Canadian Consensus Guidelines for the Diagnosis and Treatment of Autoimmune Encephalitis in Adults.

Autoimmune encephalitis is increasingly recognized as a neurologic cause of acute mental status changes with similar prevalence to infectious encephalitis. Despite rising awareness, approaches to diagnosis remain inconsistent and evidence for optimal treatment is limited. The following Canadian guidelines represent a consensus and evidence (where available) based approach to both the diagnosis and treatment of adult patients with autoimmune encephalitis. The guidelines were developed using a modified RAND process and included input from specialists in autoimmune neurology, neuropsychiatry and infectious diseases. These guidelines are targeted at front line clinicians and were created to provide a pragmatic and practical approach to managing such patients in the acute setting.

Cancer risk, disease-modifying therapy, and age in multiple sclerosis: A retrospective population-based cohort study.

BACKGROUND: Long-term population-based safety studies are needed to investigate cancer outcomes in people with multiple sclerosis (MS) treated with modern disease-modifying therapy (DMT). OBJECTIVES: To investigate if exposure to DMT increases the risk of invasive cancer in MS. METHODS: We used population-based administrative health data from Alberta, Canada between 2008 and 2018. DMT exposure was defined in two ways: first as exposure to any DMT, and second by DMT type (modulating, sequestering, depleting). Study outcome was time to first diagnosis of invasive cancer. Cancer risk was compared to the general population using standardized incidence ratios (SIRs) and to the unexposed MS cases using hazard ratios (HRs). RESULTS: The analysis included 14,313 MS cases: 5,801 (40.5 %) were exposed to DMT. Median (interquartile range) follow-up was 8.4 (4.3, 10.4) years. Compared to the general population, there was no difference in cancer risk for the overall MS population (SIR: 0.94, 95 % confidence interval [CI]: 0.87, 1.02) or the DMT-exposed MS cases (SIR: 0.89; 95 % CI: 0.75, 1.05). Compared to unexposed MS cases, we found an interaction with age for exposure to any DMT (p = 0.001) and modulating DMT (p = 0.001), indicating that a difference in the risk of cancer associated with DMT depends on age. Cancer risk was not associated with exposure to sequestering DMT (HR: 1.28, 95 % CI: 0.78, 2.08) or depleting DMT (HR: 2.29, 95 % CI: 0.86, 6.14). CONCLUSIONS: Cancer risk for MS patients was similar to the general population. In the MS population, the age-dependent effect of DMT for cancer risk suggests a higher risk of cancer with age 62 or older and a protective effect at younger age. Further investigation is required to clarify whether the interaction between DMT exposure and age is a causal effect.

Anti-N-methyl-d-aspartate receptor encephalitis: A primer for acute care healthcare professionals.

This primer summarizes the diagnosis, treatment, complications, and prognosis of anti-N-methyl-d-aspartate receptor encephalitis for healthcare professionals, especially those in acute care specialities. Anti-N-methyl-d-aspartate receptor encephalitis is an immune-mediated encephalitis that is classically paraneoplastic and associated with ovarian teratomas in young women. Other less common neoplastic triggers include testicular cancers, Hodgkin lymphoma, lung and breast cancers. It may also be triggered by infection, occurring as a para-infectious phenomenon, seen most commonly after herpes simplex-1 encephalitis. Presentation varies but typically consists of behavioural and cognitive manifestations, seizures, dysautonomia, movement disorders, central hypoventilation, and coma, necessitating intensive care unit admission. Diagnosis of anti-N-methyl-d-aspartate receptor encephalitis requires high clinical suspicion plus ancillary testing, the most sensitive being cerebrospinal fluid analysis for anti-N-methyl-d-aspartate receptor antibodies. Imaging in search of an ovarian teratoma should be exhaustive and tumours need to be surgically treated. Treatment should be expeditious with pulsed steroids and either plasma exchange or intravenous immunoglobulin. Second-line treatments include intravenous rituximab, cyclophosphamide, azathioprine, and intrathecal methotrexate. Most patients recover to be functionally independent, but the in-hospital course can be months long followed by extensive rehabilitation. Given the lengthy course of illness, we explain why education and debriefing are important for staff, and where families can obtain additional help.

Oophorectomy in NMDA receptor encephalitis and negative pelvic imaging.

Ovarian teratomas are found in one-third of females presenting with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. When a teratoma is detected on imaging, its removal is first-line therapy. Even with multiple imaging modalities, occasionally, the teratoma is found only on subsequent imaging, long after initial presentation. Very rarely, patients have undergone oophorectomy despite negative imaging, with pathology demonstrating teratoma, and resulting clinical improvement. We present a patient in whom removal of a teratoma, not visible on conventional imaging, resulted in marked clinical improvement. Such cases present a major clinical challenge, needing to consider the risks of oophorectomy, including sterilisation and early menopause, versus the possibility of death in the absence of response to first-line (eg, corticosteroids, plasma exchange, intravenous immunoglobulin), second-line (eg, rituximab) and third-line (eg, bortezomib) immunosuppression. This decision is made more difficult as patients are usually females of childbearing age who at the time lack capacity to make medical decisions. This case also highlights the lack of consensus and guidelines for imaging modalities used to detect teratoma and when to pursue oophorectomy.

Microscopic Polyangiitis with Spinal Cord Involvement: A Case Report and Review of the Literature.

BACKGROUND: Microscopic polyangiitis (MPA) is an ANCA-associated vasculitis (AAV; ANCA denotes antineutrophil cytoplasmic antibody) that causes necrotizing inflammation of small blood vessels. Renal and pulmonary manifestations are common whereas central nervous system (CNS) involvement, and in particular spinal disease, is rare. METHODS: We reviewed a case of MPA presenting with spinal intradural hemorrhage and intracerebral hemorrhage. We also summarized all reported cases of AAV with spinal cord involvement in the literature (database search included MEDLINE, Embase, Scopus, and Proquest with no date or language restriction). RESULTS: We reviewed 20 cases of AAV with spinal cord involvement (12 granulomatosis with polyangiitis [GPA], 4 eosinophilic granulomatosis with polyangiitis, 2 MPA, and 2 cases diagnosed as AAV only) and reported demographic information, clinical features, methods of diagnosis, treatment, and patient outcome. Although CNS involvement has been associated with a poor prognosis, 14 of 18 cases that reported outcome data achieved remission during follow-up. Death occurred in 3 patients diagnosed with GPA and in 1 patient with MPA. Our patient with MPA deteriorated rapidly despite use of prednisone and died. CONCLUSIONS: AAV can present with brain and spinal cord involvement, even in the absence of systemic disease. CNS disease may be responsive to immunosuppressive therapy (e.g., steroids and cyclophosphamide) in several of the cases reviewed.

The Canadian survey of health, lifestyle and ageing with multiple sclerosis: methodology and initial results.

OBJECTIVE: People with multiple sclerosis (MS) are living longer so strategies to enhance long-term health are garnering more interest. We aimed to create a profile of ageing with MS in Canada by recruiting 1250 (5% of the Canadian population above 55 years with MS) participants and focusing data collection on health and lifestyle factors, disability, participation and quality of life to determine factors associated with healthy ageing. DESIGN: National multicentre postal survey. SETTING: Recruitment from Canadian MS clinics, MS Society of Canada chapters and newspaper advertisements. PARTICIPANTS: People aged 55 years or older with MS symptoms more than 20 years. OUTCOME MEASURES: Validated outcome measures and custom-designed questions examining MS disease characteristics, living situation, disability, comorbid conditions, fatigue, health behaviours, mental health, social support, impact of MS and others. RESULTS: Of the 921 surveys, 743 were returned (80.7% response rate). Participants (mean age 64.6±6.2 years) reported living with MS symptoms for an average of 32.9±9.5 years and 28.6% were either wheelchair users or bedridden. There was only 5.4% missing data and 709 respondents provided optional qualitative information. According to data derived from the 2012 Canadian Community Health Survey of Canadians above 55 years of age, older people with MS from this survey sample are about eight times less likely to be employed full-time. Older people with MS were less likely to engage in regular physical activity (26.7%) compared with typical older Canadians (45.2%). However, they were more likely to abstain from alcohol and smoking. CONCLUSIONS: Despite barriers to participation, we were able to recruit and gather detailed responses (with good data quality) from a large proportion of older Canadians with MS. The data suggest that this sample of older people with MS is less likely to be employed, are less active and more disabled than other older Canadians.