Fatigue is a burdensome symptom for pediatric populations with neuromuscular disorders, often assessed using patient- and observer-reported outcomes. The three aims of this systematic review are to: (1) explore, summarize and critically appraise primary studies that measure fatigue in pediatric neuromuscular disorders using patient- and observer-reported outcomes; (2) compare definitions of fatigue and related terms presented within these studies; and (3) summarize evidence for validation of patient- and observer-reported outcomes used in included studies. Six electronic databases were searched. Of 6801 studies identified, 64 met the inclusion criteria of measuring fatigue with a patient- and/or observer-reported outcome and investigated populations below 22 years of age with neuromuscular disorders. Fatigue assessments included questionnaires (80%), interviews/testimonials (17%), and single-item measures (3%). To measure fatigue, 50% of studies used 1 questionnaire, 28% used 2 or more questionnaires, 6% used interviews alone, 3% used single-item measures alone, and 13% used a combination of these methods. Quality appraisal indicated 80% of included studies had moderate-high risk of bias. Of all included studies, 10 employed varying definitions of fatigue or related terms. Fatigue was commonly described as an overwhelming, multidimensional and whole-body experience. Several questionnaires used to measure fatigue were developed to measure other constructs such as quality of life. Evidence for psychometric validation of all questionnaires was limited, and evidence for validation in neuromuscular disorders and pediatric populations was scarce. This review indicates a need for coherent and standardized fatigue definitions and measures while highlighting the scarcity of evidence for validation of frequently used questionnaires.

Classifying nerve injury severity is essential for communication, prognosis, and treatment decisions. Traditional classification systems (Seddon, Sunderland) cannot account for the full spectrum of nerve pathology, from familiar phenomena such as local anesthetics to recently discovered autoimmune nodopathies. A two-dimensional framework is proposed that separates two aspects of severity conflated in previous classifications and applies to focal and diffuse nerve injuries. The first dimension, quantitative degree, is the proportion of axons involved; the second, pathological type, is the underlying pathology of the involved axons. Pathological type comprises conduction block (conduction failure in live axons) and axon loss (conduction failure of dead axons). Conduction block has two anatomic origins: axonal block, due to primary axonal dysfunction, and demyelinating block, due to primary myelin dysfunction. Axonal block can be organized into three mechanistic clusters: ionic, displacement, and nodopathic block, with distinct pathophysiology, histology, and recovery times. Both axonal and demyelinating conduction block produce electrodiagnostic features historically attributed to demyelination, although subtle differences can sometimes be identified. Severity and recovery time increase from ionic block to axon loss. A single mechanism can cause multiple pathological types, sometimes simultaneously, with the type determined by injury intensity and duration. The two dimensions integrate into assessment: quantitative degree is estimated clinically, and conduction block or axon loss is determined electrodiagnostically. This framework highlights that conduction block can result from processes at the axon or myelin. This includes autoimmune nodopathies, which are often mistaken for demyelinating disorders, but accurate identification can change treatment and may be lifesaving.