Hereditary Spastic Paraplegia

Original Editor - Andy Stoddart, Kevin DaSilva, Paul Davison, Robert Sweeney, Trevor Moore

Lead Editors  

Introduction

Hereditary spastic paraplegia (HSP) is a group of inherited neurodegenerative disorders characterized by spasticity and weakness in the lower extremities . HSP may develop at any time throughout the lifespan. Generally speaking, if the disorder is developed in early childhood, the symptoms will be non-progressive, whereas the opposite holds true if developed later in life. HSP is classified as either uncomplicated (pure) or complicated. Uncomplicated HSP, as the name suggests, means the individual presents with symptoms most typically associated with HSP, including lower extremity spasticity and weakness, urinary disturbance, and mild deficits in lower extremity vibration sense . Furthermore, uncomplicated HSP does not involve other deficits related to the upper extremities, speech, or swallowing . Complicated HSP is distinguished by the presence of uncomplicated symptoms, in addition to many other symptoms, including ataxia, seizures, intellectual disability, dementia, muscular atrophy, extrapyramidal disturbance, and peripheral neuropathy . Causes of additional symptoms are yet to be identified .

The first reported cases of HSP occurred in two middle aged siblings from the Estonia region and was documented in 1880 by a neurologist named Ernst Adolf Gustav Gottfried von Strümpell . Later that decade, Maurice Lorrain went on to publish a more detailed account of HSP. Strümpell and Lorrain's early HSP research was essential to the current knowledge-base of HSP and is referred to as Strümpell-Lorrain disease today . HSP has also been referred to as familial spastic paraparesis .

Clinically Relevant Anatomy

HSP is associated with severe degeneration of the corticospinal tract, and a usually less severe degeneration of the posterior column-medial lemniscus pathway . The corticospinal tract is the major descending motor pathway that terminates on motor neurons and interneurons in the ventral horn of the spinal cord and ultimately controls movement in the limbs and trunk (reference). On the other hand, the posterior column-medial lemniscus pathway ascends from the periphery to the primary somatosensory cortex on the post-central gyrus and conveys sensory information of fine, discriminative touch, proprioception and vibration sense (reference). HSP patients experience a marked reduction in the area and axonal density of both the corticospinal and posterior column-medial lemniscus pathways , which accounts for the presentation of lower limb spasticity, followed by generally less severe weakness and decreased vibration sense .

Clinical Presentation

Individuals with HSP will have progressive spasticity of the lower limbs along with the gradual development of improper gait patterns . Typical gait patterns seen in individuals with HSP involve walking on the tip of the toes with the ankles inverted . Individuals will also exhibit a reduced step length, increased step width, and reduced range of motion in the knee with increased range of motion in the trunk in all planes . Weakness most commonly occurs in the lower limbs, but there can also be mild upper limb weakness. It is also common to have hyperreflexia of the upper limbs, along with a lack of coordination. Urinary symptoms, such as incontinence, occur in up to 50 percent of individuals diagnosed with HSP . A positive Babinski sign can be elicited in some individuals, but the occurrence is rare. In terms of sensation, individuals with HSP may exhibit decreased, pallesthesia and proprioception . It is also likely that an individual with HSP will exhibit the physical feature of a high foot arch . Intellectual disabilities, dementia, vision loss, and hearing deficits can also occur, but the occurrence is infrequent .

Etiology

HSP, as the name indicates, is inherited genetically through the individual's parents. However, HSP is unique to other hereditary disorders as there are multiple mechanisms responsible for the development of the disorder. Specifically, individuals can express the mutation whether it was inherited in an autosomal dominant, recessive, X-linked or maternal (mitochondrial) manner . To date, there are 41 different inheritance patterns that have been identified as causes of HSP .

Each inheritance pattern of HSP has multiple different genes that could be affected. Each gene mutation is associated with different presentations of the disease, including both complicated and uncomplicated. The following are the most common clinical presentation associated with each inheritance pattern.

Autosomal Dominant (AD): The SPAST gene accounts for roughly 40% of AD HSP. Along with the majority of AD HSP, the SPAST gene causes the uncomplicated form of the disorder. Typically the onset is in early childhood, and the disease is progressive. Cognitive impairments later in life may occur .

Autosomal Recessive (AR): The majority of the genes associated with AR HSP result in complicated HSP. The most common form of AR HSP (50%) is the SPG11 gene, which causes an uncomplicated or slightly complicated form of HSP. Distinguishing factors are upper extremity weakness, dysarthria (speech complications) and nystagmus .

X-Linked: Far fewer genes are involved in the cause of HSP. A mixture of complicated and uncomplicated presentations with a common theme of intellectual disability .

Maternal (Mitochondrial): Typically results in adult onset HSP and is progressive in nature. Symptoms range from mild to severe .

Diagnosis

The diagnosis of HSP is based on how the individual presents clinically and a detailed investigation of family history . A thorough physical assessment should take place looking for the clinical features (see clinical presentation) of HSP and potential genetic testing or subjective family history strengthens the diagnosis. In the absence of a family history, exclusion of other myelopathy conditions such as the following can help:

-T-lymphotropic virus-related myelopathy

-Primary progressive multiple sclerosis

-Vitamin B12 deficiency

-Copper deficiency

-Spinal cord tumors or malformations

Prognosis

Ten to twenty percent of individuals diagnosed with HSP will be asymptomatic and in the most severe scenario, less than five percent, there will be a reliance of a wheelchair for ambulation . Diagnosis of HSP before the age of 35 leads to a better prognosis compared to diagnosis in later life. Where diagnosis of HSP after the age of 35 is associated with a more rapid progression of the disease and a greater likelihood of losing the ability to walk. Life expectancy in individuals with HSP is normal .

Medical Management

As with any disease process, medical management starts with proper diagnosis. Following diagnosis, frequent physician follow-ups should occur to follow the progression of the disease. These follow-ups should include reassessment, referrals and prescription/ adjustment of medications as needed. Referrals can include, but are not limited to physiotherapy, chiropractic or any health professional aimed improving/ maintaining functional ability. Prescriptions for managing the symptoms of HSP also occur. Oral medications such as Baclofen, Tizanidine, Gabapentin/Pregabalin are prescribed as muscle relaxants. Depending on the severity of spasticity, either injections of Botulinum toxin or an implantation of a intrathecal baclofen pump can be used as management .

Physiotherapy Management

Physiotherapy management for HSP should focus on improving functional ability, managing spasticity, and preventing contractures . Exercise programs that are utilized should be holistic incorporating stretching and strengthening of the lower limbs, along with cardiovascular training .

Pelvic floor physiotherapy plays an important role in treating individuals with HSP due to incontinence and pelvic pain during intercourse that can occur in individuals with HSP . Patient education on proper posture during defecation and micturition along with avoiding over straining of the pelvic floor muscles has been shown to be useful .  Motor control exercises for the pelvic floor muscles have also been used as an effective treatment. Furthermore, the use of an insufflated vaginal probe has also been shown to be effective in stretching the pelvic floor muscles .

In a study completed by Yanxin, Roxburgh, Huang, Parsons, & Davies (2013) the use of 10 fourty-five minute hydrotherapy sessions has been shown to increase both the walking speed and step length in individuals with HSP. However, at the same there was shown to be an increase in compensatory strategies performed by individuals rather than the performance of a typical gait pattern . Therefore, one may want to be cautious when using hydrotherapy to improve the gait of an individual with HSP. As a whole, physiotherapists  should be prescribing general balance exercises to be completed daily by in individuals with HSP such as, single- leg balance using a counter to provide stability when needed . It is likely that physiotherapists will also need to prescribe and educate patients regarding the appropriate use of a gait- aid during ambulation .

In terms of managing contractures regular stretching exercises of the gastrocnemius, soleus, tibialis posterior hamstrings and adductors is recommended. Agility training has also been said to improve range of motion . The use of serial casting and  splints may help stretch and improve the position of spastic muscles. Functional electrical stimulation may also have the potential to decrease spasticity .

Outcome Measures

add links to outcome measures here (see Outcome Measures Database)