[Moebius syndrome and narcolepsy]. / Möbius-Syndrom und Narkolepsie.

BACKGROUND: Moebius syndrome is a rare neurological disease that has a frequent association with parasomnia. CASE REPORT: We report on a patient with Moebius syndrome and the clinical presentation of a narcolepsy cataplexy syndrome. With the hypoplasia of the brainstem in the cranial magnetic resonance imaging, we were able to show the morphological correlate of Moebius syndrome. Comorbidity was detected by cognitive tests, polysomnography and detection of hypocretin in the cerebrospinal fluid. Despite normal sleep onset latency and only one episode of sleep onset rapid eye movement (REM) in the multiple sleep latency test, where expressiveness is significantly reduced in cases of paralysis of horizontal eye movement, the diagnosis of parasomnia with narcolepsy cataplexy symptoms could be made. DISCUSSION: The hypocretin level of 132 pg/ml measured in the cerebro spinal fluid is compatible with this diagnosis and shows the relevance of a detailed diagnostic of parasomnia in patients with Moebius syndrome.

S1 guidelines "lumbar puncture and cerebrospinal fluid analysis" (abridged and translated version).

INTRODUCTION: Cerebrospinal fluid (CSF) analysis is important for detecting inflammation of the nervous system and the meninges, bleeding in the area of the subarachnoid space that may not be visualized by imaging, and the spread of malignant diseases to the CSF space. In the diagnosis and differential diagnosis of neurodegenerative diseases, the importance of CSF analysis is increasing. Measuring the opening pressure of CSF in idiopathic intracranial hypertension and at spinal tap in normal pressure hydrocephalus constitute diagnostic examination procedures with therapeutic benefits.Recommendations (most important 3-5 recommendations on a glimpse): The indications and contraindications must be checked before lumbar puncture (LP) is performed, and sampling CSF requires the consent of the patient.Puncture with an atraumatic needle is associated with a lower incidence of postpuncture discomfort. The frequency of postpuncture syndrome correlates inversely with age and body mass index, and it is more common in women and patients with a history of headache. The sharp needle is preferably used in older or obese patients, also in punctures expected to be difficult.In order to avoid repeating LP, a sufficient quantity of CSF (at least 10 ml) should be collected. The CSF sample and the serum sample taken at the same time should be sent to a specialized laboratory immediately so that the emergency and basic CSF analysis program can be carried out within 2 h.The indication for LP in anticoagulant therapy should always be decided on an individual basis. The risk of interrupting anticoagulant therapy must be weighed against the increased bleeding risk of LP with anticoagulant therapy.As a quality assurance measure in CSF analysis, it is recommended that all cytological, clinical-chemical, and microbiological findings are combined in an integrated summary report and evaluated by an expert in CSF analysis. CONCLUSIONS: In view of the importance and developments in CSF analysis, the S1 guideline "Lumbar puncture and cerebrospinal fluid analysis" was recently prepared by the German Society for CSF analysis and clinical neurochemistry (DGLN) and published in German in accordance with the guidelines of the AWMF (https://www.awmf.org). /uploads/tx_szleitlinien/030-141l_S1_Lumbalpunktion_und_Liquordiagnostik_2019-08.pdf). The present article is an abridged translation of the above cited guideline. The guideline has been jointly edited by the DGLN and DGN.

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.

Corticosteroids induce expression of transforming-growth-factor-beta1 mRNA in peripheral blood mononuclear cells of patients with multiple sclerosis.

The mechanisms by which corticosteroids act in the treatment of an acute relapse in multiple sclerosis (MS) are not completely known. We investigated the mRNA and protein expression of transforming-growth-factor-beta1 (TGFbeta1), a cytokine with anti-inflammatory and immunosuppressive potentials, in peripheral blood mononuclear cells (PBMC) and serum of 10 patients with an acute relapse of MS before, during and after the treatment with 500 mg prednisolone daily over 5 days. The expression of TGFbeta1-mRNA increased at day 3-5 and declined at day 8-10. Serum levels of TGFbeta1 demonstrated a comparable course. The present data suggest that corticosteroids induce the expression of TGFbeta1 in vivo. This is might be an other mechanism by which corticosteroids mediate immunosuppression.

Immunomodulatory effects of interferon-beta-1b in vivo: induction of the expression of transforming growth factor-beta1 and its receptor type II.

The mechanisms by which interferon-beta-1b (IFNbeta-1b) acts in the treatment of patients with multiple sclerosis (MS) are not completely known. A total of 10 MS patients were treated with 8 million units of IFNbeta-1b every other day. Compared to baseline and control group the expression of TGFbeta-1-mRNA by PBMC was persistently increased at week 6, month 3 and month 6 (p < or = 0.04), that of the TGFbeta-1 receptor type II from day 5 up to month 6 (p < 0.01). The mRNA and protein expression of tumor necrosis factor-alpha (TNFalpha)-receptor (55 kDa) was only temporarily elevated at the beginning of the therapy. Serum levels of sVCAM were increased during the whole time of treatment (p < 0.01). The CD8CD38 lymphocyte subpopulation was continuously elevated from day 5 up to month 6 (p < 0.01). No persistently significant changes were demonstrable concerning the percentage of total CD4, CD8, CD19 or in CD4 subpopulations (CD4CD29, CD4CD45RA). The present data suggest that IFNbeta-1b induces the expression of TGFbeta-1- and TGFbeta-R-II-mRNA by PBMC and increases levels of sVCAM-1 and of circulating activated CD8 cells (CD8CD38) in serum. These might be other mechanisms by which IFNbeta-1b mediates its positive effects in the treatment of MS patients.

Cerebrospinal fluid cytology in granulocytic sarcoma with meningeal extension but without bone marrow involvement.

Granulocytic sarcoma (GS) is a localized tumour of immature granulocytes that is usually associated with myelogenous leukaemia. We report an unusual case of mastoid GS with meningeal extension but no bone marrow involvement on presentation. Histological examination of the surgical specimen and the characteristic cerebrospinal fluid (CSF) cytology showing cytoplasmic granulations and Auer bodies led to the diagnosis of GS. Positive cytochemical staining of the immature CSF cells for naphthol-ASD chloroacetate esterase and myeloperoxidase confirmed their myeloid origin. Immunophenotyping did not reveal common acute lymphoblastic leukaemia antigen, cytokeratin, T- or B-cell antigens. The patient underwent surgical resection of the localized tumour, followed by radiation therapy, intrathecal and systemic chemotherapy, as if he had acute myelogenous leukaemia (AML). He did not develop AML in the 21 months after the tumour resection. This case emphasizes the value of CSF cytological examination of tumour cells and the use of an immunocytochemical marker for differentiating GS from malignant lymphoma.

Potential role of transforming growth factor-beta 1 in terminating the immune response in patients with Guillain-Barré syndrome.

T-cell activation and proinflammatory cytokines seem to be important in promoting the disease activity in Guillain-Barré syndrome (GBS). Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional peptide with potent immunosuppressive activity, and can therefore be considered a putative disease-limiting cytokine. We determined levels of soluble TGF-beta 1 in the serum of 12 patients with GBS in serial investigations during the course of the disease, in 12 patients with other noninflammatory neurological diseases (OND), and in 12 healthy control subjects. Levels of biologically active and total TGF-beta 1 were significantly increased in patients with GBS compared with patients with OND and healthy controls. During the course of GBS, levels of TGF-beta 1 peaked in the plateau phase before onset of recovery. During the recovery phase levels of TGF-beta 1 decreased but still exceeded significantly the levels in patients with OND and healthy controls. The differences were more marked with biologically active than with total TGF-beta 1. The temporal relationship between increased serum levels of TGF-beta 1 and the end of the progressive phase indicates that TGF-beta 1 has a role in terminating the pathological immune response in GBS. These findings suggest that TGF-beta 1 may be important in recovery from GBS.

The soluble 60-kDa tumour necrosis factor receptor: no difference found between patients with relapsing-remitting multiple sclerosis and controls: increasing levels are associated with the recovery from Guillain-Barré syndrome.

We determined serum and cerebrospinal fluid (CSF) levels of the soluble 60-kDa tumour necrosis factor (TNF) receptor (sTNF-R p60) in 50 patients with relapsing-remitting multiple sclerosis (MS) and in 18 patients with Guillain-Barré syndrome (GBS). Neither in serum nor in CSF samples was there a statistically significant difference between mean receptor concentrations of patients with MS (serum: 1064, SD 262 pg/ml; CSF: 555, SD 130 pg/ml), with other noninflammatory neurological diseases (serum: 1008, SD 248 pg/ml; CSF: 530, SD 112 pg/ml) and with healthy control subjects (serum: 918, SD 180 pg/ml). In order to determine disease activity, magnetic resonance imaging (MRI) of the brain was performed in all MS patients. The mean sTNF-R p60 levels of patients who showed gadolinium DTPA enhancement on MRI were not different from those without enhancement (1034, SD 274 pg/ml vs 1099, SD 248 pg/ml in serum samples and 546, SD 109 pg/ml vs 565, SD 152 pg/ml in CSF samples). In GBS, the sTNF-R p60 levels of serum and CSF samples were significantly higher than in MS and all control groups except for the group with viral meningitis (VM) (GBS: 1544, SD 834 pg/ml in serum, 882, SD 147 pg/ml in CSF; VM: 1518, SD 375 pg/ml in serum, 1131, SD 611 pg/ml in CSF; P < 0.001 for serum samples and P < 0.005 for CSF samples). Serial serum sTNF-R p60 measurements in 13 patients with GBS showed an increase in receptor levels parallel with the recovery from the disease (1276, SD 374 pg/ml at the time of disease onset, 1554, SD 482 pg/ml 14-24 days later and 1787, SD 525 pg/ml after 28-32 days). From our results and the conflicting data of previous studies, we could not agree with the suggestion that the assessment of sTNF-R p60 in MS patients is a useful marker for disease activity. In GBS, subsequently increasing sTNF-R p60 levels are associated with recovery from the disease. It remains to be shown whether they might represent a relevant pathogenetic factor during this stage of GBS.

Detection of transforming growth factor beta 1 mRNA in cerebrospinal fluid cells of patients with meningitis by non-radioactive in situ hybridization.

Meningitis is a serious disease mostly caused by viral or bacterial infections. In complicated cases it may lead to brain damage and death. The infection and cell damage result in a cellular and immunological response. Following this, a high secretion of cytokines can be expected. Cytokines, especially tumour necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1), promote the inflammatory reactions in the subarachnoid space. Transforming growth factor beta 1 (TGF-beta 1) has antagonistic effects on TNF-alpha and IL-1-mediated processes. Therefore, it suppresses inflammatory reactions. To observe the expression of TGF-beta 1 in transcellular signalling in the inflammatory processes of meningitis, we investigated TGF-beta 1 mRNA in cells in the cerebrospinal fluid of three patients with meningitis by non-radioactive in situ hybridization. All patients fulfilled the usual clinical criteria of meningitis. In one case Neisseria menigitidis could be identified as the pathogenic agent. In the remainder, no agent could be isolated. In all cytological preparations of the cerebrospinal fluid of these patients a high level of TGF-beta 1 mRNA was detectable in the cell populations. It was possible to distinguish between the different cell types of the cerebrospinal fluid and to attach the mRNA expression to them. On the one hand, this makes it possible to investigate pathogenesis and defence mechanisms in bacterial and aseptic meningitis on a cellular level; on the other hand, it may open new perspectives in the control of disease development, prognosis, diagnosis and supporting therapy.

Inflammatory polyradiculoneuropathy with spinal cord involvement and lethal [correction of letal] outcome after hepatitis B vaccination.

We report on a 36-year-old man who developed an inflammatory polyradiculoneuropathy similar to Guillain-Barré syndrome 9 days after hepatitis B vaccination. Extensive immunotherapy including immunoglobulins, steroids, plasmapheresis, cyclophosphamide and methotrexate did not stop the progressive course of the disease and the patient died 4 months later due to multiorgan failure with septic shock symptoms and adult respiratory distress syndrome (ARDS).The neuropathological investigation showed severe axonal loss with mild demyelination of peripheral nerves and mononuclear cell infiltrates, predominantly T-lymphocytes, in nerve roots and spinal ganglia. In addition, there were unusual, perivascular and parenchymal lymphocytic cell infiltrates in the grey matter, especially the anterior horns of the spinal cord. The temporal relationship to hepatitis B vaccination, the strong increase of HBs-antibodies within 3 weeks after vaccination, and the presumptive immune mediated pathology of this disorder suggest a possible etiologic link with hepatitis B vaccine.

Expression of tumor necrosis factor-alpha and transforming growth factor-beta 1 in cerebrospinal fluid cells in meningitis.

Meningitis is an acute inflammatory disease of the pia and arachnoid and the fluid in the subarachnoid space, in which a participation of cytokines can be expected. While tumor necrosis factor-alpha (TNF alpha) promotes inflammatory reactions, transforming growth factor-beta 1 (TGF beta 1) has antagonistic effects and suppresses the inflammation in the subarachnoid space. We investigated the protein concentration and mRNA expression of TNF alpha and TGF beta 1 in cerebrospinal fluid (CSF) by ELISA and intracellularly by non-radioactive in situ hybridization in 23 patients with bacterial or viral meningitis. A higher amount of both cytokines on protein and mRNA level, especially of TNF alpha, could be detected in bacterial infection. While an imbalance of both cytokines with a preponderance of TNF alpha- compared to TGF beta 1-mRNA was visible in CSF cells of patients with bacterial meningitis, a balance of TNF alpha- and TGF beta 1-mRNA or a higher expression of TGF beta 1-mRNA could be detected in viral meningitis. In the acute phase of the disease neutrophil granulocytes expressed more TNF alpha- and TGF beta 1-mRNA than lymphocytes and monocytes/macrophages, while these cell types were dominating the cytokine synthesis during the healing phase. These data indicate that immunomodulatory mechanisms take place in the CSF compartment itself, regulated by CSF cells in different but specific ways. In addition, TGF beta 1 seems to be involved in the down-regulation of the inflammatory activity and to be one factor in the cytokine network, which could contribute to a lower rate of complications and positive outcomes. Moreover this study favors the possibility to monitor the immunomodulatory mechanisms by non-radioactive in situ hybridization.

A longitudinal study of circulating lymphocyte subsets in the peripheral blood during the acute stage of Guillain-Barré syndrome.

Activated T cells are implicated in the pathogenesis of Guillain-Barré syndrome (GBS). Blood samples from 16 patients with GBS were studied with flow cytometry during the acute stage of their disease to define circulating lymphocyte populations. During the progressive phase of GBS the T-suppressor/inducer (CD4/CD45RA) subset was decreased (10.3 +/- 4.4%, P < 0.05) and the T-helper/ inducer (CD4/CD29) subset was increased (34.9 +/- 9.2%, P < 0.05) compared to sex and age matched patients with other neurological diseases (OND, 15.5 +/- 5.7% and 27.8 +/- 8.6%, respectively) and healthy controls (16.5 +/- 6% and 28.1 +/- 8.5%, resp.). Within the CD8 population, the activated T-cytotoxic/suppressor (CD8/CD38) subset was increased during the progressive (13 +/- 10.1%, P < 0.05) and plateau phase (16.4 +/- 16.9%, P < 0.01) of GBS compared to OND patients (6.2 +/- 2.3%) and healthy controls (5.8 +/- 2.5%). The proportion of activated T cells (CD3/CD25) was increased during the progressive (9.3 +/- 3.8%, P < 0.05) and plateau phase (11.5 +/- 5.5%, P < 0.01) compared to OND patients (6.6 +/- 2.7%) and healthy controls (5.5 +/- 2.5%). The changes of T cell subsets normalized during the early recovery phase of GBS. 2 patients with serological evidence of antecedent cytomegalovirus (CMV) infection had abnormal high proportions (mean +/- 2 (SD) of healthy controls) of CD8 lymphocytes and correspondingly abnormal low proportions of CD4 lymphocytes during all phases of GBS. In contrast, the CD8 proportions were abnormal low in 3 patients with serological evidence of recent Campylobacter jejuni infection. There was no correlation between the proportions of lymphocyte subsets and the disability score during the maximum of the disease and after half a year. In conclusion, we found further evidence of T cell activation during the acute stage of GBS by the demonstration of an increased proportion of activated CD8+ T cells, which may be directly cytotoxic to Schwann cells. The abnormalities of the CD8 subset in some GBS patients seem to depend on the nature of the preceding infection.

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.

Phenotypic analysis of cerebrospinal fluid cells over the course of Lyme meningoradiculitis.

Cytologic cerebrospinal fluid abnormalities that most distinctly point to the diagnosis of Lyme meningoradiculitis are pronounced mononuclear pleocytosis composed mainly of T lymphocytes, large amounts of plasma cells and IgM-positive B cells. In this study, repeat examinations revealed decreasing cell numbers and almost normal cell counts 100-130 days after the onset. B cells persisted over the whole observation period in five of six patients and were not related to any clinical symptoms or signs indicative of persistent meningitis or central nervous system involvement. The CD4/CD8 ratio of the helper/inducer and suppressor/cytotoxic lymphocyte subsets declined in all the patients after antibiotic treatment. It might be useful as a marker of the disease activity.

[Thymectomy in myasthenia gravis--an analysis of current status]. / Thymektomie bei Myasthenia gravis--eine Standortanalyse.

Between May 1992 and June 1997, 11 patients with myasthenia gravis and 1 asymptomatic patient with thymoma underwent extensive thymectomy through a median sternotomy. Seven patients were male and 5 female. The mean age at onset of myasthenia gravis was 46.5 (13-73) years. The interval between the first symptom and diagnosis was 3.6 months (1 week-7 months), between the first symptom and thymectomy 8.3 months (2 weeks-36 months) and the mean follow-up period was 28.4 months (3-57 months). Clinical improvement after extensive thymectomy was noted in 80% of patients. Four patients became asymptomatic under decreased medication. Thymectomy was found to be beneficial even in older patients or patients with the purely ocular type of myasthenia gravis. There was no perioperative mortality or long-term morbidity.

[Spondylodiscitis with spinal and radicular involvement. Limits of conservative treatment]. / Spondylodiszitis mit spinaler und radikulärer Beteiligung. Grenzen der konservativen Behandlung.

During 1988 to 1992 18 patients with spondylodiscitis and neurological deficits were treated in our clinic. Tuberculous spondylodiscitis was diagnosed in 4 patients and 14 suffered from non specific spondylodiscitis. The mean age was 59 years (range 25-77). 16 (89%) of the patients had risk factors like diabetes mellitus, genitourinary tract infection, respiratory tract infection, rheumatism, intervertebral disc operation and old spine fracture. MR-tomography revealed the most valuable diagnostic method. 14 patients with progressive spinal cord compression, and root lesions because of gross vertebral damage and epidural abscess underwent operative removal of the focus with intercorporal spondylodesis. Postoperative neurological examination revealed improvement in 7 and no changes in the other 7 patients. In 4 patients with non specific spondylodicitis and radicular deficits conservative treatment was performed and spontaneous interbody fusion without persisting neurological complaints occurred.

Serum antibodies to GM1 and GM3-gangliosides in systemic lupus erythematosus with chronic inflammatory demyelinating polyradiculoneuropathy.

Acute symmetric demyelinating polyneuropathy of the Guillain-Barré type is known in systemic lupus erythematosus (SLE). Chronic idiopathic demyelinating polyneuropathy (CIDP) has been reported rarely with SLE. A case is reported of CIDP accompanying SLE with autoantibodies against GM1- and GM3-gangliosides. There was no historical evidence to suggest SLE, and CIDP was the first manifestation of SLE. The 38-year-old patient had elevated CSF-protein, slow nerve conduction velocities, sural nerve biopsy revealed mixed axon loss with demyelination and CIDP white matter lesions were observed in magnetic resonance imaging, the GM1- and GM3-autoantibodies may play a role in the pathogenesis of CIDP in SLE.

Early onset MS under the age of 16: clinical and paraclinical features.

MS in juvenile patients under the age of 16 occurred in 31 (5%) of our whole MS population of 620 patients in the time from 1975-1991. It does not differ clinically from the disease as observed in 72 patients with later onset MS in respect to symptoms at onset, course, progression rate, rate of relapses and abnormalities in CSF and MRI. However, fever, headache, nausea and vomiting with pleocytosis in CSF during the first episode and development of oligoclonal bands with passage of time may be characteristic in some juvenile patients. The presence of oligoclonal bands and MRI results are of high diagnostic value in this special group of patients.

[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.