Alternating hemiplegia of childhood: early characteristics and evolution of a neurodevelopmental syndrome.
OBJECTIVE
Alternating hemiplegia of childhood is a predominantly sporadic neurodevelopmental syndrome of uncertain etiology. In more than 3 decades since its description, little progress has been made in understanding its etiology or in identifying effective treatments. In 1998, in collaboration with the Alternating Hemiplegia of Childhood Foundation, an international registry was established to help document clinical outcomes and promote research efforts.


METHODS
We present phenotypic data on 103 patients who met existing diagnostic criteria for alternating hemiplegia of childhood. Although some of these subjects may have been included in previously published reviews, our focus was directed toward the earliest manifestations of symptoms and evolution of features over time. Data sources included written questionnaires, face-to-face and telephone interviews, clinical examination, and medical charts. Characteristics of disease onset, medical comorbidities, episode triggers, diagnostic workup, and treatment are presented.


RESULTS
Paroxysmal eye movements were the most frequent early symptom, manifesting in the first 3 months of life in 83% of patients. Hemiplegic episodes appeared by 6 months of age in 56% of infants. Background slowing shown by electroencephalography during typical paroxysmal events, including hemiplegic, tonic, or dystonic episodes was frequent (21 of 42 cases). Distinct convulsive episodes with altered consciousness believed to be epileptic in nature were reported in 41% of patients. Ataxia (96%) and cognitive impairment (100%) were frequent nonepisodic symptoms. Empiric pharmacologic treatment approaches offered little benefit in most subjects and resulted in adverse effects in 20% of patients. Prolonged episodes were completely or temporarily aborted during sleep in all subjects.


CONCLUSIONS
This descriptive analysis of a large cohort of children indicates that paroxysmal ocular movements are an early, highly suggestive symptom, followed by paroxysmal episodes of focal dystonia or flaccid, alternating hemiplegia in early infancy in the majority of subjects. Current challenges in diagnosis and management contribute to poor outcomes. Early diagnosis and multicenter collaboration are needed to facilitate trials to identify more effective therapies.
Sweney
Matthew T
MT
University of Utah School of Medicine, 30 N 1900 East, SOM Room 3R413, Salt Lake City, UT 84132, USA. sweney@genetics.utah.edu
Silver
Kenneth
K
Gerard-Blanluet
Marion
M
Pedespan
Jean-Michel
JM
Renault
Francis
F
Arzimanoglou
Alexis
A
Schlesinger-Massart
Mylynda
M
Lewelt
Aga J
AJ
Reyna
Sandra P
SP
Swoboda
Kathryn J
KJ
D000293:Adolescent; D000367:Age Factors; D001259:Ataxia / Q000175:diagnosis / Q000209:etiology; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology; D015331:Cohort Studies; D004569:Electroencephalography; D005260:Female; D005500:Follow-Up Studies; D006429:Hemiplegia / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D007223:Infant; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D009460:Neurologic Examination; D015835:Ocular Motility Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D049268:Positron-Emission Tomography; D011619:Psychotropic Drugs / Q000009:adverse effects / Q000627:therapeutic use; D012640:Seizures / Q000175:diagnosis / Q000209:etiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D055815:Young Adult
D011619:Psychotropic Drugs; D017367:Selective Serotonin Reuptake Inhibitors