Olfaction 2014 Anosmia Stinks

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

• Still about 1/3
• ?Duration of Disease

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