Is There a Prodrome to NMOSD? An Investigation of Neurologic Symptoms Preceding the First NMOSD Attack
Sydney Lee1, Ruth-Ann Marrie2, Giulia Fadda3, Liesly Lee4, Alexandra Muccilli5, Manav Vyas6, Andrea Konig7, Dalia Rotstein7
1Adult Neurology Program, University of Toronto, 2University of Manitoba, 3University of Ottawa, 4Sunnybrook Health Sciences Centre, 5Saint Michael's Hospital - Multiple Sclerosis Clinic, 6MV VYAS MEDICINE PROFESSIONAL CORPORATION, 7St. Michael's Hospital
Objective:
To evaluate if patients with aquaporin-4 antibody positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) have prodromal neurologic symptoms preceding the first NMOSD attack.
Background:
It is unknown whether patients with AQP4+ NMOSD experience a prodrome, although there are cases reported of positive AQP4 serology up to 16 years before the first attack.
Design/Methods:
We retrospectively reviewed medical records of patients from four demyelinating disease centres across Canada who were enrolled in the Canadian NMOSD and other atypical demyelinating diseases cohort study (CANOPTICS). Participants had a diagnosis of AQP4+ NMOSD by 2015 criteria. We searched for neurologic symptoms occurring at least 30 days before the first attack. We excluded episodes where diagnosis was delayed, but in retrospect symptoms were attacks consistent with 2015 criteria. Findings were summarized descriptively.
Results:
Out of 116 patients with AQP4+ NMOSD, 18 (15.5%) had prodromal neurologic symptoms. Median age was 48.5 years (range 25-83) at first attack; 17 (94.4%) were female. Patients had a history of numbness (n=9), neuropathic pain (n=5), visual disturbance (n=4), tonic spasms (n=2), Lhermitte sign (n=2), severe headache (n=2), incoordination (n=2), weakness (n=1), psychosis (n=1), seizure (n=1), or tremor (n=1). Symptoms were constant (n=11) or intermittent (n=9), and 10 (55.6%) had more than one symptom. Five of 8 (62.5%) who underwent MRI had T2 hyperintense lesions that were not classic for NMOSD. Five (27.8%) had symptoms that persisted until their first attack, while 13 (72.2%) had complete resolution of symptoms with a median duration of 4 weeks (range 2 minutes-16 weeks). Within 1.5-245 months (median 16) patients experienced their first NMOSD attack with transverse myelitis (n=10), optic neuritis (n=5), area postrema syndrome (n=1), brainstem/cerebellar syndrome (n=1), or cerebral syndrome (n=1).
Conclusions:
Some patients may experience prodromal neurologic symptoms prior to the first NMOSD attack. Further systematic investigation of a possible NMOSD prodrome is warranted.