Influence of age at disease onset on future relapses and disability progression in patients with multiple sclerosis on immunomodulatory treatment.

BACKGROUND AND PURPOSE: To investigate the relation of age at disease onset and clinical outcomes across the lifespan from adolescence in patients with multiple sclerosis (MS) on disease-modifying therapy (DMT). METHODS: We analysed data from the Swiss Association for Joint Tasks of Health Insurers database containing data from 14 718 patients with MS. Patients were included in this analysis when they were on DMT for at least 1 year. The influence of age at disease onset on future relapses and disability worsening was explored using multivariable Cox proportional hazard regression models. RESULTS: Data from 9705 patients with MS were analysed. Pediatric-onset MS patients (n = 236) had higher relapse rates and marginally slower disability worsening rates compared with adult-onset MS (n = 9469). The risk of relapses was highest in childhood and decreased continuously to about 35 years of age. It remained stable for about a decade and then again continuously decreased. In contrast, disability worsening hazards remained stable from childhood to about 32 years of age and then increased sharply around the age of 45 years. CONCLUSIONS: Age is an important factor independently affecting clinical outcomes in MS. This should be considered when designing clinical trials or choosing DMT.

Nerve ultrasound as follow-up tool in treated multifocal motor neuropathy.

BACKGROUND AND PURPOSE: High-resolution ultrasound is a valuable tool in supporting the diagnosis of multifocal motor neuropathy (MMN) but longitudinal data under therapy are lacking. METHODS: The change in peripheral nerve ultrasound pattern in patients with MMN was assessed over time. Patients with MMN received a thorough initial examination and follow-up over a period of 6-12 months using high-resolution ultrasound of the cervical roots and the nerves of the arms and legs, nerve conduction studies, Medical Research Council Sum Score (MRCSS) and Rotterdam Inflammatory Neuropathy Cause and Treatment Group (INCAT) score to evaluate changes under treatment. The Ultrasound Pattern Sum Score (UPSS) was used as standardized peripheral nerve ultrasound protocol. RESULTS: Seventeen patients with MMN received initial examinations of whom 12 were successfully followed up. All patients with MMN showed at least localized but often multifocal peripheral nerve enlargement. An enlarged overall cross-sectional area as well as enlarged single fascicles (>3 mm²) in clinically and electrophysiologically affected (>90%) and unaffected (>70%) nerves were found. The UPSS did not correlate with clinical disability at both visits. However, the change in clinical disability (evaluated as difference in MRCSS) and the change in UPSS correlated significantly inversely (P = 0.004). CONCLUSIONS: High-resolution sonography of peripheral nerves revealed multifocal nerve enlargement in MMN. Distinct enlargement patterns may support the diagnosis. Ultrasound findings did not correlate well with clinical severity or electrophysiological findings at initial presentation. As changes in UPSS correlated significantly with the clinical course in terms of muscle strength (MRCSS), sonographic assessment may represent a useful tool for therapeutic monitoring.

Muscle ultrasonography as an additional diagnostic tool for the diagnosis of amyotrophic lateral sclerosis.

OBJECTIVE: We aimed to determine the utility of muscle ultrasonography (MUS) in addition to electromyography (EMG) in the diagnosis of amyotrophic lateral sclerosis (ALS). METHODS: In all, 60 patients with ALS and 20 with other neuromuscular disorders underwent MUS and EMG. In addition, 30 healthy controls underwent only MUS. Occurrence of fasciculations and fibrillations was evaluated. Ultrasonic echogenicity was graded semiquantitatively. RESULTS: The incidence of fasciculations was significantly higher in patients undergoing MUS than in those undergoing EMG (p<0.05), even in muscles of full strength (p<0.001). However, EMG was more sensitive in detecting fibrillations (p<0.05). MUS had an overall higher sensitivity in detecting spontaneous activity in the tongue (p<0.05). Patients with ALS showed significantly increased muscle echo intensity (EI) compared to patients who were initially suspected as having ALS and normal controls (p<0.05), irrespective of the clinical or electrophysiological status. CONCLUSION: Our results showed that the sensitivity and specificity of MUS in diagnosing ALS was almost equivalent to those of EMG, using the Awaji criteria. Combination of MUS and EMG enhances the diagnostic accuracy compared to EMG alone (p<0.05). SIGNIFICANCE: The combination of EMG and MUS can be used to evaluate the lower motor neuron affection by reducing the use of the often painful and uncomfortable EMG examinations but without decreasing the diagnostic sensitivity and specificity.

Serum antibodies to conformational and linear epitopes of myelin oligodendrocyte glycoprotein are not elevated in the preclinical phase of multiple sclerosis.

BACKGROUND: The proposed predictive value of serum anti-myelin antibodies for the development of multiple sclerosis after a first clinically isolated syndrome was recently challenged. OBJECTIVE: To investigate myelin autoantibodies before first disease manifestation using different detection methods. METHODS: Patients with multiple sclerosis who had donated blood at a time prior to development of clinically isolated syndrome were identified via the German National Multiple Sclerosis Society. Control sera were obtained from age- and gender-matched blood donors. IgG-/IgM-antibodies against the extracellular part of native, cell surface-expressed myelin oligodendrocyte glycoprotein were detected by flow cytometry. Antibodies against linear epitopes were identified by immunoblot using recombinant myelin oligodendrocyte glycoprotein (aa1-125) and human myelin basic protein preparations. RESULTS: Fifty eight serum samples from 25 patients covering an interval of 7.3 years-2 months prior to disease onset were available. Longitudinal investigations were performed in 19 patients (2-14 samples per patient, 7 years-2 months prior to disease onset). No significant differences in the prevalence or titres of anti-myelin antibodies were detected between sera of preclinical individuals and healthy donors by either flow cytometry or immunoblot. There was no correlation between interval before clinically isolated syndrome and autoantibody status. Occurrence of antibodies was not associated with symptomatology/severity of clinically isolated syndrome. CONCLUSION: Neither anti-myelin autoantibodies against cell surface-expressed native myelin oligodendrocyte glycoprotein nor against linear epitopes have a predictive or discriminative role during the preclinical disease phase for developing clinically isolated syndrome or multiple sclerosis later in life.