Hereditary spastic paraplegia (HSP), also known as familial spastic paraparesis, is a term used for a group of inherited diseases that affect the upper motor neurons traveling from the brain through the spinal cord, to synapse with lower motor neurons that innervate muscles.
This condition is distinct from motor-neuron disease (MND) or amyotrophic lateral sclerosis (ALS) in which both upper and lower motor neurons degenerate.
What are the clinical characteristics of HSP?
The symptoms of HSP depend on the subtype inherited. However, in all forms of HSP, the chief features include the progressive spasticity of limb muscles i.e. muscles of the limbs become stiff or feel tight, along with functional paralysis and increased tendon reflexes. In addition, there is extensive muscle weakness and perhaps bladder control issues. Impaired pain sensation is found in the legs in a majority of HSP patients.
Other symptoms may include:
- Mild gait abnormalities (ataxia)
- Impaired balance and coordination
- Peripheral neuropathy
- Deafness and/or impaired vision
- Presence of seizures (epilepsy)
- Rarer cases may exhibit dementia and cognitive impairments including learning disabilities
Upper body muscles tend not to be affected and therefore these patients have normal facial and swallowing function. HSP is progressive and the symptoms worsen with age. However, depending on the type of HSP, symptoms may vary from very mild to severe disability. In the absence of complications, individuals with HSP may have normal life expectancy.
What causes HSP?
All forms of HSP are due to mutations of various genes. The most common among these are in spastic gait (SPG) loci; SPG4 (spastin gene) and SPG7 (paraplegin gene). There are currently over 70 known genetic variants of HSP and each subtype e.g. SPG1, is numbered in the order of its discovery.
Many of these genes are either inherited in an autosomal dominant manner, autosomal recessive, X-linked recessive, or as inherited ‘maternal’ traits due to mitochondrial DNA. Depending on the inheritance pattern, the likelihood of developing HSP varies significantly.
Examples of SPG loci include SPG3A which codes Atlastin resulting in an early-onset but slowly progressing form of HSP. Mutations to ALDH18A1 (SPG9A) causes complicated HSP with cataracts, gastroesophageal reflux, ataxia and cognitive impairment. Some SPG loci e.g. SPG23 & SPG24 contain unidentified genes, and give rise to complicated versions of HSP, usually starting in childhood and presenting with additional symptoms including vitiligo and premature graying.
Rarer forms such as SPG1, which is due to X-linked mutations to L1CAM, produces an extremely complicated form of HSP with symptoms of mental retardation (severe disability), hydrocephalus (enlarged head with high pressure), aphasia (impairment of language) and adducted thumbs.
The overall prevalence of HSP is estimated to be 2-6 /100,000 with the average age of onset being 24 years. Thege of onset can vary significantly; however, the younger the onset, the more time there is for symptoms to progress.
How is HSP diagnosed and treated?
The diagnosis of HSP depends on the clinical features, characterized by progressive spastic weakness of the lower limbs, while there is evidence of damage to the upper motor neurons. A positive family history is typically present. Genetic testing may be available to confirm the diagnosis.
There is no standard therapy or medication protocol for the treatment of HSP, and there is no cure. Treatments tend to be supportive and target symptoms such as spasticity or bladder control issues. Examples of medication include muscle relaxants, sedatives to reduce spasms, and drugs to reduce overactivity of muscles.
As with most spastic conditions, physical therapy and exercise is often a good way of maintaining and improving muscle strength and function. The overall prognosis for HSP varies significantly with the subtype of HSP inherited. Though the majority of HSP patients may have a normal lifespan, assistive measures may need to be put in place, to aid mobility, for example, depending on how disabling the symptoms are.