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Biomedical subjects

S C Cramer

Publications and source records attributed to S C Cramer.

At least 19 recordsLinked to original sources

Instructional treatment associated with changes in brain activation in children with dyslexia.

OBJECTIVE: To assess the effects of reading instruction on fMRI brain activation in children with dyslexia. BACKGROUND: fMRI differences between dyslexic and control subjects have most often involved phonologic processing tasks. However, a growing body of research documents the role of morphologic awareness in reading and reading disability. METHODS: The authors developed tasks to probe brain activation during phoneme mapping (assigning sounds to letters) and morpheme mapping (understanding the relationship of suffixed words to their roots). Ten children with dyslexia and 11 normal readers performed these tasks during fMRI scanning. Children with dyslexia then completed 28 hours of comprehensive reading instruction. Scans were repeated on both dyslexic and control subjects using the same tasks. RESULTS: Before treatment, children with dyslexia showed less activation than controls in left middle and inferior frontal gyri, right superior frontal gyrus, left middle and inferior temporal gyri, and bilateral superior parietal regions for phoneme mapping. Activation was significantly reduced for children with dyslexia on the initial morpheme mapping scan in left middle frontal gyrus, right superior parietal, and fusiform/occipital region. Treatment was associated with improved reading scores and increased brain activation during both tasks, such that quantity and pattern of activation for children with dyslexia after treatment closely resembled that of controls. The elimination of group differences at follow-up was due to both increased activation for the children with dyslexia and decreased activation for controls, presumably reflecting practice effects. CONCLUSION: These results suggest that behavioral gains from comprehensive reading instruction are associated with changes in brain function during performance of language tasks. Furthermore, these brain changes are specific to different language processes and closely resemble patterns of neural processing characteristic of normal readers.

Adolescent↗

Diffusion abnormalities in patients with Wernicke encephalopathy.

Diffusion-weighted imaging (DWI) can help to diagnose acute ischemic stroke. Other nonischemic disorders may show abnormal signals with DWI. The authors report two cases of Wernicke encephalopathy with DWI signal changes in characteristic midline locations, one with reduction in apparent diffusion constant and one without. DWI abnormalities may suggest early thiamine deficiency and are useful in diagnosing Wernicke encephalopathy.

Adult↗

Entry criteria and baseline characteristics predict outcome in acute stroke trials.

UNLABELLED: Background and Purpose-We sought to study the range of entry criteria and baseline characteristics in acute stroke trials and to understand their effects on patient outcomes. METHODS: -Randomized, placebo-controlled therapeutic trials in patients with acute ischemic stroke were identified. Entry criteria, baseline clinical characteristics, and outcome were extracted for the placebo group of each trial. The relationship between key variables was then determined. RESULTS: -Across 90 placebo groups identified, there was great variation in entry criteria and outcome measures. This was associated with divergent outcomes; for example, in some studies most placebo group patients died, while in other studies nearly all had no disability. Entry criteria were significantly correlated with outcome; for example, higher age cutoff for study entry correlated with 3-month mortality. Entry criteria also predicted baseline clinical characteristics; for example, wider time window for study entry correlated directly with time to treatment and inversely with stroke severity (initial National Institutes of Health Stroke Scale score). Baseline characteristics predicted outcome. Greater stroke severity predicted higher 3-month mortality rate; despite this, successful thrombolytic trials have enrolled more severe strokes than most trials. The mean age of enrollees also predicted 3-month mortality and was inversely related to percentage of patients with 3-month Barthel Index score >/=95. The strongest predictors of 3-month mortality were obtained with multivariate models. CONCLUSIONS: -Acute stroke studies vary widely in entry criteria and outcome measures. Across multiple studies, differences in entry criteria, and the baseline clinical characteristics they predict, influence patient outcomes along a continuum. In some studies, enrolling a specific subset of patients may have improved the chances of identifying a treatment-related effect, while in others, such chances may have been reduced. These findings may be useful in the design of future stroke therapeutic trials.

Acute Disease↗

Treatment with tissue plasminogen activator and inpatient mortality rates for patients with ischemic stroke treated in community hospitals.

BACKGROUND AND PURPOSE: Most analyses of intravenous tissue plasminogen activator (IV tPA) use for acute stroke in routine practice have been limited by sample size and generally restricted to patients treated in large academic medical facilities. In the present study, we sought to estimate among community hospitals the use of IV tPA and to identify factors associated with the use of IV tPA and inpatient mortality. METHODS: We evaluated a retrospective cohort of 23 058 patients with ischemic stroke from 137 community hospitals. RESULTS: Three hundred sixty-two (1.6%) patients were treated with IV tPA, and 9.9% of those patients died during the hospitalization period. In 35.0% of the hospitals, no patients were treated with IV tPA, whereas 14.6% of hospitals treated approximately 3.0% with IV tPA. After control for multiple factors, younger patients, more severely ill patients (OR 2.02, 95% CI 1.36 to 3.01), and patients treated in rural hospitals (OR 1.80, 95% CI 0.99 to 3.26) were more likely to receive IV tPA, whereas black patients were less likely (OR 0.54, 95% CI 0.31 to 0.95). There also was a trend showing that women were less likely to receive IV tPA (OR 0.84, 95% CI 0.69 to 1.03). Factors associated with an increased odds of inpatient mortality included receipt of IV tPA among men (OR 2.81, 95% CI 1.72 to 4.58) and increased age. Black patients were 27% less likely to die during hospitalization (95% CI 0.60 to 0.90). CONCLUSIONS: In this large, retrospective evaluation of community hospital practice, the use IV tPA and inpatient mortality rates among IV tPA-treated patients were consistent with those of other studies. The likelihood of receiving IV tPA varies by race, age, disease severity, and possibly gender. These factors may influence mortality rates.

Aged↗

Changes in motor cortex activation after recovery from spinal cord inflammation.

Diseases of the spinal cord are associated with reactive changes in cerebral cortex organization. Many studies in this area have examined spinal cord conditions not associated with recovery, making it difficult to consider the value of these cortical events in the restoration of neurological function. We studied patients with myelitis, a syndrome of transient spinal cord inflammation, in order to probe cortical changes that might contribute to recovery after disease of the spinal cord. Seven patients, each of whom showed improvement in hand motor function after a diagnosis of myelitis involving cervical spinal cord, were clinically evaluated then studied with functional MRI. During right and left index finger tapping, activation volumes were assessed in three cortical motor regions within each hemisphere. Results were compared with findings in nine control subjects. Compared to the control group, myelitis patients had larger activation volumes within contralateral sensorimotor as well as contralateral premotor cortex. The degree of daily hand use showed a significant correlation with the volume of activation in contralateral sensorimotor cortex. Recovery from myelitis is associated with an enlarged activation volume in contralateral motor cortices. This change in motor cortex function is related to behavioral experience, and thus may contribute to motor improvement. The expanded activation in motor cortex, seen with several forms of spinal cord insult may have maximal utility when corticospinal tract axons are preserved.

Adult↗

A functional MRI study of three motor tasks in the evaluation of stroke recovery.

Functional brain imaging studies have provided insights into the processes related to motor recovery after stroke. The comparative value of different motor activation tasks for probing these processes has received limited study. We hypothesized that different hand motor tasks would activate the brain differently in controls, and that this would affect control-patient comparisons. Functional magnetic resonance imaging (MRI) was used to evaluate nine control subjects and seven patients with good recovery after a left hemisphere hemiparetic stroke. The volume of activated brain in bilateral sensorimotor cortex and four other motor regions was compared during each of three tasks performed by the right hand: index-finger tapping, four-finger tapping, and squeezing. In control subjects, activation in left sensorimotor cortex was found to be significantly larger during squeezing as compared with index-finger tapping. When comparing control subjects with stroke patients, patients showed a larger volume of activation in right sensorimotor cortex during index-finger tapping but not with four-finger tapping or squeezing. In addition, patients also showed a trend toward larger activation volume than controls within left supplementary motor area during index-finger tapping but not during the other tasks. Motion artifact was more common with squeezing than with the tapping tasks. The choice of hand motor tasks used during brain mapping can influence findings in control subjects as well as the differences identified between controls and stroke patients. The results may be useful for future studies of motor recovery after stroke.

Adult↗

Decreased diffusion in central pontine myelinolysis.

Two patients with central pontine myelinolysis (CPM) were studied with diffusion-weighted MR imaging 1 week after onset of tetraplegia. In both patients, affected white matter showed hyperintensity on diffusion-weighted images associated with a decrease in apparent diffusion coefficient (ADC) values. In one patient studied serially, ADC values normalized by 3 weeks after tetraplegia. Early in the clinical course, diagnosis of CPM can sometimes be difficult. Hyperintensity on diffusion-weighted images may therefore have diagnostic utility. Decreased lesional ADC values support the notion that CPM is a consequence of relative intracellular hypotonicity.

Adult↗

Mapping clinically relevant plasticity after stroke.

After stroke, patients show a wide range in the degree of recovery. Recovery occurs on the basis of discrete physiologic events. Identifying and measuring these events will be useful for a better understanding of stroke recovery mechanisms. The most extensive experience mapping these events has been with positron emission tomography, functional magnetic resonance imaging, and transcranial magnetic stimulation. This article reviews brain mapping studies that have examined stroke recovery. Serial assessment of patients during recovery raises the need for control studies evaluating the effect of intra-subject variability over time. The clearest insights into the significance of bilateral activation during unilateral movements by the stroke-affected hand will come from studies that include bilateral electromyographic measurements. Most brain imaging studies have focused on patients with very good recovery; further study of patients with a wide range of outcomes is needed. The described brain mapping methods have complementary strengths. Insights into the biological basis of recovery may best be achieved when results are considered together. With the advent of treatments targeting stroke recovery, measurement of post-stroke restorative events may also have value as a surrogate end point in clinical trials.

Animals↗

Recovery recapitulates ontogeny.

Several studies support the hypothesis that after stroke, specific features of brain function revert to those seen at an early stage of development, with the subsequent process of recovery recapitulating ontogeny in many ways. Many clinical characteristics of stroke recovery resemble normal development, particularly in the motor system. Consistent with this, brain-mapping studies after an ischemic insult suggest re-emergence of childhood organizational patterns: recovery being associated with a return to adult patterns. Experimental animal studies demonstrate increased levels of developmental proteins, particularly in the area surrounding an infarct, suggesting an active process of reconditioning in response to cerebral ischemia. Understanding the patterns of similarity between normal development and stroke recovery might be of value in its treatment.

Adult↗

Predictors of mortality in stroke patients admitted to an intensive care unit.

OBJECTIVE: Improved pathophysiologic insight and prognostic information regarding in-hospital risk of mortality among stroke patients admitted to an intensive care unit. DESIGN: Retrospective analysis. SETTING: Neurology/neurosurgery intensive care unit in a tertiary care university medical center. PATIENTS: A total of 63 consecutive ischemic stroke patients. INTERVENTIONS: Patients were classified according to in-hospital mortality. Charts were reviewed to retrospectively generate an admitting Acute Physiology and Chronic Health Evaluation (APACHE) II score. The APACHE II score and its individual components were assessed for predicting subsequent death. MEASUREMENTS AND MAIN RESULTS: Of 63 patients, 13 died and 50 survived to either discharge or surgical intervention. The mean admitting APACHE II score of survivors (6.9) was lower than that of patients who died (17.2; p < .0001). None of the 33 patients with a score <9 died, compared with 43% of those with a score > or =9. A score > or =18 was uniformly associated with fatal outcome (n = 8). Univariate analysis identified APACHE II total score, Glasgow Coma Scale score, temperature, pH, and white blood cell count as significant predictors of death. Among multivariate logistic regression models examining the components of the APACHE II score, the model containing white blood cells, temperature, and creatinine best predicted death. CONCLUSIONS: Several features of the APACHE II score are associated with risk of death in this patient population. The findings suggest particular physiologic derangements that are associated with, and may contribute to, increased mortality in critically ill patients with acute ischemic stroke.

APACHE↗

A pilot study of somatotopic mapping after cortical infarct.

BACKGROUND AND PURPOSE: Animal studies have described remodeling of sensory and motor representational maps after cortical infarct. These changes may contribute to return of function after stroke. METHODS: Functional MRI was used to compare sensory and motor maps obtained in 35 normal control subjects with results from 2 patients with good recovery 6 months after a cortical stroke. RESULTS: During finger tapping in controls, precentral gyrus activation exceeded or matched postcentral gyrus activation in 40 of 42 cases. Patient 1 had a small infarct limited to precentral gyrus. Finger tapping activated only postcentral gyrus, a pattern not seen in any control subject. During tactile stimulation of a finger or hand in controls, postcentral gyrus activation exceeded or matched precentral gyrus activation in 11 of 14 cases. Patient 2 had a small infarct limited to postcentral gyrus and superior parietal lobule. Tactile stimulation of the finger activated only precentral gyrus, a pattern not seen in any control. In both patients, activation during pectoralis contraction was medial to the site activated during finger tapping. CONCLUSIONS: Results during finger tapping (patient 1) and finger stimulation (patient 2) may reflect amplification of a preserved component of normal sensorimotor function, a shift in the cortical site of finger representation, or both. Cortical map reorganization along the infarct rim may be an important contributor to recovery of motor and sensory function after stroke. Functional MRI is useful for assessing motor and sensory representational maps.

Adult↗

Activation of distinct motor cortex regions during ipsilateral and contralateral finger movements.

Previous studies have shown that unilateral finger movements are normally accompanied by a small activation in ipsilateral motor cortex. The magnitude of this activation has been shown to be altered in a number of conditions, particularly in association with stroke recovery. The site of this activation, however, has received limited attention. To address this question, functional magnetic resonance imaging (MRI) was used to study precentral gyrus activation in six control and three stroke patients during right index finger tapping, then during left index finger tapping. In each hemisphere, the most significantly activated site (P < 0.001 required) was identified during ipsilateral and during contralateral finger tapping. In the motor cortex of each hemisphere, the site activated during use of the ipsilateral hand differed from that found during use of the contralateral hand. Among the 11 control hemispheres showing significant activation during both motor tasks, the site for ipsilateral hand representation (relative to contralateral hand site in the same hemisphere) was significantly shifted ventrally in all 11 hemispheres (mean, 11 mm), laterally in 10/11 hemispheres (mean, 12 mm), and anteriorly in 8/11 hemispheres (mean, 10 mm). In 6 of 11 hemispheres, tapping of the contralateral finger simultaneously activated both the ipsilateral and the contralateral finger sites, suggesting bilateral motor control by the ipsilateral finger site. The sites activated during ipsilateral and contralateral hand movement showed similar differences in the unaffected hemisphere of stroke patients. The region of motor cortex activated during ipsilateral hand movements is spatially distinct from that identified during contralateral hand movements.

Brain Mapping↗

Stroke recovery. Lessons from functional MR imaging and other methods of human brain mapping.

The mechanisms underlying patient recovery after stroke remain incompletely understood. Human brain mapping methods such as functional MR imaging provide insights into stroke recovery mechanisms. After a unilateral brain insult, lasting changes take place in both hemispheres and along the rim of a cortical infarct. Such information may be of value in the design of therapies targeting stroke recovery.

Brain Mapping↗

Regional ischemia and ischemic injury in patients with acute middle cerebral artery stroke as defined by early diffusion-weighted and perfusion-weighted MRI.

BACKGROUND AND PURPOSE: We sought to map early regional ischemia and infarction in patients with middle cerebral artery (MCA) stroke and compare them with final infarct size using advanced MRI techniques. MRI can now delineate very early infarction by diffusion-weighted imaging (DWI) and abnormal tissue perfusion by perfusion-weighted imaging (PWI). METHODS: Seventeen patients seen within 12 hours of onset of MCA stroke had MR angiography, standard MRI, and PWI and DWI MRI. PWI maps were generated by analysis of the passage of intravenous contrast bolus through the brain. Cerebral blood volume (CBV) was determined after quantitative analysis of PWI data. Volumes of the initial DWI and PWI lesion were calculated and compared with a final infarct volume from a follow-up imaging study (CT scan or MRI). RESULTS: Group 1 (10 patients) had MCA stem (M1) occlusion by MR angiography. DWI lesion volumes were smaller than the volumes of CBV abnormality. In 7 patients the final stroke volume was larger or the same, and in 3 it was smaller than the initial CBV lesion. Group 2 (7 patients) had an open M1 on MR angiography with distal MCA stroke. In 6 group 2 patients, the initial DWI lesion matched the initial CBV abnormality and the final infarct. CONCLUSIONS: Most patients with M1 occlusion showed progression of infarction into the region of abnormal perfusion. In contrast, patients with open M1 had strokes consistent with distal branch occlusion and had maximal extent of injury on DWI at initial presentation. Application of these MRI techniques should improve definition of different acute stroke syndromes and facilitate clinical decision making.

Acute Disease↗

Quantitative assessment of mirror movements after stroke.

BACKGROUND AND PURPOSE: Mirror movements (MM) are involuntary synchronous movements of one limb during voluntary unilateral movements of the opposite limb. We measured MM in stroke and control subjects and evaluated whether MM after stroke are related to motor function. METHODS: Twenty-three patients and 16 control subjects were studied. A computerized dynamometer was used during two squeezing tasks to measure intended movements from the active hand as well as MM from the opposite hand. Motor deficits were measured with the arm motor component of the Fugl-Meyer scale. RESULTS: During paretic hand squeezing, MM in the unaffected hand were detected in 70% (repetitive squeeze) to 78% (sustained squeeze) of stroke patients. For both tasks, this was significantly (P < 0.05) greater than the incidence of MM in the paretic hand or in either hand of control subjects (17% to 44%), except when compared with the incidence of MM in the dominant hand of control subjects (56%; P = 0.17). The incidence of MM in the paretic hand was not significantly different from that seen in either hand of control subjects. Patients with MM in the unaffected hand had significantly greater motor deficit than patients without MM. Patients with MM in the paretic hand had significantly better motor function than patients without MM. CONCLUSIONS: Simultaneously recording motor performances of both hands provides precise information to characterize MM. MM in the unaffected hand and in the paretic hand are associated with different degrees of motor deficit after stroke. Evaluation of MM may be useful for studying mechanisms of stroke recovery.

Adult↗

Pharmacological elevation of blood pressure in acute stroke. Clinical effects and safety.

BACKGROUND AND PURPOSE: Lowering of blood pressure can adversely affect ischemic symptoms in acute stroke. The aim of our study was to determine whether induced hypertension in stroke is safe and to examine its effects on neurological deficits in patients presenting with acute cerebral ischemia. METHODS: We retrospectively reviewed all patients admitted to our neurological intensive care unit with the diagnosis of ischemic stroke over a 2.5-year period. Thirty-three patients were not given a pressor agent (Ph- group), while 30 were treated with phenylephrine (Ph+ group) in an attempt to improve cerebral perfusion. RESULTS: Baseline characteristics showed few differences between the Ph+ and Ph- groups. Intracerebral hemorrhage, brain edema, cardiac morbidity, and mortality were not increased in the Ph+ group. In 10 of 30 Ph+ patients, a systolic blood pressure threshold was identified below which ischemic deficits worsened and above which deficits improved. The mean threshold was 156 mm Hg (range, 120 to 190 mm Hg). The mean number of stenotic/occluded cerebral arteries was greater in those Ph+ patients with an identified clinical blood pressure threshold (mean, 2.1 per patient) than in Ph+ patients without a threshold (mean, 1.2 per patient; P < .05). CONCLUSIONS: The results suggest that careful use of phenylephrine induced hypertension is not associated with an increase in morbidity or mortality in acute stroke. Although based on a retrospective analysis of clinical practice, this report suggests that a subset of patients, particularly those with multiple stenosis of cerebral arteries, may improve neurologically upon elevation of the blood pressure.

Acute Disease↗