Peduncular hallucinosis due to a small hemorrhage around the substantia nigra: a case report]

An 81-year-old female developed peduncular hallucination due to a small hemorrhage around the right substantia nigra is reported. Her hallucination was visual, not accompanying any other type of hallucination. It was vivid, colorful, well described, and recognized as unreal by herself. Different from most of the previous reports, she had no sleep abnormality and the hallucination occurred in daytime and at night, not relating to eye opening or closing. As the lesion of this case was quite restricted to around the right substantia nigra and not affecting the brainstem reticular formation, we speculate that the hallucination itself was induced by the stimulation of mesocorticolimbic system. The other characteristics of the hallucination such as appearing in evening, occurring with eye closing, and accompanying sleep disturbance might be induced when the brainstem involved more widely.     

Locked-in syndrome due to bilateral cerebral peduncular infarctions with occlusion of persistent primitive trigeminal artery]

A 61-year-old woman with diabetes mellitus was admitted to our hospital with right hemiparesis and dysarthria. Brain MRI showed bilateral cerebral peduncular infarctions. Three days after admission, she was unable to generate any voluntary movements, except for those of the eye, suggesting locked-in syndrome (LIS). She could not speak, but showed good comprehension by blinking in response to verbal commands. Brain CT 5 days later revealed subarachnoid hemorrhage (SAH) around quadrigeminal and ambient cistern. Cerebral angiogram on the following day revealed no aneurysm, occlusion of right persistent primitive trigeminal artery (PPTA) and a little flow of the bilateral vertebral arteries. Eye movements were impossible in all directions on the 11th day and MRI showed new infarctions of the midbrain and the ventral portion of the pons. However, an EEG on the 20th day was almost normal. We speculated that low blood flow in the basilar artery from the PPTA caused bilateral cerebral peduncular infarctions, and that weakness of the PPTA caused SAH.     

Pharmacologic reduction of angiographic vasospasm in experimental subarachnoid hemorrhage: systematic review and meta-analysis

Animal models have been developed to simulate angiographic vasospasm secondary to subarachnoid hemorrhage (SAH) and to test pharmacologic treatments. Our aim was to evaluate the effect of pharmacologic treatments that have been tested in humans and in preclinical studies to determine if animal models inform results reported in humans. A systematic review and meta-analysis of SAH studies was performed. We investigated predictors of translation from animals to humans with multivariate logistic regression. Pharmacologic reduction of vasospasm was effective in mice, rats, rabbits, dogs, nonhuman primates (standard mean difference of -1.74; 95% confidence interval -2.04 to -1.44) and humans. Animal studies were generally of poor methodologic quality and there was evidence of publication bias. Subgroup analysis by drug and species showed that statins, tissue plasminogen activator, erythropoietin, endothelin receptor antagonists, calcium channel antagonists, fasudil, and tirilazad were effective whereas magnesium was not. Only evaluation of vasospasm >3 days after SAH was independently associated with successful translation. We conclude that reduction of vasospasm is effective in animals and humans and that evaluation of vasospasm >3 days after SAH may be preferable for preclinical models.     

Angiographic vasospasm in a contemporary series of patients with aneurysmal subarachnoid haemorrhage

Over the last decade there have been significant changes in the management of patients with aneurysmal subarachnoid haemorrhage (SAH). Many of these changes, such as haemodilutional, hypervolaemic, hypertensive therapy and the use of calcium channel blockers, have been directed at the prevention and treatment of vasospasm. The angiograms of a contemporary series of 56 consecutive surgically treated patients with aneurysmal SAH were examined to compare angiographic vasospasm with that seen in historical studies. The time course of angiographic vasospasm was found to be broadly similar to that reported in previous studies, with onset after day 3 following SAH, maximal narrowing during the second week, and resolution after day 16. The times of peak narrowing and resolution were slightly earlier in previous studies. 30% of patients had clinical vasospasm (delayed neurological deficit for which other causes had been excluded), and these patients had a trend to more severe angiographic narrowing than those without clinical vasospasm, particularly in the second week following SAH. 44 angiograms were performed between days 1-3 post SAH and repeated between days 4-16. 95% of these showed arterial narrowing at the second angiogram. Patients not achieving an independent outcome tended to have had both more clinical vasospasm and more severe angiographic spasm than those achieving independence. It is concluded that angiographic vasospasm remains a common occurrence in the modern era, and continues to be associated with clinical events and a poor outcome.     

Cisternal sustained release dihydropyridines for subarachnoid hemorrhage

Nimodipine improved outcome in patients with subarachnoid hemorrhage (SAH) although hypotension limited the dose that could be administered systemically. Subarachnoid delivery of nicardipine or nimodipine may be more efficacious. We tested the efficacy of cisternal application of sustained release nicardipine and nimodipine in SAH in monkeys and dogs, respectively. SAH was created in 13 cynomolgus macaques by placement of autologous blood clot around right middle cerebral, anterior cerebral, and internal carotid arteries. Placebo poly-D,L-lactide coglycolide (PLGA), nicardipine PLGA or mibefradil PLGA was inserted in the clots. Catheter and computed tomography angiography (CTA) were performed at baseline and 7 days later (day 7). Cerebral infarction was assessed on day 7 by magnetic resonance imaging. Six dogs underwent baseline angiography and injection of autologous blood plus PLGA or nimodipine-loaded PLGA microparticles into the cisterna magna. Blood injection was repeated 2 days later and angiography 7 and 14 days later. Animals were euthanized and brains were examined histologically. Cerebrospinal fluid and serum nimodipine concentrations were measured. Nicardipine, but not mibefradil PLGA decreased vasospasm in monkeys (paired t-tests) although there was no significant effect on infarctions see on MRI. In dogs, nimodipine-PLGA produced high local concentrations of nimodipine that were associated with reduced basilar artery vasospasm. No untoward histological effects were observed. There was no reduction in microthrombi in animals treated with nimodipine PLGA compared to placebo PLGA. Site-specific, sustained release formulations of dihydropyridines can deliver high concentrations to the cerebrospinal fluid without causing systemic side effects, and may reduce angiographic vasospasm after SAH. Since nimodipine improves outcome in patients with SAH without necessarily preventing vasospasm, further studies are warranted.     

Cerebrospinal fluid membrane-bound tissue factor and myelin basic protein in the course of vasospasm after subarachnoid hemorrhage.

No marker that predicts accurately the time of occurrence of cerebral vasospasm due to subarachnoid hemorrhage (SAH) has been reported. In the present study, membrane-bound tissue factor (mTF) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) were evaluated as a predictor of the time of occurrence of cerebral vasospasm. The mTF and MBP concentrations were measured in the CSF from 28 patients with SAH due to ruptured aneurysm. Serial assays were performed from day 4 to day 14 after SAH. CSF mTF and MBP concentrations from days 5 to 9 correlated with the volume of cerebral infarction due to vasospasm and outcome three months after SAH. From the serial assays, CSF mTF measurements predicted the time of occurrence and severity and irreversibility of symptoms due to vasospasm. In conclusion, CSF mTF is predictive of the occurrence and the recovery of cerebral vasospasm, while CSF MBP is only an indicator of severity of brain damage due to vasospasm.     

Mechanism of cerebral vasospasm following subarachnoid hemorrhage in monkeys.

This paper reviews our recent studies on the mechanism of cerebral vasospasm following subarachnoid hemorrhage (SAH) in monkeys. Middle cerebral artery (MCA) vasospasm was maximal at 7 days, resolving by 14 days, and absent at 28 days after SAH. Arterial fibrosis was not detected during vasospasm, although there was intimal hyperplasia with fibrosis 28 days after SAH. On scanning electron microscopy, smooth muscle cells from vasospastic arteries had corrugated cell membranes and appeared similar to cells contracted pharmacologically, suggesting that vasospastic smooth muscle is contracted. Morphometric analysis of arteries obtained 7 days after SAH showed no significant increases in arterial wall area of vasospastic arteries compared with normal MCAs. The results suggest vasospasm in monkeys is not due to hypertrophy, hyperplasia, or fibrosis in the arterial wall. Vasospasm may be mainly vascular smooth muscle contraction, which damages the arterial wall, leading to secondary structural changes in the arterial wall which occur after angiographic vasospasm.     

Endothelin and aneurysmal subarachnoid haemorrhage: a study of subarachnoid cisternal cerebrospinal fluid.

Endothelin (ET) is considered one of the most potent vasoconstrictor polypeptides; several experimental studies have suggested its possible role in the pathogenesis of arterial vasospasm after subarachnoid haemorrhage (SAH). Previously reported data on plasma and CSF levels of endothelin in patients with a diagnosis of SAH have been controversial. Cisternal endothelin CSF levels and the possibility that they could be related to vasospasm and other clinical patterns of SAH were investigated. CSF samples were obtained from 55 patients admitted after angiographic diagnosis of intracranial aneurysm. Levels of ET-1 and ET-3 were measured through radio-immunoassay technique. Twelve patients who had operations for unruptured aneurysms were considered control cases; 43 patients with SAH were classified according to: Hunt and Hess grading at admission, vasospasm grading, CT classification and timing of surgery. In all 55 patients ET-1 was measured, while positive levels of ET-3 were found only in 17 cases of 48. No linear correlation was found between cisternal CSF ET-1 levels when considering time of surgery, CT classification, Hunt and Hess grading at admission, and vasospasm grading. The results of ET-3 assay should be considered with great caution because of the low percentage of positive cases. Cisternal CSF levels of ET-1 and ET-3 are not directly related to the occurrence of arterial vasospasm after the aneurysm rupture, or to other major clinical patterns of SAH; however, ET-1 expression occurs either in paraphysiological (unruptured aneurysm) or in pathological conditions (SAH). It is suggested that ET may potentiate, or may be potentiated by, other factors playing a consistent pathophysiological role in the development of vasospasm.     

白细胞、血小板动态变化与蛛网膜下腔出血后脑血管痉挛的关系

目的研究蛛网膜下腔出血患者外周血白细胞及血小板动态变化,探讨其对蛛网膜下腔出血后脑血管痉挛的预测价值。方法 发病24h内的蛛网膜下腔出血病人共60例,其中男34例,女26例,平均56.1±12.8岁。根据是否发生脑血管痉挛患者分为两组:脑血管痉挛组74例,无脑血管痉挛组36例。Hunt-Hess临床分级:脑血管痉挛组Ⅱ级8例,Ⅲ级11例,Ⅳ级5例;无脑血管痉挛组Ⅰ级9例,Ⅱ级24例,Ⅲ级3例。采用全自动血细胞分析仪,对患者发病后ld及3d、7d、14d晨肘静脉血白细胞及血小板数量动态观察比较。结果 脑血管痉挛组患者发病后3d、7d、14d白细胞计数明显高于无脑血管痉挛组患者(P<0.01),两组发病后24h、3d、7d、14d血小板计数无统计学差异(P>0.05)。结论 蛛网膜下腔出血后脑血管痉挛患者外周血白细胞增加、外周血白细胞动态变化可作为预测脑血管痉挛发生的指征之一。     

Intracranial Extension of Spinal Subarachnoid Hematoma Causing Severe Cerebral Vasospasm

Spinal subarachnoid hemorrhages (SAH) can extend into the intracranial subarachnoid space, but, severe cerebral vasospasm is rare complication of the extension of intracranial SAH from a spinal subarachnoid hematoma. A 67-year-old woman started anticoagulant therapy for unstable angina. The next day, she developed severe back pain and paraplegia. MRI showed intradural and extramedullar low signal intensity at the T2-3, consistent with intradural hematoma. High signal intensity was also noted in the spinal cord from C5 to T4. We removed subarachnoid hematoma compressing the spinal cord. The following day, the patient complained of severe headache. Brain CT revealed SAH around both parietal lobes. Three days later, her consciousness decreased and left hemiplegia also developed. Brain MRI demonstrated multiple cerebral infarctions, mainly in the right posterior cerebral artery territory, left parietal lobe and right watershed area. Conventional cerebral angiography confirmed diffuse severe vasospasm of the cerebral arteries. After intensive care for a month, the patient was transferred to the rehabilitation department. After 6 months, neurologic deterioration improved partially. We speculate that surgeons should anticipate possible delayed neurological complications due to cerebral vasospasm if intracranial SAH is detected after spinal subarachnoid hematoma.     

动脉瘤性蛛网膜下腔出血患者脑脊液中一氧化氮浓度的动态变化

目的探讨蛛网膜下腔出血后脑脊液中一氧化氮浓度的动态变化及其与脑血管痉挛的关系。方法采集57例动脉瘤性蛛网膜下腔出血(aSAH)患者脑脊液标本(采集时间为入院后即刻,出血后第3、5、7、10、14天),采用镉粒还原法检测脑脊液中NO浓度。结果出血后第3天脑脊液中NO浓度即有明显降低(P<0.05),在出血后第7～10天达到最低(P<0.01),而后逐渐升高。症状性脑血管痉挛患者NO浓度明显低于未痉挛者及无症状的脑血管痉挛患者。结论症状性脑血管痉挛的发生与脑脊液中NO浓度降低有一定相关性。     

Cerebrospinal fluid membrane-bound tissue factor and myelin basic protein in the course of vasospasm after subarachnoid hemorrhage

Abstract

No marker that predicts accurately the time of occurrence of cerebral vasospasm due to subarachnoid hemorrhage (SAH) has been reported. In the present study, membrane-bound tissue factor (mTF) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) were evaluated as a predictor of the time of occurrence of cerebral vasospasm. The mTF and MBP concentrations were measured in the CSF from 28 patients with SAH due to ruptured aneurysm. Serial assays were performed from day 4 to day 14 after SAH. CSF mTF and MBP concentrations from days 5 to 9 correlated with the volume of cerebral infarction due to vasospasm and outcome three months after SAH. From the serial assays, CSF mTF measurements predicted the time of occurrence and severity and irreversibility of symptoms due to vasospasm. In conclusion, CSF mTF is predictive of the occurrence and the recovery of cerebral vasospasm, while CSF MBP is only an indicator of severity of brain damage due to vasospasm. [Neurol Res 2001; 23: 715-720]     

Effect of cilostazol on delayed cerebral vasospasm after subarachnoid hemorrhage in rats: evaluation using black blood magnetic resonance imaging

The purpose of this study was to use black blood magnetic resonance imaging (BB-MRI) to assess delayed cerebral vasospasm (DCV) after subarachnoid hemorrhage (SAH) in rats, and evaluate whether delayed treatment with the anti-platelet agent cilostazol was effective on DCV. BA vasospasm was sequentially assessed at 1, 2, and 3 h, and 1-6 days after SAH by BB-MRI. BB-MRI clearly visualized biphasic vasospasm; early vasospasm at 1 h later and the maximal DCV at day 2. Cilostazol was perorally administered twice at day 1 after having confirmed significant DCV using BB-MRI. The effect of cilostazol on DCV was evaluated at day 2. Cilostazol significantly attenuated DCV and suppressed the levels of malondialdehide and 8-isoprostane in CSF after SAH. This study shows that BB-MRI is a useful and less invasive method for the evaluation of DCV, and cilostazol may be effective on DCV.     

Experimental evaluation of the beneficial effect of an antioxidant on cerebral vasospasm

Based on the previously suggested hypothesis that generation of free radicals leading to lipid peroxidation is involved in the genesis of vasospasm following SAH, the therapeutic effect of an antioxidant on experimental vasospasm was examined. As an antioxidant suitable for this purpose, AVS(1,2-bis(nicotinamide)-propane) was used. Experimental SAH was induced in dogs by intracisternal injection of blood and subsequent changes in the basilar artery diameter was evaluated by angiography. First, intrathecal administration of AVS 3 days after SAH caused prompt resolution of pre-existing chronic vasospasm for 3-4 h. Next, the effect of continuous intravenous administration of saline (control) or AVS was started and co ntinued for 4 days. In the control group, early and chronic spasm was observed on the daily angiography. In the AVS-treated group, early spasm was only moderately inhibited, but the occurrence of chronic spasm was remarkably suppressed in a dose-dependent manner. In these experiments, no adverse effect of AVS on the neurological or systemic conditions was observed.

The data indicate that AVS may be beneficial in the treatment of vasospasm following SAH, thereby reinforcing the concept that generation of free radicals is involved in the genesis of vasospasm.     

基底动脉中Caspase3、8的表达与蛛网膜下腔出血后脑血管痉挛的关系

目的探讨天冬氨酸特异性半胱氨酸蛋白酶3、8(Caspase3、8)在蛛网膜下腔出血(SAH)后在基底动脉中的表达及其与脑血管痉挛的关系。方法新西兰大白兔36只,随机分成对照组(n=6)和实验组(n=30),后者再随机分为SAH后1、3、5、7、10d等5个亚组,每亚组各6只。采用枕大池二次注血法建立SAH模型,应用免疫组化和末端脱氧核苷酸转移酶介导的dUTP原位切口末端标记法分别检测基底动脉内皮细胞Caspase3、8表达和凋亡。结果凋亡细胞在实验组SAH后第1天出现,第7天凋亡水平达到最高。实验组Caspase3、8表达水平明显高于与对照组(P<0.05)。Caspase3、8的表达在SAH后第1天就可观察致到,第5天和第7天出现强烈表达,第l0天表达明显减弱。结论本结果提示在兔脑血管痉挛的基底动脉中存在细胞凋亡;Caspase3、8可能参与了SAH后脑血管痉挛的发生和发展。     

Intracisternal administration of SB203580, a p38 mitogen-activated protein kinase inhibitor,attenuates cerebral vasospasm via inhibition of tumor-necrosis factor-α

Tumor-necrosis factor-α (TNF-α) is critical to the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). Hence, therapeutic strategies targeting TNF-α can attenuate cerebral vasospasm. This study investigated the effects of SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor, on TNF-α concentration in the cerebral arteries and the cerebrospinal fluid (CSF) after SAH and on subsequent cerebral vasospasm. Twenty-three rabbits were divided into four groups: (i) control (without SAH), (ii) SAH (SAH only), (iii) dimethylsulfoxide (DMSO, vehicle), and (iv) SB203580. The severity of vasospasm and the immunoreactivities of TNF-α and phosphorylated p38 MAPK in the brain vessels were determined in all animals, and the concentrations of TNF-α in the CSF were also assessed. Severe vasospasm was observed in the rabbits from the SAH and DMSO groups. SB203580 reversed vasospasm after SAH. Lower immunoreactivities of TNF-α and phosphorylated p38 MAPK were found in the basilar artery in the SB203580 group than in the DMSO group. The concentration of TNF-α in the CSF increased after SAH, but treatment with SB203080 after SAH suppressed this increase. Our data show that SB203580 reversed cerebral vasospasm by inhibiting the phosphorylation of p38 MAPK in the basilar artery and by suppressing the increase in TNF-α in the basilar artery and CSF after SAH. SB203580 could therefore potentially be used for the treatment of cerebral vasospasm after SAH.     

Respiratory arrest at the onset of idiopathic childhood occipital epilepsy of Gastaut

Occipital lobe epilepsy of childhood includes two entities: Panayiotopoulos syndrome in pre-school children, and idiopathic childhood occipital epilepsy of Gastaut (ICOEG) in school-age children. The typical initial manifestation of the former is vomiting, and that of the latter is visual hallucinations. Ictal cardiopulmonary arrest at initial presentation has been reported for Panayiotopoulos syndrome, but not for ICOEG. We document a 7-year-old previously healthy girl who experienced an acute elemental visual hallucination of seeing insects, followed by a new-onset generalized seizure. Upon arrival at the local hospital, she was unconscious and soon thereafter, developed respiratory arrest. She was resuscitated and initiated on mechanical ventilation. An electroencephalogram taken three days after seizure cessation showed frequent occipital spikes, consistent with the diagnosis of ICOEG. The sequence of acute elementary visual hallucination followed by a motor seizure, and then witnessed respiratory arrest illustrated occurrence of life-threatening autonomic involvement at initial onset in ICOEG. We speculate that the epileptic propagation from the occipital lobes eventually compromised the respiratory center in the brainstem. The possibility of occipital lobe epilepsy should be considered in school-age children presenting with acute visual hallucination followed by respiratory arrest. Such a presentation should prompt an urgent electroencephalogram and initiation of antiepileptic treatment if indicated.     

Prevention of symptomatic vasospasm after SAH by constant venous infusion of nimodipine

Sixty-one patients with SAH due to rupture of a cerebral aneurysm, classified in Grades I to IV according to Hunt and Hess, received a constant venous infusion of Nimodipine in a dose of 2mg/h for at least 14 days, followed by an oral administration of 60 mg/6 h for at least 4 days. Patients admitted after the 6th day of SAH, patients with SAH but without aneurysm on the angiogram and patients in Grade V were excluded. Mortality in 30 patients of Grades I-II was 3.3%, in 31 patients of Grades III-IV 42%. In the latter group 1 patient died due to cerebral vasospasm. Transient vasospasm occurred in 2 patients of Grades I-II. Recovery was complete in both cases. Thus, incidence of cerebral vasospasm was 4.9%, the incidence of poor-outcome-vasospasm even only 1.6%. The syndrome of cerebral vasospasm seems to be more than only constriction of cerebral vessels. The deleterious effects of Ca2+ shift into vascular cells and into neural cells which causes irreversible damage are discussed. Early administration of a specific 'cerebral' calcium antagonist like Nimodipine after SAH will prevent the intracellular Ca2+ overloading, thus protecting the neural cells and preventing Ca2+-induced smooth-muscle contraction of cerebral vessels, which encourages ischaemic deficits after SAH. The preventive use of Nimodipine has markedly reduced the incidence of symptomatic vasospasm in our clinic.