The role of human endogenous retroviruses (HERVs) in disease pathogenesis is unclear. We show that HERV-K is activated in a subpopulation of patients with sporadic amyotrophic lateral sclerosis (ALS) ...and that its envelope (env) protein may contribute to neurodegeneration. The virus was expressed in cortical and spinal neurons of ALS patients, but not in neurons from control healthy individuals. Expression of HERV-K or its env protein in human neurons caused retraction and beading of neurites. Transgenic animals expressing the env gene developed progressive motor dysfunction accompanied by selective loss of volume of the motor cortex, decreased synaptic activity in pyramidal neurons, dendritic spine abnormalities, nucleolar dysfunction, and DNA damage. Injury to anterior horn cells in the spinal cord was manifested by muscle atrophy and pathological changes consistent with nerve fiber denervation and reinnervation. Expression of HERV-K was regulated by TAR (trans-activation responsive) DNA binding protein 43, which binds to the long terminal repeat region of the virus. Thus, HERV-K expression within neurons of patients with ALS may contribute to neurodegeneration and disease pathogenesis.
Summary Survival in people infected with HIV has improved because of an increasingly powerful array of antiretroviral treatments, but neurological symptoms due to comorbid conditions, including ...infection with hepatitis C virus, malnutrition, and the effects of accelerated cardiovascular disease and ageing, are increasingly salient. A therapeutic gap seems to exist between the salutary effects of antiretroviral regimens and the normalisation of neurological function in HIV-associated neurocognitive disorders. Despite the advances in antiretroviral therapy, CNS opportunistic infections remain a serious burden worldwide. Most opportunistic infections can be recognised by a combination of characteristic clinical and radiological features and are treatable, but some important challenges remain in the diagnosis and management of HIV-associated opportunistic infections.
Dietary factors have been discussed to influence risk or disease course of multiple sclerosis (MS). Specific diets are widely used among patients with MS.
To design and pilot-test an evidence based ...patient education program on dietary factors in MS.
We performed a systematic literature search on the effectiveness of dietary interventions in MS. A web-based survey among 337 patients with MS and 136 healthy controls assessed knowledge, dietary habits and information needs. An interactive group education program was developed and pilot-tested.
Fifteen randomised-controlled trials (RCTs) were included in the systematic review. Quality of evidence was low and no clear benefit could be seen. Patients with MS significantly more often adhered to a `Mediterranean Diet`(29.7% versus 14.0%, p<0.001) compared to controls. 143 (42%) of the patients with MS had tried special MS diets. Important information needs addressed effectiveness of MS diets (44%) and relation between nutrition and MS (43%). A pilot test of our newly developed patient education program with 13 participants showed excellent comprehensibility and the MS-specific content was judged as very important. However, the poor evidence base for dietary approaches in MS was perceived disappointing.
Development and pilot-testing of an evidence-based patient education program on nutrition and MS is feasible. Patient satisfaction with the program suffers from the lack of evidence. Further research should focus on generating evidence for the potential influence of lifestyle habits (diet, physical activity) on MS disease course thus meeting the needs of patients with MS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The effect of nutrition and dietary supplements on the course of multiple sclerosis (MS) is a topic of great interest to both patients and clinicians. In particular, vitamin D status has been shown ...to influence both the incidence and the course of MS. High vitamin D levels are probably protective against the development of MS, although the efficacy of vitamin D supplementation in slowing progression of MS remains to be established. The influence of polyunsaturated fatty acids (PUFAs) on the development and course of MS has also long been under investigation. Small clinical trials suggest a modest reduction in the severity and duration of relapses in patients with MS receiving PUFA supplements. Other nutritional factors have been evaluated for their effect on MS disease progression, including milk proteins, gluten, probiotics, antioxidants (uric acid, vitamins A, C and E, lipoic acid), polyphenols, Ginkgo biloba extracts and curcumin. However, further studies are needed to evaluate the effects of these dietary components on the relapse rate and progression of MS. This Review gives an overview of the literature on the nutritional factors most commonly implicated as having an effect on MS and discusses the biological rationale that is thought to underlie their influence.
Background
Little is known about quality of life (QOL) at the time of multiple sclerosis (MS) or clinically isolated syndrome (CIS) diagnosis and how it evolves in the critical adjustment period ...immediately following a new diagnosis.
Objectives
To (1) describe QOL trajectory in the first year post-MS/CIS diagnosis and (2) examine associations of demographic and biopsychosocial factors with QOL at baseline and as it evolves over the first year post-MS/CIS diagnosis.
Methods
Participants were
N
= 250 individuals newly diagnosed with MS or CIS. Participants completed self-report assessments of QOL, demographics, and biopsychosocial factors at 1, 2, 3, 6, 9, and 12 months post-diagnosis using validated measures.
Results
At 1-month post-diagnosis, QOL
M
= 75.2/100 with subsequent assessments revealing consistent ratings on average. Modelling revealed a small number of variables that were predictive of QOL at baseline and/or change in QOL over time.
Conclusion
QOL in the first year post-MS/CIS diagnosis was, on average, high and stable. A subset of modifiable factors across the biopsychosocial spectrum was associated with baseline level of QOL and change in QOL over time. The stability in QOL suggests that patients can be assessed early after diagnosis for key variables that are predictive of both current and future QOL.
Background
The COVID-19 pandemic has likely had a negative impact on rehabilitation and quality of life (QoL) research in multiple sclerosis (MS).
Method
We explored perceived barriers to research ...among 87 researchers, representing 18 countries, both prior to and since COVID-19.
Results
A Wilcoxon signed-rank test found that significantly more researchers reported experiencing barriers to research since the onset of the pandemic compared to pre-COVID-19 (p < .001), with 78% of respondents reporting at least some barriers since COVID-19. The most commonly-cited barriers related to participant access (n = 38) and interruptions/delays to projects (n = 19). Although no gender differences were found in the number of barriers reported, female respondents were more likely to cite time or competing demands as barriers to research. Females were also more likely to perceive being negatively impacted by the pandemic compared to other genders (p = .007).
Conclusions
Implications for the future landscape of rehabilitation research in MS are discussed.
This chapter will review the spectrum of immune-mediated diseases that affect the nervous system and may result in an admission to the neurological intensive care unit. Immunomodulatory strategies to ...treat acute exacerbations of neurological diseases caused by aberrant immune responses are discussed, but strategies for long-term immunosuppression are not presented. The recommendations for therapeutic intervention are based on a synthesis of the literature, and include recommendations by the Cochrane Collaborative, the American Academy of Neurology, and other key organizations. References from recent publications are provided for the disorders and therapies in which randomized clinical trials and large evidenced-based reviews do not exist. The chapter concludes with a brief review of the mechanisms of action, dosing, and side effects of commonly used immunosuppressive strategies in the neurocritical care unit.
A 38-year-old woman was diagnosed with cutaneous anaplastic T-cell lymphoma that proved refractory to methotrexate, bexarotene, denileukin diftitox, interferon γ-1b, interferon α-2b, vorinostat, and ...pralatrexate. She was therefore started on the newly approved monoclonal anti-CD30 antibody brentuximab vedotin. Treatment with brentuximab 1.8 mg/kg IV every 3 weeks quickly led to disappearance of her cutaneous tumors. The day after her second brentuximab infusion she developed word-finding difficulties and unsteady gait. Due to further neurologic deterioration, she was admitted to an outside hospital. Brain MRI revealed multifocal enhancing white matter lesions throughout bilateral cerebral hemispheres and posterior fossa (figure, A-C). Brain biopsy was performed 15 days after her last brentuximab dose to rule out metastases and she was diagnosed with progressive multifocal leukoencephalopathy (PML) (figure, J). The patient was discharged home with hospice care. Upon discharge, she was started on prednisone 50 mg daily to help treat her eczema. Her family brought her to our clinic for a second opinion.
Objective
Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase ...chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AIJCV) in the diagnosis of natalizumab‐associated PML.
Methods
AIJCV was assessed in 37 cases of natalizumab‐associated PML and 89 MS‐patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme‐linked immunosorbent assay, using JCV‐VP1 fused to glutathione S‐transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AIJCV was calculated as published.
Results
Twenty‐six of 37 (70%) patients with natalizumab‐associated PML exhibited an AIJCV > 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab‐associated PML had an AIJCV > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AIJCV > 1.5.
Interpretation
Determination of the AIJCV could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab‐associated PML. Ann Neurol 2014;76:792–801
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