eMedicine Specialties > Physical Medicine and Rehabilitation > Disorders of the Motor Unit

Hereditary Spastic Paraplegia

Author: Nam-Jong Paik, MD, PhD, Chief, Associate Professor of Rehabilitation Medicine, Rehabilitation Medicine, Seoul National University Bundang Hospital
Coauthor(s): Jae-Young Lim, MD, Assistant Professor, Department of Rehabilitation Medicine, Division of Musculoskeletal Rehabilitation, Bundang Hospital, Seoul National University College of Medicine
Contributor Information and Disclosures

Updated: Jul 29, 2008

Introduction

Background

Str ü mpell first described hereditary forms of spastic paraplegia in 1883, with Lorrain later providing more extensive detail. The common feature of these syndromes is spasticity in the lower extremities that is progressive and often severe. Hereditary spastic paraplegia (HSP) is also called familial spastic paraparesis and Str ü mpell-Lorrain syndrome.

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,¹ adrenal insufficiency, and ichthyosis.

Inheritance may be X-linked, autosomal recessive, or autosomal dominant. The most useful classifications now are based on the mode of inheritance and genetic linkage. Clinical distinctions between pure and complicated forms of HSP have some utility; however, the age of onset often has no clear relation to the HSP genotype.

Pathophysiology

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.

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.

Frequency

International

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 rate 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.

Mortality/Morbidity

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.

Age

Pure HSP may occur at any age, from infancy through late adulthood (eg, 85 y). Most patients experience the onset of symptoms between the second and fourth decades of life.

Clinical

History

• Clinical features
  • 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.
  • 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.
• Classification
  • 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.²
  • In complicated HSP, additional symptoms may include peripheral neuropathy, epilepsy, ataxia, optic neuropathy, retinopathy, dementia, ichthyosis, mental retardation, deafness, and problems with speech, swallowing, or breathing. Complicated HSP is rare.
  • 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 1 or more other disorders. For example, a person with pure HSP may have peripheral neuropathy caused by diabetes, or they may have unrelated epilepsy.
  • HSP may also be classified by the mode of inheritance (X-linked, autosomal dominant, or autosomal recessive); 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, because symptoms can vary greatly within each type.
  • 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.²
  • To date, the locations of several genes have been identified. Ten types of dominantly inherited pure or complicated HSP are known, along with 7 types of recessively inherited HSP and 3 types of X-linked HSP.
• Symptoms²
  • 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.
  • 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, sense of urgency even when bladder is not full). 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 have 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 been 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 is a decreased sense of balance. For many people, this is the first symptom that they notice.
    • Many people with HSP have an impaired sense of position in their feet. If the brain does not receive accurate signals about the body's position, it may not be able to respond properly to those signals, and loss of balance occurs.
  • 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 pure HSP kindreds, 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, <6 y) and relatively little progression of symptoms beyond adolescence.³ These patients often do not experience urinary bladder disturbances and generally remain ambulatory with assistance.

Physical

• 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.

Causes

Familial spastic paraplegia is a hereditary condition.

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