Brain changes in Kallmann syndrome.
OBJECTIVE
Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome-related brain changes with conventional and novel quantitative MR imaging analyses.


METHODS
Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9-55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value=800 s/mm2). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library.


RESULTS
Corpus callosum partial agenesis, multiple sclerosis-like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus.


CONCLUSIONS
This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex.
From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy ENT section (R.M., A.S.), Department of Neurosciences, "Federico II" University, Napoli, Italy. rmanara@unisa.it.
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Manara
Departments of Neurology (A.S.) ENT section (R.M., A.S.), Department of Neurosciences, "Federico II" University, Napoli, Italy.
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Salvalaggio
Psychiatry (A.F.), Department of Neurosciences.
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Favaro
Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy.
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Palumbo
Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy.
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Citton
Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate.
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Elefante
Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate.
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Brunetti
From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy.
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Di Salle
Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy.
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Bonanni
Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy.
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Sinisi
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000002:abnormalities*; D002648:Child; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D017436:Kallmann Syndrome / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D055815:Young Adult