Roles of Phytoestrogen in the Pathophysiology of Intracranial Aneurysm.

Background and Purpose: The incidences of intracranial aneurysm and aneurysmal subarachnoid hemorrhage are high in postmenopausal women. Although population-based studies suggest that hormone replacement therapy is beneficial for postmenopausal women with intracranial aneurysms, estrogen replacement may no longer be recommended for the prevention of chronic diseases given its association with adverse outcomes, such as cancer and ischemic stroke. The isoflavone daidzein and its intestinal metabolite equol are bioactive phytoestrogens and potent agonists of estrogen receptors. Given their estrogenic properties, we investigated whether the isoflavones daidzein and equol are protective against the formation and rupture of intracranial aneurysms in a mouse model of the postmenopausal state. Methods: We induced intracranial aneurysms in ovariectomized adult female mice using a combination of induced systemic hypertension and a single injection of elastase into the cerebrospinal fluid. We fed the mice with an isoflavone-free diet with/without daidzein supplementation, or in a combination of intraperitoneal equol, or oral vancomycin treatment. We also used estrogen receptor beta knockout mice. Results: Both dietary daidzein and supplementation with its metabolite, equol, were protective against aneurysm formation in ovariectomized mice. The protective effects of daidzein and equol required estrogen receptor-ß. The disruption of the intestinal microbial conversion of daidzein to equol abolished daidzein's protective effect against aneurysm formation. Mice treated with equol had lower inflammatory cytokines in the cerebral arteries, suggesting that phytoestrogens modulate inflammatory processes important to intracranial aneurysm pathogenesis. Conclusions: Our study establishes that both dietary daidzein and its metabolite, equol, protect against aneurysm formation in ovariectomized female mice through the activation of estrogen receptor-ß and subsequent suppression of inflammation. Dietary daidzein's protective effect required the intestinal conversion to equol. Our results indicate the potential therapeutic value of dietary daidzein and its metabolite, equol, for the prevention of the formation of intracranial aneurysms and related subarachnoid hemorrhage.

A Prospective Observational Feasibility Study of Jugular Bulb Microdialysis in Subarachnoid Hemorrhage.

BACKGROUND: Cerebral metabolic perturbations are common in aneurysmal subarachnoid hemorrhage (aSAH). Monitoring cerebral metabolism with intracerebral microdialysis (CMD) allows early detection of secondary injury and may guide decisions on neurocritical care interventions, affecting outcome. However, CMD is a regional measuring technique that is influenced by proximity to focal lesions. Continuous microdialysis of the cerebral venous drainage may provide information on global cerebral metabolism relevant for the care of aSAH patients. This observational study aimed to explore the feasibility of jugular bulb microdialysis (JBMD) in aSAH and describe the output characteristics in relation to conventional multimodal monitoring. METHODS: Patients with severe aSAH were included at admission or after in-house deterioration when local clinical guidelines prompted extended multimodal monitoring. Non-dominant frontal CMD, intracranial pressure (ICP), partial brain tissue oxygenation pressure (PbtO2), and cerebral perfusion pressure (CPP) were recorded every hour. The dominant jugular vein was accessed by retrograde insertion of a microdialysis catheter with the tip placed in the jugular bulb under ultrasound guidance. Glucose, lactate, pyruvate, lactate/pyruvate ratio, glycerol, and glutamate were studied for correlation to intracranial measurements. Modified Rankin scale was assessed at 6 months. RESULTS: Twelve adult aSAH patients were monitored during a mean 4.2 ± 2.6 days yielding 22,041 data points for analysis. No complications related to JBMD were observed. Moderate or strong significant monotonic CMD-to-JBMD correlations were observed most often for glucose (7 patients), followed by lactate (5 patients), and pyruvate, glycerol, and glutamate (3 patients). Moderate correlation for lactate/pyruvate ratio was only seen in one patient. Analysis of critical periods defined by ICP > 20, CPP < 65, or PbtO2 < 15 revealed a tendency toward stronger CMD-to-JBMD associations in patients with many or long critical periods. Possible time lags between CMD and JBMD measurements were only identified in 6 out of 60 patient variables. With the exception of pyruvate, a dichotomized outcome was associated with similar metabolite patterns in JBMD and CMD. A nonsignificant tendency toward greater differences between outcome groups was seen in JBMD. CONCLUSIONS: Continuous microdialysis monitoring of the cerebral drainage in the jugular bulb is feasible and safe. JBMD-to-CMD correlation is influenced by the type of metabolite measured, with glucose and lactate displaying the strongest associations. JBMD lactate correlated more often than CMD lactate to CPP, implying utility for detection of global cerebral metabolic perturbations. Studies comparing JBMD to other global measures of cerebral metabolism, e.g., PET CT or Xenon CT, are warranted.

[Subarachnoid Hemorrhage and Isolated Brainstem Death]. / Aneurysmatische Subarachnoidalblutung und Entwicklung eines "isolierten Hirnstammtods".

BACKGROUND: Worldwide there are differences in the procedure of determining brain death. An irreversible loss of all brain functions, including cerebrum, cerebellum and brainstem is mandatory for the diagnosis of brain death in Germany. On the basis of a case report some important aspects of the new recommendations of the German guidelines are discussed. CASE REPORT: We present the case of a 41-year old patient who was admitted to our clinic due to acute subarachnoid hemorrhage (SAH). Angiography revealed an aneurysm of the posterior inferior cerebellar artery. The patient was comatose without any brainstem reflexes and showed apnoea. However, on day 3, EEG showed alpha activity as a sign of residual cortical function. We diagnosed an isolated brainstem death. The next day EEG was isoelectric and brain death was confirmed. DISCUSSION: The diagnosis of isolated brainstem death does not allow a confirmation of death in Germany. Our case presents a primary infratentorial brain damage mandating additional confirmatory tests.

Recovery of an injured fornix in a stroke patient.

OBJECTIVE: Knowledge about recovery of an injured fornix following brain injury is limited. We describe here a patient who showed recovery of an injured fornix following stroke. CASE REPORT: A 57-year-old female patient underwent coiling for a ruptured anterior communicating cerebral artery aneurysm, and conservative management for subarachnoid and intraventricular haemorrhage. The patient showed severe cognitive impairment 6 weeks after onset. However, her cognition showed continuous improvement with time; based on the Mini-Mental State Examination and the Memory Assessment Scale, her cognition was within the normal range 7 months after onset. RESULTS: Findings from diffusion tensor tractography at 6 weeks and 7 months showed discontinuations in both columns of the fornix. The proximal portion of both crus also showed discontinuation on diffusion tensor tractography at 6 weeks and 7 months; however, on 7-month diffusion tensor tractography, the end of the fornical body was shown to be connected to the splenium of the corpus callosum and then branched to the right medial temporal lobe and right thalamus. CONCLUSION: The unusual neural connection between the injured fornix and the thalamus appears to be a recovery phenomenon, which allows the injured fornix and the medial temporal lobe to obtain cholinergic innervation from cholinergic nuclei in the brainstem rather than from cholinergic nuclei in the basal forebrain.

Trigger factors and their attributable risk for rupture of intracranial aneurysms: a case-crossover study.

BACKGROUND AND PURPOSE: Little is known about activities that trigger rupture of an intracranial aneurysm. Knowledge on what triggers aneurysmal rupture increases insight into the pathophysiology and facilitates development of prevention strategies. We therefore aimed to identify and quantify trigger factors for aneurysmal rupture and to gain insight into the pathophysiology. METHODS: During a 3-year period, 250 patients with aneurysmal subarachnoid hemorrhage completed a structured questionnaire regarding exposure to 30 potential trigger factors in the period soon before subarachnoid hemorrhage (hazard period) and for usual frequency and intensity of exposure. We assessed relative risks (RR) of rupture after exposure to triggers with the case-crossover design comparing exposure in the hazard period with the usual frequency of exposure. Additionally, we calculated population-attributable risks. RESULTS: Eight triggers increased the risk for subarachnoid hemorrhage: coffee consumption (RR, 1.7; 95% CI, 1.2-2.4), cola consumption (RR, 3.4; 95% CI,1.5-7.9), anger (RR, 6.3; 95% CI, 4.6-25), startling (RR, 23.3; 95% CI, 4.2-128), straining for defecation (RR, 7.3; 95% CI, 2.9-19), sexual intercourse (RR, 11.2; 95% CI, 5.3-24), nose blowing (RR, 2.4; 95% CI, 1.3-4.5), and vigorous physical exercise (RR, 2.4; 95% CI, 1.2-4.2). The highest population-attributable risks were found for coffee consumption (10.6%) and vigorous physical exercise (7.9%). CONCLUSIONS: We identified and quantified 8 trigger factors for aneurysmal rupture. All triggers induce a sudden and short increase in blood pressure, which seems a possible common cause for aneurysmal rupture. Some triggers are modifiable, and further studies should assess whether reduction of exposure to these factors or measures preventing sudden increase in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm.

Hemodynamic management and outcome of patients treated for cerebral vasospasm with intraarterial nicardipine and/or milrinone.

BACKGROUND: Vasospasm is a potentially devastating complication after aneurysmal subarachnoid hemorrhage. Although endovascular treatment with intraarterial nicardipine and milrinone is an accepted clinical treatment strategy, there is little information either on hemodynamic management during treatment or on outcome and consequences of the hemodynamic management. We tested 2 hypotheses: (1) intraarterial administration of nicardipine and milrinone to treat cerebral vasospasm would require increased administration of vasoconstrictor to support arterial blood pressure at target levels; and (2) high-dose vasopressors administered to increase blood pressure in these patients would lead to systemic acidosis and end-organ ischemic damage. METHODS: We conducted a single-center, retrospective review of consecutive patients with clinically symptomatic vasospasm after aneurysmal subarachnoid hemorrhage that failed medical management with "triple H therapy" and subsequently received intraarterial nicardipine and/or milrinone between March 2005 and July 2007. RESULTS: Of 160 endovascular interventions in 73 patients (aged 52 +/- 10 years; 50 women), 96 received only nicardipine, 5 only milrinone, and 59 both drugs. General anesthesia with muscle relaxation was performed for 93% of procedures. During treatment, both the number and dose of vasopressors required to maintain arterial blood pressure at target levels increased; the median dose of phenylephrine increased from 200 (n = 121) to 325 microg/min (n = 122), norepinephrine increased from 12 (n = 60) to 24.5 microg/min (n = 87), and vasopressin infusions increased from 7 to 24. Nonetheless, arterial blood pressure decreased 13% during treatment. In >90% of procedures, the postprocedure angiogram showed improved vessel caliber. A single patient demonstrated troponin T increase; no patients had a decrease in renal function, bowel or peripheral ischemia, systemic acidosis, or acute stroke. Overall mortality was 11%. CONCLUSIONS: Intraarterial administration of nicardipine and/or milrinone requires use of vasopressors to maintain arterial blood pressure. Despite high doses of vasoconstrictors, treatment has low mortality, minimal end-organ ischemic damage or systemic acidosis, and results in improved caliber of cerebral vessels affected by vasospasm.

High-dose intraarterial verapamil in the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECT: Because oral calcium channel blockers appear to reduce the severity of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH), interest in their application intraarterially has emerged for cases in which noninvasive means of alleviating vasospasm are unsuccessful. Studies to date have been limited to the administration of low intraarterial doses because of concerns about hemodynamic stability and changes in intracranial pressure. These doses, although effective in cases of milder vasospasm, were inadequate in severe cases. The authors present a series of 10 patients with cerebral vasospasm who underwent 12 procedures in which they received > or = 20 mg of intraarterial verapamil per procedure. METHODS: A retrospective review was undertaken of all patients who underwent endovascular treatment for cerebral vasospasm due to aneurysmal SAH by the senior author between February 2005 and October 2006. Ten patients were identified who had undergone a total of 12 procedures during which > or =20 mg of intraarterial verapamil had been administered. From angiography reports, anesthesia records, and nursing records, we obtained pre- and postverapamil mean arterial blood pressures (MABPs), heart rates, intracranial pressures (ICPs) (when available), and visible changes in the degree of vasospasm. RESULTS: No statistically significant changes in MABP, heart rate, or ICP were observed after administration of > or = 20 mg of intraarterial verapamil, and the degree of improvement in vasospasm was statistically significant based on our grading system. No correlation was found between the change in hemodynamic parameters and the total dose of verapamil. CONCLUSIONS: This study indicates that high-dose intraarterial verapamil may be used to treat cerebral vasospasm without compromising hemodynamic stability or increasing ICP.

Blood flow disturbance in perforating arteries attributable to aneurysm surgery.

OBJECT: The object of this study was to investigate patients with cerebral infarction in the area of the perforating arteries after aneurysm surgery. METHODS: The authors studied the incidence of cerebral infarction in 1043 patients using computed tomography or magnetic resonance imaging and the affected perforating arteries, clinical symptoms, prognosis, and operative maneuvers resulting in blood flow disturbance. RESULTS: Among 46 patients (4.4%) with infarction, the affected perforating arteries were the anterior choroidal artery (AChA) in nine patients, lenticulostriate artery (LSA) in nine patients, hypothalamic artery in two patients, posterior thalamoperforating artery in five patients, perforating artery of the vertebral artery (VA) in three patients, anterior thalamoperforating artery in nine patients, and recurrent artery of Heubner in nine patients. Sequelae persisted in 21 (45.7%) of the 46 patients; 13 (28.3%) had transient symptoms and 12 (26.1%) were asymptomatic. Sequelae developed in all patients with infarctions in perforating arteries in the area of the AChA, hypothalamic artery, or perforating artery of the VA; in four of five patients with posterior thalamoperforating artery involvement; and in two of nine with LSA involvement. The symptoms of anterior thalamoperforating artery infarction or recurrent artery of Heubner infarction were mild and/or transient. The operative maneuvers leading to blood flow disturbance in perforating arteries were aneurysmal neck clipping in 21 patients, temporary occlusion of the parent artery in nine patients, direct injury in seven patients, retraction in five patients, and trapping of the parent artery in four patients. CONCLUSIONS: The patency of the perforating artery cannot be determined by intraoperative microscopic inspection. Intraoperative motor evoked potential monitoring contributed to the detection of blood flow disturbance in the territory of the AChA and LSA.

Confirmation of blood flow in perforating arteries using fluorescein cerebral angiography during aneurysm surgery.

OBJECT: The authors performed fluorescein cerebral angiography in patients after aneurysm clip placement to confirm the patency of the parent artery, perforating artery, and other arteries around the aneurysm. METHODS: Twenty-three patients who underwent aneurysm surgery were studied. Aneurysms were located in the internal carotid artery in 12 patients, middle cerebral artery in six, anterior cerebral artery in three, basilar artery bifurcation in one, and junction of the vertebral artery (VA) and posterior inferior cerebellar artery in one. After aneurysm clip placement, the target arteries were illuminated using a beam from a blue light-emitting diode atop a 7-mm diameter pencil-type probe. In all patients, after intravenous administration of 5 ml of 10% fluorescein sodium, fluorescence in the vessels was clearly observed through a microscope and recorded on videotape. RESULTS: The excellent image quality and spatial resolution of the fluorescein angiography procedure facilitated intraoperative real-time assessment of the patency of the perforating arteries and branches near the aneurysm, including: 12 posterior communicating arteries; 12 anterior choroidal arteries; four lenticulostriate arteries; three recurrent arteries of Heubner; three hypothalamic arteries; one ophthalmic artery; one perforating artery arising from the VA; and one posterior thalamoperforating artery. All 23 patients experienced an uneventful postoperative course without clinical symptoms of perforating artery occlusion. CONCLUSIONS: Because the fluorescein angiography procedure described here allows intraoperative confirmation of the patency of perforating arteries located deep inside the surgical field, it can be practically used for preventing unexpected cerebral infarction during aneurysm surgery.

The effects of fenestration of the interpeduncular cistern membrane arousted to the opening of lamina terminalis in patients with ruptured ACoA aneurysms: a prospective, comparative study.

BACKGROUND: The incidence of chronic hydrocephalus requiring shunt placement is a well-known and common complication of aneurysmal subarachnoid hemorrhage (aSAH). It was suggested that fenestration of the lamina terminalis (LT) during microsurgery for aSAH may be associated with a reduced rate of shunt-dependent chronic hydrocephalus (SDCH). We analyzed that, fenestrations of the LT and Liliequist membrane (LM) would reduce rate of SDCH and improve rate of favorable outcome. METHODS: 145 patients who were analyzed in the study were treated in our department with ruptured anterior communicating artery (ACoA) aneurysms. We compared the rate of shunting and clinical outcome in patients in whom only fenestration of the LT (Group 1) was performed with that in patients in whom fenestrations of both the LT and LM (Group 2) were performed. RESULTS: Chronic hydrocephalus requiring shunting amounted to 9.8% (7 patients) in Group 1 and 4% (3 patients) in Group 2 (p=0.203). Also, there were no differences in the rate of shunt dependent hydrocephalus between the two groups in patients with Fisher's CT grades 3 (p=0.343) and 4 (p=0.667), and HH grades 4 (p=0.306) and 5 (p=0.361). Favorable clinical outcomes were observed with rates of 74.6% in Group 1 and 79.7% in Group 2 (p=0.693). Also there were no differences in the rates of favorable clinical outcome between the two groups in patients with Fisher's CT grades 3-4, HH grades 4-5. CONCLUSIONS: Our study shows that fenestration of the LM coupled with the opening of the LT reduced-relatively-the incidence of SDCH; this however was not significant. This positive effect was particularly noticeable in patients in whom a cisternal "overflow" was observed at surgery when opening the LM. This corresponded to cases with ventricular dilatation and a IVth ventricle with clots.

Transcranial motor evoked potentials during basilar artery aneurysm surgery: technique application for 30 consecutive patients.

OBJECTIVE: Microsurgical clipping of basilar artery aneurysms carries a risk of neurological compromise resulting from midbrain or thalamic ischemia. Somatosensory evoked potential (SSEP) monitoring and electroencephalography are the standard techniques for assessing the level of cerebroprotective anesthesia and monitoring ischemia during temporary occlusion or after permanent clipping. Transcranial motor evoked potential (TcMEP) monitoring was added to determine whether this modality improved intraoperative monitoring. METHODS: Combined SSEP/electroencephalographic/TcMEP monitoring was used for 30 consecutive patients with basilar artery apex aneurysms in the past 1.5 years. Voltage thresholds were recorded before, during, and after aneurysm treatment for the last 10 patients. RESULTS: All 30 patients underwent an orbitozygomatic craniotomy for clipping (28 patients), wrapping (1 patient), or superficial temporal artery-superior cerebellar artery bypass (1 patient). Electrophysiological changes occurred for 10 patients (33%), elicited by temporary clipping (6 patients), permanent clipping (3 patients), or retraction (1 patient). Isolated SSEP changes were observed for one patient, isolated TcMEP changes for five patients, and changes in both TcMEPs and SSEPs for four patients. Among patients with simultaneous changes, TcMEP abnormalities were more robust and occurred earlier than SSEP abnormalities. Impaired motor conduction was detected first with an increase in the voltage threshold (from 206 +/- 22 to 410 +/- 49 V, P < 0.05, n = 3) and then with loss of TcMEP responses. SSEP and TcMEP signals returned to baseline values for all patients after corrective measures were taken. CONCLUSION: TcMEP monitoring can be safely and easily added to traditional neurophysiological monitoring during basilar artery aneurysm surgery. These results suggest that TcMEPs may be more sensitive than SSEPs to basilar artery and perforating artery ischemia. This additional intraoperative information might minimize the incidence of ischemic complications attributable to prolonged temporary occlusion or inadvertent perforator occlusion.

Impact of cerebral microcirculatory changes on cerebral blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Cerebral microcirculatory changes during cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) are still controversial and uncertain. The aim of this study was to investigate the changes of cerebral microcirculation during cerebral vasospasm and to clarify the roles of microcirculatory disturbances in cerebral ischemia by measuring cerebral circulation time (CCT) and regional cerebral blood flow (rCBF). METHODS: In 24 cases with aneurysmal SAH, rCBF studies by single-photon emission CT and digital subtraction angiography (DSA) were performed on the same day between 5 and 7 days after SAH and/or within 4 hours after the onset of delayed ischemic neurological deficits. CCT was obtained by analyzing the time-density curve of the contrast media on DSA images and was divided into proximal CCT, which was the circulation time through the extraparenchymal large arteries, and peripheral CCT, which was the circulation time through the intraparenchymal small vessels. They were analyzed in association with rCBF and angiographic vasospasm. RESULTS: Severe angiographic vasospasm statistically decreased rCBF, and correlation between the degree of angiographic vasospasm and rCBF was seen (r=0.429, P=0.0006). Peripheral CCT showed strong inverse correlation with rCBF (r=-0.767, P<0.0001). Even in none/mild or moderate angiographic vasospasm, prolonged peripheral CCT was clearly associated with decreased rCBF. CONCLUSIONS: In addition to the marked luminal narrowing of large arteries detected as severe angiographic vasospasm, microcirculatory changes detected as prolonged peripheral CCT affected cerebral ischemia during cerebral vasospasm. These results suggested that impaired autoregulatory vasodilation or decreased luminal caliber in intraparenchymal vessels may take part in cerebral ischemia during cerebral vasospasm.

[Clinical application of combined acupuncture-drug anesthesia with isoflurane-induced hypotension in cerebral operation].

OBJECTIVE: To evaluate the feasibility of combined acupuncture-isoflurane anesthesia with deliberated and controlled hypotension induced by isoflurane for the neurosurgical patients. METHODS: Forty-two patients with brain tumor scheduled for selective surgery according to the methods of anesthesia, they were further divided into isoflurane anesthesia (group I, n = 21) and combined acupuncture-isoflurane anesthesia (group II, n = 21). Anesthesia was induced with fentanyl, sodium pentothal and phi avolon intravenously administered. The concentration of isoflurane was elevated to reduce mean arterial pressure (MAP) 30%-40% during dissection and occlusion of the tumor. Compare with the hemodynamic parameters (CO, CI, SV, SI, SVR, LVSWI, RPP) which were measured with Swan-Ganz technique before, during and after isoflurane-induced hypotension. In group II, during tracheal intubation the acupoint of Quanliano (SI 18), Yuyao (EX-HN4), Fengchi (GB 20) and Hegu (LI 4) were stimulated by Han's Acupoint Nerve Stimulator. Meanwhile, the isoflurane was inhalated to maintain anesthesia. RESULTS: As compared with group I, concentration of isoflurane decreased significantly, and isoflurane average dosage per hour reduced by 31%-42% in group II. SVR, PVR, RPP were significantly decreased in the duration of hypotension (P < 0.05). The range change of CO, CI, SV, SI, LVSWI, RPP during controlled hypotension was significantly lower in combined acupuncture-isoflurane anesthesia than that in isoflurane anesthesia (P < 0.05). CONCLUSION: Combined acupuncture-isoflurane anesthesia with isoflurane induced hypotension was used as a selective way for deliberated and controlled hypotension to the neurosurgical patients.

Confabulation following rupture of posterior communicating artery.

In this study we report a patient, MG, who following rupture of left posterior communicating artery exhibited an amnesic-confabulatory syndrome. Neuropsychological examination showed severe impairment on episodic memory tasks, which were marred by florid but plausible and semantically appropriate confabulation. Performance on tasks involving various kinds of semantic knowledge was normal or only mildly impaired. Performance on tasks traditionally considered sensitive to frontal dysfunction was severely impaired with the exception of Cognitive Estimates where MG's performance was completely normal. There was no evidence of structural (CT scan) or metabolic (SPECT) damage to the frontal lobe. It is argued that tasks traditionally considered sensitive to frontal dysfunction are not specifically implemented by cognitive resources based on frontal structures. MG's confabulation is discussed in terms of a possible disruption of cognitive functions involved in the control of the subjective experience of feeling of remembering.

The effect of nimodipine monotherapy and combined treatment with ketamine and lignocaine in aneurysmal subarachnoid haemorrhage.

The clinical effects of nimodipine monotherapy were compared with the effects of nimodipine combined with ketamine and lignocaine (combination therapy) in a single-centre, one investigator, open study in patients with proven aneurysmal subarachnoid haemorrhage (aSAH). After clipping of the aneurysm, nimodipine was administered intravenously until day 5-7 after clipping. Thereafter the intravenous nimodipine was substituted by oral doses of nimodipine. These were decreased gradually and then discontinued within the following 6 days. For combination therapy, nimodipine was given together with both a bolus injection of 1 microgram/kg ketamine followed by an infusion of the drug at a rate of 3 micrograms/kg/min and a bolus injection of 1.5 mg/kg lignocaine followed by an infusion of the drug at a rate of 12 micrograms/kg/min. During the study period, 173 patients were admitted to the hospital with subarachnoid haemorrhage (SAH). Of these patients, 115 with a proven aneurysm were operated on and evaluated: 66 patients received nimodipine monotherapy and 49 were given nimodipine combined with ketamine and lignocaine. These subgroups were comparable in terms of the baseline characteristics (age, Hunt and Hess score). The (baseline corrected) Hunt and Hess scores after surgery and a 0-5 clinical outcome score were applied as indices for clinical effects. Patients receiving nimodipine monotherapy and combined therapy showed a significant clinical improvement compared to baseline (P = 0.001 and P = 0.006, respectively). The beneficial effect of nimodipine monotherapy is in line with previous double-blind, placebo-controlled studies. Although nimodipine monotherapy seems to be more effective than combined treatment, this was not statistically significant. Our data indicate that combined treatment with ketamine and lignocaine is not more effective than nimodipine monotherapy in patients with mild aSAH, but this does not rule out an effect in severe cases. There was no indication of a pharmacodynamic interaction between nimodipine and co-medication. No serious or clinically relevant adverse reactions were noted during the study.

Dynamics of cerebral blood flow and metabolism in patients with cranioplasty as evaluated by 133Xe CT and 31P magnetic resonance spectroscopy.

OBJECTIVE: Prolonged improvement in neurological and mental disorders has been seen after only cranioplasty in patients initially treated with external decompression for high intracranial pressure. The objective was to evaluate, using 133Xe CT and 31P magnetic resonance spectroscopy (MRS), how restoring the bone itself can influence cerebral blood flow and cerebral energy metabolism after high intracranial pressure is attenuated. METHODS: Seven patients (45-65 years old) who had undergone external decompression to prevent uncontrollable intracranial hypertension after acute subarachnoid haemorrhage were evaluated. Cerebral blood flow and metabolic changes were evaluated before and after cranioplasty. RESULTS: The ratio of phosphocreatine to inorganic phosphate (PCr/Pi), which is a sensitive index of cerebral energy depletion, was calculated and beta-ATP was measured. The cerebral blood flow value in the thalamus was normalised, from 44 (SD 9) to 56 (SD 8) ml/100 g/min (P < 0.01) and the value in the hemisphere increased from 26 (SD 3) to 29 (SD 4) ml/100 g/min on the side with the bone defect. The PCr/Pi ratio improved greatly from 2.53 (SD 0.45) to 3.01 (SD 0.24) (P < 0.01). On the normal side, the values of cerebral blood flow and PCr/Pi increased significantly (P < 0.01) after cranioplasty, possibly due to transneural suppression. The pH of brain tissue was unchanged bilaterally after cranioplasty. CONCLUSION: Cranioplasty should be carried out as soon as oedema has disappeared, because a bone defect itself may decrease cerebral blood flow and disturb energy metabolism.

Is transcranial Doppler sonography useful in detecting late cerebral ischaemia after aneurysmal subarachnoid haemorrhage?

Transcranial Doppler (TCD) examination was performed in 109 patients with aneurysmal subarachnoid haemorrhage. Fifty-seven demonstrated flow velocities exceeding 120 cm/s in the middle cerebral artery. Of these, 23 developed delayed ischaemic deficit (DID). Mean flow velocity in this group was 170, SD 12.8 cm/s, in comparison with 155, SD 11.2 cm/s in the 34 patients without late signs of cerebral ischaemia. This difference is significant (p = 0.0269). In the 34 patients without DID, but TCD > 120 cm/s, 17 received anti-ischaemic therapy based on TCD values only, while 17 were given no additional treatment. The mean TCD values and the neurological outcome in the two groups were similar. A rapid increase in flow velocities of 50 cm/s or more during a 24-h period seemed to be a strong predictor of symptomatic vasospasm as seven out of 12 patients developed DID, five with permanent neurological sequelae. The study confirms results from other centres, that a strict correlation between high TCD flow velocities and occurrence of DID does not exist.

[Controlled hypotension against a background of nimodipine during an operation on neurosurgical patients with hypertension]. / Kontrolirana khipotoniia na fona na nimodipin pri operirane na nevrokhirurgichno bolni s khipertoniia.

Operative interventions in subarachnoid hemorrhages caused by brain vessel aneurysm require meticulous dissection of the latter. Regardless of the preoperative preparation of hypertensives, hypertension is a factor predisposing to intraoperative blood pressure fluctuation which, in turn, is extremely unfavourable and interferes with the operation proper on the aneurysm. What is more, it augments the spasm of cerebral vessels and brain edema. Any increase in blood pressure may result in a rupture of the aneurysm. As shown by a parallel study on two groups of patients with hypertension, following intraoperative administration of calcium antagonists having a preventive effect on brain, the stabilization of blood pressure attained is persistent, with the spasm of cerebral vessels and brain edema lending themselves more readily to control. The application of controlled hypotension is more easily effected, and administration of ganglioblocking agents is unnecessary.