Search

Purpose: Cognitive disorders are common in MS patients without any generally recommended treatment. Recent brain imaging studies show considerable neuroplasticity for cognitive tasks in MS patients, but also brain atrophy already early in the disease progression. We explored the benefits of a home-based cognitive training program for memory and working memory functions in relapsing-remitting MS patients controlling for whole brain and central brain atrophy as covariates., Methods: Using a single-blinded controlled study design, 42 patients were randomised into a treatment group and a control group. Home based computer training focusing on memory and working memory was started at least 4 weeks after the discontinuation of methylprednisolone treatment and lasted for 6 weeks. Two weeks later the patients were re-investigated for their clinical and cognitive performance. We assessed also quality of life (QoL), depression and fatigue using self-rating scales., Results: Training had no effect on the neurological status and on QoL or fatigue. However, the treatment group showed better verbal learning, long-delay verbal memory performance, and working memory performance. The impact of treatment on long-delay verbal memory performance was independent from the extent of brain atrophy, whereas for the other findings brain atrophy played a significant role., Conclusions: An intensive home-based cognitive training program is suitable to improve the cognitive performance of MS patients. The impact of brain atrophy on rehabilitation outcome may differ for cognitive functions.

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.

The aim of the present study was to investigate alterations in brain oscillatory activity during transient intentional encoding of abstract novel shapes in patients with Parkinson's disease (PD). Combined time-frequency analyses of alpha and theta power revealed a clear dissociation between PD patients (N=10) and age-matched healthy controls (N=10). PD patients used sub-optimal stimulus encoding strategies for subsequent maintenance and recall, whereas the controls mainly used categorization processes. In contrast to controls, PD patients showed significantly less theta increase and upper alpha suppression at frontal locations and significant laterality of early posterior theta and lower-2 alpha oscillations at right posterior locations. These findings suggest that the fronto-striatal circuits participate in visual categorization processes. Furthermore, theta and alpha oscillations appear to be involved in mediating the integration processes in mnemonic networks underlying visual categorization.

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.

Early neurological rehabilitation means starting rehabilitation of brain damaged patients already during the acute phase of the trauma or illness. It meanwhile is commonly accepted that early onset of specific neurological rehabilitation interventions will enhance medical improvement and social reintegration potential. On the other hand, the number of treatment places required for adequate early neurological rehabilitation remains a controversial, and as yet unresolved, issue in Germany. In the present study, an evaluation was undertaken for the first time to determine the local demand for early rehabilitation beds in the well-defined region of the federal state of Bremen, based on retrospective analysis of all adults treated for severe brain disease in the major Bremen clinics over a period of 22 months, i.e., between January 1992 and October 1993. A total of 146 early rehabilitation treatments was found, which is equivalent to 80 treatments a year. These results are compared with the figures and recommendations given by Kuratorium ZNS. Also, our findings document the apparent deficits in neurological rehabilitation at the time in the Land Bremen, which undoubtedly jeopardize our daily objectives, the progress and successes achieved in early intensive care.

In order to investigate activation of the innate immune system in murine toxoplasmosis, T- and B-cell-deficient SCID mice and their co-isogenic immunocompetent C.B-17 counterparts were orally infected with a low-virulent strain of Toxoplasma gondii (DX strain). SCID mice developed a fatal necrotizing toxoplasmosis, whereas CD4+ and CD8+ T cells contributing to inflammatory infiltrates conferred resistance to immunocompetent mice. Significant amounts of interferon-gamma (IFN-gamma) were detectable in SCID mice. The most likely source for this cytokine is activated natural killer (NK) cells. In comparison to immunocompetent mice IFN-gamma levels were reduced in cerebrospinal fluid (CSF) and serum of SCID mice at days 7 and 14 of disease. Similar amounts of tumour necrosis factor (TNF) were detected in both strains of mice. In addition, immunohistochemistry showed major histocompatibility complex (MHC) class II antigen expression on SCID and C.B-17 microglial cells and macrophages demonstrating activation of these cells in both strains. However, the up-regulation of MHC class II antigen on microglia was less pronounced in SCID mice, presumably due to reduced levels of IFN-gamma. Interleukin-6 (IL-6) levels in CSF and serum were elevated in both strains and correlated with systemic and intracerebral disease activity. In conclusion, our results demonstrate activation of macrophages and NK cells as the predominant defence mechanisms of the comprised SCID immune system during toxoplasma infection. This implies a major role for the innate immune system during early stages of toxoplasmosis although T cells are necessary to control the infection efficiently.

Optic neuritis (ON) is characterized by immune-mediated demyelination of the optic nerve. In this study we addressed the question of cytokine signalling as part of activation of the immune system. 20 patients with first episode of acute idiopathic unilateral ON, prolonged visual evoked potentials, but normal 1.5 tesla MRI of the brain, and normal somatosensory evoked potentials were included into the study. Paired cerebrospinal fluid (CSF) and serum samples of these patients were analyzed for the presence of interleukin (IL-)-2, soluble IL-2R (sIL2R), IL-6, tumor necrosis factor (TNF)-alpha, and IL-1 beta by an enzyme-linked immunosorbent assay (IL-2, sIL2R, TNF-alpha, IL-1 beta) or a bioassay (IL-6). IL-2 was significantly elevated in the CSF (P < 0.01), whereas sIL2R (P < 0.01) and IL-6 (P < 0.01) were significantly increased in serum. TNF-alpha could not be detected in CSF or serum, and IL-1 beta was negative in serum in all but one sample and positive in only low amount (mean 9 pg/ml) in the CSF of 6/20 patients. This cytokine pattern in ON indicates an activation of the immune system within and outside the central nervous system with a predominance of T-cell activation.

Plasminogen activator inhibitor activity was determined in patients (26 men, 6 women) with acute ischemic stroke (n = 28) and transient ischemic attack (TIA) (n = 4). Age-matched patients (22 men, 10 women) with various nonvascular neurologic diseases served as controls. Plasma levels of plasminogen activator inhibitor activity were significantly higher in the stroke group (p less than 0.003). Serum triglycerides and plasminogen activator inhibitor activity correlated positively in the stroke group (p less than 0.03) and in controls (p less than 0.0001). Our data suggest a possible involvement of plasminogen activator inhibitor activity in the pathophysiology of stroke.

The distributions of the alpha 1-adrenoceptor and its subtypes (alpha 1A and alpha 1B) in human and rat hippocampus are analysed by quantitative receptor autoradiography. alpha 1-Adrenoceptors are labelled by [3H]prazosin. The alpha 1A subtype is visualized by [3H]prazosin after irreversible blockade of alpha 1B adrenoceptors with chloroethylclonidine or directly by [3H]5-methyl-urapidil. The alpha 1B subtype is investigated by [3H]prazosin binding in the presence of the alpha 1A antagonist 5-methyl-urapidil. Considerable differences in the regional and laminar patterns of alpha 1-adrenoceptors are found between rat and human hippocampi. The rat hippocampus is characterized by a low overall density and a rather homogeneous regional and laminar distribution. This is in contrast to the human pattern, which shows a much higher overall level of alpha 1 receptor density and a restriction of alpha 1 receptors to the CA3 region of Ammon's horn and the dentate gyrus. Moreover, alpha 1A and alpha 1B receptors of the human hippocampus are differentially distributed with the alpha 1A subtype concentrated in the hilus and lucidum layer of CA3, and the alpha 1B subtype concentrated in the molecular layer of the dentate gyrus. Additionally, the distribution of alpha 1 receptors is compared with the distribution of 5-hydroxytryptamine 1A receptors. The subtype specific pattern is correlated with the distribution of glutamatergic systems in the human (but not in the rat) hippocampus. alpha 1A Receptor localization coincides with the target area of the mossy fibre system, and alpha 1B receptors are preferentially localized in the target area of the hippocampal associational fibres and partly of the perforant pathway. This result points to possible interactions between noradrenaline- and glutamate-mediated neurotransmission differentiated by topographically segregated alpha 1-adrenoceptor subtypes.

There are few reports on the relevance of evoked potentials in neurologically asymptomatic HIV seropositives. We studied 31 HIV infected males without AIDS or associated clinical neurological abnormalities. Visual evoked potentials by foveal checkerboard stimulation revealed a prolonged VEP latency in 37% of them. HIV seropositives with a pathologic VEP latency showed a significant reduction of their absolute numbers of peripheral blood T-helper cells. This increase of the mean VEP-latency was already significant in HIV seropositives with a T-helper cell count greater than 400/microliters. In 47% of the HIV seropositives the AEP peak I latency was prolonged in combination with a significant decrease of the AEP interpeak latency I-V suggesting endocochlear lesions at peripheral endings of the acoustic nerve or at the basal hair cells. HIV seropositives with a T-helper cell count less than 400/microliters revealed a significant prolongation of the mean AEP interpeak latency III-V indicating a central conduction defect in HIV-seropositives with an immune deficit. Somatosensory evoked potentials after median and tibial nerve stimulation were within the normal range. Since the VEP P100 latencies were significantly longer in HIV seropositives with a normal AEP peak I compared to those with prolonged AEP peak I latencies we postulate that there are different pathophysiological mechanisms underlying.

In chronic (relapsing) inflammatory polyneuropathy (CRIP), successful treatment with plasma exchange has led to the concept of pathogenic humoral factors. In 6 patients with CRIP, 5 of whom improved after plasma exchange, the potential pathogenic role of circulating immunoglobulin (Ig) fractions was tested by applying the systemic passive transfer model to marmoset monkeys. After continuous treatment with intramuscular injections for 2-8 weeks, monkeys injected with the crude immunoglobulin fractions or with purified IgG from 5 of the 6 patients showed a significant and partially reversible reduction of the motor nerve conduction velocity (mean 34%, P less than 0.001) when compared with pre-treatment values. In control animals the reduction was 4%. Morphological examination revealed only minor ultrastructural changes of the myelin sheath. Immunocytochemistry revealed that human IgG was able to cross the blood-nerve barrier. It is concluded that the circulating IgG-fraction of patients with CRIP contains a factor that may contribute to the disordered nerve function after crossing the blood-nerve barrier. It may be the removal of this particular factor which is responsible for the rapid recovery of nerve conduction in patients after plasma exchange.

Immunoneuropathies constitute but a small percentage of polyneuropathies, compared to metabolic or toxic neuropathies. However, refined techniques of immunochemistry and biopsy have increasingly improved the etiological characterisation of immunoneuropathies. This review deals with the present diagnostic tools for investigation of polyneuropathies in general and with special immunological means of diagnosis. After two short case reports from our department, the main groups of peripheral nerve diseases, in which immunologic pathomechanisms are postulated, are described regarding symptomatology, special diagnostics and therapy. These groups of diseases are listed with respect to scientific evidence of their immunologic etiology, ranging from acute and chronic Guillain-Barré-Syndrome to paraneoplastic and neuropathies in HIV infections. The conclusion gives a summary of general pathogenetic considerations in immunoneuropathies.

Thirteen patients with the clinical course of the juvenile type of generalized ceroid-lipofuscinosis were examined clinically, ophthalmologically, neurologically and psychiatrically. This included registration of EEG, x-ray, brain scintigraphy, motor nerve conduction velocity, ERG, fundus photography and bioptical investigations including electron microscopy. The children suffered from progressing decrease of visual acuity, decline of mental capacities, and later on speech and gait disturbances. The most characteristic findings are presented in case reports, two tables and fourteen pictures.

Clinical symptoms of the central and peripheral nervous system occur in about 40% of patients wit HIV infection. At autopsy, CNS lesions can be demonstrated in even higher percentages. Primary sequelae of HIV infection--either due to direct viral effects or the immunopathologic response of the human host--are acute aseptic meningitis or mengingo-encephalitis, HIV encephalopathy, myelopathy, neuropathy, and myositis. Secondary consequences of immunodeficiency in AIDS are opportunistic infections with other viruses, bacteria, fungi, and protozoa, e.g. CMV, HSV and HZV encephalitis, mycobacterial CNS infections, neurosyphilis, cryptococcal meningitis, and last but not least cerebral toxoplasmosis. The main secondary malignoma of the CNS is lymphoma. Together these disorders form a complex spectrum of central and peripheral neurological symptoms.

Peripheral blood lymphocytes exhibiting cytoplasmic vacuoles from eight patients with the juvenile type of generalized ceroid-lipofuscinosis were investigated by electron microscopy. Osmiophilic inclusions could be demonstrated in the vacuoles and occasionally in the cytoplasm proper, revealing a fingerprint-like ultrastructural pattern or a less defined dense granular material, sometimes with an osmiophobic component adjoined. The inclusions are compared with those demonstrated in seven of the cases by earlier investigations of rectal biopsies in a variety of cell types, mainly in nerve cells. Discrimination is attempted between the lymphocyte inclusions and "parallel tubular arrays" regarded as representing a regular lymphocyte constituent.