Imagerie des troubles

de l’olfaction JL Sarrazin, F Benoudiba, S Hibat, D Ducreux

Hôpital Américain de Paris

CHU de Bicêtre

GÉNÉRALITÉS

Sens “régressif” Système sensoriel primitif :

recherche de nourriture, recherche de partenaires sexuels

Diminution de volume : récepteurs, bulbes olfactifs, rhinencéphale

Diminution qualitative : phéromones

Evolution : développement de la vision aux dépens de l’olfaction. Favorise la collectivisation humaine

Sens à vecteur chimique Comme le goût

Exploration plus difficile

Anatomie

Récepteurs olfactifs Muqueuse nasale au contact de la lame criblée

Lame conchale Cornet supérieur septum nasal Muqueuse olfactive :

5 cm2chez l’homme,

20 cm2 chez le chat

150 cm2 chez le chien 107 récepteurs chez l’homme

2,2 108 chez le chien

Orthonasale Rétronasale

Muqueuse et Bulbes olfactifs Muqueuse

Neurones olfactifs bipolaires

Prolongement basal dans la muqueuse (8 à 20 cils)

Prolongement apical se regroupe par 10 à 100

Faisceaux d’axones myélinisés par des cellules de Schwann

Traverse la lame criblée pour entrer dans le crâne

Durée de vie 2 mois environ renouvellement constant

Bulbes

Longueur 12mm (6 -16 mm). Volume 58 mm3 avant 45 ans, 46 mm3 après 45 ans

Glomérules

Cellules périglomérulaires, cellules de grain, cellules en panache

Cellules mitrales (neurones)

dendrite : glomérule

axone : bandelette olfactive latérale

Voies olfactives

Projections corticales

Voies olfactives

Substance perforée antérieure

Trigone olfactif

Stries olfactives

latérale

médiale

(intermédiaire)

Projections corticales

Bandelette olfactive latérale

Cortex prépyriforme

Gyrus parahippocampique cortex

entorhinal, noyau amygdalien

Relai thalamique

Bandelette olfactive médiale

Aire olfactive médiale (fronto basale)

Qualitatif Quantitatif

Cacosmie

Parosmie

Hallucinations olfactives

Hyposmie

Anosmie

Hyperosmie

Classification des troubles de l’olfaction

EXPLORATION Fonctionnelle

Olfactométrie

Seuil de détection avec une concentration croissante (butanol)

Test de discrimination qualitative

Test de mémoire et de reconnaissance

Test d’identification

Examen ORL

Imagerie

TDM

IRM

Etiologies des troubles

olfactifs

Physiologie de l’odorat :4 étapes

Aéroportage : transmission des molécules de l’air ambiant au mucus nasal

Traversée du mucus nasal

Réception et transduction dans le neurone olfactif

Intégration du signal au niveau des centres olfactifs

Pas d’imagerie, scanner +/- IRM : 2/3 des causes

IRM : 1/3 des causes

Physiologie de l’odorat :4 étapes

Aéroportage : transmission des molécules de l’air ambiant au mucus nasal

Traversée du mucus nasal

Réception et transduction dans le neurone olfactif

Intégration du signal au niveau des centres sensitifs

Pas d’imagerie, scanner +/- IRM : 2/3 des causes

Trouble de l’aéroportage

Chronique et fréquent

Œdème, Inflammation, remodelage

Clinique Anosmie

Obstruction nasale

Rhinorrhée

Atteinte essentiellement ethmoïdale

bilatérale +/-autres sinus

Diagnostic : clinique et rhinoscopie

TDM : Bilan d’extension, variantes

anatomiques

Syndrome de la fente olfactive

Obstruction isolée des fentes

olfactives

R

Polypose naso sinusienne

Altération de traversée du

mucus Rhinites allergiques et non allergiques

10 à 20% de la population

Entraine une hyposmie dans 30 à 40%

Autres signes cliniques :

Obstruction nasale (80%)

Rhinorrhée post (80%)

Douleurs faciales (60%)

Augmentation du caractère hydrophile du mucus

Diminution de la concentration moléculaire

Diminution des protéines de transport

Augmentation de la distance mucus/cellules ciliées

Causes toxiques

Acétate, Chrome, Soufre Acétone Ciment Vernis,

Ammoniaque Menthol , Zinc, Azote, Fluor, Benzène,

Mercure, Carbone, Nickel, Chaux, Paprika, Chlore,

Plomb

Anosmie post rhinitique

Infection virale aiguë

dans les suites d’une rhinite aigue

Prévalence: 1 pour 400

Physiopathologie mal connue :

destruction des neurones olfactifs primaires

Résolutive spontanément dans >60% des cas

Dysosmie résiduelle définitive après 12 mois d’évolution

TDM Elimination d’une sinusite

Altération de la

transduction

Femme de 70 ans

Céphalées

Anosmie

TTT corticoïdes AB

ESTHÉSIONEUROBLASTOME

Esthésioneuroblastome

Tumeur rares des fosses nasales (3%) développée à partir de l’épithélium olfactif.

Origine neuroectodermique.

Deux pics d’âge 11-20 ans, 51-60 ans

Signes cliniques :

Anosmie, obstruction nasale, exophtalmie, épistaxis

Imagerie bilan d’extension locale, orbitaire, endocrânienne

TTT : chirurgie radio thérapie

Homme de 21 ans

Obstruction

nasale chronique

Epistaxis

Céphalées.Anosmie

Femme de 45 ans

Hyposmie globale

Obstruction nasale

Schwannome olfactif

Schwannome olfactif

A partir de filets olfactifs?

Branches méningées du nerf trijumeau

Nerf ethmoïdal antérieur (branche du V1)

Physiologie de l’odorat :4 étapes

Aéroportage : transmission des molécules de l’air ambiant au mucus nasal

Traversée du mucus nasal

Réception et transduction dans le neurone olfactif

Intégration du signal au niveau des centres sensitifs

IRM : 1/3 des causes

Altération des voies et centres

olfactifs Exploration IRM

Encéphalique

Flair, T2*, diffusion

Massif facial

Frontale T2

Echo de spin : coupes max de 2mm

T2 HR (Ciss, Fiesta, Drive,)

Volume T2 (cube, space..)

Injection si nécessaire

les Causes

Malformations

Traumatismes

Tumeurs

Pathologie dégénérative ou

inflammatoire

SYNDROME DE KALLMANN Hypogonadisme hypogonadotrope

par déficit en GnRH

micropénis et cryptorchidie chez le jeune garçon

Anosmie ou hyposmie

(avec hypoplasie ou aplasie des bulbes olfactifs)

Défaut du développement embryonnaire du système

olfactif

Prédominance des cas sporadiques

3 modes de transmission familiale : Récessif lié à l’X;

autosomique récessif , autosomique dominant

1 gène identifié : KAL-1, responsable de la forme récessive

liée à l’X

1 protéine : l’anosmine 1

Disponible en ligne sur

ScienceDirectwww.sciencedirect.com

Annales d’Endocrinologie 78 (2017) 455–461

Original article

Reconsidering olfactory bulb magnetic resonance patterns in

Kallmann syndrome

La neuroradiologie des bulbes olfactifs dans le syndrome de Kallmann revisitée

Thomas Hacquart a,b, Aïcha Ltaief-Boudrigua b, Cécile Jeannerod c, Salem Hannoun d,

Gérald Raverot e, Michel Pugeat e, Aude Brac de la Perriere e, Véronique Lapras f,

Frédérique Nugues g, Catherine Dode h, Francois Cotton a,f,i,∗

a Département universitaire d’anatomie de Rockefeller, UFR médecine Lyon-Est, 8, avenue Rockefeller, 69373 Lyon, Franceb Radiologie ostéo-articulaire et neuroradiologie, groupement hospitalier Edouard-Herriot, hospices civils de Lyon, 5, place d’Arsonval, 69437 Lyon, France

c UFR médecine Lyon-Est, 8, avenue Rockefeller, 69373 Lyon, Franced Abu-Haidar neuroscience institute, faculty of medicine, american university of Beirut, 11-0236 Riad-El-Solh, 1107 2020 Beirut, Lebanon

e Fédération d’endocrinologie, groupement hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69500 Bron, Francef Service de radiologie, centre hospitalier Lyon-Sud, hospices civils de Lyon, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France

g Imagerie pédiatrique, hôpital couple-enfant, CHU de Grenoble, boulevard de la Chantourne, 38700 La Tronche, Franceh Laboratoire de biochimie et génétique moléculaire, hôpital Cochin, APHP, université Paris-Descartes, 27, rue du Faubourg Saint-Jacques,

75014 Paris, Francei CREATIS, CNRS UMR 5220 Inserm U1044, université Lyon 1, 7, avenue Jean-Capelle, 69621 Villeurbanne, France

Abstract

Objective. – The aim of this retrospective study was to perform magnetic resonance imaging assessment of olfactory pathway and skull base

abnormalities in Kallmann syndrome (KS) patients with hypogonadotropic hypogonadism and olfaction disorder. Methods. – Magnetic resonance

brain patterns were retrospectively studied in 19 patients clinically classified as KS. Qualitative assessment of olfactory bulb region comprised bulb

atrophy and rectus and medial orbital gyrus ptosis; quantitative assessment measured olfactory fossa depth and width, sulcus depth and ethmoid

angle. Results were compared to an age- and sex-matched control population (n = 19) with no impairment in the region of interest. Sixteen of

the 19 KS patients were genetically screened for mutations associated with KS. Results. – On the above qualitative criteria, 15 of the 19 patients

presented either unilateral (n = 2) or bilateral (n = 13) olfactory bulb agenesis; 16 showed tract agenesis and 16 showed gyrus malformation (ptosis

or absence). On the quantitative criteria, 18 of the 19 patients showed abnormal sulcus depth and/or olfactory fossa malformation and/or abnormal

ethmoid angle. Conclusion. – The presence of malformation abnormalities in the olfactory fossae of 18 of the 19 patients appears to be a key factor

for etiological diagnosis of hypogonadotropic hypogonadism, and should enable targeted study of genes involved in KS.

© 2017 Elsevier Masson SAS. All rights reserved.

Keywords: Kallmann syndrome; Hypogonadism; Olfactory bulb; Olfaction Disorder; Magnetic resonance imaging

Résumé

Objectif. – L’objectif de cette étude rétrospective était d’évaluer par l’imagerie par résonance magnétique (IRM) les anomalies des voies olfactives

et de la base du crâne chez les patients atteints d’hypogonadisme hypogonadotrope avec anosmie dans le cadre du syndrome de Kallmann.

Méthodes. – Nous avons réalisé une relecture des IRM cérébrales de 19 patients atteints cliniquement d’un syndrome de Kallmann avec une

évaluation qualitative (atrophie des bulbes, ptose de gyri-orbitaire médian et rectus) et quantitative (largeur et hauteur des fosses olfactives, angles

ethmoïdaux, profondeur des sulci olfactifs) de la région des bulbes olfactifs en comparaison avec une population contrôle appariée pour l’âge et le

sexe et sans atteinte de cette région (n = 19). Une étude génétique a pu être réalisée chez 16/19 des patients Kallmann. Résultats. – Sur les 19 patients,

∗ Corresponding author. Service de radiologie, centre hospitalier Lyon-Sud – hospices civils de Lyon, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite,

France.

E-mail address: francois.cotton@chu-lyon.fr (F. Cotton).

http://dx.doi.org/10.1016/j.ando.2016.12.003

0003-4266/© 2017 Elsevier Masson SAS. All rights reserved.

Disponible en ligne sur

ScienceDirectwww.sciencedirect.com

Annales d’Endocrinologie 78 (2017) 455–461

Original article

Reconsidering olfactory bulb magnetic resonance patterns in

Kallmann syndrome

La neuroradiologie des bulbes olfactifs dans le syndrome de Kallmann revisitée

Thomas Hacquart a,b, Aïcha Ltaief-Boudrigua b, Cécile Jeannerod c, Salem Hannoun d,

Gérald Raverot e, Michel Pugeat e, Aude Brac de la Perriere e, Véronique Lapras f,

Frédérique Nugues g, Catherine Dode h, Francois Cotton a,f,i,∗

a Département universitaire d’anatomie de Rockefeller, UFR médecine Lyon-Est, 8, avenue Rockefeller, 69373 Lyon, Franceb Radiologie ostéo-articulaire et neuroradiologie, groupement hospitalier Edouard-Herriot, hospices civils de Lyon, 5, place d’Arsonval, 69437 Lyon, France

c UFR médecine Lyon-Est, 8, avenue Rockefeller, 69373 Lyon, Franced Abu-Haidar neuroscience institute, faculty of medicine, american university of Beirut, 11-0236 Riad-El-Solh, 1107 2020 Beirut, Lebanon

e Fédération d’endocrinologie, groupement hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69500 Bron, Francef Service de radiologie, centre hospitalier Lyon-Sud, hospices civils de Lyon, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France

g Imagerie pédiatrique, hôpital couple-enfant, CHU de Grenoble, boulevard de la Chantourne, 38700 La Tronche, Franceh Laboratoire de biochimie et génétique moléculaire, hôpital Cochin, APHP, université Paris-Descartes, 27, rue du Faubourg Saint-Jacques,

75014 Paris, Francei CREATIS, CNRS UMR 5220 Inserm U1044, université Lyon 1, 7, avenue Jean-Capelle, 69621 Villeurbanne, France

Abstract

Objective. – The aim of this retrospective study was to perform magnetic resonance imaging assessment of olfactory pathway and skull base

abnormalities in Kallmann syndrome (KS) patients with hypogonadotropic hypogonadism and olfaction disorder. Methods. – Magnetic resonance

brain patterns were retrospectively studied in 19 patients clinically classified as KS. Qualitative assessment of olfactory bulb region comprised bulb

atrophy and rectus and medial orbital gyrus ptosis; quantitative assessment measured olfactory fossa depth and width, sulcus depth and ethmoid

angle. Results were compared to an age- and sex-matched control population (n = 19) with no impairment in the region of interest. Sixteen of

the 19 KS patients were genetically screened for mutations associated with KS. Results. – On the above qualitative criteria, 15 of the 19 patients

presented either unilateral (n = 2) or bilateral (n = 13) olfactory bulb agenesis; 16 showed tract agenesis and 16 showed gyrus malformation (ptosis

or absence). On the quantitative criteria, 18 of the 19 patients showed abnormal sulcus depth and/or olfactory fossa malformation and/or abnormal

ethmoid angle. Conclusion. – The presence of malformation abnormalities in the olfactory fossae of 18 of the 19 patients appears to be a key factor

for etiological diagnosis of hypogonadotropic hypogonadism, and should enable targeted study of genes involved in KS.

© 2017 Elsevier Masson SAS. All rights reserved.

Keywords: Kallmann syndrome; Hypogonadism; Olfactory bulb; Olfaction Disorder; Magnetic resonance imaging

Résumé

Objectif. – L’objectif de cette étude rétrospective était d’évaluer par l’imagerie par résonance magnétique (IRM) les anomalies des voies olfactives

et de la base du crâne chez les patients atteints d’hypogonadisme hypogonadotrope avec anosmie dans le cadre du syndrome de Kallmann.

Méthodes. – Nous avons réalisé une relecture des IRM cérébrales de 19 patients atteints cliniquement d’un syndrome de Kallmann avec une

évaluation qualitative (atrophie des bulbes, ptose de gyri-orbitaire médian et rectus) et quantitative (largeur et hauteur des fosses olfactives, angles

ethmoïdaux, profondeur des sulci olfactifs) de la région des bulbes olfactifs en comparaison avec une population contrôle appariée pour l’âge et le

sexe et sans atteinte de cette région (n = 19). Une étude génétique a pu être réalisée chez 16/19 des patients Kallmann. Résultats. – Sur les 19 patients,

∗ Corresponding author. Service de radiologie, centre hospitalier Lyon-Sud – hospices civils de Lyon, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite,

France.

E-mail address: francois.cotton@chu-lyon.fr (F. Cotton).

http://dx.doi.org/10.1016/j.ando.2016.12.003

0003-4266/© 2017 Elsevier Masson SAS. All rights reserved.

TRAUMATISME

3ème cause de dysosmie

30% des traumatisés crâniens graves

5% des traumatisés crâniens légers.

Prévalence augmente si TC sévère, si

TC associé à un trauma maxillo-facial

Peut être lié à un trauma occipital

Lésions de cisaillement ou section des

axones au niveau de la lame criblée

Lésions des bulbes olfactifs.

Contusions frontales inférieures

Méningiome olfactif

Bulbes olfactifs, HPN, HTIC Structural Olfactory Nerve Changes in Patients Sufferingfrom Idiopathic Intracranial Hypertension

Christoph Schmidt1. , Edzard Wiener1. , Jan Hoffmann2, Randolf Klingeb iel1, Fel ix Schmidt 2,

Tobias Hofmann3, Lutz Harms2, Hagen Kunte2*

1 Institute of Radiology, Charit e-Universitatsmedizin Berlin, Berlin, Germany, 2 Department of Neurology, Charite-Universitatsmedizin Berlin, Berlin, Germany,

3 Department of Psychosomatic Medicine, Charite-Universitatsmedizin Berlin, Berlin, Germany

Abst ract

Background: Complications of idiopathic intracranial hypertension (IIH) are usually caused by elevated intracranial pressure(ICP). In a similar way as in the optic nerve, elevated ICP could also compromise the olfactory nerve system. On the otherside, there is growing evidence that an extensive lymphatic network system around the olfactory nerves could be disturbedin cerebrospinal fluid disorders like IIH. The hypothesis that patients with IIH suffer from hyposmia has been suggested inthe past. However, this has not been proven in clinical studies yet. This pilot study investigates whether structural changesof the olfactory nerve system can be detected in patients with IIH.

Methodology/Principal Findings: Twenty-three patients with IIH and 23 matched controls were included. Olfactory bulbvolume (OBV) and sulcus olfactorius (OS) depth were calculated by magnetic resonance techniques. While mean values oftotal OBV (128.76 38.4 vs. 130.06 32.6 mm3, p = 0.90) and mean OSdepth (8.56 1.2 vs. 8.66 1.1 mm, p = 0.91) were similar inboth groups, Pearson correlation showed that patients with a shorter medical history IIH revealed a smaller OBV (r = 0.53,p, 0.01). In untreated symptomatic patients (n = 7), the effect was greater (r = 0.76, p, 0.05). Patients who suffered from IIHfor less than one year (n = 8), total OBV was significantly smaller than in matched controls (116.66 24.3 vs. 149.36 22.2 mm3,p= 0.01). IIH patients with visual disturbances (n = 21) revealed a lower OS depth than patients without (8.36 0.9 vs.10.86 1.0 mm, p, 0.01).

Conclusions/Significance: The results suggest that morphological changes of the olfactory nerve system could be presentin IIH patients at an early stage of disease.

Citat ion: Schmidt C, Wiener E, Hoffmann J, Klingebiel R, Schmidt F, et al. (2012) Structural Olfactory Nerve Changes in Patients Suffering from IdiopathicIntracranial Hypertension. PLoS ONE 7(4): e35221. doi:10.1371/journal.pone.0035221

Editor: Kewei Chen, Banner Alzheimer’s Institute, United States of America

Received October 29, 2011; Accepted March 13, 2012; Published April 6, 2012

Copyright : ß 2012 Schmidt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: No current external funding sources for this study.

Compet ing Interests: The authors have declared that no competing interests exist.

* E-mail: hagen.kunte@charite.de

. These authors contributed equally to this work.

Int roduct ion

Idiopathic intracranial hypertension (IIH) is characterized by

increased intracranial pressure (ICP) and isaffecting mainly obese

women of childbearing age. The aetiology of the disorder is not

well understood but disturbed cerebrospinal fluid (CSF) dynamics

are assumed to be an important factor. Affected patients mostly

suffer from chronic disabling headache and other symptoms of

elevated ICP like visual disturbance, tinnitus and diplopia.

Impairment of visual function is often progressive and permanent

in up to 25% of all cases [1,2,3].

Similar to the optic nerve, the olfactory nerve (ON) is covered

by a meningeal sheath enclosing the subarachnoidal space.

Elevated intracranial pressure (ICP) is a characteristic feature of

IIH and could damage the olfactory nerves (ONs) directly by

mechanical impact. There are also case reports about nasal liquor

leakage in IIH patients [4,5]. The authors argue that an increased

ICP may break the nerve sheaths around the olfactory nerves that

allow for liquor passage via the cribriform plate. In addition, there

is growing evidence that an extensive lymphatic network system

around the ONs could play a role in CSF absorption. The

pathway of CSF absorption leads along the ONs and the

absorbing acting system is located in the submucosal space

associated with the nasal olfactory and respiratory epithelium [6].

The hypothesis that patients with IIH suffer from hyposmia has

been suggested by Kapoor [7]. Giuseffi and colleagues reported

that up to 25% of IIH patients complain about decreased smell

[8]. This assumption is clinically relevant, since undetected and

therefore untreated olfactory disordersare associated with reduced

quality of life and problems with daily life situations [9,10].

Furthermore, patients with hyposmia are at higher risk to develop

depression [11]. However, to the best of our knowledge, clinical

studies investigating the ON system in patients with IIH have not

been reported in the literature.

Decreased olfactory function is mostly associated with reduced

olfactory bulb volume (OBV) [12,13,14,15]. Buschhuter et al.

investigated a large cohort of normal volunteers and defined

normative values for minimal-normal OBV as 58 mm3 in people

, 45 years and as 46 mm3 in people . 45 years [15]. The

importance of the determination of the depth of olfactory sulcus

PLoS ONE | www.plosone.org 1 April 2012 | Volume 7 | Issue 4 | e35221

Structural Olfactory Nerve Changes in Patients Sufferingfrom Idiopathic Intracranial Hypertension

Christoph Schmidt1. , Edzard Wiener1. , Jan Hoffmann2, Randolf Klingebiel1, Felix Schmidt 2,

Tobias Hofmann3, Lutz Harms2, Hagen Kunte2*

1 Institute of Radiology, Charite-Universitatsmedizin Berlin, Berlin, Germany, 2 Department of Neurology, Charite-Universitatsmedizin Berlin, Berlin, Germany,

3 Department of Psychosomatic Medicine, Charite-Universitatsmedizin Berlin, Berlin, Germany

Abstract

Background: Complications of idiopathic intracranial hypertension (IIH) are usually caused by elevated intracranial pressure(ICP). In a similar way as in the optic nerve, elevated ICP could also compromise the olfactory nerve system. On the otherside, there isgrowing evidence that an extensive lymphatic network system around the olfactory nerves could be disturbedin cerebrospinal fluid disorders like IIH. The hypothesis that patients with IIH suffer from hyposmia has been suggested inthe past. However, this has not been proven in clinical studies yet. This pilot study investigates whether structural changesof the olfactory nerve system can be detected in patients with IIH.

Methodology/Principal Findings: Twenty-three patients with IIH and 23 matched controls were included. Olfactory bulbvolume (OBV) and sulcus olfactorius (OS) depth were calculated by magnetic resonance techniques. While mean values oftotal OBV(128.76 38.4 vs. 130.06 32.6 mm3, p=0.90) and mean OSdepth (8.56 1.2 vs. 8.66 1.1 mm, p=0.91) were similar inboth groups, Pearson correlation showed that patients with a shorter medical history IIH revealed a smaller OBV (r=0.53,p, 0.01). In untreated symptomatic patients (n=7), the effect was greater (r=0.76, p, 0.05). Patients who suffered from IIHfor less than one year (n= 8), total OBVwassignificantly smaller than in matched controls (116.66 24.3 vs. 149.36 22.2 mm3,p=0.01). IIH patients with visual disturbances (n= 21) revealed a lower OS depth than patients without (8.36 0.9 vs.10.86 1.0 mm, p, 0.01).

Conclusions/Significance: The results suggest that morphological changes of the olfactory nerve system could be presentin IIH patients at an early stage of disease.

Citation: Schmidt C, Wiener E, Hoffmann J, Klingebiel R, Schmidt F, et al. (2012) Structural Olfactory Nerve Changes in Patients Suffering from IdiopathicIntracranial Hypertension. PLoSONE7(4): e35221. doi:10.1371/journal.pone.0035221

Editor: Kewei Chen, Banner Alzheimer’s Institute, United States of America

Received October 29, 2011; Accepted March 13, 2012; Published April 6, 2012

Copyright: ß 2012 Schmidt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: No current external funding sources for this study.

Competing Interests: The authors have declared that no competing interests exist.

* E-mail: hagen.kunte@charite.de

. These authors contributed equally to this work.

Introduction

Idiopathic intracranial hypertension (IIH) is characterized by

increased intracranial pressure (ICP) and isaffecting mainly obese

women of childbearing age. The aetiology of the disorder is not

well understood but disturbed cerebrospinal fluid (CSF) dynamics

are assumed to be an important factor. Affected patients mostly

suffer from chronic disabling headache and other symptoms of

elevated ICP like visual disturbance, tinnitus and diplopia.

Impairment of visual function isoften progressive and permanent

in up to 25% of all cases [1,2,3].

Similar to the optic nerve, the olfactory nerve (ON) is covered

by a meningeal sheath enclosing the subarachnoidal space.

Elevated intracranial pressure (ICP) is a characteristic feature of

IIH and could damage the olfactory nerves (ONs) directly by

mechanical impact. There are also case reportsabout nasal liquor

leakage in IIH patients [4,5]. Theauthorsargue that an increased

ICP may break thenerve sheathsaround theolfactory nervesthat

allow for liquor passage via thecribriform plate. In addition, there

is growing evidence that an extensive lymphatic network system

around the ONs could play a role in CSF absorption. The

pathway of CSF absorption leads along the ONs and the

absorbing acting system is located in the submucosal space

associated with the nasal olfactory and respiratory epithelium [6].

The hypothesis that patients with IIH suffer from hyposmia has

been suggested by Kapoor [7]. Giuseffi and colleagues reported

that up to 25% of IIH patients complain about decreased smell

[8]. This assumption is clinically relevant, since undetected and

thereforeuntreated olfactory disordersareassociated with reduced

quality of life and problems with daily life situations [9,10].

Furthermore, patientswith hyposmia are at higher risk to develop

depression [11]. However, to the best of our knowledge, clinical

studies investigating the ON system in patients with IIH have not

been reported in the literature.

Decreased olfactory function is mostly associated with reduced

olfactory bulb volume (OBV) [12,13,14,15]. Buschhuter et al.

investigated a large cohort of normal volunteers and defined

normative values for minimal-normal OBV as 58 mm3 in people

, 45 years and as 46 mm3 in people . 45 years [15]. The

importance of the determination of the depth of olfactory sulcus

PLoSONE | www.plosone.org 1 April 2012 | Volume 7 | Issue 4 | e35221

(OS) is less well known. Previous work has indicated a correlation

between reduced olfactory function and smaller depth of OS in

patients with olfactory dysfunction since birth or early childhood

[16]. Wang and colleagues have demonstrated that the OS depth

is reduced in patients with Parkinson disease [17].

The aim of our pilot study was to investigate OBV and OS

depth to verify if the ON system is affected in IIH.

Methods

Patients fulfilling the modified Dandy criteria for IIH [18] and

an age over 18 years were screened using the hospital’s electronic

medical records system. Patients with any secondary cause of

intracranial hypertension were not eligible for inclusion in the

study. Screening period was from November 2005 until May

2010. Approval for this study was obtained from the institutional

ethics committee (Ethikausschuss 1, Charite Campus Mitte).

Written informed consent was obtained from all participants

before enrolment in the study. All clinical investigations have been

conducted according to theprinciplesexpressed in theDeclaration

of Helsinki. Seventy-one patients were potentially eligible to be

included in the study. Altogether 15 patients were excluded by the

exclusion criteria shunt surgery (n = 6), body weight over 180 kg

(n = 3), pregnancy (n = 1), and magnetic resonance imaging (MRI)

phobia (n = 4). One patient fulfilled the criteria for major

depression (diagnosed by the Becks Depression Inventory andHamilton Rating Scale for Depression) and was excluded.

Eighteen patients could not be reached by phone, eight patients

refused because effort of participation in the study wastoo high for

them, and seven subjects objected to participation without

specifying any reasons. All participants underwent clinical

examination to detect olfactory disorders with a different genesis

(e.g. post-infectious, post-traumatic, current sinunasal or upper

respiratory tract infections, tumors treated with radiation orchemotherapy, allergies, depression) at the Special Consulting

Service for Olfactory Disorders at the ENT-Department of the

Charite University in Berlin, Germany. Altogether, 23 patients

could be included in the study.

Each patient with IIH was matched with a control patient for

sex, age and body massindex (BMI). Controlswereselected from a

local obesity center and from the hospital staff. Subjects with

known history of CNS disease or episodes of continuous orrecurring headache syndromes were not eligible to be included in

the control group.

MRI was performed with a 1.5 T scanner (Siemens, Magne-

tom). MRI was obtained to exclude intracranial pathology andsinusvein thrombosisasa secondary cause of IIH. A commerciallyavailable surface coil (Siemens) with a diameter of 7 cm was used

in addition to the normal circularly polarized head coil. Thesurface coil wasplaced over one eye within the head coil and fixedwith tape. T2-weighted high-resolution coronal images were

acquired with the surface coil. A fast spin echo (FSE) sequencewith a relaxation time of 6960 msec, an echo time of 99 msec, a

field of view of 856 85 mm2, a matrix size of 2566 256 mm2 (inplane resolution 3326 332 mm2) and a slice thickness of 2 mm

were performed. The measured time scale was 7 minutes and20 seconds. The OBV as well as the OS depth were determined

using a standardized method [19]. Computer software Amira 3.2was used to calculate quantitative morphological parameters.

OBV was investigated by circumnavigating the bulb contours ofall coronal slices starting from the anterior to the posterior border

of the olfactory bulb. The slice thickness was 2 mm, therefore theOBV could be calculated using the surface areas of each coronal

section through the olfactory bulb (surface area of each coronalsection in mm26 count of sections6 2 mm). The OS depth was

identified at the level of the last coronal slice through the rearmostpart of the eyeball. The depth of the OS was then calculated by

drawing a straight line tangent to the borders of the straight gyrusand internal orbital gyrus. From this line an intergyral line to the

deepest point of the OSdetermined the OSdepth (Figure 1). MRIstudy readerswere blinded to the status and clinical characteristics

of the participating subjects to prevent observer-dependent bias.

Data were presented asmean 6 standard deviation (range) or asmedian (range), if they were not normally distributed. The chi-

square test and independent t-test were used to analyse differencesbetween IIH patients and controls. To determine age-dependent

normal OBV, data proposed by Buschhuter et al. ($ 58 mm3 inpeople , 45 years and $ 46 mm3 in people . 45 years) were used

[15]. Relationships among clinical features of IIH patients, theOBV, and the depth of OS were examined by using Pearsoncorrelation coefficient r. A difference was considered significant at

a p-value of , 0.05.

Figure 1. T2-weighted high-resolut ion coronal images of the olfactory bulb and sulcus olfactorius. Figure 1A and 1Bshow T2-weightedfast spin echo (FSE) sequences. In Figure 1A the white arrows indicate the normal dimensioned right and left bulb olfactorius. Figure 1Bdemonstratesthe calculation of the olfactory sulcus (OS) depth. The distance of the deepest point of the OSwas determined using a tangent line from the border ofthe gyrus rectus to the internal orbital gyrus.doi:10.1371/journal.pone.0035221.g001

Structural Olfactory Nerve Changes in IIH Patients

PLoS ONE | www.plosone.org 2 April 2012 | Volume 7 | Issue 4 | e35221

Bulbes olfactifs et maladie de

Parkinson

44,7 cc

37,3 cc

Test diagnostic précoce? différentiel?

Maladie d’Alzheimer

Epilepsie

HOMME DE 27 ANS

Crises olfactives

Cacosmie.

Gangliogliome Sclérose mésiale

Olfaction et dépression

EVALUATION OF OLFACTORY FUNCTIONAL MRI IN MAJOR

DEPRESSIVE PATIENTS BEFORE AND AFTER TREATMENT

Hibat-Allah S., Tran Dong K., Skeif H., Gressier F., Corruble E., Coui llet A., Ducreux D.

Neuroradiology department, Kremlin Bicêtre Hospital, 94, France.

ABSTRACT

Introduction. Olfactory disorders have been shown in major depressive patients with

increase sensitivity to unpleasant odors. The aim of our study is to evaluate patients with

major depression after 3 months of treatment using olfactory functional MRI.

Materials and methods. 10 subjects with major depression according to DSM-V criteria

were included during 15 months. Olfactory functional MRI (using BOLD method) was

performed before and after 3 months of treatment. 3 scents were used: spearmint for pleasant

odor, sandalwood for neutral odor and wine lee for unpleasant odor. Data processing and

statistical analysis was executed using matlab software (linear regression and t student test).

We performed individual analysis for every scent for the limbic lobe and for every cluster,

and global analysis.

Results.10 patients were including during 15 months. There were 80% of women with a

medium age of 36.7 years old ± 14.9 (18-65). For the global analysis, 100% of patients show

activation for wine lee versus 80% for spearmint and sandalwood with high Zscore superior to

2. For the individual analysis, after 3 months of treatment, we observe a significant difference

of activation for wine lee scent, for anterior cingulum and para-hippocampic gyrus (p‹0.05

and Zscore › 2).

Conclusion. Olfactory functional MRI shows a significant difference of activation for

unpleasant odors in patients with major depression after 3 months of treatment. The structures

mostly involved in this mechanism seem to be the cingular gyrus with the anterior cingulum.

Pr Denis Ducreux

Figure 5. Difference of activation between spearmint (left) and wine lee (right) in major depressive (21)

Courtesy Pr Ducreux Denis www.fmritools.com/teaching-files/limec-teaching-files/isipca/

10 Patients dépréssifs majeurs

Stimulation par 3 odeurs

menthe : agréable

Bois de santal : neutre

Lie de vin : désagréable

IRMf

Suivi avant et après 3 mois de ttt

Modification des activations

Cingulum antérieur

Menthe Lie de vin

Conclusion

Maturation des bulbes