Hereditary Spastic Paraplegia 

Updated: Jan 14, 2019
Author: Nam-Jong Paik, MD, PhD; Chief Editor: Stephen Kishner, MD, MHA 

Overview

Background

Hereditary spastic paraplegia (HSP) is not a single disease entity; it is a group of clinically and genetically diverse disorders that share a primary feature, which is the causation of progressive and generally severe lower extremity weakness and spasticity.[1] (See Etiology, Presentation, and Workup.) 

Strümpell first described hereditary forms of spastic paraplegia (see the image below) in 1883, with Lorrain later providing more extensive detail.[2] HSP is also called familial spastic paraparesis and Strümpell-Lorrain syndrome. (See Presentation.)

Photograph of a 16-year-old girl with complicated Photograph of a 16-year-old girl with complicated hereditary spastic paraplegia. She has a spastic gait disturbance, mental retardation, and extrapyramidal symptoms. Note the dysmorphic features.

Numerous clinical reports have documented that HSP syndromes are heterogeneous. Syndromes are classified as uncomplicated, or pure, when only spinal involvement occurs, and they are classified as complicated when they are associated with neurologic abnormalities, such as ataxia, mental retardation, dementia, extrapyramidal dysfunctions, visual or hearing dysfunctions,[3] adrenal insufficiency, and ichthyosis. Clinical distinctions between pure and complicated forms of HSP have some utility. (See Prognosis, Presentation, Workup, Treatment, and Medication.)

The most useful classifications now are based on the mode of inheritance and genetic linkage. HSP may also be classified as autosomal dominant, autosomal recessive, or X-linked, and each type has several subtypes, which are based on the location of the gene. The mode of inheritance cannot be used to predict the severity of the disorder, however, because symptoms can vary greatly within each type. (See Etiology.)

In the past, HSP was also classified as type I or type II, based on the patient's age at the onset of symptoms and on the amount of spasticity versus weakness. Because both types can appear in the same family, this method of classification is no longer in general use. (The age of onset often has no clear relation to the HSP genotype.)[4]

To date, the locations of several genes associated with HSP have been identified. Eighteen types of dominantly inherited pure or complicated HSP are known, along with 17 types of recessively inherited HSP and 3 types of X-linked HSP.[5]

Complications

Patients with HSP may have several possible complications, including the following (see Prognosis):

  • Gastrocnemius-soleus contracture

  • Cold feet

  • Fatigue

  • Back and knee pain

  • Stress and depression

A study by Schüle et al of 608 patients with HSP found that the ability to walk unassisted was maintained by these patients for a median 22 years’ disease duration but that independent walking ability was maintained longer by patients who had early onset disease.[6]

Patient education

For patient education information, see BOTOX® Injections.

Etiology

HSP causes degeneration of the ends of the corticospinal tracts within the spinal cord. The ends of the longest fibers, which supply the lower extremities, are affected to a much greater extent than are the fibers to the upper body. Although some degeneration of the fibers supplying the arms commonly takes place, most people with HSP do not have symptoms in the hands or arms.

Impaired cellular membrane trafficking, more particularly, axonal transport of macromolecules and organelles, is the best-characterized genetic mechanism of HSP. Several proteins, such as spastin (SPG4) and atlastin-1 (SPG3A), which shape membranes of the endoplasmic reticulum or endosomes, are known as such candidates.[7, 8]

Mitochondrial dysfunction is the second process that leads to HSPs. Paraplegin (SPG7) is a candidate for the development of such dysfunction. It is part of the m-AAA protease, an adenosine triphosphate (ATP) ̶ dependent proteolytic complex located at the mitochondrial inner membrane, which controls protein quality and regulates ribosome assembly.[9, 10]

In most cases of HSP, the primary problem may be disturbance of the ends of the long axons, with little or no loss of myelin and no abnormal myelin. A rare type of X-linked HSP, however, has been associated with a myelin protein gene mutation. Patients with this form of HSP generally show evidence of myelin abnormalities, which are known to affect axon function. Although genes involved with myelination of the central nervous system (CNS) are less likely to be involved with HSP than are those associated with axonal stability, these genes must be considered.

A study by Agosta et al suggested that the various neurologic disorders designated as HSP share a common neurodegenerative cascade. Magnetic resonance imaging (MRI) revealed that in patients with different clinical pictures, a similar involvement existed for the motor, association, and cerebellar white matter pathways and for the cervical cord, in relation to healthy controls.[11]

Genetics

Presently, more than 80 genetic loci have been identified. There are families with autosomal dominant patients and with autosomal recessive and sporadic patients. In a report on HSP in Japan, Koh et al stated that causative genes could not be found in 35% of autosomal dominant patients or in 52% of autosomal recessive and sporadic patients.[5, 12, 13, 14, 15, 16, 17, 18, 19]

Most cases of pure HSP are autosomal dominant, whereas complicated forms tend to be autosomal recessive. With regard to pure, autosomal dominant HSP, SPG4, SPG3A, and SPG6 account for 70-80% of families.[10]

SPG4 HSP is the single most common dominantly inherited HSP, representing approximately 40% of such cases. Hazan and colleagues discovered that mutations in a novel gene designated SPG4 (protein, spastin) are the cause of this disorder.[20] Insights into the SPG4 phenotype and spastin function can yield useful information relating to hypotheses for axonal degeneration in SPG4 HSP, such as direct cytoskeletal instability, abnormal mitochondrial distribution, and other consequences of abnormal axonal transport.[13, 10, 21, 22]

A second autosomal dominant HSP (SPG3A) shows a linkage to band 14q11-q21 and accounts for approximately 10% of cases. This is also a pure HSP. Symptoms usually begin in early childhood and are often nonprogressive. Genetic testing for SPG3A is commercially available.

A third autosomal dominant HSP, SPG6, shows a linkage to band 15q11.1. Symptoms begin in late teenage years. This kindred contains a number of affected members who have developed more severe disability than typical HSP families with other linkages. Penetrance is age dependent and high. Other genes involved in autosomal dominant HSPs are SPG8, SPG10, SPG13, SPG31, and SPG33.

SPG5, SPG7, and SPG11 are involved in autosomal recessive HSPs. A family with pure HSP demonstrated a linkage to band 8q12-q13 (SPG5 HSP). SPG7 HSP has been linked to mutations in the gene encoding for paraplegin and accounts for around 5% of autosomal recessive HSPs.[13, 23] This type of mutation produces both pure and complicated HSP phenotypes. Mutations in the gene result in impaired oxidative phosphorylation.

SPG11 HSP, which is characterized by a thin corpus callosum, is a clinically distinct form that includes cognitive impairment and severe axonal neuropathies.[15, 24, 25]  A study by Faber et al indicated that in SPG11 HSP, selective neuronal vulnerability exists, with white matter involvement being precocious and widespread and subsequent gray matter degeneration being restricted but progressive.[26]

X-linked HSP is complex but rare, and the border between pure and complicated HSP syndromes is blurred. SPG1 HSP is linked to mutations in the gene for the L1 cell adhesion molecule (L1CAM); these mutations are associated with hydrocephalus, spasticity, ataxia, mental retardation, and adducted thumbs.

SPG2 HSP is linked to a duplication mutation in the gene for proteolipid protein, which is located on band Xq21-q22. Mutations in this gene are also related to complicated X-linked HSP and to the dysmyelinating condition Pelizaeus-Merzbacher syndrome. One other rare X-linked form of HSP has been described (associated with SPG16). Affected individuals have quadriplegia, motor aphasia, reduced vision, mild mental retardation, and sphincter disturbance.[27]

Preliminary genotype-phenotype correlations

With the identification of HSP loci on chromosome X and 2p, 8q, 14q, 15q, and 16q, a comparison of phenotypes is possible in families for whom the disorder is linked to one of these loci, as well as in HSP families for whom these loci are excluded.[28]

Thus far, genetically diverse types of autosomal dominant HSP (those linked to 2p, 14q, and 15q) appear to be clinically and electrophysiologically similar. This observation suggests that the different abnormal gene products may interact in a common biochemical cascade that results in similar patterns of neuronal degeneration.

The disorder may be more severe in the 15q-linked kindred than in kindreds linked with 14q. In a study of the kindred with disease linked to 14q, only 1 patient needed a wheelchair.[29] In contrast, 9 of the patients affected in a kindred HSP linked to 15q required a wheelchair (for some patients, the need began in their 40s).

Kindreds with autosomal dominant HSP linked to 2p have exhibited (1) the prototypical adolescent- or adult-onset, progressive form and (2) the less common childhood-onset, relatively nonprogressive form. The significant variations in patients' ages at symptom onset and the degree of progression in these kindreds indicate that the complete phenotype is influenced by different mutations in the same gene or by the effects of modifying genes.

Epidemiology

In Europe, the frequency of HSP is estimated to be 1-9 cases per 100,000 population. Because HSP is rare, it is often misdiagnosed, making the actual frequency difficult to determine. A reasonable estimate, however, is that it affects approximately 3 persons per 100,000 population. This represents fewer than 10,000 cases in the United States. Further estimates indicate that about 10% of people with HSP have complicated HSP.

Pure HSP may occur at any age, from infancy through late adulthood. However, most patients experience the onset of symptoms between the second and fourth decades of life.

Prognosis

In patients with pure HSP, life expectancy typically is unaffected by the condition. Generalizations about the life expectancy of people with complicated HSP are difficult to make, because each patient has unique symptoms. Possible complications associated with HSP are described below.

Gastrocnemius-soleus contracture

This condition is more common when symptoms begin in childhood. It also occurs when physical therapy (PT) has not been sufficient.

Cold feet

Many people with HSP complain of cold feet. This is a common complaint in many disorders of the upper or lower motor neurons. Cold feet may be related to abnormal thermoregulation of cutaneous vessels; however, circulation is usually preserved.

Fatigue

Fatigue is a common symptom of HSP. One obvious cause is the extra effort required for walking, because of muscle weakness in the legs. In addition, various medications prescribed for HSP cause drowsiness or fatigue. Moreover, many patients with HSP may not get the amount of sleep they require, because of leg cramps or spasms or as a result of the frequent need to urinate during the night. A less obvious cause of fatigue may be the fact that, because of a more sedentary lifestyle, people with HSP often are not aerobically fit and therefore have reduced endurance. Stress or depression also can contribute to fatigue.

Back or knee pain

Back and/or knee pain is common in people with HSP. The pain is not directly due to HSP itself but is instead often caused by muscle weakness and gait abnormalities resulting from HSP. As certain muscles become weaker, other muscles need to compensate for that weakness. Compensatory measures create an awkward gait that causes strain on many muscles and joints. Patients may thrust their shoulders back or swing their legs outward as they walk. Use of certain mobility devices also may put a strain on the arms or back.

Stress and depression

Stress, depression, and denial are not unusual in patients with HSP or any other chronic illness. Denial is not necessarily a problem, as long as the person in denial is not depriving himself or herself of proper treatment and care. Denial allows some people to cope and set their worries aside. However, some people with HSP face denial by family members who refuse to admit that a problem exists. This can create a frustrating and stressful situation.

 

Presentation

History

As previously mentioned, hereditary spastic paraplegia (HSP) is not a single disease entity but a group of clinically and genetically diverse disorders that cause progressive and generally severe lower extremity weakness and spasticity.

Pure, autosomal dominant HSP has been reviewed. After normal gestation, delivery, and early childhood development, subjects develop leg stiffness and gait disturbance (eg, stumbling, tripping) because of difficulty in dorsiflexing the foot and as a result of weakness in hip flexion.

HSP is generally classified as pure or complicated. In pure HSP, symptoms are generally limited to gradual weakening in the legs, urinary bladder disturbance, and, sometimes, impaired sensation in the feet.[4]

In complicated HSP, a rare disorder, additional symptoms may include the following:

  • Peripheral neuropathy

  • Epilepsy

  • Ataxia

  • Optic neuropathy

  • Retinopathy

  • Dementia

  • Ichthyosis

  • Mental retardation

  • Deafness

  • Problems with speech, swallowing, or breathing

Some of these additional symptoms may be related to a separate disorder, rather than being directly caused by HSP. Patients may actually have pure HSP plus one or more other disorders. For example, a person with pure HSP may have peripheral neuropathy caused by diabetes, or he or she may have unrelated epilepsy.

Additional symptoms

The classic symptom of HSP is progressive difficulty in walking, but the severity varies. Some patients eventually may require the use of a wheelchair, while others may never need any type of assistive device. Patients usually have difficulty lifting their toes; as a result, they drag their toes when walking and catch them on stairs or on uneven sidewalks or curbs.[4]

In later stages, patients experience difficulty flexing the thigh muscle to raise the leg when walking. A reduced sense of balance is noted. Muscles weaken but also experience increased muscle tone. Some patients complain of reduced sensation in the distal regions of the legs.

Some people also experience urinary problems; eg, incontinence or a sense of urgency even when the bladder is not full.[4]  A study by Kanavin and Fjermestad found that of 108 adults with hereditary spastic paraplegia (HSP), 30.5% suffered from urinary incontinence at least daily/nightly, while 27.4% needed to urinate more than eight times daily and 51.9% experienced sudden urges to urinate. Moreover, a number of patients reported gastrointestinal problems, including constipation (14.6%), alternation of constipation and diarrhea (8.0%), fecal incontinence (11.6%), an inability to hold back stools (38.5%), and an at least daily occurrence of uncontrollable flatulence (47.6%).[30]

People with HSP also experience hyperactive reflexes. Many symptoms that are common in people with HSP are not directly caused by HSP but are instead caused indirectly by muscle spasticity, weakness, or hyperactive reflexes.

Spasticity

Spasticity is an increase in muscle tone with resulting stiffness. Muscle tone refers to the mild contraction that muscles continue to exhibit even when at rest (ie, resting muscle tone). A reflex between nerve endings in the muscle and spinal cord regulates muscle tone. Normally, the corticospinal nerves control and reduce sensitivity of this reflex. Because HSP causes deterioration of the corticospinal nerves, the reflex is not reduced as it should be, the result being an exaggerated (ie, hyperactive) reflex and increased muscle tone.

Depending on the circumstances, the amount of spasticity experienced is likely to change a good deal. Stiffening of the leg muscles is normal after long periods of sitting, because the muscles have contracted and then are stretched upon standing. Many people also notice that their muscles seem tighter when they are emotionally stressed or upset. Other factors that can affect spasticity are cold temperature, poor posture, high humidity, and illness.

Abnormal gait

Increasing stiffness in the legs is associated with frequent tripping, particularly when the patient is walking on uneven terrain.

Uncontrollable shaking of the legs may be noted when the patient ambulates. Dragging of the feet, scissoring of the legs during ambulation, weakness and giving way at the ankles, flexor spasms of the legs during the night, and a sense of unsteadiness during walking also are common.

Decreased sense of balance

A common symptom of HSP, and often the first one that patients notice, is a decreased sense of balance. Many people with HSP have an impaired sense of foot position. If the brain does not receive accurate signals relating to the body's position, it may not be able to respond properly to those signals, and loss of balance occurs.

Pure HSP kindreds

The age of symptom onset, the rate of symptom progression, and the extent of disability are variable within and between HSP kindreds. In contrast to the extent of disability and to the variable age of patients at symptom onset, the distribution of neurologic deficits in pure HSP is consistent; it consists of spastic weakness in the legs, variable impairment of vibratory sense in the feet, and variable urinary bladder disturbance.

In patients with a pure HSP kindred, the presence of additional deficits, such as visual disturbance, marked muscle wasting, fasciculations, dementia, seizures, and peripheral neuropathy, should not be attributed to variant presentations of pure HSP. Therefore, these patients should be thoroughly evaluated for concurrent or alternative neurologic disorders.

Some pure, autosomal dominant HSP kindreds exhibit an onset of progressive spastic paraplegia in childhood (ie, < P 6y) and relatively little progression of symptoms beyond adolescence.[31] ) These patients often do not experience urinary bladder disturbances generally remain ambulatory with assistance.

Physical Examination

Neurologic examination reveals no evidence of cranial nerve dysfunction or reduced mentation. Although the jaw jerk may be brisk in older subjects, no speech disturbance, difficulty swallowing, or evidence of frank corticobulbar tract dysfunction is noted.

Upper extremity muscle tone and strength are normal. In the lower extremities, muscle tone is increased at the hamstrings, quadriceps, and ankles. Results of manual muscle testing are difficult to assess because of increased tone; however, weakness is occasionally demonstrated in the legs. Weakness is most notable at the iliopsoas muscles, the tibialis anterior muscles, and, to a lesser extent, the hamstring muscles. Muscle wasting may occur in patients with pure HSP, but it is mild and is limited to atrophy of the shins in elderly, wheelchair-dependent patients.

Peripheral nerves are normal in patients with pure HSP, although decreased perception of sharp stimuli below the knees is occasionally noted. Vibratory sensation is often mildly diminished in the distal lower extremities. When it occurs, this deficit provides a diagnostic sign that helps to distinguish HSP from other disorders. Slight terminal dysmetria is occasionally observed on finger-to-nose testing in older affected individuals. Deep tendon reflexes may be brisk (2+ to 3+) in the upper extremities but are pathologically increased (3+ to 4+) in the lower extremities.

The patient's gait demonstrates circumduction owing to a difficulty with hip flexion and ankle dorsiflexion. Crossed adductor reflexes, ankle clonus, and extensor plantar responses are uniformly present. Hoffman and Tromner signs may be observed. High-arched feet (pes cavus) are generally present and are usually prominent in older patients. The photographs seen below depict patients with complicated HSP.

Dysmorphic appearance of a 16-year-old girl with c Dysmorphic appearance of a 16-year-old girl with complicated hereditary spastic paraplegia. This patient displays a short stature (145 cm) and hair loss. Anterior (left), lateral (middle), and posterior (right) views are shown.
General appearance of sisters with complicated her General appearance of sisters with complicated hereditary spastic paraplegia. They are aged 16 and 17 years. Physical examination revealed increased deep tendon reflexes in all 4 extremities, with an extensor plantar reflex. Sensory losses in the patients have affected mainly their joint positions and vibration sensations.
 

DDx

Diagnostic Considerations

Failure to rule out reversible forms of spinal cord lesions (mechanical cord compression or spinal cord tumor) when considering a diagnosis of hereditary spastic paraplegia (HSP) invites problems.

Conditions to consider in the differential diagnosis of HSP include the following:

  • Hereditary motor-sensory neuropathy type 5

  • Spondylosis

  • Atlantoaxial canal stenosis

  • Arteriovenous malformation compressing spinal cord

  • Arnold-Chiari syndrome

  • Tethered cord

  • Neoplasm

  • Granuloma

  • Spinocerebellar ataxias

  • Adrenomyeloneuropathy

  • Deficiency of vitamins B-12 and E

  • Abetalipoproteinemia

  • Mitochondrial disorders

  • Human T-cell lymphocytotrophic virus infection

  • Toxins

  • Stiff-limb syndrome

Differential Diagnoses

 

Workup

Approach Considerations

A study by Schlipf et al indicates that since clinical parameters alone are not reliable enough to differentiate between types of hereditary spastic paraplegia (HSP), specifically autosomal recessive (AR) HSP, that amplicon-based high-throughput genotyping followed by pooled next-generation sequencing (NGS) is a much more efficient approach.[32]

SPG4 HSP is the single most common dominantly inherited HSP, representing approximately 40% of such cases. Hazan and colleagues discovered that mutations in a novel gene designated SPG4 (protein, spastin) are the cause of this disorder.[20] Genetic testing for SPG4/spastin mutations is available commercially, can provide laboratory confirmation of the diagnosis, and can be applied to prenatal testing.

Electrophysiologic studies are useful for assessing peripheral nerve, muscle, dorsal column, and corticospinal tract involvement in patients with HSP.[33] Because it is uncommon to obtain permission to perform an autopsy, these studies are particularly useful for characterizing the extent of involvement.

Magnetic resonance imaging (MRI) scans may demonstrate atrophy of the spinal cords and occasionally of the cerebral cortex.[4] The cerebrospinal fluid in HSP is usually normal, although increased protein is noted in some patients.

A study by Pascual et al indicated that the appearance of the ears-of-the-lynx sign on fluid-attenuated inversion recovery (FLAIR) MRI—a sign consisting of changes to the periventricular white matter in the frontal horn region that resemble hair tufts on lynx ears—is highly specific for the presence of “the most common genetic subtypes of hereditary spastic paraplegia with a thin corpus callosum.” The sign points to the likelihood that a genetic mutation, especially one in SPG11 or SPG15, is present, even if the patient has no family history of the condition.[34]

Electrophysiologic Studies

Although the results of electrophysiologic studies are variable, a number of generalizations can be made. Most studies have found nerve conduction test results to be normal (in contrast to results in Friedrich ataxia and some other spinocerebellar ataxias). One study, however, showed that subclinical sensory impairment was common in patients with HSP, with involvement of peripheral nerves and/or spinal pathways.

Lower extremity somatosensory evoked potentials show a conduction delay in dorsal column fibers. Cortical evoked potentials used to measure neurotransmission in corticospinal tracts show greatly reduced conduction velocity in the corticospinal tract and greatly reduced amplitude of the evoked potential.

Often, no cortical evoked potentials are elicited in muscles innervated by lumbar spinal segments, but cortical evoked potentials of the arms are normal or show only mildly reduced conduction velocity. These findings indicate that decreased numbers of corticospinal tract axons are reaching the lumbar spinal cord and that the remaining axons have reduced conduction velocity.

Schady and colleagues emphasized the variable results of cortical evoked potentials.[33] In their patients, central motor conduction velocity in the upper extremities was normal except for all 5 affected members of one HSP kindred for whom responses were considerably delayed. Schady concluded that measurement of central motor conduction velocity may be a useful way of identifying clinical subgroups of HSP.[35]

Histologic Findings

The major neuropathologic feature of pure, autosomal dominant HSP is axonal degeneration that is maximal in the terminal portions of the longest descending and ascending tracts (ie, crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis, respectively). Autopsy studies have demonstrated the loss of axons in the ventral and lateral corticospinal tracts.

Spinocerebellar fibers are involved to a lesser extent. Neuronal cell bodies of degenerating fibers are preserved, and no evidence of primary demyelination is noted. Loss of anterior horn cells is observed in some cases. Dorsal root ganglia, posterior roots, and peripheral nerves are normal.

The regional pattern of axonal degeneration in pure HSP is different from that seen in system degeneration diseases, such as amyotrophic lateral sclerosis (ALS). System degeneration in ALS includes cortical (ie, pyramidal) neurons, corticospinal tracts, anterior horn cells innervated by corticospinal tracts, and skeletal muscle. Parkinson disease, characterized by loss of dopaminergic neurons in the substantia nigra pars compacta and secondary changes in brain regions that receive this dopaminergic innervation, may exemplify another system degeneration.

Axonal degeneration in pure, autosomal dominant HSP involves different classes of neurons (eg, corticospinal tract fibers from pyramidal neurons in the motor cortex; fasciculus gracilis; cuneatus to a lesser extent, from dorsal root ganglia neurons). One obvious feature shared by these degenerating axons is their length; these fibers are the longest in the CNS. Degeneration has been found to be maximal in the distal axons of these fibers.

 

Treatment

Approach Considerations

Currently, no specific treatment exists to prevent, retard, or reverse progressive disability in patients with hereditary spastic paraplegia (HSP). Nonetheless, treatment approaches used for chronic paraplegia from other causes are useful.

Moreover, a double-blind, randomized, crossover, sham-controlled study by Ardolino et al indicated that anodal transcutaneous spinal direct current stimulation (tsDCS) can significantly reduce spasticity in HSP. In comparison with the sham group, the anodal patients demonstrated improvement in the Ashworth Scale score, with the benefits still manifesting at 2-month follow-up. The investigators suggested that anodal tsDCS may offer a useful complementary spasticity treatment in HSP.[36]

Regular physical therapy (PT) is important for maintaining and improving range of motion (ROM) and muscle strength, as well as for maintaining aerobic conditioning of the cardiovascular system.

Consultations in HSP can include a physical medicine and rehabilitation specialist and a neurologist.

Physical Therapy

As stated previously, regular PT is important for maintaining and improving ROM and muscle strength. Furthermore, PT is necessary to maintain aerobic conditioning of the cardiovascular system. Although PT does not reduce the degenerative process within the spinal cord, individuals with HSP must maintain an exercise regimen performed at least several times each week, as guided by their physical therapist.

Exercise can help the patient to retain or improve muscle strength, minimize atrophy of the muscles caused by disuse, increase endurance, reduce fatigue, prevent spasms and cramps, and maintain or improve ROM. Exercise also has a positive psychological effect, helping to reduce stress and produce feelings of well-being.

Patients with HSP may experience spasticity and weakness (ie, increased muscle tone and reduced muscle strength). Because of the increased resistance to passive stretching, spasticity may make it difficult for patients to exercise certain muscles. Antispasmodic drugs may help the patient to reduce the spasticity and may allow weakened muscles to be targeted in order to improve the effectiveness of PT.

Types of exercises

The types of exercise incorporated into PT programs for patients with HSP may include strengthening, stretching, and aerobic exercises.

Strengthening exercises help to strengthen muscles that have not yet weakened. Strengthened muscles help to compensate for muscles that have weakened, decreasing the rate of functional impairment. Exercise may also help to slow the development of disuse atrophy, which occurs in muscles that are not being used (eg, in calf muscles of people who use wheelchairs). Back-strengthening exercises may help to reduce or eliminate back pain associated with HSP. Such pain is probably not due to HSP itself but to strain on the back resulting from HSP (eg, poor gait, poor posture, use of a mobility device).

Stretching exercises help to maintain or increase ROM and to reduce such problems as tendinitis, bursitis, and muscle cramps.

Aerobic exercises improve cardiovascular fitness, reduce fatigue, and increase endurance and general fitness. Walking, bicycle riding, water aerobics, and swimming are among many excellent forms of aerobic exercise.

 

Medication

Medication Summary

Many symptoms that are common in people with HSP are not caused directly by HSP but are instead caused indirectly by muscle spasticity, weakness, or hyperactive reflexes. As previously mentioned, antispastic drugs may help the patient to reduce the spasticity and may allow weakened muscles to be targeted in order to improve the effectiveness of PT.[14] However, when patients are medicated to reduce stiffness, walking may become more difficult. Moreover, adverse effects from skeletal muscle relaxants can be a problem.

Skeletal muscle relaxants

Class Summary

Antispasticity medications can be useful. However, one of the drawbacks of using these agents is that some patients find that the stiffness of spasticity helps them to overcome the muscle weakness that occurs in HSP. When patients are medicated to reduce stiffness, walking may become more difficult. Adverse effects can also be a problem.

If the patient does well with the medications, however, discomfort associated with spasticity can generally be reduced, mobility can be improved, and the effectiveness of physical therapy (PT) can be enhanced. Patients in relatively early stages of the illness have achieved symptomatic improvement with oral dantrolene, as well as with oral and intrathecal baclofen.

Baclofen (Lioresal, Gablofen)

Baclofen may induce the hyperpolarization of afferent terminals and inhibit monosynaptic and polysynaptic reflexes at the spinal level.

Tizanidine (Zanaflex)

Tizanidine is a centrally acting muscle relaxant that is metabolized in the liver and excreted in urine and feces. A single oral dose of 8mg reduces muscle tone in patients with spasticity for several hours. Blood levels and the spasmolytic effect are linearly correlated.

Dantrolene sodium (Dantrium, Revonto)

Dantrolene sodium stimulates muscle relaxation by modulating skeletal muscle contractions at the site beyond the myoneural junction and acting directly on the muscle itself. Most patients respond to 400mg/day or less.

OnabotulinumtoxinA (BOTOX®)

Botulinum toxin binds to receptor sites on motor nerve terminals and inhibits the release of acetylcholine, which in turn inhibits the transmission of impulses in neuromuscular tissue. This agent is most useful for treating spasticity in the gastrocnemius and soleus muscles; it is less effective in larger muscles (eg, quadriceps). Reexamine patients 7-14 days after the initial dose to assess for their response. Treatment may be repeated every 3-4 months.

Anxiolytics, Benzodiazepines

Class Summary

These agents may act in the spinal cord to induce muscle relaxation.

Diazepam (Valium)

Diazepam depresses all levels of the central nervous system (eg, limbic and reticular formation), possibly by increasing the activity of gamma-aminobutyric acid (GABA). Individualize the dosage, and increase it cautiously to avoid adverse effects.

 

Questions & Answers

Overview

What is hereditary spastic paraplegia (HSP)?

What are the possible complications of hereditary spastic paraplegia (HSP)?

What is the pathophysiology of hereditary spastic paraplegia (HSP)?

What are the genetic causes of hereditary spastic paraplegia (HSP)?

What is the prevalence of hereditary spastic paraplegia (HSP)?

What is the prognosis of hereditary spastic paraplegia (HSP)?

What is gastrocnemius-soleus contracture in hereditary spastic paraplegia (HSP)?

What causes cold feet in hereditary spastic paraplegia (HSP)?

What causes fatigue in hereditary spastic paraplegia (HSP)?

What causes back or knee pain in hereditary spastic paraplegia (HSP)?

How are stress and depression managed in hereditary spastic paraplegia (HSP)?

Presentation

Which clinical history findings are characteristic of hereditary spastic paraplegia (HSP)?

What are the signs and symptoms of complicated hereditary spastic paraplegia (HSP)?

What are the signs and symptoms of hereditary spastic paraplegia (HSP)?

How is spasticity characterized in hereditary spastic paraplegia (HSP)?

What are the signs and symptoms of abnormal gait in hereditary spastic paraplegia (HSP)?

What causes loss of balance in hereditary spastic paraplegia (HSP)?

Which clinical history findings are characteristic of pure hereditary spastic paraplegia (HSP)?

Which physical findings are characteristic of hereditary spastic paraplegia (HSP)?

DDX

Which conditions are included in the differential diagnoses of hereditary spastic paraplegia (HSP)?

What are the differential diagnoses for Hereditary Spastic Paraplegia?

Workup

How is hereditary spastic paraplegia (HSP) diagnosed?

What is the role of electrophysiologic studies in the workup of hereditary spastic paraplegia (HSP)?

Which histologic findings are characteristic of hereditary spastic paraplegia (HSP)?

Treatment

How is hereditary spastic paraplegia (HSP) treated?

Which specialist consultations are beneficial to patients with hereditary spastic paraplegia (HSP)?

What is the role of physical therapy in the treatment of hereditary spastic paraplegia (HSP)?

What types of exercise are included in physical therapy for hereditary spastic paraplegia (HSP)?

Medications

What is the role of medications in the treatment of hereditary spastic paraplegia (HSP)?

Which medications in the drug class Anxiolytics, Benzodiazepines are used in the treatment of Hereditary Spastic Paraplegia?

Which medications in the drug class Skeletal muscle relaxants are used in the treatment of Hereditary Spastic Paraplegia?