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The Laryngoscope C 2013 The American Laryngological, V Rhinological and Otological Society, Inc. What Is the Best Imaging Modality to Investigate Olfactory Dysfunction in the Setting of Normal Endoscopy? Thomas S. Higgins, MD, MSPH; Andrew P. Lane, MD Key Words: Olfaction, anosmia, hyposmia, imaging, computed tomography, magnetic resonance imaging. Laryngoscope, 124:4–5, 2014 BACKGROUND LITERATURE REVIEW Olfactory dysfunction is a common complaint worldwide. The workup typically includes a detailed history and physical examination, chemosensory tests, and imaging studies. Olfactory dysfunction may be broadly divided into two categories: conductive and sensorineural. Examples of conductive etiologies include sinonasal inflammatory disease or obstructive sinonasal masses, whereas sensorineural causes include post-upper respiratory infections (post-URI); traumatic, iatrogenic, aging, neurodegenerative diseases (e.g., Alzheimer’s or Parkinson’s disease); and toxic exposure. When the history, physical examination, and nasal endoscopy are indicative of sinonasal disease or a mass, computed tomography (CT) of the sinus is typically performed, and the patient’s olfactory dysfunction is managed by treating the underlying disease. A subset of patients, however, present with nonspecific historical, physical examination, or nasal endoscopic findings, which fail to reveal a definitive etiology for the olfactory dysfunction. Imaging studies are generally recommended in these cases; however, there is uncertainty among otolaryngologists as to which imaging studies are necessary to fully evaluate the etiology of olfactory dysfunction. This review describes the evidence-based decision-making process for using imaging studies to evaluate olfactory dysfunction in this setting. A study of 750 subjects evaluated from 1980 to 1986 at the University of Pennsylvania Smell and Taste Center described the etiologic characteristics of their patient sample. The most common etiologies for olfactory dysfunction seen at the center include post-upper respiratory infection (26%), idiopathic (22%), head trauma (18%), and nasal and paranasal sinus disease (15%). The incidence of a brain tumor in their sample was only 0.3%. The authors made no specific recommendations regarding imaging.1 Because this study evaluated a sample from a highly specialized center that receives many referrals from otolaryngologists, the incidence of etiologies is not likely generalizable to the general population or to a sample seen in the general otolaryngologist’s clinic. Paranasal sinus disease and brain/nasal tumors may represent a larger percentage of patients with olfactory dysfunction, as the general otolaryngologist can often readily diagnose these conditions and generally does not refer them to a subspecialist smell and taste center. A study of 1,000 subjects seen at the Nasal Dysfunction Clinic in San Diego demonstrated that inflammatory processes were the etiology of olfactory dysfunction in the vast majority of their patient sample (61.3%), followed by postviral (16.6%) and head trauma (8.7%). These three entities represented 86.6% of cases of olfactory dysfunction. Their workup comprised of history and physical examination, nasal endoscopy, smell identification testing, and CT of the sinuses in every patient. Patients were diagnosed with postviral cause if the history demonstrated a temporal relationship with the olfactory dysfunction and no inflammatory disease was noted on the CT scan; no further imaging was obtained in these patients.2 This study did not indicate the incidence of tumors or neurodegenerative processes in the sample or if any patient underwent neuroimaging such as magnetic resonance imaging (MRI). These two studies have the largest sample sizes of subjects to evaluate olfactory dysfunction. Studies with smaller cohorts of patients have been published. A few review articles have been published addressing imaging in olfactory dysfunction. A review by the From the Kentuckiana Ear, Nose, and Throat, PSC (T.S.H.) and Department of Surgery (T.S.H.), Division of Otolaryngology–Head and Neck Surgery, University of Louisville, Louisville, Kentucky; and the Department of Otolaryngology–Head and Neck Surgery (A.P.L.), Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A. Editor’s Note: This Manuscript was accepted for publication October 24, 2012. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Andrew P. Lane, MD, Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins Outpatient Center, 6th Floor, 601 N. Caroline Street, Baltimore, MD 21287-0910. E-mail: [email protected] DOI: 10.1002/lary.23892 Laryngoscope 124: January 2014 4 Higgins and Lane: Imaging Modality for Olfactory Dysfunction TABLE I. Historical Findings in Patients With Olfactory Dysfunction With Corresponding Potential Diagnoses and Recommended Imaging Modalities. Finding Upper respiratory infection at onset Potential Diagnoses Post-URI hyposmia/anosmia Recommended Imaging Modality CT scan of sinuses Head trauma Traumatic olfactory nerve sheering injury CT scan of sinuses After sinus surgery Family history of neurogenerative disease Iatrogenic or recurrent sinusitis Alzheimer’s, Parkinson’s, Huntington’s CT scan of sinuses MRI brain or other neuroimaging study Other neurologic deficits (motor or cognitive deficits, headaches, vision impairment) CVA, intracranial tumor, neurogenerative process, schizophrenia MRI brain or other neuroimaging study Olfactory hallucinations Temporal lobe mass or process, schizophrenia MRI brain or other neuroimaging study Hypogonadism or lifelong anosmia Congenital etiology (e.g., Kallman’s syndrome, encephalocele) MRI brain or other neuroimaging study CT ¼ computed tomography; CVA ¼ cerebrovascular accident; MRI ¼ magnetic resonance imaging; URI ¼ upper respiratory infection. group at the University of Pennsylvania in 1993 described neuroimaging findings that are found with several disorders related to olfactory dysfunction, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Korsakoff’s psychosis, schizophrenia, congenital disorders (Kallman’s syndrome), and head trauma.3 A more recent review described imaging techniques, pathological findings, and provided a clinically based strategy for choice of imaging. The authors’ opinion was that most patients can be screened with a CT scan without contrast of the sinuses; however, some patients with infectious or postinfectious causes of anosmia in ‘‘the appropriate clinical scenario’’ may undergo an MRI scan through the frontal lobes to ‘‘identify acute or chronic sequel of infectious neuritis or herpes encephalitis.’’ They recommended MRI with and without gadolinium when a neoplastic process was suspected; however, the authors did not indicate the findings suspicious for such processes or describe if an MRI would be recommended when the history, examination, endoscopy, and CT scan were negative. The authors did mention that olfactory meningiomas usually do not invade into the nasal cavity and thus could be missed without an MRI. However, olfactory meningiomas typically do not present as anosmia, as the gradual process of olfactory dysfunction often goes unnoticed, and instead present with other neurogenic deficits such as headache, cognitive and motor deficits, and vision impairment.4 BEST PRACTICE The etiology of most cases of olfactory dysfunction can be identified, or at least suggested, by history, physical examination, and endoscopy. Some authors recommend a CT scan of the sinuses to screen for inflammatory and obstructive processes regardless of presentation, whereas some authors recommend a more selective imaging evaluation. In cases of historical evidence as well as signs and symptoms that suggest paranasal sinus disease, trauma, iatrogenic, and post-URI etiologies, a noncontrast CT scan of the sinuses appears sufficient for evaluation. When endoscopy identifies a sinonasal tumor, imaging is tailored to the tumor type and extent. In a patient with a negative endoscopy, the choice of imaging is somewhat controversial. Based on expert opinions and large prospective cohort studies, the choice of imaging modality for evaluation of olfactory dysfunction in patients without endoscopic findings of sinonasal disease, masses, or other visualized etiologies for the olfactory dysfunction depends Laryngoscope 124: January 2014 of the patient demographics and history. In general, the practitioner uses imaging to evaluate for either: 1) a neurogenic/sensory etiology, or 2) intracranial tumor or other obstructive process not identified on endoscopy. Although an MRI scan in the setting of olfactory dysfunction without an identifiable etiology may rarely identify a tumor (0.3% in the University of Pennsylvania series), there are no large cohort studies or cost-effectiveness studies to evaluate this scenario. Table I outlines potential components of the history and physical examination that may compel the physician to consider imaging. A patient, for example, with a family history of a neurodegenerative disorder and with neurologic symptoms, such cognitive impairment or motor deficits, may benefit from an MRI of the brain to detect findings of a neurodegenerative disorder such as Alzheimer’s, Parkinson’s, Huntington’s, or Korsakoff’s psychosis. It should be noted, however, that olfactory dysfunction also occurs as a natural process in aging. Among people over the age of 80 years, up to 60% to 80% demonstrate an impaired sense of smell, and 50% have anosmia in some studies.5 The patient with a history of hypogonadism and/or anosmia for a lifetime should undergo MRI evaluation for congenital agenesis of the olfactory bulbs or Kallman’s syndrome. Patients with olfactory hallucinations should be evaluated with MRI of the brain to evaluate for temporal lobe processes. Future research should include cost-effectiveness studies and further population-based studies to clarify the incidences of etiologies for olfactory dysfunction. LEVEL OF EVIDENCE The evidence for choosing an imaging modality for evaluation of olfactory dysfunction in the setting of normal history, physical examination, and nasal endoscopy includes individual case series (level 4) and expert opinion (level 5). BIBLIOGRAPHY 1. Deems DA, Doty RL, Settle RG, et al. Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center. Arch Otolaryngol Head Neck Surg 1991;117:519–528. 2. Harris R, Davidson TM, Murphy C, Gilbert PE, Chen M. Clinical evaluation and symptoms of chemosensory impairment: one thousand consecutive cases from the Nasal Dysfunction Clinic in San Diego. Am J Rhinol 2006;20:101–108. 3. Li C, Yousem DM, Doty RL, Kennedy DW. Neuroimaging in patients with olfactory dysfunction. AJR Am J Roentgenol 1994;162:411–418. 4. Hamilton BE, Weissman JL. Imaging of chemosensory loss. Otolaryngol Clin North Am 2004;37:1255–1280. 5. Lafreniere D, Mann N. Anosmia: loss of smell in the elderly. Otolaryngol Clin North Am 2009;42:123–131. Higgins and Lane: Imaging Modality for Olfactory Dysfunction 5