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2018. Volume 7. Issue 1. Article CID e0101 _DOI: 10.15275/rusomj.2018.0101_
Review
Cranial nerve I: clinical anatomy and beyond
Serghei Covantev
State University of Medicine and Pharmacy "Nicolae Testemitanu", Chisinau, Republic of Moldova
Received 17 December 2017, Accepted 30 December 2017
© 2017, Covantev S. © 2017, Russian Open Medical Journal
Abstract: Examination of the cranial nerves is an important part of complete neurological assessment of the patient. With the development of imaging techniques, there is an increased awareness of the possible anatomical variations and anomalies and although there is extensive data on the anatomical variations of some of the cranial nerves, cranial nerve I is relatively understudied. Although the data on olfactory nerve is not abundantly present, there are several types of developmental anomalies, which can be present as aplasia, hypoplasia, olfactory bulb ventricles, and duplication/triplication of the olfactory bulb. There are also several genetic conditions, in which olfactory system malformation are common and require further evaluation. The purpose of this review is to sum up the current data on the clinical anatomy, malformations of olfactory nerve, bulb, tract and associated conditions.
Keywords: olfactory nerve, olfactory bulb, olfactory tract
Cite as Covantev S. Cranial nerve I: clinical anatomy and beyond. Russian Open Medical Journal 2018; 7: e0101. Correspondence to Serghei Covantev. E-mail: [email protected].
Macro- and Micromorphology
Introduction
Examination of the cranial nerves is an important part of complete neurological assessment of the patient [1]. With the development of imaging techniques, there is an increased awareness of the possible anatomical variations and anomalies, which are important to consider in clinical practice. Although there is extensive data on the anatomical variations of some of the cranial nerves, cranial nerve I is relatively understudied.
What is usually referred to as the olfactory nerve is properly the olfactory tract and bulb, and is an outgrowth of the forebrain [2]. Two groups of neurons are found in the nasal mucosa. The first group is the lateral olfactory nerves (12-20) which can be found at the level of the superior nasal concha. The second group is the medial olfactory nerves (12-16) which descend along the nasal septum [3]. Primary sensory neurons of this nerve are bipolar and are present in the olfactory epithelium. Their central processes make up the numerous nerves, which pass through the cribriform plate of the ethmoid bone and dura matter. There they synapse with secondary sensory neurons (deutoneuron or mitral cell) forming the olfactory bulb (average length 12 mm, width 5 mm) and tract (average length 30 mm with a transverse diameter of 5 mm in the anterior portion and 2 mm in the posterior portion). The olfactory bulb lies over the cribriform plate and anatomically is seen as an ovoid structure on the inferior surface of frontal lobe (between the right gyri and the medial orbital gyri), above the orbital plate of frontal bone [2, 4, 5]. In front of the anterior perforated substance, the tract divides in lateral, medial and intermediate stria [4].
Nevertheless, surgeons mention that the circumstances in which they find the olfactory neve, bulb and tract differ. The length and thickness of the olfactory nerve may be different as
well as is resistance against compression and tension. The olfactory bulb may sometimes be adherent to the olfactory fossa or inversely easily detachable. The olfactory tract may tear off just behind the bulb and the bulb remains, as chained on strong fila olfactoria [6].
Damage to the olfactory bulb and tract is a frequently described complication of brain surgery in the frontal region [7]. Dissecting the olfactory nerve from the orbitofrontal cortex can be performed during operations without its damage but bilateral protection is not always possible [8]. Overall mobilization of the olfactory bulb and tract is limited (29.3±6.4 mm in length) as well as frontal lobe retraction (10 to 15 mm) without compromising of the olfactory function [5, 7].
The list of conditions, which cause olfactory dysfunction, is extensive and any dysfunction in olfaction requires a radiological exploration comprising the nasal cavity, the anterior base of the skull, in particular the frontal and temporal lobes [4, 9].
The most predominant causes of olfactory dysfunctions are upper respiratory infections, head trauma, and nasal and paranasal sinus disease that damage the olfactory neuroepithelium [9].
Significant correlations between olfactory bulb volumes in relation to olfactory function were observed, independent of the subjects' age in adults [10]. Olfactory bulb volumes and olfactory function increased with age in children and adolescents, although it seems that the correlation between structure and function is mediated by the subjects' age [11]. The difference in volume between the right and left olfactory bulbs may be partly responsible for lateralized differences in olfactory function [12]. Their volume seem to increase in case of early blindness [13] and
2018. Volume 7. Issue 1. Article CID e0101 DOI: 10.15275/rusomj.2018.0101_
Macro- and Micromorphology
decrease in a variety of conditions ranging from common like postinfectious [14] and posttraumatic [15] loss of smell to less common as fibromyalgia syndrome [16], snake venom [17] and leprosy [18] {Table 1).
Similarly, olfactory sulcal depth was proposed as a biomarker of early embryonic disruption in individuals at risk for schizophrenia [19]. Schizophrenia patients had a significantly shallower olfactory sulcus compared with the controls bilaterally, but there was no group difference in its anterior-posterior length. The olfactory sulcus measures of the patients did not significantly correlate with clinical variables such as onset age, medication or symptom severity [20]. A shallow olfactory sulcus possibly reflects abnormal forebrain development during early gestation. It is still unclear whether this anomaly exists prior to the onset of psychosis. Subjects who later developed psychosis had significantly shallower olfactory sulcus at baseline as compared with who did not develop psychosis and control subjects. The depth of this sulcus became increasingly more superficial as one moved from the group who later developed psychosis to the group with firstepisode psychosis to chronic schizophrenia patients. Finally, the depth of the olfactory sulcus in the later developed psychosis subjects was negatively correlated with the severity of negative symptoms. Thus the altered depth of the olfactory sulcus, which exists before psychosis onset, could be predictive of transition to psychosis, but also suggest ongoing changes of the sulcus morphology during the course of the illness [21].
Vascularization
The olfactory nerve has intracranial vascularization by olfactory artery and accessory olfactory artery {arise from anterior cerebral artery or anterior communicating artery) and by anterior and posterior ethmoidal arteries {arise from ophthalmic artery). The extracranial vascular supply is by sphenopalatine artery {arise from external carotid artery), anterior and posterior ethmoidal arteries {arise from ophthalmic artery) [39].
The major source of the vascular supply of the bulb and tract is the olfactory artery. It originates either from the lateral surface of the anterior cerebral artery {segment A2), or from the medial frontobasal artery, and consistently provides supply in front of the olfactory trigone in the medial olfactory sulcus, the olfactory tract and olfactory bulb with a maximum of three terminal branches [40, 41].
The olfactory tract receives blood supply from a variety of sources, which include posterior orbitofrontal artery, medial orbitofrontal artery, posterior orbitofrontal artery and medial striate artery [42].
Persistent primitive olfactory artery (PPOA) is a relatively rare variation of the proximal anterior cerebral artery that originates from the terminal portion of internal carotid artery. It can have an extreme antero-inferior course and take a hairpin turn (type 1); extending to the cribriform plate to supply the nasal cavity (type 2); or coursed anteromedially along the olfactory tract making a hairpin turn posterosuperior to the midline [43, 44]. Its incidence seems to be 0.14-0.64% [45, 46]. There is a high incidence of aneurysms associated with PPOA [43, 44, 47, 48]
Vascular anomalies also should be considered in the differential diagnosis of olfactory impairment. There are a variety of conditions which can cause olfactory impairment like rare aneurysms of PPOA [47] or arteriovenous fistulae involving the anterior ethmoidal arteries [49] or mixed pial-dural arteriovenous malformations that involve PPOA [50].
Aplasia/hypoplasia of the olfactory nerve, bulb or tract
The bilateral absence of olfactory nerve, bulb and tract is a rare anomaly. It can be an isolated unilateral or bilateral anomaly as well a part of other condition.
Over the years, there have been several reports of bilateral absence or dysplasia of olfactory bulbs associated with various degrees of central nervous system (CNS) malformations [51-57]. In one of the cases, the stillborn child had extensive malformations of the CNS, cardiovascular, abdominal and skeletomuscular systems [51]. The other case of a 17-year-old male with severe mental retardation and malformations of the CNS [52].
The isolated hypoplasia or aplasia is considered rare, and may involve only the nerve or the bulb [49, 58-60]. It can also occur along with minor anomalies with little clinical significance [61]. The main feature in this case is loss of smell with no other clinical signs [62].
The anomaly can be classified morphologically into three types [63-65]: hypoplasia of the olfactory bulbs with olfactory tracts present; aplasia of the olfactory bulbs with olfactory tracts present; and aplasia of both olfactory bulbs and olfactory tracts.
Anomalies of the olfactory bulb may also be underestimated. In patients with abnormal ciliary motion and congenital heart disease, 28.5% of patients had brain abnormalities including of the olfactory bulb [66]. It seems possible that there are more conditions, which may be associated with olfactory malformations.
Accessory olfactory bulbs
In a study of 220 patients who undergone magnetic resonance imaging (MRI) with high-resolution coronal T2-weighted fast-spin echo images in the orbitofrontal region. Olfactory bulbs appeared duplicated in 11 patients and triplicated in one (5.4% of the total group). Whereas olfactory sulcal depth was similar in all patients, olfactory bulb diameter in patients with duplicate or triplicate bulbs was significantly smaller than those in subjects with single bilateral olfactory bulbs. One patient with congenital hyposmia and olfactory bulb duplication had significant impairment in olfactory acuity. In each of the 12 patients, olfactory grooves were abnormal (widened, flat or absent) [67]. Interestingly, an accessory olfactory bulb are present in animals and it receives sensory input from the vomeronasal (Jacobson's) organ [68]. Thus, the presence of an accessory olfactory bulb may be an evolutionary remnant.
Olfactory bulb ventricles and cysts
Rarely, olfactory bulb cysts can develop and represent incidental findings [69]. In some species an embryologic cavity inside the olfactory bulb persists and are called olfactory bulb ventricles. It may very well be that this embryological remnants can be found in humans. An MRI study of 122 individuals and dissection of 42 cadavers demonstrated that olfactory bulb ventricle-like structures were present in 72 out of 122 (59%) participants and in 3 out of 42 postmortem olfactory bulbs contained histologically detectable ventricles [70]. Later it was demonstrated that the fluid filled structure can be seen less frequently in 5.5% of cases and might be associated with interstitial or finely dispersed cerebrospinal fluid or with tiny, histologically detectable remnants of called olfactory bulb ventricle [71].
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Macro- and Micromorphology
Table 1. Clinical implications of olfactory bulbs volume assessment
Condition Clinical implications Refs
Temporal lobe epilepsy Olfactory function was significantly impaired and olfactory bulbs were smaller in patients compared to healthy controls. The deficit seen at the level of the olfactory bulb did not correlate with the side of the epileptic focus. Thus, the olfactory deficit in patients is due to the central nervous epileptic focus and it appears that the olfactory bulb volume is not only subject to changes in the periphery of the olfactory [22]
system, but also changes as a consequence to changes at a cortical level.
Parkinson's disease Both the left and the right olfactory bulb volume were significantly smaller in patients than in healthy [23]
controls. A significant difference in the lateralized olfactory bulb volume was observed with a larger right
olfactory bulb volume than left.
Multiple sclerosis Olfactory bulb volume correlates with its function. It also correlate with disease duration, attack frequency [24-26]
and higher depression scores.
Major depression There is a significant negative correlation between olfactory bulb volume and depression scores. The [27, 28]
volume correlates with the change of depression severity and can be a predictor factor of therapeutic
outcome.
Schizophrenia Patients exhibited 23% smaller bilateral bulb volume than comparison subjects, independent of acute [29, 30]
clinical, demographic, or treatment measures. It may also me lower in first-degree relatives of patients with
schizophrenia.
Obstructive sleep apnea The apnea-hypopnea index was significantly negatively correlated with odor identification score and both [31]
olfactory bulb volumes
Smoking Olfactory function was not different between the smokers and non-smokers groups, but olfactory bulb [32]
volumes were smaller possibly indicating a subclinical effect on the olfactory system.
Septal deviation Olfactory function was significantly lower at the narrower side. When correlating relative scores and [33]
volumes (wider minus narrower side), a significantly positive correlation between the relative measures
emerged for olfactory bulb volume and odor identification, discrimination, and thresholds.
Sinonasal polyposis There are significant reduction in olfactory bulb volume in patients with bilateral sinonasal polyposis as [34, 35]
compared to controls. Olfactory bulb volume correlated with the degree of sinonasal inflammation.
Chronic rhinosinusitis The increase in olfactory bulb volume correlated significantly with an increase in odor thresholds, but not [36]
with changes in odor discrimination or identification.
Radiotherapy in patients The loss of olfactory bulb volume might be a contributing factor to lack of appetite, cancer cachexia and [37]
with nasopharyngeal cancer consequent lowered quality of life.
Postinfectious and Significant correlation between changes in olfactory functions and initial measurement of the total olfactory [14, 15, 38]
posttraumatic olfactory loss bulb volume. Larger volumes are linked to a higher improvement of olfactory function. Total olfactory bulb volume of 40 mm(3) or less seems to indicate permanent loss of olfactory function.
Genetic syndromes
There is a link between malformations of the olfactory system and a variety of genetic conditions like Kallmann's syndrome (KS), CHARGE-syndrome (the acronym "CHARGE" came into use for newborn children with the congenital features of coloboma of the eye, heart defects, atresia of the nasal choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness. These features are no longer used in making a diagnosis alone of CHARGE syndrome, but the name remains), septo-optic dysplasia (SOD), Waardenburg syndrome (WS) and other.
KS represents a genetic syndrome the key features of which are anosmia and hypogonadotropic hypogonadism. In KS cells that normally express luteinizing hormone-releasing hormone fail to migrate from the medial olfactory placode along the terminalis nerves into the forebrain. Additionally failed neuronal migration from the lateral olfactory placode along the olfactory fila to the forebrain results in aplasia or hypoplasia of the olfactory bulbs and tracts. This explains the two key features of KS - reproductive and olfactory dysfunction [64].
The anosmia in KS is caused by absence of olfactory bulbs and tracts in 68-84% and by hypoplasia in 16-32%. Other CNS abnormalities may include temporal, frontal lobe volume loss [72] abnormalities of the rhinencephalon [73] bilateral loss of distinction between the gyrus rectus and medial orbital gyrus [74] corpus callosum defects [75] arachnoid cyst [76, 77], empty sella [77, 78], pituitary hypoplasia [79] and multiple sclerosis-like white
matter abnormalities other changes [80]. Craniofacial malformations mau include tooth agenesis, increased mandibular inclination and mandibular angulation, extreme retrognathism of both maxilla and mandible, cleft lip and/or palate and altered bone morphology [75, 81, 82]. Finally, other organ and structures can be affected [83].
Mutation in one of the KS genes can be found in up to 30% of cases. There a significant phenotypical overlaps with other conditions like CHARGE-syndrome [84], combined pituitary hormone deficiency, and SOD [85]. Thus, the current data indicate that olfactory nerve, bulb and tract hypoplasia can be a part of septo-optic dysplasia or be an overlap with KS [86-88].
In patents with CHARGE-syndrome, MRI demonstrated olfactory anomalies including either absence or hypoplasia of the olfactory bulbs and olfactory sulci [89]. It is even proposed that rhinencephalon anomalies should be included as a major criterion for the diagnosis of CHARGE-syndrome [90]. Other studies go further and demonstrate that CHARGE-syndrome include the main features of KS (hypogonadotropic hypogonadism combined with a defective sense of smell and abnormal olfactory bulb development) [91].
In WS, a genetic disorder characterized by the association between pigmentation abnormalities and deafness. However, SOX10 mutations cause a variable phenotype that spreads over the initial limits of the syndrome definition. Particularly olfactory-bulb agenesis in WS can also be present since SOX10 is also involved in KS [92, 93].
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Macro- and Micromorphology
Accessory olfactory bulbs/ olfactory bulb ventricles
Aplasia/hypoplasia of olfactory bulbs
Further evaluation
Clinical assessment (visible malformations, mental development)
Symptoms besides loss of smell
Hormone level (GnRH, LH, FSH, estradiol, testosterone, free T4, TSH)
USG of abdominal organs (kidneys, liver)
Echocardiography
Réévaluation of the brain MRI
Most likely no indications for further consult
No findings
Abnormalities
Further evaluation Further monitoring Genetic consult required
Figure 1. Evaluation of incidental abnormalities of olfactory bulbs.
GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone; TSH, thyroid-stimulating hormone; USG, ultrasonography.
Based on these findings MRI should be performed in patients with congenital deafness and in case when adequate sequences are available other CNS anomalies including olfactory bulb malformation can be detected [94, 95].
Malformations of the olfactory nerves, bulbs and tract can also be seen in other genetic conditions like Meckel-Gruber syndrome (occipital encephalocele, cystic dysplastic kidneys, and postaxial Polydactyly) [96], Fryns syndrome [97, 98], short rib-polydactyly syndrome [99, 100], Jacobsen syndrome [101], Johanson-Blizzard syndrome [101], DiGeorge sendrome [101], trisomy 13 [102], trisomy 18 [101] and other genetic abnormalities [101, 103, 104].
In children with olfactory malformations syndromic associations can be found in up to 22%. Patients may also have developmental delay (59%), seizures (34%) and neuroendocrine dysfunction (34%). Children commonly had multiple presenting symptoms (61%) [101].
Therefore, patients with malformations of the olfactory system should be evaluated to exclude the presence of any underlying genetic condition (Figure 1).
Conclusion
Variations of the development of olfactory nerve, bulb and tract are underdiagnosed. Isolated aplasia or hypoplasia is generally a rare phenomenon. Patients with aplasia and hypoplasia should be evaluated since this condition is frequently a part of other malformations and genetic syndromes. Olfactory bulb duplications and triplications, olfactory bulb ventricles seem to be a benign variations of development but the data on these subject is currently limited.
Conflict of interest: none declared.
References
1. Damodaran O, Rizk E, Rodriguez J, Lee G. Cranial nerve assessment: a concise guide to clinical examination. Clinical Anatomy 2014; 27(1): 2530. https://doi.org/10.1002/ca.22336.
2. Monkhouse S. Cranial Nerves: functional anatomy. Cambridge, UK: Cambridge University Press, 2005; 147 p.
3. Barral J-P, Croibier A. Chapter 10 - Olfactory nerve. In: Manual therapy for the cranial nerves. Edinburgh: Churchill Livingstone; 2009: 59-72.
4. Leboucq N, Menjot de Champfleur N, Menjot de Champfleur S, Bonafe A. The olfactory system. Diagnostic and Interventional Imaging 2013; 94(10): 985-991. https://doi.org/10.1016/i.diii.2013.06.006.
5. Cardali S, Romano A, Angileri FF, Conti A, La Torre D, de Divitiis O, et al. Microsurgical anatomic features of the olfactory nerve: relevance to olfaction preservation in the pterional approach. Neurosurgery 2005; 57(1 Suppl): 17-21. https://www.ncbi.nlm.nih.gov/pubmed/15987566.
6. Dietz H. Some remarks about the olfactory nerve from the surgical point of view. In: The Cranial Nerves. M. Samii and P.J. Jannetta, eds. Springer, Berlin, Heidelberg, 1981.
7. Comert A, Ugur HC, Kahilogullar G, Comert E, Elhan A, Tekdemir I. Microsurgical anatomy for intraoperative preservation of the olfactory bulb and tract. J Craniofac Surg 2011; 22(3): 1080-1082. https://doi.org/10.1097/SCS.0b013e3182139884.
8. Suzuki J, Mizoi K, Yoshimoto T. Bifrontal interhemispheric approach to aneurysms of the anterior communicating artery. J Neurosurg 1986; 64(2): 183-190. https://doi.org/10.3171/jns.1986.64.2.0183.
9. Doty RL. The olfactory system and its disorders. Semin Neurol 2009; 29(1): 74-81. https://doi.org/10.1055/s-0028-1124025.
10. Buschhuter D, Smitka M, Puschmann S, Gerber JC, Witt M, Abolmaali ND, et al. Correlation between olfactory bulb volume and olfactory function. NeuroImage 2008;42(2): 498-502. https://doi.org/10.1016/j.neuroimage.2008.05.004.
11. Hummel T, Smitka M, Puschmann S, Gerber JC, Schaal B, Buschhuter D. Correlation between olfactory bulb volume and olfactory function in children and adolescents. Exp Brain Res 2011; 214(2): 285-291. https://doi.org/10.1007/s00221-011-2832-7.
12. Hummel T, Haehner A, Hummel C, Croy I, Iannilli E. Lateralized differences in olfactory bulb volume relate to lateralized differences in
2018. Volume 7. Issue 1. Article CID e0101 DOI: 10.15275/rusomj.2018.0101_
Macro- and Micromorphology
olfactory function. Neuroscience 2013;237: 51-55. https://doi.org/10.1016/j.neuroscience.2013.01.044.
13. Rombaux P, Huart C, De Volder AG, Cuevas I, Renier L, Duprez T, et al. Increased olfactory bulb volume and olfactory function in early blind subjects. Neuroreport 2010; 21(17): 1069-1073. https://doi.org/10.1097/WNR.0b013e32833fcb8a.
14. Rombaux P, Mouraux A, Bertrand B, Nicolas G, Duprez T, Hummel T. Olfactory function and olfactory bulb volume in patients with postinfectious olfactory loss. Laryngoscope 2006;116(3): 436-439. https://doi.org/10.1097/01.MLG.0000195291.36641.1E.
15. Rombaux P, Mouraux A, Bertrand B, Nicolas G, Duprez T, Hummel T. Retronasal and orthonasal olfactory function in relation to olfactory bulb volume in patients with posttraumatic loss of smell. Laryngoscope 2006; 116(6): 901-905. https://doi.org/10.1097/01.mlg.0000217533.60311.e7.
16. Sayilir S, Cullu N. Decreased olfactory bulb volumes in patients with fibromyalgia syndrome. Clin Rheumatol 2017;36(12): 2821-2824. https://doi.org/10.1007/s10067-017-3772-9.
17. Sethi M, Cook M, Winkel KD. Persistent anosmia and olfactory bulb atrophy after mulga (Pseudechis australis) snakebite. J Clin Neurosci 2016; 29: 199-201. https://doi.org/10.1016/Mocn.2015.12.019.
18. Veyseller B, Aksoy F, Yildirim YS, Acikalin RM, Gurbuz D, Ozturan O. Olfactory dysfunction and olfactory bulb volume reduction in patients with leprosy. Indian J Otolaryngol Head Neck Surg 2012; 64(3): 261265. https://doi.org/10.1007/s12070-011-0284-9.
19. Turetsky BI, Crutchley P, Walker J, Gur RE, Moberg PJ. Depth of the olfactory sulcus: a marker of early embryonic disruption in schizophrenia? Schizophr Res 2009; 115(1): 8-11. https://doi.org/10.1016/j.schres.2009.09.005.
20. Takahashi T, Nakamura Y, Nakamura K, Ikeda E, Furuichi A, Kido M, et al. Altered depth of the olfactory sulcus in first-episode schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2013; 40: 167-172. https://doi.org/10.1016/j.pnpbp.2012.10.001.
21. Takahashi T, Wood SJ, Yung AR, Nelson B, Lin A, Yucel M, et al. Altered depth of the olfactory sulcus in ultra high-risk individuals and patients with psychotic disorders. Schizophr Res 2014; 153(1-3): 18-24. https://doi.org/10.1016/j.schres.2014.01.041.
22. Hummel T, Henkel S, Negoias S, Galvan JR, Bogdanov V, Hopp P, et al. Olfactory bulb volume in patients with temporal lobe epilepsy. J Neurol 2013; 260(4): 1004-1008. https://doi.org/10.1007/s00415-012-6741-x.
23. Li J, Gu C-z, Su J-b, Zhu L-h, Zhou Y, Huang H-y, et al. Changes in olfactory bulb volume in Parkinson's Disease: a systematic review and meta-analysis. PLoS ONE 2016; 11(2): e0149286. https://doi.org/10.1371/journal.pone.0149286.
24. Goektas O, Schmidt F, Bohner G, Erb K, Ludemann L, Dahlslett B, et al. Olfactory bulb volume and olfactory function in patients with multiple sclerosis. Rhinology 2011; 49(2): 221-226. https://doi.org/10.4193/Rhino10.136.
25. Tanik N, Serin HI, Celikbilek A, Inan LE, Gundogdu F. Olfactory bulb and olfactory sulcus depths are associated with disease duration and attack frequency in multiple sclerosis patients. J Neurol Sci 2015; 358(1-2): 304-307. https://doi.org/10.1016/j.jns.2015.09.016.
26. Yaldizli O, Penner IK, Yonekawa T, Naegelin Y, Kuhle J, Pardini M, et al. The association between olfactory bulb volume, cognitive dysfunction, physical disability and depression in multiple sclerosis. Eur J Neurol 2016; 23(3): 510-519. https://doi.org/10.1111/ene.12891.
27. Negoias S, Hummel T, Symmank A, Schellong J, Joraschky P, Croy I. Olfactory bulb volume predicts therapeutic outcome in major depression disorder. Brain Imaging Behav 2016; 10(2): 367-372. https://doi.org/10.1007/s11682-015-9400-x.
28. Negoias S, Croy I, Gerber J, Puschmann S, Petrowski K, Joraschky P, et al. Reduced olfactory bulb volume and olfactory sensitivity in patients with acute major depression. Neuroscience 2010; 169(1): 415-421. https://doi.org/10.1016/j.neuroscience.2010.05.012.
29. Turetsky BI, Moberg PJ, Yousem DM, Doty RL, Arnold SE, Gur RE. Reduced olfactory bulb volume in patients with schizophrenia. Am J Psychiatry 2000; 157(5): 828-830. https://doi.org/10.1176/appi.ajp.157.5.828.
30. Turetsky BI, Moberg PJ, Arnold SE, Doty RL, Gur RE. Low olfactory bulb volume in first-degree relatives of patients with schizophrenia. Am J Psychiatry 2003; 160(4): 703-708. https://doi.org/10.1176/appi.ajp.160.4.703.
31. Salihoglu M, Kendirli MT, Altundag A, Tekeli H, Saglam M, Cayonu M, et al. The effect of obstructive sleep apnea on olfactory functions. Laryngoscope 2014; 124(9): 2190-2194. https://doi.org/10.1002/lary.24565.
32. Schriever VA, Reither N, Gerber J, Iannilli E, Hummel T. Olfactory bulb volume in smokers. Exp Brain Res 2013; 225(2): 153-157. https://doi.org/10.1007/s00221-012-3356-5.
33. Altundag A, Salihoglu M, Tekeli H, Saglam M, Cayonu M, Hummel T. Lateralized differences in olfactory function and olfactory bulb volume relate to nasal septum deviation. J Craniofac Surg 2014; 25(2): 359362. https://doi.org/10.1097/SCS.0000000000000617.
34. Herzallah IR, Askar SM, Amer HS, Ahmed AF, El-Anwar MW, Eesa MH. Olfactory bulb volume changes in patients with sinonasal polyposis: a magnetic resonance imaging study. Otolaryngol Head Neck Surg 2013; 148(4): 689-693. https://doi.org/10.1177/0194599813477606.
35. Rombaux P, Potier H, Bertrand B, Duprez T, Hummel T. Olfactory bulb volume in patients with sinonasal disease. Am J Rhinol 2008; 22(6): 598-601. https://doi.org/10.2500/ajr.2008.22.3237.
36. Gudziol V, Buschhuter D, Abolmaali N, Gerber J, Rombaux P, Hummel T. Increasing olfactory bulb volume due to treatment of chronic rhinosinusitis--a longitudinal study. Brain 2009; 132(Pt 11): 3096-3101. https://doi.org/10.1093/brain/awp243.
37. Veyseller B, Ozucer B, Degirmenci N, Gurbuz D, Tambas M, Altun M, et al. Olfactory bulb volume and olfactory function after radiotherapy in patients with nasopharyngeal cancer. Auris Nasus Larynx 2014; 41(5): 436-440. https://doi.org/10.1016/j.anl.2014.02.004.
38. Rombaux P, Huart C, Deggouj N, Duprez T, Hummel T. Prognostic value of olfactory bulb volume measurement for recovery in postinfectious and posttraumatic olfactory loss. Otolaryngol Head Neck Surg 2012; 147(6): 1136-1141. https://doi.org/10.1177/0194599812459704.
39. Hendrix P, Griessenauer CJ, Foreman P, Shoja MM, Loukas M, Tubbs RS. Arterial supply of the upper cranial nerves: a comprehensive review. Clin Anat 2014;27(8): 1159-1166. https://doi.org/10.1002/ca.22415.
40. Favre JJ, Chaffanjon P, Passagia JG, Chirossel JP. Blood supply of the olfactory nerve. Meningeal relationships and surgical relevance. Surg Radiol Anat 1995; 17(2): 133-138, 12-4. https://www.ncbi.nlm.nih.gov/pubmed/7482150.
41. Tsutsumi S, Ono H, Yasumoto Y. Visualization of the olfactory nerve using constructive interference in steady state magnetic resonance imaging. Surg Radiol Anat 2017; 39(3): 315-321. https://doi.org/10.1007/s00276-016-1731-9.
42. Ciolkowski M, Michalik R, Ciszek B. Arteries to the proximal part of the olfactory tract. Folia Morphol (Warsz) 2004; 63(4): 455-458. https://www.ncbi.nlm.nih.gov/pubmed/15712143.
43. Sato Y, Kashimura H, Takeda M, Chida K, Kubo Y, Ogasawara K. Aneurysm of the A1 segment of the anterior cerebral artery associated with the persistent primitive olfactory artery. World Neurosurg 2015; 84(6): 2079.e7-e9. https://doi.org/10.1016/j.wneu.2015.08.017.
44. Horie N, Morikawa M, Fukuda S, Hayashi K, Suyama K, Nagata I. New variant of persistent primitive olfactory artery associated with a ruptured aneurysm. J Neurosurg 2012; 117(1): 26-28. https://doi.org/10.3171/2012.3JNS111932.
45. Uchino A, Saito N, Kozawa E, Mizukoshi W, Inoue K. Persistent primitive olfactory artery: MR angiographic diagnosis. Surg Radiol Anat 2011; 33(3): 197-201. https://doi.org/10.1007/s00276-010-0743-0.
46. Vasovic L, Trandafilovic M, Vlajkovic S, Jovanovic I, Ugrenovic S. Persistent primitive olfactory artery in Serbian population. Biomed Res Int 2013; 2013: 903460. https://doi.org/10.1155/2013/903460.
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Macro- and Micromorphology
47. Yamamoto T, Suzuki K, Yamazaki T, Tsuruta W, Tsurubuchi T, Matsumura A. Persistent primitive olfactory artery aneurysm. Neurol Med Chir (Tokyo) 2009;49(7): 303-305. https://doi.org/10.2176/nmc.49.303.
48. Tsuji T, Abe M, Tabuchi K. Aneurysm of a persistent primitive olfactory artery. Case report. J Neurosurg 1995; 83(1): 138-140. https://doi.org/10.3171/ins.1995.83.1D138.
49. Tunsuriyawong P, Pongpirul K, Chaisam T, Prajuabpansri P. Olfactory bulb agenesis with normal sexual hormones. BMJ Case Rep 2017; 2017. https://doi.org/10.1136/bcr-2017-221899.
50. Jimbo H, Ikeda Y, Izawa H, Otsuka K, Haraoka J. Mixed pial-dural arteriovenous malformation in the anterior cranial fossa--two case reports. Neurol Med Chir (Tokyo) 2010;50(6): 470-475. https://doi.org/10.2176/nmc.50.470.
51. Morton WR. Arhinencephaly and multiple developmental anomalies occurring in a human full-term foetus. Anat Rec 1947; 98(1): 45-58. https://doi.org/10.1002/ar.1090980107.
52. Stewart RM. Arhinencephaly. J Neurol Psychiatry 1939; 2(4): 303-312. https://www.ncbi.nlm.nih.gov/pubmed/21610958.
53. Yamanouchi H, Hirato J, Yokoo H, Nako Y, Morikawa A, Nakazato Y. Olfactory bulb dysplasia: a novel subtype of neuronal migration disorder. Ann Neurol 1999; 46(5): 783-786. https://www.ncbi.nlm.nih.gov/pubmed/10553998.
54. Andrews PI, Hulette CM. An infant with macrocephaly, abnormal neuronal migration and persistent olfactory ventricles. Clin Neuropathol 1993; 12(1): 13-18. https://www.ncbi.nlm.nih.gov/pubmed/8440077.
55. Yamaguchi K, Honma K. An acardiac twin with advanced development of the brain: a histologic and volumetric study. Clin Neuropathol 2014; 33(1): 84-90. https://doi.org/10.5414/NP300648.
56. Louis DN, Arriagada PV, Hyman BT, Hedley-Whyte ET. Olfactory dysgenesis or hypoplasia: a variant in the arhinencephaly spectrum? Neurology 1992; 42(1): 179-182. https://www.ncbi.nlm.nih.gov/pubmed/1734299.
57. Dhamija R, Babovic-Vuksanovic D. Hartsfield Syndrome. In: GeneReviews((R)). M.P. Adam, H.H. Ardinger, R.A. Pagon, et al., eds. Seattle WA: University of Washington, 1993.
58. Carswell AJ, Whinney D, Hollings N, Flanagan P. Isolated olfactory nerve agenesis. Br J Hosp Med (Lond) 2008; 69(8): 474. https://doi.org/10.12968/hmed.2008.69.830747.
59. Coimbra C, Cunha A, Ferreira EC, Conde A. Isolated olfactory bulbs agenesis: An extremely rare entity. Acta Otorrinolaringol Esp 2016; 67(4): 242-244. https://doi.org/10.1016/j.otorri.2015.07.004.
60. Di Rienzo L, Artuso A, Colosimo C. Isolated congenital agenesis of the olfactory bulbs and tracts in a child without Kallmann's syndrome. Ann Otol Rhinol Laryngol 2002; 111(7 Pt 1): 657-660. https://doi.org/10.1177/000348940211100715.
61. Petty PG. Absence of olfactory bulbs and tracts with an associated bilobed pineal body. Med J Aust 1965;2(12): 492-494. https://www.ncbi.nlm.nih.gov/pubmed/5827272.
62. Abolmaali ND, Hietschold V, Vogl TJ, Huttenbrink KB, Hummel T. MR evaluation in patients with isolated anosmia since birth or early childhood. AJNR Am J Neuroradiol 2002;23(1): 157-164. https://www.ncbi.nlm.nih.gov/pubmed/11827889.
63. Yousem DM, Turner WJ, Li C, Snyder PJ, Doty RL. Kallmann syndrome: MR evaluation of olfactory system. AJNR Am J Neuroradiol 1993; 14(4): 839-843. https://www.ncbi.nlm.nih.gov/pubmed/8352154.
64. Truwit CL, Barkovich AJ, Grumbach MM, Martini JJ. MR imaging of Kallmann syndrome, a genetic disorder of neuronal migration affecting the olfactory and genital systems. AJNR Am J Neuroradiol 1993; 14(4): 827-838. https://www.ncbi.nlm.nih.gov/pubmed/8352153.
65. Knorr JR, Ragland RL, Brown RS, Gelber N. Kallmann syndrome: MR findings. AJNR Am J Neuroradiol 1993; 14(4): 845-851. https://www.ncbi.nlm.nih.gov/pubmed/8352155.
66. Panigrahy A, Lee V, Ceschin R, Zuccoli G, Beluk N, Khalifa O, et al. Brain dysplasia associated with ciliary dysfunction in infants with congenital
heart disease. J Pediatr 2016;178: 141-148.e1. https://doi.Org/10.1016/i.ipeds.2016.07.041.
67. Levy LM, Degnan AJ, Sharma S, Kelahan L, Henkin RI. Morphological changes of olfactory bulbs and grooves: initial report of supernumerary olfactory bulbs. J Comput Assist Tomogr 2012; 36(4): 406-409. https://doi.org/10.1097/RCT.0b013e31825b85ab.
68. Scalia F, Winans SS. The differential projections of the olfactory bulb and accessory olfactory bulb in mammals. J Comp Neurol 1975; 161(1): 31-55. https://doi.org/10.1002/cne.901610105.
69. Roy EP, 3rd, Frost JL, Schochet SS, Jr. Persistent olfactory bulb ventricle. Clin Neuropathol 1987; 6(2): 86-87. https://www.ncbi.nlm.nih.gov/pubmed/3594978.
70. Smitka M, Abolmaali N, Witt M, Gerber JC, Neuhuber W, Buschhueter D, et al. Olfactory bulb ventricles as a frequent finding in magnetic resonance imaging studies of the olfactory system. Neuroscience 2009; 162(2): 482-485. https://doi.org/10.1016/i.neuroscience.2009.04.058.
71. Burmeister HP, Bitter T, Baltzer PA, Dietzel M, Guntinas-Lichius O, Gudziol H, et al. Olfactory bulb ventricles as a frequent finding--a myth or reality? Evaluation using high resolution 3 Tesla magnetic resonance imaging. Neuroscience 2011; 172: 547-553. https://doi.org/10.1016/i.neuroscience.2010.10.068.
72. Yousem DM, Geckle RJ, Bilker W, McKeown DA, Doty RL. MR evaluation of patients with congenital hyposmia or anosmia. AJR Am J Roentgenol 1996; 166(2): 439-443. https://doi.org/10.2214/ajr.166.2.8553963.
73. Vogl TJ, Stemmler J, Heye B, Schopohl J, Danek A, Bergman C, et al. Kallman syndrome versus idiopathic hypogonadotropic hypogonadism at MR imaging. Radiology 1994; 191(1): 53-57. https://doi.org/10.1148/radiology.191.1.8134597.
74. Dash PK, Raj DH. Biochemical and MRI findings of Kallmann's syndrome. BMJ Case Rep 2014;2014. https://doi.org/10.1136/bcr-2014-207386.
75. McCabe MJ, Gaston-Massuet C, Tziaferi V, Gregory LC, Alatzoglou KS, Signore M, et al. Novel FGF8 mutations associated with recessive holoprosencephaly, craniofacial defects, and hypothalamo-pituitary dysfunction. J Clin Endocrinol Metab 2011;96(10): E1709-E1718. https://doi.org/10.1210/ic.2011-0454.
76. Massimi L, Izzo A, Paternoster G, Frassanito P, Di Rocco C. Arachnoid cyst: a further anomaly associated with Kallmann syndrome? Childs Nerv Syst 2016;32(9): 1607-1614. https://doi.org/10.1007/s00381-016-3154-7.
77. Takahashi MP, Miyai I, Matsumura T, Nozaki S, Kang J. A case of Kallmann syndrome with empty sella and arachnoid cyst. Rinsho Shinkeigaku 1997; 37(8): 704-707. Japanese. https://www.ncbi.nlm.nih.gov/pubmed/9404149.
78. Dallago CM, Abech DD, Pereira-Lima JF, Leaes CG, Batista RL, Trarbach EB, et al. Two cases of Kallmann syndrome associated with empty sella. Pituitary 2008; 11(1): 109-112. https://doi.org/10.1007/s11102-007-0043-9.
79. Madan R, Sawlani V, Gupta S, Phadke RV. MRI findings in Kallmann syndrome. Neurol India 2004; 52(4): 501-503. https://www.ncbi.nlm.nih.gov/pubmed/15626846.
80. Manara R, Salvalaggio A, Favaro A, Palumbo V, Citton V, Elefante A, et al. Brain changes in Kallmann syndrome. AJNR Am J Neuroradiol 2014; 35(9): 1700-1706. https://doi.org/10.3174/ainr.A3946.
81. Molsted K, Kiaer I, Giwercman A, Vesterhauge S, Skakkebaek NE. Craniofacial morphology in patients with Kallmann's syndrome with and without cleft lip and palate. Cleft Palate Craniofac J 1997; 34(5): 417-424. https://www.ncbi.nlm.nih.gov/pubmed/9345610.
82. Maione L, Benadiaoud S, Eloit C, Sinisi AA, Colao A, Chanson P, et al. Computed tomography of the anterior skull base in Kallmann syndrome reveals specific ethmoid bone abnormalities associated with olfactory bulb defects. J Clin Endocrinol Metab 2013; 98(3): E537-E546. https://doi.org/10.1210/ic.2012-3553.
83. Wegenke JD, Uehling DT, Wear JB, Jr., Gordon ES, Bargman JG, Deacon JS, et al. Familial Kallmann syndrome with unilateral renal aplasia. Clin
2018. Volume 7. Issue 1. Article CID e0101 DOI: 10.15275/rusomj.2018.0101_
Macro- and Micromorphology
Genet 1975;7(5): 368-381. https://doi.org/10.1111/j.1399-0004.1975.tb00344.x.
84. Laitinen EM, Vaaralahti K, Tommiska J, Eklund E, Tervaniemi M, Valanne L, et al. Incidence, phenotypic features and molecular genetics of Kallmann syndrome in Finland. Orphanet J Rare Dis 2011; 6: 41. https://doi.org/10.1186/1750-1172-6-41.
85. Raivio T, Avbelj M, McCabe MJ, Romero CJ, Dwyer AA, Tommiska J, et al. Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia. J Clin Endocrinol Metab 2012; 97(4): E694-E699. https://doi.org/10.1210/jc.2011-2938.
86. Levine LM, Bhatti MT, Mancuso AA. Septo-optic dysplasia with olfactory tract and bulb hypoplasia. J AAPOS 2001; 5(6): 398-399. https://doi.org/10.1067/mpa.2001.118869.
87. Al-Senawi R, Al-Jabri B, Al-Zuhaibi S, Al-Azri F, Al-Yarubi S, Harikrishna B, et al. Septo-optic dysplasia complex: clinical and radiological manifestations in Omani children. Oman J Ophthalmol 2013; 6(3): 193198. https://doi.org/10.4103/0974-620X.122277.
88. Vaaralahti K, Raivio T, Koivu R, Valanne L, Laitinen EM, Tommiska J. Genetic overlap between holoprosencephaly and Kallmann syndrome. Mol Syndromol 2012; 3(1): 1-5. https://www.ncbi.nlm.nih.gov/pubmed/22855648.
89. Blustajn J, Kirsch CF, Panigrahy A, Netchine I. Olfactory anomalies in CHARGE syndrome: imaging findings of a potential major diagnostic criterion. AJNR Am J Neuroradiol 2008;29(7): 1266-1269. https://doi.org/10.3174/ajnr.A1099.
90. Chalouhi C, Faulcon P, Le Bihan C, Hertz-Pannier L, Bonfils P, Abadie V. Olfactory evaluation in children: application to the CHARGE syndrome. Pediatrics 2005; 116(1): e81-e88. https://doi.org/10.1542/peds.2004-1970.
91. Pinto G, Abadie V, Mesnage R, Blustajn J, Cabrol S, Amiel J, et al. CHARGE syndrome includes hypogonadotropic hypogonadism and abnormal olfactory bulb development. J Clin Endocrinol Metab 2005; 90(10): 5621-5626. https://doi.org/10.1210/jc.2004-2474.
92. Pingault V, Bodereau V, Baral V, Marcos S, Watanabe Y, Chaoui A, et al. Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness. Am J Hum Genet 2013;92(5): 707-724. https://doi.org/10.1016/j.ajhg.2013.03.024.
93. Barnett CP, Mendoza-Londono R, Blaser S, Gillis J, Dupuis L, Levin AV, et al. Aplasia of cochlear nerves and olfactory bulbs in association with SOX10 mutation. Am J Med Genet A 2009;149A(3): 431-436. https://doi.org/10.1002/ajmg.a32657.
94. Pingault V, Faubert E, Baral V, Gherbi S, Loundon N, Couloigner V, et al. SOX10 mutations mimic isolated hearing loss. Clin Genet 2015; 88(4): 352-359. https://doi.org/10.1111/cge.12506.
95. Elmaleh-Berges M, Baumann C, Noel-Petroff N, Sekkal A, Couloigner V, Devriendt K, et al. Spectrum of temporal bone abnormalities in patients with Waardenburg syndrome and SOX10 mutations. AJNR Am J Neuroradiol 2013; 34(6): 1257-1263. https://doi.org/10.3174/ajnr.A3367.
96. Paetau A, Salonen R, Haltia M. Brain pathology in the Meckel syndrome: a study of 59 cases. Clin Neuropathol 1985; 4(2): 56-62. https://www.ncbi.nlm.nih.gov/pubmed/3995807.
97. Van Hove JL, Spiridigliozzi GA, Heinz R, McConkie-Rosell A, Iafolla AK, Kahler SG. Fryns syndrome survivors and neurologic outcome. Am J Med Genet 1995; 59(3): 334-340. https://doi.org/10.1002/ajmg.1320590311.
98. Slavotinek AM. Fryns syndrome: a review of the phenotype and diagnostic guidelines. Am J Med Genet A 2004;124A(4): 427-433. https://doi.org/10.1002/ajmg.a.20381.
99. al-Gazali LI, Sztriha L, Dawodu A, Varady E, Bakir M, Khdir A, et al. Complex consanguinity associated with short rib-polydactyly syndrome III and congenital infection-like syndrome: a diagnostic problem in dysmorphic syndromes. J Med Genet 1999;36(6): 461-466. https://www.ncbi.nlm.nih.gov/pubmed/10874634.
100. Martinez-Frias ML, Bermejo E, Urioste M, Egues J, Lopez Soler JA. Short rib-polydactyly syndrome (SRPS) with anencephaly and other central nervous system anomalies: a new type of SRPS or a more
severe expression of a known SRPS entity? Am J Med Genet 1993; 47(5): 782-787. https://doi.org/10.1002/ajmg.1320470536.
101. Booth TN, Rollins NK. Spectrum of clinical and associated MR imaging findings in children with olfactory anomalies. AJNR Am J Neuroradiol 2016; 37(8): 1541-1548. https://doi.org/10.3174/ajnr.A4738.
102. Aziz MA. Anatomical defects in a case of trisomy 13 with a D/D translocation. Teratology 1980; 22(2): 217-227. https://doi.org/10.1002/tera.1420220211.
103. Gerber JC, Neuhann TM, Tyshchenko N, Smitka M, Hackmann K. Expanding the clinical and neuroradiological phenotype of 6q27 microdeletion: olfactory bulb aplasia and anosmia. Am J Med Genet A 2011; 155A(8): 1981-1986. https://doi.org/10.1002/ajmg.a.34079.
104. Nevado J, Mergener R, Palomares-Bralo M, Souza KR, Vallespin E, Mena R, et al. New microdeletion and microduplication syndromes: A comprehensive review. Genet Mol Biol 2014; 37(1 Suppl): 210-219. https://www.ncbi.nlm.nih.gov/pubmed/24764755.
Author:
Serghei Covantev - MD, Junior Researcher, Laboratory of Allergology and Clinical Immunology, State University of Medicine and Pharmacy "Nicolae Testemitanu", Chisinau, Republic of Moldova. http://orcid.org/0000-0001-7236-5699.
