Harold P. Adams

Design of the Trial of Org 10172 in Acute Stroke Treatment (TOAST)

TOAST is a multicenter, randomized, placebo-controlled clinical trial testing the usefulness of a new antithrombotic drug in improving the outcome of persons with acute ischemic stroke. Until recently, no clinical trial testing a treatment for ischemic stroke had demonstrated efficacy in outcome. Design problems of previously conducted trials with inconclusive results may partly explain their failures. During the design of TOAST, the investigators addressed several issues so the trial could test the treatment accurately. We report the strategies used in designing, implementing, and coordinating the trial.

Effect of Cholesterol-Lowering Medications on Progression of Mild Atherosclerotic Lesions of the Carotid Arteries and on the Risk of Stroke

The Asymptomatic Carotid Artery Progression Study (ACAPS) compared the usefulness of lovastatin alone or in combination with warfarin in the prevention of 3-year progression of mean maximum intimal-me

Treatment of acute ischemic stroke : Selecting the right treatment for the right patient

At present, thrombolytic therapy is the only therapy approved for the treatment of acute brain injury among patients with ischemic stroke. While recombinant tissue plasminogen activator (rt-PA) is efficacious, its usefulness is limited, largely because of the very limited time window for its administration. Other medications that have potential neuroprotective actions or that affect coagulation or flow have not been established as efficacious or have not been approved by regulatory authorities. Additional therapies are needed to reduce the neurological consequences of ischemic stroke. Although the number of options to treat the stroke itself is limited, physicians should remember that management is multifaceted. Even if a patient cannot be treated with rt-PA, there is much that can be done to improve outcomes. Therapies of proven value are available to prevent or control complications, to augment recovery and to forestall recurrent stroke. The choice of treatment will continue to be made on a case-by-case basis and will be influenced by a number of variables. The most important factors are the time interval from stroke, the severity of the neurological impairments, the results of the baseline brain imaging and the cause of stroke.At present, thrombolytic therapy is the only therapy approved for the treatment of acute brain injury among patients with ischemic stroke. While recombinant tissue plasminogen activator (rt-PA) is efficacious, its usefulness is limited, largely because of the very limited time window for its administration. Other medications that have potential neuroprotective actions or that affect coagulation or flow have not been established as efficacious or have not been approved by regulatory authorities. Additional therapies are needed to reduce the neurological consequences of ischemic stroke. Although the number of options to treat the stroke itself is limited, physicians should remember that management is multifaceted. Even if a patient cannot be treated with rt-PA, there is much that can be done to improve outcomes. Therapies of proven value are available to prevent or control complications, to augment recovery and to forestall recurrent stroke. The choice of treatment will continue to be made on a case-by-case basis and will be influenced by a number of variables. The most important factors are the time interval from stroke, the severity of the neurological impairments, the results of the baseline brain imaging and the cause of stroke. Copyright

Spinal Cord Hemorrhage

BACKGROUND AND PURPOSE Spinal cord hemorrhages are rare conditions that can be classified based on the primary location of bleeding into intramedullary (hematomyelia), subarachnoid hemorrhage (SAH), subdural hemorrhage, and epidural hemorrhage. We conducted a literature review to better understand the presenting symptoms, etiology, diagnosis, and treatment of spinal cord hemorrhages. METHODS We performed a literature search using PubMed with the key words spinal hemorrhage, hematomyelia, spinal subarachnoid hemorrhage, spinal subdural hematoma, and spinal epidural hematoma RESULTS: Most commonly, spinal hematomas present with acute onset of pain and myelopathy but a more insidious course also may occur. Spinal SAH may be especially difficult as it may cause cerebral symptoms. The etiologies vary based on the type (location). The most common causes are trauma, iatrogenic causes, vascular malformations, and bleeding diatheses. Management is often aimed toward rapid surgical decompression and correction of the underlying etiology if possible. Conservative management, including administration of large doses of corticosteroids, reversal of anticoagulation, and close monitoring, has been used as bridging for surgical procedure or as the mainstay of treatment for patients with mild or improving symptoms. CONCLUSIONS The variable and overlapping presentations of spinal cord hemorrhages make the diagnosis challenging. Maintaining high levels of clinical suspicion and utilizing magnetic resonance imaging may help in making the right diagnosis. Future studies should aim to create standardized outcome grading system and management guidelines for patients with spinal hemorrhage.

The NIHSS Supplementary Motor Scale: A Valid Tool for Multidisciplinary Recovery Trials

Background: There is a growing interest in therapies that may augment motor recovery that could be initiated in the acute stroke unit and maintained through the rehabilitation period. Homogenization of the currently fragmented stroke clinicometrics is necessary before such multidisciplinary trials can be conducted. The supplementary motor scale of the NIH Stroke Scale (SMS-NIHSS) is a simple and reliable scale for assessing proximal and distal motor function in the upper and lower extremities. We hypothesized that the currently underutilized SMS-NIHSS is a valid tool for assessing motor recovery with prognosticative value. Methods: We performed an analysis of SMS-NIHSS scores recorded in 1,281 patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). We plotted the probability of a favorable outcome (FO) and very favorable outcome (VFO) at 3 months based on the baseline SMS-NIHSS scores. In order to better study the relationship between SMS-NIHSS and 3-month functional outcome, we performed multivariate logistic regression analyses using both FO and VFO as outcome measures. Analyses were adjusted for potential confounders such as age, sex, side of the lesion, time from symptom onset to emergency room arrival, temperature, systolic blood pressure, blood glucose level and treatment group assignment (ORG 10172 vs. placebo). We also calculated the Spearman correlation coefficient between the SMS-NIHSS, Barthel Index (BI) and Glasgow Outcome Score (GOS) obtained at the 3-month visit. Results: The mean SMS-NIHSS scores were 8.18 at baseline and 4.68 at 3 months. The SMS-NIHSS scores showed a gradual improvement during the first 3 months after stroke. There was a linear relationship between the baseline SMS-NIHSS scores and the probability of an FO or VFO at 3 months. The SMS-NIHSS baseline score was an independent predictor of FO (OR = 0.86; 95% CI 0.84-0.87; p < 0.0001) and VFO (OR = 0.85; 95% CI 0.84-0.87; p < 0.0001) at 3 months after adjusting for confounders. The degree of improvement in the SMS-NIHSS scores from baseline to 3 months was also independently associated with FO and VFO (p < 0.0001). At 3 months, SMS-NIHSS scores showed a strong correlation with the BI (r = -0.70; p < 0.0001) and GOS (r = 0.73; p < 0.0001). Conclusions: The SMS-NIHSS is a valid scale for assessing motor recovery with prognosticative value, and may be sensitive to changes during recovery. Given that the SMS-NIHSS is an extension of the widely accepted NIHSS, it could be easily implemented in trials conducted in a variety of clinical research settings, including acute stroke hospitals and rehabilitation units.

Aneurysmal Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) accounts for 5% to 10% of all strokes and, unlike most other types of stroke, has not declined in incidence during the last 30 years. The leading cause of SAH, accounting for approximately 80% of cases, is rupture of an intracranial saccular aneurysm. This distinction is important, because patients with bleeding secondary to ruptured saccular aneurysms have a poorer prognosis and present more complicated management problems than patients with SAH of other causes.

Chapter 3 Etiologies and Mechanisms of Ischemia

Publisher Summary This chapter describes the etiologies and mechanisms of ischemia. Arterial lesions can cause stroke through two basic mechanisms: hypoperfusion and artery-to-artery embolism. Hypoperfusion results from a stenotic area that compromises the distal blood flow. This area of lumen reduction can result from a lesion of the arterial wall, dissection, compression of the vessel or arterial vasospasm. In addition, arterial lesions can also cause stroke through migration of either thrombus or fragments of an intrinsic arterial lesion, a mechanism leading to artery-to-artery embolism. Stroke may result from several cardiac problems including disturbances in the cardiac rhythm, valvular disease, cardiac wall motion abnormalities, cardiac tumors, endocarditis, and right-to-left shunt facilitating paradoxical embolization. Cardiac abnormalities causing stroke have been classified as “high-risk” and “medium-risk,” depending on the perceived risk for embolism. Hematological disorders are a relatively uncommon cause of stroke in the general population; however, they are more relevant in younger patients. Ischemic stroke can also result from systemic hypoperfusion, which can be the consequence of pump failure, hypovolemia, or vasodilatation.