The field of physiatry requires the expertise of evaluating and managing disease states, injuries, and disabilities that alter the functional level of an individual. Physiatrists need to be familiar with the fundamentals of diagnostic testing that include several basic tests and diagnostic algorithms inherent to the general practice of medicine, as well as some specialized tests that are unique to physiatry and related specialties. The uniqueness in the physiatric approach to diagnostic testing often lies in the consideration of not only how clinically relevant the diagnostic test is, but also in how such testing can lead to identifying better treatment options that improve the functional outcome of the patient. Diagnostic testing can be used to diagnose a specific disorder, help in the surveillance and monitoring of disease progression, or help confirm diagnoses, thereby aiding the physiatrist in narrowing the differential diagnosis. This overview will focus on tests commonly performed within the scope of practice of physical medicine and rehabilitation (PM&R).

Laboratory testing applicable to physiatrists includes simple blood tests, which assess electrolyte abnormalities, kidney or liver function, and blood cell counts. In addition, specific tests are applicable to certain patient populations. Wound management requires testing periodically for pre-albumin and inflammatory markers (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) to monitor progression of wound healing and ensuring optimal nutritional status for surgery, as well as assessing for the presence of infection.

Muscle disease markers like creatine phosphokinase (CPK), alkaline phosphatase, and the aforementioned inflammatory markers can be used to aid in diagnosis of inflammatory muscle diseases. Laboratory tests that may aid in the evaluation of inflammatory arthritides include rheumatoid factor (RF), antinuclear antigen (ANA), serum protein electrophoresis (SPEP), and urine protein electrophoresis (UPEP).

Urine analysis and urine culture are used in both inpatient and outpatient settings particularly to assess for underlying infection. Symptoms that might prompt a physiatrist to order these tests include dysuria, frequency of urination, incontinence, leaking of urine between voluntary voids, or when complaining of constitutional symptoms like fever, chills, and acutely altered mental status. Urine cultures should be obtained prior to starting antibiotics and followed up for organism speciation and susceptibilities to more narrowly focus antibiotic treatment.

Disease-specific biomarkers are relevant when evaluating skeletal muscle pathology. A reliable protein biomarker of muscle damage should ideally be (1) specifically expressed at a high concentration level in intracellular domains of healthy and undamaged skeletal muscle tissues; (2) highly specific in its cellular or subcellular localization under normal conditions; (3) fiber type specific within fast versus slow muscle populations; (4) varied in its extent of extramuscular presence according to the type and intensity of muscle damage; (5) able to differentiate between acute versus chronic muscle injury; and (6) a protein species that can be easily and cost-efficiently assayed by standard methodology.¹ Although many are helpful as sensitive markers of muscle damage (creatine kinase [CK], lactate dehydrogenase [LDH], tumor necrosis factor [TNF], etc.), their lack of specificity limits their clinical application. One of the limiting technical factors of assessing the complete constellation of the skeletal muscle proteome is the wide range of concentration levels and physicochemical properties of individual protein species present in contractile fibers and associated cell types.¹ Also being studied are potential neuroimaging biomarkers, but clinical usefulness of these still needs further study and looks promising for the near future.

Special laboratory testing can be performed using tissue and fluid samples obtained using procedures performed in the operating room or in the clinic. For example, arthrocentesis of a joint effusion can be utilized in new effusions and in anyone with signs/symptoms of infection or a suspected inflammatory condition such as gout. The laboratory analysis of synovial fluid can help identify the presence of infection, inflammation, crystals, and/or other foreign bodies. White cell count with differential count, cultures, Gram stain, and crystal search are particularly valuable. Arthrocentesis with injection of anesthetic can be helpful in identifying the source of pain.

Genetic testing analyzes the DNA to find changes in gene sequences or gene expression for clinical purposes.² It includes DNA-based, chromosomal, and biomechanical methods. DNA-based genetic testing is most commonly used for diagnostic purposes.² One of the uses of genetic testing is to confirm a diagnosis. It can help to further identify a molecular pathway, or it may be needed for those cases when the hereditary neuropathy findings appear de novo or have an adult onset.

Genetic testing can complement other tests like the electrodiagnostic evaluation. When the clinical picture of a peripheral neuropathy is suspected, some cases will be inherited. These are classified as axonal loss or demyelinating. The pathology in the inherited demyelinating neuropathies is associated with gene mutations expressed in the myelination process from Schwann cells, whereas inherited axonal neuropathies are associated with mutations of the neuron genes.³ In the setting of the electrodiagnostic laboratory, a child may present with signs and symptoms of sensory loss, distal muscle weakness, atrophy, pes cavus, and absent reflexes. This clinical picture, along with slow conduction velocities in the upper extremities in the range of less than 38 m/sec, raises concerns of an inherited neuropathy, such as Charcot-Marie-Tooth (CMT). Genetic testing can help classify neuropathies into CMT1/HMSN-I, CMT2/HSMNII, dominant intermediate CMT (CMTDI), or CMT4 for a recessive demyelinating form of CMT.^4,5

Another entity, hereditary neuropathy with liability for pressure palsy (HNPP), has an associated PMP22 gene.^3,5 These patients present with mild sensory motor peripheral neuropathy. More than 50% of the patients recover completely within days to months from pressure palsy, whereas others remain with deficits permanently, and others in spite of the underlying disease do not ever present with pressure palsies. Biopsy of the nerves not affected would also demonstrate changes of thickening of the myelin sheath and segmental myelination and remyelination confirming the diagnosis.

Inherited axonal neuropathies occur from mutations in the genes responsible for axonal transport.³ For example, the CAP-gly domain of dynactin (DCTN1) is responsible for a hereditary axonal motor neuropathy (HMN), whereas a recessive mutation of KIF1A causes a sensory neuropathy. These axonal neuropathies receive their names based on their clinical features, including HSN when sensory axons are involved, HSAN when sensory and autonomic axons are involved, and HMN when motor axons are involved. If spasticity is present, then it is called hereditary spastic paraplegia. For mitochondrial diseases, mutations of the mitochondrial genome are seen and thus warrant referral for genetic analysis.

The most common muscular dystrophy is Duchenne muscular dystrophy (DMD), an X-linked recessive pattern, with defects at the Xp21 locus, but also has a high spontaneous mutation rate leading to sporadic cases.⁶ In cases of progressive muscular weakness, a dystrophin protein testing can be ordered. In severe cases of DMD, dystrophin is absent, whereas in another type, Becker muscular dystrophy, dystrophin, although present, is abnormal. Spinal muscular atrophy (SMA) is an autosomal-recessive disorder of generalized muscle weakness with homozygous loss or mutation of the survival motor neuron gene (SMN1) that has various degrees of severity. There are four subtypes, the first being a major cause of mortality among infants.

Genetic analysis differentiates pathology in spite of similar clinical symptoms. For instance, progressive weakness of the shoulder and pelvic muscles but sparing of facial muscles, and findings of necrosis and regenerating muscle fibers describe patients with limb girdle muscular dystrophy. The causative gene is MYOT encoding myotilin, important for sarcomere function.⁶ Mutation of the GNE gene is associated with inclusion body myositis, a common myopathy of the elders, but that actually starts in the late teens or early adulthood. The disease manifests with initial weakness of the legs spreading to proximal hip muscles and finally to the arms.⁷

Imaging techniques, such as muscle ultrasound (US), may replace invasive muscle biopsy in the early diagnosis of suspected neuromuscular and genetic disorders in children.⁸ Musculoskeletal US measures echo intensity, assessing atrophy and changes in the muscle architecture. It correlates with fibrous tissue content to differ between normal, myopathy, and neurogenic disorders.⁹

Interpreting the results of genetic testing can be challenging, requiring the experience of specialists, a geneticist, and patient counseling.¹⁰ For instance, a negative result could mean that the altered gene was not identified rather than that the patient does not suffer or will not suffer from the disorder. Referrals for genetic testing can prove judicious as we continue to search for disease-modifying treatments.

General radiologic studies (x-rays) are frequently used as a valid and inexpensive method to screen for structural abnormalities and more urgent pathology such as fractures, dislocations, foreign bodies, and tumors.

Computerized tomography (CT) imaging can be used to delineate bony anatomy as well as screen patients for acute intracranial pathology such as hemorrhage, tumors, or hydrocephalus. CT is commonly used to better visualize the osseous vertebral anatomy, especially when magnetic resonance imaging (MRI) is not available or may not be warranted. Intravenous (IV) contrast should be considered if infection, inflammation, or malignancy is clinically suspected and there is no contraindication to its use (Table 8–1).