Kerry Mutch

Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients

Prompt treatment of neuromyelitis optica (NMO) relapses with steroids or plasma exchange (PLEX) often prevents irreversible disability. The objective of this study is to report the use of intravenous immunoglobulins (IVIG) as treatment for acute relapses in NMO. A retrospective review of 10 patients treated with IVIG for acute relapses was conducted. IVIG was used in the majority of cases because of lack of response to steroids with/without PLEX. Improvement was noted in five of 11 (45.5%) events; the remaining had no further worsening. One patient, a 79-year-old woman, had a myocardial infarction seven days after IVIG. IVIG may have a role in treating acute NMO relapses.

Brainstem manifestations in neuromyelitis optica: a multicenter study of 258 patients

Background: Neuromyelitis optica (NMO) is a severe autoimmune disease of the central nervous system characterized by spinal cord and optic nerve involvement. Brainstem manifestations have recently been described. Objective: To evaluate the time of occurrence, the frequency and the characteristics of brainstem symptoms in a cohort of patients with NMO according to the ethnic background and the serologic status for anti-aquaporin-4 antibodies (AQP4-abs). Methods: We performed a multicenter study of 258 patients with NMO according to the 2006 Wingerchuk criteria and we evaluated prospectively the frequency, the date of onset and the duration of various brainstem signs in this population. Results: Brainstem signs were observed in 81 patients (31.4%). The most frequently observed signs were vomiting (33.1%), hiccups (22.3%), oculomotor dysfunction (19.8%), pruritus (12.4%), followed by hearing loss (2.5%), facial palsy (2.5%), vertigo or vestibular ataxia (1.7%), trigeminal neuralgia (2.5%) and other cranial nerve signs (3.3%). They were inaugural in 44 patients (54.3%). The prevalence was higher in the non-Caucasian population (36.6%) than in the Caucasian population (26%) (p<0.05) and was higher in AQP4-ab-seropositive patients (32.7%) than in seronegative patients (26%) (not significant). Conclusions: This study confirms the high frequency of brainstem symptoms in NMO with a majority of vomiting and hiccups. The prevalence of these manifestations was higher in the non Caucasian population.

Long-term efficacy, tolerability and retention rate of azathioprine in 103 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients: a multicentre retrospective observational study from the UK

Background: Azathioprine (AZA) is a common immunosuppressive drug used for relapse prevention in neuromyelitis optica (NMO). Objectives: The objective of this paper is to assess efficacy, tolerability and retention of AZA in a large NMO cohort. Methods: We conducted a retrospective review of medical records of 103 aquaporin-4 antibody-positive NMO and NMO spectrum disorder (NMOSD) patients treated with AZA. Results: This is the largest reported cohort of AQP4-Ab positive patients treated with AZA. Eighty-nine per cent (n = 92) had reduction in median annualised relapse rates from 1.5 (IQR 0.6–4.0) to 0 (IQR 0–0.27, p < 0.00005) with treatment. Sixty-one per cent (n = 63) remained relapse free at a median follow-up of 18 months. Neurological function improved or stabilised in 78%. At last follow-up, treatment was discontinued in 46% (n = 47). Of these, 62% (n = 29) were because of side effects, 19% (n = 9) because of death, 15% (n = 7) because of ongoing disease activity, and 2% (n = 1) because of pregnancy. Using Kaplan-Meyer curves, we estimate that 73%, 58%, 47% and 33% of patients will remain on AZA for longer than one, three, five and 10 years, respectively, after initiation of treatment. Conclusions: AZA is a modestly effective treatment for NMO. However, many patients discontinue AZA over time and this seems to reflect poor tolerability more than lack of efficacy.

Neuropathic pruritus (itch) in neuromyelitis optica.

Background: Neuropathic pruritus (itch) is an uncommon, but well described, symptom in neurology. There are itch-specific neurons in the dorsal horn of the spinal cord. We noted excessive pruritus in patients with neuromyelitis optica (NMO). Objective: We aimed to explore the characteristics of pruritus in NMO patients. Methods: We reviewed case records of a well-defined cohort of 45 serial aquaporin-4 antibody-positive patients visiting the national NMO service. All patients were interviewed. Results: Of the 45 antibody-positive NMO patients, 44 had myelitis and 12 of those 44 (27.3%) patients reported pruritus within a week of other symptoms of transverse myelitis with central cord involvement. In three patients, pruritus was the first symptom of a relapse, while in one case, pruritus was the very first symptom of the index episode of NMO. Conclusion: Neuropathic pruritus seems to be a common, but under-recognised symptom of myelitis associated with NMO.

Characterization of neuromyelitis optica and neuromyelitis optica spectrum disorder patients with a late onset

Background: Few data are available for patients with a late onset (≥ 50 years) of neuromyelitis optica (LONMO) or neuromyelitis optica spectrum disease (LONMOSD), defined by an optic neuritis/longitudinally extensive transverse myelitis with aquaporin-4 antibodies (AQP4-Ab). Objective: To characterize LONMO and LONMOSD, and to analyze their predictive factors of disability and death. Methods: We identified 430 patients from four cohorts of NMO/NMOSD in France, Germany, Turkey and UK. We extracted the late onset patients and analyzed them for predictive factors of disability and death, using the Cox proportional model. Results: We followed up on 63 patients with LONMO and 45 with LONMOSD during a mean of 4.6 years. This LONMO/LONMOSD cohort was mainly of Caucasian origin (93%), women (80%), seropositive for AQP4-Ab (85%) and from 50 to 82.5 years of age at onset. No progressive course was noted. At last follow-up, the median Expanded Disability Status Scale (EDSS) scores were 5.5 and 6 in the LONMO and LONMOSD groups, respectively. Outcome was mainly characterized by motor disability and relatively good visual function. At last follow-up, 14 patients had died, including seven (50%) due to acute myelitis and six (43%) because of opportunistic infections. The EDSS 4 score was independently predicted by an older age at onset, as a continuous variable after 50 years of age. Death was predicted by two independent factors: an older age at onset and a high annualized relapse rate. Conclusion: LONMO/LONMOSD is particularly severe, with a high rate of motor impairment and death.

Neuropathic pain in neuromyelitis optica affects activities of daily living and quality of life

Though pain in neuromyelitis optica (NMO) has been described in two recent reports, the proportion with true neuropathic pain (NP), its features, impact on activities of daily living (ADL) and quality of life has not been well characterised. A cross-sectional study of 50 NMO patients with transverse myelitis was performed using Douleur Neuropathique 4, Brief Pain Inventory, Extended Disability Status Scale and Short Form 36. NP was identified in 62% of patients. Pain was constant in 68% affecting most ADL. Pain was associated with significant reduction of the SF36 Mental Composite Score. The high prevalence of NP and associated disability necessitates an in-depth enquiry in patients with NMO.

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.

Life on hold: the experience of living with neuromyelitis optica

Abstract Purpose: Neuromyelitis optica (NMO) is a rare autoimmune condition characterised by acute relapses of optic neuritis and extensive transverse myelitis. The aim of this qualitative study was to develop an improved understanding of the experiences of people living with NMO. Method: Fifteen participants completed a semi-structured interview and data were interpreted using a constant comparative method. Participants were recruited from the Northern UK NMO Service. Results: Five major themes were identified: diagnosis and treatment, symptoms, adjustment, identity and support. Conclusion: Results suggest NMO is a difficult condition to live with due to the unpredictability of relapses and accrued disability of visual or spinal symptoms occurring with each relapse. Poor vision, reduced mobility, bladder dysfunction and pain affected participants’ independence and experience of living with NMO. Participants reported that during relapse and recovery they would “put their life on hold”. They identified the importance of periods of stability to enable them to adjust to their condition and therefore aim for “normality” of life that they believed was comparable to their peers. Implications for Rehabilitation Disability due to NMO has a major impact on an individuals life, abilities and identity. Timely treatment of relapse is essential to reduce or prevent disability. Health care professionals need to coordinate care locally and nationally. Multi-disciplinary work is vital to promote adjustment, coping strategies and support for people living with NMO.