Primary cerebral immunoglobulin light chain amyloidoma in a patient with multiple sclerosis.

A man in his 60s, known with multiple sclerosis, presented with seizures and paresis of the left arm and leg. Brain imaging showed a white matter lesion, right parietal, which was progressive over the last 6 years and not typical for multiple sclerosis. Brain biopsy showed a B-cell infiltrate with IgA lambda monotypic plasma cell differentiation and amyloid deposits, typed as lambda immunoglobulin light chain (AL). Bone marrow biopsy and PET/CT ruled out a systemic lymphoma. Extended history taking, blood and urine testing (including cardiac biomarkers) identified no evidence of systemic amyloidosis-induced organ dysfunction.Primary cerebral AL amyloidoma is a very rare entity where optimal treatment is difficult to assess. The patient was treated with locally applied volumetric modulated arc radiotherapy, 24 Gy, divided in 12 fractions. Afterwards, the paresis of the left arm partially resolved, and the function of the left leg improved. Seizures did not occur anymore.

Self-reported work productivity in people with multiple sclerosis and its association with mental and physical health.

PURPOSE: This study aimed to identify mental health, physical health, demographic and disease characteristics relating to work productivity in people with multiple sclerosis (MS). METHODS: In this cross-sectional study, 236 employed people with MS (median age = 42 years, 78.8% female) underwent neurological and neuropsychological assessments. Additionally, they completed questionnaires inquiring about work productivity (presenteeism: reduced productivity while working, and absenteeism: loss of productivity due to absence from work), mental and physical health, demographic and disease characteristics. Multiple linear and logistic regression analyses were performed with presenteeism and absenteeism as dependent variables, respectively. RESULTS: A model with mental and physical health factors significantly predicted presenteeism F(11,202) = 11.33, p < 0.001, R2 = 0.38; a higher cognitive (p < 0.001) and physical impact (p = 0.042) of fatigue were associated with more presenteeism. A model with only mental health factors significantly predicted absenteeism; χ2(11)=37.72, p < 0.001, with R2 = 0.27 (Nagelkerke) and R2 = 0.16 (Cox and Snell). Specifically, we observed that more symptoms of depression (p = 0.041) and a higher cognitive impact of fatigue (p = 0.011) were significantly associated with more absenteeism. CONCLUSIONS: In people with MS, both cognitive and physical impact of fatigue are positively related to presenteeism, while symptoms of depression and cognitive impact of fatigue are positively related to absenteeism.Implications for rehabilitationMultiple sclerosis (MS) affects people of working age, significantly interfering with work productivity.Higher cognitive and physical impact of fatigue were associated with more presenteeism in workers with MS.A higher cognitive impact of fatigue and more depressive symptoms were associated with absenteeism in workers with MS.Occupational and healthcare professionals should be aware of the impact of both physical and mental health on work productivity in workers with MS.

Varicella zoster-associated acute retinal necrosis and central nervous system complications in natalizumab treated MS patients.

There is not much awareness of varicella zoster virus (VZV) associated central nervous system (CNS) infections under treatment with natalizumab. Here we describe two natalizumab treated MS patients who developed acute retinal necrosis combined with CNS vasculitis caused by VZV. In natalizumab treated patients, visual symptoms atypical of optic neuritis should be promptly evaluated by an ophthalmologist. Currently, a total of 12 cases of natalizumab-associated VZV CNS or retinal infections are reported in literature. Our two cases and overview of currently available data provide information on prognosis and treatment decisions of this rare but devastating complication.

A Dutch validation study of the Multiple Sclerosis Work Difficulties Questionnaire in relapsing remitting multiple sclerosis.

PURPOSE: The current study aimed to evaluate the psychometric properties of the Dutch version of the Multiple Sclerosis Work Difficulties Questionnaire-23 (MSWDQ-23). METHODS: Two hundred and thirty-nine employed persons with multiple sclerosis (MS) and 59 healthy controls completed the MSWDQ-23. To verify the factor structure, a confirmatory factor analysis was conducted. To assess construct validity, the MSWDQ-23 scores were correlated to measures of physical disability, fatigue, cognitive and neuropsychiatric problems, depression, health-related quality of life, and work-related variables. MSWDQ-23 scores were compared within different age groups, gender, education levels, and job types. Predictive validity was assessed using a logistic regression analysis to predict a deterioration in employment status after one year based on MSWDQ-23 scores. RESULTS: The internal consistency of the MSWDQ-23 was acceptable (α = 0.913, 95% CI = 0.897-0.928) and the results indicated a fair fit. The MSWDQ-23 showed acceptable construct validity, confirming 94% of the hypotheses. The total scale and the psychological/cognitive subscale were able to predict a deterioration in employment status after one year (χ2(1)=18.164, p < 0.001). CONCLUSIONS: The Dutch version of the MSWDQ-23 is a valid and internally consistent instrument to measure self-reported work difficulties in persons with MS.Implications for rehabilitationThe Dutch version of the 23-item Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ-23) is a reliable and valid tool to measure self-reported work difficulties in people with multiple sclerosis (MS).More psychological and cognitive work difficulties are predictive of a deteriorated employment status after one year.The MSWDQ-23 is a helpful tool for researchers and (occupational) health professionals to identify current work difficulties in persons with MS and identify persons at risk for a deterioration in employment one year later.

Cognitive functioning as a predictor of employment status in relapsing-remitting multiple sclerosis: a 2-year longitudinal study.

BACKGROUND: Cognitive functioning has been linked to employment outcomes in multiple sclerosis (MS) in cross-sectional studies. Longitudinal studies are however lacking and previous studies did not extensively examine executive functioning. OBJECTIVES: We examined whether baseline cognitive functioning predicts a change in employment status after 2 years, while taking into account mood, fatigue and disability level. METHODS: A total of 124 patients with relapsing-remitting MS (pwMS) and 60 healthy controls were included. They underwent neurological and neuropsychological examinations and completed online questionnaires. PwMS were divided into a stable and deteriorated employment status group (SES and DES), based on employment status 2 years after baseline. We first examined baseline differences between the SES and DES groups in cognitive functioning, mood, fatigue and disability level. A logistic regression analysis was performed, with change in employment status (SES/DES) as dependent variable. RESULTS: The DES group included 22% pwMS. Group differences were found in complex attention, executive functioning, self-reported cognitive functioning, fatigue and physical disability. More physical disability (OR = 1.90, p = 0.01) and lower executive functioning (OR = 0.30, p = 0.03) were retained as independent predictors of DES (R2 = 0.22, p ≤ 0.001). CONCLUSIONS: Baseline physical disability and executive functioning, but none of the other variables, moderately predicted a deterioration in employment status 2 years later. TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. This study is registered at the Dutch CCMO register (https://www.toetsingonline.nl).

Subacute Combined Spinal Cord Degeneration by Recreational Laughing Gas (N2O) Use.

BACKGROUND: A few young patients were brought in with subacute combined spinal cord degeneration at the Department of Neurology in our hospital. They all have used laughing gas for recreational purposes. CASE: A 30-year-old woman, known with alcohol abuse, was presented to our Department of Neurology for having paresthesia and unstable movements of arms, legs, and trunk for 9 days. She has used 50 laughing gas patterns per day. The diagnosis of laughing gas-induced combined spinal cord degeneration was evident by the low count of vitamin B12 combined with lesions shown on magnetic resonance imaging (MRI). Abstaining from the laughing gas, weekly intramuscular injections of hydroxocobalamin and revalidation, she was fully recovered in 8 weeks. CONCLUSIONS: Recreational use of laughing gas seems to be more used in our society, however, without having any knowledge of the neurological consequences. The right diagnosis and treatment can provide full recovery in these patients. Furthermore, attention for this diagnosis can help increase social awareness.

Inflammatory natalizumab-associated PML: baseline characteristics, lesion evolution and relation with PML-IRIS.

BACKGROUND AND OBJECTIVE: Natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) patients may show imaging signs suggestive of inflammation at diagnosis ('inflammatory PML'), reminiscent of PML-immune reconstitution inflammatory syndrome (PML-IRIS). We investigated the imaging characteristics of inflammatory NTZ-PML lesions and PML-IRIS to determine differentiating and overlapping features. METHODS: We scored the presence, localisation and pattern of imaging characteristics of inflammation on brain MRI scans of inflammatory NTZ-PML patients. The imaging characteristics were followed up until the occurrence of PML-IRIS. RESULTS: Ten out of the 44 NTZ-PML patients included showed signs suggestive of inflammation at the time of diagnosis. The inflammation pattern at diagnosis was similar to the pattern seen at PML-IRIS, with contrast enhancement representing the most frequent sign of inflammation (90% at diagnosis, 100% at PML-IRIS). However, the severity of inflammation differed, with absence of swelling and low frequency of perilesional oedema (10%) at diagnosis, as compared with the PML-IRIS stage (40%). CONCLUSION: Patterns of inflammation at the time of PML diagnosis and at the PML-IRIS stage overlap but differ in their severity of inflammation. This supports histopathological evidence that the inflammation seen at both stages of the same disease shares a similar underlying pathophysiology, representing the immune response to the JC virus to a variable extend.

MRI pattern in asymptomatic natalizumab-associated PML.

OBJECTIVE: To investigate the MRI manifestation pattern of asymptomatic natalizumab-associated progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS). METHODS: 18 patients with MS with natalizumab-associated PML lesions on MRI were included. In 6 patients, the PML lesions were identified on MRI prospectively and in 12 patients PML lesions were identified retrospectively. MRI sequences were analysed for PML lesion distribution, appearance, grey matter/white matter involvement and possible signs of inflammation. Lesion probability maps were created to demonstrate lesion distribution pattern. RESULTS: The frontal lobe was involved in 14 patients (77.8%) and the parietal lobe in 4 patients (22.2%). Most patients presented with focal lesions (13 patients, 72.2%) involving one single lobe (12 patients, 66.7%). The cortical grey matter was affected in 15 patients (83.3%) and 13 patients (72.2%) presented with a combination of cortical grey and white matter involvement. Signs of inflammation were detected in 7 patients (38.8%). Among patients with available diffusion-weighted imaging, 6 patients (40%) did not show high-signal-intensity lesions. A classical imaging pattern including unilateral and unilobar focal lesions in the frontal lobe affecting the cortical grey matter or the cortical grey and adjacent white matter was observed in 8 patients (44.4%). CONCLUSIONS: Asymptomatic natalizumab-associated PML manifestations on MRI show a rather localised disease, frequently located in the frontal lobes, affecting the cortical grey matter and adjacent juxtacortical white matter. Awareness of this lesion pattern facilitates an earlier diagnosis of natalizumab-associated PML in an asymptomatic stage associated with a more favourable prognosis.

Cerebrospinal Venous Outflow in Multiple Sclerosis Patients versus Fatigue and/or Depression.

BACKGROUND: Endovascular treatment of impaired cerebrospinal venous outflow has been suggested to improve the overall quality of life in multiple sclerosis (MS) patients. Fatigue and depression are key factors in measuring the quality of life in MS patients. OBJECTIVE: In the present study, we investigated the correlation between anomalous venous outflow and the seriousness of fatigue and depression in MS patients and healthy controls. METHODS: Five cerebrospinal venous outflow parameters were measured in 20 MS patients and age- and sex-matched controls using extra- and transcranial Colour Doppler sonography. All patients and volunteers filled out the Fatigue Severity Scale (FSS) and Hospital Anxiety Depression Subscale (HADS). RESULTS: Nine abnormal parameters were found in 8 MS patients, whereas five abnormal parameters were found in 3 healthy controls (no significant difference). Only 1 MS patient met the criteria for chronic cerebrospinal venous insufficiency compared to 2 healthy controls. No significant differences were found in the FSS and HADS scores between patients with and without abnormal cerebrospinal venous outflow parameters. CONCLUSIONS: We found no significantly impaired cerebrospinal venous outflow in patients with MS versus sex- and age-matched controls. Furthermore, we did not find any correlation between anxiety or depression and impaired venous outflow in MS patients.

Fatigue and health-related quality of life in relapsing-remitting multiple sclerosis after 2 years glatiramer acetate treatment are predicted by changes at 6 months: an observational multi-center study.

Observational studies of up to 12 months duration showed that glatiramer acetate (GA) treatment of relapsing-remitting multiple sclerosis may result in decreased fatigue and improves health-related quality of life (HRQoL), with no changes in disability or mood. We investigated whether in the second year of treatment these improvements are sustained, disability or mood yet improved, and 2-year changes may be predicted by changes in the first 6 or 12 months. The multi-center FOCUS-Extension study was a prospective extension of the 12-month, international, observational FOCUS study and included 67 patients (38 treatment-naïve, 29 pre-treated) of the Dutch FOCUS cohort. Fatigue, HRQoL, depression and disability were measured by the Fatigue Impact Scale (FIS), Leeds Multiple Sclerosis Quality of Life (LMSQoL) questionnaire, Beck Depression Inventory-Short Form and the Guy's Neurological Disability Scale. A 2-year period of GA treatment was associated with -0.52 and +0.66 standard deviation changes in mean FIS and LMSQoL scores compared to baseline, whereas disability and mood remained unchanged. For FIS and LMSQoL, the Pearson correlation coefficients between 6-month changes and 2-year scores were 0.47 and 0.50, and between 12-month changes and 2-year scores 0.65 and 0.62. After 2 years GA treatment, the improvements in fatigue and HRQoL observed at 1 year are sustained, whereas disability and mood remain unchanged compared to baseline. Moreover, the levels of fatigue and HRQoL at 2 years GA treatment are predicted by the improvements at 6 months.

[A woman with a postoperative lumbar swelling]. / Een vrouw met een postoperatieve lumbale zwelling.

A 65-year-old woman had developed a large lumbar swelling in a period of four weeks following lumbar laminectomy. An MRI-scan revealed a large fluid collection, which had formed from the spinal canal. The diagnosis 'liquorcele', a rare complication of spine surgery, was established.

Adverse events of interferon beta-1a: a prospective multi-centre international ICH-GCP-based CRO-supported external validation study in daily practice.

BACKGROUND: Due to methodological shortcomings the available post-registration data on the adverse events (AEs) occurring in interferon beta-1a (INFb-1a)-treated patients fail to adequately validate phase III data and only partially inform on safety in daily practice. We assessed AEs in relapsing remitting multiple sclerosis (RRMS) patients treated with intramuscular (IM) INFb-1a in daily practice using data quality assurance measures similar to those in phase III trials. METHODS: A prospective, International Conference on Harmonization (ICH) - Good Clinical Practice (GCP)-based, clinical research organization (CRO)-supported study in 36 practices in the Netherlands, Belgium, the United Kingdom and Luxembourg. During 24 months after start of IM INFb-1a treatment 275 RRMS patients were assessed for AEs' severity (mild, moderate, severe) and relationship to treatment (not, unlikely, likely, definite). Data were compared with those reported in the pivotal phase III trial. FINDINGS: 75.3% of the patients experienced one or more AEs that were likely or definitely related to INFb-1a. Of all AEs 40.5% were likely or definitely treatment-related; 68.5% of these were mild, and 3% severe. 6.6% of the patients discontinued treatment because of an AE. Compared to the pivotal phase III trial, we found statistically significantly lower incidences for most of the common AEs: headache, muscle ache, fatigue, fever, chills, nausea. One patient died following two cerebral vascular events in study month 22, both AEs were assessed as not related to INFb-1a. CONCLUSION: Three out of four RRMS patients treated with IM INFb-1a in daily practice experience treatment-related AEs, most of these being mild. Our data externally validate the favorable phase III safety profile of IM INFb-1a and suggest that the real-life incidence of treatment-related AEs is less than reported in the pivotal phase III trial. Larger studies are needed to detect rare, potentially hazardous AEs of IM INFb-1a.

Daily negative interactions and mood among patients and partners dealing with multiple sclerosis (MS): the moderating effects of emotional support.

Negative interactions with intimate partners may have adverse consequences for well-being, especially for individuals dealing with chronic illness. However, it is not clear whether negative interactions affect both dimensions of positive and negative well-being and factors that may moderate this effect have not been well-described. The aim of the present study was to examine the association between daily received negative responses from the partner and end-of-day positive and negative mood in patients with multiple sclerosis (MS) and their intimate partners. Further, the moderating role of receiving emotional support from the partner on the same day was examined. Sixty-one MS patients and their intimate partners were approached via one MS centre and the neurology department of one hospital in the Netherlands and completed computerized diaries for 14 days. Both partners filled out diaries at the end of each day, recording received negative responses, emotional support and end-of-day positive and negative mood. In line with a domain specific model, patients or partners who reported receiving negative responses on a day had higher end-of-day negative mood, whereas received negative responses were unrelated to end-of-day positive mood. Further, for both patients and partners, the adverse effect of received negative responses on end-of day mood was moderated by receiving emotional support on the same day.