Annals of the Child Neurology Society最新文献

Manganese is the 12th most common element in the Earth's crust and is an essential industrial component. Biologically, this metal plays an important role as a constituent of numerous enzymes. While manganese is required for normal biochemical and physiological processes, manganese excess can lead to significant toxicity, particularly to the central nervous system. Over the past 25 years, three inherited disorders of manganese transport have been described, leading to a model of how this essential metal is absorbed, distributed to tissues, and eliminated. The first part of this review describes the clinical features and cellular mechanisms of manganese toxicity due to occupational and environmental exposure. The remainder of the review discusses the familial disorder associated with hypomagnesemia, SLC39A8 deficiency, and the two genetic diseases resulting in hypermanganesemia, SLC30A10 deficiency and SLC39A14 deficiency. These latter two disorders are treatable, and the early recognition and institution of chelation therapy and iron supplementation can improve neurological disability. Ongoing research regarding the tissue-specific role of each transporter and their regulatory interplay, the varied mechanisms of manganese toxicity, and its treatment are also described.

This 3-month-old boy had frequent recurrent events of right-arm stiffening and right head turn suggestive of focal seizures. Continuous electroencephalogram (EEG) showed subclinical focal seizures arising independently from the right occipital and left posterior head regions. These events persisted despite escalating use of lacosamide, levetiracetam, and phenobarbital. Given the patient's age, epilepsy of infancy with migrating focal seizures (EIMFS) was suspected. Early investigation with whole-exome sequencing revealed homozygous pathogenic variants in SLC12A5 (c.986C > A, p.Ala329Asp). Early recognition is vital in this epilepsy syndrome due to the difficulty in treating and subsequent prognosis. Given the expected drug resistance, early or urgent initiation of the ketogenic diet should be considered. The overall prognosis is not favorable, as poor developmental outcomes are expected.

EIMFS is a severe infantile-onset epilepsy syndrome characterized by refractory seizures, developmental delay, and migrating focal discharges [1]. SLC12A5 mutations have been identified as a cause of EIMFS, with nine patients reported to date, but KCNT1 remains responsible for about 50% of cases [2] (Figure 1). SLC12A5 encodes the potassium-chloride cotransporter KCC2, which is crucial for maintaining synaptic inhibition [3]. Mutations in SLC12A5 lead to decreased KCC2 surface expression, impaired chloride extrusion, and reduced protein glycosylation, resulting in neuronal hyperexcitability [3]. EIMFS typically presents before 6 months of age with focal motor seizures that become multifocal and intractable [2]. Treatment options are limited, but the ketogenic diet and potassium bromide have shown potential efficacy [2]. SLC12A5-related EIMFS is inherited in an autosomal recessive manner, with both de novo and inherited mutations reported [4].

Samuel Kamoroff: conceptualization, writing – original draft, writing – review and editing, data curation. Harry Abram: writing – review and editing, data curation, supervision. Fernando Galan: conceptualization, writing – review and editing, data curation, supervision.

The authors declare no conflicts of interest.

For subspecialities like child neurology in which demand is predicted to increase and further exceed supply, understanding what attracts individuals to the field and deters individuals from it is particularly valuable. To explore this, we recently surveyed medical students and residents who had completed child neurology clerkships at US medical schools within the last approximately 7 years to investigate the antecedent factors that led to interest in these clerkships and the factors that subsequently impacted residency choice, child neurology or otherwise. Current child neurology and neurodevelopmental disabilities residents (postgraduate years [PGY] 1 through 5) and current medical students who completed at least one child neurology clerkship at a US medical institution were invited to complete an online survey through their residency program coordinators/directors or clerkship coordinators/directors. While our 38 respondents gave us useful insights, our difficulty reaching a larger sample of the population of interest (likely ~1000−5000 individuals) highlights several barriers to conducting workforce research. Here, we share relevant literature and our observations on the pipeline for careers in child neurology, current research challenges, and potential paths forward.

Early exposure to child neurology is critical for sparking interest in the field. Although studies have used different definitions of “early,” frequently referring to college and medical school [1], it is becoming more apparent that no exposure is too early for igniting interest. In our study, the most common timeframe for initial exposure to neurology was during college at 39%; however, exposure in high school or earlier was almost equally as common (37%). Popular media such as books by Oliver Sacks and fictional characters like Sherlock Holmes have been cited in residency personal statements as motivating interest in neurology [2]. These exposures along with chance encounters with neurologists through personal or family experience with neurological conditions, pediatric or otherwise, appear to be relevant when medical students are planning their career paths. It remains to be explored whether the specific exposure (pediatric, e.g., a sibling with autism, or adult, e.g., a grandparent with Alzheimer's disease) influences whether one decides to go into child neurology or adult neurology, especially given the lack of awareness among premedical and medical students that child neurology is its own specialty. Studying these types of “early” exposures could be fruitful for understanding how early lifeexperiences influence motivation to enter medicine and eventual specialty choice.

Undergraduate neuroscience courses are another crucial early exposure to the field. At present, there are inequities in access to such courses, which has implications for recruiting a diverse workforce [3]. In our survey, 24% of participants indicated tha

Percy AK, Benke TA, Marsh ED, Neul JL. Rett syndrome: The Natural History Study Journey. Ann Child Neurol Soc. 2024;2(3):189–205. doi: 10.1002/cns3.20086.

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