Quantitative magnetic resonance imaging evaluation of the olfactory system in Kallmann syndrome: correlation with a clinical smell test.

OBJECTIVES: To measure olfactory bulbs and sulci using dedicated magnetic resonance imaging (MRI) sequences and specific measurement tools in Kallmann syndrome (KS) patients with a well-established genotype and phenotype, as well as correlate MRI findings with a clinical smell test. METHODS: MRI was performed in 21 patients with KS and 16 healthy volunteers; olfactory dysfunction was assessed using the Smell Identification Test (UPSIT), a qualitative suprathreshold olfaction test. Coronal turbo spin echo T2-weighted and volumetric T1-weighted gradient echo sequences were acquired in a 1.5T system. ImageJ software was used to obtain olfactory bulb volumes and olfactory sulcus depths and lengths. Data were analyzed with SPSS 15.0 and the Kappa index was used to evaluate the agreement between the UPSIT and MRI. RESULTS: The UPSIT showed 14 patients with anosmia and 6 with moderate hyposmia. Eighteen patients (85%) presented altered rhinencephalon structures in the MRI. Sixteen patients (76%) presented olfactory bulb aplasia (14/16 bilaterally), and these patients presented a total of 16 aplastic sulci. There was moderate agreement between the MRI quantitative evaluation and the UPSIT (overall Kappa = 0.55), but when considering the presence of aplastic bulbs and anosmia, we found almost perfect agreement (Kappa = 0.87). Three patients had normal rhinencephalon structures, including one with a KAL1 gene mutation. CONCLUSION: Olfactory bulb and sulcus aplasia were the most common findings in KS patients. We objectively demonstrated agreement between MRI findings and the smell test, especially the presence of bulb aplasia and anosmia. Therefore, our findings help ascertain MRI accuracy in the diagnosis of KS, differentiating patients with hypogonadotropic hypogonadism with an apparently normal or difficult to evaluate sense of smell.

Kallmann syndrome and mirror movements: White matter quantitative evaluation with magnetic resonance imaging.

Kallmann syndrome (KS), characterized by the association of hypogonadotropic hypogonadism and anosmia, may present many other phenotypic abnormalities, including neurologic features as involuntary movements, called mirror movements (MM). MM etiology probably involves a complex mechanism comprising corticospinal tract abnormal development associated with deficient contralateral motor cortex inhibitory system. In this study, in order to address previous hypotheses concerning MM etiology, we identified and quantified white matter (WM) alterations in 21 KS patients, comparing subjects with and without MM and 16 control subjects, using magnetization transfer ratio (MTR) and T2 relaxometry (R2). Magnetization transfer and T2 double-echo images were acquired in a 1.5 T system. MTR and R2 were calculated pixel by pixel to initially create individual maps, and then, group average maps, co-registered with MNI305 stereotaxic coordinate system. After analysis of selected regions of interest, we demonstrated areas with higher T2 relaxation time and lower MTR values in KS patients, with and without MM, differently involving corticospinal tract projection, frontal lobes and corpus callosum. Higher MTR was observed only in pyramidal decussation when compared in both groups of patients with controls. In conclusion, we demonstrated that patients with KS have altered WM areas, presenting in a different manner in patients with and without MM. These data suggest axonal loss or disorganization involving abnormal pyramidal tracts and other associative/connective areas, relating to the presence or absence of MM. We also found a different pattern of alteration in pyramidal decussation, which can represent the primary area of neuronal disarrangement.