311 - Progressive Lower Extremity Paresis Secondary to Amyotrophic Lateral Sclerosis in a Patient with a History of Multiple Sclerosis

Case Diagnosis: Amyotrophic lateral sclerosis and multiple sclerosis

Case Description: 23-year-old female with prior diagnosis of MS and no family history of neurological disorders was admitted to IPR with bilateral lower extremity paresis. She was formerly independent and ambulatory, but ten months prior to admission experienced worsening bilateral lower extremity weakness and gait dysfunction. Over the next several months, the patient was admitted to acute care three separate times with comprehensive neurological work-up, including MRI brain and spine that revealed no acute demyelinating lesions, as well as LP negative for oligoclonal bands. Initial EMG/NCS revealed evidence of widespread ongoing denervation in bilateral lower extremities without sensory nerve involvement. Each admission, she was treated for suspected MS flares with persistent neurological decline. Consequently, repeat EMG was performed which also involved the left upper extremity, thoracic paraspinal, and bulbar muscles that was consistent with rapidly progressive motor neuron disease (MND). Subsequent genetic testing was positive for variants of undetermined significance, including ALS2.

Discussions: Coexistence of MS and ALS (a type of MND) is extremely rare, affecting an estimated 3 per 10 billion individuals¹. This co-occurrence may be random or due to a susceptibility to neurodegeneration involving both genetic and exogenous factors¹. Juvenile ALS refers to onset before age 25 and is associated with the ALS2 gene, but typically has a slow progression, autosomal recessive inheritance, and initially presents with UMN signs^2-3. EMG/NCS is necessary for confirmation of LMN degeneration⁴. To detect LMN in different body regions, bulbar, thoracic paraspinal, arm, and leg muscles should be sampled. In limb muscles, EMG must include abnormalities in two muscles innervated by different nerves and roots⁴.

Conclusions: Patients without imaging/laboratory evidence of MS progression and with persistent neurologic decline despite MS treatment may have a concomitant neurological disease. In these cases, EMG/NCS should include an evaluation for MND.