Primary Lateral Sclerosis

Definition/Description

Primary Lateral Sclerosis (PLS) is characterized as being a rare, non-hereditary, idiopathic, slow, and progressive degeneration of the upper motor neurons. PLS lies on a continuum of sporadic motor neuron disorders. This spectrum includes other disorders such as progressive muscular atrophy, which involves only lower motor neurons, as well as amyotrophic lateral sclerosis (ALS), characterized by both upper and lower motor neuron involvement. Many patients diagnosed with PLS continue to have high levels of independence for many years.

Epidemiology 

• Approximately 2-5% of adults in neuromuscular clinics will be diagnosed with PLS.
• The age of onset is approximately 50 years and older, though a juvenile form of PLS has been described as well.
• Although the difference is not pronounced, there is a slight male predominance over females in being diagnosed with PLS.

Etiology

The exact cause of adult-onset PLS remains unknown. PLS is a diagnosis of exclusion, meaning that individuals are diagnosed with the condition when their progressive upper motor neuron dysfunctions cannot be explained by any other possible cause.

Clinical Presentation

PLS is due to upper motor neuron (UMN) degeneration, and therefore clinical presentation is consistent with signs and symptoms of an UMN disorder in the absence of lower motor neuron (LMN) symptoms. These include;

• Spasticity
• Hyperreflexia
• Weakness

Other key features include stiffness and increasing difficulty maintaining balance with the progression of the disorder. PLS may affect the bulbar region in the medulla, causing degeneration to the lower cranial nerves. Bulbar signs and symptoms include;

• Dysphagia
• Dysarthria
• Pseudobulbar affect/ emotional lability

PLS is classified as slowly progressive. The typical pattern of progression is spreading from side to side, region to region. It may start in the bulbar region and descend down to the limbs, or it may start in the lower extremities, progress to arms, and then bulbar region. Symptoms spread slowly over many years before plateauing. 

Prognosis

A distinctive clinical feature of PLS is that it has a very slow progression, leading it to be considered to have a more benign prognosis in comparison to ALS. The longevity of individuals with PLS is unclear, but it has been estimated to be 7.9 years or longer. Individuals with PLS and minimal EMG changes appear to have a decreased ability to ambulate independently in comparison to those without EMG changes. Nonetheless, patients may still be able to ambulate without aids after several years of being diagnosed. It is common for patients to be diagnosed with PLS but later diagnosed with ALS instead. Due to their similar course of progression, misdiagnosis can occur. A detailed spectrum of PLS categories have been detailed.

Interventions

Medical and Surgical

Currently, there is no cure for primary lateral sclerosis. Therefore, treatment primarily focuses on relieving symptoms and preserving function. Depending on the patient’s presentation, treatments may include the following :

• Oral medications such as balcofen, dantrolene, and tizanadine for muscle spasticity
• Surgically implanted balcofen pump
• Anticholinergic medication or botulism toxin injections for drooling
• Feeding tube for dysphagia
• Assistive devices such as walkers or wheelchairs for gait impairments
• Physical therapy

Ultimately, patients are best managed in a multidisciplinary motor neuron disease clinic where the various potential symptoms of primary lateral sclerosis could be comprehensively addressed.

Differential Diagnoses

As PLS is a condition that lies on a continuum of sporadic motor neuron disorders, there are several potential differential diagnosis. The 2 most likely upper motor neuron diseases that is associated with PLS are:

1. Amyotrophic lateral sclerosis

• ALS presents with lower and/or upper motor deficits and has fast(er) progression; PLS is slower progression and typically only affects upper motor neurons.
• ALS is more commonly associated with stiffness then PLS (47% vs 4%)
• Both ALS and PLS can be assoicated with cognitive issues but is not present in its ‘uncomplicated’ forms

2. Hereditary spastic paraplegias

• HSP has spasticity of the lower limbs; PLS is associated with spasticity as well and slight weakness but spasticity can affect speech (spastic dysarthria)
• Complicated cases of HSP can result in dementia & mental retardation which may mimic cognitive issues possibly present in complicated cases of PLS.

Other potential, but less specific, differential considerations include: 

• Structural lesions, especially related to the spine (eg. cervical spondylmyelopathy)
• Infection (eg. HIV, syphilis)
• Demyelinating disease (eg. mutliple sclerosis)
• Metabolic / toxic (eg. vitamin E deficiency)
• Neurodegenerative (eg. Parkinsons and parkinson's-plus syndromes)

Special care must be taken when diagnosing as PLS can be misdiagnosed as the above examples, and many more.