Shahd Hamid

Clinical presentation and prognosis in MOG-antibody disease: a UK study

See de Seze (doi:10.1093/brain/awx292) for a scientific commentary on this article. A condition associated with an autoantibody against MOG has been recently recognized as a new inflammatory disease of the central nervous system, but the disease course and disability outcomes are largely unknown. In this study we investigated clinical characteristics of MOG-antibody disease on a large cohort of patients from the UK. We obtained demographic and clinical data on 252 UK patients positive for serum immunoglobulin G1 MOG antibodies as tested by the Autoimmune Neurology Group in Oxford. Disability outcomes and disease course were analysed in more detail in a cohort followed in the Neuromyelitis Optica Oxford Service (n = 75), and this included an incident cohort who were diagnosed at disease onset (n = 44). MOG-antibody disease affects females (57%) slightly more often than males, shows no ethnic bias and typically presents with isolated optic neuritis (55%, bilateral in almost half), transverse myelitis (18%) or acute disseminated encephalomyelitis-like presentations (18%). In the total Oxford cohort after a median disease duration of 28 months, 47% of patients were left with permanent disability in at least one of the following: 16% patients had visual acuity ≤6/36 in at least one eye, mobility was limited in 7% (i.e. Expanded Disability Status Scale ≥ 4.0), 5% had Expanded Disability Status Scale ≥ 6.0, 28% had permanent bladder issues, 20% had bowel dysfunction, and 21% of males had erectile dysfunction. Transverse myelitis at onset was a significant predictor of long-term disability. In the incident cohort 36% relapsed after median disease duration of 16 months. The annualized relapse rate was 0.2. Immunosuppression longer than 3 months following the onset attack was associated with a lower risk of a second relapse. MOG-antibody disease has a moderate relapse risk, which might be mitigated by medium term immunosuppression at onset. Permanent disability occurs in about half of patients and more often involves sphincter and erectile functions than vision or mobility.

The impact of 2015 neuromyelitis optica spectrum disorders criteria on diagnostic rates

Background: The international panel for neuromyelitis optica (NMO) diagnosis has proposed diagnostic criteria for neuromyelitis optica spectrum disorders (NMOSD). Objectives: We assessed the impact of these criteria on diagnostic rates in a large cohort of patients. Methods: We identified and applied the 2006 and 2015 criteria to all patients (n = 176) seen in the NMO and non-multiple sclerosis central nervous system demyelination clinic (part of the UK NMO service) from January 2013 to May 2015. Results: The 2006 criteria classified 63 of 176 (36%) patients as NMO. A total of 42 patients (67%) were aquaporin 4 (AQP4) immunoglobulin G (IgG) +ve and 21 (33%) AQP4 IgG −ve. The 2015 criteria classified 111 of 176 (63%) patients as NMOSD, of which 81 (73%) were AQP4 IgG +ve and 30 (27%) were AQP4 IgG −ve. There was an increase of 48 patients (76%) diagnosed as NMOSD using the new criteria. Conclusion: Application of the 2015 criteria led to a rise in diagnosis of NMOSD by 76%. The rise in the AQP4 IgG +ve group contributed 62% and the seronegative group contributed 14%.

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 symptom levels 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.

Seizures and Encephalitis in Myelin Oligodendrocyte Glycoprotein IgG Disease vs Aquaporin 4 IgG Disease

Importance Antibodies to myelin oligodendrocyte glycoprotein IgG (MOG-IgG) are increasingly detected in patients with non–multiple sclerosis–related demyelination, some of whom manifest a neuromyelitis optica (NMO) phenotype. Cortical involvement, encephalopathy, and seizures are rare in aquaporin 4 antibody (AQP4-IgG)–related NMO in the white European population. However, the authors encountered several patients with seizures associated with MOG-IgG disease. Objective To compare incidence of seizures and encephalitis-like presentation, or both between AQP4-IgG–positive and MOG-IgG–positive patients. Design, Setting, and Participants Retrospective case series of all patients who were seropositive for MOG-IgG (n = 34) and the last 100 patients with AQP4-IgG disease (NMO spectrum disorder) seen in the NMO service between January 2013 and December 2016, and analysis was completed January 4, 2017. All patients were seen in a tertiary neurological center, The Walton Centre NHS Foundation Trust in Liverpool, England. Main Outcomes and Measures The difference in seizure frequency between the AQP4-IgG–positive and MOG-IgG–positive patient groups was determined. Results Thirty-four patients with MOG-IgG disease (20 female) with a median age at analysis of 30.5 years (interquartile range [IQR], 15-69 years), and 100 AQP4-IgG–positive patients (86 female) with a median age at analysis of 54 years (IQR, 12-91 years) were studied. Most patients were of white race. Five of the 34 patients with MOG-IgG (14.7%) had seizures compared with 1 patient with AQP4-IgG (2-sided P < .008, Fisher test). On magnetic resonance imaging, all 5 MOG-IgG–positive patients had inflammatory cortical brain lesions associated with the seizures. In 3 of the 5 MOG-IgG–positive patients, seizures occurred as part of the index event. Four of the 5 presented with encephalopathy and seizures, and disease relapsed in all 5 patients. Four of these patients were receiving immunosuppressant medication at last follow-up, and 3 continued to take antiepileptic medication. In contrast, the only AQP4-IgG–positive patient with seizures had a diagnosis of complex partial epilepsy preceding the onset of NMO by several years and experienced no encephalitic illness; her magnetic resonance imaging results demonstrated no cortical, subcortical, or basal ganglia involvement. Conclusions and Relevance Patients with MOG-IgG–associated disease were more likely to have seizures and encephalitis-like presentation than patients with AQP4-IgG–associated disease.

Chronic neuropathic pain severity is determined by lesion level in aquaporin 4-antibody-positive myelitis

Importance Chronic, intractable neuropathic pain is a common and debilitating consequence of neuromyelitis optica spectrum disorder (NMOSD) myelitis, with no satisfactory treatment; few studies have yet to explore its aetiology. Objective To establish if myelitis-associated chronic pain in NMOSD is related to the craniocaudal location of spinal cord lesions. Method (1) Retrospective cohort of 76 aquaporin 4-antibody (AQP4-Ab)-positive patients from Oxford and Liverpools national NMOSD clinics, assessing current pain and craniocaudal location of cord lesion contemporary to pain onset. (2) Focused prospective study of 26 AQP4-Ab-positive Oxford patients, a subset of the retrospective cohort, assessing current craniocaudal lesion location and current pain. Results Patients with isolated thoracic cord myelitis at the time of pain onset were significantly more disabled and suffered more pain. Cervical and thoracic lesions that persisted from pain onset to ‘out of relapse’ follow-up (current MRI) had highly significant (p<0.01) opposing effects on pain scores (std. β=−0.46 and 0.48, respectively). Lesion length, total lesion burden and number of transverse myelitis relapses did not correlate with pain. Conclusions Persistent, caudally located (ie, thoracic) cord lesions in AQP4-Ab-positive patients associate with high postmyelitis chronic pain scores, irrespective of number of myelitis relapses, lesion length and lesion burden. Although disability correlated with pain in isolation, it became an insignificant predictor of pain when analysed alongside craniocaudal location of lesions.

Patient-reported outcome measure for neuromyelitis optica: pretesting of preliminary instrument and protocol for further development in accordance with international guidelines

Objective This study outlines the development of a patient-reported outcome measure (PROM), an instrument to obtain self-reported health status for neuromyeltis optica (NMO), a disabling neurological condition. Design Development was conducted in accordance with international guidance for PROMs including systematic review of existing literature, item generation guided by qualitative interviews, health-related quality of life conceptual framework and clinical expert panel and cognitive interviews with NMO patients. Setting Participants were identified through a national NMO clinic in a tertiary NHS neurosciences service. Participants 15 individuals with NMO participated in cognitive interviews requiring review and ranking of proposed PROM items and qualitative feedback on content, layout and response options. Results Participants endorsed the draft instrument as reflecting their experience of the condition and as being easy to understand. Rating and ranking of item relevance and importance reduced the draft instrument from 106 to 48 items. Participant feedback on overlapping items eliminated a further 2 items and resulted in a preliminary instrument of 46 items. As a direct result of participant feedback ordering of the 10 domains was revised, a 4 option Likert scale was employed and a 4-week recall period for impact of symptoms was selected. Conclusions A 46-item instrument developed in accordance with international PROM development guidelines through literature review, developed by subject matter experts and refined through pretesting examining content validity provides a preliminary measure for assessing patient-report of health status in NMO. Further evaluation is proposed including sensitivity to clinical change, and international contributions to evaluating the measure are encouraged.

A severe, relapsing case of myelin oligodendrocyte glycoprotein IgG-associated CNS inflammation

A 55-year-old man presented in October 2004 with general unease, vomiting, and gait disturbance. Initially diagnosed with an inner ear infection, the patients symptoms did not improve and he was evaluated further. MRI revealed a cerebellar lesion, which led to the suspicion of a posterior circulation stroke, and he was started on antiplatelet drugs. However, an angiogram suggested no vascular pathology. In March 2011, he had another episode of ataxia and MRI showed a right brainstem lesion. Cryptogenic stroke was reconsidered. In March 2013, the patient developed paraparesis with urinary and bowel symptoms. MRI revealed myelitis of the midthoracic spinal cord. Oligoclonal bands were present in both serum and CSF and steroids were begun. In February 2014, he was admitted with expressive aphasia and right hemiparesis. MRI (figure 1) confirmed a new T2-hyperintense lesion in the left frontal lobe and he was given IV methylprednisolone and subsequently underwent plasma exchange. Aquaporin 4 (AQP4) IgG was negative. The working diagnosis was tumefactive multiple sclerosis. He was started on glatiramer acetate in August 2014. A few months later, he developed right-sided weakness, left optic neuritis (ON), and confusion. MRI (figure 2) showed left occipital and left parietal cortical and subcortical white matter lesion spreading across the corpus callosum to the opposite side. There were changes bilaterally in the cerebellum, cerebral peduncles, and along the corticospinal tracts on the left side. Further scans showed swelling of the splenium of the corpus callosum. He was put back on prednisolone 60 mg. Markers for systemic inflammation (erythrocyte sedimentation rate, C-reactive protein) were normal and autoantibody testing (antinuclear antibodies, extractable nuclear antigen, paraneoplastic antineuronal antibodies) was negative. The diagnosis of fulminant seronegative NMO was re-entertained but AQP4 antibodies were negative. However, MOG antibodies returned positive (October 2014, live cell-based assay, John Radcliffe Hospital, Oxford, UK). Azathioprine 125 mg was begun in February 2015.

1115 Applying the 2015 neuromyelitis optica criteria in clinical practice

Background The international panel for Neuromyelitis optica diagnosis (IPND) has published consensus diagnostic criteria for NMOSD. MOG IgG is present in some seronegative NMO. Objectives Assess impact of new criteria on diagnostic rates of NMO and frequency of MOG IgG in AQP4 IgG-ve NMO Methods All eligible patients seen in the NMO and atypical CNS demyelination clinic from January 2013 to Dec 2016 were tested for AQP4 IgG. Both the 2006 and 2015 criteria were applied. MOG IgG was tested in all seronegative NMO/SD. Results 233 patients were included. The 2006 criteria classified 75 patients as NMO (49 were AQP4 IgG +ve and 26 AQP4 IgG-ve). The 2015 criteria classified 130 patients as NMOSD (94 AQP4 IgG +ve and 36 AQP4 IgG-ve) an increase of 55 patients (73% rise). MOG IgG was present in 10/26 (38%) AQP4 IgG-ve NMO cases as per 2006 criteria and 15/36 (44%) of AQP4-IgG negative cases as per 2015 criteria. Conclusion Application of the 2015 IPND criteria increases the diagnosis of NMOSD by 73%. MOG IgG is found in 38%–44% of NMO/SD cases without AQP4 IgG.

What’s new in neuromyelitis optica? A short review for the clinical neurologist

The evolution of neuromyelitis optica spectrum disorder (NMOSD) from a rare, incurable and misunderstood disease with almost universally poor outcomes to its present state in just over a decade is unprecedented in neurology and possibly in medicine. Our knowledge of NMOSD biology has led to the recognition of wider phenotypes, new disease mechanisms, and thus clinical trials of new and effective treatments. This article aims to update readers on the recent developments in NMOSD with particular emphasis on clinical advances, the 2015 diagnostic criteria, biomarkers, imaging, and therapeutic interventions.

If they are OK, we are OK: the experience of partners living with neuromyelitis optica.

Abstract Aim: Neuromyelitis optica (NMO) is a rare neuro-inflammatory condition characterized by acute relapses causing severe visual or physical disability. The impact on family members and their experiences have not been studied. The study aims were to explore the lived experience of partners of people with NMO and to investigate potential carer burden in this population. Method: A mixed-method design was used; 11 partners of people with NMO completed semi-structured interviews; 54 partners completed Zarit Burden Interview and Hospital Anxiety and Depression Scale. Results: Three qualitative themes influenced partners’ quality of life (QoL): role/relationship; it’s all about them; and the impact of NMO. Life changed dramatically for participants after the first NMO attack, necessitating responsibility for physical, financial, social, and emotional support. As NMO symptoms improved and stabilized, freedom and QoL for spouses also improved, albeit with on-going worries regarding the impact of potential devastating future relapses. Quantitative findings showed mild/moderate carer burden (46%), mild/moderate anxiety (59%), and mild/moderate depression (24%). No partner indicated severe carer burden, anxiety, or depression. Conclusion: Participants regarded themselves as partners rather than carers whom require assessment and support for their emotional and health well-being. Health-care professionals need to acknowledge the important role partners play in the dynamics of the family unit, through greater discussion and inclusion. Implications for Rehabilitation NMO has a strong impact on couples, resulting in both physical caregiving needs and anxiety regarding the unpredictability of potential devastating relapses. Partners do not necessarily experience clinically significant “burden”, anxiety or depression, and tools which screen for this may not capture the nature of their experiences. Health-care professionals need to acknowledge, consult, and respect the experience of partners during assessment and implementation of action plans. Partners should be individually assessed based upon the physical and emotional dependency created by NMO to improve their health and well-being.