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Biomedical subjects

H Hildebrandt

Publications and source records attributed to H Hildebrandt.

At least 19 recordsLinked to original sources

[Evidence based treatment of executive dysfunction].

The therapy of executive functions plays an essential role for the functional outcome and the social reintegration. Nevertheless there is a lack of cognitive oriented and evidence-based therapy programs. The purpose of our review is the classification of the present evaluation studies with regard of the principles of evidence based medicine (EbM) and of the content. Besides the EbM criteria the number of participants, the kind and number of interventions, the types of etiology and the standardisation and quality of the outcome parameters are measured. By that, an assessment should be possible, which interventions are successful for what types of dysexecutive syndrome. The present studies belong to three different types of therapy: at first, a therapy form focussing on manipulation and modification of the environment, second, a therapy form using behaviour management and a third form, which is based on practise and cognitive interventions. The heterogeneity of the therapy forms makes different types of evaluation necessary. The evaluation studies reach different classes of evidence. While the cognitive therapy forms reach comparable high evidence classes, the evaluation studies about behaviour management--mostly present as single case studies with individual outcome parameter--reach only low evidence classes. Final, we discuss, which therapy forms are effective using the strong evaluation criteria and at which point further conceptual task and further research is useful.

Cognitive Behavioral Therapy↗

Memory performance in multiple sclerosis patients correlates with central brain atrophy.

OBJECTIVE: To assess whole brain and central brain atrophy as well as their differential relation to memory, cognitive performance, fatigue, depression and quality of life in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: A 3D flow compensated gradient recalled T1-weighted MRI was acquired in 45 RRMS patients. An automated analysis tool was used to calculate brain parenchymal fraction (BPF) and ventricular brain fraction (VF). All patients were assessed with neuropsychological tests focusing on memory and self-rating scales for depression, fatigue and quality of life. Age corrected partial correlations between brain atrophy, motor performance, psychological scales and test scores were calculated. RESULTS: BPF correlated moderately (0.3 < or = r < 0.5) with duration of symptoms and disease, the Expanded Disability Status Scale (EDSS), the upper extremity motor performance, and with mental aspects of quality of life. VF correlated moderately with EDSS, upper and lower extremity motor performance and memory functions. Neither BPF nor VF correlated with fatigue and depression. Results of several cognitive tests correlated moderately with depression and fatigue, the Paced Auditory Serial Addition Test (PASAT) showing the largest correlation. CONCLUSIONS: Memory performance shows a correlation with relative ventricular size in RRMS patients, indicating the strategic location of the ventricle system along the structures of the limbic system and its vulnerability in MS. The PASAT and several other cognitive tests show moderate correlations with depression and fatigue, arguing for an inter relation between the cognitive functioning and the emotional state of patients. However, this relation is independent of measurable brain atrophy.

Adult↗

Event-related theta oscillations during working memory tasks in patients with schizophrenia and healthy controls.

Altered frontal lobe activity and executive control associated with working memory (WM) dysfunction are recognized as core deficits in schizophrenia. These impairments have been discussed as being associated with deficits in self-regulated action monitoring and anticipatory action plan generation. To study electrophysiological correlates of executive control -- specifically action monitoring and action rule switching -- under varying WM load, we used a paradigm derived from classic N-back (WM) tasks and requiring monitoring of simple actions. We focused on event-related changes in post-stimulus theta oscillatory activity during varying cognitive and WM demand in healthy controls and schizophrenia patients. The results show significant WM load and rule-switching-related increases of post-stimulus theta amplitude at fronto-central locations in controls. In patients with schizophrenia, there was no such modulation, but -- apart from an increased early theta at left temporal locations -- generally reduced late theta responses in all tasks and at all locations. Furthermore, the patients with schizophrenia showed significant differences in their error patterns, which imply differences in automation and anticipation of actions between controls and patients. These findings suggest that theta oscillations are involved in mediating frontal lobe activity and functions related to enhanced executive control. We conclude that the patients with schizophrenia showed deficits in acquiring a mental task set which appear to be associated with impairments in action monitoring and task-specific regulation of executive control.

Adult↗

Frontal lobe dysfunctions in Korsakoff's syndrome and chronic alcoholism: continuity or discontinuity?

The effect of long-term heavy alcohol consumption on brain functions is still under debate. The authors investigated a sample of 17 Korsakoff amnesics, 23 alcoholics without Korsakoff's syndrome, and 21 controls with peripheral nerve diseases, matched for intelligence and education. Executive functions were examined for word fluency, the modified Wisconsin Card Sorting Test, an alternate response task, and an "n-back" working memory task. Korsakoff amnesics, but not alcoholics, showed a marked memory impairment. They also scored lower in each of the executive tasks-the alcoholics only in the alternate response task. This task also correlated with the years of the alcohol dependency. First, the authors conclude that Korsakoff's syndrome is associated not only with a memory impairment but also with a global executive deficit. Second, the decline in the ability to alternate between different responses argues for a restricted neurotoxic effect of alcohol on some frontal lobe areas.

Adult↗

[Neglect dyslexia owing to traumatic fronto-temporal right hemisphere bleeding].

Apart from unilateral disturbance of the egocentric reference system, as it is traditionally known of neglect, there are also cases with unilateral disturbances of a stimulus-centered or object-centered reference system. In these cases the spatial position of the object, from the observer's perspective, plays only a limited role in the explanation of the problems with object perception. We describe a patient who, following head-brain trauma and a fronto-temporal bleeding, showed, beside traditional neglect, also a stimulus-centered left-sided disorder in word and object perception. Our investigations showed that this disorder (a) is independent of the position of the object in the environmental space, (b) comprises words and objects, and (c) is especially sensitive for changes in the first letters of a word. Conclusively, it yields from this case that at least three different reference systems of object representation should be distinguished in neglect, which can be disturbed independently from each other and may negatively influence the behavioral potential of the patients.

Adult↗

Visuospatial hemi-inattention following cerebellar/brain stem bleeding.

Neglect is a unilateral lack of responsiveness to stimuli caused by visuospatial hemi-inattention, a unilateral representation deficit and/or a unilateral hypokinesia. It results most frequently from right-hemisphere brain damage, particularly of the parietal lobe but also of the frontal cortex, the basal ganglia, the thalamus, and recently it has also been described after a cerebellar lesion. We report a patient with right-sided bleeding of the posterior inferior cerebellar artery, who developed a left-sided visual hemi-inattention. She had no visual field defects, yet she had problems detecting left-sided targets in visual extinction. Furthermore, she was impaired in detecting complex motion on the left side and targets in a fixation offset paradigm. Reactions to left-sided targets in covert shifts of attention were slowed in the invalid condition. Her text reading was impaired as she could not always find the initial word of the next line. However, she was aware of her deficit. Her visuoconstructive ability was normal and she gave no indication of tactile or acoustic extinction. As the cerebellar lesion was located in the right hemisphere and the inattention involved the left side of space, we suggest that the damage to the right brain stem led to a transient imbalance of the noradrenergic ascending activation system which may explain her hemi-inattention.

Brain Stem↗

Retinoic acid-induced changes in polysialyltransferase mRNA expression and NCAM polysialylation in human neuroblastoma cells.

Polysialic acid (PSA) is a dynamically regulated carbohydrate modification of the neural cell adhesion molecule NCAM, which is implicated in neural differentiation and cellular plasticity. The cloning and characterization of two polysialyltransferases, termed ST8SiaII (STX) and ST8SiaIV (PST), opened up new perspectives in the search for factors that control this unique cell surface glycosylation. In vitro and transfection approaches revealed that ST8SiaII and ST8SiaIV are independently capable of synthesizing PSA on NCAM with slightly different specificities towards the major NCAM isoforms and glycosylation sites. Their overlapping but distinct expression patterns during brain development point towards an independent transcriptional regulation. However, the factors driving their joint or distinct expression, as well as the significance of divergent expression patterns in vivo, are not yet understood. In the present study, the mRNA expression of ST8SiaII and ST8SiaIV was comparatively analyzed in neuronal differentiation of PSA-positive human neuroblastoma cell lines induced by retinoic acid (RA), phorbolester, or growth factors. Using a semiquantitative RT-PCR strategy, we demonstrated a general decrease in the mRNA level of ST8SiaII upon differentiation of SH-SY5Y and LAN-5 cells. In contrast, a drastic increase of ST8SiaIV was specifically induced by RA-treatment of SH-SY5Y cells. To explore the significance of these changes, the cellular capacity to perform PSA synthesis and the degree of NCAM polysialylation were analyzed. Our data indicate that the increased expression of ST8SiaIV enables an accelerated polysialylation of NCAM, which, however, is not converted into higher amounts of PSA.

Antigens, Surface↗

[Verbal memory disorders provoked by a variety of stokes].

In recent years a consensus has been reached about the neuroanatomical substrate of verbal memory, but this state of knowledge has not yet been implemented in clinical practice. One reason for this may be that most of the neuroscientific studies on verbal memory used different neuropsychological instruments and that only a small set of patient groups with the same etiology but different lesion sites were analysed. Returning to three earlier studies, we analyse the possibility to make differential judgements on the verbal memory impairments of four different patient groups by using the California Verbal Learning Test (CVLT). We compare patients with left-sided (n = 16) and right-sided (n = 10) posterior cerebral artery infarcts and patients with infarcts of the left (n = 10) or right (n = 21) frontal lobe, and we integrated data about their retention errors that had not been analysed so far. Our findings reveal significant differences between these patient groups, concerning the quantitative aspects of impairments, and also the profiles of memory errors (recall, interference and perseverations). Our study documents a relation between the site of the lesion and the type of verbal memory impairment, agreeing with some of the most recent neuroscientific findings. Starting from this observation we try to define a neuropsychological pattern of memory impairment which enables differential clinical diagnoses using the CVLT as a memory test.

Female↗

Are some memory deficits unique to lesions of the mammillary bodies?

The role of the mammillary bodies in human memory is still in debate. A recent model of human amnesia proposes similar functions for the mammillary bodies and the hippocampus. But the main evidence for this model comes from animal studies using the delayed non-matching to sample paradigm. We describe a patient who developed a severe memory impairment after surgical removal of a germinoma. Postsurgical high resolution MRI revealed bilaterally shrunken mammillary bodies and an infarct of the left mammillary body. There were no other relevant lesions. Neuropsychological testing showed mildly impaired frontal lobe functions (executive functions, working memory and word fluency), almost intact learning and recognition, but severely impaired free and delayed recall. Experimental investigations revealed a reduced but preserved release of proactive interference and a pronounced impairment of recency and source judgments. We conclude that the mammillary bodies do play a prominent role in human memory, although the role differs slightly from that of the hippocampus.

Adult↗

[Analysis of the need for clinical neuropsychology in inpatient neurological rehabilitation (phases C and D)--an empirical study of 788 patients].

Recently, several studies concerning the need for neuropsychologists in early or in out-patient rehabilitation settings have been submitted; however, an analysis of classical in-patient neurological rehabilitation which is most important by virtue of its numerical impact has not yet been performed. An empirical study focussing on the need for neuropsychologists during in-patient rehabilitation (phases C and D) is discussed. The two-year study records deficits observed among all patients with damage to the central nervous system (n = 788) admitted to a neurological rehabilitation clinic in north-western Germany. The deficits were divided into the following groups: memory, visual-constructional, deficits involving the planning process, attention deficits and emotional disturbances. Depending on the deficits displayed, patients were prescribed either individual or group therapy, or a combination of both. An empirical pattern of job distribution for neuropsychologists is calculated for the first time based upon findings of the study, which concern the time required for neuropsychological diagnostics, neuropsychological therapy, consultation of relatives and a fixed time-budget established for team supervision and documentation.

Adult↗

Control of NCAM polysialylation by the differential expression of polysialyltransferases ST8SiaII and ST8SiaIV.

Polysialic acid (PSA) is a developmentally regulated carbohydrate consisting of alpha-2,8-linked sialic acid residues attached to the neural cell adhesion molecule NCAM. PSA promotes plasticity of cell-cell interactions in the nervous system and appears linked to the malignant potential of several tumors. Two enzymes, the polysialyltransferases ST8SiaII (STX) and ST8SiaIV (PST) have been identified and shown to be independently able to synthesize PSA. However, in vivo studies have demonstrated that in the majority of PSA-positive tissues the two polysialyltransferases are expressed simultaneously. Therefore, this study was undertaken to elucidate in which way the individual enzymes contribute to PSA expression under in vivo conditions. Using a semiquantitative RT-PCR strategy PSA-positive human tumor cell lines were screened for expression of ST8SiaII and ST8SiaIV at the mRNA level. Divergent patterns observed in some cell lines suggest that polysialyltransferases are independently regulated at the transcriptional level. In subsequent analyses the different mRNA levels of ST8SiaII and ST8SiaIV in these tumor cells were correlated with the degree of PSA expression and the cellular capacity to rapidly synthesize PSA. Our data indicate that ST8SiaIV is the major regulator of NCAM polysialylation in vivo.

Blotting, Northern↗

Direct electrospray-ionization mass spectrometric analysis of the major ganglioside from crucian carp liver after thin layer chromatography.

Ganglioside patterns from crucian carp brain, muscle, and liver as well as liver gangliosides of roach, carp, the cichlid Oreochromis mossambicus, pigeon, dwarf hamster, and calf were comparatively analyzed by high performance thin layer chromatography (HPTLC). To achieve a rapid estimation on potentially interesting ganglioside compounds, electrospray-ionization mass spectrometry (MS) was directly applied to a chloroform/methanol extract of the major TLC band of crucian carp liver. The spectrum, obtained from a few micrograms of this crude biological sample, revealed a series of peaks corresponding to GM4-like monosialoganglioside species. GC-MS analysis revealed hydroxylated fatty acids ranging from 2 h 20 min:0 to 2 h 26 min:0 for the [M'H]- ions of m/z 1061-1145. Collision induced dissociation tandem MS/MS of the major peak with a [M'H]- ion of m/z 1117 demonstrated the presence of N-acetylneuraminic acid as sialic acid compound. The sugar composition was confirmed by GLC as galactose and sialic acid in a 1:1 molar ratio. Thus, the structure of the ion at m/z 1117 is N-acetylneuraminylgalactosylceramide (NeuAc-Gal-Cer) with the long chain base d18:1 and the hydroxylated fatty acid 2 h 24 min:0. The results demonstrate for the first time unambiguously that NeuAc-Gal-Cer is the main ganglioside fraction in fish liver and that electrospray ionization-mass spectrometry (ESI-MS) can be used to elucidate the chemical composition of a ganglioside fraction obtained by convenient extraction of a HPTLC band.

Animals↗

Visual search and visual target detection in patients with infarctions of the left or right posterior or the right middle brain artery.

We compared visual target detection and search performance of patient groups with infarctions of (1) the right middle brain artery (R-MBA) and with neglect; (2) the left posterior artery (L-PBA), (3) the right posterior artery (R-PBA), the latter two groups had contralesional hemianopias, or (4) with right hemisphere lesions without hemianopia or neglect. We found that: (1) The first three groups differed from the fourth (control) group in omissions. (2) The first three groups differed only in horizontal search but not in target detection. (3) No vertical search deficit was present for either group. (4) R-MBA patients found increasingly more targets in visual search from left to right, R-PBA patients had problems with the outermost contralesional column, L-PBA patients showed a generally slowed and more variable search pattern. Infarctions of left and R-PBA therefore resulted in different visual search patterns. The behavior of the patients with R-MBA is consistent with Kinsbourne's (1992) interactive inhibition theory of neglect.

Aged↗

Polysialic acid on the neural cell adhesion molecule correlates with expression of polysialyltransferases and promotes neuroblastoma cell growth.

Neuroblastomas and cell lines derived from these tumors bear the oncodevelopmental antigen polysialic acid (PSA) bound to the neural cell adhesion molecule. Polysialyation of neural cell adhesion molecule can be achieved by two different polysialyltransferases, ST8SiaII and ST8SiaIV. This study was undertaken to investigate the pattern of polysialyltransferases expressed in the human neuroblastoma cell line SH-SY5Y. Reverse transcription-PCR showed simultaneous expression of the two enzymes, and in situ hybridization demonstrated that the polysialyltransferase mRNA expression parallels immunoreactivity with the PSA-specific monoclonal antibody 735. After retinoic acid-induced differentiation, only the PSA-positive, neuron-like cell type gave clear signals for ST8SiaII and ST8SiaIV in in situ hybridization, whereas both signals were drastically reduced in the weakly PSA-positive substrate adherent phenotype. Like the SH-SY5Y cells, a primary, PSA-positive neuroblastoma specimen revealed expression of the two polysialyltransferases. To investigate the role of PSA for cell growth and differentiation, SH-SY5Y cells were treated with the PSA-specific endo-N-acetylneuraminidase E. Although loss of PSA was accompanied with a marked reduction of cell growth, it did not interfere with retinoic acid-induced differentiation. Together, our results suggest that PSA surface expression is regulated on the level of polysialyltransferase transcription. Moreover, the similarity to the primary neuroblastoma tissue makes SH-SY5Y cells a suitable model system to examine further the role of polysialylation in tumor cell growth and the orchestration of PSA synthesis in neuroblastoma.

Cell Differentiation↗

Region-specific activation of microglial cells in the rat septal complex following fimbria-fornix transection.

Studies of postlesional microglial activation may gain insight into microglia/neuronal interactions in processes of neurodegeneration. We compared the microglial response after axotomy of septohippocampal projection neurons with that seen after selective immunolesioning of cholinergic septohippocampal neurons with the immunotoxin 192 IgG-saporin. Using the microglial marker isolectin B4 from Griffonia simplicifolia (GSA I-B4), we found striking differences in the microglial response between these two lesion paradigms. Following axotomy of septohippocampal neurons by fimbria-fornix transection (ff-t), there was only a moderate and short-lasting microglial reaction in the medial septum (MS) in the early postlesion period. Prelabeling of septohippocampal neurons with Fluoro-Gold (FG) prior to axotomy revealed the survival of most neurons, and only very rarely were microglial cells observed that had phagocytosed FG-labeled debris. In the lateral septum (LS) containing the degenerating terminals of hippocamposeptal fibers transected by ff-t, a heavy reaction of lectin-labeled activated microglial cells associated with high phagocytotic activity was noticed. Unexpectedly, after a long survival time (6 months) following ff-t, we observed an increase in microglial GSA I-B4 labeling in the MS. In contrast, an inverse pattern of the microglial response, i.e., a strong initial reaction in the MS and very little microglial activation in the LS, was observed after immunolesioning. Our results indicate that the microglial reaction in the MS following ff-t differs substantially from that seen in other models of axotomy.

Animals↗