Acute cerebral ischemia in a critical care unit. A review of diagnosis and management.

With an increasing understanding of the pathophysiology of human brain ischemia, it appears that time is of critical essence in the diagnosis and management of the acute stroke victim. A review of the acute ischemic stroke patient in an intensive care setting is described. Recent knowledge of clinical stroke assessment is summarized, with further emphasis on in-hospital strokes. Acute stroke units are described with a focus on the general clinical approach to patients with acute cerebral ischemia: investigations, recent treatment advances, and rehabilitation. Unless patients with acute brain ischemia are given the opportunity for aggressive management, care, and enrollment into promising therapeutic protocols, ideally within an acute stroke unit setting, the tremendous burden of stroke will not be lifted.

A modified National Institutes of Health Stroke Scale for use in stroke clinical trials: preliminary reliability and validity.

BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) is accepted widely for measuring acute stroke deficits in clinical trials, but it contains items that exhibit poor reliability or do not contribute meaningful information. To improve the scale for use in clinical research, we used formal clinimetric analyses to derive a modified version, the mNIHSS. We then sought to demonstrate the validity and reliability of the new mNIHSS. METHODS: The mNIHSS was derived from our prior clinimetric studies of the NIHSS by deleting poorly reproducible or redundant items (level of consciousness, face weakness, ataxia, dysarthria) and collapsing the sensory item into 2 responses. Reliability of the mNIHSS was assessed with the certification data originally collected to assess the reliability of investigators in the National Institute of Neurological Disorders and Stroke (NINDS) rtPA (recombinant tissue plasminogen activator) Stroke TRIAL: Validity of the mNIHSS was assessed with the outcome results of the NINDS rtPA Stroke Trial: RESULTS: Reliability was improved with the mNIHSS: the number of scale items with poor kappa coefficients on either of the certification tapes decreased from 8 (20%) to 3 (14%) with the mNIHSS. With the use of factor analysis, the structure underlying the mNIHSS was found identical to the original scale. On serial use of the scale, goodness of fit coefficients were higher with the mNIHSS. With data from part I of the trial data, the proportion of patients who improved >/=4 points within 24 hours after treatment was statistically significantly increased by tPA (odds ratio, 1.3; 95% confidence limits, 1.0, 1.8; P=0.05). Likewise, the odds ratio for complete/nearly complete resolution of stroke symptoms 3 months after treatment was 1.7 (95% confidence limits, 1.2, 2.6) with the mNIHSS. Other outcomes showed the same agreement when the mNIHSS was compared with the original scale. The mNIHSS showed good responsiveness, ie, was useful in differentiating patients likely to hemorrhage or have a good outcome after stroke. CONCLUSIONS: The mNIHSS appears to be identical clinimetrically to the original NIHSS when the same data are used for validation and reliability. Power appears to be greater with the mNIHSS with the use of 24-hour end points, suggesting the need for fewer patients in trials designed to detect treatment effects comparable to rtPA. The mNIHSS contains fewer items and might be simpler to use in clinical research trials. Prospective analysis of reliability and validity, with the use of an independently collected cohort, must be obtained before the mNIHSS is used in a research setting.

Clinical deterioration following improvement in the NINDS rt-PA Stroke Trial.

BACKGROUND AND PURPOSE: Little is known in regard to cerebral arterial reocclusion after successful thrombolysis. In the absence of arteriographic information, the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial investigators prospectively identified clinical deterioration following improvement (DFI) as a possible surrogate marker of cerebral arterial reocclusion after rt-PA-induced recanalization. Also, we identified any significant clinical deterioration (CD) even if not preceded by improvement. This observational analysis was designed to determine the incidence of DFI and CD in each treatment group, to identify baseline or posttreatment variables predictive of DFI or CD, and to determine any relationship between DFI, CD, and clinical outcome. METHODS: DFI was defined as any 2-point deterioration on the NIH Stroke Scale after an initial 2-point improvement after treatment. CD was defined as any 4-point worsening after treatment compared with baseline. All data were collected prospectively by investigators blinded to treatment allocation. A noncontrast brain CT was mandated when a 2-point deterioration occurred. All cases were validated by a central review committee. RESULTS: DFI was identified in 81 of the 624 patients (13%); 44 were treated with rt-PA and 37 were treated with placebo (P:=0.48). DFI occurred more often in patients with a higher baseline NIH Stroke Scale score. CD within the first 24 hours occurred in 98 patients (16% of all patients); 43 were given rt-PA and 55 were given placebo (P:=0.19). Baseline variables associated with CD included a less frequent use of prestroke aspirin and a higher incidence of early CT changes of edema or mass effect or dense middle cerebral artery sign. Patients with CD had higher rates of increased serum glucose and fibrin degradation products, and they also had higher rates of symptomatic intracranial hemorrhage and death. Patients who experienced either DFI or CD were less likely to have a 3-month favorable outcome. CONCLUSIONS: We found no association between DFI, CD, and rt-PA treatment, and no clinical evidence to suggest reocclusion. Deterioration was strongly associated with stroke severity and poor outcome and was less frequent in patients whose stroke occurred while they were on aspirin.

Finding the most powerful measures of the effectiveness of tissue plasminogen activator in the NINDS tPA stroke trial.

BACKGROUND AND PURPOSE: We sought to identify the most powerful binary measures of the treatment effect of tissue plasminogen activator (tPA) in the National Institute of Neurological Disorders and Stroke (NINDS) rTPA Stroke Trial. METHODS: Using the Classification and Regression Tree (CART) algorithm, we evaluated binary cut points and combination of binary cut points with the 4 clinical scales and head CT imaging measures in the NINDS tPA Stroke Trial at 4 times after treatment: 2 hours, 24 hours, 7 to 10 days, and 3 months. The first analysis focused on detecting evidence of "early activity" of tPA with the use of outcome measures derived from the 2-hour and 24-hour clinical and radiographic measures. The second analysis focused on longer-term outcome and "efficacy" and used outcome measures derived from 7- to 10-day and 3-month measures. After identifying the cut points with the ability to classify patients into the tPA and placebo groups using part I data from the trial, we then used data from part II of the trial to validate the results. RESULTS: Of the 5 most powerful outcome measures for early activity of tPA, 4 involved the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours or changes in the NIHSS score from baseline to 24 hours. The best overall single outcome measure was an NIHSS score

Migraine-related stroke in the context of the International Headache Society classification of head pain.

The diagnosis of migraine-related stroke is reviewed and illustrative case histories are provided. The International Headache Society classification of "migrainous cerebral infarction" is amplified and further categorized using strictly defined diagnostic criteria. True migraine-induced stroke is revealed as only one of a number of migraine-related stroke syndromes.

The spectrum of neurologic disease associated with antiphospholipid antibodies. Lupus anticoagulants and anticardiolipin antibodies.

Lupus anticoagulants and anticardiolipin antibodies are antiphospholipid immunoglobulins, predominantly of the IgG, IgM, or mixed class. Recently, these antiphospholipid autoantibodies have been associated with neurologic conditions including focal cerebral and ocular ischemia, the myelopathy of lupoid sclerosis and Degos' disease, Guillain-Barré syndrome, migraine, chorea, and seizures. We review the neurologic manifestations associated with this group of antibodies. Recognition of these conditions may lead to further insights into pathogenesis and therapy.

Altered brain energy metabolism in demented patients with multiple subcortical ischemic lesions. Working hypotheses.

We report the results of brain metabolic studies (using magnetic resonance spectroscopy) in three groups of individuals: (1) demented patients with multiple subcortical ischemic lesions (n = 18); (2) nondemented, age-matched controls (n = 21); and (3) demented patients with neurodegenerative disease, probably of the Alzheimer type (n = 19). Patients with dementia with subcortical vascular lesions, as demonstrated by appropriate imaging studies, had an increase of phosphate energy charge in areas of the cerebral cortex (especially prominent in the frontal regions) superficial to and excluded from the subcortical lesions. We hypothesize that this increased energy charge might be caused by reduced metabolic activity of disconnected brain tissue or by astrocytic hypertrophy and hyperplasia that accompanies subtle ischemic, cortical alterations.

Factors that predict antiphospholipid immunoreactivity in young people with transient focal neurological events.

OBJECTIVE: To determine if clinical or radiological features in young people with transient focal neurological events may be used to predict the presence of antiphospholipid antibodies (aPL). DESIGN: A combined retrospective and prospective study of young people with transient focal neurological events. Likelihood ratios and confidence intervals were calculated for the proportions; logistic regression analysis was performed to determine features predictive of aPL immunoreactivity. SETTING: A referral hospital and adjacent outpatient clinic. PATIENTS: Sixty-eight patients with one or more transient focal neurological events were screened for aPL. Forty-seven patients were obtained retrospectively from medical record review of every outpatient personally seen by two of us (G.E.T. and S.R.L.) during a 4.5-year period. Twenty-one patients were prospectively added prior to retrospective analysis. Patients older than 50 years or those with multiple sclerosis or epilepsy were excluded. Five patients fulfilling study criteria were excluded because aPL assay results were unavailable. MAIN OUTCOME MEASURES: Transient neurological symptoms, stroke risk factors, occurrence of cerebral or ocular infarct or death, headache history, and serological and radiological studies were systematically obtained. RESULTS: There were 29 aPL-positive patients compared with 39 aPL-negative ones. Features that distinguished the aPL-positive group included more common monocular visual symptoms (38% vs 15%, P = .03), hemisensory symptoms (76% vs 41%, P = .004), and systemic lupus erythematosus (14% vs 0%, P = .03) and less common binocular visual symptoms (28% vs 51%, P = .05), accompanying headache (66% vs 87%, P = .03), and personal (48% vs 74%, P = .03) and family (29% vs 61%, P = .01) history of migraine. No differences were noted between the groups for age, gender, stroke risk factor profile, and radiological features. In a logistic regression analysis, the estimated odds ratio for aPL positivity in patients with monocular visual disturbance, hemisensory symptoms, and no family history of migraine were 5.3, 7.5, and 3.0, respectively, when controlling for the other variables. CONCLUSIONS: Several clinical features of transient focal neurological events in aPL-positive patients distinguish these individuals from their aPL-negative cohort. Amaurosis fugax, unilateral paresthesias, and no family history of migraine may predict aPL positivity in young persons with transient focal neurological deficits.

Recurrent stroke associated with thymoma and anticardiolipin antibodies.

A 44-year-old woman developed recurrent thrombotic cerebral cortical infarctions. IgG and IgM anticardiolipin antibodies were found, as was a thymoma. To our knowledge, these antiphospholipid antibodies, which may inhibit prostacyclin formation and alter platelet function, have not been previously associated with this thymic neoplasm, an association we believe is not coincidental.

Total quality improvement method for reduction of delays between emergency department admission and treatment of acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.

OBJECTIVE: To develop an approach for reducing time between emergency department (ED) admission and treatment in patients with acute ischemic stroke to meet the challenge of providing tissue plasminogen activator treatment within 180 minutes. DESIGN: An observational study. SETTING: Forty trial-affiliated hospitals, including 30 community hospitals. PARTICIPANTS: A total of 17,324 consecutive patients admitted to trial-affiliated hospital EDs within 24 hours of possible stroke, from January 1991 through October 1994. INTERVENTION: Appraisal of the process of triage, evaluation, diagnosis, and treatment by means of total quality improvement techniques in each hospital. Staff participating in the process identified sources of variation and modifications by flow charting the process. MAIN OUTCOME MEASURE: Time between ED admission and treatment with study medication. RESULTS: Total quality improvement methods identified hospital-specific process improvements. Many improvements were administrative, requiring no additional resources. More than 50% of screened patients arrived too late to be treated. Only 1268 patients were admitted between 0 and 125 minutes from stroke onset with no other trial exclusion criteria; 48% were treated. Of 243 patients admitted between 126 and 170 minutes from stroke onset with no exclusion criteria, 4% were treated. Mean time from ED admission to treatment was similar in teaching and community hospitals. CONCLUSIONS: Total quality improvement methods identified ED-specific sources of process variability and reduced time between ED admission and treatment. Therefore, these methods should be considered in developing and monitoring emergent stroke treatment protocols.

Common carotid artery occlusion.

Symptomatic common carotid artery occlusion (CCAO) is rare. We studied 17 patients with ischemic cerebrovascular symptoms and unilateral CCAO on angiography to help clarify clinical and radiologic features. Mean age was 62 years; 65% were women. Predominant symptoms and signs included visual-ipsilateral monocular or retrochiasmal symptoms (88%), motor weakness (88%), sensory disturbance (59%), dizziness/lightheadedness (53%), and syncope (24%). Dysarthria, headache, or involuntary limb shaking occurred less frequently. Positionally related symptoms occurred in approximately two-thirds of the patients. TIAs were often multiple and preceded a stroke or occurred without subsequent stroke in 82%. Hemispheric TIAs contralateral to the CCAO occurred in 41%. Ten patients (59%) suffered stroke, seven (70%) of which were ipsilateral to the CCAO. Vascular risk factors included cigarette use (76%), hypertension (71%), diabetes mellitus (41%), and hyperlipidemia (41%); 82% had two or more risk factors. Known cardiac disease was present in 59%. CCAO was present at the origin of the vessel in most patients. Most had atherosclerotic narrowing of multiple extracranial large vessels. During follow-up, none of the patients had a spontaneous second infarct; five had TIAs, including two with amaurosis fugax, all in the CCAO territory. More restricted external carotid collaterals may, in part, explain the higher frequency of ipsilateral stroke and contralateral TIAs than reported for internal carotid occlusion.

Large cerebral vessel occlusive disease in systemic lupus erythematosus.

We systematically investigated clinical, laboratory, radiologic, and pathologic features, including treatment and prognosis, of stroke syndromes in 30 patients, six from our institution and 24 from the literature, with systemic lupus erythematosus (SLE) and symptomatic large cerebral vessel occlusive disease, documented by angiography or autopsy. The average age at stroke onset was 35 years, and the diagnosis of SLE was made on average 4.4 years prior to that. At least 86% had active SLE at the time of their stroke. Headache was common at onset. We found major intracranial or extracranial vessel occlusive process by (1) thrombus, (2) dissection, (3) fibromuscular dysplasia or vasculitis, and (4) atherosclerosis. The presumed mechanisms were coagulopathy, cardiogenic embolism, large cerebral vessel vasculitis or occlusive vasculopathy, cervical arterial dissection, and premature atherosclerosis. The short-term death rate was 40% and the recurrent stroke rate was 13%. We conclude that symptomatic large cerebral vessel occlusive disease in SLE generally occurs several years after the diagnosis of SLE, usually during the active phase of the disease, is related to heterogeneous mechanisms, and carries a relatively poor short-term outcome.

The role of anticoagulation in cavernous sinus thrombosis.

Prior to the antibiotic (AB) era, cavernous sinus thrombosis (CST) was almost uniformly fatal. AB therapy has significantly reduced mortality, but additional treatment with anticoagulants (AC) has remained controversial. We reviewed our experience with seven cases, as well as the literature since Lyons' 1941 introduction of AC treatment, to determine effectiveness, complications, and morbidity among survivors. We divided the cases into (1) those treated with AB alone, and (2) those treated with a combination of AB and AC. We found no conclusive evidence for reduction of mortality when AC was used in combination with AB. However, early AC therapy reduced morbidity (blindness, stroke, ophthalmoplegia, hypopituitarism, focal seizures, and vascular steal syndrome), whereas delayed or inadequate use provided no apparent benefit above AB therapy alone. Complications of AC therapy were rare; cerebral venous thrombosis occurred frequently, but in association with dural sinus thrombosis as a direct result of the disease. We conclude that AC therapy is indicated early in the treatment of CST to reduce morbidity among survivors.

Cerebrovascular and neurologic disease associated with antiphospholipid antibodies: 48 cases.

Lupus anticoagulants and anticardiolipin antibodies are antiphospholipid antibodies (APLAb) with related antigenic specificities and are newly recognized markers for an increased risk of thrombosis. We studied 48 patients who presented with cerebral or visual dysfunction associated with APLAb to help clarify the diagnostic, clinical, laboratory, radiologic, and pathologic features in these patients. Most patients presented with transient cerebral ischemia or cerebral infarction. Recurrent and stereotypic events were frequent. Visual disturbances resulted from amaurosis fugax, retinal arterial or venous occlusion, occipital ischemia, diplopia, and migraine-like disturbances. Three patients presented with severe atypical classic migraine. Recurrent infarcts of brain and eye were significantly associated with the presence of cigarette smoking, hyperlipidemia, and a positive antinuclear antibody. During 44.4 patient-years of prospective follow-up, the combined stroke and systemic thrombotic event rate was 0.27 events per patient-year and was 0.54 events per patient-year if TIA and death were included. Forty (83%) of the patients did not have systemic lupus erythematosus (SLE). Thrombocytopenia was present in 15 (31%) and a false-positive VDRL in 11 (23%) of the patients. Cerebral angiography was normal or revealed large-vessel occlusion or stenosis without changes suggestive of vasculitis. Patients with only transient dysfunction generally had normal radiologic studies, including angiography. Organs and arterial vessels studied pathologically revealed thrombotic occlusive disease without vasculitis. APLAb are strongly associated with an immune-mediated thrombotic tendency, generally in the absence of SLE. Other stroke risk factors may add to the risk of recurrent ischemic events in patients with APLAb.

Intraluminal clot in the vertebrobasilar circulation: clinical and radiologic features.

We studied 15 patients with angiographically documented intraluminal clot in the vertebrobasilar (VB) circulation and ischemic stroke. Progressive brainstem signs were the most common presentation; the neurologic deficit was maximum at stroke onset in 4. Seven experienced their first symptoms during sedentary activities. Thirteen of the initial 15 CTs revealed infarcts in the VB territory, 7 with multiple foci. Intraluminal clot was present in the vertebral artery in 7 patients (2 bilateral), basilar artery in 7, posterior cerebral artery in 5, and superior cerebellar artery in 1. Multiple clots were seen in 5 patients. Stroke risk factors were present in the majority of cases. Although cardiac source embolism was the most common single etiology (4 patients), most patients had other causes including migraine, coagulopathy associated with malignancy and nephrotic syndrome in systemic lupus erythematosus, vertebral artery dissection with local embolism, delayed irradiation arteriopathy, and a fusiform, ectatic basilar artery. Six (40%) died within 5 months of follow-up. Intraluminal clot in the posterior circulation is a marker for multiple stroke mechanisms, not all of which are embolic. Intraluminal clot should prompt investigations into occult risk factors when no cause appears obvious.

Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 31 NMR spectroscopy.

We measured brain energy phosphate metabolism and intracellular pH (pHi) in a cross-sectional study of migraine patients by in vivo phosphorus 31 NMR spectroscopy. During a migraine attack the ratio ATP/total phosphate signal (mole % ATP) was preserved, but there was a decrease in mole % phosphocreatine (PCr) and an increase in mole % inorganic phosphate (Pi) resulting in a decrease of the PCr/Pi ratio, an index of brain phosphorylation potential. This was found in classic but not common migraine. Mole % Pi was also increased in combined brain regions between attacks. There was no alteration in brain pHi during or between attacks. Energy phosphate metabolism but not pHi appears disordered during a migraine attack.

Scintillating scotomata associated with internal carotid artery dissection: report of three cases.

We report three cases of cervical internal carotid artery (ICA) dissection, which presented with visual symptoms resembling the migraine aura. When prolonged and especially when associated with other neurologic symptoms, such transient and positive visual phenomena can be manifestations of ICA dissection that mimic migraine.

The effects of aging on cerebral blood flow in migraine.

We studied cerebral blood flow (CBF) with the 133xenon inhalation technique in 92 migraine patients (49 classic/complicated, 43 common), aged 19 to 85 years, in the headache-free period. We compared results to 49 control subjects, aged 22 to 80 years. CBF declined with age in both groups, but at a slower rate in migraine patients, a difference most pronounced in classic migraine. CBF was lower in migraine patients than in controls under 48 years of age. In addition, regional asymmetry of blood flow was found more frequently in young migraine patients than in controls. These results suggest that differences exist in cerebrovascular resistance tone in migraine patients, which may contribute to the threshold for a migraine attack and result in differing age-related changes in blood flow.

Sneddon's syndrome: an antiphospholipid antibody syndrome?

A 44-year-old woman with livedo reticularis, multiple ischemic strokes, and transient ischemic attacks (Sneddon's syndrome) had antiphospholipid antibodies--the lupus anticoagulant and anticardiolipin antibodies. This patient provides support for the hypothesis that these antibodies are involved in the pathogenesis of this rare but now potentially treatable disorder.

Cocaine-associated intracranial hemorrhage: absence of vasculitis in 14 cases.

Complications associated with the use of cocaine are varied, and include cerebral hemorrhage and ischemia, with vasculitis and vasospasm as possible etiologies. We reviewed selected brain samples from 14 autopsy cases of cocaine-related cerebrovascular disease. Intracerebral or subarachnoid hemorrhage was present in 12 cases. Intracranial arterioles were either normal or showed nonspecific changes. From these observations, we suggest that intracranial hemorrhages occur in the absence of readily detectable vascular abnormalities.