Time to diagnosis in multiple sclerosis: Epidemiological data from the German Multiple Sclerosis Registry.

OBJECTIVE: To investigate the time to diagnosis in multiple sclerosis (MS) in Germany. METHODS: Analysis of real-world registry data from the German Multiple Sclerosis Registry (GMSR) and performing a primary analysis in patients where month-specific registration of the dates of onset and diagnosis was available. RESULTS: As of January 2020, data of a total of 28,658 patients with MS were extracted from the GMSR, with 9836 patients included in the primary analysis. The mean time to diagnosis was shorter following the introduction of the first magnetic resonance imaging (MRI)-based McDonald criteria in 2001. This effect was most pronounced in younger adults below the age of 40 years with relapsing onset multiple sclerosis (ROMS), with a decrease from 1.9 years in 2010 to 0.9 years in 2020, while unchanged in patients aged 40-50 years (1.4 years in 2010 and 1.3 years in 2020). In the limited number of paediatric onset MS patients, the time to diagnosis was longer and did not change (2.9 years). CONCLUSION: The current sensitive MRI-based diagnostic criteria have likely contributed to an earlier diagnosis of MS in Germany in younger adults aged 18-39 years with ROMS. Whether this translated to earlier initiation of disease-modifying treatment or had a beneficial effect on patient outcomes remains to be demonstrated.

Symptomatology and symptomatic treatment in multiple sclerosis: Results from a nationwide MS registry.

BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease. Over time, symptoms accumulate leading to increased disability of patients. OBJECTIVE: The objective of this article is to analyze the prevalence of symptoms and symptomatic treatment patterns in a nationwide MS registry. METHODS: Data sets from 35,755 patients were analyzed. RESULTS: More than two-thirds of patients were women with a mean age of 46.1 (±12.8) years. Median Expanded Disability Status Score (EDSS) was 3.0. The most frequently reported symptoms were fatigue, spasticity, and voiding disorders. In patients with short disease duration, fatigue was reported most frequently. Symptomatic treatment was most common for spasticity and depression, whereas fatigue was treated only in a third of affected patients. Almost a fifth of patients with EDSS ⩽ 3.5 and neuropsychological symptoms had retired from work. CONCLUSION: Whereas treatment for spasticity and depression is common in our cohort, sexual dysfunction, dysphagia, cognitive dysfunction, and fatigue are treated to a far lesser extent. The need for psychological support, physical, and occupational therapy has to be recognized as neuropsychological symptoms have a great impact on retirement at an early stage. Overall symptomatic treatment rates for the most common symptoms have increased over the last years (p < 0.001).

Hippotherapy for patients with multiple sclerosis: A multicenter randomized controlled trial (MS-HIPPO).

BACKGROUND: Evidence-based complementary treatment options for multiple sclerosis (MS) are limited. OBJECTIVE: To investigate the effect of hippotherapy plus standard care versus standard care alone in MS patients. METHODS: A total of 70 adults with MS were recruited in five German centers and randomly allocated to the intervention group (12 weeks of hippotherapy) or the control group. Primary outcome was the change in the Berg Balance Scale (BBS) after 12 weeks, and further outcome measures included fatigue, pain, quality of life, and spasticity. RESULTS: Covariance analysis of the primary endpoint resulted in a mean difference in BBS change of 2.33 (95% confidence interval (CI): 0.03-4.63, p = 0.047) between intervention ( n = 32) and control ( n = 38) groups. Benefit on BBS was largest for the subgroup with an Expanded Disability Status Scale (EDSS) ⩾ 5 (5.1, p = 0.001). Fatigue (-6.8, p = 0.02) and spasticity (-0.9, p = 0.03) improved in the intervention group. The mean difference in change between groups was 12.0 ( p < 0.001) in physical health score and 14.4 ( p < 0.001) in mental health score of Multiple Sclerosis Quality of Life-54 (MSQoL-54). CONCLUSION: Hippotherapy plus standard care, while below the threshold of a minimal clinically important difference, significantly improved balance and also fatigue, spasticity, and quality of life in MS patients.

Mast cell activation disease: An underappreciated cause of neurologic and psychiatric symptoms and diseases.

Neurologists and psychiatrists frequently encounter patients whose central and/or peripheral neurologic and/or psychiatric symptoms (NPS) are accompanied by other symptoms for which investigation finds no unifying cause and for which empiric therapy often provides little to no benefit. Systemic mast cell activation disease (MCAD) has rarely been considered in the differential diagnosis in such situations. Traditionally, MCAD has been considered as just one rare (neoplastic) disease, mastocytosis, generally focusing on the mast cell (MC) mediators tryptase and histamine and the suggestive, blatant symptoms of flushing and anaphylaxis. Recently another form of MCAD, MC activation syndrome (MC), has been recognized, featuring inappropriate MC activation with little to no neoplasia and likely much more heterogeneously clonal and far more prevalent than mastocytosis. There also has developed greater appreciation for the truly very large menagerie of MC mediators and their complex patterns of release, engendering complex, nebulous presentations of chronic and acute illness best characterized as multisystem polymorbidity of generally inflammatory ± allergic themes--including very wide arrays of central and peripheral NPS. Significantly helpful treatment--including for neuropsychiatric issues--usually can be identified once MCAD is accurately diagnosed. We describe MCAD's pathogenesis, presentation (focusing on NPS), and therapy, especially vis-à-vis neuropsychotropes. Since MCAD patients often present NPS, neurologists and psychiatrists have the opportunity, in recognizing the diagnostic possibility of MCAD, to short-circuit the often decades-long delay in establishing the correct diagnosis required to identify optimal therapy.

Clinical case reviews and poster sessions in multiple sclerosis spasticity: main outcomes and highlights.

BACKGROUND: Individuals with multiple sclerosis (MS) spasticity present with a range of symptoms and disability levels that are frequently challenging to manage. Summary : Clinical case reviews in treatment-resistant MS spasticity were presented in five country-specific sessions conducted in parallel at the MS Experts Summit. Attendees at the Norwegian session discussed early response to new treatments for severe spasticity and highlighted the importance of titrating THC:CBD oromucosal spray (Sativex®) when adding it to baclofen. The French group focussed on MS symptoms and patient characteristics that interact with spasticity and agreed on a list of minimum ratings for diagnosis of MS spasticity symptoms. Attendees at the Spanish session concurred that THC:CBD oromucosal spray is effective and well tolerated as add-on therapy in treatment-resistant MS spasticity, particularly for pain, spasms and gait disturbances. The Italian group discussed the use of add-on THC:CBD oromucosal spray and other possible combination therapies for treatment-resistant MS spasticity. Attendees at the German session highlighted the need to address trigger factors for MS spasticity to reduce the potential for impact on activities of daily living (ADL) and quality of life (QoL). Three innovative studies of MS spasticity from the poster session were selected for closer review. The MOVE 1 EU epidemiological study indicated that, across western Europe, patients with MS spasticity continue to have unmet management needs. A literature review demonstrated that symptomatic relief of MS spasticity in patients who respond to THC:CBD oromucosal spray translates into sustainable improvements in ADL and QoL. Enriched-design studies of medications targeting the endocannabinoid system require careful interpretation due to possible pharmacodynamic 'priming', i.e. carry-over effects of successful active treatment during the enrichment phase. Key Messages: Sharing experiences of clinical practice, including experience with the use of THC:CBD oromucosal spray, may be useful to overcome some of the challenges in the overall management of patients with moderate to severe treatment-resistant MS spasticity.

REBISTART: Adherence of Patients with Multiple Sclerosis to Treatment with Subcutaneous Interferon Beta in the Context of a Patient Support Program.

INTRODUCTION: Treatment adherence is a critical success factor in the disease-modifying therapy (DMT) of multiple sclerosis (MS). The REBISTART study prospectively evaluated adherence in patients using components of a patient support program (PSP). METHODS: The 12-month non-interventional multicenter study examined the real-world adherence to subcutaneously (sc) injected interferon beta-1a (Rebif®). Patient-assessed adherence was measured by a visual analog scale (VAS) and the Morisky Medication Adherence Scale (MMAS). Objective adherence data were obtained by readouts from the RebiSmart® injection device. RESULTS: Of 333 patients, 70.9% used the nursing service as the core component of the PSP. Self-assessed VAS-based adherence was stable over time at 94.0-96.3%. Similarly, MMAS score (maximum 4) was 3.8-3.9 at all visits, also reflecting high self-assessed adherence. In 269 patients using the RebiSmart® injection device, mean readout-based objective adherence was similarly high (93.0-98.4% throughout visits). At last available visit, VAS-based adherence was independent of participation in the PSP nursing service (93.1% with participation versus 91.7% without it). Adherence was also independent of injection method or disease-related measures, including fatigue, depression, cognition, and quality of life. The most frequent reason for the premature discontinuations (38.7% of patients) was "change of treatment" (10.0%). DISCUSSION: We suggest that subgroups that may specifically benefit from PSP include patients who live alone, use multiple comedications, and are affected by cognitive impairment, depression, and/or fatigue. Further studies should investigate the potential usefulness of PSPs in these populations. CONCLUSIONS: Very high adherence rates independent of the PSP nursing service over 1 year of treatment indicate that IFN beta-1a sc is an easy-to-use and well-tolerated disease-modifying drug. TRIAL REGISTRATION NUMBER: Vfa.de: No. 892. https://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb/nis-details/_892 .

Frequency and Predictors of Relapses following SARS-CoV-2 Vaccination in Patients with Multiple Sclerosis: Interim Results from a Longitudinal Observational Study.

Despite protection from severe COVID-19 courses through vaccinations, some people with multiple sclerosis (PwMS) are vaccination-hesitant due to fear of post-vaccination side effects/increased disease activity. The aim was to reveal the frequency and predictors of post-SARS-CoV-2-vaccination relapses in PwMS. This prospective, observational study was conducted as a longitudinal Germany-wide online survey (baseline survey and two follow-ups). Inclusion criteria were age ≥18 years, MS diagnosis, and ≥1 SARS-CoV-2 vaccination. Patient-reported data included socio-demographics, MS-related data, and post-vaccination phenomena. Annualized relapse rates (ARRs) of the study cohort and reference cohorts from the German MS Registry were compared pre- and post-vaccination. Post-vaccination relapses were reported by 9.3% PwMS (247/2661). The study cohort's post-vaccination ARR was 0.189 (95% CI: 0.167-0.213). The ARR of a matched unvaccinated reference group from 2020 was 0.147 (0.129-0.167). Another reference cohort of vaccinated PwMS showed no indication of increased post-vaccination relapse activity (0.116; 0.088-0.151) compared to pre-vaccination (0.109; 0.084-0.138). Predictors of post-vaccination relapses (study cohort) were missing immunotherapy (OR = 2.09; 1.55-2.79; p < 0.001) and shorter time from the last pre-vaccination relapse to the first vaccination (OR = 0.87; 0.83-0.91; p < 0.001). Data on disease activity of the study cohort in the temporal context are expected for the third follow-up.

Occurrence and Risk Factors of Relapse Activity after Vaccination against COVID-19 in People with Multiple Sclerosis: 1-Year Follow-Up Results from a Nationwide Longitudinal Observational Study.

Several studies reported post-SARS-CoV-2-vaccination (PV) symptoms. Even people with multiple sclerosis (PwMS) have concerns about disease activity following the SARS-CoV-2 vaccination. We aimed to determine the proportion of PwMS with PV relapses, the PV annualized relapse rate (ARR), the time from vaccination to subsequent relapses, and identify sociodemographic/clinical risk factors for PV relapses. PwMS were surveyed several times at baseline and four follow-ups as part of a longitudinal observational study regarding the safety and tolerability of the SARS-CoV-2 vaccination. The inclusion criteria for this analysis were age ≥18 years, ≥1 SARS-CoV-2 vaccination, and ≥1-year observation period since initial vaccination. Of 2466 PwMS, 13.8% reported PV relapses (mostly after second [N = 147] or booster vaccination [N = 145]) at a median of 8.0 (first/third quantile: 3.55/18.1) weeks PV, with the shortest period following initial vaccination (3.95 weeks). The ARR was 0.153 (95% confidence interval: 0.138-0.168), with a median observation period since initial vaccination of 1.2 years. Risk factors for PV relapses were younger age, female gender, moderate-severe disability levels, concurrent autoimmune diseases, relapsing-remitting MS courses, no DMT, and relapses within the year prior to the first vaccination. Patients' health conditions before/during initial vaccination may play a more important role in PV relapse occurrence than vaccination per se.

SARS-CoV-2 vaccination in patients with multiple sclerosis in Germany and the United Kingdom: Gender-specific results from a longitudinal observational study.

Background: Vaccines offer people with multiple sclerosis (PwMS) an effective protection against severe COVID-19 disease courses. However, representative real-world data on the tolerability of SARS-CoV-2 vaccines in PwMS are limited. We aimed at analysing vaccination reactions (VRs) and MS deterioration following SARS-CoV-2 vaccinations in German and United Kingdom (UK) PwMS, especially regarding gender-specific differences. Methods: The German Multiple Sclerosis Society and the UK MS Registry acquired health data via an online system following the first (X1) and second SARS-CoV-2 vaccination (X2), respectively: sociodemographic and clinical data, vaccines used, VRs, MS deterioration (worsened or new MS symptoms, Germany only) and relapses (Germany only). The frequencies of VRs and MS deterioration were analysed stratified by gender. Findings: Following X1 (X2), 2346 (1835) German PwMS and 3796 (683) UK PwMS participated in the study. The most frequent vaccination scheme was two-dose tozinameran for Germany (77·1%, 1424/1847) and two-dose AZD1222 for the UK (61·3%, 419/683). The most common VRs were fatigue, headache and pain (at the injection site) and occurred more often in women compared with men. German PwMS reported VRs more frequently after X2 vs. X1 (65·4% [1201/1835] vs. 61·2% [1435/2346]), while for UK patients it was the opposite (X1 vs. X2: 48·7% [1849/3796] vs. 30·0% [205/683]). MS deterioration occurred in 19·0% (445/2346) of the German PwMS without resulting in gender-specific differences. Fatigue and gait impairment were the most frequent deteriorated MS symptoms. Interpretation: Female PwMS reported experiencing VRs more often than men. Longitudinal data are needed to enable valid statements regarding long-term MS deterioration and long-lasting VRs. Funding: German Multiple Sclerosis Society (DMSG Bundesverband e.V.), Biogen, Bristol Myers Squibb, Merck Serono, Mylan, Novartis, Roche and Sanofi.

Aneurysmal Subarachnoid Hemorrhage during the Shutdown for COVID-19.

The aim was to evaluate hospitalization rates for aneurysmal subarachnoid hemorrhage (SAH) within an interdisciplinary multicenter neurovascular network (NVN) during the shutdown for the COVID-19 pandemic along with its modifiable risk factors. In this multicenter study, admission rates for SAH were compared for the period of the shutdown for the COVID-19 pandemic in Germany (calendar weeks (cw) 12 to 16, 2020), the periods before (cw 6-11) and after the shutdown (cw 17-21 and 22-26, 2020), as well as with the corresponding cw in the years 2015-2019. Data on all-cause and pre-hospital mortality within the area of the NVN were retrieved from the Department of Health, and the responsible emergency medical services. Data on known triggers for systemic inflammation, e.g., respiratory viruses and air pollution, were analyzed. Hospitalizations for SAH decreased during the shutdown period to one-tenth within the multicenter NVN. There was a substantial decrease in acute respiratory illness rates, and of air pollution during the shutdown period. The implementation of public health measures, e.g., contact restrictions and increased personal hygiene during the shutdown, might positively influence modifiable risk factors, e.g., systemic inflammation, leading to a decrease in the incidence of SAH.

Insomnia in neurological diseases.

Insomnia is defined as difficulties of initiating and maintaining sleep, early awakening and poor subjective sleep quality despite adequate opportunity and circumstances for sleep with impairment of daytime performance. These components of insomnia - namely persistent sleep difficulties despite of adequate sleep opportunity resulting in daytime dysfunction - appear secondary or co-morbid to neurological diseases. Comorbid insomnia originates from neurodegenerative, inflammatory, traumatic or ischemic changes in sleep regulating brainstem and hypothalamic nuclei with consecutive changes of neurotransmitters. Symptoms of neurological disorders (i.e motor deficits), co-morbidities (i.e. pain, depression, anxiety) and some disease-specific pharmaceuticals may cause insomnia and/or other sleep problems.This guideline focuses on insomnias in headaches, neurodegenerative movement disorders, multiple sclerosis, traumatic brain injury, epilepsies, stroke, neuromuscular disease and dementia.The most important new recommendations are: Cognitive behavioral therapy (CBTi) is recommended to treat acute and chronic insomnia in headache patients. Insomnia is one of the most frequent sleep complaints in neurodegenerative movement disorders. Patients may benefit from CBTi, antidepressants (trazodone, doxepin), melatonin and gaba-agonists. Insomnia is a frequent precursor of MS symptoms by up to 10 years. CBTi is recommended in patients with MS, traumatic brain injury and. Melatonin may improve insomnia symptoms in children with epilepsies. Patients with insomnia after stroke can be treated with benzodiazepine receptor agonists and sedating antidepressants. For patients with dementia suffering from insomnia trazodone, light therapy and physical exercise are recommended.

Quality of life and life circumstances in German myasthenia gravis patients.

BACKGROUND: Myasthenia gravis (MG) is a chronic neuromuscular disease. Advances in medical therapy have continuously increased the life expectancy of MG patients, without definitively curing the disease. To analyze life circumstances and quality of life (QoL), a large German MG cohort was investigated. METHODS AND SAMPLE: In cooperation with the German Myasthenia Association, 2,150 patients with confirmed MG were asked to respond to a mailed questionnaire. The standardized questions related to demographic data, impairments, therapeutic course, use of complementary therapies, illness-related costs, and quality of life (SF-36). In total, 1,518 patients participated, yielding a response rate of 70.6%. The average age was 56.7 years, and the proportion of females 58.6%. RESULTS: Despite receiving recommended therapy, many patients still suffered from MG-related impairments. In particular, mobility and mental well-being were reduced; moreover, quality of life was markedly reduced. Stepwise linear regression analysis revealed illness stability, impairments, mental conditions, comorbid diseases, and employment to be determinants of QoL. CONCLUSION: Results indicate that despite prolonged life expectancy among MG patients, health-related quality of life is low. This outcome resulted mainly from impaired mobility and depression. Physical and mental well-being might be improved by additional therapy options. Additionally, health care resources could be used more efficiently in these patients.

Disability status and quality of life in multiple sclerosis: non-linearity of the Expanded Disability Status Scale (EDSS).

BACKGROUND: Progression in disability as measured by increase in the Expanded Disability Status Scale (EDSS) is commonly used as outcome variable in clinical trials concerning multiple sclerosis (MS). In this study, we addressed the question, whether there is a linear relationship between disability status and health related quality of life (HRQOL) in MS. METHODS: 7305 MS patients were sent a questionnaire containing a German version of the "Multiple Sclerosis Quality of Life (MSQOL)-54" and an assessment of self-reported disability status analogous to the EDSS. 3157 patients participated in the study. Patients were allocated to three groups according to disability status. RESULTS: Regarding the physical health composite and the mental health composite as well as most MSQOL-54 subscales, the differences between EDSS 4.5-6.5 and EDSS > or = 7 were clearly smaller than the differences between EDSS < or = 4 and EDSS 4.5-6.5. CONCLUSION: These results indicate a non-linear relationship between disability status and HRQOL in MS. The EDSS does not seem to be interval scaled as is commonly assumed. Consequently, absolute increase in EDSS does not seem to be a suitable outcome variable in MS studies.

Relapsing and progressive MS: the sex-specific perspective.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease whose aetiology is not fully understood. The female sex is clearly predominant, with a sex ratio between 2 and 3. In primary progressive MS the sex ratio almost balances out. Since the age at onset is higher for patients with progressive onset (POMS) than for relapsing onset (ROMS), it can be hypothesized that the age at onset is a decisive factor for the sex ratio. METHODS: To address this aspect, we compare clinical and demographic data between females and males for the different disease courses within the population of the German MS Register by the German MS Society. Only patients with complete details in mandatory data items and a follow-up visit since 01. Jan 2018 were included. RESULTS: A total of 18,728 patients were included in our analyses, revealing a female-to-male ratio of 2.6 (2.7 for patients with ROMS and 1.3 for POMS). The age at diagnosis is higher in patients with POMS (43.3 and 42.3 years for females and males versus 32.1 and 33.2 years, respectively). Females irrespective of disease course are statistically significantly more often affected by cognitive impairment (POMS: p = 0.013, ROMS: p = 0.001) and depression (POMS: p = 0.002, ROMS: 0.001) and suffer more often from pain (POMS and ROMS: p < 0.001). Fatigue is significantly more often seen in females with ROMS (p < 0.001) but not in POMS. Females with ROMS retire significantly (p < 0.001) earlier (42.8 versus 44.2 years) and to a greater extent than males (28 versus 24%). Disease progression was similar for women and men. CONCLUSION: Our analysis shows that clinical and demographic data differ more between disease courses than between men and women. For pain, depression and cognitive impairment the female sex is the decisive factor. Whether these factors are responsible for the earlier retirement of females with ROMS is not clear. Appropriate measures for optimization of symptomatic treatment as well as to promote employment should be taken.

Adherence to Subcutaneous IFN ß-1a in Multiple Sclerosis: Final Analysis of the Non-Interventional Study READOUTsmart Using the Dosing Log and Readout Function of RebiSmart®.

INTRODUCTION: Patient adherence is a key determinant of treatment success in multiple sclerosis (MS). The RebiSmart® autoinjector facilitates patient self-injection of subcutaneous interferon ß-1a (sc IFN ß-1a) and allows quantitative measurement of adherence via its automated dosing log. We evaluated patient adherence and patient-reported cognitive and health-economic outcomes over 2 years in patients using RebiSmart®. METHODS: In this non-interventional, single-arm study, enrolled patients were 12-65 years of age, had relapsing-remitting MS or a single demyelinating event, and had been prescribed 44 or 22 µg sc IFN ß-1a. Quantitative adherence (proportion of scheduled injections administered) and qualitative adherence (proportion of weeks with treatment schedule correctly followed) were monitored over 2 years. Other end points included self-assessed adherence, patient-reported outcomes (fatigue, depression and quality of life), cognitive outcomes and health-economic outcomes. RESULTS: A total of 368 of 392 (93.9%) enrolled patients were analyzed. Mean quantitative adherence was 85.3% overall (months 1-24), 89.6% for months 1-12 and 83.3% for months 13-24. No major impact on quantitative adherence was observed for sex, age (< 37 years vs. ≥ 37 years), prior medication or participation in the patient support program RebiSTAR®. Mean qualitative adherence was 67.0% overall (months 1-24). Self-assessed adherence was reported as being higher than RebiSmart®-monitored adherence. There was a trend toward more MS-related visits to physicians among patients with high adherence. CONCLUSIONS: Patients using RebiSmart® demonstrated high adherence to treatment that was associated with a slight improvement in information processing speed and working memory and an overall tendency for more intensive self-management. FUNDING: Merck Serono GmbH, Germany, an affiliate of Merck KGaA, Darmstadt, Germany.

Successful treatment of methicillin-resistant Staphylococcus aureus meningitis using linezolid without removal of intrathecal infusion pump. Case report.

Infection of an intrathecal pump system is a rare but serious complication and usually leads to the removal of the pump. The authors report the first case of methicillin-resistant Staphylococcus aureus (MRSA) meningitis in a patient with such a pump successfully treated with linezolid without the need for removal of the intrathecal pump. A 77-year-old woman with cervical myelopathy underwent implantation of an intrathecal pump system for baclofen administration. Two weeks after the procedure she developed meningitis caused by MRSA as isolated in cerebrospinal fluid (CSF) cultures, blood samples, and serum obtained from the pump pouch. Clinically she presented with meningism, somnolence, and signs of sepsis. When a combined intravenous antibiotic treatment regimen of vancomycin and rifampicin resulted in no clinical improvement, that regimen was discontinued and linezolid was administered intravenously as monotherapy. Within 3 days clinical and laboratory findings showed significant improvement. After 1 week of linezolid treatment, blood and CSF cultures were sterile. Intravenous treatment was administered for a total of 3 weeks, after which the patient was treated with oral linezolid for 3 months. During 18 months of follow-up, no new clinical or laboratory signs of infection were observed. These results confirm previous reports of the efficacy of linezolid for the treatment of severe infections of the central nervous system caused by multidrug-resistant Gram-positive bacteria, especially postneurosurgical infections.

Botulinum toxin in patients with multiple sclerosis.

Nearly all patients with multiple sclerosis (MS) will develop spasticity in the course of their disease. This symptom accounts for most of the handicap and impairment in the quality of life. Treatment with botulinum toxin will enable an efficient and safe alleviation of spasticity and the problems involved, given a realistic definition of the therapeutic target and a graded multimodal approach. Treatment may fail for a great number of reasons that require diligent analysis. Compared with other disorders resulting in spasticity as well, MS does not constitute a monophasic disorder but is influenced by many factors. Treatment of spasticity in MS must therefore be guided by its particular aspects.

Hashimoto's encephalopathy and motor neuron disease: a common autoimmune pathogenesis?

Hashimoto's encephalopathy is a rare complication of autoimmune thyroiditis not associated with thyroidal function decline. We report a 50-year-old man presenting with lower motor neuron symptoms evolving over 3 years and changes in behavior associated with attentive and cognitive impairment occurring in the last few months. Memory deficits, emotional instability, marked dysarthria, mild symmetric weakness of the lower extremities and fasciculations were the most striking clinical features. EEG was diffusely slow, cranial MRI revealed multiple subcortical white matter lesions, CSF protein was slightly elevated, electromyographic recordings showed acute and chronic denervation and extremely high TPO antibody titers were found in the serum. Hashimoto's encephalopathy and lower motor neuron disease were diagnosed. As repeated high-dose intravenous methylprednisolone administration followed by oral tapering improved both central nervous system and lower motor neuron symptoms, the question was raised whether there was a common autoimmune pathogenesis of both clinically distinct diseases.