Diagnosis of Spinal Muscular Atrophy
The diagnosis of spinal muscular atrophy (SMA) presently relies on a combination of medical history, physical examination, electrodiagnostics, and genetic testing. Due to the progressive nature of SMA, an earlier diagnosis is particularly important in terms of treatment: The sooner therapies are initiated, the higher are the chances that they will slow or even prevent motor neuron loss and overall disease progression.
There is presently no consensus regarding a universally accepted “gold standard” biomarker for either clinical or regulatory use in the evaluation of SMA. Instrumental biomarkers in SMA span the gamut from evaluation of bedside motor function to advanced radiological techniques. Two motor function tests widely used in neuromuscular disease are the six-minute walk test (6MWT) and the Motor Function Measure 32 (MFM32) test.
Electromyography (EMG) is a test that assesses the health of muscles and the motor neurons that control them by measuring the muscles’ electric activity, or response, when motor neurons are stimulated. Motor neurons send out electrical signals to muscles, which in turn contract and give off these signals, which can be measured.
A muscle biopsy involves the collection of a small section of muscle tissue — usually from the upper thigh — and its examination under a microscope to see whether it has SMA-associated features. These may include the absence of nerve supply and signs of many cycles of nerve loss and restoration.
Magnetic Resonance Imaging
A diagnosis of SMA does not require magnetic resonance imaging (MRI), but neuroimaging of the central nervous system is typically performed as part of a differential diagnostic evaluation in patients presenting with progressive weakness. MRI findings in SMA will vary depending on the SMA type.
SMA has differential diagnosis methods based on the type and age of onset. If a person shows common SMA symptoms and/or has a family history of the disease, further tests should be conducted so as to enable such a diagnosis.
Given the variability of symptoms across the different types of SMA, as well as some similarities with other conditions, genetic testing is the standard — and most accurate — method for a conclusive diagnosis of the disease.
SMA types 0 and 1 should be considered in the differential diagnosis of every newborn and infant < 6 months old with hypotonia, hyporeflexia, tongue fasciculations, weakness, respiratory distress, or contractures. Other potential diagnoses for hypotonia and weakness in the neonatal to < six months of age group are differentiated by category as endocrine, genetic, infectious, metabolic, and traumatic.
SMA that presents after 6 months of age will include the second most common presentation of SMA, type 2 SMA, and the least commonly observed form of childhood onset SMA, type 3. The typical presenting symptoms of types 2 and 3 SMA invites a list of differential diagnoses worth of consideration, and delay in the diagnosis of these types suggests that evaluation for SMA mimics impede efficient diagnosis. The differential diagnosis of types 2 and 3 SMA are broken down by categories as autoimmune, genetic, infectious, metabolic, and traumatic.
SMA that presents in adulthood, so-called type 4 SMA, has a more restricted differential diagnosis than types 0-3. Considerations for the adult with new mild weakness are categorized as autoimmune, genetic, infectious, metabolic, and traumatic.