Introduction

Anosmia is the complete loss of smell; this differs from hyposmia, which is a decreased sensitivity to smells.¹ Anosmia can be categorised in two different ways: either acquired or congenital. Acquired anosmia is caused by colds, head trauma and neurodegenerative diseases.² Depending on the cause, the anosmia can either be permanent or the sense of smell can return once the infection clears. Congenital anosmia can be inherited from an affected parent. Acquired anosmia can be caused in two different ways. Firstly, Anosmia can be caused by an obstruction that prevents particles from reaching the olfactory epithelium. This usually occurs in congestion or with anatomical deformities. The second cause is neurogenic anosmia, in which the particles can reach the nose, but a continuous signal from the nose to the brain is unable to occur. This can occur due to viral damage or neurodegeneration. Some red flags that anosmia might have a neurological cause are progressive anosmia without any nasal symptoms. 

In addition, if there are other symptoms such as cognitive decline or seizures, then this indicates that there is likely a neurological cause for the anosmia. On the reverse side, an impaired sense of smell can predict cognitive decline for older adults.³ Anosmia prevalence also increases with age, with 3% of people over the age of 40% being affected by it, and rises to 39% for those over the age of 80.⁴ Whilst anosmia might seem harmless, it is something to be aware of for two major reasons. Firstly, it can be a symptom that something bigger is happening, and secondly, our sense of smell is a powerful warning system for us, for example, in detecting expired foods or smelling smoke. 

Mechanism of smell 

Smell occurs when a particle lands on a specialised part of the nasal epithelium.⁵ This is then converted into an electrical signal, which occurs in a process called sensory transduction. Olfactory receptor neurons have tiny hairs (cilia) that have receptors that the particle can bind to, which can trigger an electrical signal within the neuron (nerve cell). The response then spreads through the neuron until reaching the olfactory bulb. In the olfactory bulb, the neurons form a synapse (interface) with a second-order neuron. The second-order neurons form the olfactory tract, which transmits signals directly to the brain. Using this pathway, it is clear how anosmia can be differentiated into conductive, in which the particles are unable to reach the olfactory epithelium, and neurological, in which the signal is disrupted from the sensory neuron to the brain. 

Ruling out nasal and inflammatory causes 

To determine the causes of anosmia, nasal and sinus pathology must be explored. An anterior rhinoscopy is used to view visible obstructions such as polyps or septal deviation. Anterior rhinoscopy is a non-invasive examination of the nasal cavity, using a speculum and a light source.⁶ Nasal endoscopy is a more complex technique that uses a thin flexible endoscope that is inserted into the nostril to visualise the deeper structures of the nasal cavity.⁷ This allows clinicians to view the nasal cavity, sinuses and olfactory cleft. The olfactory cleft is region is not accessible, either through physical blockage or inflammation, which can cause the area of the olfactory epithelium, where scent particles bind to the olfactory receptor neurons. If this anosmia. With these two methods of visualising the interior nostril, clinicians will be able to determine if the anosmia is caused by physical obstruction or inflammation. This could be caused by inflammation, polyps, swelling or discharge.⁸ If anosmia is suspected to be caused by polyps or inflammation, a short course of corticosteroids might be prescribed. If this does not help reduce the effect of the anosmia, then this suggests that there is a further neurological problem. 

Red flags for neurological anosmia 

There are a few major red flags to suggest that anosmia has a neurological component. Firstly, if there is no sign of physical obstruction within the nasal cavity, that would stop you from smelling. Secondly, often with obstructive anosmia caused by a cold, the anosmia tends to get better over time. In addition to the worsening anosmia over time, there can be accompanying symptoms which would suggest a neurological cause. This might be headaches or seizures.⁹

These symptoms might also occur after a recent head trauma, making it important for clinicians to ask about any recent accident the patient might have had. With neurological anosmia, there can be a progression of symptoms. Another feature that is often seen in neurological anosmia is that the loss of smell is only on one side (unilateral), which suggests that there might be a tumour present that is compressing the olfactory bulb or tract, preventing signal transmission from reaching the brain.¹⁰ Finally, if imaging shows that there is a tumour or bulb atrophy, this is a major clue that the anosmia is being caused by neurological factors, specifically neurodegenerative processes.¹¹

Neurological causes 

There are six main categories for neurological causes of anosmia. Firstly, neurodegenerative causes, such as Parkinson’s and Alzheimer’s. The olfactory bulb and pathways can be impaired by the buildup of proteins such as Lewy bodies.¹² Traumatic brain injury can also lead to a loss of sense of smell. This is because the blunt force can damage the nerve fibres that pass through a region of the skull called the cribriform plate, leading to a disruption of peripheral signal transmission. Intracranial tumours can apply pressure on the nerve tract and block transmission. If the tumour is on the cribriform plate, it can also directly damage nerve endings, preventing the signal from being passed on.  Some infectious diseases can have lasting neurological damage, which in turn can cause anosmia if the virus causes damage to the epithelium or the nerve fibres. Viral infections such as COVID-19 can cause neural inflammation and longer-lasting damage than simple obstructive nasal congestion. 

Whilst we have seen how seizures might be a symptom of neurological damage that can also cause anosmia, seizures themself can be a direct cause of anosmia. Seizures can cause electrical signals to be disrupted, and therefore lead to a disruption in the olfactory pathways in the brain. This anosmia might present as either persistent or episodic anosmia. This is especially common in patients with medial temporal lobe epilepsy, who often have reduced olfactory performance.¹³ Finally, diseases which affect the central nervous system, such as multiple sclerosis or strokes, might lead to anosmia. These diseases can lead to demyelination of the nerve fibres, as well as neural inflammation resulting in interrupted signal transmission and processing.  

Clinical implications

It is important to catch anosmia as early as possible and deduce the reason behind it. This is because anosmia can flag neurodegeneration, such as Alzheimer’s, before cognitive decline is noticed. If the diagnosis is delayed, then the progression of the disease is harder to monitor, as well as missing out on the chance to treat the disease early.¹⁴ 

Summary  

One should start to suspect a neurological cause of anosmia if there is no nasal blockage or inflammation that would suggest an obstructive reason. In addition, if the loss is unilateral (on one side) as well as progressive, this suggests that the cause is neurological. Finally, if imaging shows tumours or a bulb atrophy, then this shows that the cause of the anosmia is neurological in nature.