nucleus and the bilateral cerebellar hemisphere.
It is suggested that the abnormal eye movement in this case was caused by the combined lesions in the fibers of the posterior commissure, the descending tracts from the rostral interstitial nucleus of MLF (riMLF) to the ipsilateral oculomotor nuclei, and the oculomotor nucleus itself, resulting in the so-called vertical one-and-a-half syndrome with the ipsilateral oculomotor paresis.

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Three cases of hemiballism-hemichorea accompanied by motor weakness in the same limb (s) induced by isolated subcortical infarction were presented and the symptomatic and pathophysiological aspects of dyskinesia associated with focal brain damage were discussed.
Involuntary limb movements observed in these patients consisted of regular, rhythmic flinging movements of ballistic type more prominent in the proximal portions of limbs and also of less regular and more abrupt choreic movements in the distal portions all on one side of the body, namely hemiballism-hemichorea.
Post-apoplectic hemiballism is characterized by a sudden onset, violent nature, long duration and poor prognosis and this dyskinesia may be caused by a destructive lesion located at the subthalamic nucleus as well as other sites as the caudate head, putamen and thalamus. Review of the literature disclosed that cortical or subcortical lesions are among rare causes of hemiballism.
Limb shaking, on the other hand, is considered to be transient involuntary limb movements of a hemiballismhemichorea type manifested as a clinical sign of carotid transient ischemic attacks.
The commonly shared location of the lesions in three cases on CT or MRI is the subcortical white matter underneath the precentral gyrus and the premotor cortex contralateral to dyskinesia. None of these cases were accompanied with lesions in the vicinity of the subthalamic nucleus or basal ganglia.
Voluntarily executed movements are presumed to be checked by the cortico-striato-pallido-subthalamo-pallidothalamo-cortical negative feedback loop. Subthalamic nucleus also receives a direct excitatory neural connection from the precentral gyrus, which may also take part in the inhibitory neural feedback loop mentioned above. The presence of a subcortical damage lying so as to interfere with the neural connections from cortex to striatum or subthalamic nucleus may lead to functional suppression of the subthalamic nucleus and subsequently of the pars interna of the globus pallidus, which in turn “disinhibits” thalamus and cortex, resulting in appearance of involuntary dyskinesia.
Limb paresis caused by a cortical and/or subcortical lesion is known to abolish hemiballism induced by a subthalamic damage in cats. Hemibalism-hemichorea induced by subcortical infarction may have a higher possibility of accompanying motor paresis of the same limbs, which may bring about relatively fair prognosis as in two of the three cases.

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A 48-year-old man was admitted to our hospital because of disturbed consciousness and generalized convulsive seizures. CT scan showed an intracerebral hematoma in the subcortex of the left hemisphere. After admission, he experienced recurrent subcortical hemorrhage in the ipsilateral hemisphere following headache and nausea in acute stage. Cerebral angiography revealed nonfilling of the superior sagittal sinus (SSS). The diagnosis was subcortical hemorrhage due to thrombois of the SSS. The cortical veins in the left hemisphere were less developed than those in the right, which might have been the cause of the markedly impaired venous return.
These results indicated that it would be necessary to monitor the patients with this disease of acute stage carefully since hemorrhage might reccur in the region in which collateral circulation was insufficient.

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A 80-year-old man was admitted to our hospital 15 minutes after acutely developed consciousness disturbance, hemiplegia, unilateral spatial neglect, and hemisensory disturbance on the left, and conjugate deviation to the right. Thirty minutes later, however he showed rapid recovery of the hemispheric symptoms, and only mild hemisensory disturbance on the left remained 4 hours after the onset. Acute cardioembolic stroke was diagnosed by abrupt onset, atrial fibrillation, and marked hypercoagulable state. Diastolic blood flow of the right common carotid artery on the duplex Doppler ultrasonography was absent on admission, but reappearred 4 hours after the onset. Rapid and significant improvement of symptoms and douplex Doppler ultrasonographic findings suggested early reopening of the occluded right internal carotid artery, which corroborated the clinical entity of “Spectacular Shrinking Deficit” in acute brain embolism, described by JP Mohr (1986).

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A 61-year-old male was admitted to our hospital on July 14, 1989, with left hemiparesis and speech disturbance of acute onset. Initial CT scan revealed a tumor in the right deep temporal region. The next day his symptoms worsened; repeat CT scan 29 hours after onset demonstrated a new lesion characteristic of cerebral infarction in the right lenticular nucleus and corona radiata, territory of the lateral lenticulostriate arteries arising from the proximal portion of the middle cerebral artery. This ischemic lesion was located immediately superoposterior to the tumor; both lesions were clearly distinguishable on MR scan. Cerebral angiography revealed streched and medally i displaced perforating arteries, but showed no sclerotic changes in the intra- and extracranial major cerebral arteries. During surgery, the right proximal middle cerebral artery was found to be surrounded and compressed by the tumor. Histologically, the resected tumor was diagnosed as malignant astrocytoma. The authors speculate that the ischemic stroke was caused by obstruction of the perforating arteries of the proximal middle cerebral artery, most probably due to mechanical compression by the tumor.

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We herein described two patients with a small medullary hematoma in whom diagnoses were made not by CT but only by MRI. These patients developed mild neurologic symptoms suggestive of lower brain stem impairment. Cerebral angiography and CT scans did not reveal any abnormal findings. MRI, however, disclosed hemorrhagic lesions in the medulla oblongata in both patients.
It is generally held that cerebrovascular disorders in the medulla oblongata are mainly caused by thromboembolism. Based on our present observations and literature review, we assume that mild hemorrhages in the medulla oblongata might have been considered as infarcts because of the limited resolution of CT scans in this region.

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Central motor conduction disturbances were investigated using magnetic stimulation in patients with cerebrovascular disease (CVD). The study participants were 18 CVD patients with a supratentorial lesion and 26 healthy controls. Magnetic stimulation was performed on the skull, the neck and the lumbar with a MAGSTIM Model 200. Muscle action potentials of the thenar and the extensor digitorum brevis were recorded by a Nicolet Compact 4.
The results were as follows : 1) Central motor conduction times from the head to the neck (CMCT₁) and to the lumbar (CMCT₂) were longer on the affected side than on the healthy side and in the controls. 2) Conduction velocity from the head to the lumbar (CMCV) was significantly slower on the affected side of the patients than on the healthy side and in the controls.
In conclusion, we were able to electrophysiologically clarify the disturbances of the central motor conduction pathway.

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The purpose of this study is to investigate temporal changes of immunoreactivities of cytoskeletal proteins including 68-kD and 200-kD neurofilaments (NFs), tubulin, microtubule-associated protein (MAP) 2, glial fibrillary acidic protein (GFAP) and vimentin, in neurons and astrocytes following focal cerebral ischemia in rats subjected to middle cerebral artery occlusion with or without reperfusion. Remote areas which had not been primarily involved in ischemia, including ipsilateral ventral posterior nucleus and medial geniculate body of the thalamus, and substantia nigra pars reticulata were also studied.
MAP2 immunoreactivity in dendrites was diminished or lost after 30 min ischemia in the striatum where ischemic changes of neurons could not be detected by H & E staining and immunoreactivities for tubulin and 68-kD NF remained to be unchanged. MAP2 in dendrites may be more susceptible to ischemic degradation than tubulin and 68-kD NF. As the focal ischemia progressed, areas showing loss of immunoreactivities for cytoskeletal proteins extended to cerebral cortex. However, immunohistochemical reactions for tubulin, 68-kD and 200-kD NFs in myelinated axons decreased more gradually in comparison with those in other neuronal stractures in the infarct. Cytoskeletal proteins distributed in myelinated axons may be more resistant to ischemic degradation.
In remote areas, neurons degenerated from 7 days after reperfusion following 2 hour focal ischemia, when immunoreactivities for MAP2, tubulin and 68-kD NF in neurons and for 200-kD NF in axons began to decrease. Some neurons in remote areas showed increased immunoreactivity for tubulin, which was limited from 5 to 14 days after reperfusion.
200-kD NF-positive cell bodies and dendrites were observed in neurons around the infarct from 2 days and in remote areas from 7 days after reperfusion, which may due to the disturbance of axonal transport.
Immunoreactivities for GFAP and vimentin of astrocytes in ischemic area decreased more gradually than those of tubulin and 68 kD NF in neuronal cell bodies and dendrites. Cytoskeletal proteins of reactive astrocytes around the infarct differed from those in remote areas. Increased GFAP-positive reactive astrocytes with hypertrophy were distributed widely around the infarct from 1 day following ischemia. Vimentin, tubulin and MAP2 became stainable only in astrocytes located immediately near the edge of the infarct, and were especially remarkable 2 to 7 days after reperfusion. In remote areas, reactive astrocytes showed no immunoreactivities for vimentin, tubulin and MAP2 at any time during the experiment. Intermediate filaments and microtubules expressed in reactive astrocytes near the infarct may be necessary for maintaining hypertrophied cell body and processes during the repair of the infarct.

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