Introduction

From perceiving the tantalising aroma of freshly baked pastries to lavender-infused laundry, our sense of smell rekindles pleasant memories and creates new ones. It is estimated that humans can detect approximately 100 billion types of odour, thanks to the odour-detecting cells in our noses. Also, did you know your sense of smell is vital for survival, and the food you eat? This is why food seems flavourless when you have a blocked nose. 

However, certain conditions can cause loss of sense of smell, otherwise called anosmia. This has been linked to a neurological autoimmune condition, Multiple Sclerosis (MS), which has a diverse range of symptoms. Hence, this article sheds light on anosmia as an overlooked symptom of MS. 

Understanding anosmia and MS

Anosmia is a condition that occurs when you lose your sense of smell. Any disorder or condition that disrupts the pathway that leads to the perception of smell, either physically or along the olfactory (smell) pathway, can lead to anosmia.¹ Furthermore, problems with the sense of smell can be due to a physical obstruction (conductive) or due failure in signalling in the olfactory pathway (sensorineural). Thus, there are several causes of anosmia, which include:

• Head trauma
• Viral infections such as COVID-19² 
• Intranasal tumours
• Nasal polyps 
• Congenital conditions such as Turner syndrome and Kallman syndrome 
• Medications and chemicals such as antihistamines, nasal decongestants, ACE inhibitors, and illicit drug use³
• Neurological and neurodegenerative conditions such as Alzheimer’s disease, Parkinson's, temporal lobe epilepsy, MS, and cerebrovascular disease³

The human sense of smell naturally decreases with age. The factors associated with losing the sense of smell have consistently been older age and male sex.⁴ Some red flag symptoms to watch out for include:⁵ 

• ophthalmoplegia (weak eye muscles)
• severe frontal headache
• scabbing within the nasal cavity 
• Cacosmia (condition where smells are perceived as unpleasant or stinking) 

MS is a chronic autoimmune neurological condition characterised by damage to the myelin sheath and nerve tissue in various parts of the central nervous system (CNS).⁶ This includes the cortex, brainstem, cerebellum, and spinal cord. Consequently, this leads to impaired neuronal signalling and a broad range of symptoms. These are visual problems, dysfunctional motor control (movement disorder), impaired cognitive performance, balance, and loss of sensation.⁶ 

MS is one of the most prevalent autoimmune conditions globally and is known to cause neurological impairment in young adults. Generally, MS affects around 2.5 million people worldwide, with a greater prevalence in people assigned female at birth (AFAB).⁷ It is thought that MS occurs when the immune system, which normally works against infections, gets confused and attacks the myelin sheaths that cover the nerve fibres. This can damage the myelin and remove it from the nerve fibres completely or partially. This creates wounds that are called lesions or sclerosis. The overall prevalence of anosmia among patients with MS is 27.2%, but varies depending on age, type, and severity of MS.⁶

Why anosmia manifests in MS

Our sense of smell, or olfaction, is controlled by a complex network comprising the olfactory nerve, bulb, and tract, the orbitofrontal region and cortex, the insula, and the cerebellum. As previously mentioned, these are the same areas subject to demyelination in MS.⁸ 

Several factors can contribute to the development of olfactory dysfunction in people with MS. These include:⁹ 

• Persistent inflammation within the central nervous system
• Demyelination of the olfactory bulbs
• Plaque accumulation in parts of the brain connected with the olfactory pathway

Persistent inflammation in the CNS can affect the olfactory bulb and associated regions of the brain and can induce damage in the olfactory nerves and pathways. As the olfactory nerve and bulb lack myelin (the protective coat on neurons destroyed in MS), the entire olfactory network is involved. This occurs due to wider damage to the CNS typically seen in secondary progressive multiple sclerosis (SPMS).¹⁰ A relationship has also been established between olfactory dysfunction and the onset of psychiatric symptoms such as anxiety and depression, as well as neurologic dysfunction and disability in people with MS.¹¹

Why is Anosmia Overlooked in MS?

Anosmia is often overlooked in multiple sclerosis for several reasons, which are discussed below:

Lack of awareness 

Some people may not be aware that the loss of smell can occur in MS. This is particularly true if they have other underlying health conditions that could affect their sense of smell. Less than a quarter of people with problems in their olfactory pathway are aware of their problem unless they are tested.¹²

Differential diagnosis

Dysfunction in the olfactory system is one of the early sentinel signs of neurodegenerative conditions like Alzheimer’s disease and has other causes as well. Therefore, it could be challenging to detect anosmia in MS, especially when accompanied by other common symptoms of neurological conditions. 

More focus on other chronic symptoms

MS can elicit a range of neurological symptoms such as visual and cognitive impairment, numbness and tingling, bowel and bladder problems, etc. Thus, there is a tendency for loss of smell to be overlooked as it is comparable to other symptoms in terms of severity.

Diagnosis of anosmia in MS

When it comes to the diagnosis of olfactory dysfunction, the most effective psychophysical tests used in hospitals include:⁶ 

• The University of Pennsylvania Smell Identification Test (UPSIT)
• The Connecticut Chemosensory Clinical Research Centre Test
• The Sniffin’ Sticks Test

However, these psychophysical tests, that measure the ability to identify and differentiate odours, require complex cognitive functions and high focus which are likely compromised in the early stage of MS.⁶ Thus, there is need for an objective evaluation of olfaction for MS patients. 

Another method called Olfactory Event-Related Potentials (OERPs) has been employed to assess olfaction with the advantage of objectivity when compared to psychophysical tests.¹³ OERPs are a reliable electrophysiological method for studying the olfactory system. This method assists with the observation of changes in the functioning of the olfactory system in an objective and highly accurate way. The presence of OERPs is a strong indicator of working olfactory function, while the absence of OERPs is indicative of an olfactory loss.¹³ Notably, OERPs induced in some studies in people AFAB had a faster result and greater magnitude compared to those assigned male at birth (AMAB). This suggests that there could be a hormonal modulation of the sense of smell and differences related to gender in the neural processing of odours.¹³

Treatment and management of anosmia in MS

The treatment and management of anosmia in multiple sclerosis depend on the underlying cause. This is because anosmia is not a diagnosis but a symptom of a health condition. However, as there is no cure for MS, the treatment objective is to reduce the frequency and severity of relapses as well as delay disease progression.

The use of corticosteroids, such as methylprednisolone, over the course of three to five days (intravenously) suppresses the immune system and reduces inflammation associated with MS. Subsequently, the patient can be placed on a lower dose of oral corticosteroids. These drugs speed up recovery from MS attacks and relapses but might not alter the long-term progression of the disease.¹⁴ Additionally, some of the primary immune-modifying therapies include glatiramer acetate, dimethyl fumarate, fingolimod, interferon-beta preparations, natalizumab, and mitoxantrone.¹⁴

FAQs

Can damaged olfactory nerves be repaired in MS?

The olfactory nerves, which detect odour in the nose, can regenerate and reconnect with the olfactory bulb. This regeneration can trigger the gradual recovery of smell, but this depends on the severity of the damage caused by MS. 

Is there a cure for MS?

No, there is no cure for MS. Fortunately, there are treatment options used to manage symptoms, reduce the likelihood of relapse, and slow the progression of the disease. 

Can MS cause a permanent loss of smell?

Yes, MS can lead to a permanent loss of smell. However, some people with MS may experience a temporary or partial loss of smell, while others might experience a permanent decline in their sense of smell. This depends on a variety of factors such as age, family history, type and extent of severity of MS. 

Summary 

• Anosmia is a mild but often underrecognised condition characterised by a loss of sense of smell
• MS is a serious neurological disorder caused by the destruction of the myelin sheath due to autoimmunity
• MS is a lifelong condition that can affect the brain and spinal cord, leading to a wide range of symptoms including visual problems, motor control, cognitive abilities, balance, and overall sensation
• Anosmia manifests in MS due to inflammation, demyelination, and accumulation of plaque, which can involve various parts of the brain, including the olfactory network
• Diagnosis of anosmia in MS involves the application of psychophysical tests and OERPs, which have better objectivity and higher accuracy
• Treatment of anosmia in MS lies in accurately addressing the underlying cause and reducing symptoms
• Although overlooked, anosmia in individuals with MS can affect the physical, mental, and behavioural state as well as the overall quality of life