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Within the constraints of operational work supporting humanitarian organizations in their response to the Covid-19 pandemic, we conducted building extraction for Khartoum, Sudan. We extracted approximately 1.2 million dwellings and buildings, using a Mask R-CNN deep learning approach from a Pléiades very high-resolution satellite image with 0.5 m pixel resolution. Starting from an untrained network, we digitized a few hundred samples and iteratively increased the number of samples by validating initial classification results and adding them to the sample collection. We were able to strike a balance between the need for timely information and the accuracy of the result by combining the output from three different models, each aiming at distinctive types of buildings, in a post-processing workflow. We obtained a recall of 0.78, precision of 0.77 and F 1 score of 0.78, and were able to deliver first results in only 10 days after the initial request. The procedure shows the great potential of convolutional neural network frameworks in combination with GIS routines for dwelling extraction even in an operational setting., (© 2021 The Authors. Transactions in GIS published by John Wiley & Sons Ltd.)

Background and Purpose: Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke., Methods: This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40,000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for., Results: Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (P=0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (n=42 of 256) in the EPO and 9.0% (n=24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38; P=0.01) without any particular mechanism of death unexpected after stroke., Conclusions: Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis.

This study investigated event-related oscillations associated with a Simon task in 11 Parkinson's disease patients, 11 age-matched, and 11 young participants. During this task, participants respond faster when the relative spatial positions of stimulus and response match (no response conflict exists) than when they do not match (response conflict exists). An increased response conflict (increase in reaction times known as Simon effect) was found in elderly control and Parkinson's patients compared with young participants. Group and condition differences were found in the delta and theta frequency range, which may reflect that Parkinson's patients and matched controls use different cognitive strategies for stimulus-response processing than young controls and neurophysiological correlates of such strategy are deficient in patients compared with age-matched controls.

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.

Background and Purpose: To analyse the prospect of memory training for patients with organic brain damage., Methods: Sixty-two patients with memory disorder were assigned to three different groups: a control group (n=16) with low dose memory training, a process oriented memory training group (POT) (n=24) and a group (ST) who was taught to compensate for memory problems with different strategies (n=22). Most of the patients had suffered a stroke. Inclusion criteria were medium to weak memory impairment defined by the patients' performance in the California Verbal Learning Test. Patients with complete amnesia were excluded. Specific care was taken that the groups did not differ in age, time since illness, duration of rehabilitation effort, verbal and performance IQ, memory and attention performance. The two treatment groups received 20 hours memory training, the low dose memory training control group 7 sessions., Results: The treatment groups improved in verbal and prospective memory, but only the group with POT experienced a significant improvement compared with the control group. Training effects were specific, i. e. they affected verbal memory, but were not encapsulated, i. e. generalized to the recall of prose passages and of appointments. The POT group also showed a statistically weak outperformance compared with the ST group and some attentional improvement as well., Conclusion: Memory training is effective in patients with organic brain lesion, but only if applied frequently. Comparing the two training high intensity treatments, a POT focus seems to be superior to teaching a set of compensation strategies.

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.

Objective: To compare the neuropsychological deficits of primary progressive multiple sclerosis with those of relapsing-remitting and secondary progressive multiple sclerosis., Methods: Sixty-five patients with different clinical courses of MS were neuropsychologically tested for language, attention, memory and executive functions. Discriminant analysis was used to predict the type of clinical course either by clinical variables (age, EDSS and duration of illness) or neuropsychological test results., Results: For single neuropsychological tests, group differences were rare between the progressive courses and the relapsing-remitting course of MS or absent between the progressive courses of MS. However, discriminant analysis correctly identified 87.7 percent of the patients' courses in general, and about 90 percent of the patients with chronic progressive MS., Conclusion: Using discriminant analysis, this study found neuropsychological impairment characteristic for relapsing remitting, secondary progressive and primary progressive patients.

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.

Primary dystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained involuntary muscle contractions causing repetitive movements and/or abnormal postures. Recently, the gene locus (DYT1) and mutation responsible for a substantial number of cases suffering from early-onset primary dystonia was described. Here we report 2 German families and 1 sporadic patient with early-onset dystonia due to the DYT1 mutation in order to illustrate the variability of clinical manifestation within this molecularly defined entity. We demonstrate that writer's cramp or focal cervical dystonia is a clinical presentation of DYT1 as well as generalized dystonia.

Objectives: Our aim was to investigate the diagnostic impact of skin biopsies in CADASIL patients., Materials and Methods: Eight consenting CADASIL patients belonging to a German-Caucasian kindred were assessed clinically, genetically, by MRI and skin biopsy. Skin biopsy results were compared to 5 patients suffering from sporadic leucoencephalopathies (control group)., Results: Six CADASIL patients presented with symptoms ranging from migraine to severe tetraparesis with dementia. Two clinically unaffected patients had abnormal MRIs. On MRI 7 patients showed various degrees of leucoencephalopathy. One 22-year-old woman with migraine had a normal MRI. Granular, electron dense, osmiophilic material (GEM) was found in skin biopsies of all 8 patients including the 22-year-old woman with migraine and a normal MRI. As shown by genetic linkage analysis she was carrying the disease haplotype. GEM was not found in the control group., Conclusion: Our findings substantiate the impact of skin biopsies in defining the carrier status in CADASIL families.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized clinically by recurrent cerebral infarcts, subcortical dementia and pseudobulbar palsy, and morphologically by a granular degeneration of cerebral and, to a lesser degree, extracerebral blood vessels. We present morphological findings in a further German family affected by CADASIL. The index case showed the typical periodic acid-Schiff-positive granular degeneration of vascular smooth muscle cells (VSMC) in cerebral vessels, which did not react with antibodies against various immunoglobulins or complement factors. Ultrastructurally, granular osmiophilic material (GOM) covered the VSMC in different cerebral regions as well as in extracerebral organs (muscle, nerve, skin, small and large intestine, liver, kidney and heart). Skin biopsy samples from other family members of the last two generations also revealed GOM irrespective of the clinical symptomatology (CADASIL, migraine only or asymptomatic). Patients in the third generation had higher amounts of GOM in skin vessels than did asymptomatic or migraine patients in the fourth generation. We conclude that skin biopsy is a useful and less invasive screening method for the differential diagnosis of CADASIL.

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.

Factors which determine the pathogenesis and course of Toxoplasma encephalitis are poorly understood. In the present study, the influence of genetic factors in congenic B10 and BALB mice of H-2q, H-2k, and H-2b haplotypes was examined following oral infection with a low-virulence strain of Toxoplasma gondii (DX). There were striking differences among these strains. Whereas B10 mice were highly susceptible, BALB mice had a less severe and more protracted disease. In all animals with a fatal outcome, Toxoplasma encephalitis was the cause of death. Within the two congenic groups, the major histocompatibility complex haplotype had a strong impact on the disease. The H-2k haplotype was associated with early death in B10 mice but with a favorable outcome in BALB mice, whereas the reverse was observed for the H-2q haplotype. These findings indicate that genetically determined factors are critically involved in determining the intracerebral immune response and the course of murine toxoplasmosis. Some of these factors appear to be associated with the major histocompatibility complex haplotype, but significant differences between B10 and BALB mice point to a modulating role of additional genetic loci. Immunohistochemical studies and cytokine analyses of cerebrospinal fluid and serum revealed significant differences in the intracerebral immune response between susceptible and resistant strains. A poor outcome was associated with a large number of intracerebral parasites, significant tissue necrosis, a reduced number of intracerebral CD4+ T cells, low intrathecal tumor necrosis factor levels, and, to a lesser extent, a reduced number of intracerebral CD8+ T cells.

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 experimental infection of immunocompetent and immunodeficient athymic mice with an avirulent encephalitogenic Toxoplasma strain (DX strain) was employed to study the ensuing encephalitic process by use of histological and immunocytochemical methods. In the acute phase of the infection Toxoplasma cysts and tachyzoites were accompanied by an infiltrate composed of macrophages, CD4+ and CD8+ T cells. In the chronic stage a granulomatous encephalitis developed. In contrast to immunocompetent NMRI mice, athymic nude NMRI mice died 3 weeks post-infection because of a generalized toxoplasmosis with predominant involvement of the brain. A salient feature of murine Toxoplasma encephalitis was up-regulation of class I and II major histocompatibility complex (MHC) gene products. Class I antigen was widely expressed on microglial cells and astrocytes. Class II antigen was only expressed on microglial cells despite a considerable astrogliosis. Our results indicate a differential expression of MHC-determined antigens on brain cells in acute and chronic murine Toxoplasma encephalitis.

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.

Chronic progressive of relapsing inflammatory polyneuropathy (CRIP) can be treated effectively with immunosuppressive drugs and/or plasma exchange (PE). This report describes a patient who responded dramatically and reproducibly to PE during four successive relapses and remained in remission while on medical immunosuppression with azathioprine and corticosteroids. The clinical course was closely correlated with electrophysiologic parameters such as compound muscle action potential amplitudes and distal latencies. The purified IgG fraction of PE filtrate bound to rat and human sciatic nerve on immunohistochemistry. Furthermore, a similar staining pattern was achieved by purified Fab fragments, which was absent in all control preparations. These findings support the hypothesis that circulating plasma factors may play a role in CRIP and that one of these factors may be an IgG antibody to peripheral nerve components.

Anti-Leu 7 monoclonal antibody (MAB), a marker of natural killer cells, and a human MAB to myelin-associated glycoprotein (MAG) from a patient with a demyelinating neuropathy specifically stained Schmidt-Lanterman incisures, paranodal and periaxonal regions in peripheral nerve myelin by immunocytochemistry on thin plastic sections, while compact myelin was labelled in paraffin-embedded material. Preabsorption studies indicated that the antigen recognised was a MAG epitope shared by MAG and Leu 7. In spinal cord both MABS bound to oligodendrocytes and a subclass of anterior horn cells. Our findings support the hypothesis that shared antigens between the nervous and the immune systems do exist in situ, which may be important in the pathogenesis of demyelinating neuropathies with monoclonal gammopathies.

The effects of intracerebral inoculation of Sendai virus into young adult mice were investigated by immunofluorescence, light, and electron microscopy. Immunofluorescence of virus-specific antigens was maximal on the third day after inoculation, revealing infection of leptomeninges, ependyma, and choroid plexus. Histologically, meningitis, ependymitis, and choroiditis occurred between the second and third days. The choroiditis was associated with formation of vacuoles within the cytoplasm of epithelial cells. The vacuoles reached diameters up to 50 micrometer. The ubiquitous vacuolization of plexus epithelia resulted in a honeycomb-like pattern. Opaque viral inclusions were visible within the cytoplasm of choroidal and ependymal epithelium as well as in mononuclear inflammatory cells. On electron microscopy, they were composed of intracytoplasmic nucleocapsid accumulations. Viria lay free between microvilli of plexus epithelial cells, and budding virus structures were observed at cellular surfaces. Occasionally, complete viria occurred in the cytoplasm of plexus epithelial cells and were surrounded by a unit membrane from which they appeared to arise by budding. The formation of this small cavity can be interpreted as the first stage of vacuole formation.

A man, aged 63, had an illness which lasted 11 months from onset with pain under the left costal margin which radiated to the epigastrium, until his death from cardiac failure. His symptoms consisted principally of parasthesias and proximal weakness of both upper and lower extremities with atrophy of the shoulder and pelvic girdles. He developed pyramidal tract signs, became euphoric, emotionally unstable and mentally retarded. There was no clinical evidence of cerebellar dysfunction. Bronchogenic carcinoma was suspected from a tomograph of the thorax, but, in spite of extensive clinical and laboratory studies, the diagnosis was verified only postmortem. The CSF cell count was high at first but diminished as the disease progressed. Muscle biopsies revealed chronic generalized denervation without signs of myopathy. Neuropathologically, encephalomyeloradiculoneuritis concentrated on the spinal cord was combined with severe rarefaction of the ganglion cells of the anterior horns and with bilateral degeneration of the lateral pyramidal spinocerebellar and posterior tracts. A more diffuse process was obvious in the anterolateral tracts of the lumbar region. Polyneuropathy concentrated in the distal region was accompanied by slight inflammatory reaction in the sciatic nerve. Cerebellocortical degeneration which exceeded physiological age-related rarefaction was also present. The findings are discussed in relation to the literature.

Murine lymphocytic choriomeningitis is a T-cell-mediated pathologic immune phenomenon. The name of this experimental illness was derived from the principal histopathologic alterations of the central nervous system (CNS) of adult mice infected intracerebrally with lymphocytic choriomeningitis virus, i.e., lymphocytic infiltrations of plexus choroidei and meninges. The general assumption that the main event in the pathogenesis is damage to virus-infected target cells by cytotoxic T-lymphocytes is plausible but direct evidence is scarce. We have studied the ultrastructural alterations of both types of cells that are thought to participate in this immunopathologic interaction. Lymphocytes with signs of T-cell transformation were first evident on day 4 after infection. One day later, lymphoblasts, often extending uropods and containing cytoplasmic dense and compound multivesicular bodies, predominated. They were sometimes seen in intimate contact with connective tissue cells of the leptomeninx and epithelial cells of the choroid plexuses which were shown to be infected by immunofluorescence procedure. Lymphoblasts occasionally invaginated the cytoplasm of the putative target cells with cytoplasmic processes, and were even found inside the latter, exhibiting the phenomenon of emperipolesis. Lymphocytic transformation was at its maximum 6 days after infection. At this time, individual leptomeningeal cells and groups of plexus epithelial cells showed signs of cytolysis, and in a few instances these damaged cells were in close spatial association with lymphoblasts. Similar observations have been reported by others who studied the interaction between cytotoxic T-lymphocytes and their appropriate targeted cells in vitro. We interpret our findings as providing direct evidence for the assumption that one link in the chain of events leading to the cerebral form of lymphocytic choriomeningitis of the mouse is damage to virus-infected leptomeningeal and plexus cells by cytotoxic T-lymphocytes.

Rectal biopsies were obtained from 11 children, clinically presumed to suffer from the juvenile type of generalized ceroid-lipofuscinosis. In addition, sural nerve biopsies were performed in 4 cases. Of the various staining procedures applied for light microscopy, Sundan Black B was found to be the most useful, revealing in each of the rectal biopsies at least some nerve cells with coarse black droplets as well as numerous mucosal macrophages with a more greyish, dustlike material. In sural nerve biopsies a slight reduction of the thick myelinated nerve fibers was seen in two cases, accompanied by regeneration phenomena. The latter were also detectable in one other case, the remaining sural nerve biopsy being histologically unremarkable. By electron microscopy neuronal perikarya revealed lipopigment bodies with a fingerprint-like pattern in each of the rectal biopsies. In one case only was this pattern combined with distinct curvilinear profiles. In 4 cases, however, the fingerprint-like deposits were intermingled with different lamellated bodies, some of them reminiscent of MCB's or zebra bodies. In two of the 4 cases, these were even seen exclusively in some neurons. In each of the rectal as well as the sural nerve biopsies, most of the non-neuronal cell types presented lipopigment bodies, likewise, displaying both curvilinear and fingerpring-like profiles, with some characteristics related to the various cell types. With regard to generalized ceroid-lipofuscinosis the diagnostic value of rectal biopsies, though being disputed in the literature, appears reestablished by the findings presented.

Rabbits were immunised repeatedly with bovine brain galactocerebroside. Almost all animals developed overt polyradiculoneuropathy. Circulating IgG antibodies to galactocerebroside in the serum and deposits of IgG in the spinal roots were detectable weeks before definite clinical, morphological, and electrophysiological alterations occurred. The levels of IgG antibody titres to galactocerebroside did not correlate with the severity of the clinical disease and of nerve conduction slowing. Remyelination and a virtually complete recovery of nerve dysfunction occurred although circulating antibodies to galactocerebroside were still present.

In 13 patients with morphologically established juvenile neuronal ceroid lipofuscinosis and 13 controls, the activity of leukocyte peroxidase (myeloperoxidase) was determined under various conditions: Measurement of water-soluble enzyme, the buffer-soluble enzyme, and the leukocyte homogenate; application of phosphate buffer (pH7.0) and borate buffer (pH7.6); employment of 9mM, 28mM, and 55mMp-phenylenediamine as hydrogen donor; and measurement of the specific enzyme extinction at 10, 60, and 180 seconds. A significant difference between mean values for patients and controls could not be established. In both groups, single individuals exhibited definitely increased or reduced enzyme concentrations, leaving us, however, without an adequate explanation for these observations. Our studies indicate that determination of myeloperoxidase has no value in establishing the diagnosis of neuronal ceroid-lipofuscinoses.

To study the permeability of the blood-brain barrier (BBB) and the blood-nerve barrier (BNB) for immunoglobulin G (IgG) we adapted the avidin-biotin system for postembedding demonstration of the tracer IgG in the central and peripheral nervous system (CNS, PNS). Normal mouse and human IgG were biotinylated and injected daily into the intraperitoneal (i.p.) space of adult BDF1 mice. After 24h, IgG was detected in blood vessels and in the interstitium of various organs, but staining was restricted to the dura mater in the CNS, to the spinal ganglia, and to the perineurium of peripheral nerves. After 4 days, IgG was also present in the endoneurial connective tissue of peripheral nerves, while the brain, spinal cord, and spinal roots remained free of IgG. Our results show a partial permeability of the normal mouse BNB for homologous and heterologous IgG.

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.

Rabbits were immunized with galactocerebroside and a crush lesion was created in the tibial nerve before the onset of experimental allergic neuritis. Normal regeneration and myelination of distal peripheral nerve sprouts occurred and was identical to that of controls, although circulating antigalactocerebroside antibodies were present and nerve roots showed typical signs of beginning experimental allergic neuritis.

The capacity of the avidin-biotin system for post-embedding cytochemical detection of a biotin-labeled proteinaceous tracer was investigated. By testing modifications of the fixatives, the epoxy embedding medium, and various etching solutions, a procedure was developed to localize specifically the biotinylated tracer on 1-micron thick and thin sections. By use of this technique, a systemically administered IgG tracer was demonstrated after 24 hr throughout the endomysium of mouse skeletal muscle. In the adjoining sciatic nerve, the tracer IgG occurred at the perineurium and within endoneurial blood vessels, although the endoneurium itself was spared because of the presence of the blood-nerve barrier. Because of the small size of the biotin ligand and the non-denaturing method of labeling proteins, our mode of application of the avidin-biotin system appears suitable for tracer studies.

CCT was performed in 14 children/adolescents with juvenile ceroid lipofuscinosis (JNCL) at different stages of the disease. CCT was normal in 7 patients; mildly abnormal in 3, clearly abnormal in another 3 and severely abnormal in 1 patient. Characteristic findings were symmetrical enlargement of subarachnoid spaces and of the lateral and third ventricles. White matter showed no changes in density. In later stages also the fourth ventricle was enlarged and cerebellar atrophy was seen. CCT findings were not closely correlated with onset and/or severity of the neurological abnormalities. CCT findings were positively correlated with age of the patients: CCT was usually normal if patients were less than 10 years old, and usually abnormal if patients were more than 14 years old.

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.

In addition to ependymal epithelial cells, numerous tanycytes are found along the entire central canal of the mouse. These tanycytes are arranged in clusters in the cervical, thoracic and lumbar segments of the spinal cord. In the conus medullaris, tanycytes separate and ensheath bundles of myelinated and unmyelinated axons; their processes take part in the formation of the stratum marginale gliae. In the caudal part of the spinal cord, the ventral wall of the central canal is thin and some areas are reduced to a single-cell thickness. In this region, ependymal cells participate directly in the formation of the stratum marginale gliae. The meninges consist of the intima piae, the pia mater, the arachnoid, a subdural neurothelium and the dura mater. The subarachnoid space appears occluded and opens only around the spinal roots. In the vicinity of the spinal ganglia, the dura mater, the subdural neurothelium and the arachnoid form a cellular reticulum.

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.

A 57-year-old male was repeatedly admitted to hospital because of complex neurological symptoms, including radicular pain, disturbance of micturition, seizures, and severely impaired mental state. The diagnosis was encephalomyeloradiculitis possibly of viral origin, and treatment with immunosuppressants was initiated. An alternating course with a tendency towards improvement ensued. Two and a half years after the occurrence of the initial symptoms, identification of specific antibodies in the blood and CSF led to the diagnosis of borreliosis with CNS involvement. High-dose therapy with penicillin rapidly reduced the symptoms, beginning with those of radicular pain and followed by an improvement of the mental state. Attention is directed to the wide spectrum of clinical symptoms of chronic borreliosis with CNS involvement. Previous reports that immunosuppression may result in some improvement but with a tendency towards relapse are confirmed. Our encouraging treatment results support those of other reports that penicillin therapy may lead to improvement even at late chronic stages in patients with severe CNS deficits.

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.

The binding specificities of two monoclonal antiglioma antibodies (MAB) derived from hybrids GE2 and BF7 (Schnegg et al. 1981) were tested by indirect immunofluorescence (IF) and two immunoperoxidase (IP) methods. Studies were done on biopsies from 33 human CNS tumors, human derived glioma cells, and N-ethylnitrosourea-induced neurogenic rat cells in culture. The immunohistochemical reactions of MAB were investigated in snap-frozen tumor material, conventionally paraffin-embedded material, and tumors embedded in formol sucrose/gum sucrose/paraffin (FSGSP) by the new tissue processing technique of Bolton and Mesnard (1982), which preserves and enhances the antigenicity of tissues. The FSGSP processing offered a better immunocytochemical staining with MAB as compared to cryostat material, while the conventionally embedded paraffin sections of tumors did not stain at all. The binding of MAB revealed an affinity to both glial tumor cells and normal astrocytes. The techniques described are suitable for the identification of an astrocytic subpopulation within gliomas, and may improve the understaining of antigen expression in various stages of astrocytic dedifferentiation.

A postembedding method is described to localize antigens specific for various paramyxoviruses in sections of cells and tissues that have been fixed and embedded in epoxy resins for conventional electron microscopy. Viral antigens were localized in CV-1 cell cultures infected with simian virus 5 (SV5), brains of suckling hamsters inoculated with either neuroadapted mumps virus or hamster-adapted measles virus, and brains of adult mice infected with Sendai (parainfluenza I) virus. Both 1-micrometer-thick and thin (gold) tissue sections were etched with alcoholic sodium hydroxide-solution and then treated following either the unlabeled antibody peroxidase-antiperoxidase or the biotinylated protein A:avidin peroxidase procedure. Primary reagents included immunoglobulin isolated from hyperimmune rabbit sera with specificity to the major viral components of SV5 or SV5 hemagglutinin-neuraminidase, to whole mumps virus or mumps virus nucleocapsids, and to whole Sendai virus. Crude rabbit anti-Sendai virus antiserum and whole human subacute sclerosing panencephalitis (SSPE) sera were used in parallel. The results indicate that tissues processed for conventional evaluation by electron microscopy may be suitable, within limits, for postembedding immunocytochemical staining of paramyxovirus antigens.