[Tryptophan immunoadsorption for multiple sclerosis and neuromyelitis optica: therapy option for acute relapses during pregnancy and breastfeeding]. / Tryptophan-Immunadsorption bei Multipler Sklerose und Neuromyelitis optica : Therapieoption bei akuten Schüben in der Schwangerschaft und Stillphase.

BACKGROUND: Approximately 25 % of women with multiple sclerosis (MS) suffer clinically relevant relapses during pregnancy. Almost all disease-modifying drugs are contraindicated in pregnancy. High-dose glucocorticoids have some serious risks, especially within the first trimester. Tryptophan immunoadsorption (IA) provides a safe option to treat MS relapses during pregnancy. OBJECTIVES: In this case series we describe for the first time the use of tryptophan IA for MS and neuromyelitis optica (NMO) relapses during pregnancy and breastfeeding. PATIENTS AND METHODS: In this study a total of 9 patients were retrospectively analyzed of which 7 patients received IA treatment during pregnancy, 2 during breastfeeding and 4-6 tryptophan IA treatments were performed per patient with the single use tryptophan adsorber. Primary outcome was symptom improvement of the relapse. RESULTS: In this study four patients with MS and one with NMO relapse during pregnancy were treated with IA without preceding glucocorticoid pulse therapy. The MS patients showed improvement in the expanded disability status scale (EDSS) by at least one point, the NMO patient showed significant improvement in visual acuity and two pregnant patients with steroid-refractory relapses showed clinically relevant improvement after IA. Of the patients two suffered from steroid-refractory relapses during breastfeeding and relapse symptoms improved in both cases after treatment with IA. All treatments were well tolerated and no serious adverse events occurred. CONCLUSION: Tryptophan IA was found to be safe, well-tolerated and effective in the treatment of MS and NMO relapses during pregnancy and breastfeeding, sometimes without preceding glucocorticoid pulse therapy. A binding recommendation is limited without prospective clinical studies.

[Multimodal complex treatment in multiple sclerosis : influence on motor performance and need of care]. / Multimodale Komplexbehandlung bei Multipler Sklerose : Einfluss auf die motorische Leistungsfähigkeit und Pflegebedürftigkeit.

BACKGROUND: The concept of multimodal complex treatment combines treatment by physicians with intensive conservative treatment. The therapy duration is often 14-21 days. Investigations showing the benefit of this treatment for multiple sclerosis patients are currently missing. PATIENTS AND METHODS: A total of 220 patient records were retrospectively analyzed with respect to the Barthel index, the expanded disability status scale (EDSS) score and early rehabilitation assessment (Frühreha-Assessment). Subgroup analysis was used to examine variations in clinical severity, age and disease duration. RESULTS: The motor subscore was improved (p = 0.031) in the total sample. The subgroup analysis showed that in particular patients with an average disease duration (11-20 years) and age (41-60 years) showed the greatest benefits. In addition to the group of moderately affected patients the group of severely affected patients (Barthel index 36-64 and < 35) also showed an improvement in the Barthel index. CONCLUSIONS: Multimodal complex treatment for MS patients can lead to a significant improvement in motor abilities and reduction of the need of nursing. In particular intermediately affected patients showed the strongest improvement in contrast to the results of the current appraisal of the German Medical Review Board of the Health Insurance Funds (MDK).

Development of a Mobile-First Registry to Recruit Healthy Volunteers and Members of Underrepresented Communities for Alzheimer's Disease Prevention Studies.

BACKGROUND: Web-based participant recruitment registries can be useful tools for accelerating enrollment into studies, but existing Alzheimer's disease (AD)-focused recruitment registries have had limited success enrolling individuals from underrepresented racial and ethnic groups. Designing these registries to meet the needs of individuals from these communities, including designing mobile-first, may facilitate improvement in the enrollment of underrepresented groups. OBJECTIVES: Evaluate the usability of a prototype mobile-first participant recruitment registry for AD prevention studies; assess users' perceptions of and willingness to sign up for the registry. DESIGN AND SETTING: Quantitative usability testing and an online survey; online setting. PARTICIPANTS: We recruited 1,358 adults ages 45-75 who self-reported not having a diagnosis of mild cognitive impairment, AD, or other forms of dementia (Study 1: n=589, Study 2: n=769). Black/African American and Hispanic/Latino participants were specifically recruited, including those with lower health literacy. METHODS AND MEASUREMENTS: Study 1 measures the prototype's usability through observed task success rates, task completion times, and responses to the System Usability Scale. Study 2 uses an online survey to collect data on perceptions of and willingness to sign up for the mobile-first registry. RESULTS: Study 1 findings show the prototype mobile-first recruitment registry website demonstrates high usability and is equally usable for Black / African American, Hispanic/Latino, and White user groups. Survey results from Study 2 indicate that users from underrepresented communities understand the registry's purpose and content and express willingness to sign up for the registry on a mobile device. CONCLUSIONS: Designing mobile-first participant recruitment registries based on feedback from underrepresented communities may result in more sign-ups by individuals from minoritized communities.

[Immunoadsorption for steroid-unresponsive multiple sclerosis-relapses: clinical data of 14 patients]. / Immunadsorption bei steroidrefraktärem Schub der Multiplen Sklerose : Klinische Erfahrungen bei 14 Patienten.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating immune-mediated disease of the central nervous system, often associated with relapses. Plasma exchange (PE) has become established as an escalation therapy for steroid-unresponsive relapses in national and international guidelines. PE is a non-selective apheresis method with elimination of the entire plasma with subsequent substitution. Selective extracorporeal elimination of autoantibodies and immune complexes with immunoadsorption (IA) is increasingly replacing PE for the treatment of autoimmune neurological diseases due to its equivalent efficacy and advantageous safety profile. The use of IA for MS still remains to become established. The aim of this retrospective investigation was to evaluate efficacy and safety of IA in patients with steroid-unresponsive relapses. PATIENTS AND METHODS: Fourteen patients with steroid-unresponsive MS relapses were retrospectively analysed. Patients received six IA treatments within 2 weeks using the single-use tryptophan adsorber. Peripheral venous access was used in 11 patients, and 3 patients needed a central line. The plasma volume treated was 2 l per IA. Efficacy criteria were improvement in symptoms of MS relapses which were measured with the Kurtzke scale (EDSS, FS) and visual acuity measurements for patients with optic neuritis. RESULTS: In 12 of 14 patients the major symptom of MS relapse improved to a clinically relevant extent after tryptophan IA; no patient got worse, corresponding to a response rate of 86%. Mean EDSS and FS in patients with spastic paresis (n=4) and dizziness (n=2) as well as mean visual acuity in patients with optic neuritis (n=8) significantly improved after IA. IA treatments were safe, with good tolerability, and no severe adverse events occurred. CONCLUSION: Immunoadsorption for the treatment of steroid-unresponsive MS relapses was safe and effective. The response rate was comparable to published results with PE. With IA, in contrast to unselective PE, administration of human plasma products is not necessary, avoiding associated risks.

Effect of lower-energy, higher-fiber diets on pigs divergently selected for residual feed intake when fed higher-energy, lower-fiber diets.

Residual feed intake (RFI) is the difference between observed and predicted feed intake of an animal, based on growth and maintenance requirements. In Yorkshire pigs, divergent selection for increased (Low RFI) and decreased (High RFI) RFI was carried out over 10 generations (G) while feeding a corn- and soybean-meal-based, higher-energy, lower-fiber (HELF) diet. In G8 to G10, representing 4 replicates, barrows and gilts (n = 649) of the RFI lines were fed the HELF diet and a diet incorporating coproducts that were lower in energy and higher in dietary fiber (LEHF). The diets differed in ME, 3.32 vs. 2.87 Mcal/kg, and in neutral detergent fiber (NDF), 9.4% vs. 25.9%, respectively. The impact of the LEHF diet on 1) performance and growth, 2) diet digestibility, 3) genetic parameter estimates, and 4) responses to selection for RFI, when fed the HELF, was assessed. In general, the LEHF diet reduced the performance of both lines. When fed the HELF diet, the Low RFI pigs had lower (P < 0.05) ADFI (-12%), energy intake (-12%), ADG (-6%), and backfat depth (-12%); similar (P > 0.05) loin muscle area (LMA; +5%); and greater (P < 0.05) feed efficiency (i.e., 8% higher G:F and 7% lower RFI) than the High RFI line. These patterns of line differences were still present under the LEHF diet but differences for ADFI (-11%), energy intake (-10%), G:F (+2%), and RFI (-6%) were reduced compared to the HELF diet. Apparent total tract digestibility (ATTD) of the HELF and LEHF diets was assessed using 116 barrows and gilts from G8. When fed the HELF diet, ATTD of DM, GE, N, and NDF were similar between lines (P ≥ 0.27), but when fed the LEHF diet, the Low RFI pigs had greater digestibility (7%, 7%, 10%, and 32%) than the High RFI line (P ≤ 0.04). To measure responses to selection for RFI and estimate genetic parameters, data from all 10 generations were used (HELF; n = 2,310; LEHF, n = 317). Heritability estimates of performance traits ranged from 0.19 to 0.63, and genetic correlations of traits between diets were high and positive, ranging from 0.87 (RFI) to 0.99 (LMA). By G10, RFI in the Low RFI line was 3.86 and 1.50 genetic SD lower than in the High RFI line when fed the HELF and LEHF diets, respectively. Taken together, the results of this study demonstrate that responses to selection for RFI when fed a HELF diet are not fully realized when pigs are fed an extremely LEHF diet. Thus, feeding diets that differ from those used for selection may not maximize genetic potential for feed efficiency.

Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS.

BACKGROUND: Mitoxantrone (MITO) is associated with dose-related cardiotoxicity when administered concomitantly with other cytotoxic agents with or without radiotherapy for leukemia and solid tumors. OBJECTIVE: To review observed cardiotoxicity of single-agent MITO therapy for MS. METHODS: Records of 1,378 patients from three clinical trials of MITO treatment for MS were reviewed for signs and symptoms of cardiac dysfunction and left ventricular ejection fraction (LVEF) results. Duration of follow-up was a median of 29 months (4,084 patient-years). RESULTS: No patients experienced congestive heart failure (CHF) before treatment. Cumulative MITO doses ranged from 2 to 183 mg/m(2) (mean 60.5 mg/m(2), median 62.5 mg/m(2)), and 141 patients received >100 mg/m(2). Two of 1,378 patients experienced CHF after initiating MITO therapy. Of 1,378 patients, 779 completed baseline and scheduled follow-up LVEF testing. Baseline LVEF was >50% in all 779 patients. Seventeen of 779 patients had asymptomatic LVEF of <50% (incidence proportion = 2.18%, 95% CI = 1.28 to 3.47%). Although the incidence of asymptomatic LVEF of <50% was not significantly related to monthly versus 3-monthly therapy, duration of therapy, age, or gender, asymptomatic LVEF of <50% trended higher with a cumulative dose of >/=100 mg/m(2) (5.0%) than with <100 mg/m(2) (1.8%) (p = 0.06). CONCLUSIONS: The observed incidence of CHF in patients with MS who received a mean cumulative dose of 60.5 mg/m(2) MITO was <0.20%. Continued monitoring of patients with MS who are receiving MITO is needed to determine whether the incidence of CHF increases with higher cumulative MITO doses and prolonged follow-up.

Intrathecal baclofen therapy for stiff-man syndrome and progressive encephalomyelopathy with rigidity and myoclonus.

We report on eight patients with stiff-man syndrome (SMS) or its "plus" variant, progressive encephalomyelopathy with rigidity and myoclonus (PERM) receiving intrathecal baclofen via pump. In six of the patients, follow-ups continued for approximately 2.5 to 6.5 years after pump implantation. Intrathecal baclofen was an effective last-resort alternative for patients who responded poorly to or did not tolerate oral antispasticity medications. General mobility increased, and spasms and rigidity were reduced; however, no complete remissions were observed either before or after pump implantation. PERM patients showed more severe and rapid progression of symptoms and more attacks of autonomic dysregulation than SMS patients. They also required higher doses and more rapid dosage increases. Complications of intrathecal baclofen therapy included spasm-induced rupture of the catheter, catheter dislocation causing radicular symptoms, and pump malfunction resulting in inaccurate dosage administration. Patients suffered fewer side effects with intrathecal baclofen than with oral medication, but overdose resulted in a transient, comalike state in one patient and sudden dosage reduction due to pump failure was fatal in another.

GH, IGF-I, IGFBP-3 and IGFBP-2 in cerebrospinal fluid of infants, during puberty and in adults.

During diagnostic lumbar punctions cerbrospinal fluid (CSF) was collected for the determination of GH, IGF-I, IGFBP-3 and IGFBP-2. The patients were 0.3 to 68 years od and suffered from viral infections, leukemias, M. Hodgkin or multiple sclerosis. Only CSF samples without any pathological alterations were analysed. In infants and adults CSF GH concentrations significantly declined with age, while IGF-I and the two binding proteins were unrelated to age. GH was not correlated to IGF-I, IGFBP-3 or IGFBP-2. However, IGF-I was strongly related to IGFBP-3 (r = 0.529; < 0.001) and IGFBP-2 (r = 0.796; < 0.001) as was IGFBP-3 to IGFBP-2 (r = 0.685; < 0.001), suggesting dependence of the three variables. With IGFBP-3 or IGFBP-2 as control variables (partial correlation) IGF-I was no longer related to the binding proteins, while the relation of IGFBP-3 to IGFBP-2 remained unchanged with IGF-I as the control variable (r = 0.687; < 0.001). The results suggest that the age-related decrease of CSF GH may contribute to the age-dependent decline of GH receptors in brain, which are up-regulated by GH. Furthermore, in CSF IGF-I concentrations were determined by the two binding proteins. It may be speculated that the transfer of IGF-I through the blood CSF barrier or its production in brain may be closely related to the IGF-binding proteins.

Measurements of angular distributions of Rayleigh and Mie scattering events in biological models.

Remission spectroscopy in living tissues can only be performed because scattering processes induce a pronounced amount of backscattered light. New types of scattering chambers were constructed in order to investigate the angular distribution of light intensities caused by scattering events typical for living tissues. Different solutions and suspensions containing microspheres, haemoglobin molecules, erythrocytes and liver homogenate were used in order to gain basic information applicable to remission spectrophotometry in tissue. Reflection spectroscopy in biological tissues is only possible because of the scattering properties of the material under observation. Light which penetrates the sample is remitted from the tissue. The remission is caused by the scattering of the light by different biological structures and particles. This scattered light gives information about the optical properties of the particles and structures in an integral form. A scattering chamber for small sample volumes has been developed for measurements of the optical properties of various particles in suspension. Measurements of scattering diagrams from microspheres with an average diameter of 7 microns, artificial particles, haemoglobin solutions, mixtures of microspheres and haemoglobin as well as erythrocytes and mitochondria have been performed. The different optical behaviour of the measured signals is qualitatively discussed.

Cerebral magnetic resonance imaging pathology and cerebro-spinal fluid protein in sporadic amyotrophic lateral sclerosis (sALS).

In 3 out of 20 patients with sporadic amyotrophic lateral sclerosis (sALS), cranial magnetic resonance imaging detected multiple demyelinating lesions. All 3 patients died from definite upper and lower motor neuron degeneration. In all 3 cases total cerebro-spinal fluid (CSF) protein remained within normal ranges, and a blood-CSF barrier dysfunction was not detectable. In one of the patients multifocal CNS demyelination coincided with an intrathecal synthesis of immunoglobulin-G and autochthonous CSF oligoclonal IgG banding (OCB) early in disease. Neither absolute or age-corrected survival nor disease progression differed for patients with and without cerebral MR lesions, or normal vs. elevated CSF total protein. Evaluating the CSF in an extended patient sample (n = 29), we found the total CSF protein elevated in 5 of 16 men and none of 13 women (p < 0.05). The mean age-corrected CSF protein content [practical reference limit = (age x 3.3) + 300 mg/l] was higher in male (465 mg/l +/- 32 SE) than in female (350 mg/l +/- 26 SE) sALS patients (p < 0.01). This coincides with a male preponderance in sALS.

Effects of physiotherapy on F-wave-amplitudes in spasticity.

F-wave amplitudes have been used to demonstrate changes of motor neuron excitability in spasticity and pharmacological antispastic therapy. In this study it is shown that F-wave amplitudes can also be used to document changes of motor neuron excitability as an effect of physiotherapy. Ten F-waves were recorded immediately before and after physiotherapy in 42 legs of 21 patients with spastic paraparesis due to multiple sclerosis. Mean F-wave amplitude, maximum F-wave amplitude, mean F-wave/M-response ratio and maximum F-wave/M-response ratio were significantly lower after physiotherapy than before. Therefore the antispastic effect of physiotherapy is documented by a decrease of F-wave-amplitude parameters.

[Unilateral sensory neuropathy of the trigeminal nerve as the leading symptom of primary Sjögren syndrome ("sicca syndrome")]. / Einseitige sensorische Neuropathie des N. trigeminus als Leitsymptom eines primären Sjögren-Syndroms ("Sicca-Syndrom").

We report a case who presenting with a progressive numbness and mild hyperpathia in the second cutaneous division of the left trigeminal nerve as the leading symptom of Primary Sjögren's Syndrome. Further typical features of this autoimmune disorder are keratoconjunctivitis sicca and xerostomia. A symmetrical, predominantly sensory polyneuropathy can be revealed by sensory nerve conduction studies of the median and sural nerves. Laboratory findings mostly include elevated erythrocyte sedimentation rate, hypergammaglobulinemia and hypercomplementemia. The presence of the precipitating antinuclear antibodies SS-A and/or SS-B is pathognomonic for Sjögren's Syndrome. As long as the disease remains benign, treatment should be symptomatic. Malignant exacerbations require immunosuppressive treatment.

Increased V/D-ratio in lumbosacral SEP's as a new electrophysiological measure of spasticity.

STUDY DESIGN: Open-label, prospective study. OBJECTIVE: To establish the amplitude-ratio of V-response and D-response (V/D-ratio) as a new measure of spasticity, comparing the motor effect of the H-reflex to the sensoric input. METHODS: In 13 legs of seven patients with spasticity and in four legs of patients without central nervous system disease, maximal M-response and maximal H-reflex were recorded. Lumbosacral SEP's were recorded with the same stimulus parameters as the maximal H-reflex. H/M-ratio and V/D-ratio were compared to the increased muscle tone. RESULTS: The H/M-ratio and the V/D-ratio in legs with spasticity differed significantly from the H/M-ratio and the V/D-ratio in normal legs. But only the V/D-ratio was higher in legs with moderately or highly increased muscle tone than in legs with slightly increased muscle tone. CONCLUSION: The V/D-ratio increases in spasticity and shows an even closer relationship to increased muscle tone than the H/M-ratio.

[Immunosuppressive therapy of multiple sclerosis with mitoxantrone]. / Die immunsuppressive Therapie der multiplen Sklerose mit Mitoxantron.

Preliminary clinical results indicate that the cytostatic agent mitoxantrone is an effective and very tolerable substance for treating multiple sclerosis (ms). Our own experience, added to the findings of other pilot studies, seems to indicate that disease progression can be slowed in a majority of patients with rapidly progressive ms. Mitoxantrone is mainly excreted by the hepato-biliary pathways and therefore it can be used in patients with renal insufficiency or chronic cystopyelitis, a frequently occurring condition in ms. The side effects observed in our therapeutic scheme which could be attributed to mitoxantrone were tolerable. Mild gastrointestinal complaints were occasionally reported and vomiting was very rare. A carcinogenic effect from mitoxantrone has not been reported. A decrease in the leucocyte count is to be expected 6-15 days following treatment administration. Potential cardiotoxicity represents the primary long term adverse reaction and thus patients with cardiovascular risk factors should not be treated with mitoxantrone. Once a cumulative dosage of 140 mg/m2 is reached cardiac function tests, including echocardiography with measurement of the left ventricular ejection fraction, should be routinely carried out preceding each treatment administration in all patients. Mitoxantrone is currently not licensed for use in patients with ms and therefore should be restricted to patients with rapid disease progression where other generally accepted treatment modalities have failed.

[Communication for patients with severe motor handicaps--clinical experience with a new electronic communication aid]. / Kommunikation für motorisch Schwerstbehinderte--Klinische Erfahrungen mit einer neuen elektronischen Kommunikationshilfe.

The use of "Komhilf", a newly developed communication aid for persons with severe physical handicap, is described on the example of two patients with amyotrophic lateral sclerosis. Aside individual letter input, it provides input of complete phrases signifying basic needs or common request, without a need for letter-by-letter spelling. After a short familiarization period, both patients were able to communicate up to two to three hours daily via "Komhilf". Psychic stabilization and increased levels of activity were observed in the patients, which subsequently also entailed increased compliance with other therapeutic measures. Additional features include good transportability, use in lying and sitting (wheelchair) patients alike, easy-to-learn operation, and, not least, a competitive price.

[Clinical value of antibody titers to Borrelia burgdorferi and titer course in neurologic disease pictures]. / Klinische Wertigkeit von Antikörpertitern gegen Borrelia burgdorferi und Titerverläufe bei neurologischen Krankheitsbildern.

Over a period of 3 years, antibody titres against Borrelia burgdorferi in serum were determined for 492 patients with a wide spectrum of neurological diseases. Using the ELISA technique, we found elevated titres against Borrelia burgdorferi in about 20% of these patients. Cranial nerve paresis was often the leading symptom of an acute Neuroborreliosis. In a number of cases the diagnosis was indicated only by an elevated IgG titre in the patient's serum, or a decrease in the titre level following antibiotic treatment. The IgG titres are, however, unsuitable for control of therapy. Non-specific parameters of inflammation such as blood sedimentation rate (BSC), C-reactive protein (CRP), serum-electrophoresis or leucocyte count are also unsuitable in evaluating the therapeutic effect or for confirming the diagnosis. The most important diagnostic criterion is the demonstration of Borrelian antibodies, synthesised locally in cerebrospinal fluid (CSF). A spirochaete index above 2 suggests autochthonous intrathecal antibody production. This procedure corresponds to the determination of intrathecally produced Treponema pallidum antibodies in neurolues from quantitative TPHA values and total IgG in serum and CSF (ITpA Index according to Prange).

Early cognitive impairment in multiple sclerosis detected by a screening with a vocabulary-test.

Vocabulary deficits in multiple sclerosis patients do not fit to the concept of subcortical dementia usually applied to describe cognitive impairment in multiple sclerosis. In a screening of young patients with a vocabulary test a significant correlation was found between the age at the onset of symptoms and the score in this test. This may lead to an explanation of vocabulary deficits recently described as results of a slowed language acquisition caused by subcortical lesions in early multiple sclerosis.

[Simultaneous occurrence of sarcoidosis and MS or sarcoidosis within the clinical picture of multiple sclerosis?]. / Gemeines Auftreten von Sarkoidose und MS oder Sarkoidose mit dem Vollbild einer multiplen Sklerose?

Twelve years following the diagnosis of a histologically proved Sarcoidosis, a patient developed a central paresis of one lower limb. Two years later, tetraparesis, bladder dysfunction, ataxia and an internuclear bilateral ophthalmoplegia occurred. In CSF oligoclonal IgG without dysfunction of the blood brain barrier was found. On the basis of these data multiple sclerosis was diagnosed.

[Subacute organic psychosyndrome as a clinical manifestation of infection with stage II Borrelia burgdorferi without further neurologic manifestations]. / Subakutes organisches Psychosyndrom als klinische Manifestation einer Infektion mit Borrelia burgdorferi im Stadium II ohne weitere neurologische Störungen.

A 60-year old man developed a subacute psychoorganic syndrome over four weeks. CCT was normal, except a slight atrophy of the cerebellar superior vermiform process. In the CSF we found 1696/3 cells, suggesting a lesion of the hemato-encephalic barrier, an autochthonous IgG production and an increased specific antibody-titre (10.3) for Borrelia burgdorferi. Based on these data a Lyme-Neuroborreliosis being diagnosed. Treatment with Cefotaxim and Gentamycin was successful, a complete remission of the psychopathological symptoms had been obtained. This case is an uncommon manifestation of a Borrelia-burgdorferi-infection of the CNS with psychopathological symptoms but no neurological deficit. We conclude that an affection of the CNS with Borrelia burgdorferi must always be taken into consideration in patients presenting a subacute psychoorganic syndrome of unknown etiology.