Hereditary spastic paraplegias (HSP) constitute a category of neurodegenerative diseases, characterized by great genetic and clinical variety. Typical symptoms include hyperflexion of the legs and a gradually developing spasticity.
Uncomplicated HSP includes the typical symptomatology of the disease: progressive lower leg muscle weakness (paraplegia) and increased leg muscle tone (spasticity). Patients initially exhibit symptoms early in the course of their life, displaying walking abnormalities, such as tripping or stumbling, due to a lack of coordination when walking. Feet paresthesias and bladder dysfunction may accompany the clinical symptoms mentioned above, but no other symptoms are evident .
Complicated HSP encompasses a variety of other crucial symptoms, including ataxia, dementia, hearing impairment, seizures, peripheral and optic neuropathy and ichthyosis. Some of the symptoms may not be caused by HSP itself, but manifest as a result of a comorbidity.
The disease is progressive and during the course of the years, many patients finally rely upon supportive equipment, such as wheelchairs or crutches in order to move . Accentuated reflexes, difficulty in lifting one's toes and dragging of the feet are expected observations. it is important to keep in mind that some of the symptoms attributed to HSP may not be caused by the condition itself, but by another comorbidity.
A physical examination provides the initial vital information for HSP to be diagnosed. The most common disease type, a result of a mutated SPG4 gene, can also be diagnosed with genetic testing, both antenatally and postnatally.
Electrophysiology  can further assist in corroborating the diagnosis of HSP. Muscle tone can be evaluated, as well as the conduction ability of peripheral nerves and dorsal column. Patient s often test absolutely normally in a nerve conduction test. However, evoked potentials exhibit a considerable delay in dorsal column fibers and corticospinal tracts. A Magnetic Resonance Imaging scan can reveal atrophic spinal cords and cerebral cortex.
HSP is incurable; various treatment can be applied to ameliorate the clinical picture and improve a patient's standards of living.
The first and simplest step is physiotherapy: patients are encouraged to strengthen their body and retain a near-to-normal muscular tone.
Drugs such as baclofen have also been administered, primarily with an aim to reduce leg stiffness and aid the patients is walking . Surgical implants (pumps) may also be used in some cases: the direct administration to the spinal canal seems to be more beneficial to individuals with severe symptomatology or intolerance to per os administration of the drug. Other medications include diazepam, clonazepam, tizanidine, anticholinergics in cases of bladder dysfunction and botulinum toxin injections .
Various equipment such as ankle braces, crutches or wheelchairs (in severe cases) can also help the patient move independently.
It is important to note that each patient is individually treated and may receive further drug treatment, depending on the symptomatology of each particular case. Genetic counseling is also recommended to families of patients with HSP.
The conditions categorized under the term of hereditary spastic paraplegia are non-fatal. Patients have normal lifespans.
HSP is a rare condition of inherited diseases. Oddly enough, due to the various genetic mutations that cause the HSP phenotypes, the conditions can be inherited with an autosomal dominant, autosomal recessive and X-linked pattern of inheritance  . The genes involved in many disease types have been mapped and up to this day, 18 mutations are known to be passed down with an autosomal dominant pattern, another 17 with a recessive pattern and 3 types are inherited in an X-linked way .
Regarding the possibility of having an offspring with HSP when a parent is affected by it, physicians have to keep in mind the basic rules of gene inheritance:
HSP has an extremely variable clinical presentation; in order for an accurate prevalence to be calculated, there should be a union of criteria and methodology, which is not always the case. Due to this fact, prevalence has been estimated at approximately 2.7-4.3 per 100,000 in 3 different locations in Italy and 2 per 100,000 in Portugal . The single report that suggested the highest prevalence of HSP calculated it to be 9.6 per 100,000 in Cantabria, in Spain .
Even though the genetic mapping of many HSP types has been successfully completed, the exact pathogenesis of the conditions has yet to be understood . This group of conditions is perceived as a result of a progressive, degenerating process that affects the upper motor neurons, namely the nerve cells that are located in the brain and spinal cord and are responsible for the coordinated contraction of muscles. The lower motor neurons, responsible for the execution of a motion, remain functionally intact, but fail to receive the proper order from the higher counterparts, in order for a complete, normal movement to be carried out.
Hereditary spastic paraplegia is an inherited condition of unknown causes. there is no known way to prevent its occurrence.
Hereditary spastic paraplegia (HSP) is not a single condition, but rather a group of closely linked diseases with a similar phenotype. Patients exhibit fluctuating symptoms and even individuals with the same condition type may experience quite distinct symptomatology. Even though symptoms vary greatly, the common axis between different spastic paraplegias includes a progressively increasing tone of the leg muscles otherwise termed spasticity, and a gradually developing loss of muscle control, also in the legs (paraplegia) .
Based on the clinical picture, there are two types of HSP. The uncomplicated type features the aforementioned symptomatology without other signs of major neurological complications. Symptoms that may arise as well include bladder dysfunction or leg paresthesias. On the other hand, the complicated HSP type includes severe neurological symptoms, such as ataxia, epileptic activity, cognitive impairment and skin conditions, which further complicate the paraplegic and spastic symptomatology.
HSP is a group of inherited conditions that are caused by genetic mutations that evince great variability. The pattern of inheritance may be X-linked, autosomal recessive or autosomal dominant. Loss of muscle control and leg spasticity are the predominant, common symptoms, which gradually develop. Each patient experiences symptoms to a certain degree and most of the individuals ultimately require some kind of assistance in order to move, such as crutches or a wheelchair.
Diagnosis is achieved upon clinical examination, evaluation of muscle tone, genetic testing and electrophysiologic studies. Imaging techniques can further corroborate the suspicion of HSP. Even though no cure is available for HSp patients, they can be treated with baclofen for spasticity, anticholinergics, diazepam, clonazepam and other drugs, with an aim to alleviate some of the symptoms.
The causes are unknown. The diseases is passed down with various patterns, such as an autosomal recessive or dominant way or an X-linked pattern. up to this day, around 31 different mutations have been identified, but many more remain unknown to the scientific community.
There are two types of HSP: complicated and uncomplicated. the uncomplicated type is the simplest disease type and includes:
The complicated type of HSP includes all the symptoms described above, plus cognitive impairment (mental retardation, memory problems, speech problems), difficulty in maintaining balance when walking, epilepsy and other serious neurological defects.
Symptoms related to HSP are observed during childhood, starting with cramping legs, imbalanced and strange gait, tripping and stumbling. Patients often experience tiredness when trying to walk because their feet muscles are weakened. The problems evolve gradually and progressively, even though their greatly vary amongst individuals, even those who have the same genetic mutation. Ultimately, some kind of walking device is usually required, such as crutches, braces or wheelchair, to facilitate movement.
Diagnosis is made mainly upon exclusion, i.e other conditions that cause the same symptoms have to me excluded. Genetic testing may also be carried out, but will only diagnose the most common mutation known. An electrophysiologic study may help to confirm a potential HSP diagnosis and an MRI scan may reveal brain malformations that are compatible with the condition.
There is no way to cure HSP. Patients follow conservative treatment in order to improve their symptoms, such as physiotherapy or drugs to help their muscles relax. Medications may be taken orally or injected in the muscles (IM).