Altered serotonin transporter availability in patients with multiple sclerosis.

PURPOSE: Modulation of the immune system by the CNS may involve serotonergic regulation via the brain serotonin transporters (SERT). This regulation may be disturbed in patients with CNS disorders including multiple sclerosis (MS). Central serotonergic mechanisms have not been investigated in MS by in vivo imaging. The objective of the study was to assess the availability of SERT in antidepressant-naive patients with MS by means of PET. METHODS: Included in this study were 23 patients with MS and 22 matched healthy volunteers who were investigated with PET and the SERT-selective marker [(11)C]DASB, and distribution volume ratios were determined. Clinical assessment of the patients included the expanded disability status scale, the MS fatigue scale Würzburger Erschöpfungsinventar bei MS (WEIMuS) and the Beck Depression Inventory (BDI). The PET data were analysed with both volume-of-interest and voxel-based analyses to determine regional SERT availability. RESULTS: Patients had lower SERT availability in the cingulate cortex, the thalamus and the insula, and increased availability in the orbitofrontal cortex. Patients with relapsing/remitting MS tended to have lower SERT in the hippocampus, whereas patients with primary progressive disease showed increased SERT availability in prefrontal regions. There was a positive correlation between SERT availability in the insula and both depression and fatigue scores (r = 0.56 vs. BDI, p = 0.02; r = 0.49 vs. WEIMuS, p = 0.05). CONCLUSION: Serotonergic neurotransmission in MS patients is altered in limbic and paralimbic regions as well as in the frontal cortex that this appears to contribute to psychiatric symptoms of MS.

Pain in patients with multiple sclerosis: a complex assessment including quantitative and qualitative measurements provides for a disease-related biopsychosocial pain model.

BACKGROUND: Pain of various causes is a common phenomenon in patients with Multiple Sclerosis (MS). A biopsychosocial perspective has proven a useful theoretical construct in other chronic pain conditions and was also started in MS. To support such an approach, we aimed to investigate pain in MS with special emphasis on separating quantitative and qualitative aspects, and its interrelation to behavioral and physical aspects. MATERIALS AND METHODS: Pain intensity (NRS) and quality (SES) were measured in 38 consecutive outpatients with MS (mean age, 42.0 ± 11.5 years, 82% women). Pain-related behavior (FSR), health care utilization, bodily complaints (GBB-24) and fatigue (WEIMuS) were assessed by questionnaires, and MS-related neurological impairment by a standardized neurological examination (EDSS). RESULTS: Mean pain intensity was 4.0 (range, 0-10) and mean EDSS 3.7 (range, 0-8) in the overall sample. Currently present pain was reported by 81.6% of all patients. Disease duration and EDSS did not differ between patients with and without pain and were not correlated to quality or intensity of pain. Patients with pain had significantly higher scores of musculoskeletal complaints, but equal scores of exhaustion, gastrointestinal and cardiovascular complaints. Pain intensity correlated only with physical aspects, whereas quality of pain was additionally associated with increased avoidance, resignation and cognitive fatigue. CONCLUSION: As in other conditions, pain in MS must be assessed in a multidimensional way. Further research should be devoted to adapt existing models to a MS-specific model of pain.

Improving test-retest variability of visual-evoked responses in multiple sclerosis: implications for trial design.

Remyelination is an important repair strategy in multiple sclerosis. Latencies of visual-evoked responses are a suitable surrogate for remyelination of the optic nerve. Their test-retest variability has been incompletely evaluated, especially in pathologically delayed potentials. Visual-evoked potential was recorded twice, 2.1 +/- 3.1 (mean +/- SD) days apart, in 39 patients with definite or evaluated for multiple sclerosis. Acute optic neuritis and current steroid treatment were exclusion criteria. Mean and difference of the two recordings were calculated for latencies and amplitude, both before and after verification of cursor positioning by a physician blinded for the sequence of recordings. Before verification, the difference between first and second visual-evoked potential was -2.07 +/- 9.07 milliseconds for N75 latency, -1.18 +/- 8.02 milliseconds for P100 latency, and -0.06 +/- 2.71 muV for N75/P100 amplitude (n = 77 eyes, mean +/- SD). Independent verification judged two eyes as unsuitable for analysis. The differences in the remaining 75 eyes were reduced to -1.22 +/- 6.86 milliseconds (N75), -0.7 +/- 3.85 milliseconds (P100) and -0.04 +/- 2.53 microV (amplitude). These effects do not differ between delayed and nondelayed eyes. Similar to magnetic resonance imaging, use of evoked potentials in multiple sclerosis remyelination trials will require independent verification, ideally by a central evaluating facility. Reproducibility should be verified individually at screening.

Anxiety, depression and impaired health-related quality of life are therapeutic challenges in patients with multiple sclerosis.

Anxiety, depression and impaired health-related quality of life (HRQoL) are commonly reported in patients with multiple sclerosis (MS) and are of great interest for therapeutic approaches. Based on regional differences a quantitative assessment of these factors in comparison to the general population, and the consideration of demographic cofactors, would be useful when designing specific interventions. We adopted such an approach in a German cohort of MS patients. Anxiety, depression (HADS) and HRQoL (SF-36) were measured in 49 consecutive outpatients with MS and compared to age- and gender-adjusted control groups (n=1330 for HADS; n=5087 for SF-36) extracted from German National Health Surveys. Patients with MS showed significantly increased levels of anxiety and depression as well as decreased HRQoL with the exception of mental health; the effect sizes ranged from 0.39 (depression) to 1.06 (physical functioning). As could be expected, MS patients with relapsing-remitting clinical course had better physical functioning than patients with secondary progressive MS. There were strong relations between anxiety and depression (r=0.54; P<0.01), and between neurological impairment (EDSS) and physical functioning (r=-0.80; P<0.001) as well as depression (r=0.48; P<0.05). This investigation of MS patients confirms the prevalence and impact of anxiety, depression and most of the HRQoL dimensions in MS patients and provides evidence for the usefulness of a quantitative comparison to a region-specific general population as a starting point for therapeutic approaches.