CNS aquaporin-4 autoimmunity in children.
BACKGROUND
In adult patients, autoantibodies targeting the water channel aquaporin-4 (AQP4) are a biomarker for a spectrum of CNS inflammatory demyelinating disorders with predilection for optic nerves and spinal cord (neuromyelitis optica [NMO]). Here we describe the neurologic, serologic, and radiographic findings associated with CNS AQP4 autoimmunity in childhood.


METHODS
A total of 88 consecutive seropositive children were identified through service evaluation for NMO-IgG. Sera of 75 were tested for coexisting autoantibodies. Clinical information was available for 58.


RESULTS
Forty-two patients (73%) were non-Caucasian, and 20 (34%) had African ethnicity. Median age at symptom onset was 12 years (range 4-18). Fifty-seven (98%) had attacks of either optic neuritis (n = 48; 83%) or transverse myelitis (n = 45; 78%), or both. Twenty-six (45%) had episodic cerebral symptoms (encephalopathy, ophthalmoparesis, ataxia, seizures, intractable vomiting, or hiccups). Thirty-eight (68%) had brain MRI abnormalities, predominantly involving periventricular areas (in descending order of frequency): the medulla, supratentorial and infratentorial white matter, midbrain, cerebellum, thalamus, and hypothalamus. Additional autoantibodies were detected in 57 of 75 patients (76%), and 16 of 38 (42%) had a coexisting autoimmune disorder recorded (systemic lupus erythematosus, Sjögren syndrome, juvenile rheumatoid arthritis, Graves disease). Attacks were recurrent in 54 patients (93%; median follow-up, 12 months). Forty-three of 48 patients (90%) had residual disability: 26 (54%) visual impairment and 21 (44%) motor deficits (median Expanded Disability Status Scale 4.0 at 12 months).


CONCLUSIONS
Aquaporin-4 autoimmunity is a distinctive recurrent and widespread inflammatory CNS disease in children.
Departments of Neurology and Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
A
A
McKeon
V A
VA
Lennon
T
T
Lotze
S
S
Tenenbaum
J M
JM
Ness
M
M
Rensel
N L
NL
Kuntz
J P
JP
Fryer
H
H
Homburger
J
J
Hunter
B G
BG
Weinshenker
K
K
Krecke
C F
CF
Lucchinetti
S J
SJ
Pittock
D000293:Adolescent; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis*; D015551:Autoimmunity; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D009188:Myelitis, Transverse / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D009471:Neuromyelitis Optica / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D012008:Recurrence; D012698:Serologic Tests
D051401:Aquaporin 4; D001323:Autoantibodies; D015415:Biomarkers; D008775:Methylprednisolone