xRead - Olfactory Disorders (September 2023)

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PATEL et al.

with migraine when compared with healthy controls, with no difference in olfactory sulcus length. 909 Fewer than 1% of migraine patients report olfactory hal lucinations, which usually correlates with osmophobia and migraine severity. 910 Phantosmia in migraine is almost always unpleasant and patients may be able to identify the specific odor. The duration of hallucinations in migraine exceeds epileptic phantosmia, usually lasting 5 to 60 min utes, leading some to speculate it is a migraine aura. 911 More data are needed to determine the true extent of OD in patients with primary headache syndromes. OD can be related to primary headache syndromes. Aggregate grade of evidence : B (Level 1: one study; Level 3: three studies; Level 4: two studies). M Congenital Unlike acquired smell loss, congenital smell loss is present at birth and may be either isolated or syndromic. 912 Isolated congenital anosmia (ICA) is a rare form of OD (0%–4%) and is a diagnosis of exclusion in nonsyndromic patients with no memory of smell, a history which may be difficult to accurately obtain. 57,299,912,913 Patients may seek care in childhood because of parental concerns but often do not present until adulthood. 914 While patients may occasionally have specific anosmia for particular odorants, one study showed a 93.1% rate of total anosmia in patients with ICA. 915,916 ICA may be the result of sinonasal malformations impairing odorant transport to the olfactory neuroep ithelium (eg, choanal atresia and OC maldevelopment), disrupted signal transduction, or pathology of cortical structures necessary for olfactory processing. 912 Charac teristic MRI findings include underdevelopment of the OB or sulcus, an imperforate cribriform plate, and/or distinct changes in the volume of cortical regions associated with olfactory memory. 540,917–920 Biopsies may yield respira tory rather than OE findings. 921 Genetic factors likely play some role and family clusters have been identified with CNGA2 and TENMI1 mutations on whole exome sequencing. 922–925 Progress has been made to identify genes associated with syndromic presentations. Kallmann syndrome is a form of hypogonadotropic hypogonadism with up to 60% of patients experiencing anosmia. 926 Associations have been noted between anosmia and CHARGE syndrome, with CHD7 and other gene mutations identified on gene sequencing. 924,927 Congenital insensitivity to pain is asso ciated with hyposmia through a SCN9A mutation. 928 Syn dromic ciliopathies, such as Bardet-Biedl, have also been associated with congenital hyposmia from basic research on mechanisms 929,930 and by a match-controlled study. 931

Holoprosencephaly associated with absence of the entire olfactory apparatus leads to smell loss but often goes unnoticed. 912 Population data rely on retrospective case series, case control studies, and rare cross-sectional studies. Clinical experience at one high-volume center estimates an over all prevalence of ICA of 5000 to 10,000. 57 One retrospec tive analysis of clinical visits for confirmed smell loss in children revealed 67% with ICA. 299 While one series cites a high rate of congenital anosmia and head trauma among all anosmic children, a different study focused on patients with subjective rhinologic complaints and found sinonasal and obstructive causes as more common, demonstrating the impact of patient selection and inclusion criteria on study results. 914,932 A cross-sectional study found those with congenital anosmia had the worst thresholds among all causes, typically with no measurable OF. 914 In regards to the evaluation and management of con genital anosmia, multiple studies have demonstrated the value of MRI with a relatively high rate of abnormalities identified. 932–935 The role of CT is less clear but may be helpful to evaluate choanal atresia or nasal cavity hypoplasia. 935 Total anosmia, which is common to con genital anosmia, is associated with a worse prognosis for functional recovery. Olfactory ERPs can provide prognos tic information in ICA. 936 Treatment remains challenging, with 0% of patients with ICA in one series demonstrating improvement compared with 59.6% of postviral patients. 937 There is some evidence that individuals with ICA and an intact olfactory pathway may demonstrate central percep tion of odorant stimuli on fMRI, and theophylline has been evaluated, although in a very low evidence study, to poten tially have benefit for some of these individuals. 937–939 Most importantly, counseling on prognosis remains critical for setting expectations for individuals with ICA. ICA is a rare condition with limited knowledge and data. Further well-designed studies will be required for a pooled analysis to more accurately characterize and iden tify potential treatment options. There are various congenital causes of smell loss. Aggregate grade of evidence : C (Level 2: one study; Level 3: one study; Level 4: 15 studies). N Related to extremely high or low body mass index (BMI) Anorexia nervosa (AN) and obesity may play a role in the pathogenesis of OD. The literature evaluating the impact of extremely low body mass index (BMI) on OF included one meta analysis, 940 which concluded that OF is mainly intact in