[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.

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.

Postictal paresis in focal epilepsies--incidence, duration, and causes: a video-EEG monitoring study.

BACKGROUND: Although familiar to every neurologist, postictal paresis (PP) has only rarely been analyzed systematically. OBJECTIVE: To describe the frequency and duration of PP in patients undergoing video-EEG monitoring, the semiology characteristics of seizures preceding PP, and the pattern of associated symptoms and signs. METHODS: The records of 513 consecutive patients who underwent prolonged video-EEG monitoring during presurgical epilepsy evaluation were reviewed for postictal motor deficit. Three hundred twenty-eight patients fulfilled the inclusion criteria. The videotapes of patients with PP were subsequently analyzed with a careful analysis of ictal motor phenomena at the side of the PP. RESULTS: PP was found in 44 patients (13.4%). PP was always unilateral and always contralateral to the seizure focus and had a median duration of 173.5 seconds (range 11 seconds to 22 minutes). Of all seizures with PP, 77.8% were accompanied by evident and 9.7% by very slight ictal motor phenomena ipsilateral to the side of PP, whereas 9.7% of the seizures showed no motor signs (two seizures [2.8%] could not be evaluated for motor phenomena). The most common ictal lateralizing sign was unilateral clonic activity in 55.6% of all seizures. Concomitant dystonic posturing was found in 47.9% and ictal limb immobility in 24.6% of the seizures. PP was of longer duration if ictal clonic activity was present and after tonic-clonic seizures. CONCLUSIONS: PP is relatively frequent (13.4%), is easy to detect, and has a high lateralizing value. The high incidences of dystonic posturing and of ictal limb immobility in our patients with PP may indicate that an active inhibitory process is involved in its pathogenesis.

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.

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.

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.

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.

The role of conceptual knowledge in object use evidence from semantic dementia.

It has been reported that patients with semantic dementia function well in everyday life and sometimes show striking preservation of the ability to use objects, even those specific objects for which the patient has degraded conceptual information. To explore this phenomenon in nine cases of semantic dementia, we designed a set of semantic tests regarding 20 everyday objects and compared performance on these with the patients' ability to demonstrate the correct use of the same items. We also administered a test of mechanical problem solving utilizing novel tools, on which the patients had completely normal ability. All but the mildest affected patient showed significant deficits of naming and on the visually based semantic matching tasks. Object use was markedly impaired and, most importantly, correlated strongly with naming and semantic knowledge. In a small number of instances, there was appropriate use of an object for which the patient's knowledge on the semantic matching tasks was no better than chance; but this typically applied to objects with a rather obvious relationship between appearance and use, or was achieved by trial and error. The results suggest that object use is heavily dependent upon object-specific conceptual knowledge, supplemented to some degree by a combination of visual affordances and mechanical problem solving.

[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.

[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.

"What" and "how": evidence for the dissociation of object knowledge and mechanical problem-solving skills in the human brain.

Patients with profound semantic deterioration resulting from temporal lobe atrophy have been reported to use many real objects appropriately. Does this preserved ability reflect (i) a separate component of the conceptual knowledge system ("action semantics") or (ii) the operation of a system that is independent of conceptual knowledge of specific objects, and rather is responsible for general mechanical problem-solving skills, triggered by object affordances? We contrast the performance of three patients-two with semantic dementia and focal temporal lobe atrophy and the third with corticobasal degeneration and biparietal atrophy-on tests of real object identification and usage, picture-based tests of functional semantic knowledge, and a task requiring selection and use of novel tools. The patient with corticobasal degeneration showed poor novel tool selection and impaired use of real objects, despite near normal semantic knowledge of the same objects' functions. The patients with semantic dementia had the expected deficit in object identification and functional semantics, but achieved flawless and effortless performance on the novel tool task. Their attempts to use this same mechanical problem-solving ability to deduce (sometimes successfully but often incorrectly) the use of the real objects provide no support for the hypothesis of a separate action-semantic system. Although the temporal lobe system clearly is necessary to identify "what" an object is, we suggest that sensory inputs to a parietal "how" system can trigger the use of objects without reference to object-specific conceptual knowledge.

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.

Reliability of automatic and visual analysis of interictal spikes in lateralising an epileptic focus during video-EEG monitoring.

We evaluated 2 h of two night recordings of surface EEG of 10 patients with drug-resistant focal epilepsy using video-EEG monitoring, giving 40 h of EEG. The raw data of the automatic spike analysis according to the Gotman algorithm was visually corrected by rejecting false detections. Furthermore, the complete EEG recordings were analysed independently visually by two experienced electroencephalographers. For each method we analysed the total count of detections and the topographical distribution (left-right) of spikes. The total number of detections was significantly higher (243%) in the raw data and significantly lower after elimination of false detections (57%) in comparison to conventional analysis (100%). Lateralisation was concordant between the methods in 9/10 patients. The extent (< 75%, 75-90%, > or = 90%) was concordant in 80% between the two human raters. The automatic analysis with elimination of false detections was concordant with each of the human raters in 60% of patients. Extent of concordance was dependent of the total number of spikes with patients having more spikes being more reliably lateralised. Our results suggest that visually corrected automatic spike analysis is an economical method to use interictal epileptogenic activity as an independent indicator of the side of the epileptogenic focus in the setting of non-invasive presurgical evaluation. This is especially true in patients with many spikes.

Psychosocial long-term outcome of severe head injury as perceived by patients, relatives, and professionals.

OBJECTIVE: We systematically compared information on psychosocial outcome of severe head injury (SHI) gathered from different informants. MATERIAL AND METHODS: We evaluated psychosocial outcome in 33 subjects 8.1 +/- 1.4 years after having suffered SHI using data gathered from the patients themselves, caring relatives, and an assessing neurologist. RESULTS: Our data confirm long-lasting negative effects of SHI on psychosocial functioning even in patients with only mild or moderate neurological impairment. Specific problems in social intercourse, stemming from impaired self-control, are regularly reported by the relatives and probably underestimated by the patients and by the doctors. In contrast, we found a remarkable agreement between self-report and professional estimation in other aspects of psychological consequences of SHI such as depressed mood and social withdrawal. CONCLUSIONS: Our results challenge the common view that patients having suffered from severe SHI are altogether unreliable informants. However, SHI patients tend to have difficulties in monitoring their specific problems of control of behaviour in social relationships. Therefore information gathered from the caring relatives should always be included when evaluating psychosocial sequels of severe SHI.

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.

Kinematic analysis of movement imitation in apraxia.

Accuracy of the final position and kinematics of movement were analysed during the imitation of meaningless gestures in patients with unilateral brain lesions who performed with the hand ipsilateral to the lesion and in control subjects. Controls imitated the gestures virtually without spatial errors. The kinematics of their movements was characterized by single-peaked and approximately bell-shaped velocity profiles of the transport phase combined with no or only minor corrective movements in the final phase. Patients with right brain damage (RBD) performed as well as control subjects with respect to both spatial accuracy of final hand-positions and kinematic parameters of the movement trajectories. Patients with left brain damage (LBD) committed spatial parapraxias and had a much higher frequency of kinematic abnormalities. However, there was no correlation between kinematic abnormalities and apraxic errors. There were kinematically abnormal movements which reached a correct final position as well as kinematically normal movements leading to apraxic errors. One possible explanation for the combined occurrence of kinematic abnormalities and parapraxias in LBD patients would be that they are independent sequels of left hemisphere lesions. An alternative account is that the associations and dissociations result from an interaction between one common basic deficit and strategies to cope with this deficit. The basic deficit may concern the mental representation of the target position. The LBD patients may react to the absence of an appropriate representation of the target by one of two alternative strategies; they may switch to a strategy of slowed, on-line controlled movements to find the required final position, or they may move their hand smoothly at normal speed to a roughly specified location without taking note of their deficiency. Depending on whether these strategies are successful or not they would lead to the observed associations and dissociations between kinematic abnormalities and spatial parapraxias.

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.

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.

Dopamine D2 receptor binding is reduced in Wilson's disease: correlation of neurological deficits with striatal 123I-iodobenzamide binding.

To visualise and quantify dopamine D2 receptor binding in the corpus striatum of patients with neurological Wilson's disease (WD) 123I-Iodobenzamide (IBZM) binding was measured using single photon emission computer tomography (SPECT). Ratios of striatal to frontal countrates were calculated in 8 patients and in 21 healthy control subjects. We found reduced IBZM binding ratios in all patients with WD in comparison to those in controls (1.48 +/- 0.13 vs. 1.73 +/- 0.09). The reduction in IBZM binding was correlated with the overall severity of neurological deficits and the severity of dysarthria (correlation coefficients -0.86 [p < 0.01] and -0.79 [p < 0.01], respectively). When patients of three different subgroups of neurological WD were compared no differences in IBZM binding were found. We conclude that assessing basal ganglia function in vivo using IBZM-SPECT is a valuable diagnostic tool in WD.