Stefan Merkelbach - Academia.edu (original) (raw)

Papers by Stefan Merkelbach

Einleitung Bei der Multiplen Sklerose (MS, Encephalomyelitis disseminata) handelt es sich um eine... more Einleitung Bei der Multiplen Sklerose (MS, Encephalomyelitis disseminata) handelt es sich um eine chronische, multilokulare demyelinisierende Erkrankung des Zentralen Nervensystems, deren Ursachen bisher nicht exakt geklart werden konnten. Die im ZNS disseminiert auftretenden Entzundungsund Entmarkungsherde sind Ursache der sehr unterschiedlich verlaufenden klinischen Symptomatik u.a. mit multifokalen sensiblen Ausfallen, Paresen, Hirnnervenbefall, zerebellaren Storungen, Blasenstorungen sowie neuropsychologischen Defiziten (z.B. hirnorganisches Psychosyndrom). Bei einer Pravalenz von etwa 50-100/100.000 und einer Inzidenz von 4-6/100.000 in Deutschland betragt das Verhaltnis von Frauen zu Mannern etwa 2:1. Atiologisch werden u.a. T-Zell-vermittelte Autoimmunmechanismen, Virusinfektionen, genetische Dispositionen und der Einflus verschiedener Umweltfaktoren diskutiert. Es stellt sich auch die Frage nach erhohten Belastungen mit chlororganischen Schadstoffen und Metallen.

LaboratoriumsMedizin, 1998

Die diagnostische Relevanz und die Pathogenität von Autoantikörpern gegen zentralnervöse (ZNS) od... more Die diagnostische Relevanz und die Pathogenität von Autoantikörpern gegen zentralnervöse (ZNS) oder peripheraervöse (PNS) Strukturen sind bisher weitgehend unklar. Mittels eines indirekten Immunfluoreszenztests wurden in dieser Studie Seren und Liquores von 116 neurologisch erkrankten Patienten auf das Vorkommen von Antikörpern gegen ZNS-oder PNS-Sturkturen untersucht. Während Patienten mit Multipler Sklerose, Neuroborreliose oder amyotropher Lateralsklerose keine signifikanten Unterschiede gegenüber einer Kontrollgruppe mit nicht autoimmun bedingten neurologischen Erkrankungen zeigten, waren bei Patienten mit Polyradikulitis Guillain-Barro häufiger und höhertitrig Antikörper gegen Strukturen des peripheren Nervensystems nachweisbar (p jeweils < 0,01). Antikörper gegen Neurone oder gegen Purkinjezellen treten wahrscheinlich im Rahmen einer antitumoralen Immunantwort als Kreuzreaktion zwischen Tumor-und Nervenzellproteinen auf. Antineuronale Antikörper waren bei allen Patienten mit paraneoplastischen neurologischen Syndromen und bei 42% der Karzinompatienten ohne neurologische Symptomatik, jedoch bei keinem anderen Patienten nachweisbar (p<0,005). Dabei traten diese Antikörper in der Paraneoplasiegruppe in höheren Titern als in der Karzinomgruppe auf (p<0,005). Eine intrathekale Synthese dieser Autoantikörper ließ sich in 85,7% der Paraneoplasiepatienten, jedoch nicht bei Karzinompatienten ohne neurologische Störungen nachweisen (p<0,05).__Der immunfluoreszenzmikroskopische Nachweis von Autoantikörpern gegen Strukturen des Nervensystems erweist sich als hochspezifische Nlethode zur Erkennung paraneoplastischer neurologischer Syndrome. Positive Resultate in der Immunfluoreszenz sollten mittels Immunblot bestätigt werden. Möglicherweise können bestimmte Tumorerkrankungen ohne begleitende neurologische Symptomatik bei geringerer Sensitivität, aber ebenfalls hoher Spezifitat, früher erkannt werden.

Ultrasound in Medicine & Biology, 1996

Transcranial Doppler sonography (TCD) of the middle, anterior and posterior cerebral arteries and... more Transcranial Doppler sonography (TCD) of the middle, anterior and posterior cerebral arteries and of the basilar artery was used to evaluate the mean blood velocity (V ,,,.) and the pulsatility index IPI = (VSyst"liC-vdiss*olicYVnlea" ] as a vas,cular resistance index in 63 patients (male 40, female 23, mean age 43 2 19 y) with bacterial meningitis (n = 33, including 2 patients with fungal meningitis) and viral meningitis (n = 30) within 12 h after admission of the patients. The findings were similar for all intracranial arteries. Compared with reference values of 69 healthy volunteers [ V mean of middle cerebral artery [ MCA] 57 + 13 cm/s, MCA-PI 0.83 2 0.151, MCA-V,,,. was increased in patients with Glasgow coma scale (GCS) scores of 14 and 15 (71-C 18 cm/s; t-test: p < O.OOl), not significantly different in the patients with GCS scores of lo-13 (55 + 21 cm/s) and decreased in those with GCS scores of 3-9 (42 ? 21 cm/s, p < 0.01). The MCA-PI increased from 0.93 + 0.22 in the patients with GCS scores of 14-15 to 2.81 ? 2.06 in those with GCS scores of 3-9 (p < 0.001 vs. controls). By regression analysis, MCA-V,,.. decreased and MCA-PI increased with decreasing GCS scores (p < 0.001). Only in patients with bacterial meningitis was the Glasgow outcome scale (GOS) score lower the more the MCA-PI was increased (regression analysis p < 0.001). We conclude that in patients with bacterial and viral meningitis, and in a good clinical state, the cerebral blood flow seems increased by hyperemia; with clinical deterioration the cerebral haemodynamics worsen. However, the early assessment of the cerebral blood flow by TCD seems useful for predicting outcome in bacterial meningitis only.

Multiple Sclerosis Journal, 2001

Both cardiovascular disturbances and fatigue are frequent in multiple sclerosis (MS). We investig... more 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 ...

Journal of Neurology, 1998

To evaluate the influence of cerebral artery stenosis on the outcome of patients with bacterial m... more 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.

Infection, 1999

The predictive usefulness of clinical scores in patients with acute bacterial meningitis was inve... more The predictive usefulness of clinical scores in patients with acute bacterial meningitis was investigated. Fiftyone 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.

European Journal of Neurology, 1998

Paraneoplastic neurological syndromes in patients with Hodgkin's disease are rare finding... more 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.

Der Radiologe, 2000

ABSTRACT Die Encephalomyelitis disseminata oder Multiple Sklerose (ED oder MS) gilt als T-Zell-ve... more ABSTRACT Die Encephalomyelitis disseminata oder Multiple Sklerose (ED oder MS) gilt als T-Zell-vermittelte Autoimmunerkrankung. Schubförmig oder chronisch progredient kommt es im Zentralnervensystem infolge einer Demyelinisierung der weißen Substanz und axonaler Schädigungen zu einer Vielzahl neurologischer Symptome. Basierend auf pathogenetischen Erkenntnissen werden derzeit immunmodulative und immunsuppressive Therapien eingesetzt, die den Krankheitsverlauf zumindest bremsen. Klinische Symptome, diagnostische Kriterien, pathogenetische Überlegungen und sich daraus ableitende Therapiekonzepte werden zusammenfassend dargestellt. 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.

Clinical Neurology and Neurosurgery, 1997

Acta Neurologica Scandinavica, 2003

ABSTRACT To determine the impact of personality characteristics on feelings of fatigue in multipl... more ABSTRACT 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. 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. 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). 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.

Stroke, 1995

Background and Purpose We sought to examine the frequency and clinical relevance of intracranial ... more Background and Purpose We sought to examine the frequency and clinical relevance of intracranial artery stenoses in patients with bacterial meningitis in whom the occurrence of stroke has angiographically been reported to be associated with stenoses or occlusions of the large basal cerebral arteries. Methods Thirty-five unselected patients (24 men, 11 women; mean age, 51±18 years) with bacterial (n=33) or fungal (n=2) meningitis prospectively underwent serial transcranial Doppler sonography recordings of mean blood velocity (MBV) and pulsatility index in the middle (MCA) and anterior (ACA) cerebral arteries, as well as recordings of the ratio of the MBV of the MCA and internal carotid artery (MCA/ICA ratio) on days 1, 3, 5, 8, 14, and 21 after admission. The results were correlated with the Glasgow Coma Scale (days 1 to 14), the occurrence of focal cerebral signs, and the Glasgow Outcome Scale (short-term outcome, day 21). An MCA stenosis was diagnosed by an MBV of 120 cm/s or more ...

Therapeutic Advances in Neurological Disorders, 2016

Objectives: Approximately one in two patients with multiple sclerosis (MS) suffer from comorbid d... more Objectives: Approximately one in two patients with multiple sclerosis (MS) suffer from comorbid depression. The primary objective of this study was to evaluate the safety and tolerability of fingolimod and antidepressant combination in relapsing-remitting MS patients with mild-to-moderate depression. Efficacy outcome variables were quality of life (QoL), fatigue, disability and depression. Methods: Patients received open-label fingolimod 0.5 mg over 2 weeks, followed by fingolimod plus citalopram (40 mg), fluoxetine (40 mg) or venlafaxine (150 mg) over 16 weeks. The antidepressant was selected at the physician's discretion. Results: In total, 54 patients were recruited at 25 centres across Germany. No new safety signals (including cardiac) emerged compared with previous clinical studies. Adverse events (mostly mild-to-moderate) were reported in 43 patients. A total of three patients had serious adverse events and 10 discontinued the study. QoL (mean [95% confidence interval]) improved by 2.2 (−3.3, −1.2; Patient Reported Indices for MS questionnaire), fatigue by 8.2 (−13.1, −3.3; modified Fatigue Impact Scale) and depression by 6.3 (−8.4, −4.2; Hamilton Depression Scale) points. However, the results must be interpreted cautiously owing to limited patient numbers. Conclusions: Combination of fingolimod with antidepressant medication showed no unexpected safety signals. Patient-reported outcomes (QoL, disability, fatigue and depression) remained stable or improved.

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Der Nervenarzt, 1995

Serial (days 1, 3, 5, 8, 14, 21 after admission) transcranial Doppler ultrasound measurements of ... more Serial (days 1, 3, 5, 8, 14, 21 after admission) transcranial Doppler ultrasound measurements of the mean blood velocity (Vmean) and the pulsatility index (PI) in the middle, anterior and posterior cerebral arteries (MCA, ACA, PCA) and the basilar artery were performed in 35 consecutive patients (male, 20, female, 15, mean age: 37 +/- 19 years) with acute meningitis or meningoencephalitis thought to have arisen from viral infections. The Glasgow Coma Scale (GCS) and the TCD findings on days 1-8 were compared with the Glasgow Outcome Scale on day 21 (GOS, short-term outcome). Compared with the reference values recorded in 69 healthy volunteers, Vmean was significantly elevated in the MCA, ACA and PCA on days 1-3, and on day 5 in the MCA (P< 0.01-0.05). The PI was significantly increased on days 1-8 in all intracranial arteries (P < 0.001-0.05). With respect to the outcome, patients with a poor outcome (GOS score 1-3) were found to have had significantly more markedly elevated P...

Journal of Neurology, 1999

The treatment of paraneoplastic neurological syndromes (e.g., tumor therapy, immunosuppressive th... more 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.

Journal of Neurology, 2002

Journal of Neuroimaging, 2001

To evaluate the utility of different scales for clinical assessment, over time, in acute bacteria... more 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.

The Journal of Nervous and Mental Disease, 2002

Acta Neurologica Scandinavica, 2000

Objective ± To evaluate long-term cognitive de®cits in unselected patients with previously diagno... more Objective ± To evaluate long-term cognitive de®cits in unselected patients with previously diagnosed meningitis and to compare these de®cits to neurologic and psychopathologic impairment. Patients and methods ± Twenty-two unselected patients (mean age 52.5t17.1 years) were examined neurologically, psychiatrically, and psychometrically 30t11 months after the acute stage of bacterial meningitis. Results of psychometric tests were compared with clinical long-term de®cits. Psychometric tests were additionally applied on 17 healthy controls (mean age 49.2t14.2 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 signi®cantly in patients as compared to controls. Verbal intelligence was less affected than performance ef®ciency. Patients with pneumococcal meningitis had signi®cantly lower test results than patients with other pathogens. The psychometric test results were only slightly related with clinical ®ndings of the follow-up examination. Conclusion ± Psychometric de®cits 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.

The Lancet Neurology, 2021

BACKGROUND Systematic electrocardiogram (ECG) monitoring improves detection of covert atrial fibr... more BACKGROUND Systematic electrocardiogram (ECG) monitoring improves detection of covert atrial fibrillation in stroke survivors but the effect on secondary prevention is unknown. We aimed to assess the effect of systematic ECG monitoring of patients in hospital on the rate of oral anticoagulant use after 12 months. METHODS In this investigator-initiated, randomised, open-label, parallel-group multicentre study with masked endpoint adjudication, we recruited patients aged at least 18 years with acute ischaemic stroke or transient ischaemic attack without known atrial fibrillation in 38 certified stroke units in Germany. Patients were randomly assigned (1:1) to usual diagnostic procedures for atrial fibrillation detection (control group) or additional Holter-ECG recording for up to 7 days in hospital (intervention group). Patients were stratified by centre using a random permuted block design. The primary outcome was the proportion of patients on oral anticoagulants at 12 months after the index event in the intention-to-treat population. Secondary outcomes included the number of patients with newly diagnosed atrial fibrillation in hospital and the composite of recurrent stroke, major bleeding, myocardial infarction, or death after 6 months, 12 months, and 24 months. This trial was registered with ClinicalTrials.gov, NCT02204267, and is completed and closed for participants. FINDINGS Between Dec 9, 2014, and Sept 11, 2017, 3465 patients were randomly assigned, 1735 (50·1%) to the intervention group and 1730 (49·9%) to the control group. Oral anticoagulation status was available in 2920 (84·3%) patients at 12 months (1484 [50·8%] in the intervention group and 1436 [49·2%] in the control group). For the primary outcome, at 12 months, 203 (13·7%) of 1484 patients in the intervention group versus 169 (11·8%) of 1436 in the control group were on oral anticoagulants (odds ratio [OR] 1·2 [95% CI 0·9-1·5]; p=0·13). Atrial fibrillation was newly detected in patients in hospital in 97 (5·8%) of 1714 in the intervention group versus 68 (4·0%) of 1717 in the control group (hazard ratio [HR] 1·4 [95% CI 1·0-2·0]; p=0·024). The composite of cardiovascular outcomes and death did not differ between patients randomly assigned to the intervention group versus the control group at 24 months (232 [13·5%] of 1714 vs 249 [14·5%] of 1717; HR 0·9 [0·8-1·1]; p=0·43). Skin reactions due to study ECG electrodes were reported in 56 (3·3%) patients in the intervention group. All-cause death occured in 73 (4·3%) patients in the intervention group and in 103 (6·0%) patients in the control group (OR 0·7 [0·5-0·9]). INTERPRETATION Systematic core centrally reviewed ECG monitoring is feasible and increases the detection rate of atrial fibrillation in unselected patients hospitalised with acute ischaemic stroke or transient ischaemic attack, if added to usual diagnostic care in certified German stroke units. However, we found no effect of systematic ECG monitoring on the rate of oral anticoagulant use after 12 months and further efforts are needed to improve secondary stroke prevention. FUNDING Bayer Vital. TRANSLATION For the German translation of the abstract see Supplementary Materials section.

Multiple Sclerosis, 2006

Intravenous immunoglobulins (IVIG) have been effective in reducing multiple sclerosis (MS) diseas... more 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.