Annals of the Child Neurology Society最新文献

This previously healthy neurotypical 3-year-old boy presented for frequent stereotyped episodes of left facial and arm twitching with maintained awareness. An electroencephalogram (EEG) and brain magnetic resonance imaging were normal. However, due to a high concern for focal motor seizures, he was discharged on daily levetiracetam. Six days later, he was readmitted for increased irritability and continued left hemibody movements while awake and asleep. Continuous EEG captured the episodes of concern without an EEG correlate. The evaluation for toxic, metabolic, and infectious conditions, including cerebrospinal fluid studies, was unremarkable. His agitation was concerning for an adverse effect of levetiracetam, so he was switched to lacosamide. The evaluation was broadened to include autoimmune disorders.

His agitation did not improve, and then he developed low-grade fevers with continued irritability. His left hemibody movements evolved to orofacial dyskinesia and choreoathetoid movements (Video S1). He was started on intravenous immunoglobulins and methylprednisolone for probable autoimmune etiology. He was later found to have antibodies to the NMDA receptor in the cerebrospinal fluid (titer 1:5), confirming the diagnosis of anti-N-methyl-d-aspartate (NMDA)-receptor encephalitis, consistent with his behavioral change and movement disorder.

This boy illustrates the clinical presentation of anti-NMDA encephalitis in a child presenting with stereotypical hemibody movements unresponsive to antiseizure medication. His findings highlight the importance of a comprehensive evaluation and early treatment of potential autoimmune causes of acute behavioral and motor changes without signs of infection or previous seizures.

Devan J. Peterson: Conceptualization; investigation; supervision; visualization; writing— original draft; writing—review and editing. Olivia S. Yale: Conceptualization; investigation; writing—original draft; writing—review and editing. Janetta L. Arellano: Conceptualization; investigation; supervision; writing—original draft; writing—review and editing.

The authors declare no conflicts of interest.

Understanding clinical features and disease progression of Rett syndrome (RTT) and establishing clinical trial readiness was enhanced by the RTT Natural History Study (NHS). The NHS benefited from two key developments: one, the Orphan Drug Act passed by Congress in 1983 defining criteria for rare disorders in the United States and creating opportunities for pharmaceutical companies to develop products for individuals with rare disorders, and two, the Rare Diseases Act of 2002, which established the National Institutes of Health Office of Rare Diseases and provided research funding. Funding for the RTT and related disorders NHS was obtained in 2003, creating a broad network of experienced clinical investigators across the United States and producing critical results not only for RTT but also for related disorders: CDKL5 deficiency disorder, FOXG1 disorder, and MECP2 duplication syndrome. Longitudinal information from over 1800 participants (more than 1600 diagnosed with RTT) led to multiple reports describing their clinical features and natural progression and identified putative biomarkers and clinical outcome measures. Establishing clinical trial readiness assisted in evaluating the first FDA-approved medication for RTT in 2023 and continues to provide opportunities to develop potentially life-altering therapies. The experiences of the RTT NHS journey provide informative guidance for studying other rare neurological disorders. These lessons include positive features of developing productive collaborations focused on improving lives of people and families with RTT and related disorders, as well as lessons learned through retrospective analysis for improving overall conduct of natural history studies in rare disorders.

Pilocytic astrocytomas (PA) are slow-growing gliomas that account for 15% of all central nervous system tumors.¹ Focal seizures are well-reported sequelae of PAs but present heterogeneously.² We describe a unique ictal “shushing” behavior in a pediatric patient with a PA of the isthmus of the cingulate gyrus.

This 14-year-old right-handed boy with no significant past medical history presented due to concern for seizures. Three to four months prior, he began experiencing daily episodes of an unusual gesture. During these episodes, he would walk toward his family or friends, place his pointer finger on his lips, and tell them to “shush” without any other vocalizations. He was aware of these episodes as they occurred but incapable of stopping them. Each episode was preceded by abdominal pain, nausea, and dizziness and followed by headaches and sleeping. Vomiting occurred after several episodes. During one episode that occurred while sleeping, his eyes rolled back for one minute, and then he awoke and promptly returned to sleep, but there were no additional seizure manifestations.

A subsequent 2-hour electroencephalogram (EEG) and continuous EEG monitoring were normal. Due to high clinical suspicion of focal seizures with impaired awareness, an MRI of the brain was ordered, and he was prescribed levetiracetam. The MRI demonstrated a lesion within the isthmus of the right cingulate gyrus that was cystic and contained a heterogeneously enhancing mural nodule (Figure 1).

Two days later, the patient underwent surgical resection of the lesion, a PA with eosinophilic granular bodies and Rosenthal fibers on histology. After the operation, he was alert but exhibited left-sided hemineglect and homonymous hemianopsia. Seven months after surgery, he stopped taking his levetiracetam, and the “shushing” behavior did not recur and there were no other seizure manifestations. Subsequent imaging demonstrated no tumor recurrence.

This patient exhibited an unusual ictal “shushing” behavior due to tumor-related epilepsy. Ictal shushing as a manifestation of a focal seizure has not been previously described in a pediatric patient. For pediatric patients with similar behaviors, both focal seizures and PAs should be on the differential.

The location of this patient's lesion in the isthmus of the right cingulate gyrus and its proximity to the temporal lobe may have contributed to his semiology. In patients with mesial temporal sclerosis, seizures arise in the hippocampus and propagate to the cortex.³ Specifically, impulses from the temporal lobe may propagate through the supplementary motor area to produce index finger pointing in localization-related epilepsy.⁴ Although similar ictal shushing has been reported as a “hush sign” in two adult patients, this report highlights the first presentation in a pediatric patient with a focal lesion.