The neural basis of tool use.

Misuse of tools and objects by patients with left brain damage is generally recognized as a manifestation of apraxia, caused by parietal lobe damage. The use of tools and objects can, however, be subdivided in several components. The purpose of our study was to find out which of these are dependent on parietal lobe function. Thirty-eight patients with left brain damage and aphasia were examined using tests to assess the retrieval of functional knowledge from semantic memory (Functional Associations), mechanical problem solving (Novel Tools) and use of everyday tools and objects (Common Tools). Voxel-wise analysis of magnetic resonance images revealed two regions where lesions had a significant impact on the test results. One extended rostrally from the central region and ventrally through the middle frontal cortex to the dorsal margin of the inferior frontal gyrus. The other reached dorsally and caudally from the supramarginal gyrus, through the inferior, to superior parietal lobe. Whereas the frontal lesions had an adverse influence on all experimental tests as well as on the subtests of the Aachen Aphasia test, parietal lesions impaired Novel and Common Tools, but did not have an adverse effect on the Functional Associates. An association between Functional Associations and temporal lesions became apparent when patients with only a selective deficit in the test were considered, but did not show up in the whole group analysis. The parietal influence was as strong for the selection as for the use of either novel or common tools, although choice of appropriate manual configuration and movements was more important for use than for selection. We conclude that the contribution of the parietal lobe to tool use concerns general principles of tool use rather than knowledge about the prototypical use of common tools and objects, and the comprehension of mechanical interactions of the tool with other tools, recipients or material rather than the selection of grip formation and manual movements.

[Consensus statement "Dementia 2010" of the Austrian Alzheimer Society]. / Konsensusstatement "Demenz 2010" der Osterreichischen Alzheimer Gesellschaft.

The Austrian Alzheimer Society developed evidence-based guidelines based on a systematic literature search and criteria-guided assessment with subsequent transparent determination of grades of clinical recommendation. The authors evaluated currently available therapeutic approaches for the most common forms of dementia and focused on diagnosis and pharmacological intervention, taking into consideration the situation in Austria. The purpose of these guidelines is the rational and cost-effective use of diagnostic and therapeutic measures in dementing illnesses. Users are physicians and all other providers of care for patients with dementia in Austria.

Wilson's disease: evidence of subgroups derived from clinical findings and brain lesions.

Using exploratory factor analysis, we prospectively investigated neuropsychiatric symptoms and structural brain lesions of 47 patients with proven Wilson's disease and identified three subgroups. The first subgroup clinically exhibited bradykinesia, rigidity, cognitive impairment, and an organic mood syndrome and by MRI showed a dilatation of the third ventricle. The second subgroup was characterized by ataxia, tremor, reduced functional capacity, and focal thalamic lesions. The third subgroup showed dyskinesia, dysarthria, an organic personality syndrome, and focal lesions in the putamen and in the pallidum.

Ideomotor apraxia and cerebral dominance for motor control.

Ideomotor apraxia is a symptom of left hemisphere damage. Patients with ideomotor apraxia commit errors when imitating movements with their left, non-paralyzed hand. This has been taken as evidence for a motor dominance of the left hemisphere. It has been hypothesized that the left hemisphere is dominant for internal preprogramming of skilled movements of either hand. We investigated the kinematics of movement trajectories of imitation of meaningless gestures. Group analysis confirmed that hesitant, feedback-controlled movement prevail in patients with apraxia, but analysis of single cases revealed the existence of kinematically normal movements leading to apractic errors. Enhanced reliance on feedback-control appears to be a compensatory strategy rather than the source of apractic errors. In a second study we explored the alternative hypothesis that patients with apraxia lack a general concept of the human body which is necessary to mediate the translation of a target position seen on the model into a target position on the patient's body. Imitation of movements was examined on oneself and on a mannikin. Patients with apraxia who made errors when imitating on themselves committed errors also when imitating on the mannikin. Taken together, both studies support the view that the source of errors in the imitation of gestures is to be sought at a conceptual level. This casts doubts on the alleged dominance of the left hemisphere for motor control.

Infusion of nifedipine after coronary artery bypass grafting decreases the incidence of early postoperative myocardial ischemia.

We performed a randomized study on patients undergoing elective coronary bypass grafting to examine whether postoperative infusion of nifedipine (n = 25) could reduce the incidence of isolated transient myocardial ischemia, myocardial infarction, or both. The control group (n = 25) received nitroglycerin. Hemodynamic and Holter monitoring and serial assessment of enzymatic and electrocardiographic changes were performed for all patients. Both groups showed comparable preoperative and operative data. The incidence of myocardial infarction was significantly lower in the nifedipine group (n = 1) as compared with the control group (n = 4), whereas the number of patients with isolated transient myocardial ischemia was similar in both groups (nifedipine, 3; control, 4). At the time of peak activity, levels of creatine kinase (350 +/- 129 versus 511 +/- 287 IU/mL), creatine kinase-MB (8.4 +/- 5.4 versus 17.1 +/- 11.0 IU/mL), and glutamate-oxaloacetate-transaminase (30.4 +/- 4.4 versus 41.0 +/- 7.9 IU/mL) were markedly lower in the nifedipine group (p less than 0.05). We conclude that infusion of nifedipine after elective coronary artery bypass grafting effectively decreases the incidence of myocardial infarction and the extent of myocardial necrosis during the early postoperative period.

Epileptic and non-epileptic seizures in multiple sclerosis.

Knowledge concerning the relationship between multiple sclerosis and epilepsy is reviewed. Epidemiological studies have established that epileptic seizures are more frequent in multiple sclerosis than predicted by chance. Partial epilepsies with focal seizures often with atypical symptoms and with or without secondary generalisation are the usual pattern. In the survey special emphasis is laid on the direct correlation between paroxysmal phenomena and plaques now demonstrable by modern imaging techniques. These images have shown that epileptic seizures can be caused by cortical and subcortical lesions and by their accompanying oedema. We extend the review to non-epileptic paroxysmal symptoms, such as tonic spasm, which may be confused with epileptic seizures. As far as they are supported by data, recommendations for diagnosis and therapy are given. Open questions are identified and issues for further research are suggested.

A 28-week, double-blind, placebo-controlled study with Cerebrolysin in patients with mild to moderate Alzheimer's disease.

Cerebrolysin (Cere) is a compound with neurotrophic activity which has been shown to be effective in the treatment of Alzheimer's disease (AD) in earlier trials. The efficacy and safety of repeated treatments with Cere were investigated in this randomized, double-blind, placebo-controlled, parallel-group study. One hundred and forty-nine patients were enrolled (76 Cere; 73 placebo). Patients received i.v. infusions of 30 ml Cere or placebo 5 days per week for 4 weeks. This treatment was repeated after a 2-month therapy-free interval. Effects on cognition and clinical global impressions were evaluated 4, 12, 16, and 28 weeks after the beginning of the infusions using the Clinical Global Impression (CGI) and the Alzheimer's Disease Assessment Scale-cognitive subpart (ADAS-cog). All assessments, including the 28-week follow-up visit were performed under double-blind conditions. At week 16, the responder rate of the Cere group was 63.5% on the CGI, compared to 41.4% in the placebo group (P < 0.004). In the ADAS-cog, an efficacy difference of 3.2 points in favour of Cere was observed (P < 0.0001). Notably, improvements were largely maintained in the Cere group until week 28, 3 months after the end of treatment. Adverse events were recorded in 43% of Cere and 38% of placebo patients. Cere treatment was well tolerated and led to significant improvement in cognition and global clinical impression. A sustained benefit was still evident 3 months after drug withdrawal.

Ictal visual hallucinations and post-ictal hemianopia with anosognosia.

We report the case history of an adult who developed seizures with nearly pure visual symptoms due to an occipital vascular lesion. The seizures were characterized by elementary visual hallucinations in the right visual field. Interictally, a dense homonymous hemianopia was demonstrated in the clinical examination and by using perimetry, but was not recognized by the patient himself. The seizures vanished and the visual fields normalized completely after initiation of anticonvulsive treatment.

Subjective perception of seizure precipitants: results of a questionnaire study.

We evaluated self-perception of seizure precipitants in 149 adult subjects with epilepsy: 71% of the subjects reported at least one factor that, according to the perception, increased the risk of suffering from a seizure. The subjects most often reported psychological stress, change of weather and sleep deprivation. Among the disease-related factors, seizure frequency and the state of consciousness at the onset of the seizures influenced perception of precipitants. Furthermore the perception of some precipitants was dependent on such social variables as rural versus urban surroundings. It is argued that the perception of seizure precipitants is the result of a combination of physiologically based temporal and causal correlations and of beliefs of the patient about such relationships. Hence reports of seizure precipitants are determined by somatic as well as psychological factors. Efforts to clarify the relationship between possible precipitants and the occurrence of seizures should be intensified. In addition the great importance of seizure precipitants in lay theories of epilepsies should be considered in counselling patients with epilepsies.

Influence of size and site of cerebral lesions on spontaneous recovery of aphasia and on success of language therapy.

Changes in linguistic competence were assessed with the Aachen Aphasia Test in 18 aphasic patients across 8 weeks of spontaneous recovery, 8 weeks of intensive language therapy, and after a follow-up period of 8 weeks without therapy. CT scans were obtained from all patients and were evaluated for size of lesion and for affection of Wernicke's area, adjacent regions of superior and middle temporal gyrus, inferior parietal lesions, and temporobasal lesions. Size of lesion had a negative influence on recovery in all phases. Patients with lesions to temporobasal regions showed less improvement during therapy and less total recovery, but a similar amount of spontaneous recovery than patients without such lesions. Lesions that affected the temporobasal regions were on average larger than those which spared them, but the dissociation between reduced therapy success and unaffected spontaneous recovery became even more conspicuous when the concurrent effect of lesion size was minimized by appropriate selection of patients. Possibly, temporobasal lesions cause a disconnection between the hippocampal formation and perisylvian language areas and hinder explicit learning of linguistic knowledge and compensatory strategies.

Perioperative infusion of nifedipine and metoprolol provides antiischemic and antiarrhythmic protection in patients undergoing elective aortocoronary by-pass surgery.

A randomised study was performed on 70 patients undergoing elective coronary by-pass procedure to examine whether the combined, perioperative, 24-hour infusion of nifedipine and metoprolol reduces the incidence of perioperative myocardial ischemia and arrhythmias. The control group received nifedipine only. Repeated assessments of serum enzyme levels and 12-lead-ECG together with a 3-channel Holter monitoring over 48h were used to classify perioperative myocardial ischemia and supraventricular and ventricular arrhythmias. The two groups did not differ with respect to their demographic data, extracorporeal circulation, aortic cross-clamping time, or number of distal anastomosis. No perioperative myocardial infarction in either group was detected. However, a significantly lower incidence of transient ischemic event was observed in the NM group as compared transient ischemic events was observed in the NM group as compared to the N group. In addition, there was a tendency towards lower CK-MB-level and peak-values of CK- and CK-MB-enzymes in the NM group. With regard to perioperative dysrhythmias, there was a significantly lower incidence of sinus tachycardia and atrial flutter/fibrillation in the NM group as compared to the N group. In addition, postoperative heart rate was lower in the NM group starting from the 6th hour after opening the aortic cross-clamp. In conclusion, the combined perioperative infusion of nifedipine and metoprolol is superior in preventing perioperative myocardial ischemia and decreasing the incidence of supraventricular arrhythmias as compared to a single-drug regimen with nifedipine.

[Therapy of epilepsy in the elderly]. / Zur Therapie der Altersepilepsie.

The incidence of epileptic seizures is high in childhood, but shows regression during adult life until the age of 65 when there is again a marked, age-dependent increase in frequency. The specific problems of anticonvulsive therapy in the elderly are discussed in the light of the sparse literature on this subject. Pathophysiological influences of aging on the pharmacodynamics and pharmacokinetics of antiepileptic drugs have to be taken into account, such as changes in the renal, hepatic and intestinal functions as well as increased neuronal receptor sensitivity, among other factors. The optimal time to start therapy is controversial. In selecting the antiepileptic drug, particular attention must be paid on cognitive dysfunction and impairment of impulse conduction. Moreover, age-dependent side effects, as well as possible additive effects due to interaction with other medication have to be taken into consideration. In view of the high rate of relapses great caution has to be taken to withdraw the antiepileptic drugs in completion of the therapeutic regimen.

[Current problems in epilepsy]. / Aktuelle Fragen der Epilepsie.

Three new aspects of epilepsy are discussed: the mesiotemporal syndrome, vagus nerve stimulation, and epilepsy and driving fitness. In recent years mesiotemporal epilepsy has been recognised as the most frequent epileptic syndrome in adults. The main clinical features are febrile convulsions during childhood, followed by characteristic focal seizures in the second decade of life. The typical seizure is characterised by an aura, followed by loss of consciousness, with motor phenomena and automatisms followed by longer periods of postictal confusion. Atrophy of the hippocampus and sclerosis are observed in MRI. The syndrome is frequently drug resistant, however, 80% of the patients are free of seizure after surgical treatment. Vagus nerve stimulation is a new option in the treatment of patients with drug resistant epilepsy (partial seizures with or without secondary generalization, Lennox-Gastaut syndrome), especially when surgical intervention is not indicated. Worldwide a total of more than 4000 patients have been treated. More than 50% reduction in the frequency of seizures can be obtained in 35-40% of drug resistant patients. Complications are rare. Finally, the issue of driving fitness and epilepsy as well as provoked seizures are discussed. The current regulations and laws are taken into consideration and revised regulations for Austria are suggested.

Evaluation of a simulation of human performance on random-digit generation: measures of concept and redundancy.

Ginsburg and Karpiuk in 1995 introduced an algorithm that simulates human performance in tasks of generating random digits. We have compared sequences produced by this algorithm with human performance and truly random sequences. It is shown that the algorithm can be used to simulate human performance according to the measures on which it had been constructed. However, other peculiarities of human performance are not captured by the algorithm. The results are discussed with regard to current theories of human random digit generation.

[The importance of Arnold Pick for modern concepts of degenerative dementia. Retrospect and appreciation]. / Die Bedeutung Arnold Picks für moderne Konzepte degenerativer Demenzen. Erinnerung und Würdigung.

It will be shown that the contribution of Arnold Pick (1851-1924) goes far beyond the first description of the disorder associated with his name. His view that the process of dementia should not be conceptualised as a diffuse degradation of mental abilities but as a mosaic of circumscribed neuropsychological deficits is as modern now as it was then and is a prerequisite for the differential diagnosis of degenerative dementias during life.

Components of random generation by normal subjects and patients with dysexecutive syndrome.

The study presents a hypothesis on how randomness could be simulated by human subjects. Three sources of deviation from randomness are predicted: (1) the preferred application of overlearned production schemata for producing sequences of digits, (2) a wrong concept of randomness, and (3) the impossibility to monitor for redundancies of higher- than those of first-order. Deviations of random generation of digits produced by healthy subjects, patients with chronic frontal lobe damage, and patients with Parkinson's disease from random sequences produced by a computer program can be explained by the differential influence of these factors. Whereas incorrect concepts of randomness and limits on monitoring capacity distinguished all sequences produced by humans from actual random sequences, persistence on a single production strategy distinguished brain-damaged patients from controls. Random generation of digits appears to be a theoretically transparent and clinically useful test of executive function.

Double dissociations between neglect tests: possible relation to lesion site.

In 20 patients who had suffered a first right hemisphere stroke, we examined the prevalence of double dissociations between the results of a star cancellation and a line bisection test. Both are common methods to assess spatial hemineglect. Within the group of neglect patients, we found no significant correlation between the two tasks. Furthermore, 5 patients with impaired performance on one of the tests were within the normal range on the other one. In agreement with experimental studies, we argue that spatial hemineglect is not a unitary syndrome. Furthermore, the findings in one of our patients are compatible with the view that an isolated deficit on cancellation tasks might follow from a lesion in the right anterior cingulate gyrus.

Speed of motor execution and apraxia.

We used a reaction time paradigm to explore the relationship between motor execution and apraxia. The task required reaching for one to three keys. The instruction was varied by introducing a model of a hand indicating which fingers to use. Whereas patients with right-brain damage were slower than controls regardless of condition, the performance of patients with left-brain damage was only impaired when movements had to be carried out according to the model. Although this indicates a deficit in movement planning, there was no correlation between the impairment of patients with left-brain damage and clinical manifestations of apraxia. It thus remains an open question whether the impairment reflects an aspect of motor dominance of the left hemisphere that is too subtle to be detected by clinical apraxia testing, or whether it is related to task demands outside the domain of motor control. In any case, the results of this study demonstrate the need to control cognitive task demands when exploring motor capabilities of patients with left-brain damage.

Simple dysphasic seizures as the sole manifestation of relapse in multiple sclerosis.

In a patient with multiple sclerosis (MS), dysphasic seizures were the only manifestation of a relapse. There was a strong correlation between time course of seizures and EEG, and between a localized EEG focus and a magnetic resonance imaging (MRI)-verified encephalitic plaque in the left temporal lobe.