Primary lateral sclerosis (PLS

Primary lateral sclerosis (PLS) is a rare neuromuscular disease characterized by progressive

muscle weakness in the voluntary muscles. PLS belongs to a group of disorders known as motor
neuron diseases. Motor neuron diseases develop when the nerve cells that control voluntary
muscle movement degenerate and die, causing weakness in the muscles they control.

PLS only affects upper motor neurons.[3] There is no evidence of the degeneration of spinal motor
neurons or muscle wasting (amyotrophy) that occurs in amyotrophic lateral sclerosis (ALS).

Causes

In primary lateral sclerosis (PLS), the nerve cells in the brain that control movement fail
over time. This loss causes movement problems, such as slow movements, balance
problems and clumsiness.

Adult primary lateral sclerosis

The cause of adult primary lateral sclerosis is unknown. In most cases, it's not an inherited
disease, and it's not known why or how it begins.

Juvenile primary lateral sclerosis

Juvenile primary lateral sclerosis is caused by mutations in a gene called ALS2.

Although researchers don't understand how this gene causes the disease, they know that
the ALS2 gene gives instructions for creating a protein called alsin, which is present in
motor neuron cells.

When the instructions are changed in someone with juvenile PLS, the protein alsin
becomes unstable and doesn't work properly, which in turn impairs normal muscle
function.

Juvenile primary lateral sclerosis is an autosomal recessive disease, meaning that both
parents have to be carriers of the gene to pass it to their child, even though they don't
have the disease themselvess

Symptoms
Signs and symptoms of primary lateral sclerosis (PLS) usually take years to progress.
They include:

● Stiffness, weakness and muscle spasms (spasticity) in your legs, often starting
in one leg
● Tripping, difficulty with balance and clumsiness as the leg muscles weaken
● Weakness and stiffness progressing to your trunk, then your arms, hands,
tongue and jaw
● Hoarseness, as well as slowed, slurred speech and drooling as the facial
muscles weaken
● Difficulties with swallowing and occasionally breathing late in the disease

Less commonly, PLS begins in your tongue or hands and then progresses down your
spinal cord to your legs.
When to see a doctor

Make an appointment to see your doctor if you have persistent problems with stiffness or
weakness in your legs, or with swallowing or speaking.

If your child develops involuntary muscle spasms or seems to be losing balance more
often than usual, make an appointment with a pediatrician for an evaluation

Diagnosis

There is no single test that confirms a diagnosis of primary lateral sclerosis (PLS). In fact,
because the disease can mimic signs and symptoms of other neurological diseases such
as multiple sclerosis and ALS, your doctor is likely to order several tests to rule out other
diseases.

After taking a careful record of your medical history and family history and performing a
neurological examination, your doctor might order the following tests:

● Bloodwork. Blood tests check for infections or other possible causes of

muscle weakness.
● MRI. An MRI or other imaging tests of your brain or spine might reveal signs of
nerve cell degeneration.
An MRI can show other causes of your symptoms, such as structural
abnormalities, multiple sclerosis or spinal cord tumors.
● Electromyogram (EMG). During an EMG, your doctor inserts a needle
electrode through your skin into various muscles. The test evaluates the
electrical activity of your muscles when they contract and when they're at rest.
 This test can measure the involvement of lower motor neurons, which can help
to differentiate between PLS and ALS.

● Nerve conduction studies. These tests use a low amount of electrical current

to measure your nerves' ability to send impulses to muscles in different areas

of your body. This test can determine if you have nerve damage.
● Spinal tap (lumbar puncture). Your doctor uses a thin, hollow needle to
remove from your spinal canal small samples of the fluid that surrounds your
brain and spinal cord (cerebrospinal fluid) for laboratory analysis. A spinal tap

can help rule out multiple sclerosis, infections and other conditions.

Treatment
There are no treatments to prevent, stop or reverse PLS. Treatment, which focus on
relieving symptoms and preserving function, include:

● Medication. Your doctor might prescribe medication such as baclofen,

tizanidine (Zanaflex) or clonazepam (Klonopin) to relieve muscle spasms
(spasticity). These medications are taken by mouth.
If your spasticity isn't controlled with oral medication, your doctor might
recommend surgically implanting a medication pump to deliver baclofen
directly to your spinal fluid (intrathecal baclofen).
If you have depression, your doctor might prescribe antidepressants.
Amitriptyline and other drugs also can help drooling problems.
● Physical therapy. Stretching and strengthening exercises can help maintain
muscle strength, flexibility and range of motion, and prevent joint immobility.
Heating pads can help relieve muscle pain.
● Speech therapy. If your facial muscles are affected by PLS, speech therapy
might help.

● Assistive devices. Physical or occupational therapists might evaluate you

periodically to determine whether you need assistive devices, such as a cane,
walker or wheelchair, as PLS progresses.

Imaging of glia activation in people with

primary lateral sclerosis
Highlights
•

Is there a relationship between glia activation, cortical atrophy, and

subcortical white matter abnormalities in people with primary lateral
sclerosis (PLS)?

In this cross-sectional in vivo multi-modal (MR-PET) neuroimaging study,

we show evidence of glia activation in the motor regions in PLS patients
compared to healthy controls. The increased glia activation co-localizes with
areas of structural abnormalities including cortical atrophy and subcortical
white matter changes.

MR-PET neuroimaging is a powerful technique to localize and quantify glia

activation and structural abnormalities, and may represent a novel in vivo
biomarker of disease mechanisms in PLS.

Abstract
Background
Glia activation is thought to contribute to neuronal damage in several
neurodegenerative diseases based on preclinical and human post-mortem
studies, but its role in primary lateral sclerosis (PLS) is unknown.

Objectives
To localize and measure glia activation in people with PLS compared to healthy
controls (HC).

Methods
Ten participants with PLS and ten age-matched HCs underwent simultaneous
magnetic resonance (MR) and proton emission tomography (PET). The
radiotracer [11C]-PBR28 was used to obtain PET-based measures of 18 kDa
translocator protein (TSPO) expression, a marker of activated glial cells. MR
techniques included a structural sequence to measure cortical thickness and
diffusion tensor imaging (DTI) to assess white matter integrity.

Results
PET data showed increased [11C]-PBR28 uptake in anatomically-relevant motor
regions which co-localized with areas of regional gray matter atrophy and
decreased subcortical fractional anisotropy.

Conclusions
This study supports a link between glia activation and neuronal degeneration in
PLS, and suggests that these disease mechanisms can be measured in vivo in
PLS. Future studies are needed to determine the longitudinal changes of these
imaging measures and to clarify if MR-PET with [11C]-PBR28 can be used as a
biomarker for drug development in the context of clinical trials for PLS.
Refrences.

https:https://www.mayoclinic.org/diseases-conditions/primary-lateral-sclerosis/diagnosis-
treatment/drc-20353972//rarediseases.org/rare-diseases/primary-lateral-sclerosis/

https://jnnp.bmj.com/content/71/5/615