Validity of the FOUR score coma scale in the medical intensive care unit.

OBJECTIVE: To evaluate the validity of the FOUR (Full Outline of UnResponsiveness) score (ranging from 0 to 16), a new coma scale consisting of 4 components (eye response, motor response, brainstem reflexes, and respiration pattern), when used by the staff members of a medical intensive care unit (ICU). PATIENTS AND METHODS: This interobserver agreement study prospectively evaluated the use of the FOUR score to describe the condition of 100 critically ill patients from May 1, 2007, to April 30, 2008. We compared the FOUR score to the Glasgow Coma Scale (GCS) score. For each patient, the FOUR score and the GCS score were determined by a randomly selected staff pair (nurse/fellow, nurse/consultant, fellow/fellow, or fellow/consultant). Pair wise weighted kappa values were calculated for both scores for each observer pair. RESULTS: The interrater agreement with the FOUR score was excellent (weighted kappa: eye response, 0.96; motor response, 0.97; brainstem reflex, 0.98; respiration pattern, 1.00) and similar to that obtained with the GCS (weighted kappa: eye response, 0.96; motor response, 0.97; verbal response, 0.98). In terms of the predictive power for poor neurologic outcome (Modified Rankin Scale score, 3-6), the area under the receiver operating characteristic curve was 0.75 for the FOUR score and 0.76 for the GCS score. The mortality rate for patients with the lowest FOUR score of 0 (89%) was higher than that for patients with the lowest GCS score of 3 (71%). CONCLUSION: The interrater agreement of FOUR score results was excellent among medical intensivists. In contrast to the GCS, all components of the FOUR score can be rated even when patients have undergone intubation. The FOUR score is a good predictor of the prognosis of critically ill patients and has important advantages over the GCS in the ICU setting.

Deep venous thrombosis prophylaxis in cerebral hemorrhage.

Deep vein thrombosis (DVT) is a risk factor for patients with acute stroke. Subclinical DVT is more common than clinically apparent DVT. DVT manifests with lower extremity swelling that might be associated with pain. Venous duplex ultrasound is a simple diagnostic procedure for detection of a DVT. However, as many as 30% of patients with acute pulmonary embolism show no evidence of lower extremity DVT, and thus a negative venous duplex ultrasound does not exclude the diagnosis of acute pulmonary embolism. Data suggest that heparin, of any type, may reduce the risk of venous thromboembolism in neurosurgical patients. One trial has shown that mechanical devices, such as intermittent pneumatic compression, significantly decrease the occurrence of asymptomatic DVT for patients with intracerebral hemorrhage as compared with elastic stockings alone, although this advantage was not found in a meta-analysis of prospective studies. Limitations in DVT prophylaxis raise a question about the need for more aggressive DVT surveillance.

Brain lesions in cerebral venous sinus thrombosis.

BACKGROUND AND PURPOSE: Analyze the relationship between the location and extent of sinus thrombosis and presence and severity of brain lesions. METHODS: Retrospective chart and neuroimaging review of patients with documented CVST. A CVST score was devised to quantify the extent of cerebral venous sinus thrombosis. RESULTS: Nineteen of 56 (34%) patients had brain lesions. The extent of sinus thrombus was associated with increased risk of brain lesions (CVST score 1.9 among patients without brain lesions versus 3.1 in those with lesions; P=0.006). Age, sex, and acquired or hereditary thrombophilias were not associated with the risk of parenchymal lesions. Functional outcomes were favorable even in patients with extensive CVST and parenchymal lesions at presentation. CONCLUSIONS: The extent of the sinus involvement correlates with the risk of brain lesions in patients with CVST, but additional factors might also contribute to their occurrence.

Successful recovery from carotid terminus occlusion after mechanical embolectomy in a fully anticoagulated patient.

CASE DESCRIPTION: We describe a case of the patient with multiple contraindications for thrombolysis who underwent successful mechanical embolectomy for occlusion of the right carotid terminus. Her pre-procedural NIHSS was 16. DISCUSSION: The patient demonstrated remarkable recovery within an hour of the procedure, and this clinical improvement was sustained at followup. RESULTS: This case illustrates that mechanical embolectomy is a safe and potentially very effective intervention to treat major intracranial vessel occlusions in patients with multiple contraindications for thrombolysis.

Massive tongue swelling in refractory status epilepticus treated with high-dose pentobarbital.

INTRODUCTION: The potential causes of acquired macroglossia are extensive. The authors report two cases of subacute marked tongue swelling resulting in airway compromise in patients with refractory status epilepticus requiring prolonged pentobarbital coma. METHOD: The hospitalization histories of the reported patients were retrospectively reviewed. RESULT: The tongue swelling completely resolved in one case and significantly improved in the other after discontinuation of pentobarbital infusion or switching to phenobarbital. The authors speculate that the causes were multifarious, likely a combination of localized angioedema due to barbiturate vehicle and triggered by an initial tongue bite. CONCLUSION: Progressive tongue swelling causing airway obstruction can occur well beyond the acute phase of status epilepticus and may potentially cause problems with extubation in nontracheotomized patients.

Medical management of cerebral vasospasm: present and future.

Cerebral vasospasm is one of the major complications of subarachnoid hemorrhage. The delayed occurrence of this complication allows for preventive management and early therapeutic interventions. Yet, accurate and timely diagnosis remains challenging and therapeutic options are rather limited. This review discusses new developments in the diagnosis and medical management of cerebral vasospasm made possible by technological advances and growing understanding of the complex pathophysiology of this disorder. CT protocols including CT perfusion and MRI with diffusion and perfusion sequences are increasingly employed in the evaluation of patients with suspected vasospasm. These radiological studies can add important information to that provided by transcranial Doppler and conventional angiography. Nimodipine for the prevention of delayed functional sequelae and hemodynamic augmentation therapy for the treatment of symptomatic vasospasm remains the mainstay of medical management. Novel strategies under investigation include the use of endothelin receptor antagonists, magnesium sulphate and statins. The value of albumin is being formally studied in an ongoing trial. Interventions to enhance nitric oxide may prove viable in the near future.

Predictors of outcome in warfarin-related intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) associated with warfarin sodium therapy is becoming more common as the use of this medication increases in the aging population. OBJECTIVE: To delineate factors associated with early mortality, determine variables responsible for poor functional outcome, and evaluate possible reasons for expansion of hemorrhage and associated parenchymal edema. DESIGN: Retrospective study of clinical and radiologic information for 88 patients with warfarin-associated ICH. SETTING: A single hospital. Patients Eighty-eight consecutive patients with warfarin-associated ICH. METHODS: Patients were included if the international normalized ratio (INR) at presentation with ICH was 1.5 or greater. Computed tomographic scans were reviewed for volumetric analysis of hematoma and perihematomal edema volume. Outcome variables included 7-day mortality, hematoma enlargement, and functional outcome based on the modified Rankin Scale score. RESULTS: Seven-day mortality (39.8%) was associated with a lower Glasgow Coma Scale sum score and larger ICH volume at presentation. Univariate analysis revealed that a lower Glasgow Coma Score sum score, larger initial ICH volume, higher initial and 48-hour maximum glucose concentrations, and higher percentage of ICH expansion were significantly associated with poor functional outcome at hospital discharge. At multivariate analysis, only Glasgow Coma Score and ICH volume remained significantly associated with functional outcome measured at hospital discharge and at the last follow-up visit. Conversely, INR at presentation, time to INR correction, initial blood pressure, and enlargement of edema were not associated with functional outcome either at hospital discharge or at the last follow-up. Neither serum glucose concentration at admission nor highest level during the first 48 hours had any correlation with ICH or parenchymal edema enlargement. In addition, neither initial INR nor time to INR correction correlated with expansion of ICH or parenchymal edema. CONCLUSIONS: Lower level of consciousness at presentation and larger initial ICH volume predict poor prognosis in patients with warfarin-associated ICH. In our study population, INR at presentation was not associated with functional outcome.

Restarting anticoagulation therapy after warfarin-associated intracerebral hemorrhage.

BACKGROUND: Reinitiating warfarin sodium therapy in a patient with a recent warfarin-related intracerebral hemorrhage (WAICH) is a difficult clinical decision. Therefore, it is important to assess the outcome of resumption or discontinuation of warfarin therapy after WAICH. OBJECTIVE: To compare patients who survived an episode of WAICH and restarted warfarin therapy with a group of WAICH patients who did not resume warfarin therapy. Design, Setting, and Patients We conducted a follow-up study from November 1, 2001, through December 31, 2005, in a cohort from a single center. Long-term outcome was assessed at last clinical follow-up or via questionnaire. MAIN OUTCOME MEASURES: Recurrent WAICH and thromboembolic events. RESULTS: Fifty-two patients were discharged from the hospital after a diagnosis of WAICH. Four patients were lost to follow-up. Mean follow-up among all patients was 43 (range, 1-108) months. Of the 23 patients who restarted warfarin therapy, 1 had a recurrent nontraumatic WAICH, 2 had traumatic intracerebral hemorrhages, and 2 had major extracranial hemorrhages. Of the 25 patients who did not restart warfarin therapy, 3 had a thromboembolic stroke, 1 had a pulmonary embolus, and 1 had a distal arterial embolus. CONCLUSIONS: Restarting warfarin therapy in patients with a recent WAICH is associated with a low risk of recurrence, but patients are subjected to known, substantial risks of warfarin use. Withholding warfarin therapy is associated with a risk of thromboembolization.

Rate of arterial occlusion in patients with acute ischemic stroke.

OBJECTIVE: Computed tomographic angiography (CTA) was invented more than 20 years ago, but only gained acceptance recently, thanks to advancements in the computer technology. It can demonstrate areas of arterial stenosis or occlusion with accuracy nearly that of digital subtraction angiography (DSA). It is also able to clearly illustrate calcification, which is more difficult to define on magnetic resonance angiography and is not clearly depicted on DSA. METHODS: Our retrospective study attempted to clarify the rate of occlusion or stenosis in the patients with acute ischemic stroke. RESULTS: Over the period of 7 months, 93 consecutive patients were admitted with acute ischemic stroke. Fifty-six patients underwent CTA and were included in this study. Most of the patients were admitted after 6 hours following onset of symptoms. There were 28 men and 28 women, and 80.4% of the cohort was of African-American origin. The majority of strokes were attributed to small-vessel disease (25/56). The rest of the cases were deemed secondary to atheroembolism (15/56), cardioembolism (9/56) or of unclear etiology (7/56). In 24 (42.9%) patients, CTA failed to reveal any abnormalities of the cerebrovascular tree. CTA demonstrated arterial occlusion in ten (17.9%) patients and stenosis of extracranial or intracranial arteries on the symptomatic side in 22 (39.2%) patients. There was very good correlation between CTA and ultrasound techniques (carotid duplex and transcranial Doppler). CTA was superior in demonstrating distal intracranial stenosis. CONCLUSION: Overall, CTA is an extremely valuable and fast way to emergently evaluate the cerebrovascular anatomy, making it very useful for pre-thrombolysis evaluation of patients with ischemic stroke.

Following the clot in spectacular shrinking deficit.

A subset of patients with major cerebral hemispheric ischemia due to distal internal carotid artery or proximal middle cerebral artery occlusion has rapid spontaneous improvement of neurologic deficits. This phenomenon has been designated the "spectacular shrinking deficit." A 79-year-old woman had the sudden onset of neurologic deficits consistent with a large right middle cerebral artery territory infarct. Serial multimodality imaging studies documented distal propagation and fragmentation of a proximal middle cerebral artery thrombus coinciding with rapid clinical improvement. Spectacular shrinking deficit provides a unique insight into the underlying characteristics of a patient population not treated with thrombolytics with impressive recovery from major hemispheric ischemia.

Prolonged refractory status epilepticus related to thrombotic thrombocytopenic purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is an extremely rare cause of status epilepticus. Review of literature demonstrated only four cases of brief status epilepticus (SE) associated with TTP. CASE: We describe a young woman with yet incomplete neurological recovery after prolonged refractory status epilepticus. Management required pentobarbital-induced coma for 60 days. Five months after onset, she was conversant and oriented with continued neuromuscular deficits. CONCLUSIONS: This is an unusual presentation of severe refractory SE associated with TTP. With aggressive life support and prolonged pentobarbital infusion, however, survival and the chance of meaningful recovery appear to be possible.

Antiepileptic drugs in aneurysmal subarachnoid hemorrhage.

Seizures may occur during or soon after rupture of an intracranial aneurysm. The use of antiepileptic drugs (AEDs) is a controversial issue. The overall conclusions from 2 recent studies in aneurysmal subarachnoid hemorrhage are that 1) many patients receive AEDs but should not; 2) long-term use is associated with worse outcome; and 3) short-term use is safer. Phenytoin may not be the first choice for seizure prophylaxis; newer AEDs such as levetiracetam might be more helpful in prevention and treatment of seizures.

Primary systemic amyloidosis with ischemic stroke as a presenting complication.

BACKGROUND: Amyloidosis is an uncommon disorder that ultimately leads to fatal multiorgan failure. Ischemic strokes have been sporadically described but are not well characterized. The purpose of this study was to review the pathophysiologic relationship between primary systemic amyloidosis and ischemic stroke, and to determine how often stroke is the first defining manifestation. METHODS: Retrospective study of 49 patients with confirmed primary amyloidosis and ischemic stroke. All included patients had biopsy proven amyloidosis. RESULTS: Forty patients were included in the study. Ischemic strokes occurred in 13 patients (32.5%) as the initial presentation of amyloidosis. Patients with initial stroke presentation had the worst outcome, with average survival of 6.9 months after established diagnosis with amyloidosis; strokes developed 9.6 months before diagnosis with primary amyloidosis. Thirty-seven percent experienced recurrent ischemic stroke. The majority (70%) of patients had cardioembolic infarctions. CONCLUSIONS: Ischemic stroke is an underappreciated complication of primary amyloidosis. In the absence of obvious clinical and cardiogenic manifestations, primary amyloidosis should be considered when echocardiography demonstrates thickening of the valves, restrictive pattern, and increased echogenicity. Ischemic strokes as an initial presentation of primary amyloidosis carries a worse prognosis.

Subarachnoid hemorrhage as a presentation of basilar artery dissection.

INTRODUCTION: Subarachnoid hemorrhages caused by intracranial dissections are rare. The management of dissections in these cases not clear. METHODS: Case report. RESULTS: An 82-year-old woman presented with acute drowsiness and vomiting. CT scan demonstrated extensive subarachnoid hemorrhage and hydrocephalus that subsequently required placement of ventriculoperitoneal shunt. Angiography revealed extensive basilar artery dissection and no aneurysms. The dissection did not produce a critical stenosis and, taking into consideration that the patient had a previous occlusion of her distal left vertebral artery, it was decided to manage the patient conservatively. On a 3-month follow-up, the patient was free of recurrent events. CONCLUSION: Basilar artery dissection can present with subarachnoid hemorrhage. No guidelines are available for management of basilar artery dissections and treatment should be tailored to the individual patient.

Bilateral internal carotid artery occlusions resulting in near total acute brain infraction.

INTRODUCTION: Acute bilateral acute carotid arteries occlusion is a very rare condition. We describe a patient with initial right middle cerebral artery syndrome who developed coma and quadriplegia 1 h after thrombolysis with intravenous tPA and was found to have bilateral cervical internal carotid artery occlusion.

Signal transduction pathways in cerebral vasospasm.

Cerebral vasospasm is a deadly complication following the rupture of intracranial aneurysms. The time course of cerebral vasospasm is unique in that it is slow developing, usually takes 4-7 days to peak, but lasts up to 2-3 weeks, and is resistant to most known vasodilators. These special features make cerebral vasospasm the most important determinant in the outcome of patients suffering subarachnoid hemorrhage. The available treatment strategies include mechanical dilation of spastic cerebral arteries (angioplasty) and non-selective vasodilatation such as by Ca(2+) channel blockers. One new development in the experimental treatment of cerebral vasospasm is the looming target of signaling pathways. Understanding vasospastic signals in cerebral arteries might offer a new avenue for selective treatment of cerebral vasospasm in the future.

Preliminary study of the effects of caspase inhibitors on vasospasm in dog penetrating arteries.

This preliminary study was undertaken to explore the possible protective effect of caspase inhibitors Z-VDVAD-FMK and Z-DEVD-FMK in apoptosis and vasospasm in penetrating arteries during cerebral vasospasm. Experimental subarachnoid hemorrhage (SAH) was induced in 16 dogs by an intracisternal injection of autologous arterial blood (0.4 ml/kg) on Day 0 and Day 2. The dogs were then randomly divided into four groups: control-SAH, vehicle-control, and two treatment groups. In the treatment groups, caspase inhibitors (10 microM) were intracisternally injected each day beginning on Day 2 until Day 6. Effects of the inhibitors were analyzed utilizing angiography, the clinical status of the dogs (activity, appetite, and neurological deficits), and transmission electron microscopy of the penetrating arteries. All the dogs were sacrificed on Day 7. In control-SAH and vehicle-control groups, severe angiographic vasospasm, poor clinical status, and penetrating vasospasm were registered in all the dogs. In the treatment groups, all the dogs developed angiographic vasospasm and vasospasm in penetrating arteries, however, with benign clinical statues. The occurrence of apoptosis in endothelial cells was reduced by caspase-2 but not by caspase-3 inhibitor. Caspase inhibitors failed to prevent vasospasm either in major or in penetrating arteries. The improvement of clinical scores by the caspase inhibitors may be related to their protection of the endothelial cells. Further investigations using more rigorous clinical scoring system and quantitative information on the degree of apoptosis in the vessels, as well as in the brain parenchyma are recommended.

Morphological changes of cerebral arteries in a canine double hemorrhage model.

Cerebral vasospasm is a major cause of morbidity and mortality in patients suffering from subarachnoid hemorrhage (SAH). Despite numerous studies, the pathogenesis of this deadly disorder is not clearly understood. Alterations in endothelial cells are a distinct morphological feature of cerebral vasospasm and some recent studies suggest that apoptosis might play a role in the cells' death. The goal of the present study is to examine the time course of apoptosis in endothelial cells of spastic cerebral arteries following experimental subarachnoid hemorrhage. Fifteen dogs were used in the present study. Twelve of them were divided into three groups (four per group) and subjected to a double-hemorrhage method of SAH. Following SAH, groups were sacrificed respectively on days 3, 5, and 7. Three dogs served as controls without blood injection. The basilar arteries were studied with the transmission electron microscopy and with angiography. Angiographic vasospasm began on day 3 and peaked on day 7. In morphologic studies, control dogs did not demonstrate apoptotic-like changes in endothelial cells of the basilar arteries. Beginning with day 3, apoptotic-like changes were noted in endothelial cells and consisted of condensation of peripheral nuclear chromatin, blebbing of the cell membrane, and condensation of the cytoplasm. Such changes progressed with time and were maximally developed by day 7. This is the first study that demonstrates the time course of apoptotic-like changes in the endothelial cells in the vasospastic basilar artery. Apoptosis might play an important role in the pathogenesis of vasospasm.