Tuesday, December 22, 2015

Neuromyelitis optica

Chitnis T, Ness J, Krupp L, Waubant E, Hunt T, Olsen CS, Rodriguez M, Lotze T,
Gorman M, Benson L, Belman A, Weinstock-Guttman B, Aaen G, Graves J, Patterson M,
Rose JW, Casper TC. Clinical features of neuromyelitis optica in children: US
Network of Pediatric MS Centers report. Neurology. 2015 Dec 18. pii:
10.1212/WNL.0000000000002283. [Epub ahead of print]



To compare clinical features of pediatric neuromyelitis optica (NMO) to other pediatric demyelinating diseases.


Review of a prospective multicenter database on children with demyelinating diseases. Case summaries documenting clinical and laboratory features were reviewed by an adjudication panel. Diagnoses were assigned in the following categories: multiple sclerosis (MS), acute disseminated encephalomyelitis, NMO, and recurrent demyelinating disease not otherwise specified.


Thirty-eight cases of NMO were identified by review panel, 97% of which met the revised International Panel on NMO Diagnosis NMO-SD 2014 criteria, but only 49% met 2006 Wingerchuk criteria. Serum or CSF NMO immunoglobulin G (IgG) was positive in 65% of NMO cases that were tested; however, some patients became seropositive more than 3 years after onset despite serial testing. No patient had positive CSF NMO IgG and negative serum NMO IgG in contemporaneous samples. Other than race (p = 0.02) and borderline findings for sex (p = 0.07), NMO IgG seropositive patients did not differ in demographic, clinical, or laboratory features from seronegatives. Visual, motor, and constitutional symptoms (including vomiting, fever, and seizures) were the most common presenting features of NMO. Initiation of disease-modifying treatment was delayed in NMO vs MS. Two years after onset, patients with NMO had higher attack rates, greater disability accrual measured by overall Expanded Disability Status Scale score, and visual scores than did patients with MS.


The new criteria for NMO spectrum disorders apply well to the pediatric setting, and given significant delay in treatment of NMO compared to pediatric MS and worse short-term outcomes, it is imperative to apply these to improve access to treatment.

From the article:
Fulfillment of diagnostic criteria for NMO. We tested recent NMO criteria in 37/38 patients. One patient did not have sufficient information. Only 49% (18/ 37) of the reviewer-classified patients with NMO met the 2006 Wingerchuk diagnostic criteria for NMO.  Thirteen patients were NMO IgG seropositive, yet had only one of the 2 core symptoms of ON or transverse myelitis. A total of 28/37 patients with NMO had LETM on their first available MRI scans. Of the reviewer-classified patients with NMO, approximately 1/3 (12/37) met Paty MRI criteria, including 9 who also met Barkhof MRI criteria: 7/37 (Paty) and 3/37 (Barkhof) on their first available scan.
Updated diagnostic criteria for NMO have been proposed recently. Using this subset of criteria features as described in the methods, 36/37 (97%) reviewer-defined patients with NMO fit the updated diagnostic criteria.
First attack features. We compared first symptoms as well as first attack locations in the different groups. Visual, motor, and constitutional symptoms including vomiting, fever, and seizures) were the most common presenting features of NMO, and the most frequent first attack localizations were to the optic nerve, brainstem, and spinal cord. Of the NMO group, 5/38 (13%) had both spinal cord and optic nerve localization at the first event. A total of 4/5 of these patients had further attacks. We investigated the proportion of patients who presented with vomiting, since this has been identified as a first presenting symptom in adult NMO.15 Vomiting was an initial presenting symptom in 38% of patients with NMO, as well as in 46% of patients with ADEM (p = 0.60 vs NMO), and in 10% of patients with MS (p < 0.01 vs NMO).
Treatment of pediatric NMO. Median time from dis­ease onset to disease-modifying treatment for the 34 patients with NMO with documented treatments was 286 days (IQR 95836 days), compared to 153 days (IQR 56391 days, p = 0.04 comparing NMO and MS) for the 136 patients with MS; for the 9 patients with recurrent DD-NOS with documented treatments, median time to treatment was 523 days (456587 days, p = 0.19 comparing NMO and recurrent DD-NOS).
Among treatments for NMO and recurrent DD-NOS groups, rituximab (47% and 8%), mycopheno-late mofetil (39% and 12%), and azathioprine (24% and 12%) were the most often reported treatments in the NMO and recurrent DD-NOS groups
Although not considered a disease-modifying ther­apy in the above analysis, 39% of patients with NMO were ever treated with plasma exchange (PLEX). In the ADEM group, 2 (8%) patients were treated with PLEX; 9 (6%) of the MS group were treated with PLEX. None of the patients with DD-NOS was trea­ted with PLEX.


  1. Yuksel D, Senbil N, Yilmaz D, Yavuz Gurer YK. Devic's neuromyelitis optica in an infant case. J Child Neurol. 2007 Sep;22(9):1143-6.


    Devic's neuromyelitis optica was orginally described as an acute severe monophasic syndrome characterised by myelitis and optic neuritis. The mean age at onset was reported to be around 40 years, with a wide range. However, Devic's neuromyelitis optica has also been seen in children. Prognosis of the syndrome was poor, and no satisfactory treatment was known. This article reports a 23-month-old boy with acute myelitis and optic neuritis who was diagnosed with Devic's neuromyelitis optica. The response of the patient to therapy was poor, and he developed severe sequelae.

  2. Jeffery AR, Buncic JR. Pediatric Devic's neuromyelitis optica. J Pediatr Ophthalmol Strabismus. 1996 Sep-Oct;33(5):223-9.



    Neuromyelitis optica (Devic's disease) is a rare clinical syndrome of unilateral or bilateral optic neuritis (ON) and transverse myelitis (TM) occurring within an 8-week time interval. All reports mainly involve adults and describe a poor neurologic and ophthalmic clinical course without specific attention to their few pediatric cases. The purpose of this study was to develop a clinical profile in the pediatric population.


    A retrospective chart review over 15 years revealed nine cases of neuromyelitis optica. A literature search was undertaken and all cases of pediatric neuromyelitis optica were tabulated and analyzed separately.


    The average age of onset was 7 years with a preceding viral prodrome in all patients. The optic neuritis was bilateral in eight of nine patients (89%). Visual loss ranged from 20/30 to light perception. Moderate anterior disc edema was seen in all 17 affected eyes. The clinical course was characterized by a rapid visual and neurologic recovery. The average follow up was 5.3 years, with five patients followed for 6 years or longer. None of the nine patients had any visual or neurologic recurrence or other significant subsequent illness. Visual system follow up showed 20/20 in each eye of all patients with mild optic atrophy, identified in 47% of eyes.


    Devic's neuromyelitis optica occurs in the pediatric population as a distinct clinical entity with an excellent prognosis for visual and systemic recovery and no future recurrence or long-term sequelae.