<p><strong>Importance: </strong>Children with severe neurological impairment (SNI) often take multiple medications to treat problematic symptoms. However, for children who cannot self-report symptoms, no system exists to assess multiple symptoms and their association with medication use.</p>

<p><strong>Objectives: </strong>To assess the prevalence of 28 distinct symptoms, test whether higher global symptom scores (GSS) were associated with use of more medications, and assess the associations between specific symptoms and medications.</p>

<p><strong>Design, Setting, and Participants: </strong>This cross-sectional study was conducted between April 1, 2019, and December 31, 2019, using structured parent-reported symptom data paired with clinical and pharmacy data, at a single-center, large, hospital-based special health care needs clinic. Participants included children aged 1 to 18 years with SNI and 5 or more prescribed medications. Data analysis was performed from April to June 2020.</p>

<p><strong>Exposure: </strong>During routine clinical visits, parent-reported symptoms were collected using the validated 28-symptom Memorial Symptom Assessment Scale (MSAS) and merged with clinical and pharmacy data.</p>

<p><strong>Main Outcomes and Measures: </strong>Symptom prevalence, counts, and GSS (scored 0-100, with 100 being the worst) were calculated, and the association of GSS with medications was examined. To evaluate associations between symptom-medication pairs, the proportion of patients with a symptom who used a medication class or specific medication was calculated.</p>

<p><strong>Results: </strong>Of 100 patients, 55.0% were boys, the median (interquartile range [IQR]) age was 9 (5-12) years, 62.0% had 3 or more complex chronic conditions, 76.0% took 10 or more medications, and none were able to complete the MSAS themselves. Parents reported a median (IQR) of 7 (4-10) concurrent active symptoms. The median (IQR) GSS was 12.1 (5.4-20.8) (range, 0.0-41.2) and the GSS was 9.8 points (95% CI, 5.5-14.1 points) higher for those with worse recent health than usual. Irritability (65.0%), insomnia (55.0%), and pain (54.0%) were the most prevalent symptoms. Each 10-point GSS increase was associated with 12% (95% CI, 4%-19%) higher medication counts, adjusted for age and complex chronic condition count. Among the 54.0% of children with reported pain, 61.0% were prescribed an analgesic.</p>

<p><strong>Conclusions and Relevance: </strong>These findings suggest that children with SNI reportedly experience substantial symptom burdens and that higher symptom scores are associated with increased medication use. Paired symptom-medication data may help clinicians identify targets for personalized symptom management, including underrecognized or undertreated symptoms.</p>