Approach Considerations
As previously mentioned, patients with primary lateral sclerosis (PLS) occasionally have mild, nonspecific, and nonprogressive findings of denervation on electrodiagnostic testing. [11] The severity of the denervation and reinnervation does not resemble that seen in ALS and does not justify these patients' being classified as having ALS.
Whether serial electromyography (EMG) has a role in the diagnosis of PLS is uncertain; EMG might be used to look for the evolution of lower motor neuron findings in the absence of clinical evidence to suggest a change into ALS, but the clinical implication would be uncertain.
Despite the availability of supporting imaging and clinical neurophysiologic features, described best in patients with established disease, the initial diagnosis of PLS is usually made on clinical grounds.
Lab Studies
Laboratory studies for primary lateral sclerosis (PLS) should include hemogram, erythrocyte sedimentation rate, vitamin B-12 level, and, as indicated, Venereal Disease Research Laboratory (VDRL) (or rapid plasma reagent [RPR]), Lyme, HIV-1/HIV-2, and HTLV-1 serology tests.
Cerebrospinal fluid (CSF) analysis should include protein and glucose concentrations, cell count, and an MS panel. [12]
Imaging Studies
MRI studies are obtained to exclude alternative diagnoses. MRI, MRS, SPECT scan, and PET scan changes have been described in some patients, but the usefulness of these studies in making the diagnosis early in the presentation of primary lateral sclerosis (PLS) is not known.
Similarly, diffusion tensor imaging and magnetization transfer imaging may provide insight into the pathophysiologic process of ALS and PLS by providing objective imaging evidence to support the clinical findings of upper motor neuron dysfunction.
Further investigation is needed to determine and to compare the utility of various neuroimaging markers in making the diagnosis of PLS, in comparison with the clinical examination findings.
At this time, therefore, these advanced imaging techniques cannot be used alone to confirm or exclude the diagnosis of PLS.
Motor and Sensory Nerve Conduction Studies and Needle EMG
Motor and sensory nerve conduction studies should be normal.
Needle EMG helps to distinguish primary lateral sclerosis (PLS) from ALS by identifying, in ALS, electrophysiologic evidence of widespread lower motor neuron involvement. The changes in PLS are minimal or absent.
Electrodiagnostic Testing and Electrophysiologic Testing
Repeat electrodiagnostic testing occasionally is considered to determine whether lower motor neurons are involved.
As overall activity diminishes, muscle atrophy may suggest lower motor neuron involvement. Such changes may be distinguished from muscle atrophy due to disuse secondary to upper motor neuron impairment on clinical grounds (eg, no fasciculations) and, more definitively, by electrophysiologic testing. Occasionally, sparse, scattered, nonprogressive changes of denervation (ie, fibrillation potentials) may be seen in distal muscles.
Motor Evoked Potentials and Lower Extremity Somatosensory Evoked Potentials
Motor evoked potentials may show abnormalities of the upper motor neurons, but this test is not readily available in many centers.
Lower extremity somatosensory evoked potentials occasionally show prolonged latencies in patients with primary lateral sclerosis (PLS), in the absence of sensory symptoms. This subclinical involvement of central sensory axons suggests that in those patients, the disease pathophysiology is not restricted to upper motor neurons but instead affects them preferentially.
Lumbar Puncture and Genetic Testing
A lumbar puncture should be considered to rule out other causes of spasticity (eg, MS) after appropriate imaging studies have been obtained.
Genetic testing for HSP may be considered if the presentation and family history suggest the condition. Confirmation of a diagnosis of HSP results in an expectation for slower disease progression and a more limited range of clinical involvement, and affects management of the patient. Appropriate genetic counseling should be offered to patients with suspected HSP before they are referred for genetic testing.
