Juvenile primary lateral sclerosis

Juvenile primary lateral sclerosis (JPLS), also known as juvenile-onset primary lateral sclerosis, is an extremely rare neurodegenerative disorder characterized by progressive dysfunction of the upper motor neurons (corticospinal tract neurons) beginning in early childhood. Unlike adult-onset primary lateral sclerosis, the juvenile form typically manifests before the age of 10 years and is caused by biallelic pathogenic variants in the ALS2 gene (also known as alsin), which encodes the protein alsin. This protein plays a role in cellular processes including endosomal trafficking and is particularly important for motor neuron health. The disease primarily affects the motor system, leading to progressive spasticity (stiffness) of the limbs, difficulty with walking, slurred speech (dysarthria), difficulty swallowing (dysphagia), and exaggerated reflexes (hyperreflexia). Symptoms typically begin in the lower limbs with gait abnormalities and gradually ascend to involve the upper limbs, bulbar muscles, and facial muscles. Importantly, JPLS is distinguished from amyotrophic lateral sclerosis (ALS) by the predominant involvement of upper motor neurons with relative sparing of lower motor neurons, meaning that muscle wasting (amyotrophy) and fasciculations are typically absent or minimal. Cognitive function is generally preserved, though some patients may develop mild cognitive difficulties over time. The disease progresses slowly over years to decades, often leading to wheelchair dependence. There is currently no cure or disease-modifying treatment for juvenile primary lateral sclerosis. Management is supportive and symptomatic, focusing on physical therapy to maintain mobility and reduce contractures, antispasticity medications such as baclofen or tizanidine, speech therapy for dysarthria, and assistive devices as needed. Orthopedic interventions may be required for severe contractures. A multidisciplinary approach involving neurologists, physiatrists, physical therapists, occupational therapists, and speech-language pathologists is recommended to optimize quality of life.

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