Effect of external decompression on the development of delayed ischemic neurological deficits after subarachnoid hemorrhage

The protective effect of a large decompressive craniectomy against delayed ischemic neurological deficits (DIND) was evaluated in patients operated on after subarachnoid hemorrhage due to a ruptured aneurysm. In 54 cases, a large decompressive craniectomy was performed (Group D), and 41 patients underwent conventional craniotomy (Group ND). Transient DIND appeared in three (17%) of the 18 Group D patients of Hunt and Kosnik grade I or II, but permanent deficits were not observed in this group. In Group ND, permanent DIND developed in seven (21%) of the 33 grade I or II patients, despite their having received the same medical care. This difference was statistically significant. However, there were no differences in outcome among patients of grades III, IV, and V. These results suggest that, at least in patients of grade I or II, a large decompressive craniectomy, performed early, will prevent DIND after subarachnoid hemorrhage. The procedure may prevent the increase in intracranial pressure and decrease in perfusion pressure brought on by vasospasm and the development of brain edema.     

Serum inflammatory adhesion molecules and high-sensitivity C-reactive protein correlates with delayed ischemic neurologic deficits after subarachnoid hemorrhage

BACKGROUND: The purpose of the present study was to investigate the relationship between serum concentrations of the immunoglobulin-like superfamily, selectins, hsCRP, and the development of DIND in patients with aneurysmal SAH. METHODS: Serum ICAM-1, VCAM-1, E-selectin, P-selectin, L-selectin, and hsCRP were measured in 33 patients with SAH who underwent aneurysmal clipping within 48 hours of the onset of symptoms. Serum samples were obtained during the early period (day 0) and the late period (day 7). RESULTS: The serum concentrations of ICAM-1 (P = .009), VCAM-1 (P = .0383) and hsCRP (P = .0014) during the early period were significantly higher in patients with SAH than in control patients. Further, serum hsCRP concentration during the late period was significantly higher in patients with SAH than in control patients (P = 0033). Finally, serum concentrations of ICAM-1, VCAM-1, and hsCRP during the early (P = .0055, P = .0266, and P = .0266) and late (P = .0423, P = .0041, and P = .0004) period were significantly higher in patients with DIND than in patients without DIND. CONCLUSIONS: Serum levels of ICAM-1, VCAM-1 and hsCRP during the early and late period following SAH correlate with DIND.     

Systematic review of the prevention of delayed ischemic neurological deficits with hypertension,hypervolemia, and hemodilution therapy following subarachnoid hemorrhage

OBJECT: There is uncertainty about the efficacy of hypertension, hypervolemia, and hemodilution (triple-H) therapy in reducing the occurrence of delayed ischemic neurological deficits (DINDs) and death after subarachnoid hemorrhage.The authors therefore conducted a systematic review to evaluate the efficacy of triple-H prevention in decreasing the rate of clinical vasospasm, DINDs, and death. METHODS: The authors systematically reviewed studies identified based on a MEDLINE, EMBASE, and COCHRANE Register search of articles published between 1966 and 2001, and reference lists of identified articles. An independent assessment of each study's methodological quality, population, intervention, and outcomes (rates of symptomatic vasospasm, DINDs, and death) was performed. Summary relative risk estimates were calculated for the main outcomes using fixed- or random-effect models, as appropriate. Only four prospective, comparative studies with a total of 488 patients were identified. The median internal validity score was 0.5 (range 0-2); the median external validity score was 3 (range 2-6). Compared with no prevention, triple-H therapy was associated with a reduced risk of symptomatic vasospasm (relative risk [RR] 0.45, 95% confidence interval [CI] 0.32-0.65), but not DIND (RR 0.54, 95% CI 0.2-1.49). The risk of death was higher (RR 0.68, 95% CI 0.53-0.87). Sensitivity analyses including only randomized, controlled trials showed no evidence of statistically significant results for these major end points. CONCLUSIONS: The paucity of information and important limitations in the design of the studies analyzed preclude evaluation of the efficacy of triple-H prevention and formulation of any recommendations regarding its use for the prevention of cerebral vasospasm.     

Predicting delayed ischemic deficits after aneurysmal subarachnoid hemorrhage using a transient hyperemic response test of cerebral autoregulation

OBJECTIVE: To assess whether the development of delayed ischemic deficits (DIDs) after aneurysmal subarachnoid hemorrhage can be predicted using transcranial Doppler ultrasonography and the transient hyperemic response test (THRT). METHODS: An increase in the middle cerebral artery peak flow velocity (FV) of more than 9% of baseline values after 5 to 9 seconds of carotid artery compression was defined as a normal THRT result, indicating good autoregulatory reserve. The transcranial Doppler criteria for vasospasm were a FV of more than 120 cm/s and a Lindegaard ratio of more than 3. Twenty patients with no immediate postoperative neurological deficits were studied. The FVs at all of the major cerebral arteries were measured daily after surgery, and the THRT results were assessed bilaterally. RESULTS: Five of six patients with abnormal THRT results in the first examination after surgery (primary THRT impairment) developed DIDs; none of the remaining patients developed DIDs (Fisher exact test, P = 0.0004). All five patients with DIDs initially exhibited low FVs but all subsequently developed increases in FVs to values of more than 150 cm/s and four exhibited FVs of more than 200 cm/s. The time of onset of DIDs corresponded to the time of onset of moderate vasospasm (FV > 150 cm/s). None of the patients with initially normal THRT results developed DIDs, although four patients did exhibit late (secondary) THRT impairment, which was associated with FVs of more than 120 cm/s. CONCLUSION: When the effects of primarily impaired (after surgery) autoregulation are magnified by vasospasm, the risk of DIDs seems to be very high. Vasospasm alone does not seem to cause DIDs. The development of DIDs could therefore be predicted using the THRT for patients after aneurysm clipping.     

Dipyridamole and postoperative ischemic deficits in aneurysmal subarachnoid hemorrhage

Recent evidence has suggested that the delayed cerebral ischemic deficits that often follow surgery for aneurysmal subarachnoid hemorrhage (SAH) may be due to a proliferative vasculopathy. This vascular pathology may result from an interaction between the platelets and the vessel wall. A single-blind controlled trial of dipyridamole administration in 677 patients presenting with SAH (of whom 348 came to surgery) was undertaken to test the hypothesis that the modification of platelet behavior might reduce the incidence of ischemic deficits. Blind independent assessment of the outcome in the surgical group based on the Glasgow Outcome Scale and the specific neurological deficits revealed no significant differences between the control and treatment groups.     

Prediction and prevention of delayed ischemic dysfunction after aneurysmal subarachnoid hemorrhage and early operation

Mean hemispheric cerebral blood flow (CBF) was studied after the intravenous administration of xenon-133 in 20 anesthetized patients with aneurysmal subarachnoid hemorrhage. Before early aneurysm operation, repeated CBF measurements were made to evaluate the cerebral vascular reactivity to controlled hyperventilation. Thirteen individuals received intravenous treatment with the calcium channel blocker nimodipine, whereas the other seven patients did not receive such specific antiischemic treatment. Five of the latter patients had an impaired CO2 response, and three showed delayed ischemic deterioration (DID), whereas none of the seven nimodipine-treated patients with impaired CO2 response showed DID. One nimodipine-treated patient with a preserved CO2 response, in whom operation was complicated, developed DID. The observed findings indicate that DID after uncomplicated early aneurysm operation may be associated with an early disturbance of cerebral vasoreactivity. Treatment with nimodipine may counteract the development of DID in patients with an impaired CBF CO2 response.     

Delayed neurological deficits detected by an ischemic pattern in the extracellular cerebral metabolites in patients with aneurysmal subarachnoid hemorrhage

OBJECT: In the treatment of patients with aneurysmal subarachnoid hemorrhage (SAH), early occlusion of the aneurysm is necessary as well as monitoring and treatment of complications following the primary bleeding episode. Monitoring with microdialysis has been studied for its ability to indicate and predict the occurrence of delayed ischemic neurological deficits (DINDs) in patients with SAH. METHODS: In 42 patients with aneurysmal SAH microdialysis monitoring of metabolites was performed using a 0.3-microl/minute perfusion flow over several days, and the results were correlated to clinical events and to brain infarction observed on computerized tomography scans. The microdialysis probe was inserted into the territory of the parent artery of the aneurysm. The authors defined an ischemic pattern as increases in the lactate/glucose (L/G) and lactate/pyruvate (L/P) ratios that were greater than 20% followed by a 20% increase in glycerol concentration. This ischemic pattern was found in 17 of 18 patients who experienced a DIND and in three of 24 patients who did not experience a delayed clinical deterioration. The ischemic pattern preceded the occurrence of a DIND by a mean interval of 11 hours. Maximum L/G and L/P ratios did not correlate with the presence of DIND or outcome, and there was no association between the glycerol level and subsequent brain infarction. CONCLUSIONS: Microdialysis monitoring of the cerebral metabolism in patients with SAH may predict with high sensitivity and specificity the occurrence of a DIND. Whether an earlier diagnosis results in better treatment of DINDs and, therefore, in overall better outcomes remains to be proven, as it is linked to an efficacious treatment of cerebral vasospasm.     

Nicardipine in the prevention of spasm-induced neurological deficits after subarachnoid hemorrhage: a dose-ranging study.

The tolerability of four doses of intravenous nicardipine (0.03, 0.08, 0.11, and 0.15 mg/kg/h) was assessed in this randomized multicenter, parallel-group study. Fifty-two patients with Hunt and Hess grade I-III aneurysmal subarachnoid hemorrhage were treated with intravenous nicardipine beginning within 4 days of bleeding, for a mean duration of 12.6 days; this treatment was followed by administration of oral nicardipine 90-120 mg until day 30. Hypotension was the main side effect, and it occurred only in the two groups that received the highest doses. However, it was possible to continue nicardipine in all cases at lower doses or even without modification, and hypotension was never responsible for any deleterious clinical effect.     

Vertebral arterial dissection with subarachnoid hemorrhage after ischemic onset

A case is reported of the vertebral arterial dissection presenting initially with cerebellar infarction, and which subsequently occurred with subarachnoid hemorrhage 14 days later. A 75-year old male was admitted because of vertigo and ataxia. MR T2-weighted imaging showed a hyperintensity areas on the left cerebellar hemisphere and MR angiography showed multiple stenotic lesions in the left vertebral artery. We diagnosed his illness as dissection of the left vertebral artery and antiplatelet therapy and the blood pressure control were carried out. Fourteen days after the onset, the patient complained of sudden onset of headache and subarachnoid hemorrhage was confirmed on CT scan. Proximal clip occlusion of the left vertebral artery and OA-PICA anastomosis was carried out immediately. The patient was discharged with slight truncal ataxia. We evaluated the features of this vertebral arterial dissection presenting with subarachnoid hemorrhage after ischemic stroke with reference to another reported cases.     

Effect of naloxone on deficits after aneurysmal subarachnoid hemorrhage

The opiate antagonist naloxone was suggested for the amelioration of cerebral ischemia after subarachnoid hemorrhage (SAH) following the 1981 report of clinical improvement of ischemic deficits in 2 patients. The deficit in 1 patient was exacerbated by morphine, suggesting that analgesics acting on opiate receptors should be avoided after SAH, and this would include codeine phosphate and dihydrocodeine, both widely used for post-SAH headache. We studied 21 consecutive patients with aneurysmal SAH whose condition was worse than Grade 1 on the Hunt and Hess scale. A single observer graded them to avoid interobserver error, and they were also given a score on the Glasgow coma scale. Each patient was then given an intravenous injection of 0.9% saline as placebo or 0.4 mg (7 patients) or 2.0 mg (14 patients) of naloxone. Five minutes later, the same observer regraded the patient. After 30 minutes, a second injection of placebo or naloxone was given, and the patient was regraded a third time. Each patient received placebo in one injection and naloxone in the other, but the order was randomized and unknown to the observer. There was no beneficial effect of 0.4 mg of naloxone after aneurysmal SAH, and we did not find an elevated level of the endogenous opiate beta-endorphin in the cerebrospinal fluid in the majority (6 of 8 of the patients in whom it was assayed). Five of the patients given 2.0 mg of naloxone did improve transiently, and none deteriorated after the drug, suggesting that naloxone in a high dose may have a place in the management of some post-SAH deficits.(ABSTRACT TRUNCATED AT 250 WORDS)     

A pilot study of dendroaspis natriuretic peptide in aneurysmal subarachnoid hemorrhage

OBJECTIVE: Hypovolemia after aneurysmal subarachnoid hemorrhage (SAH) may be mediated by natriuretic peptides and can further impair cerebral perfusion in dysautoregulated and vasospastic arterial territories. Dendroaspis natriuretic peptide (DNP), derived from the venom of Dendroaspis augusticeps, the Green Mamba snake, has recently been discovered in human plasma and atrial myocardium. There is no information regarding the presence or putative role of this peptide in patients with aneurysmal SAH. METHODS: A sensitive and specific DNP radioimmunoassay was performed on venous blood samples obtained on post-SAH Days 1, 3, and 7 from 10 consecutive SAH patients (cases) and randomly from 9 healthy volunteers (controls). Clinical and laboratory data, including daily serum sodium concentration and fluid balance, were collected prospectively up to 7 days after the ictus. RESULTS: Increase in plasma DNP levels occurred in five (63%) of eight patients who had DNP levels measured on Days 1 and 3 (mean increase, 29%). An increase in DNP level was significantly associated with development of a negative fluid balance (P = 0.003) and hyponatremia (P = 0.008). Three (75%) of the four patients who developed cerebral vasospasm during this study experienced an increase in DNP levels from Days 1 to 3. CONCLUSION: The present study is the first to find a significant association between elevated levels of DNP, a new member of the natriuretic peptide family, and the development of diuresis and natriuresis in patients with aneurysmal SAH. Our findings warrant further investigation by means of a large-scale, prospective, case-control study.     

Management of ischemic complications after subarachnoid hemorrhage.

The author reviews a form of management for patients deteriorating preoperatively or postoperatively from apparent ischemia attributed to progressive vasospasm after a subarachnoid hemorrhage. The clinical picture and relative frequency of this complication are considered in relationship to the status (grade) of the patient, location of the aneurysm, and ultimate neurological recovery. Experience suggests that the drug regimen reported is useful when instituted early after the onset of symptoms and is safe with proper monitoring techniques. The data do not justify early operative intervention after a subarachnoid hemorrhage, operation when there is angiographic evidence of severe spasm, or expectation of a dramatic effect in patients with a profound deficit or a fixed deficit several hours old.     

Pituitary cyst presenting with hyponatremia and increased secretion of brain natriuretic peptide. Case report

In most cases of pituitary cyst there are no clinical symptoms and the lesions are found incidentally. The authors report the case of a 60-year-old man with a pituitary cyst causing visual disturbance and hyponatremia. The patient presented with appetite loss and general fatigue. On admission, blood workup showed severe hyponatremia (112 mEq/L), and bitemporal hemianopsia was observed on neurological examination. Magnetic resonance imaging revealed an intra- and suprasellar region cystic mass extending to the frontal base and hypothalamic area. The serum level of brain natriuretic peptide (BNP) was elevated (92 pg/ml) with polyuria and excessive Na excretion. Transsphenoidal surgery was performed to drain the cyst. The cyst wall was partially excised and the cystic fluid was aspirated. The secretion of BNP normalized postoperatively, and the hyponatremia and visual symptoms resolved. Histological examination, including an electron microscopy study, confirmed the diagnosis of a simple cyst. This appears to be the first reported case of a pituitary simple cyst associated with hyponatremia and an elevated BNP level.     

Leukotriene production in gerbil brain after ischemic insult, subarachnoid hemorrhage, and concussive injury

A leukotriene-like immunoreactivity was measured by radioimmunoassay in the gerbil forebrain following ischemia and reperfusion, subarachnoid hemorrhage (SAH), or nonlethal concussive brain injury. In each paradigm an increase in immunoreactivity levels was found. Peak levels were reached 15 to 30 minutes after each insult, and slowly returned to baseline over the next 24 hours. The study supports the suggestion that cerebral vessels and circulating blood are capable of producing leukotrienes, and that a major source of production is a nonvascular component within gray matter, possibly the cortical neuron. Leukotrienes may play a role in the pathophysiology of cerebral edema formation, cerebral vasospasm, seizure activity, and other central nervous system abnormalities. These studies are the first to demonstrate leukotriene production in gerbil brain following SAH or concussive brain injury.     

Early treatment with diltiazem reduces delayed cerebral vascular narrowing after subarachnoid hemorrhage

Using a primate model of subarachnoid hemorrhage, we have demonstrated the ability of diltiazem to reduce delayed, experimental narrowing of cerebral vessels under clinically realistic conditions. Twelve monkeys were treated identically, except that six received oral diltiazem (20 mg/kg t.i.d.) starting 24 hours after a subarachnoid hemorrhage (SAH) and continuing for 5 days. Neurological examination showed that all untreated monkeys were hyperreflexic and hypotonic on the side contralateral to the SAH. Only two of the six of the diltiazem-treated monkeys had a similar deficit. Control angiograms taken before the SAH were compared with those taken 5 days later. The average vessel diameter at six standard sites in monkeys without diltiazem was 61% of control, whereas the average diameter at the same positions in the diltiazem-treated monkeys was 92% of control (P less than 0.01). In each group, the diameter of the most narrowed artery of each monkey was compared with values at the same site before SAH. The average diameter in the untreated group was 22% of control, significantly smaller than the corresponding value from the diltiazem-treated group, which was 68% (P less than 0.005). Delaying diltiazem treatment until 24 hours after hemorrhage still provides some protection, but less than that given by pretreatment with the drug. This suggests that the processes that eventually result in chronic cerebral vascular narrowing are initiated during the 24-hour period immediately after SAH. We propose that there is initially an acute, severe, calcium-dependent contraction of vascular smooth muscle and associated injury to the vessel wall, including its innervation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increase and uncoupling of adrenomedullin from the natriuretic peptide system in aneurysmal subarachnoid hemorrhage

OBJECT: Natriuresis is a common systemic manifestation of aneurysmal subarachnoid hemorrhage (SAH). Natriuresis and its accompanying hypovolemia may be a major contributing factor in the pathophysiology of symptomatic cerebral vasospasm. METHODS: The authors studied 14 consecutive patients with aneurysmal SAH and compared levels of adrenomedullin (ADM), a novel endogenous natriuretic peptide that possesses additional profound vasodilatory properties, with the natriuretic peptide system by using radioimmunoassay. The mean ADM values on admission were 24.8 pg/ml, a twofold increase over control values, but no correlation was found with atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-natriuretic peptide (CNP) from the natriuretic peptide system. At Day 5 post-SAH, ADM levels were significantly elevated in patients with vasospasm documented angiographically or on transcranial Doppler studies as compared with those who suffered no vasospasm (mean 61.9 pg/ml compared with 15.3 pg/ml, p < 0.01). CONCLUSIONS: The authors conclude that an elevation of ADM in plasma may indicate a physiological regulatory attempt to induce cerebral vasodilation. The regulation of ADM is uncoupled from ANP, BNP, and CNP.