Defective Glucose Transport across the Blood-Brain Barrier as a Cause of Persistent Hypoglycorrhachia, Seizures, and Developmental Delay

Vivo, Darryl C. De; Trifiletti, Rosario Rich; Jacobson, Ronald I.; Ronen, Gabriel M.; Behmand, Ramin A.; Harik, Sami I.

doi:10.1056/nejm199109053251006

Cited by 723 publications

(512 citation statements)

References 38 publications

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“…Mean GLUT1 expression and standard deviations are plotted for each sample and each operator. Results were highly correlated between operators (all R 2 > 0.98). No significant difference was found between days, operators, nor labs; results were highly reproducible (Levene's test; all p values, > 0.93).…”

Section: Resultsmentioning

confidence: 87%

A simple blood test expedites the diagnosis of glucose transporter type 1 deficiency syndrome

Gras

Cousin²,

Kappeler

et al. 2017

Annals of Neurology

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Glucose transporter type 1 (GLUT1) deficiency syndrome (GLUT1‐DS) leads to a wide range of neurological symptoms. Ketogenic diets are very efficient to control epilepsy and movement disorders. We tested a novel simple and rapid blood test in 30 patients with GLUT1‐DS with predominant movement disorders, 18 patients with movement disorders attributed to other genetic defects, and 346 healthy controls. We detected significantly reduced GLUT1 expression only on red blood cells from patients with GLUT1‐DS (23 patients; 78%), including patients with inconclusive genetic analysis. This test opens perspectives for the screening of GLUT1‐DS in children and adults with cognitive impairment, movement disorder, or epilepsy. Ann Neurol 2017;82:133–138

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Section: Resultsmentioning

confidence: 87%

A simple blood test expedites the diagnosis of glucose transporter type 1 deficiency syndrome

Gras

Cousin²,

Kappeler

et al. 2017

Annals of Neurology

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“…It is unclear whether this decreased transport is due to a primary defect in BBB function or is in response to a decreased metabolic demand from the brain. Impaired transport of glucose across the BBB has been reported by (89) in a family with seizures and mental retardation and transport is decreased in Alzheimer's disease.…”

Section: Unique Aspects Of Diabetes Mellitus In the Elderlymentioning

confidence: 99%

Endocrine and metabolic changes in human aging

Banks

Morley

2000

AGE

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"Aging and death are inevitable. We have no desire to prolong life, if such prolongation entails only added days and years of misery and suffering. On the other hand, for the first time in history, man has within his grasp potent medications of many kinds, among the more important of which are specific hormones capable of retarding if not stopping some of the undesirable features of growing old". Thomas Hodge McGavack Geriatrics 18:181-191 (1963) ABSTRACT Numerous alterations in hormonal secretion occur with aging. In general, these tend towards a disintegration of the normal cyclic secretory patterns resulting in lower total circulating levels. In addition, declines in receptors and postreceptor function further decreases the ability of the hormonal orchestra to maintain coordinated function throughout the organism. Clues to some of these agerelated changes in humans may come from the study of simpler organisms where regulatory systems are known to modulate the aging process. In particular, the interactions among the environment, hormones, and insulin receptor genes have led to new insights into the genetic control of longevity and the development of syndrome X.It is now well established, as summarized in Table 1, that the levels of many hormones are altered with aging (1). Some hormonal levels decrease, reflecting endocrine gland failure, whereas others increase, often because of end organ failure due to a decrease in receptors or a failure of postreceptor function. In the last decade, it has become popular to look to hormone replacement therapy as a mechanism to reverse the aging process. It has become popular to consider this the "hormonal fountain of youth". With aging, dysregulation of food intake accompanied by sarcopenia ('wasting of the flesh") occurs (2). A number of hormonal mechanisms are related to the physiological anorexia of aging (3). In particular, recent studies have suggested that alterations in circulating testosterone levels lead in males to increased leptin levels and thus to anorexia (4).Another area of intense interest in understanding the mechanisms of aging in humans has been the alterations that occur in glucose metabolism with aging and the role of age-related glucose end products (AGE) in accelerating the aging process (5). This area has been closely linked with the changes in nutrition that occur with aging, with insulin resistance, and more recently, with the genes that encode for the insulin receptor. It is of interest that the hormonal changes produced by dietary restriction in rodents are similar to the agerelated hormonal changes in humans, as shown in Table 2 (6). This raises the possibility that these hormonal changes are protective, i,e. slow down metabolism and thus slow down the aging process. This creates a "chicken or egg" hypothesis, illustrated in Figure 1, which asks the question: do aging changes occur because of the decline in hormones or do high hormone levels produce aging changes?This review will briefly examine the available data in each of these areas and...

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“…Another example is the metabolic condition of glucose transporter 1 deficiency, for which the ketogenic diet is the usual therapeutic approach. This can be regarded as an etiology that causes epilepsy syndromes as diverse as juvenile absence epilepsy and epilepsy with myoclonic‐atonic seizures in addition to the well‐known GLUT1 encephalopathy 13, 14, 15. Thus, one genetic cause may be associated with several epilepsy syndromes.…”

Section: Proposal For a Framework For Epilepsy Classification And Diamentioning

confidence: 99%

Classification of the epilepsies: New concepts for discussion and debate—Special report of the ILAE Classification Task Force of the Commission for Classification and Terminology

et al. 2016

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SummaryThe ILAE Task Force on Classification presents a road map for the development of an updated, relevant classification of the epilepsies. Our objective is to explain the process to date and the plan moving forward as well as to invite further discussion about the newly proposed terms and concepts. Here, we present our response to feedback about the 2010 Organization of the Epilepsies and clarify the reintroduction of the word “classification” to map out a framework for epilepsy diagnosis. We introduce some new concepts and suggest four diagnostic levels: seizure type, epilepsy category, epilepsy syndrome, and epilepsy with (specific) etiology to denote specific levels of diagnosis. We expand the etiological categories to six, focusing on those with treatment implications. Finally, we discuss the changes in terminology originally suggested and modifications in response to comments from the epilepsy community. We welcome feedback and discussion from the global epilepsy community, particularly for the new suggested terms, so that we can cement a classification that both reflects current thinking and scientific understanding and provides a dynamic, evolving framework.

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Defective Glucose Transport across the Blood-Brain Barrier as a Cause of Persistent Hypoglycorrhachia, Seizures, and Developmental Delay

Cited by 723 publications

References 38 publications

A simple blood test expedites the diagnosis of glucose transporter type 1 deficiency syndrome

A simple blood test expedites the diagnosis of glucose transporter type 1 deficiency syndrome

Endocrine and metabolic changes in human aging

Classification of the epilepsies: New concepts for discussion and debate—Special report of the ILAE Classification Task Force of the Commission for Classification and Terminology

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