Increase of CD8+ T-effector memory cells in peripheral blood of patients with relapsing-remitting multiple sclerosis compared to healthy controls.

CCR7 and CD45RA expression on CD4+ and CD8+ T-cells in blood (PB) of 16 patients with multiple sclerosis (MS) and 16 healthy controls and cerebrospinal fluid (CSF) of 10 patients suffering from MS were analysed by flow cytometric measurements. T-cells were divided by their distinct homing potentials and effector-functions in three groups: naïve T-cells (CCR7+, CD45RA+), central memory T-cells (TCM) (CCR7+, CD45RA-) and effector memory T-cells (TEM) (CCR7-, CD45RA-). There was a significant increase of CD8+ TEM-cells in PB of MS patients compared to healthy controls, indicating systemic immune activation. Further we found a relative depletion of CD8+ TEM-cells in CSF of MS patients compared to matching blood samples, suggesting that these cells represent the effector arm of the immune response and infiltrate the brain tissue at the sites of inflammation.

Driving simulator and neuropsychological [corrected] testing in OSAS before and under CPAP therapy.

Patients with obstructive sleep apnoea syndrome (OSAS) have an increased car accident rate. Investigations on accident frequency are based on case history, insurance reports and driving simulator studies. The present study combines neuropsychological testing of different attention aspects engaged in driving a car and driving simulation to evaluate a suitable instrument for assessing therapeutic effects of continuous positive airway pressure (CPAP). Driving simulator investigation and neuropsychological testing of alertness, vigilance and divided attention were performed in 31 patients with polysomnographically confirmed OSAS (apnoea-hypopnoea index 24.8+/-21.5.h(-1)) before, and 2 and 42 days after initiation of CPAP. Divided attention and alertness improved significantly during CPAP, whereas vigilance remained unchanged. However, accident frequency (OSAS before therapy: 2.7+/-2.0; 2 days after CPAP: 1.5+/-1.4; 42 days after CPAP: 0.9+/-1.3) and frequency of concentration faults (OSAS before therapy: 12.4+/-5.1; 2 days after CPAP: 6.5+/-3.9; 42 days after CPAP: 4.9+/-3.3) decreased in the simulated driving situation after 2 and 42 days of therapy. There was no relation between accident frequency, concentration faults and daytime sleepiness, as measured by the Epworth Sleepiness Scale, and polysomnographic or neuropsychological findings, respectively. In conclusion, the present results suggest that driving simulation is a possible benchmark parameter of driving performance in obstructive sleep apnoea syndrome patients.

[Psychological abnormalities in patients with complex regional pain syndrome (CRPS)]. / Psychische Veränderungen bei Patienten mit komplexem regionalem Schmerzsyndrom (CRPS).

QUESTION: Do comorbid psychological disorders, dysfunctional pain processing, and psychosocial pain coping occur with complex regional pain syndrome (CRPS) and is a connection between clinical and psychological manifestations apparent? METHODS: In addition to securing information on case histories and performing clinical neurological examinations of chronic CRPS patients, the structured clinical interview (SCID), pain perception scale, and the Kiel Pain Inventory were employed. RESULTS: The structured clinical interview revealed evidence of a depressive episode in 65% of CRPS patients. Pain perception is similar to neuropathic pain syndromes and patient history revealed a slightly increased frequency of anxiety and affective disorders. Depressive syndrome occurred significantly more often in right-sided CRPS; otherwise, there were no significant correlations between medical history, clinical examination, and frequency of psychological disorders. However, CRPS patients with allodynia manifest clinical signs of special psychological distress. CONCLUSION: In chronic CRPS depressive syndrome frequently develops and psychological treatment can be recommended.

[Clinical findings in patients with chronic complex regional pain syndrome]. / Klinische Auffälligkeiten bei Patienten mit chronischem komplexen regionalen Schmerzsyndrom (sympathische Reflexdystrophie/Kausalgie).

PURPOSE: What are the clinical findings in patients with chronic complex regional pain syndrome (CRPS)? METHODS: Bedside examination was performed in 40 patients with CRPS and a mean illness duration of 43 months. To evaluate motor and autonomic disturbances, rating scales were developed and applied. Quantitative sensory testing (QST) was conducted in 24 patients. RESULTS: Clinical examination revealed sensory abnormalities in 93% of patients examined (in 56% limited to the affected limb, in 7% in the upper quadrant of the body, in 30% hemisensory impairment of the ipsilateral body side), and 60% of the patients suffered from mechanical allodynia in the affected limb. Patients with generalized sensory impairment had a significantly longer illness duration, pain intensity and significantly higher frequency of mechanical allodynia/hyperalgesia than patients with sensory deficits limited to the limb affected. In patients with generalized sensory abnormalities, QST revealed significant changes of cold, warm and touch thresholds on the ipsilateral compared to the contralateral body side. Mild/moderate motor abnormalities could be demonstrated in 45% of patients, tremor (50%), impaired joint movements, 45%, and 40% of patients revealed autonomic disturbances. CONCLUSION: In chronic CRPS, among clinical symptoms and signs, pain and sensory impairment play a major role. Mechanical allodynia reveals the highest level of subjective disability among all symptoms. With respect to hemisensory impairment, functional disturbances of central pain processing in the nucleus ventralis posterior of the thalamus are postulated.

[Visual cortex in the Tolosa-Hunt syndrome. Functional imaging for the detection of a psychogenic disorder--a case report]. / Visusstörungen beim Tolosa-Hunt-Syndrom. Untersuchung mit der funktionellen Magnetresonanztomographie zur Abgrenzung psychogener Störungen--Ein Fallbericht.

Besides painful ophthalmoplegia, patients suffering from Tolosa-Hunt syndrome often present increasing loss of visual perception. The impairment of the optic nerve leads to a delay of the VEP (visual evoked potentials) responses. Using the method of magnetic resonance imaging (MRI), some patients present unspecific alterations in the vicinity of the optic nerve. However, both methods (VEP and MRI) are unsuitable to assess the effect of an impaired optic nerve function on neuronal processing in the visual cortex. We report one patient suffering from Tolosa-Hunt syndrome affecting the optic nerve. We used fMRI (functional magnetic resonance imaging) to show how this impairment of the optic nerve alters cortical processing of visual information. The activity of the unaffected visual cortex was bilaterally reduced when compared to healthy volunteers but greater that obtained from patients suffering from bilateral occipital infarction. Our results offer new opportunities to assess the efficiency of therapy in patients with increasing loss of visual perception due to the Tolosa-Hunt syndrome. Further studies are necessary to investigate, whether fMRI also provides the possibility to assess the efficiency of drug therapy on optic nerve function.

Amphetamine enhances training-induced motor cortex plasticity.

OBJECTIVES: Repetitive synchronized movements lead to short-term plastic changes in the primary motor cortex, which can be assessed by transcranial magnetic stimulation (TMS). Drugs which enhance such plastic changes could be of therapeutical interest, e.g. in patients with cerebral lesions. MATERIAL AND METHODS: We studied the effect of amphetamine on motor performance and plastic changes in the motor cortex as revealed by TMS mapping in healthy humans, who had to train a repetitive synchronized movement over 1 h. RESULTS: Cortical plastic changes observed after 1 h of training were more pronounced with amphetamine, whereas motor performance did not differ between training sessions with and without amphetamine. CONCLUSION: We conclude that amphetamine is able to enhance training-induced motor cortex plasticity. This effect could be due to its known influence on the GABAergic and glutamatergic system, but might also result from its role as an indirect catecholaminergic agonist.

[Sleepiness and fatigue in multiple sclerosis - comparison of different measuring instruments]. / Differenzierung von Müdigkeit und Fatigue bei Multipler Sklerose - Vergleich unterschiedlicher Messinstrumente.

INTRODUCTION: Patients suffering from multiple sclerosis often complain of fatigue and sleepiness. Patients often cannot distinguish between these symptoms. Daytime sleepiness, attention and concentration deficits affect life quality severely. Usually symptoms of MS are characterized by the Expanded Disability Status Scale (EDSS). In new studies the MSFC proves to be a more sensitive method especially estimating the cognitive deficits. METHODS: 31 RRMS patients (18 women, 13 men, mean age 35.6 +/- 8.3 years) and 19 healthy controls (9 men, 1 woman, age: 55.1 +/- 7.8 years) were assessed by: 1) morning and evening protocols of the German Sleep Society, 2) Epworth Sleepiness Scale (ESS), 3) Extended Disability Status Scale (EDSS), 4) MS Functional Composite (MSFC) based on arm function, ambulation and cognition (paced auditory serial addition test, PASAT), 5) Fatigue Severity Scale (FSS). RESULTS: The EDSS-Score ranged from 1.0 to 6.5 (2.8 +/- 1.4). Mean Z-Score of MSFC was -0.19 +/- 0.63. Most deficits could be shown in the PASAT. Total sleep time correlated with recovery capacity of sleep (r = 0.42, P < 0.05). The ESS-Score was 6.1 +/- 2.9 (1 - 14). FSS-Score was raised with intraindividual variability (4,33 +/- 1.62, 1.4 - 7). The EDSS failed to correlate with the ESS- or FSS-Score. FSS correlated significantly with arm function (r = 0.465) und ambulation (r = 0.436) in the MSFC (P < 0.05). DISCUSSION: MS-Patients are often not able to distinguish between fatigue and sleepiness. By using different scales judging sleepiness and fatigue significant differences could be evaluated. Fatigue is mainly linked to motoric deficits scored by the MSFC. Therefore medication with stimulants seems not to be useful in fatigue therapy.

NMDA-mediated mechanisms in cortical excitability changes after limb amputation.

OBJECTIVES: The aim of our study was to determine the role of N-methyl-d-aspartate (NMDA)-mediated mechanisms in cortical excitability changes after limb amputation, and their possible relationship to phantom pain. MATERIALS AND METHODS: Sixteen upper limb amputees who were suffering from chronic phantom pain received the NMDA-antagonist memantine or placebo for 3 weeks. Intracortical inhibition (ICI) and intracortical facilitation (ICF) were determined at baseline and on day 21 using transcranial magnetic stimulation. Simultaneously, phantom pain intensity was assessed. RESULTS: Memantine reduced ICF and enhanced ICI to roughly the same extent as seen in healthy subjects in a previous study. These changes were not correlated to the reduction of phantom pain. CONCLUSION: We therefore conclude that NMDA-mediated mechanisms influence changes of ICI and ICF occurring after limb amputation. However, our results suggest that these cortical excitability changes and phantom pain are independent of each other.

Adult polyglucosan body disease: a postmortem correlation study.

Autopsy of a 50-year-old woman with adult polyglucosan body disease and missense mutations (Arg515His, Arg524Gln) in the glycogen branching enzyme gene (GBE) revealed accumulation of polyglucosan bodies in the heart, brain, and nerve. GBE activity was decreased in the morphologically affected tissues but was normal in unaffected tissues. GBE mRNA transcripts were similar in all tissues and in controls, which confirms the lack of tissue-specific GBE isoforms.

[Accidents caused by sleepiness--prediction by neurophysiologic/psychologic testing and simulated driving studies]. / Unfälle durch Müdigkeit--Prädiktionsmöglichkeit durch neurophysio-/psychologische Testung und Fahrsimulatoruntersuchungen.

Daytime sleepiness is a leading symptom of various diseases, and is an important cause of accidents at the workplace and on the road. For the evaluation of accident frequency, the medical history, neurophysiological and neuropsychological tests, and driving simulator performance are applied. The present paper describes these different methods, and assesses their value in predicting accidents. In the last resort, no single test suffices to evaluate the accident risk of patients suffering from daytime sleepiness--rather, a combination of the methods described is needed, in particular when an expert opinion on a patient's ability to drive is required. To date, no controlled studies have been done to compare the predictive value of the methods considered herein. Our results suggest that the nearness of driving simulation to reality makes it a suitable additional test method, in particular for the monitoring of results under treatment.

Herpes zoster guideline of the German Dermatology Society (DDG).

Varicella zoster virus (VZV) causes varicella (chickenpox), remains dormant in dorsal root and cranial nerve ganglia and can be reactivated as a consequence of declining VZV-specific cellular immunity leading to herpes zoster (shingles). Patients older than 50 years of age affected by herpes zoster may suffer a significant decrease of quality of life. These patients and immunocompromised individuals are at increased risks for severe complications, involving the eye, the peripheral and the central nervous system (prolonged pain, postherpetic neuralgia). Such complications occur with and without cutaneous symptoms. The German Dermatology Society (DDG) has released guidelines in order to guarantee updated management to anyone affected by herpes zoster. Diagnosis is primarily clinical. The gold standard of laboratory diagnosis comprises PCR and direct identification of VZV in cell cultures. Detection of IgM- and IgA-anti VZV antibodies may be helpful in immunocompromised patients. Therapy has become very effective in the last years. Systemic antiviral therapy is able to shorten the healing process of acute herpes zoster, to prevent or to alleviate pain and other acute and chronic complications, particularly, when given within 48 h to a maximum of 72 h after onset of the rash. Systemic antiviral therapy is urgently indicated in patients beyond the age of 50 years and in patients at any age with herpes zoster in the head and neck area, especially in patients with zoster ophthalmicus. Further urgent indications are severe herpes zoster on the trunk and on the extremities, herpes zoster in immunosuppressed patients and in patients with severe atopic dermatitis and severe ekzema. Only relative indications for antiviral therapy exist in patients younger than 50 years with zoster on the trunk and on the extremities. In Germany acyclovir, valacyclovir, famciclovir and brivudin are approved for the systemic antiviral treatment of herpes zoster. These compounds are all well tolerated by the patients and do not differ with regard to efficacy and safety. Brivudin has a markedly higher anti-VZV potency than oral acyclovir, valacyclovir and famciclovir and thus offers a simpler dosing regimen. It must be given only once daily during 7 days in comparison to three and five times dosing per day of valacyclovir, famciclovir and acyclovir, respectively. Brivudin is an antiviral agent with no nephrotoxic properties, which is an advantage when compared to acyclovir. The most important aim of therapy of herpes zoster is to achieve painlessness. Appropriately dosed analgesics in combination with a neuroactive agent (i.e. amitriptylin) are very helpful when given together with antiviral therapy. The additive therapy with corticosteroids may shorten the degree and duration of acute zoster pain, but has no essential effect on the development of postherpetic neuralgia, which is a very difficult condition to treat. Thus early presentation to a pain therapist is recommended in specific cases.

[Fatal cardiomyopathy in adult in polyglucosan body disease]. / Letale Kardiomyopathie bei adulter Polyglukosankörperkrankheit.

Adult polyglucosan body disease (APBD) is a rare genetic disorder, inherited in an autosomal recessive mode. The disease is caused by mutations of the gene coding for the glycogen-branching enzyme, which is essential for branching of polyglucose chains in the normal glycogen molecule. The age of clinical manifestation of the disease mostly is between 40 and 60 years and its course is slowly progressive. Characteristic globular deposits (polyglucosan bodies, PGB) can be detected in biopsies of skin and skeletal muscle as well as in the peripheral and central nervous system. Biochemically, PGBs consist of poorly branched glycogen molecules with abnormally long polysaccharide chains. We report the case of a 50-year-old female patient with APBD who suffered from neurological symptoms such as spastic tetraparesis, urinary incontinence, hypesthesia and dementia. She died unexpectedly of cardiac failure. At autopsy a severe cardiomyopathy with abundant PGBs in the heart muscle fibres could be proven as the cause of death. This observation shows that in addition to the known deposition of PGBs in nervous system and skeletal muscle, an involvement of the heart has to be considered in APBD as well.

Changes of the MS functional composite and EDSS during and after treatment of relapses with methylprednisolone in patients with multiple sclerosis.

OBJECTIVES: The Multiple Sclerosis Functional Composite (MSFC) comprises quantitative functional measures of leg, hand/arm and cognitive function. We examined the responsiveness of the MSFC compared with the Expanded Disability Status Scale (EDSS) during treatment of relapses in patients with multiple sclerosis (MS). PATIENTS AND METHODS: 27 patients received 1000 mg intravenous methylprednisolone (i.v.-MP) for 5 days, followed by oral methylprednisolone for 14 days. The MSFC and the EDSS-score were assessed on day 0, before the first corticosteroid treatment, on day 5, after the last course of i.v. MP, and on day 20 after the treatment was finished. Before the first administration of the MSFC, patients were trained for the paced auditory addition test (PASAT) performing three test trials. In order to analyse practice effects, 10 MS patients without an acute exacerbation were tested three times under the same conditions as the treated group. RESULTS: The median EDSS-score was 2.5 in both groups. On day 5 it remained unchanged in all treated patients, on day 20 a decrease of 0.5 EDSS point occurred in five patients, and in two patients an improvement with a decrease of more than 0.5 point was observed. There was no statistically significant difference between the EDSS-scores on day 0, 5 and 20. The mean MSFC-score in the treated group was -0.14 +/- 0.63 on day 0, 0.17 +/- 0.66 on day 5, and 0.42 +/- 0.59 on day 20. On the last study day, 26 patients improved compared with day 0. The differences between the MSFC-scores at the three points of time were statistically significant for the treated group (P < 0.001), but not for the control group. CONCLUSION: During and after treatment of relapses in patients with MS, the MSFC appears to be more sensitive in detecting changes in function than the EDSS.

[Estimation of accident risk in obstructive sleep apnea syndrome (OSAS) by driving simulation]. / Abschätzung des Unfallrisikos bei obstruktivem Schlafapnoe-Syndrom (OSAS) durch Fahrsimulation.

Abstract. Patients with obstructive sleep apnea syndrome (OSAS) have an accident rate between two and seven times higher than normals. Investigations on accident frequency are based on case history, insurancy reports, and driving simulator investigations. The present controlled study was planned to test whether an increased accident risk could be demonstrated in patients with OSAS before and on CPAP (continuous positive airway pressure)-therapy using the driving simulator C.A.R. Driving simulator performance was investigated in 31 patients with polysomnographically confirmed OSAS (apnea-hypopnea-index 24.8 +/- 21.5/h) before, 2 and 42 days after initiation of CPAP and was compared to 10 healthy controls in whom OSAS was excluded by polysomnography. Driving simulator performance was significantly worse in OSAS as compared to normals especially in terms of accident frequency (OSAS: 2.7 +/- 2.0, controls: 1.3 +/- 1.5, p < 0.05) and concentration faults (OSAS: 12.4 +/- 5.1, controls: 7.1 +/- 3.2, p < 0.01). On CPAP accident frequency (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 1.5 +/- 1.4, p < 0.01; 42 days CPAP: 0.9 +/- 1.3, p < 0.001) and frequency of concentration faults (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 6.5 +/- 3.9, p < 0.001; 42 days CPAP: 4.9 +/- 3.3, p < 0.001) could be lowered significantly both in the short and medium term of therapy. The driving simulator C.A.R. is an adequate tool for the evaluation of an increased accident risk in OSAS-patients and demonstrates the efficiency of CPAP-therapy.

Repetitive training of a synchronised movement induces short-term plastic changes in the human primary somatosensory cortex.

The aim of our study was to assess possible short-term plastic changes in the human primary somatosensory cortex (S1) induced by a repetitive synchronised movement of the right thumb and shoulder. We therefore performed a source localisation of somatosensory evoked potentials after median nerve stimulation in twelve healthy subjects before and after 1 h of motor training. We found a significant medial shift of the N20 dipole on the left hemisphere after training, whereas the dipole location on the right hemisphere remained unchanged. However, no significant correlation was seen between the dipole shift and the improvement in motor performance. We conclude that repetitive synchronised movements are able to induce plastic changes in the contralateral S1, which might be mainly due to the synchronised proprioceptive input.

Shifts in cortical representations predict human discrimination improvement.

We report experiments combining assessment of spatial tactile discrimination behavior and measurements of somatosensory-evoked potentials in human subjects before and after short-term plastic changes to demonstrate a causal link between the degree of altered performance and reorganization. Plastic changes were induced by a Hebbian coactivation protocol of simultaneous pairing of tactile stimuli. As a result of coactivation, spatial discrimination thresholds were lowered; however, the amount of discrimination improvement was variable across subjects. Analysis of somatosensory-evoked potentials revealed a significant, but also variable shift in the localization of the N20-dipole of the index finger that was coactivated. The Euclidean distance between the dipole pre- and post-coactivation was significantly larger on the coactivated side (mean 9.13 +/- 3.4 mm) than on the control side (mean 4.90 +/- 2.7 mm, P = 0.008). Changes of polar angles indicated a lateral and inferior shift on the postcentral gyrus of the left hemisphere representing the coactivated index finger. To explore how far the variability of improvement was reflected in the degree of reorganization, we correlated the perceptual changes with the N20-dipole shifts. We found that the changes in discrimination abilities could be predicted from the changes in dipole localization. Little gain in spatial discrimination was associated with small changes in dipole shifts. In contrast, subjects who showed a large cortical reorganization also had lowest thresholds. All changes were highly selective as no transfer to the index finger of the opposite, non-coactivated hand was found. Our results indicate that human spatial discrimination performance is subject to improvement on a short time scale by a Hebbian stimulation protocol without invoking training, attention, or reinforcement. Plastic processes related to the improvement were localized in primary somatosensory cortex and were scaled with the degree of the individual perceptual improvement.

Differential release of beta-chemokines in serum and CSF of patients with relapsing-remitting multiple sclerosis.

OBJECTIVE: beta-chemokines were recently demonstrated in active MS-lesions. We tested whether MCP-1 and RANTES can also be detected in CSF and serum of patients with MS and whether release is associated with inflammatory disease activity. MATERIALS AND METHODS: CSF and serum from 34 patients with newly diagnosed relapsing-remitting MS (RR-MS), 17 patients with viral meningitis (VM) and 19 patients with non-inflammatory neurological diseases (NIND) were investigated by ELISA. RR-MS patients underwent lumbar puncture and Gd-enhanced MRI examinations within 2 days. RESULTS: MCP-1 was strong intrathecally released in all patients. Compared to NIND CSF-levels were increased in VM (P<0.001) and were decreased in RR-MS (P<0.05). RANTES was only detected in serum in all patients. Levels were higher in VM and RR-MS compared to NIND (P<0.05). A total of 14/34 RR-MS patients exhibited active Gd-enhancing lesions on MRI. They had lower MCP-1 levels in CSF (P<0.001) and serum (P<0.05) and higher serum levels of RANTES (P<0.05) as compared to patients without active lesions. CONCLUSIONS: MCP-1 and RANTES are differentially released during acute attacks of RR-MS, which might reflect different immunregulatory roles of these beta-chemokines in RR-MS.

Respiratory monitoring in neuromuscular disease - capnography as an additional tool?

Daytime complaints like fatigue, sleepiness and cognitive dysfunction in neuromuscular disease can be due to nocturnal hypercapnia and hypoxemia. Daytime respiratory diagnostics does not reflect sleep disordered breathing. Nocturnal pulse oxymetry and capnography were performed in 11 patients (15-75 years old) with different slowly progressive neuromuscular diseases. Only four patients complained of dyspnea. Pulmonary function was abnormal in three patients. Blood gas samples showed a hypoxemia in three patients. Pulse oxymetry results were pathological in six patients. Nine patients presented abnormal capnographies. According to these results either nocturnal oxygen application was initiated or ventilatory parameters were modified. Daytime symptoms and muscular strength improved markedly. Capnography and pulse oxymetry should be performed during the course of neuromuscular disease to detect respiratory insufficiency. Capnography seems to be a more sensitive indicator for respiratory impairment especially when artificial ventilation has been initiated.

Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease.

Hereditary rippling muscle disease (RMD) is an autosomal dominant human disorder characterized by mechanically triggered contractions of skeletal muscle. Genome-wide linkage analysis has identified an RMD locus on chromosome 3p25. We found missense mutations in positional candidate CAV3 (encoding caveolin 3; ref. 5) in all five families analyzed. Mutations in CAV3 have also been described in limb-girdle muscular dystrophy type 1C (LGMD1C; refs. 6,7), demonstrating the allelism of dystrophic and non-dystrophic muscle diseases.

Immunomodulatory effects of interferon-beta-1b in patients with multiple sclerosis.

The mechanisms by which IFN beta-1b acts in the treatment of patients with multiple sclerosis (MS) are not completely known. Immunomodulatory effects of IFN beta-1b were investigated in patients with relapsing-remitting (RR) MS in vivo and in vitro. Compared to baseline and controls, defined as patients with RR-MS without immunomodulatory therapy, the expression of TGF beta-1-mRNA by peripheral blood mononuclear cells (PBMC) was persistently increased at week 6, month 3 and month 6 (p < or = 0.05), that of the TGF beta-1 receptor type II from day 5 up to month 6 (p < 0.01). The expression of TNF alpha-mRNA decreased from day 1 to month 3 compared to day 0 and the controls (p < 0.01). The in vitro investigations performed on isolated peripheral blood lymphocytes demonstrated that these effects were dose-dependent. The mRNA and protein expression of TNF alpha-R-I (55 kD-receptor) was only temporarily elevated at the beginning of the therapy in vivo. The expression of TNF alpha-R-I-mRNA increased dose-dependently after stimulation with IFN beta-1b for 24 h in vitro. Serum levels of soluble vascular cell adhesion molecule (sVCAM) were increased during the whole time of in vivo treatment (p < 0.01). The CD8CD38 lymphocyte subpopulation was continuously elevated from day 5 up to month 6 (p < 0.01) in the MS patients treated with IFN beta-1b in vivo. No persistent, significant changes were demonstrable concerning the percentage of total CD4, CD8, CD19 nor in CD4 subpopulations (CD4CD29, CD4CD45RA). The present data suggest that IFN beta-1b induces the mRNA expression of TGF beta-1 and TGF beta-R-II by PBMC, decreases that of TNF alpha and increases levels of sVCAM-1 and of circulating activated CD8 cells (CD8CD38) in blood. These might be other mechanisms by which IFN beta-1b mediates its positive effects in the treatment of MS patients.