[Telemedicine in stroke-pertinent to stroke care in Germany]. / Telemedizin in der Schlaganfallversorgung ­ versorgungsrelevant für Deutschland.

BACKGROUND AND OBJECTIVE: Telemedical stroke networks improve stroke care and provide access to time-dependent acute stroke treatment in predominantly rural regions. The aim is a presentation of data on its utility and regional distribution. METHODS: The working group on telemedical stroke care of the German Stroke Society performed a survey study among all telestroke networks. RESULTS: Currently, 22 telemedical stroke networks including 43 centers (per network: median 1.5, interquartile range, IQR, 1-3) as well as 225 cooperating hospitals (per network: median 9, IQR 4-17) operate in Germany and contribute to acute stroke care delivery to 48 million people. In 2018, 38,211 teleconsultations (per network: median 1340, IQR 319-2758) were performed. The thrombolysis rate was 14.1% (95% confidence interval 13.6-14.7%) and transfer for thrombectomy was initiated in 7.9% (95% confidence interval 7.5-8.4%) of ischemic stroke patients. Financial reimbursement differs regionally with compensation for telemedical stroke care in only three federal states. CONCLUSION: Telemedical stroke care is utilized in about 1 out of 10 stroke patients in Germany. Telemedical stroke networks achieve similar rates of thrombolysis and transfer for thrombectomy compared with neurological stroke units and contribute to stroke care in rural regions. Standardization of network structures, financial assurance and uniform quality measurements may further strengthen the importance of telestroke networks in the future.

Fatigue, sleepiness, and physical activity in patients with multiple sclerosis.

Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS). The objective of the study was to compare fatigue and sleepiness in MS, and their relationship to physical activity. Eighty patients with MS rated the extent of experienced fatigue (Fatigue Severity Scale, FSS) and sleepiness (Epworth Sleepiness Scale, ESS). The relationship between the scales was analysed for the scales as a whole and for single items. The clinical status of the patients was measured with the Extended Disability Status Scale (EDSS). In addition, physical activity was recorded continuously for 1 week by wrist actigraphy. The mean scores of fatigue and sleepiness were significantly correlated (FSS vs. ESS r=0.42). Single item analysis suggests that fatigue and sleepiness converge for situations that demand self-paced activation, while they differ for situations in which external cues contribute to the level of activation. While fatigue correlated significantly with age (r=0.40), disease severity (EDSS, r=0.38), and disease duration (r=0.25), this was not the case for sleepiness. Single patient analysis showed a larger scatter of sleepiness scores in fatigued patients (FSS>4) than in non-fatigued patients. Probably, there is a subgroup of MS patients with sleep disturbances that rate high on ESS and FSS. The amount of physical activity, which was measured actigraphically, decreased with disease severity (EDSS) while it did not correlate with fatigue or sleepiness.

No effect of intravenous immunoglobulins on cytokine-producing lymphocytes in secondary progressive multiple sclerosis.

Intravenous immunoglobulins (IVIG) have been effective in reducing multiple sclerosis (MS) disease activity and improving disability scores. However, the mechanism by which this beneficial effect is achieved remains unclear. An effect of IVIG on pro- and anti-inflammatory cytokines which are thought to play a role in the disease process - has been postulated in a number of animal and ex vivo studies. Hence, we performed a study on 34 patients with secondary progressive (SP) MS being treated with monthly IVIG or placebo for two years according to the protocol of the ESIMS study. Clinical outcome measures and cytokine production (interferon gamma, tumour necrosis factor alpha, interleukin-4 and -10) were recorded in all patients and compared with respect to the treatment group. Against our expectations, IVIG did not reduce the relapse rate or the progression of disability or cytokine production. Our data argue against an enduring immunomodulating effect of IVIG, at least in SPMS.

Personality traits in multiple sclerosis (MS) patients with and without fatigue experience.

OBJECTIVES: To determine the impact of personality characteristics on feelings of fatigue in multiple sclerosis (MS) patients and to compare the results with the impact of bodily impairment. PATIENTS AND METHODS: Eighty patients with definite MS (mean age 38.5 +/- 9.0 years, 62 females) were surveyed using questionnaires assessing fatigue experience and personality traits (German Freiburg Personality Inventory-Revised; FPI-R) and by clinical examination assessing the Expanded Disability Status Scale. RESULTS: Increased levels of "neuroticism", and "excitability" and decreased levels of "extraversion" were found to relate independent of fatigue scores (0.21 < beta < 0.52; 0.05 < P < 0.0001). The impact of these personality traits on fatigue (partial R2 ranging up to 0.32; 0.02 < P < 0.0001) was much higher than the impact of physical impairment (partial R2 ranging up to 0.04; not significant). CONCLUSION: Our results support a psychological model of fatigue in MS. FPI-R-items over-weighted somatic sources of the fatigue syndrome in MS and may specifically relate to fatigue experience in chronical disorders.

Low interleukin-10 production is associated with higher disability and MRI lesion load in secondary progressive multiple sclerosis.

Abnormalities in T-cell-derived cytokine production are a well-known phenomenon in multiple sclerosis (MS). An association between disability and the production of interferon gamma has been demonstrated recently. The present study investigated associations between disability, cytokine production in stimulated blood lymphocytes and magnetic resonance imaging data in 37 patients with the secondary progressive course in the stable phase of the disease. Patients with high interleukin-10 (IL-10) production had significantly lower disability scores (p=0.009) and lower T2 lesion load (p=0.03). Interleukin-10 might not only play a role in the pathological process of multiple sclerosis but has an impact on disease outcome as well.

Cardiovascular autonomic dysregulation and fatigue in multiple sclerosis.

Both cardiovascular disturbances and fatigue are frequent in multiple sclerosis (MS). We investigated their relationship in 84 MS patients (mean age 39.9 +/- 8.9 years) using five established autonomic tests and three different fatigue questionnaires. 64.2% of the patients were categorised as being fatigued Fatigue perception was weakly related to EDSS. Moderate cardiovascular disturbances were found in 16.6% of the patients, and 10.7% had severe cardiovascular autonomic abnormalities. Cardiovascular dysfunction was slightly related to age and to EDSS. In 19.4% of all patients signs of autonomic failure and fatigue were co-existent Using correlation analysis, we found only weakly significant correlation coefficients between some single autonomic test parameters and fatigue scores, which were confounded by age effects. The analysis of dichotomised data revealed slightly significant differences in fatigue experience between patients with and without abnormalities regarding the handgrip test and the Valsalva reaction. Thus, autonomic disturbances might contribute to fatigue symptoms in a MS subgroup, but the overall influence of the autonomic cardiovascular regulation towards fatigue experience seems to be of minor relevance.

The use of clinical scales in depicting cerebrovascular complications in bacterial meningitis.

To evaluate the utility of different scales for clinical assessment, over time, in acute bacterial meningitis, the authors investigated 53 consecutive patients (mean age 53 +/- 17 years). Clinical status on days 1, 3, 5, 8, and 14 after admission was determined by the Scandinavian Stroke Scale (SSS), Glasgow Coma Scale (GCS), and Hunt and Hess Scale (HH), and, on day 21, by the Glasgow Outcome Scale (GOS). Transcranial Doppler examinations were performed serially to assess for disease-related arterial narrowing. This was observed in 27 patients (51%) within 2 weeks of admission. All scales were observed to correlate with the 21-day GOS. Patients with cerebral arterial narrowing had significantly decreased SSS scores between days 1 and 8 and worse GCS and HH scores between days 3 and 5. Mean blood flow velocity in the middle cerebral artery on days 5 and 8 significantly correlated with GOS (r = 0.268, P < .008; r = -0.324, P < .003, respectively). The use of such clinical scales allows standardized assessment of patients with bacterial meningitis and provides prognostic information. Cerebral arterial narrowing was observed to correlate with neurologic impairment.

Cognitive outcome after bacterial meningitis.

OBJECTIVE: To evaluate long-term cognitive deficits in unselected patients with previously diagnosed meningitis and to compare these deficits to neurologic and psychopathologic impairment. PATIENTS AND METHODS: Twenty-two unselected patients (mean age 52.5 +/- 17.1 years) were examined neurologically, psychiatrically, and psychometrically 30 +/- 11 months after the acute stage of bacterial meningitis. Results of psychometric tests were compared with clinical long-term deficits. Psychometric tests were additionally applied on 17 healthy controls (mean age 49.2 +/- 14.2 years). RESULTS: Neurologic or psychopathologic symptoms were found in 16 patients. Psychometrically, the speed of cognitive processes and psychomotor performance, concentration, visuoconstructive capacity, and memory functions were reduced significantly in patients as compared to controls. Verbal intelligence was less affected than performance efficiency. Patients with pneumococcal meningitis had significantly lower test results than patients with other pathogens. The psychometric test results were only slightly related with clinical findings of the follow-up examination. CONCLUSION: Psychometric deficits are frequent after bacterial meningitis, and their relation with neurologic and psychopathologic symptoms is loose. The pattern of neuropsychologic impairment accentuates psychomotor slowing combined with memory disturbances, and resembles features observed in subcortical cognitive impairment.

[Encephalomyelitis disseminata: clinical aspects, pathogenesis and current therapy concepts]. / Encephalomyelitis disseminata: Klinik, Pathogenese und aktuelle Therapiekonzepte.

Multiple sclerosis (MS) is considered as a T-cell mediated autoimmune disease. Caused by central nervous system demyelination and axonal damage varying clinical signs do occur either with relapsing-remitting or with chronic progressive course. Based on pathogenetic considerations immunomodulative and immunosuppressive therapeutical approaches are used to limit the disease progression. Clinical symptoms, diagnostic criteria, pathogenetical considerations, and consecutive therapeutical interventions are summarized.

[Neuroradiological aspects of encephalitis disseminata]. / Neuroradiologische Aspekte bei Encephalitis disseminata.

Magnetic resonance imaging (MRI) has developed without doubt to the most important investigation method in multiple sclerosis. MRI is very sensitive to detect MS lesions but unfortunately of limited specificity. The purpose of this review is 1. to work up the MRI characteristics of MS lesions, 2. to derive recommendations for MRT-protocolls for daily radiological work and 3. to discuss new MR developments. MS lesions in the acute inflammatory stage show first an enhancement of GD-DTPA due to break down of the blood brain barrier and develop a T2-hyperintensity due to an edema. The following disease course is categorized in a phase of reparation and remyelinisation respectively, of gliosis and a defect stage. MS-plaques in the remyelinisation and gliotic phase appear as hyperintens lesions on T2-weighted scans. Chronic MS lesions with a defect are also T2-hyperintens and demonstrate additionally due to severe axonal loss a hypointensity on short TR SE scans. MS lesions exhibit a characteristic distribution. They are found typically periventricular, in the corpus callosum and at the calloso-septal interface, cortico-subcortical and infratentorial. The most important MR criteria to predict conversion from suspected (CSMS) to clinical definite MS (CDMS) are GD-DTPA enhancement and juxtacortical lesion localisation followed by the parameter periventricular and infratentorial localisation. Based on guidelines for the use of MRI in drug studies and on equivalent recommendations for the routine diagnostic we suggest rational and economic MRT protocols for cerebral, spinal, and N. opticus investigations. Such standardised protocols shall help to make MRI investigations more efficient and better comparable. New MR developments include measurement of magnetisation transfer and T2-relaxation, diffusion weighted imaging, proton MR spectroscopy, and quantification of lesion load. These methods can analyse more specifically tissue changes in MS plaques and yet can reveal changes in normal appearing white matter.

Intravenous immunoglobulins in the therapy of paraneoplastic neurological disorders.

The treatment of paraneoplastic neurological syndromes (e.g., tumor therapy, immunosuppressive therapy, plasmapheresis) rarely leads to an improvement in the neurological symptoms. We treated four patients suffering from paraneoplastic neurological syndromes with intravenous immunoglobulins. All four had high titers of antineuronal antibodies in serum and CSF. Two of the patients, one suffering from paraneoplastic cerebellar degeneration and the other from paraneoplastic brain stem encephalitis and polyneuropathy, received intravenous immunoglobulin treatment within 3 weeks of the onset of neurological symptoms. Both patients showed clinical improvement within 2 weeks after the initiation of therapy. They also showed a decline in the intrathecal antibody synthesis of the antineuronal antibody. Two other patients, who had suffered from paraneoplastic neuropathy for 3 and 6 months showed no improvement with the intravenous immunoglobulin therapy. In these cases there was no effect on intrathecal antibody synthesis. When started early, intravenous immunoglobulins may be of therapeutical value in treating paraneoplastic neurological syndromes. Specific intrathecal antibody synthesis may be a better measure of clinical course that autoantibody serum titers.

Usefulness of clinical scores to predict outcome in bacterial meningitis.

The predictive usefulness of clinical scores in patients with acute bacterial meningitis was investigated. Fifty-one consecutive patients with acute bacterial meningitis were scored on days 1, 3, 5, 8, and 14 after admission according to the Sandinavian Stroke Scale (SSS), Glasgow Coma-Scale (GCS) and Hunt & Hess Scale (HH). As an index of their usefulness to predict the outcome, the scales were correlated with short-term outcome on day 21 assessed by the Glasgow Outcome Scale (GOS). The scores of all three scales correlated highly significantly with short-term outcome. Depending on the day of assessment, Spearman correlation coefficients ranged between 0.52 and 0.88 for SSS, between 0.50 and 0.84 for GCS, and between -0.47 and -0.82 for HH. The scales differed in their ability to predict outcome on and after day 1: mortality was best predicted by GCS, and complete recovery was best predicted by SSS. The use of scales in bacterial meningitis provides a rational quantitative basis to predict outcome more graduated than in dead or alive. Because the scales accentuate different aspects of outcome (e.g. mortality, restitution), the selection of a scale to be used in clinical trials should take into consideration the main focus of the study.

Alteration of cerebral blood flow in patients with bacterial and viral meningoencephalitis.

PURPOSE: Our purpose was to investigate cerebral blood flow disturbances in patients with bacterial and viral meningoencephalitis. METHODS: Forty-two patients with acute bacterial and viral meningoencephalitis and 14 control subjects were studied using 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography (SPECT). SPECT images were evaluated semiquantitatively. The results were compared with clinical severity of the meningoencephalitis assessed at the time of the SPECT study with the Hunt and Hess scale, with separately recorded focal clinical signs, and with the Glasgow outcome scale (GOS) after 3 weeks. RESULTS: Count density values were significantly reduced in patients with bacterial meningoencephalitis as compared with the control subjects. Inhomogeneous tracer accumulation assessed by asymmetry indexes was significantly greater in patients than in the control group. With increasing Hunt and Hess scores, the count density values decreased and the asymmetry indexes increased. Patients with a poor outcome (GOS 1 to 3) had significantly higher asymmetry indexes and lower CDV values than did patients with a good outcome. CONCLUSION: Global and focal alterations of cerebral perfusion are frequent in bacterial and viral meningoencephalitis and correlate with acute clinical state.

Relationship between short-term outcome and occurrence of cerebral artery stenosis in survivors of bacterial meningitis.

To evaluate the influence of cerebral artery stenosis on the outcome of patients with bacterial meningitis we examined prospectively 47 consecutive patients [33 men, 14 women, mean (SD) age, 53 (17) years, range 18-81] with bacterial meningitis caused by various bacterial pathogens. The patients were examined with the use of the Glasgow Coma Scale (GCS) on days 1, 3, 5, 8, 14 and with the use of the Glasgow Outcome Scale (GOS) on day 21 after admission. In addition, focal cerebral signs were recorded separately. At each clinical examination, the patients underwent transcranial Doppler sonography recordings of the mean blood velocity (MBV) and the pulsatility index in all of the main intracranial arteries and in the submandibular internal carotid artery (ICA). A stenosis of the middle cerebral artery (MCA) was diagnosed by an MBV of > or = 120 cm/s or by an MBV ratio > 3 between the MCA and the ICA. An anterior cerebral artery (ACA) stenosis was indicated by an MBV > or = 100 cm/s, a posterior cerebral artery (PCA) stenosis by an MBV of > or = 85 cm/s, and a basilar artery (BA) stenosis by an MBV of > or = 95 cm/s. Twenty-five patients developed stenosis of the cerebral arteries (apart from 1, all within 8 days), 22 patients remained without stenosis. Of 29 focal cerebral signs, 27 occurred within 8 days. For outcome analysis, outcome was classified into two groups: not handicapped (GOS 5) versus handicapped (GOS 2-4) and dead (GOS 1). Based on the disease course up to day 8, risk factors for a handicapped/dead outcome after day 8 were advancing age (odds ratio per year, 1.06; 95% confidence interval (CI), 1.01-1.11; P = 0.03) and the presence of arterial stenosis (odds ratio, 7.3; 95% CI, 1.1-45) using a multivariate logistic regression analysis model. GCS on day 1, cerebrospinal fluid total protein content and the presence of focal cerebral signs were not significantly related to outcome in this series. The patients with stenosis exhibited significantly more frequently a poorer GCS on days 1-5 (Mann-Whitney U test; P < 0.05). In conclusion, the early occurrence of stenosis of the cerebral arteries in bacterial meningitis predicted a worse clinical course of the disease and a poorer short-term outcome of the survivors.

Antineuronal antibody-associated paraneoplastic neuropathy in Hodgkin's disease.

Paraneoplastic neurological syndromes in patients with Hodgkin's disease are rare findings. Subacute, paraneoplastic cerebellar degeneration or autonomic dysfunctions were described before. In some of these cases, autoantibodies against central or peripheral nervous system structures were found in serum and CSF. We present a 30-year-old white male who developed a progredient, clinical and electrophysiological distal sensomotoric neuropathy. Six months after the beginning of the neurological disturbances, Hodgkin's disease (Stadium III BE) was diagnosed. Other reasons for neuropathy, such as direct impairment of the peripheral nervous system by tumor masses or drug-induced neuropathy, were excluded. Cerebrospinal fluid (CSF) analysis showed a mild pleocytosis, elevated total protein (9.8 g/l) and identical oligoclonal bands in serum and CSF. Blood-CSF barrier damage was detected by Reiber formula. Indirect immunofluorescence and western blot analysis demonstrated an autoantibody against peripheral and central nervous system structures in serum and CSF. Although the autoantibody responded to a 38-40 kDa-protein in western blot and showed nuclear staining of myenteric plexus and Purkinje cell nuclei in the immunofluorescence test, this antibody was shown to be not identical to anti-Hu. An intrathecal synthesis of the antineuronal antibody was detected by antibody specificity index. Tumor therapy, plasmapheresis and treatment with intravenous immunoglobulins did not improve the neuropathy. According to our knowledge this is the first case of antineuronal antibody-associated sensomotoric neuropathy in Hodgkin's disease.

Novel enzyme immunoassay and optimized DNA extraction for the detection of polymerase-chain-reaction-amplified viral DNA from paraffin-embedded tissue.

Four different DNA extraction methods were compared to determine their ability to provide DNA for amplification of viral sequences from paraffin-embedded human tissue samples by polymerase chain reaction (PCR). The suitability of extraction methods was assessed using parameters like DNA yield, length of recovered DNA fragments, and duration. Furthermore, the efficiency of amplifying a human single-copy gene, the beta-globin gene, from DNA samples was tested. The best preservation of DNA molecules could be achieved by binding the DNA onto a silica column before further purification. Viral DNA sequences could be amplified by PCR in DNA extracted from routinely processed paraffin blocks from cases with clinically or morphologically suspected cytomegalovirus or Epstein-Barr virus infections. The PCR products were specified by a novel liquid hybridization assay called PCR-enzyme-linked immunosorbent assay. Using this assay, the time-consuming Southern hybridization could be replaced and the time requirement for the detection of PCR products could be reduced from 1 day to 4 hours. The assay system described here represents a reliable, sensitive, and specific method for the detection of viral DNA from paraffin-embedded tissue samples.

Effects of altered phosphoenolpyruvate carboxylase activities on transgenic C3 plant Solanum tuberosum.

Phosphoenolpyruvate carboxylase (PEPC) genes from Corynebacterium glutamicum (cppc), Escherichia coli (eppc) or Flaveria trinervia (fppc) were transferred to Solanum tuberosum. Plant regenerants producing foreign PEPC were identified by Western blot analysis. Maximum PEPC activities measured in eppc and fppc plants grown in the greenhouse were doubled compared to control plants. For cppc a transgenic plant line could be selected which exhibited a fourfold increase in PEPC activity. In the presence of acetyl-CoA, a known activator of the procaryotic PEPC, a sixfold higher activity level was observed. In cppc plants grown in axenic culture PEPC activities were even higher. There was a 6-fold or 12-fold increase in the PEPC activities compared to the controls measured in the absence or presence of acetyl-CoA, respectively. Comparable results were obtained by transient expression in Nicotiana tabacum protoplasts. PEPC of C. glutamicum (PEPC C.g.) in S. tuberosum leaf extracts displays its characteristic K(m) (PEP) value. Plant growth was examined with plants showing high expression of PEPC and, moreover, with a plant cell line expressing an antisense S. tuberosum (anti-sppc) gene. In axenic culture the growth rate of a cppc plant cell line was appreciably diminished, whereas growth rates of an anti-sppc line were similar or slightly higher than in controls. Malate levels were increased in cppc plants and decreased in antisense plants. There were no significant differences in photosynthetic electron transport or steady state CO2 assimilation between control plants and transformants overexpressing PEPC C.g. or anti-sppc plants. However, a prolonged dark treatment resulted in a delayed induction of photosynthetic electron transport in plants with less PEPC. Rates of CO2 release in the dark determined after a 45 min illumination period at a high proton flux density were considerably enhanced in cppc plants and slightly diminished in anti-sppc plants. When CO2 assimilation rates were corrected for estimated rates of mitochondrial respiration in the light, the electron requirement for CO2 assimilation determined in low CO2 was slightly lower in transformants with higher PEPC, whereas transformants with decreased PEPC exhibited an appreciably elevated electron requirement. The CO2 compensation point remained unchanged in plants (cppc) with high PEPC activity, but might be increased in an antisense plant cell line. Stomatal opening was delayed in antisense plants, but was accelerated in plants overexpressing PEPC C.g. compared to the controls.

Cerebral hemodynamics in the posterior circulation of patients with bacterial meningitis.

OBJECTIVES: Stenoses of the middle and anterior cerebral artery (MCA,ACA) are a clinical relevant complication of bacterial meningitis. We examined the involvement of the posterior cerebral (PCA) and of the basilar artery (BA) into the inflammatory process. MATERIAL & METHODS: 39 unselected patients (26 men, 13 women; mean +/- SD age, 49 +/- 17 years) with bacterial (n = 37) and fungal (n = 2) meningitis underwent serial transcranial Doppler sonography recordings of the mean blood velocity (MBV) and the pulsatility index (PI) in the MCA, ACA and PCA, in the BA and in the submandibular internal carotid artery on Days 1, 3, 5, 8, 14 and 21 after admission. The results of the PCA and of the BA were compared to normal reference values and correlated to corresponding neurological signs. The criterion to assume a stenosis was: for the BA an MBV > or = 95 cm/s, for the PCA an MBV > or = 85 cm/s. RESULTS: Compared with the controls MBV in both arteries was normal on Days 1 and 8-21, but significantly increased on Days 3 and 5. The PI was significantly increased in the BA on all days and in the PCA on Days 1 and 8-21. Stenoses of the PCA (4 of 43) and of the BA (4 of 32) remained without corresponding neurological signs, and occurred only in patients with two or more narrowed arteries of the anterior circulation (p < 0.05). CONCLUSION: In bacterial meningitis, hemodynamic disturbances in the posterior circulation are less severe than in the anterior circulation and are clinically well tolerated.

Diagnosis of non-Hodgkin lymphoma of the maxilla with support of polymerase chain reaction.

Primary non-Hodgkin lymphoma of bone is an unusual extranodal presentation, and considerable difficulty exists in diagnosing some extranodal osseous lymphomas that develop in the head and neck region. Frequently, malignancies of the jawbones appear clinically as inflammatory diseases. Recognition of these cases usually occurs after the inflammatory-like symptoms have failed to respond to conventional therapy. This case report presents an extranodal non-Hodgkin lymphoma of the maxilla, which clinically imposed as odontogenic infection in a 45-year-old woman. The definite diagnosis was made by histologic means and confirmed by polymerase chain reaction (PCR). The latter is a molecular biologic method, which in unclear cases may be helpful in early differentiation of inflammatory from malignant processes.