Corrigendum to "A new pathogenic POLG variant" [Molecular Genetics and Metabolism Reports 32 (2022) 100890].

[This corrects the article DOI: 10.1016/j.ymgmr.2022.100890.].

A new pathogenic POLG variant.

POLG gene mutations are the most common causes of inherited mitochondrial disorders. The enzyme produced by this gene is responsible for the replication and repair of mitochondrial DNA. To date, around 300 pathogenic variants have been described in this gene. The resulting clinical outcomes of POLG mutations are widely variable in both phenotype and severity. There is considerable overlap in the phenotype of the so-called POLG syndromes with no clear genotype-phenotype correlation. Here we describe a newly discovered pathogenic variant in the POLG gene in a 7-year-old male that died of uncontrollable refractory status epilepticus. Genetic epilepsy panel sequencing identified two variants in the POLG gene, the common p.A467T pathological mutation and a novel p.S809R POLG variant found in trans with the p.A467T POLG that accompanied a severely reduced mitochondrial DNA level in the patient's tissues.

Indications for Inpatient Magnetoencephalography in Children - An Institution's Experience.

Magnetoencephalography (MEG) is recognized as a valuable non-invasive clinical method for localization of the epileptogenic zone and critical functional areas, as part of a pre-surgical evaluation for patients with pharmaco-resistant epilepsy. MEG is also useful in localizing functional areas as part of pre-surgical planning for tumor resection. MEG is usually performed in an outpatient setting, as one part of an evaluation that can include a variety of other testing modalities including 3-Tesla MRI and inpatient video-electroencephalography monitoring. In some clinical circumstances, however, completion of the MEG as an inpatient can provide crucial ictal or interictal localization data during an ongoing inpatient evaluation, in order to expedite medical or surgical planning. Despite well-established clinical indications for performing MEG in general, there are no current reports that discuss indications or considerations for completion of MEG on an inpatient basis. We conducted a retrospective institutional review of all pediatric MEGs performed between January 2012 and December 2020, and identified 34 cases where MEG was completed as an inpatient. We then reviewed all relevant medical records to determine clinical history, all associated diagnostic procedures, and subsequent treatment plans including epilepsy surgery and post-surgical outcomes. In doing so, we were able to identify five indications for completing the MEG on an inpatient basis: (1) super-refractory status epilepticus (SRSE), (2) intractable epilepsy with frequent electroclinical seizures, and/or frequent or repeated episodes of status epilepticus, (3) intractable epilepsy with infrequent epileptiform discharges on EEG or outpatient MEG, or other special circumstances necessitating inpatient monitoring for successful and safe MEG data acquisition, (4) MEG mapping of eloquent cortex or interictal spike localization in the setting of tumor resection or other urgent neurosurgical intervention, and (5) international or long-distance patients, where outpatient MEG is not possible or practical. MEG contributed to surgical decision-making in the majority of our cases (32 of 34). Our clinical experience suggests that MEG should be considered on an inpatient basis in certain clinical circumstances, where MEG data can provide essential information regarding the localization of epileptogenic activity or eloquent cortex, and be used to develop a treatment plan for surgical management of children with complicated or intractable epilepsy.

The Preoperative Evaluation of Drug-Resistant Epilepsy.

Antiepileptic drugs afford good seizure control for approximately 70% of individuals with epilepsy. Epilepsy surgery is extremely helpful for appropriate individuals with drug resistance. Since antiquity, trephination was a crude and invasive technique to manage epilepsy. The late 1800s saw the advent of a more evidence-based approach with attempts to define seizure foci and determine areas of function. Seizure localization initially required direct brain stimulation during surgery before resection. Fortunately, improved knowledge of seizure semiology and advancements in preoperative investigations have enabled epilepsy specialists to better analyze the benefit of seizure reduction versus risk of functional harm. This preoperative phase and the investigative techniques used to analyze surgical candidacy will be discussed in this article.

A direct visuosensory cortical connectivity of the human limbic system. Dissecting the trajectory of the parieto-occipito-hypothalamic tract in the human brain using diffusion weighted tractography.

The human hypothalamus is at the center of the human limbic system anatomically and physiologically. The hypothalamus plays pivotal roles in controlling autonomic responses and instinctive behaviors such as regulating fear, aggression, learning, feeding behavior, circadian rhythm, and reproductive activities. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. The inhibitory effect of the cerebral cortex on the hypothalamus in many autonomic responses, suggests the presence of direct connection between the cortex and hypothalamic nuclei. While, there is ample information to support the cortico-hypothalamic association between the prefrontal cortex and hypothalamic nuclei, the information regarding a direct posterior cortico-hypothalamic alliance is scant. The visuosensory information may be crucial for the limbic system to regulate some of the important limbic functions. Multiple dissection animal studies revealed direct posterior cortical connectivity with the hypothalamic nuclei. However, a direct cortico-hypothalamic connectivity from the parieto-occipital cortices has not been revealed in the human brain yet. Diffusion weighted imaging (DWI) may be helpful in better visualizing the anatomy of this direct posterior cortico-limbic connectivity noninvasively in the human brain. We studied 30 healthy human subjects. Using a high-spatial and high angular resolution diffusion weighted tractography technique, for the first time, we were able to delineate and reconstruct the trajectory of the parieto-occipito-hypothalamic tract.

Mercury-induced autoimmunity: Report of two adolescent siblings with Morvan syndrome "plus" and review of the literature.

Heavy metal toxicity is a global health concern. Mercury intoxication has been implicated in the etiology and pathogenesis of autoimmune disease, including Morvan syndrome. We describe two siblings with overlapping features of distinct autoimmune syndromes following accidental exposure to elemental mercury. Morvan syndrome was the predominant clinical phenotype. In addition to the characteristic anti-leucine-rich glioma-inactivated protein 1 (LGI1) and anti-contactin-associated protein-like 2 (Caspr2) autoantibodies, glutamic acid decarboxylase 65-kilodalton isoform (GAD65), and N-type and P/Q-type voltage-gated calcium channel (VGCC) antibodies were detected. Treatment with chelation therapy, glucocorticoids, and intravenous immunoglobulin was unsuccessful, but complete resolution of symptoms was achieved following treatment with rituximab. Herein, we perform an extensive review of the literature with a focus on the emerging concepts of mercury-induced autoimmunity and the role of mercury in the etiopathogenesis of autoimmune diseases of the nervous system.