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Cognitive and psychiatric comorbidities in neuromyelitis optica

Objective

Our primary objective was to examine the neuropsychological and psychopathological profile of patients with neuromyelitis optica (NMO) and compare these to multiple sclerosis (MS) and healthy control (HC) groups. We also examined for relationships between cognitive and psychiatric variables and clinical factors including accumulated neurological disability and disease duration.

Methods

A neuropsychological test battery was administered along with a structured psychiatric interview and quantitative measures of mood symptoms.

Results

42 NMO, 42 MS and 42 HC participants were assessed. Cognitive impairments were observed in 67% of NMO patients. The prevalence and profile of cognitive impairments and lifetime prevalence of depression was similar between NMO and MS groups. However, significantly higher rates of recurrent depression and suicidality were observed in NMO patients. Correlational analyses revealed higher levels of anxiety symptoms were associated with shorter disease duration in NMO, while higher depression symptomlevels were associated with higher neurological disability and poorer cognition.

Conclusions

Our results demonstrate substantial cognitive and psychiatric comorbidities in NMO patients. Similar rates of lifetime and current depression between NMO and MS appear to mask greater underlying psychiatric burden in NMO and further understandings of the course of neurobehavioural comorbidities is required to better comprehend the additional morbidity in NMO. Our data support a role for cognitive and psychiatric assessments in the comprehensive care of NMO patients.

via J of the Neurol Sci

Linear lesions may assist early diagnosis of neuromyelitis optica and longitudinally extensive transverse myelitis, two subtypes of NMOSD

Purpose: To investigate the relationship between linear lesions (LL) and the development of longitudinally extensive spinal cord lesions (LESCL) in Chinese patients with neuromyelitis optica or longitudinally extensive transverse myelitis.

Method: The clinical records of 143 patients with these conditions were reviewed. Forty-one patients with LL were divided into three groups according to the order of appearance of LL and LESCL (simultaneously [n = 10], LL first [n = 26], or LESCL first [n = 5]). The remaining 102 patients without LL were used as a control group.

Results: Patients who developed LL first demonstrated a lower annualized relapse rate than those in the simultaneous group (1.00 [0.23–10.00] vs. 4.38 [0.60–6.67], p = 0.017) and the control group (1.00 [0.23–10.00] vs. 2.00 [0.24–10.00], p = 0.007). Among all patients with LL, there were significantly more who developed them before LESCL than those who developed them after LESCL (p < 0.001) or at the same time (p = 0.008). The mean time before the appearance of LESCL was 9.0 months (2–35 months) in the ‘LL-first’ group, which was shorter than that in the control group (12 months [1–60 months], p = 0.010). The rate of positivity for anti-aquaporin 4 IgG antibodies was higher in patients with LL compared with controls (90.24% vs. 64.71%, p = 0.002).

Conclusion: LL may be a precursor to LESCL and assist early diagnosis of neuromyelitis optica and longitudinally extensive transverse myelitis.

via J of the Neurol Sci

Remyelination Therapy in Multiple Sclerosis

Multiple sclerosis (MS) is an immune-mediated disorder of the central nervous system that results in destruction of the myelin sheath that surrounds axons and eventual neurodegeneration. Current treatments approved for the treatment of relapsing forms of MS target the aberrant immune response and successfully reduce the severity of attacks and frequency of relapses. Therapies are still needed that can repair damage particularly for the treatment of progressive forms of MS for which current therapies are relatively ineffective. Remyelination can restore neuronal function and prevent further neuronal loss and clinical disability. Recent advancements in our understanding of the molecular and cellular mechanisms regulating myelination, as well as the development of high-throughput screens to identify agents that enhance myelination, have lead to the identification of many potential remyelination therapies currently in preclinical and early clinical development. One problem that has plagued the development of treatments to promote remyelination is the difficulty in assessing remyelination in patients with current imaging techniques. Powerful new imaging technologies are making it easier to discern remyelination in patients, which is critical for the assessment of these new therapeutic strategies during clinical trials. This review will summarize what is currently known about remyelination failure in MS, strategies to overcome this failure, new therapeutic treatments in the pipeline for promoting remyelination in MS patients, and new imaging technologies for measuring remyelination in patients.

via Front Neurol

Reviewing the Unmet Needs of Patients with Multiple Sclerosis

Significant innovations in the treatment of patients with multiple sclerosis (MS) have primarily addressed the frequency of flare-ups in relapsing-remitting MS (RRMS). Many advances have been made in this area, and the medical community may be on the verge of a serious discussion of what constitutes a truly effective MS treatment. Certainly, it is important to further delay MS flare-ups and more effectively treat RRMS symptoms. However, great strides in reducing or preventing MS-related disability and providing neuroprotection have been elusive. Many unmet needs are still voiced by patients with MS, clinicians, and caregivers. Current information on the need for progress in various areas is reviewed in this article, including psychosocial care, treatments for progressive MS, biomarker identification, functional outcome measures, individualization of treatment, reducing side effects of medications, and improving medication adherence.

via Am Health Drug Benefits

The Latest Innovations in the Drug Pipeline for Multiple Sclerosis

Several new medications are being investigated in late-phase studies for the treatment of patients with relapsing or progressive multiple sclerosis (MS). These agents represent a variety of mechanisms of action and provide not only lower relapse rates but also improvement in disabilities. The majority of investigational trials involve selective sphingosine-1-phosphate receptor 1 immunomodulators, such as laquinimod, ozanimod, ponesimod, and siponimod, in an effort to build on the success of fingolimod. Ocrelizumab is a CD20-positive B-cell–targeting monoclonal antibody with a promising new mechanism of action. Ofatumumab is also a CD20 inhibitor. Daclizumab, an interleukin-2 inhibitor, has evidence of good efficacy but is associated with unfavorable side effects. Masitinib is a mast-cell inhibitor that also has shown efficacy in Alzheimer’s disease and amyotrophic lateral sclerosis. Phase 3 trials for some of these agents will conclude in the next 12 months, and their manufacturers are expected to apply for US Food and Drug Administration approval soon thereafter. This review article summarizes data for newly approved and late-phase investigational agents for the treatment of patients with MS.

A chronic disease of the central nervous system, multiple sclerosis (MS) is considered an immune-mediated disorder in which the immune system attacks healthy neuronal tissue. MS affects more than 2.3 million people worldwide. Its most common symptoms include overwhelming fatigue, visual disturbances, altered sensation, and difficulties with mobility. Symptoms vary in type and severity from patient to patient.1

Research and development in the treatment of MS has been rapid and active. For this review, the Clinical Trials.gov database was searched for phase 3 studies in MS that have been updated since December 1, 2014. “Multiple sclerosis” was the sole search term. Ninety-five results were returned, which covered approved agents being studied not only to treat patients with relapsing or progressive MS but also to address the symptoms of acute disease and its comorbidities. Moreover, the pipeline includes several new agents with different mechanisms of action. In addition to relapse prevention, an important focus of the newest classes of MS agents is to prevent disability.

This article summarizes data for the agents most recently approved for treatment of patients with MS as well as data for the key investigational agents, which, if phase 3 results continue to show promise, may prove to be significant additions to the therapeutic armamentarium.

via Am Health Drug Benefits

Anti-SPAG16 antibodies in primary progressive multiple sclerosis are associated with an elevated progression index

Background and purpose

Sperm-associated antigen 16 (SPAG16), a sperm protein which is upregulated in reactive astrocytes in multiple sclerosis (MS) lesions, has recently been identified as a novel autoantibody target in MS. The aim of this study was to investigate whether anti-SPAG16 antibody levels differ between MS subtypes (relapsing−remitting, RR; primary or secondary progressive, PP, SP) and whether antibody positivity is associated with clinical characteristics.

Methods

Plasma anti-SPAG16 antibody levels were determined by recombinant protein enzyme-linked immunosorbent assay (ELISA) in 374 MS patients (274 RRMS, 39 SPMS and 61 PPMS) and 106 healthy controls.

Results

Significantly elevated anti-SPAG16 antibodies were found in 22% of MS patients with 93% specificity. Anti-SPAG16 seropositivity was associated with an increased Expanded Disability Status Scale (EDSS) in overall MS. A higher proportion of PPMS patients showed anti-SPAG16 antibody reactivity (34%) compared to RRMS (19%) and SPMS (26%), and presented with higher anti-SPAG16 antibody levels. Seropositive PPMS patients had a significantly increased progression index compared to seronegative patients.

Conclusions

Anti-SPAG16 antibodies are associated with an increased EDSS in overall MS, indicating that they are linked to a worse MS disease outcome. Moreover, the presence of anti-SPAG16 antibodies may be a biomarker for a more severe disease in PPMS patients, as indicated by an increased progression index.

via Eur J Neurol