Juhani Vilkki

The Met Allele of the BDNF Val66Met Polymorphism Predicts Poor Outcome Among Survivors of Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— Brain-derived neurotrophic factor (BDNF) plays a role in neuronal survival, plasticity and neurogenesis. The BDNF gene contains a common Val66Met polymorphism; the Met allele is associated with lower depolarization-induced BDNF release and differences in memory functions and brain morphology. We hypothesized that the Met allele is associated with poor recovery from subarachnoid hemorrhage. Methods— A sample of 105 survivors was assessed at 3 months after subarachnoid hemorrhage using Glascow Outcome Scale. Poor outcome was defined as severe disability or worse. DNA samples were genotyped for the Val66Met polymorphism. Results— Higher percentage of the Met carriers had a poor outcome (29%) as compared with the Val/Val group (10%; P=0.011). In multiple logistic regression, this association between the Met allele and poor outcome was independent of several other prognostic factors such as patient age, clinical condition, and radiological severity of the bleeding (odds ratio 8.40; 95% CI, 1.60 to 44.00; P=0.012). Conclusions— Genetically influenced variation in BDNF function plays a role in recovery from subarachnoid hemorrhage. These data indicate that augmentation of BDNF signaling may be beneficial to recovery from brain injury.

Amnesic syndromes after surgery of anterior communicating artery aneurysms.

Five patients had severe generalized disorder of memory, which lasted for several months after anterior communicating artery aneurysm surgery. Two of them had no signs of frontal lobe lesions. They were confused for not more than four days after surgery. One of them performed normally on the non-memory tests and short-term memory tests. Cues did not substantially improve his poor memory performance. The other patient had similar test results, but he had poor imagination in an inkblot perception test. Three patients had frontal lobe lesions. Two of them were restless, confused and confabulating, with one showing apathetic and stereotyped behaviour for more than a month after surgery. On the memory tests they showed disinhibition of irrelevant associations or deficient initiative. Cueing markedly improved their poor retrieval. These defects seem to be associated with frontal lobe lesions and can affect memory but are not obligatory features of amnesia.

Prediction of psychosocial recovery after head injury with cognitive tests and neurobehavioral ratings

A series of 53 patients was studied using a battery of tests and a neurobehavioral rating scale on average 4 months after closed-head injury (CHI). Social outcome was assessed 1 year after injury by interviewing a family member. The results supported the hypothesis that tests of flexibility and programming rather than tests of cognitive skills predict psychosocial recovery after CHI. Spatial Learning with Self-Set Goals and Sorting were measures of flexibility and programming. Contrary to expectation, word fluency performance was unrelated to these measures, but was associated with conventional intelligence tests, which did not predict psychosocial recovery. Cognition/Energy deficit on the Neurobehavioral Rating Scale and increased age were useful predictors of poor psychosocial outcome, whereas computed tomography findings or the Glasgow Coma Score were weakly related to the outcome indices. Evidently, cognitive flexibility and mental programming are very important psychological prerequisites of social recovery after CHI.

Dual task performance after focal cerebral lesions and closed head injuries.

The aim of this study was to demonstrate that focal frontal lobe lesions and closed head injuries cause a deficit in the deliberate minimizing of dual task decrements that follow when two separate tasks should be done concurrently. In single tasks, subjects counted backwards and cancelled visual targets as quickly and accurately as possible on separate 1 min trials. In the dual task, they were required to do both tasks simultaneously, taking care that performance on neither task would be notably more impaired than on the other, as only the performance showing a larger percentage decrement from the corresponding single task performance was taken into account as the result of the test. Patients with acute closed head injury displayed more pronounced dual task decrement than the controls. This deficit was not secondary to inefficiency on the single tasks but was related to the depth of coma at admission, the acuteness of injury and age. Contrary to expectation, patients with focal frontal lobe lesions or patients with subacute closed head injury did not demonstrate abnormal dual task decrement.

Unawareness of deficits after right hemisphere stroke: Double-dissociations of anosognosias

Objectives– The aim was to study whether anosognosia for hemiparesis, anosognosia for neglect and general unawareness of illness double‐dissociate, indicating that anosognosias are specific and independent impairments of awareness. On the other hand, anosognosias may be associated with one another and with general cognitive dysfunction, which decreases awareness of deficits. The persistence and predictive value of anosognosias was examined during a 1‐year follow‐up. Patients and methods– Fifty‐seven consecutive patients with acute right hemisphere infarction underwent neurological and neuroradiological examinations, neuropsychological testing and an interview 10 days, 3 months and 1 year after onset. Results– Anosognosia for neglect and anosognosia for hemiparesis double‐dissociated, as did unawareness of illness and anosognosia for neglect. Patients showing unawareness of illness or anosognosia for neglect and anosognosia for hemiparesis had poorer orientation and verbal memory than patients who were aware of these defects. Unawareness of illness and anosognosia for hemiparesis disappeared during 3‐month follow‐up. Conclusion– Double‐dissociations demonstrate that anosognosias for different defects are independent and specific impairments of awareness, although general cognitive disorder may also reduce awareness of defects. Unawareness of illness and anosognosia for hemiparesis disappear rapidly and can hardly be direct causes of poor long‐term recovery. However, transient anosognosia may be associated with persistent disorders which result in poor outcome.

Social outcome related to cognitive performance and computed tomographic findings after surgery for a ruptured intracranial aneurysm

A series of 83 patients was examined with a battery of cognitive tests, a clinical interview, and computed tomography 1 year after surgery for a ruptured intracranial aneurysm. Disability on the Glasgow Outcome Scale (33%), failure to return to work (25%), impaired social relations (25%), and subjective or clinical mental impairment (56%) were found to be related to each other and to poor performance on cognitive tests, especially to verbal impairments in patients with left lateral infarctions and to memory deficits and cognitive inflexibility in patients with frontal medial infarctions. Furthermore, cognitive deficits and poor outcome were associated with diffuse brain damage. Depression and anxiety were unrelated to test performances, but were frequently reported by patients with right lateral infarctions.

Cognitive deficits related to computed tomographic findings after surgery for a ruptured intracranial aneurysm

A consecutive series of 118 patients operated on for ruptured intracranial arterial aneurysms was studied. Ninety-six of them could be adequately examined with a battery of psychological tests and computed tomographic scans 1 year after a subarachnoid hemorrhage. Seventeen orthopedic control patients with no history of brain damage were also tested. The pattern of cognitive deficits was strongly related to the findings on the computed tomographic scans. Patients with left lateral infarctions had deficits on performances requiring verbal efficiency, including memory and classification tasks, whereas patients who had right lateral infarctions were poor on a visuoconstructional task (the copying of Reys Figure). These deficits were pronounced when lateral infarction was associated with diffuse brain damage. Patients with frontal medial infarctions had low scores on memory tests; the inefficiency in verbal fluency, categorical reasoning, and memory was related to diffuse brain damage. The patients who had no infarctions did not differ significantly from the control group. Cognitive impairments after left lateral and frontal medial infarctions, as well as diffuse brain damage, correlated with the Glasgow Outcome Scale.

Frontal Tests Do Not Detect Frontal Infarctions after Ruptured Intracranial Aneurysm

The series of 155 patients operated on for a ruptured intracranial arterial aneurysm was examined using typical frontal tests (the Stroop test, word fluency tasks, and a sorting task), as well as a learning and memory test. Patients with frontal infarction were not significantly inferior to patients with non-frontal infarction or to patients with no infarction. Frontal patients, however, were unable to return to work as often as non-frontal patients and more frequently than those with no infarction. These results indicate that the frontal tests used in this study are not selectively sensitive to mainly medial frontal infarctions that follow the rupture of an anterior cerebral artery aneurysm.

Word list learning and prediction of recall after frontal lobe lesions

The effect of frontal lobe lesions on the accuracy of prediction of recall in a word list learning task was studied. Fifty-nine patients with a focal brain lesion and 21 non-brain-damaged control patients memorized a word list by selective reminding and predicted before each recall trial the number of words they would be able to recall. The patients with left frontal lesions, who were inferior to the patients with right frontal lesions and the control patients in word list recall, overpredicted their recall more than the other brain-damaged patients or the control patients, especially on the 1st trial. The patients with right frontal lesions were less accurate in the prediction of recall than the patients with right posterior lesions or the control patients.

Relationship of local infarctions to cognitive and psychosocial impairments after aneurysmal subarachnoid hemorrhage.

OBJECTIVE:Previous studies suggest that cognitive and psychosocial impairments after subarachnoid hemorrhage (SAH) result from diffuse brain damage caused by the initial bleeding rather than from focal lesions. We describe the relationship of local infarctions to these impairments and explore how well test and questionnaire results explain psychosocial outcome. METHODS:A total of 170 patients, selected from a consecutive series of patients with aneurysmal SAH, underwent neurological and neuroradiological examinations, and 138 of them were assessed with neuropsychological tests and questionnaires 1 year after SAH. RESULTS:Patients with left and bilateral infarctions performed worse on verbal memory tests than the other patients, and patients with left infarctions had more impaired working capacity than those with no infarction. The indices of the severity of SAH were related to reductions in both working capacity and social activity but less clearly to poor test performances. Whereas the modified Rankin scale was the most important correlate of working capacity, performance on cognitive tests was associated with return to work, and questionnaire ratings of mental impairments correlated with reduced working capacity and decreased social activity. CONCLUSION:Left-hemisphere infarctions cause deficits in verbal memory and working capacity. The severity of SAH is associated with impairments in working capacity and social activity rather than with specific cognitive deficits. Patients’ and partners’ opinions on patients’ mental impairments could provide complementary information to clinical grades and cognitive tests in the evaluation of outcome after SAH.