The etiology of multiple sclerosis (MS) may involve exposure to infectious, chemical or physical agents damaging the blood-brain barrier and an autoimmune reaction against myelin breakdown products. Here we report a pooled analysis of 174 MS cases and 815 population controls from two case-control studies with regard to such a potentially damaging exposure, namely X-ray examinations, radiological work and treatment with ionizing radiation. Exposure was assessed by questionnaires to the subjects. We obtained odds ratios of 4.4 (95% confidence interval, CI, 1.6-11.6) and 1.8 (95% CI 1.2-2.6) for radiological work and X-ray examinations, respectively, 5 cases, but no controls, in one of the studies had been treated with ionizing radiation. Our data and some other observations reported in the literature suggest a contributory role for ionizing radiation to the development of MS in some cases.

Aims: To use the human blink reflex (BR) to explore possible neuropathic pain mechanisms in patients with atypical odontalgia (AO). Methods: In 13 AO patients, the BR was elicited using a concentric electrode and recorded bilaterally with surface electromyographic (EMG) electrodes on both orbicularis oculi muscles. Electrical stimuli were applied to the skin above branches of the V1, V2, and V3 nerves and to the V branch contralateral to the painful branch. Sensory and pain thresholds were determined. The BR examination of the painful V branch was repeated during a capsaicin pain-provocation test. The data were analyzed with nonparametric statistics. Results: The BR responses (R2 and R3) evoked by stimulation of V3 were significantly smaller than the BR responses evoked by stimulation of V1 and V2 (P < .004). There were no differences in BR (R2 or R3) between the painful and nonpainful sides (P > .569), and the BR (R2 and R3) was not significantly modulated by experimental pain (P > .080). The sensory thresholds were significantly lower on the painful side compared to the nonpainful side (P = .014). The pain thresholds were not different between sides (P > .910). Conclusion: No major differences between the V nociceptive pathways on the right and left sides were found in a relatively small group of AO patients. Future studies that compare BRs in AO patients and healthy volunteers are needed to provide further knowledge on the pain mechanisms in AO.

The Paths of Pain celebrates 30 years of pain research and management by the world's leading basic scientists and clinicians in the field. Combining history and science, it provides an unrivalled, authoritative selection of chapters that examine the problems and achievements in the topic. It looks at the way pain has been understood, investigated, and treated from before the foundation of the IASP up to the present time.The achievements of this period include the development and refinement of the gate control theory of pain in physiology, as well as enormous strides in the identification of cellular and molecular mechanisms of pain, a better appreciation of the psychological aspects of pain, the evolution of more effective analgesics, coordinated comprehensive pain clinics, acute pain services, and the improved definition of painful illnesses. The reader has the opportunity to explore a book by many hands in which the description of the advances is often provided by those who achieved them.

This volume is the first comprehensive text devoted to fibromyalgia and other centrally mediated chronic pain syndromes. Leading experts examine the latest research findings on these syndromes and present evidence-based reviews of current controversies. Chapters discuss the definition, epidemiology, and pathophysiology of chronic pain and fibromyalgia, the clinical presentations of fibromyalgia syndrome, and central sensitization syndromes associated with chronic neuromuscular pain. The contributors thoroughly examine various approaches to evaluation and management of patients with fibromyalgia and chronic pain. Other chapters focus on disability issues, prognosis, and future research directions. A critically reviewed listing of Websites and other resources is included.

This volume is the first comprehensive text devoted to fibromyalgia and other centrally mediated chronic pain syndromes. Leading experts examine the latest research findings on these syndromes and present evidence-based reviews of current controversies.

Chapters discuss the definition, epidemiology, and pathophysiology of chronic pain and fibromyalgia, the clinical presentations of fibromyalgia syndrome, and central sensitization syndromes associated with chronic neuromuscular pain. The contributors thoroughly examine various approaches to evaluation and management of patients with fibromyalgia and chronic pain. Other chapters focus on disability issues, prognosis, and future research directions. A critically reviewed listing of Websites and other resources is included.

Previous epidemiological studies have indicated that the county of Värmland in western Sweden may be a high-risk zone for multiple sclerosis (MS). The objective of this study was to determine the prevalence in the area. Hospital and general practice medical files were scrutinized. The diagnostic criteria of Poser were used, with 31 December 2002 as prevalence day. The prevalence was 170.07 per 100,000 inhabitants. The average annual incidence was 6.39 to 6.46 per 100,000 (1991—1995, 1996—2000). Multiple sclerosis was 2.3 times more common among women than men. There was a variation in prevalence among the 16 municipalities, however it was not statistically significant. The rates seemed highest in the southwestern part of the county, roughly similar in location to findings some 70 years earlier. When the prevalence ratios by geographical units for the county in 1933 were applied to the current prevalence, the distribution from these estimated cases differed from homogeneity with very high significance (p < 0.00001 ). In conclusion, this study supports previous reports indicating that Värmland continues to be a high-risk zone for MS and shares in the diffusion of the disease at the county level which we had presented for the country as a whole.

Purpose: Language lateralisation in patients with epilepsy is more often atypical compared to a normal population. The Wada procedure for testing language and memory has some shortcomings; it is invasive and there is always a risk that the patient becomes too sedated, leading to difficulties in performing the tests. fMR1have shown promising results, showing good correlation to the Wadaprocedure concerning language-lateralisation. The aim of this studywas to investigate if fMRI could be used to determine which hemisphere was language dominant and compare the fMR1 results with the Wada-tests with a focus on patients with a complicated lateralisation.

Method: 4 subjects were tested and they had a heterogeneous (I left handed, I ambidexter and 2 right handed) lateralisation and one had a severe dyslexia. A standard Wada procedure was used and compared with a fMRl investigation using a language paradigm.

Results: The patients studied showed different language lateralisation patterns (2 left hemisphere and 2 bilateral). In two patients the two tests were fully concordant, in the others the fMRI showed a more bilateral pattern.

Conclusion: fMR1 adds valuable information in the pre-surgical investigation for patients with a complex language lateralisation.

We analysed HLA haplotypes in pairs of 78 sporadic multiple sclerosis (MS) patients and 78 healthy siblings. The presence of 2 oligoclonal IgG bands, detected by immunoblotting of the cerebrospinal fluid in healthy siblings, has previously been defined as MS immunopathic trait (MSIT), based on a cut-off derived from healthy unrelated volunteers. The frequency of MSIT was 17.9% (n=14/78 siblings). The HLA-DR(15)2 allelle was present in 21.4% (n=3/14) of the siblings with MSIT, in 40.6% (n =26/64) of the siblings without MSIT, and in 59% (n =46/78) of the patients with clinically-definite (CD) MS. The distribution of zero, one or two HLA-DR(2)15 alleles was significantly skewed towards a lower allelle count in the siblings with MSIT compared with the group of unrelated siblings with MS (P=0.002), and also lower than their related siblings with MS (P=0.1). These results suggest that the MS susceptibility gene, HLA-DR(2)15 type, does not induce MSIT, and conceivably these are two separate risk factors in the development of MS. The effect of HLA-DR(2)15 and MSIT in sporadic MS appears to be synergistic.

Objectives – When surveying the county of Värmland in Sweden in order to determine the prevalence of multiple sclerosis (MS), we observed an aggregation of MS cases originating from the parish of Lysvik in the local region called Fryksdalen. Our intention was to analyse this cluster thoroughly, confirming the MS diagnosis and seeing if a hereditary or environmental background was plausible.

Methods – The medical files were studied and the cases were classified by a neurologist according to Poser's criteria. Hereditary factors were analysed.

Results – Sixteen living cases of MS were found, either living in the parish (n = 6) or born or raised there and had later moved to another place (n = 10). All patients had clinically definite MS. Eleven patients had relatives with MS, all of these being descendants of the Suhoinen family. Another two cases were Suhoinen descendants who did not have relatives with MS. Other common ancestors were also identified. Two cases were adopted. Eleven deceased MS patients from Lysvik were found, 10 of them had Suhoinen ancestry.

Conclusion – We report a cluster of MS cases with a common ancestry indicating heredity for MS in 85% of the cases. Lysvik is a parish where Finnish immigration was pronounced in the 17th century and there has been inbreeding to a certain extent through marriage between cousins. Thus, we interpret this aggregation as possibly being genetically based, and neurogenetic studies are now being performed. However, as two of the cases were adopted environmental factors must also be considered.

T-lymphocytes are probably involved in the pathogenesis of Guillain-Barré syndrome (GBS). T-helper-1 (Th1) cytokines activate macrophages and induce a delayed type hypersensitivity (DTH) inflammatory response, consistent with the morphology of the demyelination in GBS. Th2 cytokines encourage antibody production and downregulate Th1 responses. To study the Th1/Th2 cytokines in relation to the clinical course of GBS an ELISPOT method for determination of single cells secreting interferon-γ, IFN-γ (Th1) or interleukin-4, IL-4 (Th2) was used. We serially investigated antigen-induced cytokine secretion from circulating T-cells stimulated with human peptides from the P0 and P2 proteins in seven patients and compared to results from seven serially investigated healthy controls. Most patients (five of seven) showed IL-4 responses during the plateau- or recovery-phase as compared to controls. One patient with a prolonged disease course, on the other hand, had an IFN-γ dominated reactivity. We suggest that the IL-4 responses are beneficial in GBS, and may have a role in terminating the disease process in this self-limiting inflammatory disease.

We used ELISPOT and cell ELISA to study secretion of IL-4, IFN-γ, TGF-β, IL-6, and TNF-α by circulating mononuclear cells during the course of Guillain-Barré syndrome (GBS). Compared to healthy controls, patients with GBS had higher numbers of TGF-β-secreting cells and the number of individuals with myelin-peptide-induced IL-4 and TGF-β secretion was higher in the GBS group. No significant differences were seen concerning the predominantly pro-inflammatory cytokines IFN-γ, IL-6 or TNF-α. Our findings indicate a down-regulatory role for TGF-β and IL-4 in GBS.

T lymphocytes are probably of pathogenic importance in many autoimmune diseases. Recently, deviations of circulating T-helper (CD4⁺) subpopulations have been noticed. Blood samples from 12 patients with Guillain-Barré syndrome (GBS) were studied with flow cytometry during their disease to define circulating T cell populations. The proportion of T-helper cells (CD4⁺) was decreased (mean value 41±15%, P = 0.01) and the proportion of T cytotoxic/suppressor cells (CD8⁺) was increased (35±18%, P = 0.0006) as compared to the control group of healthy blood donors (47±8% and 26±7% respectively). The CD4⁺ population is divided into the helper/inducer (CD4⁺ CD29⁺) and suppressor/inducer (CD4⁺ CD45RA⁺) subsets. which normally are equally distributed (mean values in our control group were 45±15% and 44±15%, respectively). In patients with GBS, the helper/inducer (CD4⁺ CD29⁺) subset was increased (54±10%, P = 0.05) and the suppressor/inducer (CD4⁺ CD45RA⁺) subset was decreased (31±9, P = 0.005) compared to the controls. The proportion of activated HLA-DR-expressing T cells was increased (7±8%, P = 0.005) as compared to control (3±3%). The total proportions of T cells (CD2⁺), B cells (CD19⁺) and natural killer (NK) cells (CD56⁺) were similar in pateints and controls. The CD4⁺ and CD8⁺ populations, as well as the activated HLA-DR⁺ T cells, normalized during the disease course. The derivations within the CD4⁺ population also tended to normalize, but even at follow up after 6–33 (mean 23) months, some abnormalities remained. In conclusion, we confirm previous reports of T cell activation in peripheral blood from patients with GBS. A new finding is the derivation of T helper subpopulations with an increased helper/inducer (CD4⁺ CD29⁺) subset and a decreased suppressor/inducer (CD4⁺ CD45RA⁺) subset, which indicates a possible autoimmune character of GBS.

The unique absence of major histocompatibility complex class I antigen (MHC-I) expression in normal muscle is one possible mechanism protecting striated muscle. In order to define their possible involvement in protection of normal muscle. we investigated the expression of molecules involved in muscle fibre death and survival mechanisms (Bcl-2, Fas, Fas-ligand and TRAIL), focusing on disorders with possible involvement of cytotoxic T cells. We studied muscle biopsies from 20 healthy volunteers, from 10 patients affected by polymyositis and 10 by Duchenne muscular dystrophy. By using immunohistochemistry, Western blot and real-time PCR we detected a constitutional expression of Bcl-2 in healthy muscle, whereas the expression was weaker in disease processes. Fas-L and TRAIL were not detected in muscle fibres, and Fas only in muscle affected by disease. Our findings indicate that the major apoptotic protein Bcl-2 might have a hitherto unrecognized role in the protection of normal muscle.

A causal role of IL-4 (Th2) production for recovery in experimental allergic neuritis (EAN) was indicated by experiments where Th1-like autoreactive cell populations, taken from the induction phase of the disease, were deviated to extensive secretion of IL-4 in a selective fashion, by ex vivo stimulation with autoantigen in the presence of IL-4. The deviated cells were adoptively transferred to EAN rats at a time just prior to the onset of clinical signs. This treatment ameliorated EAN compared with sham treatment. This therapeutic approach, with generation of autoreactive IL-4-secreting cells ex vivo followed by subsequent adoptive transfer, may become a new selective treatment of organ-specific autoimmune diseases since, in contrast to previous attempts, it is done in a physiological and technically easy way.

Functional magnetic resonance imaging (fMRI) paradigms on sensory–motor and language functions are reviewed from a clinical user’s perspective. The objective was to identify special requirements regarding the design of fMRI paradigms for clinical applications. A wide range of methods for setting up fMRI examinations were found in the literature. It was concluded that there is a need for standardised procedures adapted for clinical settings. Sensory–motor activation patterns do not vary much at different hand motion tasks. Nevertheless it is one of the most important clinical tests. In contrast, the language system is much more complex. In several studies it has been observed that word production tasks are preferable in determination of language lateralisation. Broca’s area is activated by most tasks, whereas sentence processing and semantic decision also involve activation in temporoparietal and frontal areas. However, combined task analysis (CTA) of several different tasks has been found to be more robust and reliable for clinical fMRI compared to separate task analysis.

This community-based study of Parkinson's disease (PD) investigated age at death and cause of death in a cohort of 170 previously studied patients. The current study is a 9-year follow-up, and the results are compared to 510 sex- and age-matched controls from the same area. A total of 170 patients were diagnosed with PD on August 31, 1989, within a defined area of Sweden. A control group of 510 persons from the same area and with the same age and sex distribution was also examined regarding age at death and cause of death. After 9.4 years, 121 cases (71.1%) and 229 controls (44.9%) were no longer alive. Thus, the mortality rate ratio was 1.6 (95% confidence interval [CI], 1.3-1.8) when comparing PD patients with controls. The all-cause hazard ratio for cases compared to controls was 2.4 (95% CI, 1.9-3.0). The mean age at death for the cases was 81.9 (95% CI, 80.3-83.0) years and for the controls 82.9 (95% CI, 82.0-83.7) years. Survival analysis also showed a shorter survival time (P < 0.001) for PD patients. Only 53% of the death certificates for the deceased patients recorded PD as an underlying or contributory cause of death. Many PD patients reached a high age but had a shorter survival than the controls. There was a significant increase in deaths from pneumonia.

Fatigue is not only a complex phenomenon accompanying different illness conditions but is also a common complaint among individuals in the general population. Among individuals diagnosed with the chronic neurological disease multiple sclerosis (MS), one-third describe fatigue as the very first symptom, however it is invisible to others. When adopting an action-theoretic approach to health, fatigue may be considered to influence the individual’s goals of life and subjectively perceived health. The aim of this study was to describe perceived fatigue in relation to perceived health among working-aged individuals diagnosed with MS (n = 155), and in a comparative group of individuals randomly selected from the general population living in the same geographical area (n = 190). A self-report questionnaire including the Fatigue Impact Scale, a checklist of six symptoms, questions covering perceived health and levels of and perceptions of fatigue was used for the data collection. The responses on perceived health were dichotomized into two categories: ‘good health’ and ‘ill health’. Of the individuals with MS, 50% graded their perceived health as ill compared with 18% in the reference group (p < 0.001), and 68% graded fatigue as one of their worst symptoms compared with 21% in the reference group. In both groups, higher presence of symptoms and impact of fatigue in daily activities correlated negatively to perceived health. Compared with the individuals in the reference group, the individuals with MS reported higher impact of fatigue in physical areas in both the category of ‘good health’ (p < 0.001) and ‘ill health’ (p < 0.01). The perceived impact of fatigue was mirrored in increased problems in social and family activities. In conclusion, individuals with MS perceive fatigue as one of their worst symptoms three times as often as individuals in the general population. However, individuals with MS probably also adapt themselves or shift in their response to fatigue more than individuals in the general population.

Objectives – Forty percent of patients with aneurysmal subarachnoid hemorrhage have prodromal warning episodes and difficulties in identifying these events are repeatedly documented. Modifications of diagnostic and referral patterns through educational programs of local doctors may help to identify such patients before a major devastating rupture occurs.

Materials and methods– A teaching program about sudden onset headache, targeting referring doctors, was systematically applied and its impact on early misdiagnosis of ruptured aneurysms was prospectively studied.

Results– Forty percent of all studied patients experienced a warning episode, manifested as apoplectic headache, prior to hospitalization. An initial diagnostic error was evident in 12% of the patients. Diagnostic errors were reduced by 77% as a result of continuous interaction between neurosurgeons and local physicians.

Conclusion– Misdiagnosed warning episodes cause greater loss of lives and higher morbidity on a population basis than does delayed ischemic complications from vasospasm in aneurysmal SAH. Teaching programs focused on local physicians have a profound impact on outcome at low cost.

The aim of this study was to elucidate the mechanisms of action for potential targets of therapeutic intervention related to the arachidonic acid cascade in muscular dystrophy. Primary cultures from a Duchenne patient were used to study the expression of dystrophin-1, utrophin, desmin, neonatal myosin heavy chain (MHCn) and Bcl-2 during inhibition of phospholipase A2 (PLA2), cyclooxygenase (COX) and lipoxygenase (LOX). Hypo-osmotic treatment was applied in order to trigger Ca2+ influx and PLA2 activity. Inhibition of PLA2 and LOX with prednisolone and nordihydroguaiaretic acid (NDGA) caused a semi-quantitative increase of utrophin and Bcl-2-, and a dose-dependent, quantitative increase of desmin expression, an effect that was augmented by hypo-osmotic treatment. Our results indicate that LOX inhibitors, similarly to corticosteroids, can be beneficial in the treatment of muscular dystrophies. © 2007 Elsevier Ltd. All rights reserved.

Syftet med rapporten är att sammanfatta det vetenskapliga underlaget rörande effekter, biverkningar samt kostnadseffektivitet för metoder som används för att behandla långvarig, icke-cancerrelaterad smärta. Behandling som innebär öppen kirurgi har exkluderats från genomgången.

Epidemiological studies show that susceptibility to multiple sclerosis (MS) has a strong genetic component, but apart from the HLA gene complex, additional genetic factors have proven difficult to map in the general population. Thus, localized populations, where MS patients are assumed to be more closely related, may offer a better opportunity to identify shared chromosomal regions. We have performed a genome-wide scan with 834 microsatellite markers in a data set consisting of 54 MS patients and 114 healthy family members. A group of families from a small village were possible to track back to common ancestors living in the 17th century. We used single marker- and haplotype-based transmission disequilibrium test (TDT) analysis and nonparametric linkage analysis to analyze genotyping data. Regions on chromosomes 2q23–31, 6p24–21, 6q25–27, 14q24–32, 16p13–12 and 17q12–24 were found to be in transmission disequilibrium with MS. Strong transmission disequilibrium was detected in 14q24–32, where several dimarker haplotypes were in transmission disequilibrium in affected individuals. Several regions showed modest evidence for linkage, but linkage and TDT were both clearly positive only for 17q12–24. All patients and controls were also typed for HLA class II genes; however, no evidence for a gene–gene interaction was observed.

Background: The medical care of patients with acute stroke varies considerably between countries. This could lead to measurable differences in mortality and functional outcome. Objective: To compare case mix, clinical management, and functional outcome in stroke between 11 countries. Methods: All 1484 patients from 11 countries who were enrolled into the tinzaparin in acute ischaemic stroke trial (TAIST) were included in this substudy. Information collected prospectively on demographics, risk factors, clinical features, measures of service quality (for example, admission to a stroke unit), and outcome were assessed. Outcomes were adjusted for treatment assignment, case mix, and service relative to the British Isles. Results: Differences in case mix (mostly minor) and clinical service (many of prognostic relevance) were present between the countries. Significant differences in outcome were present between the countries. When assessed by geographical region, death or dependency were lower in North America (odds ratio (OR) adjusted for treatment group only = 0.52 (95% confidence interval, 0.39 to 0.71) and north west Europe (OR = 0.54 (0.37 to 0.78)) relative to the British Isles, similar reductions were found when adjustments were made for 11 case mix variables and five service quality measures. Similarly, case fatality rates were lower in North America (OR = 0.44 (0.30 to 0.66)) and Scandinavia (OR = 0.50 (0.33 to 0.74)) relative to the British Isles, whether crude or adjusted for case mix and service quality. Conclusions: Both functional outcome and case fatality vary considerably between countries, even when adjusted for prognostic case mix variables and measures of good stroke care. Differing health care systems and the management of patients with acute stroke may contribute to these findings.

A series of investigations have been performed to study secular trends of motor neuron disease (MND) morbidity and mortality in Sweden, to identify time and/or space clusters, if any, and to uncover risk factors. The occurrence of the disease was estimated from incidence, prevalence and mortality rates, and the strength of various determinants was evaluated by means of the case-control approach, using population controls. The studies comprised different periods of time between 1961 and 1990.

The mortality rate from MND in Sweden, for both genders taken together, doubled from 1961 to 1985, reaching 2.5 per 100,000 person-years, and the incidence rates were of a similar magnitude. The age-specific mortality rates peaked at 70 to 75 years of age. Regarding separate birth cohorts the peak was less clear, however, and the mortality rates tended to increase continuously with advancing age. An epidemic of MND was identified in the county of Skaraborg during the period 1973-1984, when three times as many males as expected had onset of MND, especially involving the farm-working population. In the community surveys involving the counties of Viirmland and Skaraborg the 50% survival rate was slightly more than two years.

Among males high adjusted odds ratios were obtained for electricity work (0R=6.7, 95% Cl 1.0-32.1), welding (0R=3.7, 95% Cl 1.1-13.0) and exposure to impregnating agents (0R=3.5, 95% Cl 0.9-13.1). Heredity with regard to a neurodegenerative disease and/or thyroid disease yielded OR=2.1, 95% Cl 1.0-4.3. The highest odds ratio was found for the combination of such heredity, exposure to solvents and male gender (0R=l5.6, 95% Cl 2.8-87.0).

In sum, an increase in MND seems to have taken place during the last few decades. The regional epidemic especially among males in agricultural work, the high risk estimates regarding some occupational exposures of mainly chemical nature, and the interaction with heredity, indicate that environmental factors might play a role in the pathogenesis of MND, and that a subpopulation might be particularly susceptible.

BACKGROUND AND PURPOSE: Spectroscopic studies (¹H-MR spectroscopy) of normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) with MR imaging brain lesions have already been performed, but our intention was to investigate NAWM in MS patients who lack brain lesions to elucidate whether the same pathologic changes could be identified.

MATERIALS AND METHODS: We checked 350 medical files of patients with MS who are registered in our institution. Fourteen patients (11 women and 3 men; mean age, 48.6 years; handicap score, Expanded Disability Status Scale [EDSS] 2.9; range, 1–6.5) with clinically definite MS and a normal MR imaging of the brain were included. ¹H-MR spectroscopy was performed in 4 voxels (size approximately 17 × 17 × 17 mm³) using absolute quantification of metabolite concentrations. Fourteen healthy control subjects (11 women and 3 men; mean age, 43.3 years) were analyzed in the same way.

RESULTS: Significant differences in absolute metabolite concentrations were observed, with the patients with MS showing a lower total concentration of N-acetyl compounds (tNA), including N-acetylaspartate and N-acetyl aspartylglutamate (13.5 mmol/L versus 14.6 mmol/L; P = .002) compared with the healthy control subjects. Unexpectedly, patients with MS presented significantly lower choline-containing compounds (Cho) compared with healthy control subjects (2.2 mmol/L versus 2.4 mmol/L; P < .001). The EDSS showed a positive correlation to myo-inositol concentrations (0.14 mmol/L per EDSS; r² = 0.06) and a negative correlation to tNA concentrations (−0.41 mmol/L per EDSS; r² = 0.22).

CONCLUSION: The unexpected finding of lower Cho concentrations has not been reported previously. We suggest that patients with MS who lack lesions in the brain constitute a separate entity and may have increased protective or healing abilities.

This study aimed at investigating if selective ex vivo immune deviation of myelin-specific cytokine secretion towards Th2 is possible in blood cells from patients with multiple sclerosis (MS). Interleukin (IL)-4 (Th2) and interferon-γ (Th1) secreting cells were recorded by ELISPOT in 13 MS patients. Deviation was successful in 10 patients. Interleukin-4 alone was most effective in inducing myelin-specific immune deviation in MS patients whereas IL-1 or IL-15 in combination with IL-4 did not improve the results. Further studies and improvements are needed before ex vivo immune deviation can be considered a potential treatment in patients with MS. © 2005 Elsevier B.V. All rights reserved.

Neuropathic pain is a disabling chronic condition with limited therapeutic options. Few studies have addressed patient's experience and strategies. The aim of this study was to explore dilemmas experienced in order to improve care and rehabilitation. An interview study with 39 patients suffering from neuropathic pain of different origin was performed. We used the critical incident technique to collect data. Questions on occasions when patients had been hindered by or reminded of their neuropathic pain were included, and the self-perceived consequences and management of such occasions. The interviews were transcribed verbatim and analysed qualitatively. A broad range of experiences categorised into dilemmas, disturbances, consequences and managements from most parts of everyday life was identified. The dilemmas were ‘housework’, ‘sitting’, ‘physical activity’, ‘personal hygiene’, ‘sleeping difficulties’, ‘hypersensitivity to external stimuli’, ‘social relationships’, ‘transportation’ and ‘leisure time’. Disturbances were ‘failures’, ‘inabilities’ and ‘restrictions’. Consequences were ‘increased pain’, ‘psychological reactions’ and ‘physical symptoms’. The majority of the patients used activity-oriented strategies to manage their pain such as alternative ways of performing the task, a cognitive approach or simply ignoring the pain. This is one of the first studies presenting detailed data on everyday dilemmas, disturbances and consequences of patients with chronic neuropathic pain. Such information is important in clinical settings to improve care and rehabilitation.

The objective of this study was to investigate tolerability and possible neurotrophic effects of growth hormone (GH) in treatment of multiple system atrophy (MSA). In this double-blind pilot study, MSA patients were randomized to recombinant human growth hormone (r-hGH, n = 22), 1 mg every second day (6 months) followed by alternating daily injections of 1 mg and 0.5 mg (6 months), or matched placebo (n = 21). Safety analysis demonstrated no obvious between-group differences. In both groups, there was progressive worsening of Unified Parkinson's Disease Rating Scale total score, which tended to be less in r-hGH-treated patients (12.9% at 6 months, 25.3% at 12 months) than in placebo (17.0% and 35.7%). Similarly, there was a trend to less worsening in Unified MSA Rating Scale total score with r-hGH (13.2% and 21.2%) than with placebo (21.1% and 36.5%). Cardiovascular reflex autonomic testing also tended to show less deterioration with r-hGH than with placebo at 12 months. However, 95% CI did not indicate treatment differences for any efficacy measures. In conclusion, r-hGH administration in MSA patients for up to 1 year appears safe and might influence disease symptoms, signs and, possibly, progression. The results support further studies utilizing higher doses in more patients. © 2007 Movement Disorder Society.

Objective: To investigate if women with multiple sclerosis (MS) experience changes in MS symptoms related to pregnancy, the postpartum period, menopause or use of oral contraception (OC) or postmenopausal hormone therapy (HT). Methods: Women with diagnosed MS were recruited from registers of all MS patients known in two counties of Sweden, respectively. Ninety-four women were recruited in Linköping and 52 in Sundsvall. The women answered a questionnaire with categorized alternatives regarding their MS symptoms related to menstruation, pregnancy, delivery, menopause and use of OC or HT. Results: Forty percent of the women reported worsening of MS symptoms related to menopause, whereas 56% reported no change of symptoms and 5% reported decreased symptoms. More than a fourth of the women reported decreased symptoms during pregnancy, 64% reported unchanged symptoms and 10% reported increased symptoms. Every third woman reported increased symptoms after delivery, 59% reported no change and 5% reported decreased symptoms. Few women reported changes in MS symptoms in relation to use of HT or OC. Conclusion: The presented data indicate a relationship between high-oestrogen states and ameliorated symptoms whereas low-oestrogen states seem to relate to a worsening of the disease. A majority of women, however, reported no changes in MS symptoms in relation to the different oestrogen states. © 2005 Elsevier Ireland Ltd. All rights reserved.

We sought to determine whether Swedish patients with multiple sclerosis (MS) with and without oligoclonal bands (OCBs) in the CSF constitute distinct subpopulations, clinically and immunogenetically. Our findings indicate that OCB-negative MS shares the same clinical features as OCB-positive MS regarding female predominance, age at onset, proportion of primary progressive cases, rate of MRI positivity, and disease severity. Our HLA-DRB1 genotyping results suggest, however, that OCB-positive and OCB-negative MS are immunogenetically distinct. Copyright © 2006 by AAN Enterprises, Inc.

Objectives: The aims of this study were to describe the quality of life in patients with multiple sclerosis (MS) given immunological treatment and in those not given immunological treatment and to investigate the relationship between impairment and quality of life. Methods: Twenty nine patients given immunological treatment were matched with the same number of patients not given such treatment. Matching variables were sex, Kurtzke's Expanded Disability Status Scale (EDSS), years since diagnosis, and age (total n = 58). The patients were interviewed using the self-reported impairment checklist and they answered two questionnaires on quality of life, the 36-Item Short-Form Health Survey (SF-36) and the Subjective -Estimation of Quality of Life (SQoL). Results: The self-reported impairment checklist captured a more differentiated picture of the patients' symptoms of MS than the EDSS. Health related quality of life was markedly reduced, while the subjective quality of life was less affected. There was a stronger association between self-reported ratings of impairment and health related quality of life on the SF-36 than between impairment and global ratings of quality of life on the SQoL. Subjective quality of life on the SQoL was not directly dependent on impairment expressed in physical limitations. There were no statistically significant differences between the treated and untreated groups. A non-significant trend towards better health related quality of life was found in favour of the treated group with respect to emotional role, physical role, and social function on the SF-36. Conclusions: The self-reported impairment checklist and SF-36 proved to be valuable complements to the well established EDSS in describing the diverse symptoms of MS. Measuring both health related quality of life and subjective wellbeing provides valuable knowledge about the consequences of MS.

The mechanisms behind the beneficial effects of interferon-β1a (IFN-β1a) and glatiramer acetate (GA) in the treatment of multiple sclerosis (MS) are still uncertain. Altered cytokine patterns have been suggested including inhibition of proinflammatory cytokines like interferon-γ (IFN-γ) and enhancement of anti-inflammatory cytokines such as interleukin-4 (IL-4). Twenty-nine patients with MS (10 untreated, nine treated with IFN-β1a and 10 with GA) were investigated with elispot of peripheral blood mononuclear cells. Spontaneous and myelin induced (myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG)-14-39 and MOG 63-87) IFN-γ, IL-4, IL-5 and IL-10 secretion was studied. We found a significant reduction of spontaneous IFN-γ, IL-4 and IL-5, but no difference in IL-10 secreting cells in both groups of treated patients compared with the untreated patients. Myelin-specific responses showed a significant decrease of IFN-γ and an increase of IL-5, but no change in IL-4 and IL-10 secreting cells in treated compared with untreated patients. Both treatment groups revealed similar cytokine secretion patterns except for a more pronounced decrease of both spontaneous and MOG 14-39 induced IL-4 secretion in the IFN-β1a treated group. Thus, immunological effects of IFN-β1a and GA were similar showing that disease promoting Th1 (IFN-γ) cells were reduced while the potentially beneficial Th2 response (IL-4) was maintained.

This study describes changes in a rat facial muscle innervated by the mandibular and buccal facial nerve branches 4 months after nerve injury and repair. The following groups were studied: (A) normal controls; (B) spontaneous reinnervation by collateral or terminal sprouting; (C) reinnervation after surgical repair of the mandibular branch; and (D) chronic denervation. The normal muscle contained 1200 exclusively fast fibers, mainly myosin heavy chain (MyHC) IIB fibers. In group B, fiber number and fiber type proportions were normal. In group C, fiber number was subnormal. Diameters and proportions of MyHC IIA and hybrid fibers were above normal. The proportion of MyHC IIB fibers was subnormal. Immediate and delayed repair gave similar results with respect to the parameters examined. Group D rats underwent severe atrophic and degenerative changes. Hybrid fibers prevailed. These data suggest that spontaneous regeneration of the rat facial nerve is superior to regeneration after surgical repair and that immediacy does not give better results than moderate delay with respect to surgical repair. Long delays are shown to be detrimental.

Pain in multiple sclerosis (MS) is more common than has previously been believed. About 28% of all MS patients suffer from central pain (CP), a pain that is difficult to treat. In the present study we have investigated the responsiveness of this pain to morphine. Fourteen opioid-free patients (eight woman and six men) with constant, non-fluctuating, long-lasting CP caused by MS were investigated. Placebo (normal saline), morphine and naloxone were given intravenously in a standardized manner. The study design was non-randomized, single blind and placebo controlled. Ten patients experienced less than 50% pain reduction by placebo and less than 50% pain reduction by morphine. Four patients were opioid responders, i.e. had minimal or no effect on pain by placebo, >50% pain reduction after morphine and >25% pain increase after naloxone, given intravenously following morphine. However, this response was obtained after high doses of morphine (43 mg, 47 mg, 50 mg and 25 mg; mean 41 mg). Thus, compared with nociceptive pain, only a minority of the patients with CP due to MS responded to morphine and only at high doses. The present results are in accord with experimental studies indicating that neuropathic pain is poorly responsive but not totally unresponsive to opioids. The results do not support the routine use of strong opioids in MS patients with CP.

Proinflammatory cytokines like IFN-γ and TNF-α seem to have disease-promoting roles in multiple sclerosis (MS) whereas anti-inflammatory cytokines like IL-10 and TGF-ß may downregulate the disease. IFN-ß treatment reduces the frequency and severity of relapses, however, the mechanisms of action for IFN-ß are only partly understood and modulation of cytokine secretion could be one possible explanation for the therapeutic effects. The IFN-ß products approved for the treatment of MS differ in their composition and effects, and recently differences in effects on cytokine secretion were reported. Peripheral blood was collected from 25 patients with MS, both IFN-ß1a and IFN-ß1b treated, before onset of treatment and after 6 weeks, 3 months, 6 months and one year. Spontaneous as well as myelin specific secretion of IL-4, IFN-γ and IL-10 was analysed with the ELISPOT technique. PHA stimulated secretion of IL-13 and IL-17 was analysed in cell supernatants with ELISA. A general finding was that surprisingly few changes occurred, and that most changes occurred early (6 weeks - 3 months). We found a shift in the cytokine balance towards more IL-4 and IL-10 secretion and/or less IFN-γ secretion during the treatment as the ratios of IL-4!IFN-y as well as of IL-10/IFN-γ were increased. The interesting pro-inflammatory cytokine IL-17, that has been associated with T-cell mediated autoimmunity, has not been previously investigated during IFN-ß treatment in MS. Our findings of decreased IL-17 levels after one year of treatment, following an increase in early treatment, could be a beneficial result of the IFN-ß treatment. Further we noticed differences in effects on cytokines of IFN-ß1a and IFN-ß1b respectively; the latter seemed to have more effects on cytokine secretion.

Monoclonal expansion of B cells and plasma cells, producing antibodies against ‘self’ molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenström’s macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P₀, using beads coated with P₀. P₀-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein–Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P₀ antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5⁺ positive, although the expression declined in vitro over time. The anti-P₀ antibodies were of IgM-λ type. The antibodies belonged to the V_H3 gene family with presence of somatic mutations. The IgM reacted with P₀ and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5⁺ clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P₀-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation.

Several famous religious personalities have been discussed as possibly having had epilepsy. Partial epileptic fits can be accompanied by religious experiences. The Swedish St Birgitta of Vadstena is focused on from this perspective as the exterior of the skull thought to belong to her has a prominent tuberculum with a corresponding interior indentation possibly indicating the previous existence of a meningioma, a well known cause of epilepsy. This article scrutinises arguments for and against the possibility of epileptic features in the revelations of the saint, as well as in her life story.

"Sensed presence," a religious emotion, has been the focus of recent neurotheological research because it has been claimed that weak transcranial magnetic stimulation can evoke such experiences. Some researchers have recently questioned this claim. However, religion and epilepsy have been linked through history, clinical observations, and research. This article describes the "sensed presence" as an aura in one patient who did not interpret his experience in a religious way. He had bilateral hypoperfusion of the temporal lobes when investigated by SPECT, and hypoplasia of the dorsal part of the left hippocampus when examined by magnetic resonance imaging. This case report illustrates that "sensed presence" can occur as an epileptic aura with or without religious interpretation. © 2006 Elsevier Inc. All rights reserved.

Erectile dysfunction in men with multiple sclerosis (MS) is a very common symptom that often leads to a reduced quality of life. It is related to neurological dysfunction, psychological factors, side effects of medication or generalized MS symptoms, such as fatigue or micturition problems, usually in combination. The question of sexual dysfunction should always be broached during routine follow-up, regardless of age and social status. The possibility that erection problems can be a side-effect of drugs commonly used in MS must also be remembered. There are several effective pharmacological treatments, such as phosphodiesterase inhibitors and prostaglandin E1 (alprostadil). The contraindications and side effects should be familiar to the MS doctor. Dose titration in the initial stages is recommended to avoid priapism. In the future, combinations of impotence drugs may be tested. © 2006 Future Drugs Ltd.

We have performed a study of 137 consecutive patients with thunderclap headache (TCH), showing that a large majority of the patients do not have a subarachnoidal haemorrhage (SAH). It is concluded that 11% of all TCH is caused by SAH and that history and findings in the clinical neurological examination cannot discriminate safely between an SAH and a more benign cause. All patients should be investigated with a CT scan and an analyses of the cerebrospinal fluid to exclude a SAH if the CT scan did not show an SAH. The 10-year follow-up showed that none of the patients with TH without SAH had a cerebral haemorrhage of any kind. Pathological results on CT and CSF examinations were found in 14 of the patients with non-SAH TCH, including five with cerebral infarction, three with intracerebral haemorrhage, four with aseptic meningitis and one with venous sinus thrombosis.