Jl sarrazin olfaction jfim hanoi 2015

OLFACTION JL Sarrazin, F Benoudiba, S Hibat, D Ducreux

Hôpital Américain de Paris CHU de Bicêtre

Hanoi, nov 2015

BACKGROUND

« Regressive » sense (?)•  Primitif sensoriel system :

search for food, search for sexual partners.

•  Decrease of volume : receptors, olfactory bulbs, rhinencephalon

•  Quantitative decrease : Pheromones

•  Human species evolution : vision development/olfactory regression. Promote community life

BACKGROUND

Chemical stimulation-based sense

•  Like taste•  Vision, hearing, touch :

Physical stimulation-based senses

•  Olfaction : more difficult to explore, to quantify

Anatomy

Olfactory receptors Nasal mucosa in contact with cribriforme plate

�  Nasal septum �  Superior turbinateOlfactory mucosa:

5 cm2 in human, 20 cm2 in cats 150 cm2 in dogs

Receptors 107in human 2,2 108 in dog

Olfactory mucosa Bipolary olfactory neurons

Extension within the mucosa ( by 8 to 20 cilia)

Apical extension with clustering of 10 to 100 fibers Bundles of myelinated axons (Schwann cells)

Go through the cribriform plate to reach olfactory bulbs

Lifetime : 2 months. Constant renewal.

Olfactory Bulbs Length 12mm (6 -16 mm). Volume 58 mm3 before 45 yo, 46 mm3 after 45 yo

Mitral cells (neurons) dendrite : glomerulus axons : Olfactory tract

Perigomerular cells….,

Olfactory nerve

Maturation of olfactory bulbs

correlating with the signal intensity of the cerebral white mat-ter were seen in all cases (Fig 1).

At a median age of 287 days (age range, 4 days–22 months)the OBs demonstrated thinning and slight concave deforma-tion of their superior aspect, leading to a U-shaped appearancein 48 studies. The periphery still showed identical signal inten-sity to the cerebral cortex, and the central area also showedsimilar signal intensity compared with cerebral white matter(Fig 2).

At a median age of 5.2 years (age range, 107 days–19.6years), the OBs demonstrated an adult-type form that wassmaller than those of the previous stages, with a predomi-nantly round or slightly J-shaped aspect in 39 studies. In manycases, the lateral part of the bulbs was more prominent thanthe medial part. The central part was no longer distinct fromthe periphery and, as in the previous stages, showed a signalintensity that was identical to the myelinated cerebral whitematter (Fig 3).

No correlation with the sex of the children was found. Agedistribution according to the form and signal intensity patternof the OB can be seen in Fig 4.

DiscussionMR imaging has been successfully used to analyze the normaladult anatomy of the OBs1-4 and to depict abnormal olfactorypathways.5-7 Embryonic and fetal maturational changes havebeen studied in a fixed specimen.8 To date, only 1 study hasreported on the appearance of fetal OBs in vivo.9 Our studyfocused on postnatal development, and our results demon-strate that OBs are well-organized structures that undergo apredefined and predictable maturational process, with rapidlydeveloping olfactory activity ensuing.

Olfactory activity has been demonstrated to begin in utero,

with an active intake of chemosensory information as part ofthe normal fetal experience that shapes the development ofsubsequent chemosensory sensitivities and preferences. Theimmature fetal brain is able to register amniotic odor orcues.10 Neonates actively encode odor cues associated withtheir mothers’ breast and discriminate the odor of their moth-er’s skin or milk from those of other mothers. This abilityallows them to modify their feeding behavior according to themilk flavor.11-13 In general, the neonate brain is extremely re-ceptive to the odor environment. During the first years of life,the role of olfaction is probably very important to mother-child bonding.14

In opposition to other cranial nerves, with the exception ofthe optic nerve, the OB is a true neocerebral extension. Theprimordial of the olfactory apparatus appears in late somiteembryos as 2 ectodermal thickenings, the olfactory or nasalplacodes situated above the stomatodeum and below and lat-eral to the forebrain. By the proliferation of the surroundingmesoderm, these placodes become depressed to form the ol-factory pits that represent the future site of the olfactory nerve.Further growth of the mesoderm causes the epithelium of eachnasal placode to lie in the medial and lateral walls of the upperfifth of the corresponding nasal cavity. Conversely, the neuro-blasts in the olfactory epithelium itself differentiate into nervecells and give origin to olfactory nerve fibers that grow towardthe apical region of the corresponding cerebral hemisphere. Intheir course, the fibers pierce the roof of the cartilaginous nasalcapsule, which has developed around the primitive nasal cav-

Fig 1. Pattern 1 of OBs (black arrows) shows a continuous external neuronal layer and acentral area of T2-hyperintense unmyelinated white matter.

Fig 2. Pattern 2 of OBs (black arrows) shows a thinning of the superior aspect and a stillT2-hyperintense, not yet fully myelinated, central white matter area.

Fig 3. Pattern 3 of OBs (black arrows) shows a slightly J-shaped form with a moreprominent lateral neuronal layer and a now fully myelinated central white matter area.

Fig 4. Demographics and age repartition according to the MR imaging pattern of OBs.

1150 Schneider ! AJNR 30 ! Jun-Jul 2009 ! www.ajnr.org



























ity. They penetrate into the apical region of the hemisphere,which projects ventrally toward the olfactory placode, whichin turn will become the elongated OBs. Eventually, the exten-sion of the ventricular cavity into the OBs will becomeobliterated.

Reflecting their embryologic origin, the external layer ofthe OBs, as suggested by our study, consists of a rim of neuronsoriginally derived from the cortex of the telencephalic vesicle.Cytoarchitectural studies have shown that in rodents, periph-eral neurons are, to some extent, derived from migratory neu-rons originating from the prestriatal subventricular zone butcan also originate from progenitor cells organized around thecore of the OBs.15,16 A similar migratory pathway has onlybeen identified once in humans,17 but this finding is contro-versial.18 These peripheral cells will eventually serve as a relayto the olfactory neurons from the nasal cavity. Therefore, con-sidering that primary olfactory neurons project from beneathand from the side into the OB, the first maturational changewe could recognize was a thinning of the upper aspect of thebulb itself, which might reflect reorganization of those neuro-nal layers that do not receive olfactory inputs. At the peripheryof the OB, the external olfactory nerve layer and the glomeru-lar cells layer located immediately beneath show a prominentlateral and inferior protrusion, whereas the superior aspect isextremely thin to nonexistent (Fig 5). The asymmetric laminarneuronal distribution has been demonstrated in rodents and isseen more pronounced in adult humans.19 This is in contrastto embryonic and fetal human specimens, in which an even,circular distribution of the peripheral layer of the immatureOB is seen.8 In the later stages of postnatal development, weobserved that the lateral part of the OBs (which becomessomewhat J shaped) will become more prominent than itsmedial counterpart. This can be attributed to the fact that thelateral stria as a posterior extension of the OB is the predom-inant anatomic bundle that projects to the primary olfactorycenters of the limbic system.20

Considering the central area of the OBs, it not only consistsof bundles of axons that project to the primary olfactory area

but also consists of a rich extracellular matrix and multipleinterneurons coming from the anterior part of the ganglioniceminence (aGE). These axons and synaptic networks undergoprogressive myelination that is reflected by the fact that thesignal intensity of the center of the OBs parallels the signalintensity of the cerebral white matter. On the other hand, thereis reduction in an extracellular matrix and a correspondingreduction of signal intensity on T2-weighted images. Bothprocesses lead to almost identical signal intensity between thecentral and peripheral layers after the normal adult-type pat-tern is reached. As shown in Fig 3, pattern 2 was seen only upto 22 months after birth, confirming that the adultlike pattern3 is seen in all cases after completion of the second year of life.This parallels the visual end of myelination, as seen on T2-weighted images for the cerebral white matter. It has beenpostulated that this central T2-hyperintensity could representfluid-filled remnants of the ventricular cavity extension intothe OBs as in other mammals,17 which has been disputed18

and is not reflected by our results.The interpretation of our results is subject to some limita-

tions. First, although all 3 maturation steps of the OBs doalways occur, there is a large interindividual variability in the

Fig 6. Serial MR imaging examinations (from top to bottom: ages 2 months, 8 months, and18 months) in the same child show all 3 maturational steps.

Fig 5. Schematic drawing with a coronal cut through the OB, demonstrating asymmetricneuronal layering in an adult OB. a, Nasal olfactory epithelium. b, Cribriform plate. c,Glomerular layer. d, Mitral cell layer. e, Olfactory bulb. f, Olfactory tract.

AJNR Am J Neuroradiol 30:1149 –52 ! Jun-Jul 2009 ! www.ajnr.org 1151


















AJNR Am J Neuroradiol 30:1149 –52 ! Jun-Jul 2009 ! www.ajnr.org 1151ORIGINALRESEARCH

Maturation of the Olfactory Bulbs: MR ImagingFindings

J.F. SchneiderF. Floemer

BACKGROUND AND PURPOSE: The detection of time-related maturational changes of the olfactory bulb(OB) on MR imaging may help early identification of patients with abnormal OB development andanatomic-based odor-cueing anomalies.

MATERIALS AND METHODS: Two separate reviewers retrospectively analyzed coronal T2-weightedspin-echo MR images of the frontobasal region in 121 patients. There were 22 patients who under-went MR imaging examinations several times, accounting for a total of 156 studies. Age range was 1day to 19.6 years. OBs were bilaterally identified in all cases and categorized according to their shapeand signal intensity.

RESULTS: Three different anatomic patterns were identified. In pattern 1 (median age, 15 days; agerange, 1–168 days), the OBs were round to oval with a continuous external T2-hypointense rim and aprominent T2-hyperintense central area. In pattern 2 (median age, 287 days; age range, 4 days–22months), the OBs were U shaped, with thinning and concave deformation of the superior layer. Ahyperintense central area on T2-weighted images was still visible. In pattern 3 (median age, 5.2 years;age range, 107 days–19.6 years), the OBs were small, round, or J shaped with a more prominent lateralpart. No difference in signal intensity between the central area and the peripheral layer was identifiedanymore.

CONCLUSIONS: The OBs show time-related maturational changes on MR imaging. There is a progres-sive reorganization of the peripheral neuronal layers and signal intensity changes of the central area,which are completed at the end of the second year, paralleling cerebral maturational changes.

Normal anatomy of the olfactory pathways and many con-genital or acquired anomalies have been repetitively de-

scribed.1-6 Despite considerable advance in knowledge regard-ing the complex neuronal network associated with olfactorystimulation, information describing the normal maturationprocess in the neonatal period and childhood is scarce. Thereis experimental evidence that anomalies of the face are linkedto abnormal development of the olfactory placode and bulbs.7

The importance of early detection of congenital anomalies ofthe development of the olfactory bulbs (OBs) is not only toidentify patients with odor-coding deficiencies, but also totrigger thorough examination of the frontobasal area andmidline structures, which are embryologically related, and tolook for associated cerebral malformations. Because it is rec-ognized that OBs and nerves are not real cranial nerves butextensions of the telencephalic vesicles, we postulated thattheir maturation should parallel cerebral maturation and bedetected by MR imaging. Therefore, the purpose of our studywas to identify and characterize age-dependent maturationalchanges in the OBs and tracts.

Materials and Methods

PatientsTwo reviewers retrospectively analyzed all routine brain MR exami-nations done at our institution between January 2004 and January2007. The local ethics committee approved the study. Examinations

were excluded in cases of preterm neonates, incomplete visualization

of the OBs, and evidence of brain malformation or generalized brain

pathologic conditions.

A total of 121 children were considered eligible for the study, of

which 22 children had 2 or more consecutive studies. There were a

total of 156 cranial MR imaging examinations, of which 57 were mul-

tiple follow-ups. There were 66 boys (55%) and 53 girls (44%). Age

range was 1 day to 19.6 years (median, 373 days). Written informed

consent before examination was obtained for all patients.

Image Data AnalysisCranial MR imaging examinations were performed on a clinical 1.5T

MR imaging system (Picker 1.5T; Picker International, Cleveland,

Ohio) and included coronal T2-weighted fast spin-echo (FSE) se-

quence, which is part of our routine examination protocol. Scan pa-

rameters were TR, 8490 ms; TE, 119 ms; matrix, 256 ! 384; FOV, 160

mm; section thickness, 3 mm; NEX, 2; and number of sections, 31.

The OBs were identified as prominent structures located above the

cribriform plate with a posterior thinning into the olfactory tracts,

which could be followed in all cases up to their frontobasal and, some-

times, to their limbic projectional areas. Visual inspection on coronal

T2-weighted FSE images were consensually analyzed by 2 observers

(F.F. and J.F.S.), and the OBs were discriminated according to their

shape and signal intensity pattern.

Median age and demographic distribution graphs were performed

with JMP software (JMP IN, version 5.1.2; SAS, Cary, NC).

ResultsImmediately after birth, at a median age of 15 days (age range,1–168 days), the OBs had a round to oval shape in 69 studies.At that stage, a continuous external T2-hypointense rim thatdemonstrated the same signal intensity as that of the corticallayer of cerebral hemispheres, and a central T2-hyperintensity

Received July 4, 2008; accepted after revision December 17.

From the Department of Pediatric Radiology, University Children’s Hospital UKBB, Basel,Switzerland.

Please address correspondence to J.F. Schneider, Department of Pediatric Radiology,University Children’s Hospital UKBB, Romergaße 8, 4058 Basel, Switzerland; e-mail:[email protected]

DOI 10.3174/ajnr.A1501

PEDIATRICSORIGIN

ALRESEARCH


ORIGINALRESEARCH

Maturation of the Olfactory Bulbs: MR ImagingFindings

J.F. SchneiderF. Floemer

BACKGROUND AND PURPOSE: The detection of time-related maturational changes of the olfactory bulb(OB) on MR imaging may help early identification of patients with abnormal OB development andanatomic-based odor-cueing anomalies.

MATERIALS AND METHODS: Two separate reviewers retrospectively analyzed coronal T2-weightedspin-echo MR images of the frontobasal region in 121 patients. There were 22 patients who under-went MR imaging examinations several times, accounting for a total of 156 studies. Age range was 1day to 19.6 years. OBs were bilaterally identified in all cases and categorized according to their shapeand signal intensity.

RESULTS: Three different anatomic patterns were identified. In pattern 1 (median age, 15 days; agerange, 1–168 days), the OBs were round to oval with a continuous external T2-hypointense rim and aprominent T2-hyperintense central area. In pattern 2 (median age, 287 days; age range, 4 days–22months), the OBs were U shaped, with thinning and concave deformation of the superior layer. Ahyperintense central area on T2-weighted images was still visible. In pattern 3 (median age, 5.2 years;age range, 107 days–19.6 years), the OBs were small, round, or J shaped with a more prominent lateralpart. No difference in signal intensity between the central area and the peripheral layer was identifiedanymore.

CONCLUSIONS: The OBs show time-related maturational changes on MR imaging. There is a progres-sive reorganization of the peripheral neuronal layers and signal intensity changes of the central area,which are completed at the end of the second year, paralleling cerebral maturational changes.

Normal anatomy of the olfactory pathways and many con-genital or acquired anomalies have been repetitively de-

scribed.1-6 Despite considerable advance in knowledge regard-ing the complex neuronal network associated with olfactorystimulation, information describing the normal maturationprocess in the neonatal period and childhood is scarce. Thereis experimental evidence that anomalies of the face are linkedto abnormal development of the olfactory placode and bulbs.7

The importance of early detection of congenital anomalies ofthe development of the olfactory bulbs (OBs) is not only toidentify patients with odor-coding deficiencies, but also totrigger thorough examination of the frontobasal area andmidline structures, which are embryologically related, and tolook for associated cerebral malformations. Because it is rec-ognized that OBs and nerves are not real cranial nerves butextensions of the telencephalic vesicles, we postulated thattheir maturation should parallel cerebral maturation and bedetected by MR imaging. Therefore, the purpose of our studywas to identify and characterize age-dependent maturationalchanges in the OBs and tracts.


PatientsTwo reviewers retrospectively analyzed all routine brain MR exami-nations done at our institution between January 2004 and January2007. The local ethics committee approved the study. Examinations

were excluded in cases of preterm neonates, incomplete visualization

of the OBs, and evidence of brain malformation or generalized brain

pathologic conditions.

A total of 121 children were considered eligible for the study, of

which 22 children had 2 or more consecutive studies. There were a

total of 156 cranial MR imaging examinations, of which 57 were mul-

tiple follow-ups. There were 66 boys (55%) and 53 girls (44%). Age

range was 1 day to 19.6 years (median, 373 days). Written informed

consent before examination was obtained for all patients.

Image Data AnalysisCranial MR imaging examinations were performed on a clinical 1.5T

MR imaging system (Picker 1.5T; Picker International, Cleveland,

Ohio) and included coronal T2-weighted fast spin-echo (FSE) se-

quence, which is part of our routine examination protocol. Scan pa-

rameters were TR, 8490 ms; TE, 119 ms; matrix, 256 ! 384; FOV, 160

mm; section thickness, 3 mm; NEX, 2; and number of sections, 31.

The OBs were identified as prominent structures located above the

cribriform plate with a posterior thinning into the olfactory tracts,

which could be followed in all cases up to their frontobasal and, some-

times, to their limbic projectional areas. Visual inspection on coronal

T2-weighted FSE images were consensually analyzed by 2 observers

(F.F. and J.F.S.), and the OBs were discriminated according to their

shape and signal intensity pattern.

Median age and demographic distribution graphs were performed

with JMP software (JMP IN, version 5.1.2; SAS, Cary, NC).

ResultsImmediately after birth, at a median age of 15 days (age range,1–168 days), the OBs had a round to oval shape in 69 studies.At that stage, a continuous external T2-hypointense rim thatdemonstrated the same signal intensity as that of the corticallayer of cerebral hemispheres, and a central T2-hyperintensity

Received July 4, 2008; accepted after revision December 17.

From the Department of Pediatric Radiology, University Children’s Hospital UKBB, Basel,Switzerland.

Please address correspondence to J.F. Schneider, Department of Pediatric Radiology,University Children’s Hospital UKBB, Romergaße 8, 4058 Basel, Switzerland; e-mail:[email protected]

DOI 10.3174/ajnr.A1501

PEDIATRICSORIGIN

ALRESEARCH


Gyrus rectus

Gyrus orbitaire

Olfactory sulcus

Olfactory bulbs and tracts

Olfactory tracts

Anterior perforated Substance

Olfactory trigon

Olfactory Striae

Lateral

Medial

Intermediate

Central connections Lateral Stria

Pyriforme Cortex

Entorhinal Cortex Amygdaloid Complex

Thalamus

Medial Stria Anterior olfactory nucleus (fronto basal)

Qualitative Quantitative�  Cacosmia

�  Parosmia

�  Olfactoryhallucinations

�  Hyposmia

�  Anosmia

�  Hyperosmia

Abnomalities of Olfaction

Aetiologies of Olfactory Abnormalities

EXPLORATIONOlfactometry

Thresholdofdetection

Discriminationtest

Recognitionandmemorytest

Identificationtest

HeadandNeckclinicalexamination

ImagingCTscanner

MRI

Smell physiology :4 steps

MRI : 1/3 of etiologies

⇒  AirborneTransmissionofscentmoleculestonasalmucosa

⇒  NasalMucosatransit

⇒  Tranductionwithinthebipolaryneuron

⇒  CentralIntégration

No Imaging, CT scanner +/- MRI: 2/3 of etiologies






No Imaging, CT scanner +/- MRI: 2/3 of etiologies

Disturbance of Airborne transmission

Chronic inflamatory disease

Edema, inflammation, remodelling

Symptoms

Anosmia

Nasal obstruction

Rhinorrhea

Common disease

Ethmoid sinus

Nasal polyposis

Diagnosis

Symptoms

Rhinoscopy

Ct scanner

Evaluation of extent

Anatomic varaitions

R

Isolated inflammatory obstruction des

of olfactory splits (3%)

Alteration of mucosa transit

Allergic and non allergic rhinitis

Common disease

Symptoms : dysosmia (30%)

Another symptoms: nasal obsttruction (80%)

Posterior Rhinorhea(80%)

Facial pain (60%)

Increase of hydrophilicity of mucosa

Decrease of molecular concentration

Decrease of transporter proteins

Increase of thickness of mucosa

Ct scanner Search of sinusitis

Alteration of transduction

Toxic causes Acétate Chrome Soufre

Acétone Ciment Vernis

Ammoniaque Menthol Zinc

Azote Fluor

Benzène Mercure

Carbone Nickel

Chaux Paprika

Chlore Plomb

Post rhinitic Anosmia

Viral infection

Physiopathologiy :

Destruction of bipolary neurons

Recovery : 60% of cases

Residual dysosmia after 12 months

TDM Search of Sinusitis

Lymphoma

70 yo female Headaches Anosmia

TTT corticoïdes AB

Esthesioneuroblastoma

Esthesioneuroblastoma Rare malignant neoplasm of nasal cavities (3%) arising from olfactory neurepithelium

Neuroectodermal origin

Peaks : the second and sixth decades

Symptoms:

Anosmia, nasal obstruction, exophthalmia, epistaxis

Imaging : local extent, orbitary and encephalic extent.

TTT : surgery, Radiotherapy

21 yo male Chronic Nasal Obstruction

Epistaxis Headache. Anosmia

2 Case Reports in Otolaryngology

Figure 1: T2 weighted MRI with gadolinium showing enhancingmass in left lateral nasal wall and maxillary sinus.

Figure 2: CT sinus demonstrating indolent mass with stippledcalcifications centered at left middle turbinate.

with a nadir serum sodium of 114 mEq/L. Her sodiumlevels normalized each time with saline administration,and so her hyponatremia was believed to be secondary togastroenteritis and dehydration. In July 2007, she was seenagain for malaise and recurrent emesis and was admittedwith a sodium level at 112 mEq/L. Endocrinology was con-sulted for further workup. Their evaluation was significantfor low calcium level (7.8 mg/dL), low serum osmolality(247 mOsm/kg), low urine osmolality (419 mOsm/kg), lowphosphorus level (2.9 mg/dL), and low parathyroid hormonelevel (2.9 pg/mL). A repeat urine osmolality was elevated(1026 mOsm/kg). The remainder of her chemistry panel,urine sodium, cortisol, and thyroid function studies werenormal. The endocrinology service diagnosed her withchronic SIADH and placed her on an oral course ofdemeclocycline to maintain sodium levels.

2.1. Radiographic Studies. An abdominal CT scan revealedbilateral nephrolithiasis without any evidence of neoplasticprocesses. A brain MRI with gadolinium demonstrated aheterogeneous mass in the left nasal cavity, with high T2 andlow T1 signal, with no intracranial involvement (Figure 1).

Figure 3: Low power view showing a nested proliferation ofsmall hyperchromatic cells, prominent fibrillary background, focalmicrocalcification, and overlying respiratory epithelium.

CT scan evaluation of the sinuses showed an indolent-appearing mass with stippled calcifications that was centeredat the left ostiomeatal unit and middle turbinate, protrudinginto the left maxillary sinus, and extending superiorly towardthe cribriform plate (Figure 2).

2.2. Surgical Treatment. The patient was referred to oto-laryngology for evaluation of the nasal mass. Endoscopicevaluation revealed a 2 cm smooth-bordered, polypoid massat the left ostiomeatal unit which extended superiorly andtoward the nasal septum. Outpatient tissue biopsy of thismass was consistent with glial tissue, most likely glioma.This tumor was believed to be the underlying cause of thepatient’s SIADH, and surgical excision was recommended.During this time, however, the patient also discoveredthat she was 10-week pregnant. In consultation with theObstetrics department, the decision was made to performsurgical excision because of the potential risk of recurrenthyponatremia throughout the pregnancy. During secondtrimester, the patient underwent endoscopic total resectionof the neoplasm. The tumor was noted to emanate from thelateral nasal wall and dissected easily from the underlyingbone. Although it extended superiorly to the cribriform area,there was no apparent attachment to the superior nasalcavity.

2.3. Pathological Evaluation. Histologic examination ofhematoxylin and eosin-stained slides demonstrated a prolif-eration of small, hyperchromatic cells exhibiting a predom-inantly nested pattern, in a background of fibrillar materialwith prominent dystrophic calcifications and a few pseu-dorosettes (Figure 3). The tumor was immunoreactive forchromogranin, glial fibrillary acid protein, pancytokeratin,neurofilament protein, neuron-specific enolase, Neu-N, S-100, and synaptophysin. The final pathology interpretationof the excised mass was consistent with grade 1 esthe-sioneuroblastoma with involvement of the middle turbinateremnant that was submitted as a margin.



















Hindawi Publishing CorporationCase Reports in OtolaryngologyVolume 2012, Article ID 582180, 6 pagesdoi:10.1155/2012/582180

Case ReportLow-Grade Esthesioneuroblastoma Presenting as SIADH:A Review of Atypical Manifestations

Andrew Senchak,1 Judy Freeman,2 Douglas Ruhl,3 Jordan Senchak,4 and Christopher Klem3

1 Department of Otolaryngology, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue Bethesda,MD 20889-5600, USA

2 Department of Pathology, Tripler Army Medical Center, Honolulu, HI 96859 5000, USA3 Department of Otolaryngology, Tripler Army Medical Center, Tripler AMC, Honolulu, HI 96859 5000, USA4 Grove City College, Grove City, PA 16127, USA

Correspondence should be addressed to Andrew Senchak, [email protected]

Received 17 October 2012; Accepted 8 November 2012

Academic Editors: J. I. De Diego, M. T. Kalcioglu, K. Morshed, C.-S. Rhee, and G. Zhou

Copyright © 2012 Andrew Senchak et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Esthesioneuroblastoma (ENB) is a neuroendocrine tumor that typically manifests as advanced stage malignancy in the superiornasal cavity. The hallmark symptoms include nasal obstruction and epistaxis, which result from local tissue invasion. Atypicalclinical features can also arise and must be considered when diagnosing and treating ENB. These can include origin in an ectopiclocation, unusual presenting symptoms, and associated paraneoplastic syndromes. The case described here reports a nasal cavityENB with atypical clinical features that occurred in a young female. Her tumor was low grade, appeared to arise primarily fromthe middle nasal cavity, and presented as syndrome of inappropriate antidiuretic hormone (SIADH). She also became pregnantshortly after diagnosis, which had implications on her surgical management. We review the atypical features that uncommonlyoccur with ENB and the clinical considerations that arise from these unusual characteristics.

1. Introduction

Esthesioneuroblastoma is a rare nasal malignancy thataccounts for 3% of all intranasal tumors [1]. A review ofthe world literature revealed up to 1000 published cases andsuggested that the true incidence may be underestimated [2].ENBs have a bimodal age of onset in the second and sixthdecades of life and most commonly manifest as aggressivetumors in the superior aspect of the nasal cavity in closeproximity to the cribriform plate [3]. The typical symptomsinclude unilateral nasal obstruction and epistaxis whichpresent in later stages of disease, as early lesions are usuallyslow growing and asymptomatic [4].

ENBs arise from cells of neuroectodermal origin. In thenasal cavity, this type of tissue occurs in olfactory epitheliumwhich can be found in the superior nasal cavity at the areaof the cribriform plate, along the superior septum, and at thesuperior turbinate [5]. The pathologic features of this tumorare distinct and include nesting, low-grade stippled nuclei

and neurofibrillary stroma with formation of pseudorosettes[6]. Like many malignancies, ENBs primarily cause invasionand destruction of surrounding structures, with potential formetastasis.

We describe a patient with ENB that presented inseveral atypical ways—low-grade tumor which appeared tooriginate in the middle nasal cavity, presentation as syn-drome of inappropriate antidiuretic hormone (SIADH), anddiagnosis during pregnancy. We review the unusual charac-teristics that may uncommonly occur in ENBs and whichmust be considered when evaluating patients with thismalignancy.

2. Case

A 28-year-old female presented with recurrent episodes ofemesis, malaise, and diarrhea over a 3-year time period, from2004 to 2007. She was admitted twice for hyponatremia,

Hindawi Publishing CorporationCase Reports in OtolaryngologyVolume 2012, Article ID 582180, 6 pagesdoi:10.1155/2012/582180

Case ReportLow-Grade Esthesioneuroblastoma Presenting as SIADH:A Review of Atypical Manifestations

Andrew Senchak,1 Judy Freeman,2 Douglas Ruhl,3 Jordan Senchak,4 and Christopher Klem3

1 Department of Otolaryngology, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue Bethesda,MD 20889-5600, USA

2 Department of Pathology, Tripler Army Medical Center, Honolulu, HI 96859 5000, USA3 Department of Otolaryngology, Tripler Army Medical Center, Tripler AMC, Honolulu, HI 96859 5000, USA4 Grove City College, Grove City, PA 16127, USA

Correspondence should be addressed to Andrew Senchak, [email protected]

Received 17 October 2012; Accepted 8 November 2012

Academic Editors: J. I. De Diego, M. T. Kalcioglu, K. Morshed, C.-S. Rhee, and G. Zhou

Copyright © 2012 Andrew Senchak et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Esthesioneuroblastoma (ENB) is a neuroendocrine tumor that typically manifests as advanced stage malignancy in the superiornasal cavity. The hallmark symptoms include nasal obstruction and epistaxis, which result from local tissue invasion. Atypicalclinical features can also arise and must be considered when diagnosing and treating ENB. These can include origin in an ectopiclocation, unusual presenting symptoms, and associated paraneoplastic syndromes. The case described here reports a nasal cavityENB with atypical clinical features that occurred in a young female. Her tumor was low grade, appeared to arise primarily fromthe middle nasal cavity, and presented as syndrome of inappropriate antidiuretic hormone (SIADH). She also became pregnantshortly after diagnosis, which had implications on her surgical management. We review the atypical features that uncommonlyoccur with ENB and the clinical considerations that arise from these unusual characteristics.

1. Introduction

Esthesioneuroblastoma is a rare nasal malignancy thataccounts for 3% of all intranasal tumors [1]. A review ofthe world literature revealed up to 1000 published cases andsuggested that the true incidence may be underestimated [2].ENBs have a bimodal age of onset in the second and sixthdecades of life and most commonly manifest as aggressivetumors in the superior aspect of the nasal cavity in closeproximity to the cribriform plate [3]. The typical symptomsinclude unilateral nasal obstruction and epistaxis whichpresent in later stages of disease, as early lesions are usuallyslow growing and asymptomatic [4].

ENBs arise from cells of neuroectodermal origin. In thenasal cavity, this type of tissue occurs in olfactory epitheliumwhich can be found in the superior nasal cavity at the areaof the cribriform plate, along the superior septum, and at thesuperior turbinate [5]. The pathologic features of this tumorare distinct and include nesting, low-grade stippled nuclei

and neurofibrillary stroma with formation of pseudorosettes[6]. Like many malignancies, ENBs primarily cause invasionand destruction of surrounding structures, with potential formetastasis.

We describe a patient with ENB that presented inseveral atypical ways—low-grade tumor which appeared tooriginate in the middle nasal cavity, presentation as syn-drome of inappropriate antidiuretic hormone (SIADH), anddiagnosis during pregnancy. We review the unusual charac-teristics that may uncommonly occur in ENBs and whichmust be considered when evaluating patients with thismalignancy.

2. Case

A 28-year-old female presented with recurrent episodes ofemesis, malaise, and diarrhea over a 3-year time period, from2004 to 2007. She was admitted twice for hyponatremia,

TREATMENT MODALITIESThe various treatment modalities used in the mana-gement of ENB are surgery, chemotherapy, radiation therapy (RT) and palliative care. Nowadays, the multi-modal approach is recommended for improved survival and quality of life of the patients.

SurgeryThe mainstay of the treatment is surgery. The advantage of surgery is tumor removal, immediate improvement in compressive symptoms, proper tissue for histo-pathological and prognostic evaluation. Intracranial extension and close proximity to the cribriform plate and ethmoidal roof requires a combined transfacial and neurosurgical approach[12]. For T1 tumors, craniotomy is not justified when there is clear radiological evidence

of a normal cribriform plate and upper ethmoid cells. All other patients should be managed by combined craniofacial approach. Dulguerov et al[5]

showed 100%

local control with craniofacial resection as compared

to 40% local control with other surgical resections.

Similarly, Spaulding et al[13] at the University of Virginia

showed reduction of 20% local recurrence rate with the

craniofacial resection as compared to non-craniofacial approach. An international collaborative study of 17 centres reported the role of craniofacial resection in ENB in 2012. Five-year overall survival was 78% and

5-year recurrence-free survival was 64%[14]. Craniofacial resection allows en bloc resection of the tumour with better assessment of intracranial extension and protection of the brain and optic nerves. The current accepted practice is open or endoscopic craniofacial surgical resection.

RT Specimens from the nasal cavity and paranasal sinuses,

even en bloc, are difficult to orient, and surgical margins

are difficult to analyze properly. Due to locally infiltrative

nature of the disease, surgically clear margins are difficult to achieve. Thus there is a role of adjuvant RT to

minimize the risk of local recurrence[12,15]. Adjuvant RT

is indicated for Kadish stage B and C, whereas Kadish A disease can be managed with surgery alone. RT is delivered to the tumor bed and local extension with nodal irradiation reserved for involved nodes. Elective nodal irradiation is not practiced routinely. The RT doses have varied from 50 to 60 Gy in the literature

[16,17]. With higher RT doses, there is always a risk of long term neural toxicity. But with advancement in technologies in delivery of RT with Intensity modulated RT (IMRT),

Image guided RT and proton therapy, the long term neural toxicities can be minimized. RT is also used

in neoadjuvant settings in locally advanced tumors and in palliation in metastatic settings. In small local recurrences, stereotactic radiosurgery and stereotactic radiotherapy can be used even for re-radiation[18].

Chemotherapy The role of chemotherapy is not very clear in adjuvant settings in early tumors, but in locally advanced and metastatic tumors it has a definitive role. It decreases the

chances of systemic failure by acting on systemic micro-

776 September 16, 2015|Volume 3|Issue 9|WJCC|www.wjgnet.com

Table 3 Tumor, node, metastasis staging system

T1 Tumour involving the nasal cavity and/or paranasal sinuses (excluding sphenoid), sparing the most superior ethmoidal cells

T2 Tumour involving the nasal cavity and/or paranasal sinuses (including the sphenoid) with extension to or erosion of the cribriform plate

T3 Tumour extending into the orbit or protruding into the anterior cranial fossa, without dural invasion

T4 Tumour involving the brainN0 No cervical lymph-node metastasisN1 Any form of cervical lymph-node metastasisM0 No metastasesM1 Distant metastasis

A B

Figure 2 T1 W sagital section (A) and axial section (B) magnetic resonance imaging showing locally advanced esthesioneuroblastoma. Reprinted with permission from medscape drugs and diseases (http://emedicine.medscape.com/), 2015, Available from: URL: http://emedicine.medscape.com/article/250237-overview.

Table 2 Modified kadish staging

Stage A: Tumour limited to the nasal fossaStage B: Tumour extension into the paranasal sinusesStage C: Tumour extension beyond the paranasal sinuses and nasal cavityStage D: Distant metastasis

Kumar R. Esthesioneuroblastoma: Multimodal management

45 yo female Hyposmia Nasal Obstruction

Olfactory Schwannoma

Olfactory schwannoma

�  from olfactory bundles?

�  From meningeal branches of trijeminal nerve?

�  From anterior ethmoidal nerve (branche of V1)?

T2-weighted magnetic resonance images (MRI)revealed a subfrontal tumor; it was hyperintense andiso-mixed intense to the white matter (Fig. 1A). Itextended into the left ethmoid sinus and was hypoin-tense on T1-weighted images and heterogeneouslyenhanced (Fig. 1B). Coronal bone CT showed thinningof the left cribriform plate and medial endofrontal foveawith marked compression in the direction of the nasalcavity (Fig. 1C). A left carotid angiogram disclosed ahypervascular mass in the base of the anterior cranialfossa mainly; it was fed by the left anterior ethmoidalartery and displaced the anterior cerebral artery upward(Fig. 2). Positron emission tomography (PET) scan-ning with 18-fluorodeoxyglucose (FDG) and 11-meth-ylmethionine was performed to rule out metastaticdisease and carcinoma of the ethmoid sinus (Fig. 3).Methionine PET revealed moderate accumulation ofthe tracer compared with surrounding cerebral tissue;the tumor was depicted as a low-accumulation area onFDG PET. The preoperative diagnosis included neu-roblastoma and olfactory groove meningioma.

We performed bifrontal craniotomy. Upon open-ing the dura mater, on the left frontal lobe we found anextra-axial mass partially attached to the dura of the leftfrontal base. It was elastic, hard, and hypervascular. Aftercauterization of the large feeding artery arising from thecribriform plate, we performed internal decompression.The tumor was separated from arachnoid tissue coveringthe frontal lobe. The dura mater of the frontal basewas thin and almost absent at the lowermost part of thetumor. The bone of the frontal base was depressedtoward the nasal cavity; however, the bone cortex waspreserved. The left olfactory nerve was thinned andstretched medially but anatomically preserved. The tu-mor did not attach to the falx. It was totally resected.The defect in the left frontal base was filled withabdominal fat and covered with a periosteal flap secured

with fibrin glue. The craniotomy was closed and dressedin standard fashion. Postoperative MRI confirmed totalresection of the tumor (Fig. 4).

Histological examination disclosed proliferationof spindle cells with columnar nuclei exhibiting a fas-cicular pattern and focal nuclear palisading (Fig. 5).Loose myxoid stroma and hyalinized vessels were alsonoted. Some areas of fibrosis with calcification andvascular proliferation were noted. There was no necrosisor cellular atypia. Immunohistochemical staining re-vealed tumor-cell positivity for S-100 and CD57.

The patient’s hyposmia improved postoperatively,and he was discharged without any neurological deficit at19 days after the operation.

Figure 1 (A) Axial T2-weighted magnetic resonance imaging (MRI) revealing a subfrontal heterogeneously hyperintensemass. (B) Sagittal MRI with gadolinium demonstrating an enhanced subfrontal mass with extension to the ethmoid sinus. (C)Coronal computed tomography showing erosion of the left cribriform plate.

Figure 2 Digital subtraction angiogram with left internalcarotid artery injection showing the hypertrophic ophthalmicartery feeding the subfrontal mass.

60 SKULL BASE REPORTS/VOLUME 1, NUMBER 1 2011

37. Bando K, Obayashi M, Tsuneharu F. A case of subfrontalschwannoma. No Shinkei Geka 1992;20:1189–1194[Japanese, with English abstract]

38. Harada T, Kawauchi M, Watanabe M, Kyoshima K, KobayashiS. Subfrontal schwannoma—case report. Neurol Med Chir1992;32:957–960

39. Gatsher S, Love S, Coakham HB. Giant nasal schwannomawith intracranial extension. J Neurosurg 1998;89:161

40. Bezircioglu H, Sucu HK, Rezanko T, Minoglu M. Nasal-subfrontal giant schwannoma. Turkish Neurosurg 2008;18:412–414

64 SKULL BASE REPORTS/VOLUME 1, NUMBER 1 2011

Subfrontal Schwannoma MimickingNeuroblastoma: Case ReportHitoshi Yamahata, M.D.,1 Kazuho Hirahara, M.D.,1 Tetsuzou Tomosugi, M.D.,1

Masahiko Yamada, M.D.,1 Takeshi Ishii, M.D.,1 Takashi Ishigami, M.D.,1

Koichi Uetsuhara, M.D.,1 Kazunobu Sueyoshi, M.D.,2 Sumika Matsukida, M.D.,2

Kazutaka Yatsushiro, M.D.,3 and Kazunori Arita, M.D.3

ABSTRACT

Computed tomography (CT), performed in a healthy 28-year-old man afterminor head injury, detected a frontal base tumor. Neurological examination revealed lefthyposmia. On magnetic resonance imaging scans, there was a heterogeneously enhancedtumor located in the left paramedian frontal base with extension into the left ethmoidsinus. Angiography showed a hypervascular mass in the left anterior cranial fossa; it wasmainly fed by the left ethmoidal artery. Positron emission tomography scanning showedmoderate accumulation of 11-methylmethionine and low accumulation of 18-fluorodeox-yglucose (FDG) at the tumor site. Bone image CT disclosed compressive, nondestructivedeformation of the left frontal base. The preoperative diagnosis was olfactory neuro-blastoma or meningioma. The tumor was totally resected via bifrontal craniotomy. Thetumor was histologically diagnosed as typical schwannoma; it was positive for S-100protein. We report a rare subfrontal schwannoma with extension into the nasal cavity thatmimicked neuroblastoma. Low FDG accumulation and compressive deformation of theanterior skull base may help in the differential diagnosis of these tumors.

KEYWORDS: Subfrontal schwannoma, olfactory nerve, neuroblastoma, skull base

Schwannomas arise from the nerve sheaths ofperipheral and cranial nerves. They account for 6 to 8%of all intracranial tumors.1,2 They commonly arisefrom the vestibular nerve and less commonly from thefifth, ninth, and tenth cranial nerves. Schwannomasof the olfactory groove or subfrontal region are rare;49 cases have been reported to date.3–26 Because of theirrarity, these tumors can be misdiagnosed preoperativelyas meningioma or olfactory neuroblastoma. We report arare anterior cranial fossa schwannoma with extensioninto the ethmoid sinus and highlight factors that can

contribute to the preoperative differential diagnosis ofthese tumors.

CASE REPORTThis 28-year-old man underwent computed tomography(CT) after a minor head injury. It revealed a tumor at theanterior skull base. His neurological and general exami-nations were normal except for left hyposmia. Theresults of intravenous olfaction tests were within normallimits.

Departments of 1Neurosurgery and 2Clinical Pathology, KagoshimaCity Hospital; 3Department of Neurosurgery, Graduate School ofMedical and Dental Sciences, Kagoshima University, Kagoshima,Japan.

Address for correspondence and reprint requests: Hitoshi Yamahata,M.D., Department of Neurosurgery, Graduate School of Medical andDental Sciences, Kagoshima University, 8-35-1 Sakuragaoka,Kagoshim-shi, Kagoshima 890-8520, Japan (e-mail: yamahata-nsu@

umin.net).Skull Base Rep 2011;1:59–64. Copyright # 2011 by Thieme

Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001,USA. Tel: +1(212) 584-4662.

Received: December 9, 2010. Accepted: January 17, 2011. Publishedonline: March 25, 2011.DOI: http://dx.doi.org/10.1055/s-0031-1275637.ISSN 2157-6971.

59

ORIGINAL ARTICLE

The Puzzling Olfactory Groove Schwannoma:A Systematic ReviewEberval Gadelha Figueiredo, M.D., Ph.D.,1 Yougi Soga, M.D.,2

Robson Luis Oliveira Amorim, M.D.,1 Arthur Maynart Pereira Oliveira, M.D.,1

and Manoel Jacobsen Teixeira, M.D., Ph.D.1

ABSTRACT

We systematically reviewed the literature concerning the anterior cranial fossaschwannomas to understand their pathogenesis, determine their origin, and standardizethe terminology. We performed a MEDLINE, EMBASE, and Science Citation IndexExpanded search of the literature; age, gender, clinical presentation, presence or absence ofhyposmia, radiological features, and apparent origin were analyzed and tabulated. Cases ina context of neurofibromatosis and nasal schwannomas with intracranial extension were notincluded. Age varied between 14 and 63 years (mean¼ 30.9). There were 22 male and 11female patients. The clinical presentation included seizures (n¼ 15), headache (n¼ 16),visual deficits (n¼ 7), cognitive disturbances (n¼ 3), and rhinorrhea (n¼ 1). Hyposmiawas present in 14 cases, absent in 13 cases (39.3%), and unreported in five. Homogeneousand heterogeneous contrast enhancement was observed in 14 and 15 cases, respectively.The region of the olfactory groove was the probable site in 96.5%. Olfactory tract could beidentified in 39.3%. The most probable origin is the meningeal branches of trigeminalnerve or anterior ethmoidal nerves. Thus, olfactory groove schwannoma would better describeits origin and pathogenesis and should be the term preferentially used to name it.

KEYWORDS: Anterior cranial fossa, olfactory groove, olfactory nerve, schwannomas,subfrontal tumors

Schwannomas are benign, slowly growing nervesheath tumors.1–4 They account for "8% of all intra-cranial tumors and can arise from any nerve containingSchwann cells.4–7 The most common location is thevestibular portion of the VIIIth cranial nerve and, lesscommonly, the Vth, IXth, Xth, and VIIth cranialnerves.4–9 The occurrence of a schwannoma not relatedto cranial nerves is exceedingly rare, with the mostcommon location being the anterior cranial fossa. Insuch instances, they have been described under differentdesignations, such as subfrontal, olfactory, and olfactory

groove schwannomas,1–6,8–28 reflecting their enigmaticorigin. However, these terminologies have contributedto the confusion concerning pathogenesis and havecreated a great deal of speculation about it. It is stillnot clear which type of cell gives rise to these schwan-nomas and even whether they are derived from thecerebral parenchyma.4 This uncertainty is partially dueto the incompleteness of the previous literature reviews,which have provided only limited contribution. Toaddress these issues, the authors performed a systematicreview of the literature.

1Division of Neurological Surgery, University of Sao Paulo, School ofMedicine, Sao Paulo, Brazil; 2Department of Neurosurgery, BrainResearch Institute, Nigata University, Nigata, Japan.

Address for correspondence and reprint requests: Eberval G.Figueiredo, M.D., Ph.D., Rua Oscar Freire, 1399, AP 171, CEP05409-010, Sao Paulo-SP, Brazil (e-mail: [email protected]).

Skull Base 2011;21:31–36. Copyright # 2011 by Thieme Medical

Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.Tel: +1 (212) 584-4662.

Received: February 17, 2010. Accepted after revision: May 25,2010. Published online: July 26, 2010.DOI: http://dx.doi.org/10.1055/s-0030-1262945.ISSN 1531-5010.

31

METHODSThe authors first performed a MEDLINE, EMBASE,and Science Citation Index Expanded search of theliterature of the last 30 years with the use of four keywords in all relevant combinations: schwannoma, olfac-tory, olfactory groove,and anterior cranial fossa.

Additionally, the reference lists of all retrievedpublications were scrutinized. The references of thepublications thus found were checked again for addi-tional studies. This method of cross-checking wascontinued until no further publications were found.

Inclusion and Exclusion CriteriaPapers reporting anterior fossa schwannomas pub-lished in English, Japanese, German, Spanish, andPortuguese were reviewed. Data such as age, gender,clinical presentation, presence or absence of hyposmia,radiological features, and apparent origin were ana-lyzed and tabulated. Site of origin was defined byradiological features coupled with surgical description,when this information was available. Studies reportingautopsy cases in a context of neurofibromatosis wereexcluded from the review. Papers describing nasalschwannomas with intracranial extension were alsonot included.

RESULTSThis systematic review is summarized in Table 1.Thirty-three cases of anterior fossa schwannomas wereidentified.

Age, Gender, and Clinical PresentationAge varied between 14 and 63 years (mean¼ 30.9).There were 22 male (66.6%) and 11 female (33.3%)patients. Clinical presentation included seizures, themost common finding (n¼ 15; 45% of the cases); head-ache (n¼ 16; 48% of the cases); visual deficits (n¼ 7;21.2% of the cases); cognitive disturbances (n¼ 3; 9% ofthe cases); and rhinorrhea (n¼ 1; 3% of the cases).Anosmia/hyposmia was present in 14 cases (42.4%),absent in 13 cases (39.3%), and unreported in 5 cases(15.1%). Therefore, anosmia/hyposmia was absent in54.4% of the cases in which this information could beretrieved.

Radiological Features and Apparent OriginTumor was solid in 19 patients (57.5%) and cystic in10 (30.3%). Radiological appearance was unreportedin 5 cases (15.1%). Homogeneous and heterogeneouscontrast enhancement was observed in 14 (42.4%) and15 cases (45.4%), respectively. Enhancement was notreported in five patients (15.1%).

In most of the cases (n¼ 31; 93.9%), the lesionwas located in the midline with close relationship withthe olfactory groove. In just one case, the lesion was notclearly related with the olfactory groove. In one case, theorigin could not be determined, as the author described arecurrence of the primary tumor. Therefore, the regionof the olfactory groove was the apparent origin in 96.5%of all cases where the origin was clearly reported.

Olfactory TractOlfactory tract was identified but involved in six cases(18.1%), individualized and thinned in six (18.1%), anddistant from the tumor in one (3.4%). Olfactory tractwas not identified in 10 cases (34%). The involvement ofthe olfactory tract was unreported in 11 cases (33.3%).Olfactory tract could be identified in 39.3% (n¼ 13) ofthe cases that reported its status.

DISCUSSIONIntracranial schwannomas unrelated to the cranial nervesare extremely uncommon.5–7,16,29 They occur more fre-quently in the anterior cranial fossa, mainly in the mid-line. In these instances, they have been described assubfrontal schwannomas, olfactory schwannomas, or olfac-tory groove schwannomas.1–6,8–28 These different termi-nologies, associated with their rarity and enigmaticorigin, further complicate the study of intracranialschwannomas.1,2,4 Schwannomas mainly arise fromnerve sheaths of peripheral and cranial nerves (exceptfor first and second cranial nerves). However, thepathogenesis of intracranial schwannomas not directlyassociated with cranial nerves has been puzzling.1–7

Additionally, considerable debate exists whetherthese schwannomas are primarily intra- or extra-axiallesions.1,2,4

There are several hypotheses concerning theirprobable origin. Developmental theories advocate thatthese lesions primarily arise from aberrant Schwann cellsin the central nervous system.1,4 Russel and Rubinstein30

have proposed that mesenchymal pial cells may trans-form into ectodermal Schwann cells, explaining theoccurrence of intraparenchymal schwannomas. Addi-tionally, peripheral-type myelin has been found inpathological conditions such as multiple sclerosis andcerebral infarctions, presumably originating fromSchwann cells in the central nervous system.31 Othertheories suggest an origin from multipotential mesen-chymal cells or displacement of neural crest cells formingthe focus of Schwann cells within brain parenchyma(schwannosis).30

These developmental theories adequately explainthe origin of intraparenchymal schwannomas.1,2,4,32

However, the subtype of schwannomas located in thebase of the frontal lobe and intimately related to the

32 SKULL BASE/VOLUME 21, NUMBER 1 2011

15 yo male Headache, visula disorders Rapidly evolutive anosmia

Rhabdomyosarcoma


MRI : 1/3 of etiologies





Alteration of olfatory tracts and cortical areas

MRI

Brain

Flair, T2*, diffusion

Skull basa:

Coronal T2w

Spin echo : 2mm

T2 HR (Ciss, Fiesta, Drive,)

Volume T2 (cube, space..)

Injection if necessary

Alteration of olfatory tracts and cortical areas

Malformation

Traumatisms

Tumors

Degenerative or inflammatory pathologies

Congenital Dysosmia Holoprosencéphalie

CHARGE syndrom (colobome, cardiopathie, atrésie des choanes, retard de développement, anomalies des oreilles et génitales)

Kallmann syndrom Hypogonadotropic Hypogonadism

GnRH deficiency micopenis,cryptochidism

Anosmia or hyposmia

Olfatory bulbs hypoplasia or aplasia

Failure Olfatory system development

Sporadic or genetic transmission

TRAUMATISM 3ème cause of dysosmia

30% of severe head injuries

5% of mild brain traumatism.

Maxillo facial trauma

Occipital trauma

Shearing of olfactory axons at level of cribirform plate

Olfactory bulbs tearing

Inferior frontal contusion

DIAGNOSTIC NEURORADIOLOGY

Olfactory bulb volume in patients with idiopathic normalpressure hydrocephalus

Dino Podlesek & Mario Leimert & Benno Schuster &

Johannes Gerber & Gabriele Schackert &Matthias Kirsch & Thomas Hummel

Received: 21 March 2012 /Accepted: 28 May 2012 /Published online: 9 June 2012# Springer-Verlag 2012

AbstractIntroduction An important pathological feature of idiopathicnormal pressure hydrocephalus (iNPH) is a dysfunction ofcerebrospinal fluid dynamics. Considering the delicate olfac-tory structures it appears possible that the olfactory bulb (OB)is compromised by this disease. Reports on the anatomy of theolfactory bulb and smell function in patients with idiopathicnormal pressure hydrocephalus are absent in the literature.The main purpose of the present study was to evaluate theolfactory bulb (OB) volume and smell function in iNPH.Methods The study comprised 17 patients with iNPH (sevenwomen and ten men, mean age066 years); they were com-pared to a group of 24 healthy people (11 women and 13men, mean age062 years). Comprehensive assessment ofolfactory function was conducted with the "Sniffin’ Sticks"test kit. In an additional pilot study, in a small subgroup ofeight patients, measurements were performed before andapproximately 7 months after surgical treatment of thehydrocephalus.

Results The OB volume in patients with iNPH was signif-icantly smaller compared to healthy controls. In our smallpostoperative patient population (n08), there was no signif-icant change of the OB volume.Conclusion In conclusion our results suggest that iNPHsignificantly affects OB volumes.

Keywords Hydrocephalus . Olfactory bulb volume .

Olfaction . Smell . Brain plasticity

Introduction

Hydrocephalus is characterized by an increased accumulationof cerebrospinal fluid within ventricles and subarachnoidspace. The triad of gait disturbance, incontinence, and demen-tia is known as the Hakim triad [1, 2] and represents thecardinal symptoms of idiopathic normal pressure hydroceph-alus (iNPH). The average age at the diagnosis of iNPH isabove 60 years with male predominance. The clinical presen-tation, the enlargement of the cerebral ventricles in contrast tothe narrow supratentorial pericerebral space, plus the flattenedcortical sulci is central to the diagnosis of iNPH. Themagneticresonance imaging (MRI) of iNPH patients often demon-strates deep white matter hyperintensity and subcortical lacu-nar infarctions. Intrusion of the CSF into the periventricularwhite matter and periventricular gliosis are one of the neuro-imaging and histologic characteristics of iNPH [3]. Recently,the temporal changes in apparent diffusion coefficient of thefrontal white matter during cardiac cycle were detected as apotential marker for the diagnosis of iNPH [4].

On average, there is intermittent increase of intracranialpressure. Acute hydrocephalus can lead to papilledema, andthe chronic disruption of cerebrospinal fluid dynamics may

D. Podlesek (*) :M. Leimert :G. Schackert :M. KirschDepartment of Neurosurgery, Technical Universityof Dresden Carl–Gustav–Carus Medical School,Fetscherstrasse 74 01307, Germanye-mail: [email protected]

B. Schuster : T. HummelDepartment of Otorhinolaryngology, Smell and Taste Clinic,Technical University of Dresden(Technische Universität Dresden),Fetscherstrasse 74 01307, Germany

J. GerberDepartment of Neuroradiology, Technical Universityof Dresden (Technische Universität Dresden),Fetscherstrasse 74 01307, Germany

Neuroradiology (2012) 54:1229–1233DOI 10.1007/s00234-012-1050-8

DIAGNOSTIC NEURORADIOLOGY

Olfactory bulb volume in patients with idiopathic normalpressure hydrocephalus

Dino Podlesek & Mario Leimert & Benno Schuster &

Johannes Gerber & Gabriele Schackert &Matthias Kirsch & Thomas Hummel

Received: 21 March 2012 /Accepted: 28 May 2012 /Published online: 9 June 2012# Springer-Verlag 2012

AbstractIntroduction An important pathological feature of idiopathicnormal pressure hydrocephalus (iNPH) is a dysfunction ofcerebrospinal fluid dynamics. Considering the delicate olfac-tory structures it appears possible that the olfactory bulb (OB)is compromised by this disease. Reports on the anatomy of theolfactory bulb and smell function in patients with idiopathicnormal pressure hydrocephalus are absent in the literature.The main purpose of the present study was to evaluate theolfactory bulb (OB) volume and smell function in iNPH.Methods The study comprised 17 patients with iNPH (sevenwomen and ten men, mean age066 years); they were com-pared to a group of 24 healthy people (11 women and 13men, mean age062 years). Comprehensive assessment ofolfactory function was conducted with the "Sniffin’ Sticks"test kit. In an additional pilot study, in a small subgroup ofeight patients, measurements were performed before andapproximately 7 months after surgical treatment of thehydrocephalus.

Results The OB volume in patients with iNPH was signif-icantly smaller compared to healthy controls. In our smallpostoperative patient population (n08), there was no signif-icant change of the OB volume.Conclusion In conclusion our results suggest that iNPHsignificantly affects OB volumes.

Keywords Hydrocephalus . Olfactory bulb volume .

Olfaction . Smell . Brain plasticity

Introduction

Hydrocephalus is characterized by an increased accumulationof cerebrospinal fluid within ventricles and subarachnoidspace. The triad of gait disturbance, incontinence, and demen-tia is known as the Hakim triad [1, 2] and represents thecardinal symptoms of idiopathic normal pressure hydroceph-alus (iNPH). The average age at the diagnosis of iNPH isabove 60 years with male predominance. The clinical presen-tation, the enlargement of the cerebral ventricles in contrast tothe narrow supratentorial pericerebral space, plus the flattenedcortical sulci is central to the diagnosis of iNPH. Themagneticresonance imaging (MRI) of iNPH patients often demon-strates deep white matter hyperintensity and subcortical lacu-nar infarctions. Intrusion of the CSF into the periventricularwhite matter and periventricular gliosis are one of the neuro-imaging and histologic characteristics of iNPH [3]. Recently,the temporal changes in apparent diffusion coefficient of thefrontal white matter during cardiac cycle were detected as apotential marker for the diagnosis of iNPH [4].

On average, there is intermittent increase of intracranialpressure. Acute hydrocephalus can lead to papilledema, andthe chronic disruption of cerebrospinal fluid dynamics may

D. Podlesek (*) :M. Leimert :G. Schackert :M. KirschDepartment of Neurosurgery, Technical Universityof Dresden Carl–Gustav–Carus Medical School,Fetscherstrasse 74 01307, Germanye-mail: [email protected]

B. Schuster : T. HummelDepartment of Otorhinolaryngology, Smell and Taste Clinic,Technical University of Dresden(Technische Universität Dresden),Fetscherstrasse 74 01307, Germany

J. GerberDepartment of Neuroradiology, Technical Universityof Dresden (Technische Universität Dresden),Fetscherstrasse 74 01307, Germany

Neuroradiology (2012) 54:1229–1233DOI 10.1007/s00234-012-1050-8

volumetric measurements of the olfactory bulbs, tracts andthe temporal lobes can be reliably and accurately reproducedfrom MR images.

Statistical analyses

All statistics were performed using SPSS software version17.0 (SPSS, Inc., Chicago, IL, USA). T tests for independent(group comparisons) and paired samples (pre-/postsurgerycomparisons) were used. Correlations according to Pearsonwere computed between volumetric measurements of the OBand functional measurements. The level of significance wasset at 0.05.

Results

Descriptive and comparative statistics for olfactory parame-ters are listed in Table 1. The two groups were significantlydifferent with patients exhibiting smaller OBs (p<0.02); inaddition, patients had lower olfactory function than controlsas indicated by decreased scores in all three subtests, odorthresholds, odor discrimination, and odor identification (p<0.04). With regard to the TDI score, only two iNPH patientswere normosmic, while nine were hyposmic and three hadfunctional anosmia (scores were not present from threepatients).

Within the context of a pilot study in eight subjects it waspossible to obtain measures also after surgery. When com-paring results before and after surgery, however, no signif-icant differences emerged (Table 2).

Discussion

In our study, we have shown that patients with iNPH symp-toms and hydrocephalus characteristics in MRI have signif-icantly smaller OB volumes than healthy controls. Weexamined the olfaction in those patients due to the describedCSF absorption via olfactory pathway through the cribri-form plate to nasal submucosa [6]. The majority of thepatients with iNPH were hyposmic before the implantationof the ventriculoperitoneal shunt. Although our patientsonly have had minor demential symptoms, if any, the defi-cits in odor identification could already be an expression ofa beginning dementia.

MRI volumetrics can be reliably used to assess the olfac-tory system [13]. The volume of OB has been evaluated andmeasured in several neurologic and otorhinolaryngologicdiseases [10, 14]. Patients with idiopathic intracranial hy-pertension present at early stage with significantly smallerOB volume compared to healthy controls [5]. Regarding themissing effect of surgery in our pilot study, it may be that theobservation time was too short, although Gudziol et al. haveseen OB changes after 3 months of observation time in theirpatient group with chronic rhinitis [10]. Thus, a follow-up

Fig. 1 Olfactory bulb from a patient with iNPH (71-year-old male) and ahealthy control subject (76-year-old male), a (TSE) sequence, coronalplane healthy subject. b (TSE) sequence, coronal plane iNPH patient. c(TSE) sequence, coronal plane, manual volumetry of OB

Neuroradiology (2012) 54:1229–1233 1231

study will consider longer testing intervals between surgeryand second measurement.

Limitations of the study

Underdiagnosis of iNPH and in many cases ambiguous dis-tinction to other neurological diseases in elderly is one of thebiggest limitations in general. One of the criteria is the clinicaldevelopment of the disease. Although our study tried to narrowthis with development of additional MRI parameters, it isrestrainted by a small number of patients. Future studies shouldalso incorporate patients with different clinical development ofiNPH and other hydrocephalus forms.

Because of a very narrow diagnostic window and studycriteria that included only patients without dementia or withminor symptoms of dementia, significantly more controlsthan patients were included in our study. Patients with majordementia were not compliant and did not fulfill the studycriteria.

Why is the OB volume decreased in iNPH? Numeroushypotheses have been proposed for the development ofiNPH [15, 16]. In the case of transiently increased intracra-nial pressure, it is imaginable that the consequent loweringof the cerebral blood flow and function of anatomic struc-tures might be affected. In accordance to anatomic impair-ment of the optic nerve in hydrocephalus, the smaller OBcould also result from local CSF pressure. Alternatively,plasticity of the OB could be slowed.

Conclusions

Preoperative OB volumes in patients with iNPH were sig-nificantly smaller compared to healthy controls. A longitu-dinal study in a larger group of patients might be needed todetect possible volume changes of OB after the placement ofventriculoperitoneal shunt and normalisation of the intracranialpressure.

Table 1 Descriptive (means andstandard deviations) and com-parative statistics (results from ttests for independent samples)for patients (n017) and healthycontrols (n024)

Mean Standarddeviation

T value Degrees offreedom

P value

Age (in years) Patients 66.4 6.4 1.72 39 0.094

Controls 62.4 7.9

OB right (in mm3) Patients 47.9 12.7 3.11 39 0.004

Controls 59.4 10.8

OB left (in mm3) Patients 48.5 13.7 2.59 39 0.013

Controls 59.4 13.1

Odor threshold (in dilution steps) Patients 5.3 2.8 2.24 36 0.031

Controls 7.1 2.3

Odor discrimination (number correct) Patients 8.7 2.8 3.28 36 0.002

Controls 11.9 2.9

Odor identification (number correct) Patients 9.6 3.1 5.03 36 <0.001

Controls 13.5 1.6

Table 2 Descriptive (means andstandard deviations) and compar-ative statistics (results from t testsfor paired samples) for patients(n08) before and after surgery

Mean Standarddeviation

T value Degrees offreedom

P value

OB right before surgery (mm3) 45.3 9.3 0.23 7 0.82OB right after surgery (mm3) 44.6 6.9

OB left before surgery (mm3) 45.8 10.6 0.31 7 0.76OB left after surgery (mm3) 45.1 6.5

Odor thresholds before surgery (dilution steps) 5.6 2.4 1.41 4 0.23Odor thresholds after surgery (dilution steps) 5.0 2.1

Odor discrimination before surgery (number correct) 10.6 2.8 0.56 4 0.61Odor discrimination after surgery (number correct) 9.0 4.1

Odor identification before surgery (number correct) 9.2 3.1 1.84 4 0.14Odor identification after surgery (number correct) 10.8 2.6

1232 Neuroradiology (2012) 54:1229–1233

NPH and olfactory bulbs

Idiopathic Intracranial hypertension and olfactory bulbs

Structural Olfactory Nerve Changes in Patients Sufferingfrom Idiopathic Intracranial HypertensionChristoph Schmidt1., Edzard Wiener1., Jan Hoffmann2, Randolf Klingebiel1, Felix Schmidt2,

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 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 (128.7638.4 vs. 130.0632.6 mm3, p = 0.90) and mean OS depth (8.561.2 vs. 8.661.1 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 (116.6624.3 vs. 149.3622.2 mm3,p = 0.01). IIH patients with visual disturbances (n = 21) revealed a lower OS depth than patients without (8.360.9 vs.10.861.0 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. 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: ! 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: [email protected]

. These authors contributed equally to this work.

Introduction

Idiopathic intracranial hypertension (IIH) is characterized byincreased intracranial pressure (ICP) and is affecting mainly obesewomen of childbearing age. The aetiology of the disorder is notwell understood but disturbed cerebrospinal fluid (CSF) dynamicsare assumed to be an important factor. Affected patients mostlysuffer from chronic disabling headache and other symptoms ofelevated ICP like visual disturbance, tinnitus and diplopia.Impairment of visual function is often progressive and permanentin up to 25% of all cases [1,2,3].

Similar to the optic nerve, the olfactory nerve (ON) is coveredby a meningeal sheath enclosing the subarachnoidal space.Elevated intracranial pressure (ICP) is a characteristic feature ofIIH and could damage the olfactory nerves (ONs) directly bymechanical impact. There are also case reports about nasal liquorleakage in IIH patients [4,5]. The authors argue that an increasedICP may break the nerve sheaths around the olfactory nerves thatallow for liquor passage via the cribriform plate. In addition, thereis growing evidence that an extensive lymphatic network system

around the ONs could play a role in CSF absorption. Thepathway of CSF absorption leads along the ONs and theabsorbing acting system is located in the submucosal spaceassociated with the nasal olfactory and respiratory epithelium [6].The hypothesis that patients with IIH suffer from hyposmia hasbeen suggested by Kapoor [7]. Giuseffi and colleagues reportedthat up to 25% of IIH patients complain about decreased smell[8]. This assumption is clinically relevant, since undetected andtherefore untreated olfactory disorders are associated with reducedquality of life and problems with daily life situations [9,10].Furthermore, patients with hyposmia are at higher risk to developdepression [11]. However, to the best of our knowledge, clinicalstudies investigating the ON system in patients with IIH have notbeen reported in the literature.

Decreased olfactory function is mostly associated with reducedolfactory bulb volume (OBV) [12,13,14,15]. Buschhuter et al.investigated a large cohort of normal volunteers and definednormative values for minimal-normal OBV as 58 mm3 in people,45 years and as 46 mm3 in people .45 years [15]. Theimportance of the determination of the depth of olfactory sulcus

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





Abstract












Introduction










Abstract












Introduction






(OS) is less well known. Previous work has indicated a correlationbetween reduced olfactory function and smaller depth of OS inpatients with olfactory dysfunction since birth or early childhood[16]. Wang and colleagues have demonstrated that the OS depthis reduced in patients with Parkinson disease [17].

The aim of our pilot study was to investigate OBV and OSdepth to verify if the ON system is affected in IIH.

Methods

Patients fulfilling the modified Dandy criteria for IIH [18] andan age over 18 years were screened using the hospital’s electronicmedical records system. Patients with any secondary cause ofintracranial hypertension were not eligible for inclusion in thestudy. Screening period was from November 2005 until May2010. Approval for this study was obtained from the institutionalethics committee (Ethikausschuss 1, Charite Campus Mitte).Written informed consent was obtained from all participantsbefore enrolment in the study. All clinical investigations have beenconducted according to the principles expressed in the Declarationof Helsinki. Seventy-one patients were potentially eligible to beincluded in the study. Altogether 15 patients were excluded by theexclusion 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 majordepression (diagnosed by the Becks Depression Inventory andHamilton Rating Scale for Depression) and was excluded.Eighteen patients could not be reached by phone, eight patientsrefused because effort of participation in the study was too high forthem, and seven subjects objected to participation withoutspecifying any reasons. All participants underwent clinicalexamination to detect olfactory disorders with a different genesis(e.g. post-infectious, post-traumatic, current sinunasal or upperrespiratory tract infections, tumors treated with radiation orchemotherapy, allergies, depression) at the Special ConsultingService for Olfactory Disorders at the ENT-Department of theCharite University in Berlin, Germany. Altogether, 23 patientscould be included in the study.

Each patient with IIH was matched with a control patient forsex, age and body mass index (BMI). Controls were selected from alocal 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 inthe control group.

MRI was performed with a 1.5 T scanner (Siemens, Magne-tom). MRI was obtained to exclude intracranial pathology andsinus vein thrombosis as a secondary cause of IIH. A commerciallyavailable surface coil (Siemens) with a diameter of 7 cm was usedin addition to the normal circularly polarized head coil. Thesurface coil was placed over one eye within the head coil and fixedwith tape. T2-weighted high-resolution coronal images wereacquired with the surface coil. A fast spin echo (FSE) sequencewith a relaxation time of 6960 msec, an echo time of 99 msec, afield of view of 85685 mm2, a matrix size of 2566256 mm2 (inplane resolution 3326332 mm2) and a slice thickness of 2 mmwere performed. The measured time scale was 7 minutes and20 seconds. The OBV as well as the OS depth were determinedusing 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 borderof the olfactory bulb. The slice thickness was 2 mm, therefore theOBV could be calculated using the surface areas of each coronalsection through the olfactory bulb (surface area of each coronalsection in mm2 6 count of sections 6 2 mm). The OS depth wasidentified at the level of the last coronal slice through the rearmostpart of the eyeball. The depth of the OS was then calculated bydrawing a straight line tangent to the borders of the straight gyrusand internal orbital gyrus. From this line an intergyral line to thedeepest point of the OS determined the OS depth (Figure 1). MRIstudy readers were blinded to the status and clinical characteristicsof the participating subjects to prevent observer-dependent bias.

Data were presented as mean 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-dependentnormal 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 ata p-value of ,0.05.

Figure 1. T2-weighted high-resolution coronal images of the olfactory bulb and sulcus olfactorius. Figure 1A and 1B show T2-weightedfast spin echo (FSE) sequences. In Figure 1A the white arrows indicate the normal dimensioned right and left bulb olfactorius. Figure 1B demonstratesthe calculation of the olfactory sulcus (OS) depth. The distance of the deepest point of the OS was 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


Parkinson disease and olfactory bulbs

ORIGINALRESEARCH

Association of Olfactory Bulb Volume andOlfactory Sulcus Depth with Olfactory Function inPatients with Parkinson Disease

J. WangH. You

J.-F. LiuD.-F. Ni

Z.-X. ZhangJ. Guan

BACKGROUND AND PURPOSE: Olfactory dysfunction is commonly associated with IPD. We here reportthe association of OB volume and OS depth with olfactory function in patients with PD.

MATERIALS AND METHODS: Morphometric analyses by using MR imaging and the Japanese T&Tolfactometer threshold test were used to evaluate olfactory structure and function in 29 patients withPD and 29 age- and sex-matched healthy controls.

RESULTS: The olfactory recognition thresholds were significantly higher in patients with PD than inhealthy controls (3.82 ! 1.25 versus 0.45 ! 0.65, P " .001). Olfactory atrophy with reductions in thevolume of the OB (37.30 ! 10.23 mm3 versus 44.87 ! 11.84 mm3, P " .05) and in the depth of OS(8.90 ! 1.42 mm versus 9.67 ! 1.24 mm, P " .05) was observed in patients with PD but not incontrols. Positive correlations between olfactory performance and OB volumes were observed in bothpatients with PD (r # $0.45, P " .0001) and in controls (r # $0.42, P " .0001). In contrast, there wasno significant correlation between the depth of OS and olfactory function in either cohort.

CONCLUSIONS: The results provide evidence that early olfactory dysfunction in patients with PD maybe a primary consequence of damage to the OB. Neuroimaging of olfactory structures together withthe assessment of olfactory function may be used to identify patients with PD.

ABBREVIATIONS: DWI # diffusion-weighted imaging; IPD # idiopathic Parkinson disease; OB #olfactory bulb; OS # olfactory sulcus; PD # Parkinson disease; SEM # standard error of the mean;SNpc # substantia nigra pars compacta; T&T # Toyota and Takagi

Olfactory deficits are common in patients with IPD, occur-ring at about the same frequency as resting tremor.1-3 Be-

tween 70% and 90% of patients with PD have olfactory deficitsindependent of disease severity and duration.4,5 Olfactory dys-function is thus the second most common feature of this dis-order, following rigidity and akinesia.6 The high prevalence ofolfactory dysfunction in patients with IPD suggests that IPDmay actually be an olfactory disease.5,6 Recent neuropatho-logic advances suggest that the olfactory system is among theearliest brain regions involved in PD7 and olfactory deficits areassociated with the presence of incidental Lewy bodies in thebrains of decedents without parkinsonism or dementia duringlife.8 Results from postmortem studies revealed Lewy bodies inthe OB9 but also in other brain regions related to olfaction,such as the anterior olfactory nucleus,10 the piriform cortex,11

the amygdaloid complex,12 the entorhinal cortex, and the hip-pocampal formation.12 A recent study demonstrated that ol-factory dysfunction in PD is related to atrophy in olfactory-eloquent regions of the limbic and paralimbic cortices.13

These olfactory deficits have been linked to structural and/orfunctional changes at the level of the OB 9,12,14,15 and OS.16

There is evidence from numerous studies that MR imagingcan be used to reliably evaluate the volume of the OB and the

depth of OS.15-18 It has been suggested that analysis of OBvolume might be helpful in differential and early diagnosis ofPD.15,18 However, recent studies did not show significant dif-ferences in OB volume between patients with PD and healthycontrols.15,18 These results are surprising in light of the signif-icant decrease in dopaminergic neurons in the anterior olfac-tory nucleus, which is part of the OB.19 Moreover, the depthsof the bilateral OS measured from the coronal view in MRimaging were not different between the patients with PD andcontrol groups.16 Therefore, it was unclear whether OB struc-tural changes are associated with olfactory dysfunction in PD.

This study, therefore, set out to assess the OB volumes andOS depths and their correlations with olfactory function inpatients with PD and in healthy controls. Olfactory functionwas correlated with reductions in the volume of OB and thedepth of OS in patients with PD. Therefore, neuroimaging ofthe olfactory structure together with the assessment of olfac-tory function may be relevant to PD diagnosis.


SubjectsA total of 30 patients with PD (15 men and 15 women; mean age, 61.7years; range, 43–78 years) and 30 age- and sex-matched healthy con-trols (15 men and 15 women; mean age, 62.6 years, range, 42– 81years) were initially included in the study. The volume of the OB inthe 19th patient with PD was more than the value of mean ! 3 SD,thus this sample and the matched control were excluded. Therefore,there were only 29 patients with PD and 29 healthy controls includedfor statistical analysis. All participants were recruited through the De-partment of Neurology at the University of Peking Union MedicalCollege Hospital. Diagnoses were made according to the diagnostic

Received May 11, 2010; accepted after revision September 7.

From the Department of Otolaryngology, Peking Union Medical College Hospital, Beijing,China.

Jian Wang and Hui You contributed equally to this work.

Please address correspondence to Dao-Feng Ni, Prof. MD, Department of Otolaryngology,Peking Union Medical College Hospital, Beijing 100730, China; e-mail: [email protected]

DOI 10.3174/ajnr.A2350

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DOI 10.3174/ajnr.A2350

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J.-F. LiuD.-F. Ni

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Statistical AnalysesData were expressed as mean ! SEM. The various measures wereassessed by using the Statistical Package for the Social Sciences, Ver-sion 11.5 (SPSS, Chicago, Illinois). Differences between patients withPD and healthy controls were analyzed by a paired-samples t test.Relationships among olfactory function, the volume of OB, and thedepth of OS were examined by using Pearson correlation coefficients.Values of P " .05 were assumed to be statistically significant.

Results

Olfactory Function Decreased in Patients with PDCompared with Healthy ControlsSeveral tests have been used for olfactory assessment, includ-ing tests of odor identification, detection, discrimination,memory, suprathreshold odor intensity, and pleasantness per-ception. Previous studies have demonstrated that the test-re-test reliability was equivalent for the T&T olfactometer and theUniversity of Pennsylvania Smell Identification Test.25,26 Inthis study, we used the T&T olfactometer to evaluate the ol-factory performance. As shown in Fig 2, the means of recog-nition thresholds were significantly higher in patients with PDthan in control subjects (3.82 ! 1.25 and 0.45 ! 0.65 respec-tively; t # 14.59, P " .0001).

OB Volume and OS Depth Lower in Patients with PDCompared with ControlsNumerous studies have demonstrated that OB volume as-sessed by MR imaging is correlated to olfactory function inhealthy subjects and in patients with pathologic conditions.27

MR imaging was used to compare the structures of the OB andthe OS in patients with PD and healthy controls. As shown inFig 1, the OB and OS could be seen by using both T1-weightedand T2-weighted imaging sequences. Quantitative analysesshowed that the volume of the OB varied from 26 to 90 mm3,with a mean of 44.87 ! 11.84 mm3, in the control group (Fig3). In contrast, the patients with PD had mean OB volume of

37.30 ! 10.23 mm3, which was statistically different from thatof the controls (t # 2.98, P " .01). The mean depth of the OSwas statistically smaller in patients with PD than in controlsubjects (8.90 ! 1.42 mm and 9.67 ! 1.24 mm, respectively;t # 2.32, P " .05).

Correlations among Olfactory Function, OB Volume, andOS DepthAs shown in Fig 4, the volume of the OB correlated positivelywith odor recognition threshold scores as obtained by T&Tolfactometry in both patients with PD and in controls, (r #$0.448 and P " .0001 for patients with PD; r # $0.420, P ".05 for controls). In contrast, there was not a significant cor-relation between the depth of the OS and olfactory perfor-mance in either cohort (r # $0.045, P # 0.81 for patients withPD; r # $0.09, P # .61 for controls).

DiscussionAlthough most patients with PD have olfactory defi-cits,1,2,13,18,19,28 the pathologic mechanism is unknown. Thepresent study indicated that there was atrophy of the olfactorysystem in the patients with PD, as shown by lower OB volumeand OS depth compared with healthy controls. Most impor-tant, the OB volume correlated positively with olfactory dys-function in patients with PD. This will provide insight into thecritical interplay of olfactory functional loss and structural ab-normalities in PD.

Idiopathic PD is traditionally considered a movement dis-order, with hallmark lesions located in the SNpc. However,recent histopathologic studies suggest the possibility that PD isa multisystem disorder that progresses in a predictable se-quence as described in the staging criteria of Braak et al.12,29

The disease process starts in the dorsal motor nucleus of thevagus and anterior olfactory nucleus and bulb and spreadsthrough the brain stem nuclei to ultimately reach the SNpc,progressing through stages 1, 2, and 3.30 Early diagnosis of PDin stages 1 and 2, when degenerative changes have not yetreached the SNpc, may allow progression of the disease to behalted or delayed. Braak et al29,31 and Hawkes et al32 found thatthe initial changes in stage 1 of the disease start simultaneouslyin the dorsal nucleus of the vagus nerve and in the olfactorynucleus and bulb where the olfactory neuroepithelium is inthe entry zone. It is possible that initial changes in the olfactorynucleus and bulb may contribute to the early loss of olfactoryfunction observed in patients with PD.

The early diagnostic procedures incorporating olfactoryevaluation such as the University of Pennsylvania Smell Iden-tification Test33 are already used. To further diagnose the na-ture of the olfactory deficit, MR imaging can be used.13,15-18 Arecent DWI study confirmed disruption of the olfactory tractin patients with early stages of PD,34 and DWI would add anobserver-independent and quantitative measure of symptomsin at-risk subjects. More recently, a morphometric analysis ofMR imaging, called voxel-based morphometry, was used toinvestigate gray matter atrophy related to psychophysicallymeasured scores of olfactory function in patients with earlyPD, patients with moderately advanced PD, and age-matchedhealthy controls.13 The results provided first evidence that ol-factory dysfunction in PD is related to atrophy in olfactory-eloquent regions of the limbic and paralimbic cortex.

Fig 2. T&T olfactometer threshold tests in patients with PD and in healthy controls. Themeans of recognition thresholds are significantly higher in patients with PD than in controlsubjects. Data are expressed as means ! SEM.


Recently, several studies have been set out to investigate thestructural changes at the level of the OB and OS in patientswith PD.15-18 The OB ends with the olfactory tract and isclosely related to the OS of the frontal lobe. The OB collects thesensory afferents of the olfactory receptor cells located in theolfactory neuroepithelium. It has been shown that OB volumedecreases with the duration of the olfactory loss.27 However,comparison of OB volumes did not yield significant differ-ences between patients with PD (n ! 11) with anosmia andhealthy normosmic controls.15 Support for the results of anonsignificant difference in OB volume between patients withPD and controls comes from reports by Mueller et al18 andHuisman et al,9 though there were only 11 and 10 patients withPD in these studies, respectively. In the present study, 29 pa-tients with PD and 29 age- and sex-matched healthy controlswere included, providing more statistical power. Because ol-faction may be processed predominantly in the right hemi-sphere,23,35,36 both sides of each individual were measured,and the greater OB volume was used in our analysis, in whichwe observed significant differences in OB volume between pa-tients with PD and controls. In addition, the OS depth wassignificantly smaller in patients with PD than in controls; thisresult differed from that of another study in which no differ-ence in OS depth was found between patients with PD (n !42) and controls.16 Therefore, further studies of more subjectsare needed.

Our study using the T&T olfactometer threshold test con-firmed that patients with PD experience olfactory loss, consis-tent with previous studies.2,19 The correlation of olfactoryfunction with volume of the human OB has been estab-lished.24,37 In this study, a positive correlation between olfac-tory deficit and OB volume was found both in patients with

PD and controls. It may be that olfactory dysfunction in PD isrelated to loss of olfactory neurons or disrupted input to theOB. We found no correlation of olfactory performance andOS depth, indicating that olfactory loss does not parallel thestructural changes to the OS in patients with PD. Together,these data support the idea that olfactory loss in the earlieststages of PD (stage 1 according to Braak et al12) is not a con-sequence of damage to the OS but rather results from OBatrophy.

ConclusionsIn summary, the present study was performed with a largesample size, well-validated test instruments, standardizedneurologic examinations, and published diagnostic criteria.The results provide evidence that olfactory impairment is avaluable biomarker for PD. Olfactory testing together withneuroimaging of olfactory structures may provide a simpleand relatively economic means of identifying individuals athigh risk for development of PD.

AcknowledgmentsWe thank Medjaden Bioscience Limited for assisting in thepreparation of this article.

References1. Ansari KA, Johnson A. Olfactory function in patients with Parkinson’s dis-

ease. J Chronic Dis 1975;28:493–972. Doty RL, Deems DA, Stellar S. Olfactory dysfunction in parkinsonism: a gen-

eral deficit unrelated to neurologic signs, disease stage, or disease duration.Neurology 1988;38:1237– 44

3. Mesholam RI, Moberg PJ, Mahr RN, et al. Olfaction in neurodegenerativedisease: a meta-analysis of olfactory functioning in Alzheimer’s and Parkin-son’s diseases. Arch Neurol 1998;55:84 –90

Fig 3. OB volume (A) and OS depth (B) in patients with PD and in healthy controls. The mean OB volumes and the mean OS depths are statistically smaller in patients with PD than incontrol subjects. Data are expressed as means " SEM.

Fig 4. Correlation of the volume of OB with olfactory performance in patients with PD (A) and in healthy controls (B). In patients with PD and in controls, the OB volumes correlate positivelywith odor recognition threshold scores.

680 Wang ! AJNR 32 ! Apr 2011 ! www.ajnr.org

44,7 cc

37,3 cc

Test for early diagnosis? for differential diagnosis?

Olfactory Meningioma

retractions that may potentially increase thedegree of brain swelling.The classical bifrontal craniotomy does

not allow a safe exposure of large OGMs, asdemonstrated by the incidence of life-threatening complications related to brainretraction (1, 5, 11, 18, 21). Alternative sur-gical routes include the pterional andorbitolateral approaches (1, 2, 11, 15, 17, 19,21, 23, 24), which expose the posterolateralsurface of the tumor from a lateral view,and the fronto-basal-orbital approach (8,21), in which the tumor is accessed fromthe underneath exposing its dural attach-ment first. Here, we report our experiencewith 99 OGMs and correlate the clinicaloutcome of the patients with the surgicalapproach used to remove the tumor. Wealso define the clinical and pathologicpredictors of prognosis in OGMs.

CLINICAL MATERIAL AND METHODS

Patient PopulationNinety-nine consecutive patients withOGMs who had been surgically treated be-tween 1984 and 2010 at the Institute ofNeurosurgery, Università Cattolica del SacroCuore, Rome, entered this study. Therewere 35 men (35.4%) and 64 women(64.6%) who ranged in age from 17 to 82years (median 58, mean 57 years) (Table 1and Supplementary Table S1). The mostfrequent complaint was anosmia (59.6%),followed by visual impairment (46.5%),headache (38.4%), and mental changes(35.4); no complaints were present in 4patients (4%) (Table 2). The tumor wasimaged by magnetic resonance in 85 casesand/or by computed tomography in 57cases. Angiography was performed in 7cases; in 3 cases preoperative embolizationwas performed. In 80 cases, the tumor waslocalized to the olfactory groove byreviewing the preoperative radiologicimages; in the remaining 19 cases,radiographic reports and surgery noteswere used. Ethmoidal invasion wasdefined as paranasal sinus extension ofenhancing tumor through the floor of theanterior cranial fossa. Two patients hadundergone previous surgery and werereferred at our institution for recurrenttumors (Supplementary Table S1).The median follow-up was 89 months

(range, 2e324 months). All patients werefollowed up with clinical examination and

computed tomography/magnetic resonancestudies 6 months and 1 year after surgery. Inthe following 10 years, patients were re-examined at 1- or 2-year intervals. There-after, intervals were based on each follow-up result. Tumor recurrence was definedas at least a 20% increase in residual tumoror the appearance of a new lesion with at

least 10 mm in longest diameter on follow-up neuroimaging (4). Surgical mortalitywas defined as death occurring within 30days from the date of surgery.

Size and Extension of TumorsOverall, the mean tumor size was 5.4 cm.Meningioma size was small (!3 cm) in 15 of99 cases (15.2%), medium (3e6 cm) in 33 of99 (33.3%), and large ("6 cm) in 51 of 99(51.5%) of cases (Table 3 and SupplementaryTable S2). The mean tumor size was 2.4 cm(range 1.8e3 cm), 4.4 cm (range 3.5e5.5cm), and 6.9 cm (range 6e9 cm) in small,medium, and large OGMs, respectively.Small OGMs had no locoregionalextension. Ethmoidal invasion was presentin 4 of 33 cases (12.1%) of medium OGMsand in 7 of 51 cases (13.7%) of large OGMs(Table 3). Optic nerve involvement waspresent in 12 of 33 (36.4%) and 24 of 51(47.1%) patients of medium and largeOGMs, respectively. Vascular encasementwas evident in 2 of 33 (6.1%) and 7 of 51(13.7%) patients of medium and largeOGMs, respectively. In one patientsuffering from type II neurofibromatosis,the tumor extended through the middlecranial fossa of one side to the petrousregion where it collided with a vestibularschwannoma (14). Hyperostosis of theanterior cranial fossa was found in 28 cases(28.3%).

Table 1. Basic Demographic Chart in99 Patients with OGMs

Characteristic No. patients

Sex, n (%)

Male 35 (35.4)

Female 64 (64.6)

Age, years

Median 58

Range 17e82

Preoperative KPS

Median 80

Range 40e100

Follow-up, months

Median 89

Range 2e324

OGM, olfactory groove meningioma; KPS, Karnofskyperformance status.

Table 2. Presenting Symptoms andSigns in 99 Patients with OGMs

Symptoms and Signs No. Patients (%)

Anosmia 59 (59.6)

Visual impairment 46 (46.5)

Headache 38 (38.4)

Mental changes 35 (35.4)

Seizures 19 (19.2)

Papilledema 9 (9.1)

Hemiparesis 7 (7.1)

Incontinence 7 (7.1)

Optic atrophy 6 (6.1)

Epistaxis 6 (6.1)

Foster-Kennedy 3 (3.0)

Incidental 4 (4.0)

OGMs, olfactory groove meningiomas.

Table 3. Tumor Size and GrowthPatterns of 99 OGMs

Tumor Diameter andExtension

No. Patients(%)

!3 cm 15 (15.2)

Ethmoidal invasion 0 (0)

Optic nerve involvement 0 (0)

ACoA complex involvement 0 (0)

3-6 cm 33 (33.3)

Ethmoidal invasion 4 (12.1)

Optic nerve involvement 12 (36.4)

ACoA complex involvement 2 (6.1)

"6 cm 51 (51.5)

Ethmoidal invasion 7 (13.7)

Optic nerve involvement 24 (47.1)

ACoA complex involvement 7 (13.7)

OGM, olfactory groove meningiomas; ACoA, anteriorcommunicating artery.

220 www.SCIENCEDIRECT.com WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2014.11.001

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ROBERTO PALLINI ET AL. OLFACTORY GROOVE MENINGIOMA

Alzheimer disease

LE JOURNAL FAXÉ DE L’O. R. L. Sous l’égide du Conseil National de l’O. R. L.

C. F. O. R. L. ( S. F. O. R. L. ( S. N. O. R. L.

Comité Scientifique : F Chabolle � JM Faugère � EN Garabedian � R Hanlet � P Lerault � P Narcy � P Tran Ba Huy � F Vaneecloo � A Vuong Comité Editorial : D Ayache � O Deguine � F Denoyelle � J-M Faugère � O Laccourreye � R Véricel

Les tests olfactifs pourraient être de grande utilité dans la maladie d’Alzheimer

La maladie d’Alzheimer est un véritable problème de santé publique dans la population des personnes âgées. Sa prévalence augmente régulièrement du fait du vieillissement de la population dans les pays industrialisés. La classification définitive de la maladie repose sur l’examen histopathologique du cerveau associé à des évaluations basées sur des marqueurs biologiques et comportementaux établies lors du vivant du patient. La recherche de marqueurs précoces de cette maladie fait l’objet de nombreuses études, notamment depuis l’apparition de molécules susceptibles de modifier l’évolution de la maladie d’Alzheimer. Pour beaucoup d’auteurs, le marqueur clinique idéal devrait être un témoin de l’importance de la neuropathologie de cette maladie.

Les troubles olfactifs sont très fréquents dans la maladie dMAlzheimer. La première description a été effectuée dès 1974 par Waldton 1. Les tests olfactifs dMidentification, de mémorisation, et lMappréciation des seuils olfactifs sont utilisés dans le bilan de la maladie dMAlzheimer ; il a été suggéré que ces résultats soient inclus dans les critères diagnostiques de la maladie 2.

Une étude récente 3 a consisté à suivre 383 patients âgés nMayant aucun des critères usuels dMune maladie dMAlzheimer. Tous ont eu une étude de leur olfaction par le « Brief Smell Identification Test » (BSIT). Le BSIT consistait à présenter une odeur et à demander de lMidentifier avec lMaide de 4 propositions. Douze odeurs étaient testées ; le score maximum était donc de 12/12 lors de la reconnaissance de toutes les odeurs. LMâge moyen des sujets était de 79,3 ans au moment de leur inclusion dans cette étude. Il y avait 76,2 % de femmes. Tous les ans, les sujets inclus étaient à nouveau évalués avec un examen médical comprenant un bilan neurologique complet, vingt et un tests cognitifs et le test olfactif BSIT. Lors du décès, une étude histopathologique standardisée était effectuée. Un génotypage de lMapolipoprotéine E a été réalisé. Le suivi de cette étude a été de 5,5 années. Parmi les 383 patients inclus, 155 (40,4 %) ont développé un trouble cognitif modéré, précurseur de la démence de la maladie dMAlzheimer. Un mauvais score olfactif lors du test BSIT était lié au déclin de la mémoire épisodique et à une augmentation du risque de développer un trouble cognitif modéré. Ainsi, une personne qui faisait quatre erreurs lors du test de reconnaissance olfactive (score 8/12) avait un risque majoré dMenviron 50 % de développer un trouble cognitif modéré par rapport à une personne qui ne faisait quMune erreur (score 11/12). Le déclin de la mémoire épisodique est lMune des premières manifestations de la

maladie dMAlzheimer, survenant parfois plusieurs années avant lMétablissement du diagnostic formel. La diminution des scores olfactifs était fortement associée (p < 0,001) à un déclin plus rapide de la mémoire épisodique. Enfin, 34 sujets sont décédés durant lMétude (âge moyen 85,2 ans). Les résultats olfactifs étaient corrélés à lMatteinte histopathologique cérébrale. Cette étude suggère que les sujets âgés sans aucune manifestation clinique de démence ou de trouble cognitif modéré, les pertes olfactives révélées sont corrélées avec un risque dMapparition plus élevé de trouble cognitif modéré et de maladie dMAlzheimer.

Cette forte association entre odorat et maladie dMAlzheimer a conduit certains auteurs à proposer le suivi de patients bénéficiant dMun traitement par, outre les tests cognitifs usuels, des tests olfactifs 4. Ainsi, 25 patients ayant une maladie dMAlzheimer légère à modérée et bénéficiant dMun traitement par le donépezil (un inhibiteur de lMacétylcholinestérase) ont été suivis par divers tests cognitifs (Mini-mental State Examination, Neuropsychiatric Inventory, Bristol Activities of Daily Living) et par un test olfactif : lMUPSIT (University of Pennsylvania Smell Identification Test). Lors du suivi de lMamélioration de lMétat des patients après trois mois de traitement, il existait une corrélation entre lMamélioration des tests cognitifs et olfactifs. Les auteurs concluent que les tests dMidentification des odeurs peuvent être utilisés comme test clinique de contrôle des effets thérapeutiques dans le cadre de la maladie dMAlzheimer. Cette étude « ouverte » doit être vérifiée par des études contrôlées mais vont dans le sens actuel de lMutilisation des tests olfactifs dMidentification dans lMévaluation et le suivi des patients âgés avec des troubles cognitifs.

Pr Pierre BONFILS, Paris, 27 novembre 2009

1) Waldton S. Clinical observations of impaired cranial function in senile dementia. Acta Psychiatr Scand 1974, 50 : 539-547. 2) Foster J, Sohrabi H, Verdile G. Research criteria for the diagnosis of Alzheimer’s disease : genetic risk factors, blood biomarkers and olfactory dysfunction. Int Psychogeriatr 2008, 20 : 853-855. 3) Wilson RS, Arnold SE, Schneider JA et al. Olfactory impairment in presymptomatic Alzheimer Disease. Ann N Y Acad Sci 2009, 1170 : 730-735. 4) Velayudhan L, Lovestone S. Smell identification test as a treatment response marker in patients with Alzheimer Disease receiving Donapezil. J Clin Psychopharmaco 2009, 29 : 387-390.

Consultez tous les articles parus dans le Journal Faxé d’ORL sur le site www .regifax.fr (recherche multicritères)

VASTAREL 35 mg, comprimé pelliculé à libération modifiée. Composition et forme : Boîte de 60 cp pelliculés à libération modifiée de dichlorhydrate de trimétazidine dosés à 35 mg. Indications thérapeutiques : � En cardiologie : traitement prophylactique de la crise d'angine de poitrine, � En ORL : traitement symptomatique d'appoint des vertiges et des acouphènes, � En ophtalmologie : traitement d'appoint des baisses d'acuité et des troubles du champ visuel présumés d'origine vasculaire. Propriétés : Propriétés pharmacodynamiques : AUTRE MÉDICAMENT EN CARDIOLOGIE À VISÉE ANTIANGINEUSE. La trimétazidine, en préservant le métabolisme énergétique de la cellule exposée à l'hypoxie ou à l'ischémie, empêche l'abaissement du taux intracellulaire de l'ATP. Elle assure ainsi le

fonctionnement des pompes ioniques et des flux transmembranaires Na+-K+ et maintient l'homéostasie cellulaire. Les études contrôlées, chez l'angoreux, ont montré que la trimétazidine : � augmente la réserve coronaire (le délai d'apparition des troubles ischémiques liés à l'effort), dès le 15e j du traitement, � limite les à-coups tensionnels liés à l'effort, sans entraîner de variations significatives de la fréquence cardiaque, � diminue significativement la fréquence des crises angineuses, � entraîne une diminution significative de la consommation de trinitrine. Dans une étude réalisée sur 2 mois, chez des patients recevant 50 mg dMaténolol, lMajout de 1 cp à libération modifiée de trimétazidine 35 mg entraîne, par rapport au placebo, un allongement significatif du délai dMapparition dMun sous-décalage de 1 mm du segment ST à lMépreuve dMeffort 12 h après la prise. Propriétés pharmacocinétiques : � Sur 24 h, la concentration plasmatique se maintient à des concentrations � 75 % de la Cmax pendant 11 h. Contre-indications : Hypersensibilité à lMun des constituants du produit. Grossesse et allaitement : Éviter de prescrire pendant la grossesse ( allaitement déconseillé. Mises en garde et précautions particulières d'emploi : Généralement

1 comprimé matin et soir1 boîte par mois de traitement

Epilepsy

27 yo male Olfactory seizures with cacosmia

Ganglioglioma

Smell and depression

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., Couillet 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 major depressive patients dépréssifs majeurs Odorants stimuli

spearmint: positive odor sandalwood : neutral odor Wine lee : negative odor

fMRI before and after 3 months with venlafaxine

Mint Wine lee

Conclusion

Health & Medicine

Jl sarrazin olfaction jfim hanoi 2015