Olfaction 2014 Anosmia Stinks



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tarix07.03.2017
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Olfaction 2014

  • Anosmia Stinks

  • Robert L Pincus MD

  • NY Sinus Center/ NYOG


Olfaction 2014

  • Considerable new work over last year or two- (since Dr. Gold’s presentation)



Olfaction 2014

  • Taste- involves Glossopharyngeal, Facial and Vagal nerves- recognizes basic tastes- sweet sour, salty, bittter and umami (glutamate)

  • Olfactory Nerve- wide range of odorants- odor molecules pass to olfactory epithelim

  • Trigeminal Nerve- Sharpness of horseradish, cooling of menthol



Olfaction 2014

  • Olfactory receptor neurons in olfactory epithelium are exposed

  • Olfactory cells regenerate continuously, but diminishes with age (good news)

  • Odor molecule must diffuse through the mucous to get to mucous membranes



Olfactory Disturbances

  • Affect up to 20% of population

  • Negative impact on quality of life-

    • Enjoyment of food
    • Detection of dangerous odors/spoiled food
    • Associated with mild-severe depression
    • Alterations in food intake


Olfaction 2014

  • Smell becomes worse the more medications are taken

  • Life expectancy negatively associated with lowered olfactory abilities

  • Women superior to men in olfactory function



Causes of Loss of Olfaction

  • Common

    • Nasal and sinus Disease-obstructive/inflammatory
    • Post Viral
    • Head Trauma
    • Smoking
    • Neurodegenerative Disease
    • Age


Less common Causes

  • Medications

  • Cocaine

  • Toxic exposure- benzene, butyl acetate.chlroine, formaldehyde, ethyl acetate, paint solvents, others

  • Industrial exposure-heavy metals,

  • Nutritonal Factors- Vitamin A, B6, B12, trace metal deficiencies



Uncommon causes

  • Neoplasia

  • Radiation

  • Psychiatric

  • Endocrine- cushings, diabetes, hypothryoidism, Kallman’s syndrome

  • Olfactory aura in seizures/migraines

  • CVA,

  • Autoimmune- Sjogrens, Lupus



Medications

  • Just about every medication from antibiotics to statins has been indicated



Zinc

  • Zinc gluconate applied intranasally caused anosmia in rats

  • (food finding time)

  • Zicam



Olfaction 2014 Parksinon’s

  • Smell disorder in 95 per cent

  • Olfactory distorder may precede motor symptoms by 4-6 years on average



Olfaction/Alzheimer’s

  • Study: Patients with mild cognitive deficits

  • Those with lower olfactory scores were more likely to develop Alzheimer’s at 2 year follow up



Olfaction/Alzheimer’s

  • 308 community patients in Australia 2013- high risk normals 46-86 yoa

  • Follow up at 3 years

  • Those with diminished olfaction were significantly more likely to have cognitive decline at 3 years.

  • ?use as predictor of cognitive decline?



Newer Work



Exercise

  • Schubert et al 10/2013

  • 10 year follow up of normals- cumulative incidence of anosmia 27.6%

  • (worse if older, male)

  • 40% rate if exercised once a week

  • ( to work up sweat)

  • ? Exercised because healthier???



Tumor Necrosis Factor- alpha

  • TNF alpha- inflammatory cytokine- causes loss of smell in rats

  • Treatment with oral steroids prevented this loss

  • ? Use of prednisone in loss of smell



Interleukin 6 in Hyposmia

  • IL-6 is an inflammatory mediator- pro inflammatory cytokine

  • Henkin et al 2013

  • IL-6 is increased in nasal mucous of patients with hyposmia compared to controls

  • Highest in pts with burning mouth syndrome, post viral, head trauma and lowest with allergic rhinitis



Measurement of Olfactory Bulb (OB)

  • Correlates to loss of smell

  • Diminishes in size with loss of function

  • (laryngectomy, polyps)

  • Predictor of return of sense of smell



Coronal T2 MRI Olfactory Bulb- normals



Olfactory Bulb



OB size and return of olfcation

  • Rombaux et al 2012

  • 60 patients with acquired hyposmia

  • 28 post infectious 32 post trauma

  • Sniffin test at first eval and 15 months

  • 36% post infectious improved-

  • 25% post trauma improved



OB size and return of Olfaction

  • NO patients with OB <40 mm3 had return of function

  • Initial measurement of OB is significant prognosticator of return of smell



Effects of Nasal Polyps on OB

  • Herzallah et al 2013

  • 11 pts with polyps mean 10.14 mm3

  • 11 pts w/o polyps mean 47.66 mm3

  • Olfactory bulb volume decreased in pts with nasal polyps

  • May help predict which patients will have improved sense of smell post FESS



OB and laryngectomy

  • Significant decrease in average volume of OB at 6 months-

  • 64.2 mm3 to 47.1mm3



OB and stimulation

  • OB seems to diminish in size with lack of olfactory stimulation

  • (nasal polyps, laryngectomy)

  • Treat obstruction more aggressively?



Prognosis after Loss of Smell

  • Women and younger> males and older

  • Post infectious > post traumatic



Is Treatment Possible?

  • Costanzo et al 2011

  • Sensory neurons in the olfactory epithelium showed to undergo continuous regeneration, grow new axons and reestablish connections with the olfactory bulb through life



Neural Regeneration

  • Basic fibroblast growth factor applied to nasal epithelium improved neural anosmia in rats (CK?)



Effect of FESS on Smell

  • Most studies show that this is difficult to predict

  • Patients with nasal polyposis tend to have better chance of improvement



Olfaction and FESS

  • 50-83 % improvement in Olfaction with FESS- greater in those with polyps and swelling in olfactory groove-

  • 45-50% improvement in revision surgery at 16 months

  • One study showed no improvement post FESS- and most patients remain severely hyposmic



Nasal Surgery and Olfaction

  • Schreiver et al 2013

  • Nasal polyps- 32 % improved sense of smell at 12 months

  • No significant improvement for sinus surgery (17%) or septal surgery (0%) without polyps at 12 months



Impaired Sense of Smell- nasal surgery

  • Briner 2004

  • 84% of patients with pre-operative losses (16/19) were aware

  • 4/184 nasal/sinus patients with new onset of impaired olfaction post surgery

  • ? Smell test pre-op?

  • ? MRI of OB to help predict improvement?



MRI Screening for Anosmia

  • Northwestern University

  • 122 patients with anosmia

    • Normal MRI 44.3 %
    • Dysosmia related findings 25.4% most common frontoethmoiditis
    • Incidental findings 40.2% -( eg small vessel disease 21.1%)
    • 9 patients with intracranial findings- 6 intracranial neoplasms (4.9%) including olfactory meningiomas


MRI Screening for Anosmia

  • Cost $48,880 per intracranial neoplasm found

  • Cost $146,600 per intracranial neoplasm found that was cause of anosmia

  • Average malpractice settlements for missed diagnosis or delayed treatment for intracranial neoplasm 1997-2003 was between $600,000 and $6,000,000

  • ????? Not sure that this makes sense but they felt one should therefore do MRI.. Did not compare to general well population..



Treatment

  • Konstandinidis et al 2013

  • 119 patients with new onset anosmia - post traumatic and post infectious

  • 16 weeks of Olfactory Therapy



Olfactory Therapy

  • Twice daily training with 4 odorants for 16 weeks

  • Rose, eucalyptus, lemon, cloves

  • Significant increase in olfaction in 2/3 post-infectious and 1/3 post-traumatic vs. controls



Olfactory Therapy

  • “16 week short term exposure to specific odors may increase olfactory sensitivity in patients with post-infectious and post-traumatic olfactory dysfunction.”



Olfactory Therapy Parkinson’s

  • Haehner et al

  • 70 patients with PD - 35 Olfactory therapy

  • 12 weeks

  • Significant increase in olfactory function with training, vs. no change in controls



Olfactory Training

  • 18 weeks high training vs low training

  • Post infectious

  • Duration High training Low

  • <24 months 26% 15%

  • <12 months 63% 19%

  • OT clearly helpful in those with post infectious loss of <12 months



Treatment of Loss of Smell

  • Methylprednisone for 14 days

  • 425 patients

  • 26.6% improved- (36.7% if sinus disease)

  • No controls



Medical Therapy

  • Heilings 2009

  • Both nasal and sytemic steroids showed improvement in smell function in patients with and without polyps- ? Obstruction to smell vs. inflammatory mediators. (IL6?)



Medical Therapy

  • Post traumatic Anosmia- Prednisone

  • 19/116 (16.4%) improved with steroids- (but no controls)



Treatment of Loss of Smell

  • Reden 2012

  • Vitamin A 10,000 units/day for 3 months

  • Post Traumatic and Post Viral

  • No significant difference in placebo vs. Vitamin A



Medical Therapy

  • Henkin et al 2011

  • 312 patients with hyposmia treated with oral theophylline

  • > 50% with improved smell function

  • All had low levels of cAMP and cGMP before teatment- responders tended to normalize



Medical Therapy

  • Intranasal Theophylline

  • Decreased cAMP and cGMP in nasal mucous in patients with loss of smell and taste

  • Oral theophylline led to increases in >50% and correlated to increased smell acuity

  • Systemic side effects



Medical Therapy

  • Intranasal theophylline (20ug in 0.4ml saline) once daily

  • 10 patients: 3 atopy, 3 post viral 2 post trauma 2 idiopathic

  • 8/10 with signficant improvement at 1-4 weeks- rx stopped - 4 persisted at 10 weeks-



Intranasal Theophylline

  • No blood levels of theophylline

  • ? Diminishes allergic inflammation

  • ? effect on OB

  • ? Through blood brain barrier



Treatment for Loss of Smell

  • Steroids- possibly more aggressive treatment of nasal obstruction to prevent OB changes

  • Alpha Lipoic Acid- Himmel for post infectious

  • Theophylline- intranasal (Pasteur)

  • Smell Therapy

  • ?

  • Unproven: estrogens, zinc, minocycline, Vitamin A

  • ? MRI for prognosis/ intracranial pathology



SO WHY THIS LECTURE?

  • NYOG SINUS CENTER PROTOCOL

  • 1. ANOSMIA



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