Hemiplegic migraine, seizures, progressive spastic paraparesis, mood disorder, and coma in siblings with low systemic serotonin.
BACKGROUND
Serotonin has an important role in vascular resistance and blood pressure control, and a functional serotonin transporter polymorphism has been associated with migraine. Disturbances in serotonin metabolism have been associated with autism, depression, and myoclonus related conditions, but serotonin has far more functions in the body. Familial hemiplegic migraine is a rare autosomal dominant subtype of migraine with aura in which attacks are associated with hemiparesis.


METHODS
We present two siblings with hemiplegic migraine, depression, progressive spastic paraparesis, myelopathy, and spinal cord atrophy. One of the sisters presented with prolonged coma after a migraine episode. Both sisters were found to have low cerebrospinal fluid serotonin metabolite (5-hydroxyindoleacetic acid), low platelet serotonin levels, and diminished serotonin transport capacity. Their clinical symptoms improved on 5-hydroxytryptophan replacement therapy. Mutational analysis of the CACNA1A and ATP1A2 genes was negative.


CONCLUSIONS
This is the first time that systemic serotonin deficiency has been described in familial hemiplegic migraine. We hypothesize that the deficiency of serotonin transport may be part of a complex cellular membrane trafficking dysfunction involving not only the serotonin transporter but also other transporters and ion channels.
British Columbia Children's Hospital, Canada.
Gabriella A
GA
Horvath
Kathryn
K
Selby
Ken
K
Poskitt
Keith
K
Hyland
Paula J
PJ
Waters
Marion
M
Coulter-Mackie
Sylvia G
SG
Stockler-Ipsiroglu
D000293:Adolescent; D002648:Child; D003128:Coma / Q000097:blood* / Q000134:cerebrospinal fluid / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D020325:Migraine with Aura / Q000097:blood* / Q000134:cerebrospinal fluid / Q000151:congenital; D019964:Mood Disorders / Q000097:blood* / Q000134:cerebrospinal fluid / Q000235:genetics; D012640:Seizures / Q000097:blood* / Q000134:cerebrospinal fluid / Q000235:genetics; D012701:Serotonin / Q000097:blood* / Q000134:cerebrospinal fluid; D035781:Siblings
D012701:Serotonin