The symptoms of hereditary spastic paraplegia vary widely among patients, even within families in terms of symptoms and age of onset. Generally, muscle weakness and stiffness, cramps or spasms make walking difficult and increase the risk of falls. The reflexes of the lower limbs are generally greatly increased.
Symptoms of Spastic Paraplegia
These symptoms are accompanied by extreme physical fatigue.
In some patients, the signs get worse over time, while others may stop after adolescence. In 10% of cases, patients develop eye problems, intellectual deficits, loss of muscle control or deafness due to brain damage.
Patients with spastic paraplegia may have symptoms suggestive of other neurodegenerative pathologies such as amyotrophic lateral sclerosis or cerebellar ataxia. MRI of the brain or spinal cord, a recording of electrical signals in the brain or muscles can help with diagnosis. Genetic diagnosis can often confirm the disease by showing a genetic mutation.
At Paris Brain Institute
Our researchers are carrying out projects aimed at both developing diagnostic tools and identifying the genes responsible for the variability observed between patients.
Giovanni STEVANIN’s team has developed, through a collaborative effort involving the Genotyping-Sequencing Platform of Paris Brain Institute, a diagnostic kit capable of sequencing all the genes known to be involved in hereditary spastic paraplegia in a few hours with high reliability. The development of this kit represents a considerable saving of time and a major advance in the molecular diagnosis of these pathologies. This kit is distributed nationally and internationally.
A study by Professor Alexandra DURR has led to the discovery of factors influencing the age of onset of hereditary spastic paraplegia type 4. These initial findings are very important in the search for modifiers of hereditary spastic paraplegia type 4 and open new avenues of investigation into the impact of mutation and gender on the age of onset and severity of the disease.
The team also investigated a potential link between type 7 spastic paraplegia and cerebellar ataxia. A number of patients with spastic paraplegia also have symptoms of cerebellar ataxia and are only diagnosed retrospectively. The results of this research could lead to earlier diagnosis and management of patients.
Khalid H. El Hachimi and colleagues showed similarities in nervous system lesions between spastic paraplegia type 11 and Amyotrophic Lateral Sclerosis. This discovery will enable clinicians to make an accurate and early diagnosis of “atypical” ALS, via a search for a mutation in the SPG11 gene. On the other hand, understanding the mechanisms involved in these pathologies paves the way for the development of new targeted therapeutics.
