Mechanisms of pain in multiple sclerosis: a combined clinical and neurophysiological study.

In this clinical and neurophysiological study, we examined the clinical characteristics and underlying mechanisms of neuropathic pain related to multiple sclerosis. A total of 302 consecutive patients with multiple sclerosis were screened for neuropathic pain by clinical examination and the DN4 tool. In patients selected for having ongoing extremity pain or Lhermitte's phenomenon, we recorded somatosensory evoked potentials, mediated by Aß non-nociceptive fibres, and laser evoked potentials, mediated by Aδ nociceptive fibres. Of the 302 patients, 92 had pain (30%), and 42 (14%) neuropathic pain. Patients with neuropathic pain had more severe multiple sclerosis, as assessed by the expanded disability severity score, than those without pain. Whereas, in patients with ongoing neuropathic pain, laser evoked potentials were more frequently abnormal than somatosensory evoked potentials, we found the opposite in patients with Lhermitte's phenomenon. Our data underline the clinical importance of pain in multiple sclerosis and indicate that a more severe disease is associated with a higher risk of developing neuropathic pain. The prevalence of pain that we found, which was lower than that reported in previous studies, may reflect the lesser disease severity in our patients. Neurophysiological data show that whereas ongoing extremity pain is associated with spinothalamic pathway damage, Lhermitte's phenomenon is related to damage of non-nociceptive pathways. These findings may be useful in designing a new therapeutic approach to neuropathic pain related to multiple sclerosis.

Duloxetine for the treatment of overactive bladder syndrome in multiple sclerosis: a pilot study.

OBJECTIVES: Overactive bladder (OAB) syndrome represents one of the main urinary disorders associated with multiple sclerosis (MS). At present, no widely accepted effective treatment is available. Duloxetine, an antidepressant acting as a selective serotonin-norepinephrine reuptake inhibitor, has been shown to be effective in the treatment of some symptoms of stress urinary incontinence and OAB because of etiology other than MS.The present study aims at establishing the efficacy and tolerability of duloxetine in the treatment of OAB in patients affected by remitting-relapsing MS and secondary progressive MS. MATERIALS AND METHODS: Twenty-three patients with MS, 13 of which with remitting-relapsing MS and 10 with secondary progressive MS, have been treated with duloxetine and placebo for a total period of 8 weeks during a single-blinded cross-over trial. At each programmed visit, patients have been screened for the following: (1) quantitative evaluation of maximal bladder capacity and postmicturition residual volume; (2) questionnaire administration to evaluate bladder disorder--Overactive Bladder Questionnaire, quality of life--Visual Analogue Scale-Quality of life, fatigue--Fatigue Severity Scale, and depression--Beck Depression Inventory. RESULTS: Three patients did not complete the study because of duloxetine-related adverse events. A statistically significant improvement in bladder disorder, as measured by OAB-Q, has been observed after duloxetine treatment compared with both basal levels and placebo with values of 21.8 ± 1.1 versus 34.2 ± 1.2 (P < 0.0001) and 21.8 ± 1.1 versus 30.1 ± 1.7 (P < 0.003), respectively.In addition, a decrease in postmicturition residual volume has also been observed compared with basal level (6.8 ± 3.2 ml vs 38.1 ± 12.2 ml, P = 0.06) together with an improvement in quality of life (7.1 ± 0.5 vs 6.3 ± 0.4, P = 0.07). Both these changes were close to being statistically significant. CONCLUSIONS: It emerges from this study that duloxetine might become an effective therapeutic alternative to be investigated in a larger number of MS patients for the treatment of OAB. Duloxetine should be considered a first-choice drug in the treatment of MS patients presenting both depression and OAB; in addition, it should also be considered as a suitable alternative or as concomitant treatment in MS patients with OAB but not experiencing depression.

The prevalence of multiple sclerosis in central Italy.

BACKGROUND: The prevalence of multiple sclerosis varies considerably throughout the world. OBJECTIVE: To better define the prevalence of MS in central Italy. METHODS: This is a population-based study conducted in the province of Frosinone, which is situated in the Lazio region, central Italy. The selected prevalence day was 1 January 2007. A total of 467 patients, with a definite diagnosis of multiple sclerosis, were considered for crude, age- and sex-specific prevalence estimation. RESULTS: The overall crude prevalence rate was 95.0 cases per 100,000 (95% confidence interval (CI) 86.6-104.0). A significantly higher prevalence rate was recorded in females (134.9, 95% CI 121.0-150.1) than in males (53.3, 95% CI 44.4-63.3) (p = 0.001). Age-specific prevalence peaked in the 25-34 year, 35-44 year and 45-54 year age groups; moreover, it was found to increase up to the 35-44 year age group in males and the 45-54 year age group in females, decreasing thereafter. The female to male ratio was 2.6. CONCLUSIONS: The results confirm that MS occurs more frequently in central Italy than might be expected on the basis of the geographic-related distribution model, thus supporting the view that this is a high-risk area for the disease.

Detection of human herpesviruses and polyomaviruses DNA in a group of patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system whose pathological features consist of white matter plaques of primary demyelinization and loss of oligodendrocytes. Various risk factors have been associated with MS susceptibility. We have focused this study on different viruses. In particular in the present study we used PCR to search for the genomic DNA of HHV-1, HHV-2, HHV-8, BKV and JCV in urine and peripheral blood mononuclear cells (PBMC) samples from 44 relapsing-remitting MS (RRMS) patients. No viral DNA was found in any urine sample, whereas 29.5% of RRMS PBMC samples were positive. It is suggestive that Human herpesviruses (HHV-1 and HHV-8) were constantly present in all positive samples, indicating that viral agents could contribute to create the demyelination plaques and cause MS.

Prevalence and clinical features of hedonistic homeostatic dysregulation in Parkinson's disease.

Hedonistic homeostatic dysregulation (HHD) is a neuropsychiatric disorder recently described in Parkinson's disease (PD), which is characterized by self-medication and addiction to dopaminergic drugs. To understand the prevalence of this disorder, we screened 202 PD patients attending our movement disorder unit for HHD. The clinical features of the patients identified as affected by this syndrome were then compared with those of control PD patients in an attempt to ascertain the possible risk factors for HHD. Results showed 7 subjects who fulfilled the HHD criteria. The analysis of a case-control study showed a significant correlation between HHD and a previous history of mood disorders, and the use of dopamine agonists, either in monotherapy or in combination. The prevalence of HHD in our study is similar to the one reported in the United Kingdom by the authors who first described this syndrome in PD. Of interest, our patients showed a somewhat different pattern of the disorder, suggesting that cultural and environmental factors may play a role in the phenomenology of HHD.

Mirtazapine in L-dopa-induced dyskinesias.

Mirtazapine is a novel antidepressant with a pharmacologic profile (alpha-2 antagonist, 5HT-(1A) agonist, and 5HT-(2) antagonist) that renders it potentially useful for l-dopa-induced dyskinesias. Drugs with 5HT-(1A) agonistic activity, such as buspirone and tandospirone, have been reported to be effective in reducing l-dopa-induced dyskinesias. Furthermore, 5HT-(2) antagonism may, by reducing substantia nigra pars reticulata hyperactivity, play a role in the improvement of Parkinsonian symptoms and l-dopa-induced dyskinesias, as has been observed with ritanserin, a 5HT-(2) antagonist. Alpha-2 antagonists, such as idazoxan, have recently also been reported to improve l-dopa-induced dyskinesias. The authors investigated the antidyskinetic properties of mirtazapine by designing an open-label study of 20 Parkinsonian patients with l-dopa-induced dyskinesias. Mirtazapine proved to be moderately effective in reducing l-dopa-induced dyskinesias, either alone or in association with amantadine. Mirtazapine may be of use in patients who do not respond or are intolerant to amantadine.