EEG biomarkers for the diagnosis and treatment of infantile spasms

Early diagnosis and treatment are critical for young children with infantile spasms (IS), as this maximizes the possibility of the best possible child-specific outcome. However, there are major barriers to achieving this, including high rates of misdiagnosis or failure to recognize the seizures, medication failure, and relapse. There are currently no validated tools to aid clinicians in assessing objective diagnostic criteria, predicting or measuring medication response, or predicting the likelihood of relapse. However, the pivotal role of EEG in the clinical management of IS has prompted many recent studies of potential EEG biomarkers of the disease. These include both visual EEG biomarkers based on human visual interpretation of the EEG and computational EEG biomarkers in which computers calculate quantitative features of the EEG. Here, we review the literature on both types of biomarkers, organized based on the application (diagnosis, treatment response, prediction, etc.). Visual biomarkers include the assessment of hypsarrhythmia, epileptiform discharges, fast oscillations, and the Burden of AmplitudeS and Epileptiform Discharges (BASED) score. Computational markers include EEG amplitude and power spectrum, entropy, functional connectivity, high frequency oscillations (HFOs), long-range temporal correlations, and phase-amplitude coupling. We also introduce each of the computational measures and provide representative examples. Finally, we highlight remaining gaps in the literature, describe practical guidelines for future biomarker discovery and validation studies, and discuss remaining roadblocks to clinical implementation, with the goal of facilitating future work in this critical area

Response to treatment in a prospective national infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/1/ana24594.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/2/ana24594_am.pd

Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/1/epi13557_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/2/epi13557.pd

Crisis Standard of Care: Management of Infantile Spasms during COVID‐19

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156180/2/ana25792_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156180/1/ana25792.pd

Adrenal Function Testing Following Hormone Therapy for Infantile Spasms: Case Series and Review of Literature

Prednisolone and adrenocorticotropic hormone (ACTH) are hormone therapies for infantile spasms. There is limited data on the occurrence of decreased adrenal reserve or signs of clinical adrenal insufficiency after hormone therapy. This is a retrospective medical record review of patients referred to our Infantile Spasms Program. Our standardized infantile spasms management guideline began in September 2012 and initially included a post-hormone laboratory assessment of adrenal function. Medical records were assessed for hormone treatments, adrenal function testing, and signs of adrenal insufficiency. Forty-two patients who received one or both hormone therapies met inclusion criteria. A post-hormone laboratory assessment of adrenal function was done in 14 patients. Of these 14 patients, two had an abnormal laboratory assessment of adrenal function, both by adrenal stimulation testing – one after ACTH and one after prednisolone. One patient received hydrocortisone replacement and the other received stress dose hydrocortisone as needed; neither patient developed signs of adrenal insufficiency. Another patient treated with both types of hormone therapy in tandem, who did not have a post-hormone laboratory assessment, developed signs of mild adrenal insufficiency and required replacement hydrocortisone. Our study suggests that adrenal suppression can occur after modern hormone therapy regimens. We found two patients with abnormal adrenal function testing after hormone therapy and another patient with signs adrenal insufficiency. Given the seriousness of adrenal crisis, caregiver education on the signs of adrenal insufficiency is critical. Greater vigilance may be indicated in patients receiving both types of hormone therapy in tandem. Although a routine post-hormone laboratory assessment of adrenal function may not be feasible in all patients, replacement or stress dose hydrocortisone is necessary for all patients with suspected adrenal insufficiency

Infantile Spasms Respond Poorly to Topiramate

Introduction: Infantile spasms are seizures typical of an age-related epileptic encephalopathy. Although evidence supporting topiramate for infantile spasms is lacking, many clinicians use it for this indication. The aim of this study was to determine the rate of infantile spasm remission with topiramate at our institution. A low rate of infantile spasm remission was hypothesized. Methods: This was a single-center retrospective medical record review of patients treated with topiramate for infantile spasms between January 2009 and September 2013. Records were reviewed for accuracy of diagnosis and outcome. Clinical remission of infantile spasms was defined as resolution for at least 28 days at any time during treatment with topiramate. For patients with clinical remission, posttreatment electroencephalographs were reviewed to assess for electrographic remission. To assess for confounding variables affecting remission rate, demographics and outcomes were compared with patients treated with adrenocorticotropic hormone within the same period using the same criteria for remission. Results: Three of 31 (9.7%) patients achieved clinical remission with topiramate, two of whom also experienced electrographic remission. The third patient had electrographic remission with previous adrenocorticotropic hormone treatment but infantile spasm remission only after receiving topiramate. All three of these patients experienced subsequent electroclinical relapse during topiramate therapy. Although there were no significant demographic differences between the topiramate and adrenocorticotropic hormone cohorts, more adrenocorticotropic hormone patients achieved clinical remission (9.7% versus 56%; P \u3c 0.001). Discussion: Remission of infantile spasms with topiramate was uncommon and no patient experienced persistent electroclinical remission. These findings suggest that infantile spasms respond poorly to topiramate