What is Primary Lateral Sclerosis (PLS)?
Primary Lateral Sclerosis is a rare motor neuron disease that affects the upper motor neuron pathways from your brain to your spinal cord. Unlike ALS, it leaves the lower motor neurons largely intact — which is why most people with PLS live for decades after diagnosis.
What is PLS?
Your nervous system controls movement through two types of motor neurons working in series. Upper motor neurons (UMN) originate in the motor cortex of your brain — specifically in large cells called Betz cells — and send signals down the corticospinal tracts to the spinal cord. Lower motor neurons (LMN) sit in the spinal cord and brainstem, receive those signals, and relay them directly to your muscles.
In PLS, it is the upper motor neurons that degenerate. The lower motor neurons remain largely intact. This distinction is fundamental. When lower motor neurons are lost — as they are in ALS — muscles lose their nerve supply entirely and begin to waste away rapidly. When only upper motor neurons are affected, as in PLS, muscles remain connected to their nerve supply but receive abnormal signals, producing stiffness, spasms, and gradually increasing weakness rather than rapid wasting.
Some researchers now view PLS as sitting on a continuum with ALS rather than being a fully separate disease. Genetic and neuroimaging studies show meaningful overlap between the two conditions. For clinical purposes, however, the distinction between PLS and ALS remains meaningful and important for prognosis.
How common is PLS?
PLS is rare. It represents approximately 1–4% of all motor neuron disease cases. Because it is rare, obtaining precise incidence and prevalence figures has been difficult — diagnoses are often delayed, and many people receive an initial ALS diagnosis that is later revised as the disease course becomes clearer.
PLS predominantly affects adults in their 5th and 6th decade of life (roughly ages 40–60), though onset outside this range does occur. There is a slight male predominance, similar to ALS. The disease appears to occur across all ethnicities and geographies, though population-based data remain limited.
What are the symptoms?
The central symptom: spasticity
Spasticity is the hallmark of PLS. It is a velocity-dependent increase in muscle tone — meaning the faster you try to move a stiff muscle, the more resistance you encounter. In practical terms, muscles feel tight and locked, movement requires more effort, and limbs may jerk or catch unexpectedly. Spasticity in PLS arises because the upper motor neurons that normally modulate muscle tone are no longer functioning correctly.
How symptoms typically begin
In 56–84% of cases, PLS symptoms begin in the lower limbs. You may notice that one leg feels stiff or heavy, that your gait has changed, or that you are tripping more than you used to. Balance difficulties are a common early complaint. Over time, symptoms spread upward to the arms and, in many cases, to the bulbar muscles controlling speech and swallowing.
In approximately 19% of cases, symptoms begin with the bulbar muscles (corticobulbar onset), producing early changes in speech or swallowing rather than the legs.
The full symptom picture
Limb symptoms:
- Progressive stiffness (spasticity) in legs and, later, arms
- Weakness — less severe and slower to develop than in ALS
- Difficulty walking, with a stiff or scissor-like gait
- Falls and balance difficulties
- Muscle cramps and involuntary spasms
Bulbar symptoms (affecting speech and swallowing):
- Slowed, effortful speech — dysarthria
- Occasional difficulty swallowing
- Jaw tightness
Research shows 88% of PLS patients retain good, serviceable speech function. Bulbar involvement in PLS tends to be far milder than in ALS.
Pseudobulbar affect: Episodes of laughing or crying that are disproportionate to or inconsistent with your emotional state. This is not a psychiatric condition but a neurological one, caused by disruption of motor pathways that regulate emotional expression. It is treatable.
Respiratory function is preserved in the vast majority of PLS patients. Research shows that 96% of people with PLS retain good respiratory function — in stark contrast to ALS, where respiratory failure is the typical cause of death.
PLS does not cause the muscle fasciculations (visible twitching) or rapid muscle atrophy seen in ALS. Sensory function is not affected. Cognitive function is generally preserved, though emerging neuroimaging research has identified some extramotor brain changes in a subset of people.
Juvenile PLS
Juvenile-onset PLS (PLSJ, OMIM 606353) is a distinct form that begins in childhood or adolescence. It is caused by mutations in the ALS2 gene, which encodes a protein called alsin important for the survival of motor neurons. It is inherited in an autosomal recessive pattern and is extremely rare.
Juvenile PLS has a different genetic basis and clinical course from adult-onset sporadic PLS. If your child has been diagnosed with juvenile PLS, genetic testing and referral to a specialist center with experience in pediatric motor neuron diseases is strongly recommended. ALS2 gene sequence analysis — covering all coding exons — is available through clinical genetic testing laboratories.