Distribution of brain oedema in the contralateral hemisphere after cerebral infarction: repeated MRI measurement in the rat.

The appearance of local cerebral dysfunction at remote regions from the focus in the acute stage of stroke (diaschisis) is well known, but its mechanism has not been established. We have analysed serial MR images of the infarcted brain of rats to evaluate the distribution of oedema. Forty-seven Sprague-Dawley rats were anaesthetized with halothane, and the right middle cerebral artery (MCA) was permanently occluded via the intraluminal approach using a nylon 2-0 suture. At 3, 6, 9 and 24 hours after the occlusion, coronal T(2)-weighted MR images were taken and the signal intensity (SI) was computed at each region of the brain. After occlusion of the right MCA, SI increased diachronically up to 24 hours on the occluded side of the cortex (52.9+/-3.2 to 104.8+/-22.4) and striatum, which are within the perfusion territory of the MCA. SI increment was also observed at the hippocampus, alveus hippocampi and pyriform lobe, which are not within the territory of the MCA, and at some regions of the contralateral side (52.5+/-4.8 to 69.4+/-14.8 at the cortex). These changes were prominent in ischaemia-vulnerable portions, mild in the cortex, and minimal in the striatum. This contralateral side SI increment indicates remote oedema, which corresponds to diaschisis. We suggest that the mechanism of this remote contralateral oedema is the movement of extravasated protein from the lesion.

Modern Japanese medical history and the European influence.

Before the first European visited Japan in 1549, traditional Chinese medicine was mainly employed in Japan. Francisco de Xavier, a missionary of the Society of Jesus, tried to promote the introduction of Christianity by providing a medical service for Japanese citizens. However, Japan implemented a national isolation policy in 1639 and cut off diplomatic relations with the rest of the world, except Holland and China. For over 200 years, until the American admiral Matthew Perry forced Japan to open its doors in 1853, Japan learned about western medicine only from doctors of the Dutch merchants' office or from Dutch medical books. After 1853, Western medicine was rapidly introduced into Japan, and great achievements by Japanese medical doctors soon followed, such as the serum therapy for tetanus, the discovery of the plague and dysentery bacilli, the invention of Salvarsan for the treatment of syphilis, and the demonstration of the neurosyphilis spirochete.

[A case of codon 232 mutation-induced Creutzfeldt-Jakob disease visualized by the MRI-FLAIR images with atypical clinical symptoms].

A 50-year-old man was admitted to our hospital because of disorientation and nocturnal restlessness. The patient presented chronically progressive dementia. No myoclonus or periodic synchronous discharge (PSD) was found over time, with abnormal evidence in MRI-FLAIR (fluid-attenuated inversion recovery) images alone. Brain biopsy and prion protein gene analysis led to the final diagnosis of Creutzfeldt-Jakob disease (CJD) induced by the point mutation at codon 232 (Met to Arg). To date the cases of M232R mutation-induced CJD have been reported to present clinical symptoms and pathological evidences similar to sporadic CJD cases, and differential diagnosis between the types has been believed to be difficult. Our case suggests that some types of CJD induced by point mutation at codon 232 cannot be easily inferred from clinical findings.

Experimental models and treatment trials for cerebral infarction.

Recent progress in both experimental and clinical studies of cerebral infarction is outlined, and research on delayed neuronal death and ischemic penumbra is described. Development of animal models to study clinical pathophysiology is reviewed, and our focal cerebral ischemia model which has been used for many years is introduced. With elucidation of the pathophysiology of cerebral ischemia, various pharmaceutical agents have appeared recently in the clinical setting and our experimental trials on the treatment of cerebral ischemia are also introduced. From the clinical aspect, practical methods of treatment including antiplatelet therapy are explained. Cerebrovascular dementia and its prevention are also described.

How to use cerebral vasodilators and metabolic activators.

Cerebral vasodilators and metabolic activators (enhancers) for the treatment of cerebrovascular disorders (CVD) have been categorized and introduced into clinical practice according to their pharmacological actions and clinical indications. The main therapeutic goal of these drugs is to relieve residual subjective symptoms and neuropsychological dysfunction, which reduce the quality of life of patients in the chronic stage of stroke. Selection of the most suitable drug for the individual symptoms of each patient is an important therapeutic principle.

Rapid changes in pial arterial diameter and cerebral blood flow caused by ipsilateral carotid artery occlusion in rats.

We investigated rapid changes in pial arterial diameter and in cerebral blood flow (CBF) caused by transient ipsilateral common carotid artery occlusion (CCA-O) in anesthetized rats in order to elucidate how the cerebral circulation reacts to acute stem artery occlusion. In separate groups of rats, pial arterial diameter was recorded through a closed cranial window and CBF was recorded by laser-Doppler flowmetry. CCA-O was performed for 5 minutes under normotension and normocapnia (control) and under graded hypotension, hypercapnia and hypocapnia. In the control condition, pial arterial diameter increased rapidly, triggered by CCA-O. It took 12 +/- 3 s to reach the maximum of 204 +/- 42% of the value before CCA-O, and 60 +/- 24 s to become stable at 131 +/- 11%. CBF decreased rapidly to 66 +/- 11%, then increased reactively to 135 +/- 9%, and again decreased to 91 +/- 3%. The reactive increase in CBF caused by CCA-O decreased in parallel with the degree of hypotension, and also became barely detectable under hypercapnia. Our data suggest that active vascular dilation in the territory of the occluded artery is important for inducing collateral circulation.

Exclusion of the expansion of CAG/CTG repeats at thirteen loci on chromosome 12 as a candidate genetic mutation in scapuloperoneal spinal muscular atrophy with anticipation.

Scapuloperoneal spinal muscular atrophy (SPSMA) is a neuromuscular disorder characterized by weakness in the distribution of shoulder girdle and peroneal muscles. We have previously described a large New England kindred with autosomal dominant SPSMA and have subsequently linked this family trait to 12q24.1-q24.31. In this family, disease expression becomes more severe and progressive in successive generations, suggesting genetic anticipation. Accordingly, we have investigated the thirteen known CAG/CTG repeat loci on chromosome 12 that could be tested by using the polymerase chain reaction as candidate genetic mutations in SPSMA. None of these loci is expanded.

Superacute phase blood pressure elevation may relate to massive hematoma in hypertensive putaminal hemorrhage.

A restrospective clinical investigation has been performed to elucidate the relationship between hematoma size in putaminal hemorrhage and blood pressure (BP) changes during the immediate post-hemorrhagic phase in the emergency room (ER). Thirty-seven adult patients brought to the emergency department by ambulance within 6 hours after onset of symptoms with a confirmed diagnosis of acute putaminal hemorrhage on CT have been involved. Two BP measurements during the superacute phase in the ER have been studied: immediately after arrival at the ER (BP-I), and immediately prior to CT examination (BP-II). Patients have been divided into 6 categories: 1) those whose BP decreased with treatment (D+), 2) those whose BP decreased without treatment (D-), 3) those whose BP increased in spite of treatment (I+), 4) those whose BP increased without treatment (I-), 5) those whose BP remained unchanged in spite of treatment (U+), and 6) those whose BP remained unchanged without treatment (U-). Hematoma size has been compared among 5 categories (D+, D-, I-, U+, U-) using factorial ANOVA (analysis of variance). The hematoma sizes have been found to be (D+) 54 +/- 44 ml, (D-) 22 +/- 25 ml, (I-) 102 +/- 58 ml, (U+) 11 +/- 5 ml, (U-) 21 +/- 9 ml (mean +/- S.D.), respectively. (I-) has been significantly larger than any of the other categories (p < 0.001 - 0.05). Additional ANOVA has shown that BP-II in category (I-) was significantly higher than that of the other categories. Patients with putaminal hemorrhage whose BP was elevating during the superacute phase in the ER were shown to have massive hematomas.

Linkage of scapuloperoneal spinal muscular atrophy to chromosome 12q24.1-q24.31.

Scapuloperoneal (SP) syndromes are heterogeneous neuromuscular disorders which are characterized by weakness in the distribution of shoulder girdle and peroneal muscles. SP syndromes can resemble facioscapulohumeral muscular dystrophy (FSH) due to scapular weakness or Charcot-Marie-Tooth disease (CMT) due to atrophy of peroneal muscles. Both neurogenic and myopathic SP syndromes have been described. Locus for the myopathic form of SP syndrome (scapuloperoneal muscular dystrophy, SPMD) has recently been assigned to chromosome 12q. We previously described a large New England kindred exhibiting an autosomal dominant neurogenic SP syndrome (scapuloperoneal spinal muscular atrophy, SPSMA). Disease expression was more severe and progressive in successive generations, which suggested genetic anticipation. We performed genetic linkage analysis of this family with microsatellite markers and excluded the loci for FSH, CMT, SPMD and SMA (spinal muscular atrophy) in our family. Linkage in our SPSMA family (lod score > 3) was established to seven microsatellite markers that map to chromosome 12q24.1-q24.31. The highest lod score with two-point linkage analysis was 6.67 (theta = 0.00) with marker D12S353. Multipoint analysis gave maximum lod scores of 7.38 between D12S354 and D12S79, and also 7.38 between D12S369 and NOS1 (neuronal nitric oxide synthase). The gene for SPSMA lies within the 19 cM interval between D12S338 and D12S366. This report establishes a locus for the neurogenic form of SP syndrome approximately 20 cM telomeric to the one described for the myopathic form of SP syndrome.

[A case of posttraumatic spinal pseudomeningocele which caused spinal cord compression 20 years after injury].

We reported an extremely rare case of posttraumatic spinal pseudomeningocele which caused spinal cord compression 20 years after getting injury, and demonstrated that sequelae of an injury may occur many years after the original wound. A 39-year-old man, who got left cervical root avulsion due to a traffic accident when he was 17 years old, began to complain of progressive muscle atrophy and weakness of left lower extremity 1 year ago. Myelography demonstrated pseudomeningocele at left C6-C8 level, and MRI and CT myelography revealed that the pseudomeningocele extends through the intervertebral foramen and compresses the spinal cord to the right side in the spinal canal. Bilateral functional compression of spinal cord dorsal and lateral column was also verified with SEP and MEP electrophysiologically.

Effect of sympathetic stimulation on cerebral circulation.

The role of sympathetic regulation in cerebral circulation was studied in the cat by continuous measurement of cerebral tissue oxygen tension (BrPO2), carbon dioxide tension (BrPCO2), pH(BrpH) and blood pressure. The ipsilateral superior cervical ganglion was electrically stimulated for 3 min. A slight decrease in BrPO2 and a slight but significant increase in BrPCO2 were observed during sympathetic stimulation. These changes suggested that sympathetic stimulation slightly decreased cerebral blood flow. The present results do not rule out a significant role for sympathetic regulation of cerebral circulation. Sympathetic constriction of the extraparenchymal vessels might be compensated for by secondary dilation of the intraparenchymal vessels elicited by a chemical control (escape phenomenon).

Distribution and origins of cerebrovascular NADPH-diaphorase-containing nerve fibers in the rat.

Neuronal NADPH-diaphorase has been proved to be nitric oxide synthase itself. In this study, we investigated distribution and origins of NADPH-diaphorase-containing nerve fibers in the cerebral vessels in the rat. Adult male Sprague-Dawley rats were divided into 4 groups. Nasociliary nerves were transected bilaterally in group 1. In group 2, intracranial branches of the sphenopalatine ganglion were transected bilaterally. In group 3, both of these structures were transected. The remaining animals were served as control (group 4). Two weeks after the above procedures, they were perfused with paraformaldehyde and glutaraldehyde. The pial arteries and superior cervical, trigeminal, internal carotid, otic and sphenopalatine ganglia were dissected. All specimens were processed for NADPH-diaphorase histochemistry. Numerous NADPH-diaphorase-containing nerve fibers with varicosities forming plexuses were observed in the circle of Willis and its branches. Relatively thick nerve bundles were noted in the anterior half of the circle of Willis. They are most abundant in the internal ethmoidal artery. Approximately 5% of such fibers in anterior half of the circle of Willis disappeared in group 1, 90% in group 2, and no fibers were seen to remain in group 3. NADPH-diaphorase reaction was positive in the neurons of sphenopalatine, otic trigeminal and internal carotid ganglia. Among these ganglia, the reaction was prominent in sphenopalatine, otic and internal carotid ganglia. In summary: (1) NADPH-diaphorase-containing nerve fibers distribute to the circle of Willis and its branches.(ABSTRACT TRUNCATED AT 250 WORDS)

A MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) mtDNA mutation that induces subacute dementia which mimicks Creutzfeldt-Jakob disease.

A 50-year-old woman with subacute dementia and brain atrophy on CT showed periodic synchronous discharge (PSD) on electroencephalogram (EEG) and myoclonus. She was initially suspected of suffering from Creutzfeldt-Jakob disease (CJD), but dramatically recovered over 5 months. Based on further investigations, the final diagnosis was mitochondrial encephalomyopathy with an A-to-G substitution at nucleotide position 3243 in mitochondrial DNA (mtDNA), commonly seen in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). This case suggests that patients suspected of suffering from CJD should be evaluated for mitochondrial encephalomyopathy.

Cerebral ischemia-induced amplification phenomenon of somatosensory evoked potentials in cats.

We elucidate the amplification phenomenon of median nerve somatosensory evoked potentials (SEPs) induced in cats by cerebral ischemia and also analyse the relationship between such amplification and cerebral blood flow (CBF). Transient focal cerebral ischemia was carried out by inducing only middle cerebral artery occlusion or jointly with bilateral common carotid artery occlusion. Various SEP alteration patterns were observed with CBF changes; with our overall results suggesting for the first time that the SEP amplification phenomenon occurs only under relatively mild cerebral ischemia.

Mechanisms of CBF augmentation during hypoxia in cats: probable participation of prostacyclin, nitric oxide and adenosine.

To elucidate the mechanisms of CBF augmentation during hypoxemic hypoxia, we applied continuous monitoring of CBF and metabolism to examine the participation of prostacyclin, nitric oxide (NO), and/or adenosine in these mechanisms. Cats (n = 32) were anesthetized and ventilated artificially. Cerebrovascular reactivity to hypoxia was assessed by changes in CBF, brain tissue oxygen and carbon dioxide tensions, and mean arterial blood pressure (delta CBF, delta BrPO2, delta BrPCO2, and delta MABP) during a 3-min inhalation of 10% O2 + 90% N2 before and after the intracarotid administration of (1) indomethacin (1 mg/kg, a cyclooxygenase inhibitor, n = 11), (2) L-NG-monomethyl-arginine (LNMMA, 1 mumol/kg/min, an inhibitor of nitric oxide synthesis, n = 11), and (3) caffeine (20 mg/kg, an adenosine antagonist, n = 10). BrPO2 decreased significantly in all groups during the produced hypoxemic hypoxia. CBF significantly increased in this state before the administration of indomethacin, LNMMA, or caffeine, whereas it contrastively did not significantly increase after the administration of indomethacin or caffeine. In addition, CBF significantly decreased under hypoxia during the administration of LNMMA. Taken together, these results suggest that prostacyclin (PGI2), nitric oxide (NO), and adenosine may jointly participate in CBF augmentation during hypoxia.

Effect of sympathetic nervous system stimulation on cerebrovascular CO2 responsiveness.

Cerebrovascular CO2 responsiveness, following noradrenaline (NA) infusion, was studied in the cat by continuous measurement of cerebral tissue oxygen tension (BrPO2), carbon dioxide tension (BrPCO2), pH (BrpH), and blood pressure (BP). Intravenous infusion of NA (1 microgram/kg/min) was done to stimulate the adrenergic nervous system. Inhalation of 5% CO2+air was performed for 3 minutes before, during, and after NA infusion. Cerebrovascular CO2 responsiveness was estimated from changes in BrPO2, BrPCO2, and BrpH. CO2 inhalation increased BrPO2, BrPCO2, and BP, but decreased BrpH, in the respective 3 stages. delta BrPO2 decreased significantly during NA infusion, but recovered after cessation of NA. NA infusion caused a decrease in CO2 responsiveness. This suggests that sympathetic hyperactivity can modify cerebrovascular CO2 responsiveness.