Initial Cerebellar Ataxia in Hereditary Adult-Onset Primary Lateral Sclerosis

Area of Science:

• Neurology
• Neuroscience
• Genetics

Background:

• Primary Lateral Sclerosis (PLS) is a rare, adult-onset motor neuron disease characterized by progressive spasticity.
• The typical presentation involves progressive spasticity in the limbs and bulbar muscles.
• Understanding the full clinical spectrum and genetic basis of PLS is crucial for diagnosis and potential therapies.

Observation:

• Three individuals from two kindreds presented with cerebellar ataxia preceding the onset of primary lateral sclerosis (PLS) symptoms.
• The disease onset was in the sixth decade or later, with an insidious progression exceeding 11 years.
• Initial symptoms included gait instability and hand dysmetria, followed years later by spasticity, paraparesis, and quadriparesis.

Findings:

• Cerebellar ataxia was the sole manifestation for at least 5 years before the appearance of spasticity in affected individuals.
• Neurological examination revealed spasticity, hyperreflexia, and pseudobulbar symptoms, alongside limb dysmetria and ataxic gait.
• Electromyography and MRI studies were largely unremarkable for motor unit abnormalities or cerebellar/brainstem structural changes, respectively.

Implications:

• This suggests cerebellar ataxia may be an early, distinct clinical feature in some hereditary, adult-onset forms of PLS.
• The findings expand the recognized clinical spectrum of PLS and highlight the importance of considering ataxia in its differential diagnosis.
• Further research is needed to elucidate the genetic underpinnings and precise pathochronic relationships in these cases of adult-onset PLS.