Search

ABSTRACT:We present five cases of pediatric drug-resistant epilepsy (DRE) that failed management using high cannabidiol (CBD) doses, but had significant reduction in seizure frequency with reintroduction or increasing doses of tetrahydrocannabinol (THC). There is growing evidence supporting the use of whole-plant CBD-rich extracts (containing THC and other cannabinoids) in the treatment of pediatric DRE. Based on our experiences and reports in the literature, we propose that, in patients who fail management with an initial trial of high-dose CBD-focused therapy, there may be a role for add-on THC-focused formulations.

ABSTRACT:Background:Continuous EEG monitoring, in the form of amplitude-integrated (aEEG) or conventional EEG (cEEG), is used in the neonatal intensive care unit (NICU) to detect subclinical central nervous system pathologies, inform management, and prognosticate neurodevelopmental outcomes. To learn more about provider attitudes and current practices in Canada, we evaluated neurologist and neonatologist opinions regarding NICU EEG monitoring. Methods:A 15-item electronic questionnaire was distributed to 114 pediatric neurologists and 176 neonatologists working across 25 sites. Results:The survey was completed by 87 of 290 physicians. Continuous EEG monitoring is utilized by 97% of pediatric neurologists and 92% of neonatologists. Neurologists and neonatologists differ in their EEG monitoring preferences. For seizure detection and diagnosis of encephalopathy, significantly more neonatologists favor aEEG alone or in combination with cEEG, whereas most neurologists prefer cEEG (p= 0.047, 0.001). There is a significant difference in the perceived gaps in monitoring patients with cEEG between neonatologists (13% would monitor more) and neurologists (41% would monitor more) (p= 0.007). Half of all respondents (53%) reported that they would be interested in attending an education session on neonatal EEG monitoring. Conclusions:Canadian neurologists and neonatologists do not agree on the best monitoring approach for critically ill neonates. Furthermore, neonatologists perceive a smaller cEEG monitoring gap as compared with neurologists. However, many participants from both specialties would like to increase long-term EEG monitoring in the NICU setting. Facilitating access to EEG monitoring and enhancing education may help to address these needs.

White matter lesions have been described in patients with PTENhamartoma tumor syndrome (PHTS). How these lesions correlate with the neurocognitive features associated with PTENmutations, such as autism spectrum disorder (ASD) or developmental delay, has not been well established. We report nine patients with PTENmutations and white matter changes on brain magnetic resonance imaging (MRI), eight of whom were referred for reasons other than developmental delay or ASD. Their clinical presentations ranged from asymptomatic macrocephaly with normal development/intellect, to obsessive compulsive disorder, and debilitating neurological disease. To our knowledge, this report constitutes the first detailed description of PTEN‐related white matter changes in adult patients and in children with normal development and intelligence. We present a detailed assessment of the neuropsychological phenotype of our patients and discuss the relationship between the wide array of neuropsychiatric features and observed white matter findings in the context of these individuals.

We report the case of an infant with KCNQ2‐related neonatal epileptic encephalopathy presenting with intractable seizures beginning on the second day of life, which were resistant to multiple antiepileptic drugs. Continuous EEG recordings starting on the sixth day of life demonstrated a unique pattern of inter‐and postictal focal rhythmic pointed theta waves of lambdoid morphology in the immediate postictal period, localizing to the side of the antecedent seizure. Interictal EEG exhibited discontinuous background, including patterns of burst suppression and multifocal discharges, predominantly in the centrotemporal regions, which were aggravated during sleep. MRI demonstrated T1 signal abnormalities in the basal ganglia, bilaterally. Genetic testing revealed a de novomissense mutation in KCNQ2at position c.545 T>G, encoding a previously unreported substitution (p.Val182Gly). Seizure control was achieved immediately after starting a lidocaine infusion at age 4 weeks. The patient remained largely seizure‐free following add‐on oral carbamazepine for maintenance therapy and weaning off lidocaine. This is the first report of a patient with KCNQ2‐related neonatal epileptic encephalopathy and therapy‐refractory seizures aborted by lidocaine, demonstrating a unique EEG pattern of inter‐ and postictal focal rhythmic pointed theta waves. Whether this pattern could be an early EEG marker for this disorder remains to be confirmed. [Published with video sequences onwww.epilepticdisorders.com]

Mitochondrial fission and fusion are dynamic processes vital to mitochondrial quality control and the maintenance of cellular respiration. In dividing mitochondria, membrane scission is accomplished by a dynamin-related GTPase, DNM1L, that oligomerizes at the site of fission and constricts in a GTP-dependent manner. There is only a single previous report of DNM1L-related clinical disease: a female neonate with encephalopathy due to defective mitochondrial and peroxisomal fission (EMPF; OMIM #614388), a lethal disorder characterized by cerebral dysgenesis, seizures, lactic acidosis, elevated very long chain fatty acids, and abnormally elongated mitochondria and peroxisomes. Here, we describe a second individual, diagnosed via whole-exome sequencing, who presented with developmental delay, refractory epilepsy, prolonged survival, and no evidence of mitochondrial or peroxisomal dysfunction on standard screening investigations in blood and urine. EEG was nonspecific, showing background slowing with frequent epileptiform activity at the frontal and central head regions. Electron microscopy of skeletal muscle showed subtle, nonspecific abnormalities of cristal organization, and confocal microscopy of patient fibroblasts showed striking hyperfusion of the mitochondrial network. A panel of further bioenergetic studies in patient fibroblasts showed no significant differences versus controls. The proband’s de novo DNM1L variant, NM_012062.4:c.1085G>A; NP_036192.2:p.(Gly362Asp), falls within the middle (oligomerization) domain of DNM1L, implying a likely dominant-negative mechanism. This disorder, which presents nonspecifically and affords few diagnostic clues, can be diagnosed by means of DNM1L sequencing and/or confocal microscopy.

AbstractObjective: Headaches are a common problem in the pediatric population. In 2002, the American Academy of Neurology (AAN) developed guidelines on neuroimaging for patients presenting with headache. Our objective was to determine the frequency of computed tomographic (CT) scanning ordered by a range of medical practitioners for pediatric patients presenting with primary headache.Methods: A retrospective chart review was conducted at the Children’s Hospital of Eastern Ontario (CHEO), a tertiary care centre in Ontario. One hundred fifty-one records of patients referred to the outpatient neurology clinic at CHEO with ‘‘headache’’ or ‘‘migraine’’ as the primary complaint from 2004 to 2009 were randomly selected. Ninety-nine patients with normal neurologic examinations were ultimately included.Results:Thirty-four patients (34%; 95% CI 25–45) had undergone CT scanning. None of the 34 CT scans (0%; 95% CI 0–10) showed significant findings, and none changed the headache diagnosis or management. Eleven (32%) of the CT scans were ordered by CHEO neurologists, 15 (44%) by community physicians, and 8 (24%) by CHEO emergency physicians.Conclusion:A high proportion of children presenting with primary headaches and a normal neurologic examination undergo CT scanning, despite well-established AAN guidelines regarding neuroimaging. Most of these CT scans do not appear to alter diagnosis and management. A variety of non–evidencebased factors may be encouraging physicians to overinvestigate this population and, as a result, increasing the risk of adverse events due to radiation exposure. Implementing initiatives at a site-based level that promote the use of established guidelines before performing CT scanning in this population may be beneficial.