Hereditary Spastic Paraplegia

Primary Lateral Sclerosis

What is it?

A group of hereditary, degenerative, neurologic disorders primarily affecting upper motor neurons and principally causing progressive spastic weakness of the legs. Also known as familial spastic paraplegia or paraparesis (FSP, Strumpell-Lorrain syndrome and Spastic Paraplegia (when family history is not evident).

A group of degenerative, neurological disorders primarily affecting upper motor neurons and causing progressive spastic weakness of the legs, arms and the bulbar (speech/swallowing) muscles. It may take several years or more for full expression.

Incidence rate

Estimated at 20,000 individuals in the U.S. Researchers suggest it may be higher as it is frequently misdiagnosed or undiagnosed.

Estimated at 500 individuals in the U.S. Researchers suggest this may be an underestimate.

Predominant features

Insidious, progressive spasticity and weakness of the legs that often gets severe, requiring assistive devices. There is also difficulty with balance, clumsiness, and often muscle spasms.

Progressive spasticity and weakness of the legs that often gets severe, requiring assistive devices. There may be muscle spasms. Weakness and spasticity in the arms and hands also occurs, as well as in the bulbar muscles, causing slurred speech and difficulty swallowing. Sometimes, symptoms begin in the upper body first.

Secondary features

Urinary urgency and frequency is common and high arched feet are often present. Very rare types can present speech problems, ataxia, mental retardation, dementia, visual or hearing dysfunctions, extrapyramidal dysfunctions, adrenal insufficiency, or ichthyosis. While the arms are not generally affected enough to produce symptoms, some patients report minor spasticity and weakness in the arms.

None

What causes it?

HSP is hereditary, with some 30 genes thought to cause different types of HSP. Most forms are autosomal dominant, others are X-linked or autosomal recessive.

PLS is thought to be spontaneous. There is a rare, hereditary form.

What is going wrong?

“Upper motor neurons” in the brain and spinal cord degenerate. Upper motor neurons control voluntary movement. They deliver signals to lower motor neurons in the brain stem and spinal cord, which carry messages to the muscles.

When upper motor neurons degenerate, nerve impulses cannot transmit correctly to lower motor neurons. Therefore, the lower motor neurons cannot relay the correct messages out to the muscles.

This causes spasticity (increased muscle tone/stiffness) and weakness in the muscles. HSP affects the longest nerves in the spinal cord, thus primarily affecting the legs. As degeneration continues, symptoms worsen.

“Upper motor neurons” in the brain and spinal cord degenerate. Upper motor neurons control voluntary movement. They deliver signals to lower motor neurons in the brainstem and spinal cord, which carry messages to muscles.

When upper motor neurons degenerate, nerve impulses cannot transmit correctly to the lower motor neurons. Therefore, the lower motor neurons cannot relay the correct messages out to the muscles.

This causes spasticity (increased muscle tone/stiffness) and weakness in the muscles. PLS affects the longest nerves in the spinal cord, which affect the legs, and shorter nerves in the spinal cord and brainstem, which control the arms and bulbar muscles. As degeneration continues, symptoms worsen.

How is it diagnosed?

HSP is a clinical diagnosis made through careful observation and testing, exclusion of other conditions, family history and sometimes genetic testing.

Absence of documented family history cannot rule out HSP. Experts predict about 1/3 of individuals showing all the signs and symptoms of HSP do not show family history. Gene testing can confirm dominantly inherited HSP in 45% of patients.

Early stages of HSP can mimic PLS or ALS. In the absence of family history to confirm HSP, neurologists watch for further symptom development . This observation period is generally five years.

PLS is a clinical diagnosis made through careful observation and testing and exclusion of other conditions.

Early stages of PLS can mimic ALS or HSP. Neurologists continue testing and watch for further symptom development as well as development of family history. A diagnosis of ALS is generally evident within 3-5 years.

Age of onset

Symptoms can begin at any age from childhood through late adulthood. Most patients experience onset of symptoms in the second - fourth decades of life.

The reported age of onset ranges from 35-66 years with a median of 50.5 years. A rare, child-onset form has been reported.

What is the prognosis?

It affects the quality of life. Difficulty walking usually gets slowly worse, often requiring canes, walkers, or wheelchairs. However, some individuals with childhood-onset of symptoms experience very little worsening.

There is currently no cure.

It affects the quality of life. Difficulty walking usually gets slowly worse, often requiring canes, walkers, or wheelchairs. Speech and swallowing difficulty may become severe, as well as arm involvement.

There is currently no cure.

What is the treatment?

There is no treatment to prevent, retard or reverse the degenerative process. Treatment is focused on symptom relief (medications for spasticity), physical therapy and exercise, assistive devices and supportive therapy.

There is no treatment to prevent, retard or reverse the degenerative process. Treatment is focused on symptom relief (medications for spasticity), physical therapy and exercise, assistive devices, speech therapy and supportive therapy.

What research is being done?

Research on HSP and related neurologic conditions is accelerating. Many HSP genes have been discovered and animal models are underway. Important discoveries are being made for other motor neuron diseases, related neurologic disorders and recovery from spinal cord injury. There is much to be hopeful for that cures for these conditions will be found.

Research on PLS and related neurologic conditions is accelerating. A gene for a rare, familial childhood form of PLS has been identified. An animal model is underway. Important discoveries are being made for other motor neuron diseases, related neurologic disorders and recovery from spinal cord injury. There is much to be hopeful for that cures for these conditions will be found.