M.T. Whitehead and G. Vezina
Department of Neuroradiology
Children’s National Medical Center
Washington, DC

We have several comments regarding the article “Asymptomatic Interhypothalamic Adhesions in Children.”¹ We agree with the main message of the article: Referable hypothalamic–pituitary axis symptoms are rare in patients with interhypothalamic adhesions. However, because symptoms can be present on occasion, it is prudent to exclude endocrinopathy on clinical grounds. We have encountered a few cases of patients with interhypothalamic adhesions and pituitary axis disturbances, one associated with Kallmann syndrome²; 2 with septo-optic dysplasia; and 1, with abnormal weight gain.

We agree with the authors’ theory that interhypothalamic adhesions may be the result of “incomplete hypothalamic cleavage, failed apoptosis, or abnormal neuronal migration” and acknowledge the association with “gray matter heterotopia.” Therefore, additional midline abnormalities would be expected. However, the authors did not identify additional abnormalities in most patients. Nonetheless, concurrent gray matter heterotopia was present in 40%, a considerably large percentage of patients, and they proposed that heterotopia associated with interhypothalamic adhesions may be part of an unknown genetic disorder.

All portions of the brain, including the midline, must be carefully examined in patients with interhypothalamic adhesions because they represent a potential marker for brain malformation. Additional midline anomalies/abnormalities are quite common in our experience.^2⇓–4 These may be subtle and insignificant (hypoplasia of the falx, underrotated hippocampi, and so forth) or obvious and potentially of great consequence (malformations of brain development).^2⇓–4 Indeed, review of Fig 1 demonstrates subtle midline anomalies not mentioned in the article, including hypogenesis or volume loss of the splenium (Figs 1A and E) and a partially fenestrated, persistent cavum septum pellucidum (Fig 1D).¹ In normal brains, the callosal splenium is typically equal to or larger in caliber than the genu. While a cavum septum pellucidum is a normal variation, it is uncommon in the general population beyond the neonatal period.

We strongly believe that the midline should be closely scrutinized for additional anomalies/abnormalities in patients with an interhypothalamic adhesion. Only after the brain has been carefully examined and signs/symptoms have been carefully considered can an interhypothalamic adhesion be considered an incidental and isolated finding.

References

1. Ahmed FN, Stence NV, Mirsky DM. Asymptomatic interhypothalamic adhesions in children. AJNR Am J Neuroradiol 2015 Dec 3. [Epub ahead of print]
2. Whitehead MT, Angel JD. Interhypothalamic adhesion in a 9-month-old male with cleft palate. Case Rep Radiol 2013;2013:197415
3. Whitehead MT, Vezina G. Interhypothalamic adhesion: a series of 13 cases. AJNR Am J Neuroradiol 2014;35:2002–06
4. Whitehead MT, Lee B. Neuroimaging features of San Luis Valley syndrome. Case Rep Radiol 2015;2015:748413

Reply

D.M. Mirsky
Department of Radiology
Children’s Hospital Colorado
Aurora, Colorado

F.N. Ahmed
Department of Radiology
University of Colorado Anschutz Medical Campus
Aurora, Colorado

N.V. Stence
Department of Radiology
Children’s Hospital Colorado
Aurora, Colorado

As indicated in our article,¹ approximately 70% of our patients with interhypothalamic adhesions had no symptoms referable to hypothalamic-pituitary dysfunction (40 of 57). We have since identified 72 additional patients, of whom 51 had no clinical symptoms. Thus, in the appropriate patient population in which associated symptoms are absent, interhypothalamic adhesions may be incidental.

Furthermore, in our experience, none of the asymptomatic patients and only 4 of the symptomatic population had additional midline abnormalities. We re-reviewed the imaging in all of our patients and found the numbers to hold true. None of the patients used for the figures had hypogenesis of the splenium or posterior periventricular white matter volume loss to cause splenium volume loss. The patient in Fig 1D did have a cavum septum pellucidum, a normal variant, but did not have partial fenestration on review of the images in 3 orthogonal planes.

Last, we agree with the Whitehead and Vezina² thesis that “the midline should be closely scrutinized for additional anomalies/abnormalities in patients harboring an interhypothalamic adhesion. Only after the brain has been carefully examined and signs/symptoms have been carefully considered can an interhypothalamic adhesion be considered an incidental and isolated finding.”³ It mirrors ours, “While associations between IHAs [interhypothalamic adhesions] and other syndromes likely exist, in the appropriate patient population lacking referable symptoms and with few or no other structural abnormalities, interhypothalamic adhesions may be incidental and of no clinical significance.”

References

1. Ahmed FN, Stence NV, Mirsky DM. Asymptomatic interhypothalamic adhesions in children. AJNR Am J Neuroradiol 2015 Dec 3. [Epub ahead of print]
2. Whitehead MT, Vezina G. Asymptomatic interhypothalamic adhesions in children. AJNR Am J Neuroradiol 2016 Feb 25. [Epub ahead of print]
3. Whitehead MT, Vezina G. Interhypothalamic adhesion: a series of 13 cases. AJNR Am J Neuroradiol 2014;35:2002–06