Olfactory and Trigeminal Functions in Patients With Multiple Sclerosis: Case-control Study

Study Overview
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Brief Summary
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The sensation of smell is influenced by the somatosensory and chemesthetic sensati¬ons of the nose: for example, the cooling sensation of menthol or the prickle of carbon dioxide from carbonated drinks. These sensations are mediated in the nose by the trigeminal nerve and there is increasing evidence that trigeminal and olfactory functions are closely linked and potentially interdependent. In addition, trigeminal activation is crucial to the perception of nasal airflow. Some researchers speculate about the impact of trigeminal nerve on the entire olfactory sensation and about the presence of some specific trigeminal cells into the nose.Patients with Multiple sclerosis (MS) can suffer from quantitative olfactory disorders that generally are of light entity and do not interfere with daily life activities but it is important to underline that olfactory loss can be an onset sign of the MS. Considering the trigeminal component in the olfaction, because trigeminal nerve inflammation is quite common in MS patients due to central and peripheral inflammation, it could be possible that these patients suffer from changes in the quantitative, but more in the qualitative smell functions that are generally not identified because poorly investigated.

Detailed Description
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From a theoretically point of view pain in the trigeminal nerve increases the surrounding perception, including the perception of the odors. It has been shown that by using sweet food it is possible to reduce the level of pain; on the other side, sweet food in contrast to the bitter one was able to reduce the sensation of odor unpleasantness present with pain increase. To date no studies have investigated the relationship between trigeminal inflammation, odors and pain in a cohort of patients with MS. This study aims at investigating the possible correlation between alteration in trigeminal functions and perception of odors using Sniffin' Stick Threshold, Detection and Identification test and quality smell questionnaire in a sample of healthy patients compared to MS patients.

Official Title
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Olfactory and Trigeminal Functions in Patients With Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Diagnostic Test: TDI
* Diagnostic Test: Trigeminal Test
* Diagnostic Test: Cognitive Evaluation by Montreal Cognitive Assessment
* Diagnostic Test: Anxiety and Depression questionnaire
* Diagnostic Test: Visual Analogue Scale Ratings
* Diagnostic Test: Quality of smell Questionnaire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult women (age 18 to 55) diagnosed with multiple sclerosis using the 2017 McDonald Criteria under treatment with Disease Modifying Therapy (DMTs) with or without trigeminal concerns, or newly diagnosed with MS Exclusion Criteria: Chronic rhinosinusitis with and without nasal polyposis; current allergic rhinitis; other nasal issues that lead to olfactory dysfunction anamnestic COVID with incomplete recovery Neurodegenerative disorders (Parkinson, Alzheimer, Fronto-temporal Dementia, cognitive impairment and brain vascular diseases) History of stroke in the last three years Depression or any psychiatric condition intake of drugs with sedating side effects major health issues that might affect olfactory function (e.g., significant renal insufficiency, uncontrolled diabetes) Chronic alcoholism / drug abuse Severe head trauma Severe facial injuries Smoker over 20 cigarettes day or smoking from more than 15 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control<br>Healthy patients | Diagnostic Test: TDI<br>* Sniffin' Sticks Threshold and Identification Test<br>Diagnostic Test: Trigeminal Test<br>* Test the trigeminal smell answer by a device that releases air and a substance that stimulates the trigeminal response<br>Diagnostic Test: Visual Analogue Scale Ratings<br>* Smell ability (How is your sense of smell right now? 0 cannot smell, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal) Nasal breathing (How well can you breathe through your nose right now? 0 complete nasal obstruction, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal)<br>Diagnostic Test: Quality of smell Questionnaire<br>* Patients will answer to a validated questionnaire<br>|
| Multiple Sclerosis 1<br>Patients with multiple Sclerosis and Trigeminal disorders | Diagnostic Test: TDI<br>* Sniffin' Sticks Threshold and Identification Test<br>Diagnostic Test: Trigeminal Test<br>* Test the trigeminal smell answer by a device that releases air and a substance that stimulates the trigeminal response<br>Diagnostic Test: Cognitive Evaluation by Montreal Cognitive Assessment<br>* Montreal Cognitive assessment<br>Diagnostic Test: Anxiety and Depression questionnaire<br>* Specific test to evaluate patient's mood<br>Diagnostic Test: Visual Analogue Scale Ratings<br>* Smell ability (How is your sense of smell right now? 0 cannot smell, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal) Nasal breathing (How well can you breathe through your nose right now? 0 complete nasal obstruction, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal)<br>Diagnostic Test: Quality of smell Questionnaire<br>* Patients will answer to a validated questionnaire<br>|
| Multiple Sclerosis 2<br>Patients with Multiple Sclerosis without trigeminal concerns | Diagnostic Test: TDI<br>* Sniffin' Sticks Threshold and Identification Test<br>Diagnostic Test: Trigeminal Test<br>* Test the trigeminal smell answer by a device that releases air and a substance that stimulates the trigeminal response<br>Diagnostic Test: Cognitive Evaluation by Montreal Cognitive Assessment<br>* Montreal Cognitive assessment<br>Diagnostic Test: Anxiety and Depression questionnaire<br>* Specific test to evaluate patient's mood<br>Diagnostic Test: Visual Analogue Scale Ratings<br>* Smell ability (How is your sense of smell right now? 0 cannot smell, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal) Nasal breathing (How well can you breathe through your nose right now? 0 complete nasal obstruction, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal)<br>Diagnostic Test: Quality of smell Questionnaire<br>* Patients will answer to a validated questionnaire<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trigeminal component | One bottle contains 10ml Eucalyptol (pure / 99%), the other bottle contains only air 15ml stimuli would be released from both bottles using the squeezer device A 3cm long, 4mm inner diameter silicon tubing is placed over the nozzle of each bottle to minimize irritation at the nostrils Silicon tubing should reach beyond the nasal valve area Trigeminal intensity ratings (How intense is the tickling or cool sensation in the nose? 0 no feeling, 10 very strong feeling) The trial can be done on the left nostril, then on the right nostril and this already corresponds to the first presentation for the actual test Total of 20 presentations (10 on each side) with interstimulus interval of around 10 seconds between each presentation, and a longer pause of 30 seconds every 5 presentations The score is the sum of correct lateralizations | 12 months |