Cerebral edema in children with diabetic ketoacidosis: vasogenic rather than cellular?

Abstract

Cerebral edema (CE) is accumulation of water in the intracellular or extracellular spaces of the brain. Vasogenic edema occurs when there is breakdown of the tight endothelial junctions of the blood-brain barrier (BBB), leading to extravasation of intravascular protein and fluid into the interstitial space of the brain. In cellular edema the BBB remains intact and there is swelling of astrocytes with corresponding reduction in extracellular space. In this review we bring together clinical evidence from neuropathology and cerebral magnetic resonance (MR) studies in pediatric patients presenting in diabetic ketoacidosis (DKA), and use applied physiology to understand whether CE complicating DKA is vasogenic, rather than cellular in origin. Because the first-line of defense against CE is the interface between the intravascular compartment and the extracellular space in the brain much of the focus in this review is the BBB. The principal pathologic finding in fatal cases is perivascular with BBB disruption and albumin extravasation, suggesting increased vascular permeability. DKA induces an inflammatory response and the mechanism of BBB transcellular permeability may be an immunologic cascade that disrupts tight junctions. The principal MR finding in subclinical cases of CE is vasogenic rather than cellular edema. We propose that the following physiology be considered when treating cases: bolus dose of intravenous mannitol may result in fall in serum sodium concentration, and therefore clinical worsening. Failure to respond to mannitol should prompt the use of 3% hypertonic saline (HS). Bolus dose of intravenous 3% HS is expected to effect vasogenic edema provided that the reflection coefficient is close to 1. Failure to respond to 3% HS should prompt the use of mannitol.

Measurement of corneal thickness, optic nerve sheath diameter and retinal nerve fiber layer as potential new non-invasive methods in assessing a risk of cerebral edema in type 1 diabetes in children

“…The precise pathological mechanism of CE development has not yet been fully understood. Currently, the most popular hypotheses are related to astrocyte edema caused by a decrease in extracellular volume (cellular edema) and breaking down of the blood–brain barrier caused by an increasing permeability of endothelial vessels (vasogenic edema) or an increase in proinflammatory cytokines or cerebral cell anoxia also associated with an increase in hypocapnia [2, 4–6]. The main risk factors of the development of CE in patients with DKA include: reduction of extracellular osmolarity, intensification of hypocapnia and metabolic acidosis, degree of dehydration, variability of sodium concentration during therapy, and iatrogenic errors mainly related to the supply of sodium bicarbonate to compensate acidosis [1, 4, 7].…”

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

“…Brain oedema is the accumulation of excess fluid in the brain, either in the intracellular (cytotoxic oedema) or extracellular compartments (vasogenic oedema) [123], though these two types of fluid accumulation rarely occur independently (e.g., certain pathologies including diabetes, stroke, and traumatic brain injury may involve both vasogenic and cytotoxic oedema [55,175]). Cytotoxic (cellular) oedema can result from toxic agents (including many in common use such as dinitrophenol (weight loss agent), hexachlorophene (disinfectant), and organophosphates including insecticides [28]), ischaemic stroke, or hypoxia; in cytotoxic oedema, the BBB may stay intact, but disturbance of cellular metabolism impairs ion transport in glial cell membranes, leading to cellular retention of sodium and water, and cell swelling especially in astrocytes in gray and white matters.…”

Subclinical cerebral edema in diabetic ketoacidosis in children

“…In the study period of 1982‐1997, Marcin et al treated most of their cerebral edema patients with GCS score between 11 and 15 with mannitol therapy. Treatment of cerebral edema in DKA with hyperosmolar agents is recommended as the pathophysiology of cerebral edema is not very well understood . An ischemic and/or vasogenic process is proposed to play a role in the genesis of DKA related cerebral edema.…”