Brachial Plexus Neuropathies

The brachial plexus is a network of nerves that exit the spinal cord from the C5-T1 nerve roots and provide all motor and sensory function to the arm from the shoulder to the fingers. Injury to the brachial plexus due to traction forces during labor and/or delivery causing the nerves to stretch or tear occurs in 0.9 out of 1000 live births. As many as 30% of infants with brachial plexus birth injury (BPBI) have paralysis or weakness in one arm resulting in lifelong impairment in arm function with joint contractures, the shortening of tendons, ligaments and muscles, leading to reduced range of motion (ROM), being a common complication and major source of disability. A primary goal of early management of BPBI is to use passive range of motion (PROM) (stretching) to improve and/or maintaining shoulder ROM due to the known risk of shoulder contracture within the first year of life. Infants who develop contractures face challenges in overall sensory-motor development and are less able to participate in meaningful occupations and activities of daily living due to limited upper extremity ROM. They are also at risk for subsequent surgeries throughout their lives. Occupational therapy practitioners (OTPs) and physicians who specialize in treating infants with BPBI recommend caregivers to perform PROM at every diaper change, which is every 1-3 hours in the first months of life, and every 4-6 hours by age one. A survey study by one of the investigators on this proposed project found that 85% of OTPs who specialize in BPBI make this recommendation for performing PROM at every diaper change; however, there is no research to support this frequency to prevent or decrease contractures. Clinical observations suggest that infants who receive consistent daily PROM seem to avoid development of shoulder contractures while those who receive no or infrequent PROM seem to develop early and significant contractures. In a retrospective pilot study we found that children whose parents consistently performed PROM two times daily starting before age two months were less likely to develop shoulder contractures than children whose parents were inconsistent in performing PROM. These findings, along with our clinical observations suggest that frequency of PROM might be less important than consistency. In order to assess the efficacy of different levels of frequency (e.g., at every diaper change vs. two times per day), it is imperative to identify methods that support caregivers in performing PROM every day. Therefore, the proposed study will pilot a caregiver training method which, if successful in facilitating daily adherence, will be used as part of a larger planned study that will compare differences in recommended frequencies of stretching.
In a survey study and scoping literature review performed by one of the co-investigators on this project, caregiver adherence to home therapy recommendations was found to be facilitated by confidence in the training they received and by their confidence in ability to carry-out recommendations; lack of confidence in performing the home therapy recommendations was found to be a common barrier. Therefore, the objective of the proposed work is to assess the efficacy of a pilot training protocol for caregivers of infants with BPBI. Our central hypothesis is that the pilot training protocol will improve caregiver efficacy and increase their confidence in performing the recommended PROM/stretching procedure, thus facilitating adherence which we hope to later demonstrate will decrease the risk of shoulder contracture in infants with BPBI. The significance of this work is that it will evaluate and provide evidence for the use of the pilot training protocol so that this training protocol can later be used in a larger study on the efficacy of different frequencies of PROM to reduce the development of shoulder contracture in infants with BPBI, and thus contribute to developing evidenced-based standards of care for this population.
The objectives of this clinical trial are to:
1. determine whether caregivers who receive a pilot training protocol for performing PROM demonstrate improved efficacy in performing PROM compared to caregivers who receive standard training
2. determine whether caregivers who receive a pilot training protocol for performing PROM demonstrate improved self-confidence in performing PROM compared to caregivers who receive standard training
3. determine whether caregivers who receive a pilot training protocol for performing PROM report better daily adherence to daily PROM compared to caregivers who receive standard training

MEK inhibitors (trametinib, cobimetinib, selumetinib or binimetinib) have been used since 2016 to treat metastatic melanoma, by targeting the MAPK pathway Neuromuscular complications (neuropathy, myasthenia or myositis) have been reported in patients treated with MEK inhibitors.
With the growing use of these new oncology therapies, neurologists, oncologists and other clinicians are likely to be increasingly confronted with MEK inhibitor-induced neuropathy, myasthenia or myositis.
Yet, so far, these complications have only been documented in a few single case reports.
Our aim was to characterize the neuromuscular complications associated with MEK inhibitors used either alone or in combination.