Differential behavioral and biochemical effects of right and left hemispheric cerebral infarction in the rat.

Following ligation of the right middle cerebral artery, rats were hyperactive for 2 to 3 weeks whether activity was measured by running wheel revolutions or open field observations. Assays of brain catecholamines revealed 30 percent reductions of norepinephrine in the injured and uninjured cortex and locus coeruleus and a 20 percent reduction of dopamine in the substantia nigra. In contrast, rats with left middle cerebral artery ligations did not become hyperactive and did not show any significant change in catecholamines in any of the brain areas studied. Right and left hemispheric infarctions were comparable in their locations and extent of tissue damage. This lateralization of behavioral and biochemical response to cerebral infarction may be the consequence of anatomical or physiological asymmetries in the brain.

Anosognosia for hemiplegia after stroke is a multifaceted phenomenon: a systematic review of the literature.

Anosognosia is the lack of awareness or the underestimation of a specific deficit in sensory, perceptual, motor, affective or cognitive functioning due to a brain lesion. This self-awareness deficit has been studied mainly in stroke hemiplegic patients, who may report no deficit, overestimate their abilities or deny that they are unable to move a paretic limb. In this review, a detailed search of the literature was conducted to illustrate clinical manifestations, pathogenetic models, diagnostic procedures and unresolved issues in anosognosia for motor impairment after stroke. English and French language papers spanning the period January 1990-January 2007 were selected using PubMed Services and utilizing research words stroke, anosognosia, awareness, denial, unawareness, hemiplegia. Papers reporting sign-based definitions, neurological and neuropsychological data and the results of clinical trials or historical trends in diagnosis were chosen. As a result, a very complex and multifaceted phenomenon emerges, whose variable behavioural manifestations often produce uncertainties in conceptual definitions and diagnostic procedures. Although a number of questionnaires and diagnostic methods have been developed to assess anosognosia following stroke in the last 30 years, they are often limited by insufficient discriminative power or a narrow focus on specific deficits. As a consequence, epidemiological estimates are variable and incidence rates have ranged from 7 to 77% in stroke. In addition, the pathogenesis of anosognosia is widely debated. The most recent neuropsychological models have suggested a defect in the feedforward system, while neuro-anatomical studies have consistently reported on the involvement of the right cerebral hemisphere, particularly the prefrontal and parieto-temporal cortex, as well as insula and thalamus. We highlight the need for a multidimensional assessment procedure and suggest some potentially productive directions for future research about unawareness of illness.

Insight and danger in Alzheimer's disease.

To determine the frequency, and demographic and clinical correlates of dangerous behaviours in Alzheimer's disease (AD). We assessed a consecutive series of 278 patients with AD and 45 age-comparable healthy controls with a comprehensive psychiatric and neuropsychological evaluation. Caregivers rated the frequency of patients' exposure to dangerous situations or commission of dangerous behaviours. The frequency of dangerous behaviours was 16% in the AD group and 2% in the healthy control group. The presence of anosognosia was associated with a threefold increase in the risk of dangerous behaviours, but there was no significant association between dangerous behaviours and patients' age, years of education, diagnosis of major or minor depression and presence of suicide ideation. Sixteen per cent of a consecutive series of patients with AD had dangerous behaviours during the month preceding the clinical evaluation. Anosognosia was the main clinical correlate of dangerous behaviours in this population.

A diagnostic formulation for anosognosia in Alzheimer's disease.

OBJECTIVE: To determine the earliest symptoms of anosognosia in people with Alzheimer's disease and to validate a criteria-guided strategy to diagnose anosognosia in dementia. METHODS: A consecutive series of 750 patients with very mild or probable Alzheimer's disease attending a memory clinic, as well as their respective care givers, was assessed using a comprehensive psychiatric evaluation. RESULTS: The factors of anosognosia for (1) basic activities of daily living (bADL), (2) instrumental activities of daily living (iADL), (3) depression and (4) disinhibition were produced by a principal component analysis on the differential scores (ie, caregiver score minus patient score) on the anosognosia questionnaire for dementia. A discrepancy of two or more points in the anosognosia-iADL factor was found to have a high sensitivity and specificity to identify clinically diagnosed anosognosia in people with Alzheimer's disease. By logistic regression analysis, the severity of dementia and apathy were both shown to be noticeably associated with anosognosia in people with Alzheimer's disease. CONCLUSION: Anosognosia in those with Alzheimer's disease is manifested as poor awareness of deficits in iADL and bADL, depressive changes and behavioural disinhibition. The frequency of anosognosia is found to increase considerably with the severity of dementia. The validity of a specific set of criteria to diagnose anosognosia in people with Alzheimer's disease was shown, which may contribute to the early identification of this condition.

Comparison of patients with and without poststroke major depression matched for size and location of lesion.

Patients who developed major depression within two years following stroke (n = 13) were compared with patients who did not become depressed in the same period (n = 13) but who did have a similar size and location of lesion as in the depressed group. Although the depressed patients were not significantly different from the nondepressed patients in background characteristics, history of depressive disorder, neurological impairment, or social functioning, the depressed group had greater cognitive impairment as measured by Mini-Mental State score. In addition, the depressed group had significantly larger lateral and third ventricular to brain ratios than nondepressed patients on computed tomographic scan analysis. The results suggest that poststroke depression itself may produce an intellectual impairment; subcortical atrophy, which likely preceded the stroke lesion, may produce a vulnerability for depression following stroke.

Relationship between anxiety disorders and depressive disorders in patients with cerebrovascular injury.

The interaction between anxiety disorder and major depressive disorder in patients with cerebrovascular lesions was examined in a controlled, 2 x 2 study design. A consecutive series of 24 patients who met criteria for major depression only were compared with 6 patients who met criteria for both major depression and generalized anxiety disorder, and 45 patients who did not meet criteria for either major depression of generalized anxiety. Among patients with positive computed tomographic scans, the anxious-depressed group (n = 19) showed a significantly higher frequency of cortical lesions, while patients with major depression only (n = 15) had a significantly higher frequency of subcortical (basal ganglia) strokes. No significant between-group differences were found in other variables, such as demographic variables, familial and personal history of psychiatric disorders, and neurologic deficits. These findings suggest that, in this mostly black, low-socioeconomic-status population, cortical vs subcortical lesion location may play an important role in determining whether severe anxiety occurs in patients with post-stroke major depression.

Parathyroid adenoma with coexistent sarcoid granulomas. A hypercalcemic patient.

A 56-year-old woman had hypercalcemia. Clinical symptoms and chest roentgenograms were suggestive of sarcoidosis. Results of laboratory studies, however, were compatible with primary hyperparathyroidism. At surgical exploration of the neck, a parathyroid adenoma was found. Microscopically, sarcoid-like granulomas were present within the adenoma. The association between hypercalcemic sarcoidosis and primary hyperparathyroidism is reviewed, and the importance of this finding is discussed.

Contributing diagnoses in osteoporosis. The value of a complete medical evaluation.

Osteoporosis often occurs as a consequence of, or is accelerated by, many medical diseases, drug exposures, or other conditions. We called these conditions contributing diagnoses. Although technological advances permit the accurate measurement of bone density, identifying osteoporosis without searching for contributing diagnoses may result in remediable diseases being missed or in the initiation of inadvisable therapy. The value of comprehensive medical evaluation in conjunction with appropriate diagnostic studies was demonstrated in an osteoporosis referral center. We studied 300 consecutive persons who presented to an osteoporosis clinic. Using strict criteria, 180 patients (60%) had osteoporosis. Of these 180 patients, 83 (46%) had one or more contributing diagnosis, ie, a condition thought to accelerate bone loss. The largest single group was composed of persons with past or present exposure to glucocorticoids; the second largest group consisted of women who had undergone premature menopause. In all, 27 different contributing diagnoses were identified. Additionally, in 19 (11%) of the 180 patients with osteoporosis, a contributing diagnosis new to those patients was made. The evaluation of osteoporosis does not only entail measurement of bone density but must also take into consideration a patient's entire medical milieu.

Prognosis for recovery of function in acute renal failure. Value of the renal image obtained using iodohippurate sodium I 131.

Twenty-four survivors of acute, nonobstructive, nonnephritic renal failure had a renal scan using iodohippurate sodium I 131 performed early in the acute illness. Scans were judged according to whether the renal images were prominent, faint, or absent during the first 30 minutes after intravenous injection of 100 to 250 microcuries of iodohippurate sodium I 131. All ten patients with prominent renal images attained life-sustaining renal function with an average postrecovery creatinine clearance of 80 ml/min. Of the seven patients with faint renal images, six recovered life-sustaining renal function (average creatinine clearance of 39 ml/min), and one required chronic hemodialysis. Seven patients had no renal image initially; four recovered life-sustaining renal function with an average creatinine clearance of 25 ml/min; three required chronic hemodialysis. We conclude that, for patients with acute renal failure, the appearance of the renal image obtained using this substance is an important indicator of renal viability and of the likelihood for functional recovery.

Estrogen and progesterone replacement therapy reduces glucocorticoid-induced bone loss.

This is a retrospective study of 15 postmenopausal or amenorrheic women aged 34-78 years who had taken prednisone for 6-108 months and were followed for 1 year while continuing to take doses of 5-15 mg/day. A total of 8 patients were treated with 0.6256 mg Premarin daily for 25 days and 5 mg/day of medroxyprogesterone on days 15-25 (ERT, group 2); 7 were followed without ERT (group 1). A group of 17 women, matched for age, were randomly selected from our computerized data base to serve as a control group (group 3), and 10 women of similar age who were taking ERT only (group 4) were selected to compare the response to ERT to that of group 2. Bone density (BD) was measured in the lumbar spine baseline and at 1 year using dual-photon or dual-energy x-ray absorptiometry. Spine density did not change significantly during the year of observation in group 1. Although BD decreased in 5 of 7 patients, the change was not significant (-0.034 +/- 0.018 g/cm2, p = 0.10). In group 2 BD increased significantly, with 7 of 8 patients showing an increase (0.037 +/- 0.011 g/cm2, p = 0.008). BD did not change significantly in the control group (0.013 +/- 0.008 g/cm2, p = 0.16). Loss of bone from the spine was significantly greater in group 1 than in controls (p = 0.02), but changes in group 2 were similar to those in the control group (p = 0.66).(ABSTRACT TRUNCATED AT 250 WORDS)

Improved recovery in activities of daily living associated with remission of poststroke depression.

BACKGROUND AND PURPOSE: Poststroke depression is associated with impaired recovery of activities of daily living (ADL) function compared with similar nondepressed patients. We examined the differences on recovery of ADL functions among poststroke depressed patients with remission of their depression compared with poststroke depressed patients without mood recovery over the first 3 to 6 months after stroke. METHODS: On the basis of a semistructured psychiatric examination and DSM-IV diagnostic criteria, a consecutive series of patients with poststroke major or minor depression (n=55) were selected. Their impairment in ADL function was assessed by means of the Johns Hopkins Functioning Examination during acute hospitalization and either 3 or 6 months later. RESULTS: Patients whose mood improved at follow-up (n=21) had significantly greater recovery in ADL functions at follow-up than patients whose mood did not improve (n=34). There were no differences in demographic variables, lesion characteristics, and neurological symptoms between the two groups. Furthermore, patients with either major or minor depression at the initial evaluation showed the same amount of recovery in ADL function if they improved at follow-up. CONCLUSIONS: Our findings suggest that remission of poststroke depression over the first few months after stroke is associated with greater recovery in ADL function than continued depression. Early effective treatment of depression may have a positive effect on the rehabilitation outcome of stroke patients.

Pharmacological treatment following experimental cerebral infarction: implications for understanding psychological symptoms of human stroke.

Middle cerebral artery ligation in the rat produces decreases in catecholamine concentrations at brain sites uninjured by ischemic damage and a transient increase in spontaneous horizontal activity. Development of this hyperactivity can be blocked by postoperative treatment with the antidepressant, desmethylimipramine, or by preoperative destruction of norepinephrine terminals with 6-hydroxydopamine. These results suggest that ischemic damage to the cerebral cortex which injures some axonal branches of elaborately arborizing catecholamine-containing neurons may alter the biochemical and functional state of the entire system in its intact collateral axons. Thus the concept of stroke as a local injury producing symptoms by local structure-function relationships is conceptually inadequate, and poststroke symptoms must be evaluated with these "whole brain" concepts in mind. We suggest that the poststroke symptoms of apathy and depression may represent emotional changes which result from pathophysiological processes in catecholamine neurons far from the site of the stroke.

The relationship between poststroke depression and lesion location in long-term follow-up.

BACKGROUND: We have previously reported that during the acute poststroke period, poststroke major depression was significantly associated with left anterior lesions. Furthermore, we found that proximity of the lesion to the left frontal pole was correlated with severity of depression. Several investigators, however, have failed to replicate these findings when patients were studied beyond the acute stroke period. METHODS: We longitudinally examined the relationship between lesion size, lesion location, impairment variables, and the presence and severity of depression in 60 single lesion patients examined in-hospital and at short-term (3-6 months) and long-term (1-2 years) follow-up. RESULTS: Only in-hospital depression was significantly associated with left anterior hemisphere lesion location. At short-term follow-up, proximity of the lesion to the frontal pole, and lesion volume correlated with depression in both right and left hemisphere. At 1-2 years poststroke, depression was significantly associated with right-hemisphere lesion volume and proximity of the lesion to the occipital pole. CONCLUSIONS: The anatomical correlates of poststroke depression change over time and may explain interstudy differences in the association of lesion location with poststroke depression.

Manic-depressive and pure manic states after brain lesions.

Although mania is a rare complication of brain lesions, recent reports have emphasized the importance of lesion location and genetic predisposition in these patients. In the present study we compared patients who developed a bipolar affective disorder (i.e., mania and depression) after a brain lesion with patients who only developed mania. Although no significant between-group differences were found on demographic variables, the manic-depressed group showed significantly more impairments on the Mini Mental State Exam than the mania only group. All the bipolar patients had subcortical lesions (mainly right head of the caudate and right thalamus), while patients with unipolar mania had significantly higher frequency of cortical involvement (mainly right orbitofrontal and basotemporal cortices). It is suggested that subcortical and cortical right hemisphere lesions may produce different neurochemical and/or remote metabolic brain changes that may underlie the production of either a bipolar disease or a unipolar mania.

Prolongation of gastric emptying by oral propantheline.

The present study shows that a single oral recommended dose of propantheline bromide normally doubles the mean gastric half-emptying time in man. In a prospective, double-blind, randomized crossover design 13 normal subjects were given 30 mg propantheline or placebo 90 min before taking a 113m-indium-labeled liquid test meal, the volume of which was adjusted to body weight. The disappearance of radioisotope from the area of the stomach was determined by external gamma counting. After placebo the mean half-emptying time was 68 min and after propantheline it was 135 min (p less than 0.005). Although salivary flow decreased and pulse rate increased there were no visual disturbances. In studies already reported maximally tolerated oral doses of quaternary ammonium anticholinergic drugs have not consistently retarded gastric emptying in man.

Oral anticholinergics and gastric emptying.

The quarternary ammonium antimuscarinic drugs propantheline bromide and clidinium bromide, given orally at the usual therapeutic doses, delayed gastric emptying of a swallowed radiolabeled liquid meal as measured by a gamma camera. Delay of emptying was dose dependent. If an identical meal was given by gastric tube, there was no slowing of emptying by propantheline in the group as a whole. Six subjects who emptied the intubated meal more quickly with placebo had slowed emptying after 30 mg propantheline. In five others, intubation alone slowed gastric emptying while the addition of 30 mg propantheline caused a paradoxical acceleration of gastric emptying. Clidinium bromide, 5 mg, delayed gastric emptying to the same extent as 15 mg propantheline bromide without the marked suppression of salivary secretion induced by the latter.

Clinical correlates of early-onset and late-onset poststroke generalized anxiety.

OBJECTIVE: The authors' goal was to determine if generalized anxiety diagnosed while a patient was hospitalized for stroke (early onset) had the same clinical correlates as anxiety beginning 3 months or more after the stroke (late onset). METHOD: Patients with acute stroke (N = 142) were examined while they were in the hospital and 3, 6, 12, and 24 months later for the presence of anxiety symptoms. Patients underwent a structured psychiatric interview as well as assessment of cognitive, physical, and social function at each visit. Patients with early-onset and late-onset poststroke generalized anxiety were identified and compared to patients without poststroke generalized anxiety. RESULTS: The frequency of early-onset poststroke generalized anxiety was 27% and that of late-onset poststroke generalized anxiety was 23%. Three-quarters of the anxious patients had comorbid major or minor depression. Patients who developed early-onset or late-onset poststroke generalized anxiety were no more socially, cognitively, or physically impaired than patients who did not develop anxiety. Early-onset but not late-onset anxiety was associated with a previous history of psychiatric disorder. The median duration of late-onset anxiety was 3.0 months, and that of early-onset anxiety was 1.5 months. The presence of anxiety was significantly associated with depression; onset of depression and onset of anxiety occurred at approximately the same time. CONCLUSIONS: These findings suggest that although early-onset and late-onset poststroke generalized anxiety are phenomenologically similar, they may be the result of different pathophysiological mechanisms.

Two-year longitudinal study of post-stroke mood disorders: comparison of acute-onset with delayed-onset depression.

Patients who developed post-stroke depression 3 to 24 months after hospital discharge (N = 21) were compared with patients who developed depression during hospitalization (N = 26) and patients who never developed depression over 24 months of follow-up (N = 15). During the acute hospitalization and at follow-up, the three groups were not significantly different in their demographic characteristics, neurological impairment, intellectual impairment, or quality of social support. The acute depression group, however, showed an increased correlation between impairment and depression from hospitalization to follow-up. Findings suggest that impairment does not produce depression, but, once depression occurs, it may interact with impairment to influence post-stroke recovery.

Pathological laughing and crying following stroke: validation of a measurement scale and a double-blind treatment study.

OBJECTIVE: This study was undertaken to test the reliability and validity of the Pathological Laughter and Crying Scale and the effectiveness of nortriptyline treatment for patients with emotional lability following stroke. METHOD: Eighty-two patients with ischemic brain injury-54 who had been hospitalized with acute stroke and 28 others who requested treatment for pathological laughing and crying--were given standardized psychiatric and neurological assessments and then administered the Pathological Laughter and Crying Scale. The 54 acute stroke patients were used to evaluate the Pathological Laughter and Crying Scale, and the 28 patients with pathological emotional display were randomly assigned to nortriptyline treatment or placebo in a 6-week double-blind trial to assess the efficacy of a tricyclic antidepressant in treatment of this disorder. RESULTS: The interrater reliability on the Pathological Laughter and Crying Scale for a subgroup of 15 patients was 0.93, and the test-retest reliability of the scale was excellent. After 4 and 6 weeks of treatment, scores on the Pathological Laughter and Crying Scale showed significantly greater improvement in the 14 patients given nortriptyline than in the 14 given placebo. Although almost one-half of these patients also had major depression, the improvement in emotional lability was independent of depression status. In addition, response to treatment was not significantly affected by lesion location or time since stroke. CONCLUSIONS: The severity of symptoms in pathological emotional display can be reliably quantified with the Pathological Laughter and Crying Scale, and treatment with nortriptyline can effectively ameliorate this emotional disorder.

Association of depression with 10-year poststroke mortality.

OBJECTIVE: Depression has been linked to higher than expected mortality from natural causes, particularly among elderly patients with physical illness. The authors examined the effect of depression on mortality among a group of stroke patients followed up for 10 years. METHOD: A consecutive series of 103 patients was assessed for major or dysthymic (minor) depression approximately 2 weeks after stroke with the use of a structured mental status examination and DSM-III diagnostic criteria. Vital status was determined for 91 of these patients 10 years later. RESULTS: Forty-eight (53%) of the 91 patients had died. Patients with diagnoses of either major or minor depression were 3.4 times more likely to have died during the follow-up period than were nondepressed patients, and this relationship was independent of other measured risk factors such as age, sex, social class, type of stroke, lesion location, and level of social functioning. The mortality rate among depressed patients with few social contacts was especially high: over 90% had died. CONCLUSIONS: These results indicate that depressed mood following stroke is associated with an increased risk of subsequent mortality. Patients who are depressed and socially isolated seem to be particularly vulnerable.