What are the diagnostic criteria and management options for Spinal and Bulbar Muscular Atrophy (SBMA) or Kennedy disease?

Spinal and Bulbar Muscular Atrophy (SBMA/Kennedy Disease): Diagnostic Criteria and Management

Diagnostic Criteria

The diagnosis of SBMA should be suspected in adult males presenting with slowly progressive lower motor neuron symptoms, typically affecting the lower limbs initially, combined with signs of androgen insensitivity such as gynecomastia. 1

Clinical Presentation

When to suspect SBMA:

• Adult male (typically mid-40s) with progressive proximal or distal limb weakness and muscle wasting that may be symmetric or asymmetric 2, 3
• Bulbar involvement manifesting as dysarthria and dysphagia, often appearing later in disease course 1
• Gynecomastia (not constant but highly suggestive when present) 1, 2
• Reduced fertility and other signs of androgen resistance 2, 3
• Muscle cramps and fasciculations in affected muscles 2
• Sensory disturbances (may be subclinical) 4
• Postural tremor of the hands 2

Diagnostic Testing Algorithm

Step 1: Initial Laboratory Studies

• Serum creatine kinase (CK) - typically elevated (mild to severe hyper-CK-emia) 2, 4
• Testosterone and other sex hormones - may be elevated 2

Step 2: Electrophysiological Studies

• Electromyography (EMG) showing diffuse motor neuron involvement with chronic denervation patterns 1
• Nerve conduction studies demonstrating abnormal motor and sensory findings, often with asymptomatic sensory changes 1, 2

Step 3: Genetic Confirmation

• Genetic testing for CAG repeat expansion in exon 1 of the androgen receptor (AR) gene on chromosome Xq11-12 1, 2
• Diagnosis confirmed when CAG repeats exceed 38-40 (pathogenic threshold) 2, 4
• This is the definitive diagnostic test 1

Step 4: Optional Studies

• Muscle biopsy may show neuropathic or rarely myopathic alterations, with evidence of primary myopathy in some cases 2, 4

Multidisciplinary Assessment Post-Diagnosis

The initial evaluation and confirmation should occur in a tertiary referral center for motor neuron diseases with an experienced multidisciplinary team. 1

Comprehensive assessment must include:

• Cardiac evaluation for repolarization abnormalities including Brugada syndrome screening (ECG) 1
• Endocrine and metabolic screening for glucose intolerance and hyperlipidemia 1
• Genitourinary assessment for abnormalities related to androgen resistance 1
• Respiratory function testing to establish baseline 1

Management Options

Symptomatic and Supportive Care

There are currently no effective disease-modifying therapies for SBMA; management focuses on symptomatic support and monitoring for complications. 1, 3

Rehabilitation Strategies:

• Physiotherapy to maintain mobility, prevent contractures, and optimize muscle function 1
• Speech therapy for bulbar symptoms (dysarthria and dysphagia) 1

Nutritional Management:

• Expert dietician evaluation is essential 1
• Enteral nutrition via gastrostomy may be required for severe dysphagia 1

Respiratory Management:

• Detection and treatment of bronchial obstructions 1
• Screening for aspiration pneumonia with aggressive management when present 1
• Chest physiotherapy, drainage, positioning, breath stacking 1
• Mechanical insufflation-exsufflation and cough assist devices as needed 1
• Antibiotics for respiratory infections 1
• Non-invasive mechanical ventilation is seldom needed but should be available 1, 2

Pharmaceutical Symptomatic Therapy:

• Pain management as needed 1
• Endocrine and metabolic interventions for glucose intolerance and hyperlipidemia 1
• Management of muscle cramps 2
• Treatment of tremor if functionally limiting 2

Important Caveats

There is no evidence supporting androgen substitution therapy in SBMA. 1 This is a critical point, as the disease is androgen-dependent and results from toxic gain of AR function 5.

The European Association of Urology recognizes Kennedy disease (SBMA) as a congenital/developmental cause of hypogonadism related to CAG repeat extensions. 6 However, androgen replacement is contraindicated as it may worsen the disease.

Prognosis and Monitoring

• The course is slowly progressive with ability to walk typically preserved until late in life 2
• Life expectancy is only slightly compromised 2, 4
• Only few patients require ventilatory support 2
• Regular monitoring by the multidisciplinary team is essential for early detection and management of complications 1