Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice.

Importance: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. Objective: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. Design, Setting, and Participants: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. Exposures: Genetic test results. Main Outcomes and Measures: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. Results: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). Conclusions and Relevance: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.

Sport-related concussions in adolescent athletes: a critical public health problem for which prevention remains an elusive goal.

Sport-related concussions in young athletes are common, generally under reported and often unrecognized. Preventive strategies include education, modification of sport rules, use of equipment such as headgears, face masks and mouth guards, and neck muscle training. Evidence is limited to support effectiveness of these preventive measures with the exception of rule modification in some sports. In the United States, laws have been enacted that require medical evaluation and clearance prior to return to play; however, evidence thus far does not show that laws have been effective in reducing the incidence of concussions in sport. More research is needed in all areas of preventive measures. Sports participation is a complex personal decision on the part of the adolescent and his or her family. They should be provided with all information on inherent risks so that they can make an informed decision.

Evaluation and management of sport-related concussions in adolescent athletes.

Sport-related concussions in young athletes are common, generally under reported and often go unrecognized. Concussion in sport may result either from a direct impact to the head or from indirect forces transmitted to the brain from impact elsewhere on the body. Concussions may also result from sudden acceleration, deceleration or rotational forces to the brain. The key features of concussion include confusion, impaired memory and reduced speed of information processing. Recovery may occur from a few days to several weeks or months. Both physical and cognitive rests are recommended for recovery. Long-term cognitive and behavioral complications are a concern. Preventive strategies include education, modification of sport rules, use of equipment such as headgears, face masks and mouth guards, and neck muscle training. Evidence is limited to support effectiveness of these preventive measures with the exception of rule modification in some sports. Laws have been enacted that require medical evaluation and clearance prior to return to play; however, evidence thus far does not show that laws have been effective in reducing the incidence of concussions in sport. More research is needed in all areas of preventive measures. Sports participation is a complex personal decision on the part of adolescent and his or her family. They should be provided with all information on inherent risks so that they can make an informed decision.

Neurological problems in the adolescent population.

Adolescent patients pose a unique challenge to child neurologists. Although there are a number of neurological disorders that present in childhood and persist through adolescence, there are some disorders like juvenile myoclonic epilepsy (JME) that occur more commonly in this age group. We discuss common neurological disorders encountered by adolescent medicine physicians that have been affected by recent advances in the field of adolescent neurology. We also address the challenges of transitioning care to an adult neurologist.

Evaluation of the child with acute ataxia: a systematic review.

Evaluation of acute ataxia in a child poses a dilemma for the clinician in determining the extent and timing of initial screening tests. This article reviews the evidence concerning the diagnostic yield of commonly ordered tests in evaluating the child with acute ataxia. The literature revealed the following frequencies of laboratory screening abnormalities in children with acute ataxia: CT (∼2.5%), MRI (∼5%), lumbar puncture (43%), EEG (42%), and toxicology (49%). In most studies, abnormalities detected by these screening tests were nondiagnostic. There are insufficient data to assess yields of testing for autoimmune disorders or inborn errors of metabolism. A toxicology screen should be considered in all children presenting with acute ataxia. Neuroimaging should be considered in all children with new onset ataxia. Cerebrospinal fluid analysis has limited diagnostic specificity unless clinically indicated. Studies to examine neurophysiology testing did have sufficient evidence to support their use. There is insufficient evidence to establish a role for autoantibody testing or for routine screening for inborn error of metabolism in children presenting with acute ataxia. Finally, in a child presenting with ataxia and opsoclonus myoclonus, urine catecholamine testing for occult neuroblastoma is recommended. Nuclear scan may be considered, however, there is insufficient evidence for additional body imaging.