John P. Szalai

The Sunnybrook Stroke Study A Prospective Study of Depressive Symptoms and Functional Outcome

BACKGROUND AND PURPOSE To assess the prevalence of depressive symptoms, their clinical correlates, and the effects of depressive symptoms on stroke recovery, a relatively unselected, well-diagnosed cohort of consecutive stroke survivors was followed prospectively. METHODS Consecutive admissions to a regional stroke center who met World Health Organization and National Institute of Neurological Disorders and Stroke criteria for stroke were eligible. Subarachnoid hemorrhage and brain stem strokes were excluded. Patients underwent CT, single-photon emission CT, and standardized neurological and cognitive examinations at entry. At 3 months and 1 year after stroke, depressive symptoms were assessed with the Montgomery Asberg Depression Rating Scale (MADRS) and the Zung Self-Rating Depression Scale (SDS). Functional outcome was measured with the Functional Independence Measure, and handicap was assessed by the Oxford Handicap Scale. RESULTS We assessed 436 patients at entry (mean +/- SD age, 74.9 +/- 11.6 years). There were 150 patients available for assessment at 3 months and 136 at 1 year. Marked depressive symptoms were noted in 22% (SDS) to 27% (MADRS) at 3 months and 21% (SDS) to 22% (MADRS) at 1 year. Patents with marked depressive symptoms had more neurological impairment (P<.008), were more likely to be female (P<.05), and were more likely to have previous histories of depression (P<.03). There was no relationship between depressive symptoms and age, lesion volume, or side of lesion. Depressive symptoms were correlated with functional outcome (r = -.31, P<.0001) and handicap (r = .41, P<.0001) at 3 months and 1 year (r= -.28, P<.001; r = .35, P<.0001). CONCLUSIONS Depressive symptoms and functional outcome are correlated. In view of the prevalence of depressive symptoms in this population, diagnosis and treatment of depression are important in optimizing recovery.

Beyond the hippocampus: MRI volumetry confirms widespread limbic atrophy in AD

Objective: To examine volumetric changes in limbic structures in patients with probable AD using planimetric measures on MRI. Method: Limbic structures (i.e., hippocampus, amygdala, anterior thalamus, hypothalamus, mamillary bodies, basal forebrain, septal area, fornix, and cingulate, orbitofrontal, and parahippocampal cortices) were traced on 3D T1-weighted MR images of 40 patients with mild to moderate AD and 40 age-, sex-, and education-matched normal control subjects. Limbic volumes were compared between groups and the predictive ability was assessed. Results: Overall, limbic structures showed significant atrophy in AD patients compared with normal control subjects. Differences (p < 0.05) were found in all limbic regions except the anterior cingulate cortex. The greatest percentage volumetric losses occurred in the septal area (34%), hippocampus (28%), amygdala (21%), parahippocampal cortex (21%), and posterior cingulate cortex (20%). Combining volumetric measures of amygdala and septal area distinguished patients with AD from normal control subjects with 93% accuracy. Conclusions: These results verify that system-wide limbic degeneration occurs in patients with AD. In addition, atrophy in selected limbic structures was used to distinguish patients with AD from normal elderly individuals with over 90% accuracy in this select clinical sample. The measures require further exploration in samples more representative of those seen by primary care physicians before their utility can be accurately assessed.

Brain-behavior correlations in hemispatial neglect using CT and SPECT The Sunnybrook Stroke Study

Objective: Structural and functional lesion localization in patients with hemispatial neglect. Design: Location and severity of brain damage on CT and SPECT correlated with neglect performance as assessed with a battery of drawings, line bisection, and line and shape cancellation subtests. Patients: Participants included 120 consecutive stroke patients with a single right-hemisphere-damaged lesion on CT who were admitted to the Acute Stroke Care Unit at Sunnybrook Health Science Centre. Of these, 88 also had a SPECT. Results: On CT, 82 patients with neglect (compared with 38 without neglect) had more extensive damage in the parietal and sensorimotor cortex and white matter fiber bundles, including the posterior-superior longitudinal and inferior-frontal fasciculi (p < 0.05). Parietal and anterior cingulate damage best predicted neglect score using the CT data (p< 0.05), and regional blood flow in the parietal cortex best predicted neglect score using the SPECT data (p < 0.05) after controlling for the influence of age and lesion size on multiple linear regression. Conclusions: Damage in the parietal and anterior cingulate cortex and posterior white matter fiber bundles correlated with hemispatial neglect. Combining structural- and functional-imaging techniques with neurobehavioral analysis can elucidate brain-behavior relationships.

Functional and Neuroanatomic Correlations in Poststroke Depression The Sunnybrook Stroke Study

BACKGROUND AND PURPOSE The purpose of our study was to determine the functional and neuroanatomic correlates of poststroke depressive symptoms. METHODS Patients with consecutive admissions to a regional stroke center for new-onset unilateral hemispheric stroke who met World Health Organization and National Institute of Neurological and Communicative Disorders and Stroke criteria were eligible for inclusion in a longitudinal study. Acutely, patients underwent CT scanning, and at 3 months and 1 year after stroke, depressive symptoms were assessed by using both the Montgomery-Asberg Depression Rating Scale and the Zung Self-Rating Depression Scale. The Functional Independence Measure (FIM) served as an indication of functional outcome and was obtained at 1 month, 3 months, and 1 year after stroke, along with other demographic information. The Talairach and Tournoux stereotactic atlas was used for the primary determination of CT lesion localization. Lesion proximity to the anterior frontal pole was also measured. RESULTS Eighty-one patients participated in the longitudinal study. Stepwise linear regression analyses generated a highly significant model (F(3,76)=9.8, R(2)=28%, P<0.0005), with lower 1-month total FIM scores, living at home, and damage to the inferior frontal region predicting higher depression scores at 3 months. Similarly, lower 3-month total FIM scores correlated with higher 3-month depression scores, and lower 1-year total FIM scores correlated with higher 1-year depression scores. CONCLUSIONS Functional measures correlated with poststroke depression across time and, together with neuroanatomic measures, predicted depressive symptoms longitudinally. Although inferior frontal lesion location, irrespective of side, appeared to play a role as a risk factor in this study, the degree of functional dependence after stroke imparted the greatest risk.

Mild Cognitive Impairment: An Operational Definition and Its Conversion Rate to Alzheimer’s Disease

Objective: Because of discrepant findings regarding the accuracy of mild cognitive impairment (MCI) in predicting Alzheimer’s disease (AD), further study of this construct and conversion rates is essential before use in clinical settings. We aimed to develop an operational definition of MCI consistent with criteria proposed by the Mayo Alzheimer’s Disease Center, and to examine its conversion rate to AD. Methods: Patients were identified from an inception cohort of patients with at least a 3-month history of memory problems, and referred to a 2-year university teaching hospital investigation by primary care physicians. We classified 161 nondemented patients at baseline using MCI criteria. Diagnostic workups were completed annually, and patients were classified as meeting criteria for AD or showing no evidence of dementia after 1 and 2 years. Results: Of 161 patients, 35% met MCI criteria at baseline. Conversion rates to AD were 41% after 1 year, and 64% after 2 years. Logistic regression analyses to examine predictive accuracy of MCI after 1 and 2 years, with age and education as covariates, were significant (p < 0.0001). After 1 year, MCI showed an optimal sensitivity of 91% and specificity of 79%, and after 2 years, these values were 88 and 83%, respectively. Conclusions: MCI is an accurate predictor of AD over 1 and 2 years in patients referred by their primary care physicians. Discrepancies in conversion rates may be due to the manner in which patients are recruited to studies as well as the use of different measures to operationalize the construct.

Are stentless valves hemodynamically superior to stented valves? A prospective randomized trial

BACKGROUND Although stentless aortic bioprostheses are believed to offer improved outcomes, hemodynamic benefits remain unsubstantiated. METHODS Fifty-three patients were randomized to receive the stented C-E pericardial valve (CE) and 46 patients the Toronto Stentless Porcine valve (SPV). Annuli were sized for the optimal insertion of both valve types, such that surgeons were required to commit to specific valve sizes before randomization. Echocardiographic measurements and functional status (Duke Activity Status Index) were assessed at 3 and 12 months postoperatively. RESULTS Although cardiopulmonary bypass times (CE: 118.6+/-36.3 minutes; SPV: 148.5+/-30.9 minutes; p = 0.0001) and aortic cross-clamp times (CE: 95.4+/-28.6 minutes; SPV: 123.6+/-24.1 minutes; p = 0.0001) were significantly prolonged in the SPV group, perioperative morbidity and mortality was similar between groups. Neither valve offered a superior internal diameter for any given annular diameter (mean decrease in left ventricular outflow tract diameter after valvular implantation: SPV: 3.4+/-1.11 mm versus CE: 3.7+/-1.33 mm; p = 0.25). Although labeled mean valve size was significantly larger in the SPV group, the actual mean valve size based on internal valvular diameter was no different between groups (CE: 21.9+/-2.0 mm; SPV: 22.3+/-2.0 mm; p = 0.286). Although effective orifice areas increased, and mean and peak transvalvular gradients decreased in both groups over time, no differences were demonstrated between groups at 12 months. Similarly, although significant regression of left ventricular mass was accomplished in both groups over time, no differences were demonstrated between groups. Finally, Duke Activity Status Index scores of functional status improved in both groups over time; however, no differences were noted between groups at 12 months postoperatively. CONCLUSIONS Although offering excellent outcomes, stentless valves did not demonstrate superior hemodynamic indices in comparison to stented valves up to 12 months after implantation.

Lack of association between outcome measures of nerve regeneration

Studies of nerve regeneration in rodents utilize at least one of three classes of outcome measures: electrophysiology, morphometry, and functional tests. The assumption that these measures are correlated was tested utilizing a data set of 16 variables. Significant correlations (Spearmans rho, P ⩽ 0.05) were found within variable classes; however, none were found between classes. The three commonly utilized outcome measures do not measure the same phenomenon but rather discrete aspects of nerve regeneration.

Response to Desipramine Treatment in Adolescent Depression: A Fixed-Dose, Placebo-Controlled Trial

OBJECTIVE To determine the efficacy and tolerability of the tricyclic antidepressant desipramine (DMI) in the treatment of DSM-III-R-diagnosed major depressive disorder in adolescents. METHOD Sixty adolescents (42 female, 18 male; aged 15 to 19 years) diagnosed with major depressive disorder using clinical interview and Schedule for Affective Disorders and Schizophrenia for School-Age Children were randomized to receive either DMI (200 mg daily in divided doses) or placebo for six consecutive weeks following a 1-week placebo period. Treatment outcome was determined using the Hamilton Depression Rating Scale and the Beck Depression Inventory. Tolerability was determined using a symptom side effects scale. In addition, a variety of laboratory and cardiovascular monitoring was performed. RESULTS No significant differences in treatment outcome between DMI- and placebo-treated groups were determined. Neither DMI, nor its metabolite 2-hydroxy-DMI, nor their ratio, was positively correlated to treatment outcome. The DMI group endorsed more side effects but there were no significant between-group differences in any laboratory, electrocardiographic, or other cardiovascular parameters apart from heart rate, which was increased in the DMI-treated group (p = .03). CONCLUSIONS Given the findings of this study and our review of previously published reports of tricyclic antidepressant treatment in this population, the routine use of short-term (6 weeks) DMI in the treatment of adolescent depression is not supported by the data on hand. Further investigations into what constitutes optimal psychopharmacological treatment of adolescent depression are warranted.

Physiotherapy Coupled With Dextroamphetamine for Rehabilitation After Hemiparetic Stroke A Randomized, Double-Blind, Placebo-Controlled Trial

Background and Purpose— Hemiparesis is the commonest disabling deficit caused by stroke. In animals, dextroamphetamine (AMPH) paired with training enhances motor recovery, but its clinical efficacy is uncertain. Methods— In a randomized, double-blind, placebo-controlled trial, 71 stroke patients were stratified by hemiparesis severity and randomly assigned to 10 sessions of physiotherapy coupled with either 10 mg AMPH or placebo. Study treatments were administered by 1 physiotherapist, beginning 5 to 10 days after stroke and continuing twice per week for 5 weeks. Outcomes were assessed by 1 physiotherapist at baseline, after each treatment session, at 6 weeks, and at 3 months. The primary outcome was motor recovery (impairment level) on the Fugl-Meyer (FM) scale. Secondary outcomes assessed mobility, ambulation, arm/hand function, and independence in activities of daily living. Results— Baseline hemiparesis was severe overall (mean FM score 27.7±20.0). Motor scores improved during treatment in both groups (mean change, baseline to 3 months 29.5±16.6). Repeated-measures ANOVA revealed no significant differences in recovery between the treatment groups for the entire cohort (n=67) or for subgroups with a severe hemiparesis (n=43), moderate hemiparesis (n=24), or cortically based stroke (n=26). In the moderate subgroup, there was a significant drug×time interaction for upper extremity motor recovery (F=5.14; P<0.001), although there was a significant baseline imbalance in motor scores in this subgroup. Conclusion— In stroke patients with a severe motor deficit, 10 mg AMPH coupled with physiotherapy twice per week for 5 weeks in the early poststroke period provided no additional benefit in motor or functional recovery compared with physiotherapy alone. Patients with moderate severity hemiparesis deserve further investigation. Increased intensity and longer duration drug/therapy dosing regimens should be explored, targeting the upper and lower limbs separately.

The efficacy and safety of divalproex sodium in the treatment of acute mania in adolescents and young adults: an open clinical trial.

This open clinical trial investigated the potential short-term efficacy and safety of divalproex sodium in the treatment of adolescents and young adults with bipolar affective disorder in an acute manic phase. Fifteen subjects were treated for 7 weeks with divalproex sodium (mean drug level in blood +/- the standard deviation at trial completion, 642.85 +/- 183.08 mumol/liter) and were assessed weekly with the Modified Mania Rating Scale (MMRS), the Brief Psychiatric Rating Scale (BPRS), the Global Assessment Scale (GAS), and the Clinical Global Impressions Scale (CGI). Of the 15 subjects who entered the study, 8 showed marked improvement on the MMRS (pre-post decrease of > or = 75%), 4 showed moderate improvement (pre-post decrease of 50 to 74%), 1 showed some improvement (pre-post decrease of 25 to 49%), 1 showed no improvement and was withdrawn before the seventh study week because of lack of response, and 1 withdrew because of side effects. The mean MMRS score was significantly changed by 7 weeks of treatment in the 13 subjects who completed the 7-week trial (69.54 +/- 24.21 to 18.08 +/- 8.70; t = 7.72; p < 0.0001), as were the BPRS (36.31 +/- 12.22 to 12.00 +/- 4.22; t = 7.53; p < 0.0001), the GAS (30.23 +/- 9.05 to 54.69 +/- 9.40; t = 7.50; p < 0.0001), and the CGI (5.38 +/- 0.96 to 2.38 +/- 0.87; t = 10.01; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)