MR imaging and spectroscopic study of epileptogenic hypothalamic hamartomas: analysis of 72 cases

Abstract

Background and purpose: 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.

Fig 1.

Reformatted T1-weighted (fast spoiled gradient-echo) midsagittal and tilted coronal view MR images of three patients show the range of hypothalamic hamartoma sizes and their locations with respect to regions of the hypothalamus. The smaller lesion (A) is wholly intraventricular and confined to the mammillary region, without encroaching onto the tuber cinereum. The larger lesion (C) extends to the lamina terminalis in the preoptic region, abuts the optic chiasm, and displaces the pituitary stalk. Two hamartomas (A,C) are slightly hypointense relative to cortical and deep gray matter.

Fig 2.

T1-weighted coronal view and T2-weighted midsagittal view MR images show a rare example of an epileptogenic hamartoma located entirely below the floor of the third ventricle. The attachment of this small (6 × 5 × 8 mm diameter) hamartoma is narrowed at the level of the tuber cinereum, and a connection to the right mammillary body can be seen in the sagittal view image, but no distortion of third ventricular outline. This 12-year-old female patient had episodes of crying and laughing from 3 months of age, with increased seizure frequency and associated blank staring, disorientation, and fearfulness from age 9 years; interictal EEG findings were initially normal, but the patient later developed right occipital epileptiform discharges during sleep.

Fig 3.

T1-weighted midsagittal view and T2-weighted axial view MR images show the cystic components of two large hamartomas with interpeduncular, prepontine extension. A, In the first case, the cyst extends above the roof of the third ventricle and compresses the foramen of Monro on the right, resulting in dilation of the lateral ventricle (arrows). B, In the second case, the cyst is within and extends below the third ventricle.

Fig 4.

T2-weighted tilted coronal view image shows an example of a hamartoma with unilateral attachment to the hypothalamus (arrow).

Fig 5.

T2-weighted MR images with magnified views (insets) show the relation of the intra-hypothalamic component of the hamartoma to myelinated fiber tracts and gray matter of the hypothalamus in two patients. A, Axial section shows anterolateral displacement of the postcommissural fornix on the left when compared with the unaffected right fornix, plus increased T2 signal intensity of the hamartoma relative to the hypothalamus. B, Parasagittal section obtained at the level of the fornix shows the hamartoma between the postcommissural fornix anteriorly and the mammillothalamic tract posteriorly. Labeled are the postcommissural fornices (black arrows), mammillothalamic tracts (white arrows), and anterior commissure (arrowhead).

Fig 6.

Magnified T2-weighted images of two patients at the level of the mammillary bodies. A, Axial sections in the first case show inferior displacement and crescent-shaped distortion of the right mammillary body with less marked abnormality on the right. B, Midsagittal section in the second case shows inferior displacement of the right mammillary body. Axial section is similar in appearance to that shown in A. Labeled are the mammillary bodies (arrows).

Fig 7.

Single voxel MR spectrum recorded from a hypothalamic hamartoma showing (from left to right) signal intensity from myoinositol (mI, elevated), total choline (Cho), creatine/phosphocreatine (Cr), and N-acetylaspartate (NAA, reduced) content. The spectrum was recorded from a 4-cm³ region tailored to the hypothalamic hamartomas by using a point-resolved spectroscopy sequence with 3000/30 (TR/TE). The solid line overlaid on the spectrum shows the fitted spectrum produced by LCModel (24), and the upper panel shows the residual of the fit.

Fig 8.

T2-weighted tilted coronal view MR images show an example of bilateral white matter signal intensity abnormality and decreased gray-white matter differentiation in the anterior temporal lobes (image on the left), with normal signal intensity and differentiation in the posterior temporal lobes at the level of the hypothalamic hamartomas (image on the right).

Fig 9.

Arachnoid cysts associated with hypothalamic hamartomas. A, T1-weighted coronal view MR image shows a large suprasellar and temporal fossa arachnoid cyst, hypoplasia and compression of the right temporal lobe (bloom artifact due to previous cyst-peritoneal shunt insertion), and cavum septum pellucidum (arrow). B, T1-weighted coronal view MR image shows a suprasellar arachnoid cyst extending within the hamartoma. C, T2-weighted axial view MR image shows an anterior temporal arachnoid cyst (arrowhead) remote from the hamartoma (not shown).

Fig 10.

Malformations of cortical development associated with hypothalamic hamartomas in two patients. A, T2-weighted axial and coronal view MR images in the first case show periventricular nodular heterotopia and focal dilation of the left lateral ventricle, plus overlying calcarine and temporal-parietal-occipital junction cortical thickening and abnormal gyral configuration (white arrows). The hypothalamic hamartoma is seen in the axial view image (arrowhead). B, Inversion recovery coronal view image obtained at the level of the posterior hippocampus in the second case shows an atypical configuration of the medial occipitotemporal and posterior parahippocampal gyri (black arrow), with slight cortical thickening and indistinct gray-white boundary.