Materials and Methods
Ethical considerations
The study was approved by the ethics committee of [removed for blind
peer review], and written informed consent was obtained from patients.
Patients and Endoscopic exam
6 patients who had exhibited anosmia since early childhood were included
in this study (5 males, 1 females; age range 15-55 years). Patients had
no history of sinusitis or chronic congestion and no other complaints,
and demonstrated normal psychomotor development and appropriate Tanner
classification for their age. They also had no family history of anosmia
or delayed puberty. Endoscopic examination revealed no mucoid discharge
or polyps, and both olfactory clefts were patent.
Olfactory function test, and chemical and electro-gustatory test
An olfactory function test (the Korean version of Sniffin’s Stick Test,
KVSS II, Burghart, Germany) was performed on all patients. A chemical
and electro-gustatory test was also performed using an
electro-gustometer (Gustometer; Rion, Tokyo, Japan).
MRI scans
MRI scans were performed in 5 patients using a 3T scanner (Signa HDxT;
GE Healthcare, Milwaukee, Wisconsin) to exclude anatomical causes of
olfactory loss in 5 patients. To check the olfactory bulb, T2-weighted
3D images in the coronal plane were obtained using a spin-echo sequence
(field of view 150 × 150 mm2; section thickness 0.8 mm).
Simultaneous functional MRI and olfactory event-related potential (OERP)
Simultaneous functional MRI and OERPs were performed in 5 patients.
Simultaneous functional MRI and OERP recording can achieve high spatial
and temporal resolution. Patients wore a specialized 32-channel
electroencephalogram monitoring device (Professional Braincap; Easycap,
Herrsching, Germany) compatible with the MRI environment. MRI was
performed using the same 3T scanner as for the structural scan, using an
8-channel head coil (Figure 1). First, T1-weighted 3D images in the
axial plane were obtained using a fast-spoiled gradient-recalled
sequence (field of view 240 × 240 mm2; section thickness 1.3 mm). The
functional imaging sequence used was gradient recalled echo-planar
imaging (field of view 240 × 240 mm2; section thickness 3.5 mm).
Functional MRI and OERP data were obtained during a five-minute timespan
consisting of five odor exposure periods and five normal breathing
periods. Odorants were presented to patients through a custom-built
olfactometer with continuous air flow (4 L/min). In the exposure period,
we presented odors to patients for 10 seconds followed by 20 seconds of
odorless air. The periods of odor presentation were marked on the
electroencephalograms. In the normal breathing periods, patients
continuously received odorless air. We used two odorants: CIT (0.2 mL of
10 mmol/L citral) as a pleasant odor, and BME (0.2 mL of 1 mmol/L
β-mercaptoethanol) as an unpleasant odor. In the first five-minute
session, CIT was presented via the olfactometer and the patient breathed
regularly without sniffing. In the second session, BME was presented
with the same protocol.1 To minimize noise, the lights
were dimmed, and there was no other stimulation except the odorants.
Endocrinological study
An endocrinological study was performed to detect hypogonadotropic
hypogonadism in 6 patients. Follicle-stimulating hormone, luteinizing
hormone, and testosterone levels were checked.