Orthopaedic Surgery - Friedreich Ataxia

Basics

Friedreich ataxia is an uncommon inherited neurodegenerative disorder characterized by progressive degeneration of the spinal cord and peripheral nervous system, with prominent involvement of coordination and gait.

The musculoskeletal manifestations most frequently encountered are scoliosis and cavovarus foot deformity, while progressive ataxia represents the major neurologic feature.

Systems Involved

Friedreich ataxia primarily affects the central and peripheral nervous systems, cardiovascular system, and musculoskeletal system.

Endocrine abnormalities, particularly diabetes mellitus, may also occur.

Classification

There are no major orthopaedic subclassifications of Friedreich ataxia.

It belongs to the broader group of hereditary ataxic or spinocerebellar degenerative disorders.

Epidemiology

Friedreich ataxia is rare.

Older estimates placed its prevalence at approximately 1 in 50,000 individuals, while more recent molecularly based estimates have suggested a prevalence closer to 1 in 29,000 in some populations.

Age at Presentation

Symptoms most commonly become apparent between approximately 5 and 25 years of age.

Earlier onset is generally associated with more severe and rapidly progressive disease.

Sex

Males and females are affected approximately equally.

Population Distribution

The condition is more common in populations of European ancestry and has historically been reported with increased frequency in some French-Canadian populations.

Genetics

Friedreich ataxia is inherited in an autosomal recessive pattern.

Affected individuals generally inherit a pathogenic allele from each parent.

Frataxin Gene

The disorder is caused by pathogenic changes involving the FXN gene on chromosome 9, which encodes the mitochondrial protein frataxin.

GAA Trinucleotide Repeat

The most common genetic abnormality is expansion of a GAA trinucleotide repeat within the FXN gene.

This reduces expression of frataxin.

Relationship to Disease Severity

In general, larger GAA repeat expansions are associated with earlier onset and more severe disease, although clinical variability is considerable.

Frataxin Function

Frataxin is a mitochondrial protein involved in cellular iron handling and normal mitochondrial energy metabolism.

Loss of adequate frataxin function contributes to oxidative injury and progressive neurologic and cardiac dysfunction.

Associated Conditions

Important associated conditions include hypertrophic cardiomyopathy, diabetes mellitus, scoliosis, and cavovarus deformity of the feet.

Diagnosis

The diagnosis is established primarily through molecular genetic testing identifying pathogenic variants in the FXN gene.

Historically, diagnosis relied more heavily on clinical manifestations and neurophysiologic findings.

Clinical Features

Classic Neurologic Findings

A characteristic clinical combination includes:

Progressive ataxia, loss or reduction of deep tendon reflexes, and an extensor plantar response or Babinski sign.

Ataxia

Progressive impairment of coordination affects standing, walking, and fine motor tasks.

Gait becomes broad-based and unstable as disease advances.

Areflexia

Deep tendon reflexes, particularly in the lower extremities, are commonly reduced or absent because of peripheral nerve involvement.

Babinski Sign

Despite reduced peripheral reflexes, corticospinal tract disease may produce an extensor plantar response.

Additional Signs

Other findings may include pes cavus or cavovarus feet, optic atrophy, nystagmus, abnormal electrocardiographic findings, scoliosis, and kyphosis.

Symptoms

Patients may experience progressive loss of coordination, weakness, painful muscle spasms, hearing impairment, fatigue, and depression.

Symptoms related to diabetes mellitus may also occur when endocrine involvement is present.

Physical Examination

Gait and Coordination

Gait should be observed carefully.

Tandem, or heel-to-toe, walking is useful for demonstrating impaired balance and coordination.

The finger-to-nose test can assess upper-extremity dysmetria and cerebellar dysfunction.

Spine Examination

Standing alignment should be assessed for excessive kyphosis and scoliosis.

The forward-bend test is useful for detecting rotational prominence associated with scoliosis.

Reflexes

Upper- and lower-extremity deep tendon reflexes should be documented.

Plantar responses should also be assessed.

Foot Examination

The feet should be evaluated for cavus, hindfoot varus, equinus, clawing of the toes, calluses, and skin pressure areas.

The examiner should determine whether the deformity remains flexible or has become rigid.

Muscle Strength

Muscle strength should be documented throughout the upper and lower extremities.

Weakness progresses with disease and ultimately contributes substantially to loss of ambulation.

Laboratory Tests

Creatine Kinase

Creatine phosphokinase or creatine kinase levels are generally normal, helping distinguish Friedreich ataxia from some primary muscular dystrophies.

Glucose Testing

Fasting serum glucose or other appropriate diabetic screening should be obtained because of the increased prevalence of diabetes mellitus.

Cardiac Assessment

Because cardiomyopathy is common, cardiac evaluation is important.

An electrocardiogram should be obtained before major surgery, and echocardiography should be performed when clinically indicated.

Cardiomyopathy

Hypertrophic cardiomyopathy is an important cause of morbidity and mortality and substantially influences perioperative planning.

Electrodiagnostic Testing

Electromyography may demonstrate polyphasic potentials.

Nerve conduction studies can show mild slowing or other evidence of peripheral neuropathy.

Imaging

Spine Radiographs

Standing posteroanterior and lateral radiographs of the spine should be obtained when scoliosis or kyphosis is identified.

Long-Term Spinal Surveillance

Spinal deformity can continue to progress even after skeletal maturity.

Periodic radiographic monitoring is therefore appropriate in patients with established scoliosis.

Foot Radiographs

Weight-bearing radiographs of the feet may be useful when cavovarus deformity is substantial, progressive, painful, or being considered for surgery.

Differential Diagnosis

Cerebellar Tumor

Intracranial lesions affecting the cerebellum may produce ataxia and should be considered when the presentation is atypical or asymmetric.

Chiari Malformation

Chiari malformation can produce neurologic abnormalities, gait disturbance, and scoliosis.

Muscular Dystrophy

Muscular dystrophies may produce progressive weakness and spinal deformity but have a different neurologic and laboratory profile.

Spinal Dysraphism

Spinal dysraphism can produce scoliosis, cavus foot deformity, weakness, and abnormal reflexes and should be considered in the differential diagnosis.

Treatment

General Principles

Management is multidisciplinary because the disorder affects neurologic, cardiac, endocrine, and musculoskeletal systems.

Orthopaedic care focuses primarily on preserving ambulation, maintaining plantigrade feet, treating painful deformity, and monitoring scoliosis.

Orthopaedic Surveillance

Foot and spinal deformities should be monitored by an orthopaedic surgeon even when surgery is not currently planned.

Progression may occur relatively rapidly, particularly in patients with early-onset disease.

Ambulation

Walking should be maintained safely for as long as possible.

Bracing, assistive devices, therapy, and correction of severe deformity can help preserve mobility.

Foot Deformity

Stretching and nighttime positioning or bracing may help delay progression of flexible cavovarus and equinus deformities.

The aim is to maintain a painless, braceable, plantigrade foot.

Scoliosis Bracing

For scoliosis measuring approximately 25–45°, bracing may be attempted in selected patients.

Bracing may slow progression but is less reliable at permanently controlling the curve than in idiopathic scoliosis.

Physical Therapy

Physical therapy is important for maintaining strength, balance, mobility, joint range of motion, transfers, and functional independence.

It is also essential after orthopaedic surgery.

Stretching

Regular stretching of the plantar fascia, Achilles tendon, and ankle musculature may help delay fixed cavovarus and equinus deformity.

Medication

Medical treatment is primarily directed by neurology and other relevant specialists.

Symptomatic medications may be required for associated problems.

Muscle Spasms

Painful spasticity or muscle spasms may be treated with medications such as baclofen or diazepam in selected patients.

Scoliosis Surgery

Preoperative Evaluation

Because of the high prevalence of cardiomyopathy and potential respiratory impairment, a detailed cardiopulmonary assessment is required before major spinal surgery.

Risk of Progression

Rapid scoliosis progression is particularly associated with onset of Friedreich ataxia before approximately 10 years of age and development of scoliosis before approximately 15 years.

Surgical Indications

Severe progressive curves, particularly those exceeding approximately 60°, often require posterior spinal fusion and instrumentation to prevent further deformity and loss of trunk balance.

Curves of 40–60°

Curves between approximately 40° and 60° require individualized treatment.

Factors include rate of progression, skeletal maturity, neurologic status, sitting or standing balance, pulmonary function, and overall medical condition.

Bracing or surgery may be appropriate depending on these factors.

Fusion Levels

Fusion frequently extends across a long segment of the thoracic and lumbar spine because deformity may be extensive and progressive.

Modern segmental instrumentation is used to obtain correction and stability.

Severe Rigid Curves

Large, rigid, or markedly unbalanced deformities may require additional techniques to improve flexibility and correction.

Historically, anterior release procedures were sometimes used, although contemporary approaches depend on individual anatomy and modern posterior techniques.

Spinal Cord Monitoring

Intraoperative neuromonitoring may be technically challenging because baseline neurologic abnormalities are common.

Both sensory and motor modalities should be used when feasible.

Postoperative Immobilization

Routine external postoperative immobilization is generally unnecessary after stable modern internal fixation.

Cavovarus Foot Surgery

Surgery is considered when the deformity becomes painful, progressive, rigid, poorly braceable, or interferes with standing and walking.

Soft-Tissue Procedures

Flexible deformities may require procedures such as Achilles tendon lengthening and tendon balancing or transfer.

Posterior tibial tendon procedures may be incorporated when its deforming force contributes to cavovarus.

Arthrodesis

Rigid severe deformities may require fusion procedures, including triple arthrodesis, to obtain a stable plantigrade foot.

Follow-Up

Specialist Coordination

A neurologist is generally best positioned to coordinate overall disease management, with input from orthopaedics, cardiology, endocrinology, rehabilitation medicine, physical therapy, and other specialists.

Prognosis

Friedreich ataxia is a progressive disorder.

The clinical course varies according to age of onset, genetic findings, cardiac involvement, and severity of neurologic disease.

Scoliosis Prognosis

Scoliosis developing before approximately 15 years of age is more likely to become severe and may ultimately require operative correction.

Ambulation

Progressive neurologic deterioration commonly leads to loss of independent walking.

Historically, many affected individuals became wheelchair dependent during the second or third decade of life, although progression varies substantially among patients.

Survival

Cardiomyopathy and respiratory complications are major determinants of long-term survival.

Historically, severe disease was associated with reduced life expectancy, although contemporary multidisciplinary management continues to improve supportive care.

Complications

Cardiomyopathy

Cardiac involvement is one of the most important systemic complications and can lead to arrhythmia or heart failure.

Foot Skin Problems

Cavovarus deformity may create abnormal pressure points, producing calluses, painful keratoses, or skin breakdown.

Respiratory Complications

Progressive neuromuscular weakness, scoliosis, and impaired swallowing may increase the risk of pneumonia and aspiration.

Progressive Loss of Mobility

Weakness, ataxia, contracture, and deformity progressively reduce walking endurance and may ultimately result in wheelchair dependence.

Patient Monitoring

Because Friedreich ataxia is progressive, patients require regular multidisciplinary follow-up.

Walking distance, muscle strength, coordination, foot alignment, skin condition, and overall functional status may be reassessed approximately every 3–6 months, depending on severity.

Scoliosis Monitoring

Once scoliosis is identified, clinical and radiographic assessment approximately every 6 months is appropriate during periods of growth or documented progression.

Long-term surveillance may remain necessary after skeletal maturity because curves can continue to worsen.