Genetic Advancements in Infantile Epileptic Spasms Syndrome and Opportunities for Precision Medicine.

Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, 60% of cases are thought to be structural, metabolic or infectious in nature, with the remainder genetic or of unknown cause. Epilepsy genetics is a growing field, and over 28 copy number variants and 70 single gene pathogenic variants related to IESS have been discovered to date. While not exhaustive, some of the most commonly reported genetic aetiologies include trisomy 21 and pathogenic variants in genes such as TSC1, TSC2, CDKL5, ARX, KCNQ2, STXBP1 and SCN2A. Understanding the genetic mechanisms of IESS may provide the opportunity to better discern IESS pathophysiology and improve treatments for this condition. This narrative review presents an overview of our current understanding of IESS genetics, with an emphasis on animal models of IESS pathogenesis, the spectrum of genetic aetiologies of IESS (i.e., chromosomal disorders, single-gene disorders, trinucleotide repeat disorders and mitochondrial disorders), as well as available genetic testing methods and their respective diagnostic yields. Future opportunities as they relate to precision medicine and epilepsy genetics in the treatment of IESS are also explored.

Significant vomiting and weight loss in a pediatric epilepsy patient secondary to vagus nerve stimulation: A case report and review of the literature.

Vagus nerve stimulation is a neuromodulatory treatment option for individuals with drug resistant epilepsy who are not resective surgical candidates. As the vagus nerve has widespread neural connections, stimulation can lead to an array of adverse effects. While vomiting and weight loss are known side effects of vagus nerve stimulation, these are typically transient, mild, and do not limit the ability to continue treatment. We describe a 17-year-old female with drug resistant focal epilepsy secondary to tuberous sclerosis complex, who began to experience daily emesis and significant weight loss approximately 2.5 years after VNS device insertion. Her body mass index progressively fell from between the 75th-85th percentiles to less than the first percentile. She underwent extensive workup by neurology, gastroenterology, and adolescent medicine services with no obvious cause identified. Prior to the insertion of an enteral tube for feeding support and urgent weight restoration, her vagus nerve stimulator was switched off, resulting in immediate cessation of her vomiting and a dramatically rapid recovery of weight over the ensuing few months. This case emphasizes the need to consider adverse effects of vagus nerve stimulation in the differential diagnosis of patients with otherwise unexplained new medical sequelae, and provides evidence potentially linking vagal stimulation to significant malnutrition-related complications. Outside of GI-related effects, few studies have shown late-onset adverse effects from VNS, including laryngeal and facial pain as well as bradyarrhythmia. Further research is needed to elucidate the exact mechanisms of vagus nerve stimulation to better anticipate and mitigate adverse effects, and to understand the pathophysiology of late-onset adverse effects in previously tolerant VNS patients.

Artery of Percheron infarction with persistent amnesia: a case report of bilateral paramedian thalamic syndrome.

BACKGROUND: The artery of Percheron is an uncommon anatomic variant which supplies the bilateral paramedian thalami and rostral midbrain. While infarction of its vascular territory can result in a wide range of symptoms, paramedian thalamic syndrome is classically described as a triad of symptoms including vertical gaze disturbances, fluctuating level of consciousness, and amnesia. There is minimal evidence to date to characterize the long-term cognitive consequences of infarction of the artery of Percheron utilizing neuropsychological assessment. CASE PRESENTATION: We describe a 40-year-old female patient initially presenting with dizziness, confusion and falls with unremarkable head CT scans. Subsequent MRI, more than 24 h after symptom onset, identified evidence of bilateral thalamic and rostral midbrain infarction. Neuropsychological testing was administered at 4 months post-stroke, with follow up testing at 1 year. The patient was found to have profound anterograde and retrograde amnesia, which did not change significantly over the first year of rehabilitation, and which was not easily identifiable in everyday encounters due to her relatively intact working memory and social skills. CONCLUSIONS: As early diagnosis of infarction of the artery of Percheron is challenging, patients have frequently missed the time window for acute management of ischemic stroke. Moreover, this case study highlights the need for further research in deciphering the role of the paramedian thalamus in memory and cognition, as well as the importance of standardized neuropsychological testing for the artery of Percheron stroke patients to identify safety and rehabilitation concerns that may be overlooked.