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Chronic electrical stimulation of the thalamic unspecific activating system in a patient with coma due to midbrain and upper brain stem infarction.

Chronic intermittent bipolar electrical stimulation of the left nucleus reticulatus polaris thalami was performed in a patient in a state of subcoma due to ischaemic infarction of wide medial parts of the midbrain, mainly the tegmentum, and the right-sided mediobasal parts of the forebrain. Stimulation immediately resulted in autonomic reactions and behavioural arousal reactions during the periods of stimulation. Longterm effect consisted of a rise in the level of clinical responsiveness for a period of seven weeks. A preexistent severe pneumonia disappeared completely after one week of stimulation and returned after seven weeks. The results are discussed on the basis of the pathoanatomical findings and of the physiological functions of the damaged as well as of the stimulated areas.

Aged↗

Acute administration of Ginkgo biloba extract (EGb 761) affords neuroprotection against permanent and transient focal cerebral ischemia in Sprague-Dawley rats.

We examined the neuroprotective action of a standardized extract of Ginkgo biloba leaves (EGb 761) in permanent and transient middle cerebral artery (MCA) occlusion models in Sprague-Dawley rats. Forty-four animals were given either EGb 761 (50-200 mg/kg) or vehicle intraperitoneally, 1 hr before permanent MCA occlusion, to evaluate the dose-response effects. An additional 58 animals received EGb 761 (200 mg/kg) or vehicle, 0.5- 4 hr after permanent MCA occlusion, for establishing the therapeutic window. Delayed treatment was also employed in 110 animals treated with either EGb 761 (100-200 mg/kg) or vehicle at 2-3 hr following transient focal cerebral ischemia induced by MCA occlusion for 2 hr. Neurobehavioral scores were determined 22-24 hr after permanent MCA occlusion and either 3 or 7 days after transient MCA occlusion, and brain infarction volumes were measured upon sacrifice. Local cortical blood flow (LCBF) was serially measured in a subset of animals receiving EGb 761 (100-200 mg/kg) or vehicle, 0.5 hr and 2 hr after permanent and transient MCA occlusion, respectively. Relative to vehicle-treated controls, rats pretreated with EGb761 (100 and 200 mg/kg) had significantly reduced infarct volumes, by 36% and 49%, respectively, and improved sensory behavior (P < 0.05). Delayed treatment with EGb 761 also significantly reduced brain infarction, by 20-29% and 31%, when given up to 2 and 3 hr following transient and permanent MCA occlusion, respectively, whereas improved neurobehavioral scores were noted up to 2 hr after the onset of MCA occlusion (P < 0.05). LCBF was significantly improved in the ipsilateral cortex following the EGb 761 treatment, whereas a higher dose showed a more sustained effect. In conclusion, EGb 761 protected against transient and permanent focal cerebral ischemia and was effective after a prolonged reperfusion period even when therapy is delayed up to 2 hr. This neuroprotection may be at least partially attributed to the beneficial effects of selectively improved LCBF in the area at risk of infarction.

Animals↗

Homozygous MTHFR C677T gene mutation and recurrent stroke in an infant.

The role of homozygosity for the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene as an independent risk factor for primary and recurrent stroke has been questioned, although recent data appear to be supportive. However, the association of homozygous C677T MTHFR mutation with silent brain infarctions in infancy has not been reported. The authors describe an 11-month-old male who had suffered a silent brain infarction followed by a symptomatic arterial stroke. The evaluation revealed mildly elevated homocysteine levels secondary to homozygous C677T alleles for MTHFR and iron deficiency anemia. An extensive evaluation for other causes of infarction was negative. We suggest that the mother's homozygous MTHFR status played a role in the early onset of stroke and that iron deficiency anemia may have contributed to the recurrence. The patient was treated with anticoagulation therapy, folic acid, and iron supplementation and has not had a recurrent event during 3 years of follow-up. This case provides further evidence that homozygous MTHFR mutation is a predisposing factor for early and recurrent pediatric stroke, including silent infarcts, especially in the presence of other risk factors.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

Clinical features of leuko-araiosis.

OBJECTIVE: To study the clinical features of leuko-araiosis. METHODS: Age matched groups of patients with a CT finding of pure leukoaraiosis (n = 26) and a control group with a normal CT finding (n = 26) were formed (mean ages 78.6 (SD 3.3) v 76.5 (SD 4.6) years; NS). RESULTS: Dementia, vascular dementia, central brain atrophy on CT, disability in activities of daily living and instrumental activities of daily living, urinary incontinence, gait disorder (assistance needed), personality change, and night time confusion were found to be more commonly present in leuko-araiosis positive patients than in controls, whereas focal neurological symptoms and signs were not associated with leuko-araiosis. The occurrences of heart failure and systolic hypotension-but not hypertension-were higher in the leuko-araiosis positive group than in the controls. Leuko-araiosis was also found to be related to a less sudden onset of symptoms and a lower Hachinski score than true brain infarction(s). CONCLUSIONS: Leuko-araiosis on CT in these elderly patients seems to be a vascular disorder aetiologically different from brain infarction, with clinical manifestations of subtle onset and general disabling nature and no prominent focal neurological signs or symptoms.

Activities of Daily Living↗

Immediate anticoagulation of embolic stroke: a randomized trial. Cerebral Embolism Study Group.

A randomized trial of immediate versus delayed anticoagulation of patients with cardiogenic embolic brain infarction was carried out in a multi-centered study. Patients who were within 48 hours of onset of deficit and who had no evidence of hemorrhage on computed tomography (CT) were randomized to receive either immediate heparinization or no anticoagulants for the initial 14 days following stroke. There were 63 patients with embolic stroke identified during the study period. Eighteen patients were not randomized because of specific exclusion criteria or delayed identification more than 48 hours after stroke. Of 45 patients who were randomized, 44 patients (98%) completed the initial week of the protocol: 24 were immediately heparinized at an average of 32 hours after stroke, 21 received no immediate anticoagulation. Two patients developed delayed hemorrhagic infarction and two patients experienced early recurrent embolism, all among the nonanticoagulated group. Of all patients with embolic stroke who were not receiving coumadin at onset of stroke, only two of 56 (4%) had hemorrhagic infarction on initial CT. Follow-up CT in 40 of these patients showed late developing hemorrhagic infarction in two additional patients (5%). All four hemorrhagic infarctions occurred in 18 non-anticoagulated patients with large infarcts. There were no major complications associated with immediate heparinization of 24 unselected patients with all sizes of embolic infarction. A trend toward reduction of early recurrent embolism was apparent. These data support immediate anticoagulation of nonhypertensive patients with embolic brain infarction who have no evidence of hemorrhage on CT performed 24-48 hours after stroke.

Adult↗

Homozygous protein C deficiency: early treatment with warfarin.

We present a case of homozygous protein C deficiency with neonatal purpura fulminans and disseminated intravascular coagulopathy (DIC) starting shortly after birth. In addition, the infant had vitreal eye hemorrhages and intraparenchymal brain infarction, apparently as intrauterine events. Within 15 hours of institution of fresh frozen plasma (FFP) infusions the DIC resolved and the progression of purpura fulminans reversed. Warfarin (0.4 mg/kg/day) was started on the fifth day of life, followed by gradual tapering of the FFP infusions. There were no recurrences of purpura, areas of skin necrosis healed without the need for skin grafting, and the areas of brain infarction resolved without apparent sequelae. The eye and brain lesions may be intrauterine events and appear to be a regular feature of this syndrome. Family studies are essential to establish the diagnosis, although there may be no family history of thromboembolic events, as in this case. Homozygous protein C deficiency is a rare disorder, but one in which early recognition and intervention may be lifesaving. Ours is the youngest patient yet reported to be treated with warfarin anticoagulation. We were thus able to avoid the complications of long-term plasma therapy as well as the potential thrombotic complications of central venous catheter placement.

Female↗

Electroencephalogram analysis and neuroprotective profile of the N-acetylated-alpha-linked acidic dipeptidase inhibitor, GPI5232, in normal and brain-injured rats.

We have evaluated the effects of the N-acetylated-alpha-linked acidic dipeptidase (NAALADase) inhibitor, GPI5232 [2-[(pentafluorophenylmethyl)hydroxyphosphinyl]methyl)-pentanedioic acid], to not only decrease brain injury but also to alter the inherent electroencephalographic (EEG) changes observed in a rat model of transient middle cerebral artery occlusion (MCAo). Continuous i.v. infusion of GPI5232 starting 1 h after injury resulted in more than a 50% reduction in brain infarct volume caused by 2 h of MCAo. This effect was dose-dependent and significant even when first treatment was delayed for 2 h post-MCAo. At 24 h post-MCAo, EEG spectral analysis of the injured hemisphere revealed functional improvement in GPI5232-treated rats. Significant recovery in high-frequency EEG power (8-30 Hz) was measured in GPI5232-treated animals in both parietal and temporal brain regions but not in vehicle-treated animals. MCAo-injured rats were also predisposed to developing cortical brain seizures, and GPI5232-treated rats had significantly fewer brain seizures than vehicle-treated animals. In separate experiments, acute high doses of GPI5232 in normal rats did not significantly alter EEG brain activity as evaluated by spectral analysis and did not produce any signs of seizure activity or behavioral abnormalities. These results show GPI5232 to be an effective neuroprotective treatment when given postinjury by reducing brain infarction and ameliorating the pathological EEG associated with focal brain ischemia.

Animals↗

Elevated velocity of prostacyclin degradation in blood as a possible risk factor in patients with cerebrovascular disorders.

Blood and plasma from 193 patients at risk of cerebrovascular disorders and 87 patients with brain infarction were tested to study prostacyclin (PGI2) degradation. It has been reported that patients at risk for cerebrovascular disorders and especially with brain infarction have an enhanced velocity of PGI2 degradation. The increase in velocity was more marked in blood than in plasma. A direct relation between this enhancement and the manifestation of intravascular platelet activation was observed. These data suggest that elevated PGI2 degradation might be a risk factor for thromboembolic events in patients with cerebrovascular disorders.

Cardiovascular Diseases↗

[Evaluation of cerebral blood perfusion in patients undergoing carotid endarterectomy using densitometric analysis of conventional cranial CT].

OBJECTIVE: To evaluate the efficacy of densitometric analysis of cranial CT imaging in the measurement of areas with low cerebral blood flow and lack of hemodynamic reserve in patients undergoing carotid endarterectomy. PATIENTS AND METHODS: 40 consecutive patients undergoing carotid endarterectomy have been included in the study. All of them had preoperative cranial CT, pre and postoperative basal and acetazolamide SPECT. Cranial CT imaging after digitalization and computer processing were obtained with 4 densitometric patterns: 1). normal cerebral blood perfusion; 2). ischemic or low brain blood perfusion (patron I); 3). parenchyma without cerebral hemodynamic reserve (patron nR), and 4). brain infarction. RESULTS: 32 out of 40 (80 %) patients had abnormal densitometric patterns: 19 nR patterns (47.5 %), 11 I pattern (27.5 %) and 2 established brain infarction. The correlation between densitometric cranial TC imaging and SPECT was 92% when analyzing areas with hypoperfusion (S: 96.5 %; E: 82 %). Cranial CT detected 12/13 of patients who lacked cerebral hemodynamic reserve in the SPECT analysis (S: 74 %; E: 92 %; Vpp: 95 %). CONCLUSIONS: There is a good correlation between analysis of densitometric cranial TC imaging and SPECT in determining low cerebral blood flow areas and lack of cerebral hemodynamic reserve. This method could help to improve carotid surgery indications in patients with carotid stenosis.

Aged↗

Induction of cyclooxygenase-2 in the rat brain after a mild episode of focal ischemia without tissue inflammation or neural cell damage.

Cyclooxygenase-2, a key enzyme in prostanoid synthesis, is induced by inflammatory stimuli and it is associated with cell death after cerebral ischemia. Here we evaluated whether cyclooxygenase-2 was induced after a short (10-min) episode of focal ischemia, mild enough not to cause inflammation or cell death. One-hour ischemia leading to brain infarct was studied for comparative purposes. Induction of cyclooxygenase-2 mRNA and protein was detected after both 10-min and 1-h ischemia. However, signs of edema were only apparent after 1-h, but not 10-min ischemia, and only rats subjected to 1-h ischemia had developed brain infarct at 4 days. Therefore, cyclooxygenase-2, not linked with neural cell death or inflammation, is induced after focal ischemia.

Animals↗

Cardiovascular consequences of clinical stroke.

In clinical stroke cardiovascular abnormalities are frequently neglected although they occur more often than it is generally assumed. However, cardiac arrhythmias, pathological ECG findings, and changes of circadian blood pressure patterns are significantly increased in patients with acute cerebrovascular lesions and are associated with an increased mortality. Several clinical studies have shown that cerebral infarctions may cause different cardiovascular abnormalities depending on the location and the size of the stroke. Hereby, the prolongation of the QT interval and the expansion of the QRS-complex as the most frequent ECG abnormalities are regarded as indicators of the electrical instability of the ventricular myocardium. Furthermore, cardiac enzyme increases are interpreted as an indicator of myocardial damage during the acute phase after cerebral ischaemia. Since the autonomic nervous system plays a major role in the regulation of blood pressure, alterations of sympatho-adrenergic activity can also affect the diurnal blood pressure profile. Some studies report frequent changes of the circadian blood pressure patterns with a decreased night-time blood pressure decline or a pathological night-time blood pressure elevation. Several studies proved the importance of infarct location. The insular cortex in particular has an important role in the genesis of the pathological activation of the sympathetic nervous system. Hence, a highly significant relationship between the extent of circadian blood pressure variation and percentage insular infarction could be found. Some findings implied that the mechanism of cardiovascular instability following stroke relates to the disinhibition of the insular cortex and a reacting augmentation of the sympathetic tone. A further important aspect is given by the strong evidence that sympathetic activation ] is lateralized following hemispheric brain infarction. Accordingly, patients with a right-sided hemispheric infarction showed a significantly diminished circadian blood pressure variation as compared with patients with left-sided hemispheric infarction. The results in patients with brain stem infarction were heterogeneous. On the one hand, patients with brain stem infarction had substantially higher mean plasma norepinephrine levels than did patients with hemispheric infarction; on the other hand, hemispheric lesions were associated with a significantly higher incidence of cardiac arrhythmias when compared to patients with brain stem infarction.

Animals↗

Computed tomography in reversible ischaemic attacks: clinical and prognostic correlations in a prospective study.

Two hundred and nineteen patients admitted with reversible atherothrombotic ischaemic attacks were prospectively evaluated by computed tomography. Of these patients, 122 were diagnosed as suffering from transient ischaemic attacks, 58 from reversible ischaemic neurological deficits and 39 from reversible ischaemic neurological deficits with incomplete resolution. In 133 cases the ischaemic event affected the carotid system, in 63 the vertebrobasilar system and in 23 cases the system could not be determined. Brain infarctions were observed in 64 patients (29.2%), cerebral atrophy in 96 (44.4%) and dilatation of a ventricle in 17 (7.8%). The frequency of brain infarction was related to the duration of the neurological deficit, being 20.5% in those with transient ischaemic attacks, 37.9% in those with reversible ischaemic neurological deficits and 43.6% in patients with reversible ischaemic neurological deficits with incomplete resolution (P = 0.005). Ischaemic lesions were closely correlated with abnormalities on supra-aortic trunk angiography or Doppler ultrasonography. During an average follow-up period of 21 months, a higher percentage of recurrence was found in those patients with CT infarctions, but the difference was not significant.

Cerebral Infarction↗

[Respiratory sleep disorders in the elderly].

Ageing is often associated with a decrease in the quality of sleep. In older subjects, sleep-related breathing disorders (SRBD) are increasingly recognized as being responsible for alterations in the quality of sleep. The prevalence of obstructive sleep apnea (OSA) increases with ageing; despite sometimes major disturbances in sleep structure, clinical symptoms are often subtle in this age group. Central apnea and periodic breathing, also more frequent in older subjects, most often occur in patients suffering either from neurological problems (such as tumors, brain infarcts, sequelae of infection, diffuse encephalopathies) or moderate to severe heart failure. In fact, patients suffering from cerebro-vascular diseases (such as brain infarcts or transient ischemic attacks) have a higher prevalence of SRBD than a control age-matched population. In these patients, SRBD are associated with a poorer prognosis in terms of functional recovery and survival. The clinical impact of SRBD on cognitive function appears to be modest in patients without dementia, albeit for a slight increase in daytime somnolence. However, in patients suffering from Alzheimer's disease, SRBD occur more frequently than in non-demented subjects, and indexes of severity of SRBD have been correlated with the importance of cognitive impairment. The hypothesis of a causal relationship between SRBD and the degree neuropsychological impairment in either Alzheimer's disease or multi-infarct dementia remains a matter of controversy. SRBD should be considered as a possible cause of "reversible dementia" and sought for in the presence of daytime somnolence, delirium, or unexplained right-sided heart failure in older patients.

Age Distribution↗

[Stroke in young adults in Japan].

The details of stroke in young adults remain unknown in Japan. We performed a multicenter survey to establish a stroke data bank for young adults in Japan. We collected clinical data of 7,245 acute stroke patients admitted to 18 hospitals in Japan. In patients admitted within the first 7 days of stroke, patients aged = < 50, = < 45, and = < 40 accounted for 8.9%, 4.2%, and 2.2%, respectively. Hypertension, diabetes mellitus, hypercholesterolemia, and non-valvular atrial fibrillation were significantly more frequent in the non-young than in the young, but smoking habits and patent foramen ovale were more frequent in the young than in the non-young. Brain infarction was the most predominant stroke subtype in the non-young, but not so in the young (62.6% vs. 36.7%, p < 0.01). Brain hemorrhage (20.8% vs. 32.1%, p < 0.01) and subarachnoid hemorrhage (7.3% vs. 26.1%, p < 0.01) were more frequent in the young. Causes of brain infarction and hemorrhage were often atypical in the young (2.8% vs. 25.1%, p < 0.001 and 4.6% vs. 20.2%, p < 0.0001, respectively). Causes of stroke in the young was often atypical, such as cerebral arterial dissection, Moyamoya disease, antiphospholipid syndrome, arteriovenous malformation, et al. Because causes and underlying risk factors of stroke in young adults were quite different from those in older patients, we need to establish the data bank and to explore optimal measures of the diagnosis and management for young stroke patients.

Adolescent↗

Intracranial acute arterial ischemia of the anterior circulation: evaluation with three-dimensional time-of-flight magnetic resonance angiography.

BACKGROUND: Stroke has been the second most common cause of death, after cancer, in Taiwan since 1983. The cost of stroke to society in terms of morbidity, mortality and economics is profound. Heightened interest in the early diagnosis and treatment of acute stroke challenges neuroimagers to optimize available modalities and to develop new techniques for the evaluation of cerebrovascular disease. The aim of this study was to investigate the effectiveness of magnetic resonance angiography (MRA) in conjunction with spin-echo imaging in patients with acute brain infarction of the anterior circulation. METHODS: Magnetic resonance imaging and three-dimensional Fourier transformed time-of-flight MRA studies, performed on 50 patients within one week after the onset of cerebral ischemia, were retrospectively reviewed and correlated with clinical records. Five of the 50 MRAs were considered nondiagnostic and excluded because of poor patient cooperation. RESULTS: In 41 of the 45 cases, the area of infarct corresponding to the clinical deficit at the time of study was identified on T2-weighted spin-echo images. Arterial occlusions or severe stenoses that corresponded to ischemic manifestations were identified with MRA in 37 of the 45 patients. A focal discontinuity with decreased arterial caliber corresponded to stenosis and nonvisualization of distal branches represented arterial occlusion. MRA provided information for 23 cases not obtained from the MR images. CONCLUSIONS: Vascular lesions demonstrated on intracranial MRA show a high correlation with infarct distribution. MRA, which provides information adjunctive to conventional MR imaging in a majority of cases, is concluded to be an important component of the complete evaluation of brain infarction.

Acute Disease↗

Treatment with statins after induction of focal ischemia in rats reduces the extent of brain damage.

OBJECTIVE: In the present study, MRI has been used to investigate therapeutic intervention with statins in a model of permanent focal cerebral ischemia in rat. METHODS AND RESULTS: Brain ischemia was induced in rats by the permanent occlusion of middle cerebral artery (MCAO) and the brain infarct size followed up in alive animals 2, 24, and 48 hours after MCAO, using the trace of apparent diffusion coefficient [Tr(D)] maps and T2-weighted images. In vehicle-treated rats, the infarct volumes increased by 38.5% and 89% after 24 and 48 hours, respectively, compared with the damage detected at 2 hours after MCAO. Treatment with simvastatin (20 mg/kg) after MCAO prevented the increase in brain infarct volume occurring at 24 hours and induced a 46.6% reduction after 48 hours. This effect was similar to that observed when simvastatin was administered before the induction of focal ischemia. T2W-MRI images confirmed these findings. The neuroprotective effects of simvastatin were paralleled by an increase in endothelial NO synthase immunoreactivity, detectable in the brain of simvastatin-treated rats. CONCLUSIONS: Statins, in addition to their preventive effect on cerebral ischemia, exert a neuroprotective role in the attenuation of brain damage after acute stroke.

Animals↗

Myocardial infarction in the differential diagnosis of dementias in the elderly.

The incidence of cerebral lesions in relation to myocardial infarction (MI) was evaluated on the basis of data obtained from medical records and autopsy reports on 269 psychogeriatric patients, in a 13-year retrospective study. Among 84 demented patients with MI, brain infarcts and hemorrhages were found in 42 percent, and Alzheimer's disease in 17 percent; (combination in 8 percent). In contrast, among 70 demented patients without MI, brain infarcts and hemorrhages were found in 11 percent, and Alzheimer's disease in 43 percent; (combination in 6 percent). Therefore, when it is difficult to differentiate senile dementia (Alzheimer's disease) from dementia due to cerebrovascular impairment, data on the presence or absence of myocardial infarction may prove useful.

Aged↗

[So-called laryngeal nystagmus. Progressive myoclonus as a symptom of a cerebellar and brain stem infarct].

The present article describes a patient with ischemia in the vascular territory of the posterior inferior cerebellar artery, who developed in addition to other typical signs of the dorsolateral medulla oblongata, myoclonic movements of the ipsilateral vocal cord. Within a period of one year, the myoclonic movement progressed, leading to bilateral involvement of the velo-pharyngeal muscles. The essential neuropathological lesion is considered to be an impairment of the dentato-olivary System. In this respect there is a close relationship to other types of rhythmical myoclonus due to lesions of the brain-stem and cerebellum.

Brain Stem↗