Introduction

Sclerosis, or multiple sclerosis (MS) is a condition affecting the nerves responsible for movement. It leads to muscular malfunction in different parts of the body, causing problems with vision, movement of the limbs, sensation, and balance. In this article, we will be focusing on a specific type of sclerosis known as primary lateral sclerosis (PLS) – a very rare neuromuscular disorder.

What is Primary Lateral Sclerosis (PLS)? 

As we already know, the brain is our control centre, responsible for the regulation of many internal and external functions in our body. Coordinated regulation of many functions requires proper communication between the brain and other parts of the body. This is where the spinal cord comes in. The spinal cord is responsible for conducting information (sensory impulses) from different parts of the body to the brain through the afferent nerve fibres and the conduction of directions from the brain (motor impulses) to the target organ through efferent nerve fibres. 

Primary Lateral Sclerosis is a rare neurodegenerative disorder accounting for 3-5% of the total motor neuronal diseases recorded.⁴ This is a central nervous system related disorder that occurs due to the destruction of the motor neurons of the nerve cells in the brain responsible for the regulation of the hand, legs, arms and tongue. 

This is a specific type of sclerosis which develops slowly, causing muscle stiffness in the arms and legs. Due to muscle stiffness, patients with PLS start losing the ability to move their arms and legs.¹ Adding to this, dysfunction in the nerve region responsible for connecting the facial region with the brain (corticobulbar tract) can cause the immobility of the tongue, which is a very rare symptom of PLS.^1,2,3 

Unlike the other types of multiple sclerosis, the PLS develops its symptoms quite slowly. Moreover, the disease primarily affects the function of the upper motor neurons. 

PLS symptoms are closely related to another type of sclerosis called amyotrophic lateral sclerosis (ALS), but the progression of PLS is much slower than that of ALS. PLS typically develops over 20 years.

In most cases, the symptoms of PLS are not fatal.2 In addition, the symptoms of the upper and lower motor dysfunctions may not be visible in PLS, which is on the other hand inevitable in ALS.^1,5 Due to this confusion, it is important to disentangle those differences.

Causes of primary lateral sclerosis

Currently, the causes of PLS are unknown, and it is thought to occur randomly. However, the involvement of genes and environmental factors has been proposed.

Genetics 

The genes ALS2 and ERLIN2 have been implicated in juvenile-onset PLS, and C9orf72 in adult-onset PLS. Involvement of other genes such as SPG7, FIG4, and OPTIN has been hypothesised. More research is hence needed to elucidate the genetic causes of PLS.

Environmental factors

There are several environmental factors that have been hypothesised to induce or influence the genetic mutation related to PLS in the human body:

• smoking
• metals in the human body (e.g. lead)
• trauma
• excessive physical exercise 
• agricultural chemicals are claimed to be responsible for inducing genetic mutations related with⁹ 

Although, no direct association has been reported between the disease and the factors. Adding to this, some other natural factors like UV radiation might be capable of influencing the genetic mutation in some cases.⁶ 

Symptoms of PLS

Symptoms include:²

1. Slowed movement with having trouble in maintaining balance due to the damage in one or more nerve tracts
2. Impaired speech
3. Mood swings and emotional distress
4. Difficulty in swallowing (dysphagia)
5. Paralysis 

The upper motor neurons are a part of the primary motor cortex which are responsible for the regulation of voluntary muscle movement with the help of several nerve tracts (corticospinal, corticobulbar etc.). Disruption in any of the nerve tracts may result in creating all these malfunctions. 

Disruption in the corticobulbar tract (specific part of upper motor neurons) may result in impaired speech, problems with chewing and swallowing. 

In addition, damage to the nerve cells responsible for the primary sensations in the human body can cause reduction in sensations which eventually results in paralysis.

Diagnosis of PLS

Diagnosis of PLS can be done by using several methods as the symptoms of PLS are quite similar with another type of sclerosis called Amyotrophic Lateral Sclerosis (ALS).¹ Hence, several confirmatory tests are required.

1. In the initial stage, it is important to figure out the possible causes of weakness by performing a blood test as we already know that the removal of required nutrients from the body can cause weakness. It does not have to be mandatory due to the muscle immobility
2. For further confirmation, magnetic resonance imaging (MRI) can be performed to determine whether there is a breakdown in nerve cells¹⁰
3. To distinguish between ALS and PLS it can be helpful to use electromyography (EMG) as it is capable of measuring the electrical activity in response to nerve stimulation to a muscle cell.¹¹ As we already know, PLS specifically affects the upper motor neurons. On the other hand, ALS affects both the upper and lower motor neurons. By measuring the electrical activity in muscles, PLS can be easily confirmed by this test
4. Nerve conduction studies can be performed by measuring the electrical current (nerve impulses) which might help in determining the nerve damage. A comparatively low electric current in a certain area can testify to the fact that, due to the damage in the nerve cells, that particular area of the nervous system is incapable of demonstrating its optimum function

Treatment of PLS

Unfortunately, till date, there are no conventional ways of preventing or curing PLS but efforts are being made to restore the normal functions and relieve the symptoms related with PLS through medication, physiotherapy etc.

1. Muscle stiffness and muscle cramps can be relieved by oral administration of Baclofen, Tizanidine^10,12
2. Diazepam can be used for the relaxation of affected muscles^10,12
3. Physiotherapy can be helpful as it can help maintain muscle flexibility and also can prevent the immobility of muscle joints¹⁰
4. Antidepressants can be recommended by registered practitioners for mental and emotional distress.
5. Cognitive therapy or speech therapy can be done to recover from speech impairment

In a recent study, the researchers have demonstrated that the disease symptoms can nearly be cured using symptomatic treatment and disease-modifying therapy. They further claimed that developing a specific biomarker (used to specifically detect a disease) for PLS can show a ray of hope in the advancement of the treatment of PLS.¹³

Summary

In summary, PLS remains a complex neurological condition characterised by the progressive degeneration of upper motor neurons within the brain and spinal cord. While the exact causes of PLS remains elusive, current research suggests a multifactorial interplay of genetic predisposition, environmental factors, and potential autoimmune mechanisms. Although rare, PLS significantly impacts the quality of life of the affected individuals, manifesting through a spectrum of motor symptoms such as muscle stiffness, weakness, spasticity, and eventual loss of voluntary muscle control.

Despite advancements in medical understanding, there are challenges in diagnosing PLS due to its similarities with other motor neuron diseases such as amyotrophic lateral sclerosis (ALS). This underscores the importance of comprehensive clinical evaluation including neurological examinations, electromyography, and neuroimaging studies to accurately differentiate PLS from other similar conditions. The management of PLS primarily revolves around symptomatic treatment aimed at alleviating muscle stiffness and spasticity, enhancing mobility, and improving the quality of life. Physical therapy, assistive devices, and medications targeting spasticity are commonly employed to address these symptoms. However, there remains a pressing need for targeted therapies to halt or slow down the progression of PLS, highlighting the importance of ongoing research efforts in understanding its underlying mechanisms. 

In summary, while PLS poses significant challenges in diagnosis and management, advancements in medical research offer hope for improvised outcomes and potential therapeutic interventions in the future. By fostering a collaboration between clinicians, researchers, and affected individuals, we can strive towards a better understanding of PLS and develop more effective strategies to mitigate its impact on individuals and their families.