MR imaging and spectroscopic study of epileptogenic hypothalamic hamartomas: analysis of 72 cases.
OBJECTIVE
Reports of MR imaging in hypothalamic hamartomas associated with epilepsy are few, and the number of patients studied is small. We aimed to detail the relationship of hypothalamic hamartomas to surrounding structures, to determine the frequency and nature of associated abnormalities, and to gain insight into mechanisms of epileptogenesis.


METHODS
We systematically examined MR imaging studies of 72 patients with hypothalamic hamartoma and refractory epilepsy (patient age, 22 months to 31 years). A dedicated imaging protocol was used in 38 cases. Proton MR spectroscopy of the hypothalamic hamartoma was performed for 19 patients and compared with the metabolite profile of the thalamus in 10 normal children and the frontal lobe in 10 normal adults.


RESULTS
Compared with normal gray matter, hypothalamic hamartomas were hyperintense on T2-weighted images (93%), hypointense on T1-weighted images (74%), and had reduced N-acetylaspartate and increased myoinositol content shown by MR spectroscopy. Hypothalamic hamartomas always involved the mammillary region of the hypothalamus, with attachment to one or both mammillary bodies. Intrahypothalamic extension (noted in 97%) tended to displace the postcommissural fornix and hypothalamic gray matter anterolaterally, such that the hypothalamic hamartomas nestled between the fornix, the mammillary body, and the mammillothalamic tract. Larger hamartoma size was associated with central precocious puberty. Associated findings of questionable epileptic significance included anterior temporal white matter signal intensity abnormalities (16%) and arachnoid cysts (6%). Malformations of cortical development were observed in only two patients, and hippocampal sclerosis was not observed.


CONCLUSIONS
Hypothalamic hamartomas can be readily distinguished from normal hypothalamic gray and adjacent myelinated fiber tracts, best appreciated on thin T2-weighted images. MR imaging and spectroscopy suggest reduced neuronal density and relative gliosis compared with normal gray matter. Associated epileptogenic lesions are rare, supporting the view that the hypothalamic hamartoma alone is responsible for the typical clinical features of the syndrome. The intimate relationship to the mammillary body, fornix, and mammillothalamic tract suggests a role for these structures in epileptogenesis associated with hypothalamic hamartomas.
Freeman
Jeremy L
JL
Children's Epilepsy Program, Department of Neurology, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.
Coleman
Lee T
LT
Wellard
R Mark
RM
Kean
Michael J
MJ
Rosenfeld
Jeffrey V
JV
Jackson
Graeme D
GD
Berkovic
Samuel F
SF
Harvey
A Simon
AS
D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002452:Cell Count; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D004292:Dominance, Cerebral / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D004827:Epilepsy / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D005260:Female; D005911:Gliosis / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D006222:Hamartoma / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D007027:Hypothalamic Diseases / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D007031:Hypothalamus / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D007089:Image Enhancement; D007091:Image Processing, Computer-Assisted; D007294:Inositol / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008326:Mammillary Bodies / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D009474:Neurons / Q000473:pathology / Q000502:physiology; D011379:Prognosis; D013577:Syndrome; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology / Q000601:surgery
D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate