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Advanced Neurology Seizures and CKD

mechanism involving the kidneys, primarily the renin- shown to increase blood viscosity, peripheral vascular
angiotensin-aldosterone system. Excess sodium and fluid resistance, and blood pressure, further aggravating the
retention in CKD may trigger autoregulation. In response existing predisposition to hypertension. This is the likely
to excessive blood flow, tissue arterioles vasoconstrict explanation of ESA-related seizures [55,71,72] .
and increase peripheral vascular resistance, activating Many medications prescribed in clinical practice
the renin-angiotensin-aldosterone system, leading to display effects on seizure thresholds through direct and
disruption in the regulation of blood pressure [60-62] . indirect effects on the CNS. CKD and dialysis alter the
If hypertension persists, multiple organs in the body may distribution, metabolism, and clearance of medications
be affected, including the brain (which normally maintains from the body. Patients with CKD are therefore more
its blood flow within a narrow perfusion pressure window susceptible to the effects of these medications and their
of 60 – 150 mmHg) [63,64] . With persistent, uncontrolled metabolites, and are more likely to have a lower seizure
hypertension, the cerebral arterioles undergo structural threshold than individuals without CKD and/or those not
changes such as degeneration of elastin fibers, depositions receiving dialytic treatments [16,73] . Dosing, time-course
of collagen, and calcification of vessels [65,66] . These of drug action, serum drug concentration, and systemic
changes lead to arterial stiffness, exacerbating cerebral reactions with concurrent pathophysiologies and other
hypertension, and further aggravating local neurovascular medications administered determine the tendencies of
[74]
damage . These damaged cerebral arterioles are no longer medication-associated seizures during dialysis .
[65]
able to appropriately respond to acute changes in blood Complications during dialysis, especially dialysis
pressure, thus impairing autoregulation, and threatening disequilibrium syndrome (DDS) and air embolism, may also
the maintenance of this narrow pressure window [65,66] . trigger seizure activity. DDS occurs during or immediately
Raised intracerebral blood pressure may then cause after dialysis. Symptoms range from mild muscle cramps,
fluid to diffuse across the capillary membranes into the anorexia, nausea, and headache to confusion, seizures,
brain parenchyma, leading to cerebral edema, increased coma, and death . DDS has been reported predominantly
[75]
intracranial pressure and, potentially, seizures [65,66] . in HD patients. Risk factors include over-rapid and excessive
2.6. PRES dialytic treatment, underlying severe metabolic acidosis
and electrolyte abnormalities, age and frailty, history of pre-
PRES is an under-recognized cause of acute symptomatic existing CNS disease, and previous seizures . The most
[76]
seizures [67,68] . Its cause is multifactorial, including CKD- likely pathogenesis is the rapid removal of urea from the
associated hypertensive disease; rheumatological conditions extracellular compartment, creating an osmotic gradient
such as lupus and vasculitis; genetic conditions such as leading to a net flow of water into brain cells with resultant
tuberous sclerosis; thrombotic diseases including thrombotic transient cerebral edema (supported by measurements of
microangiopathies; medication and immunosuppression- urea in blood and CSF, which demonstrate a substantial
induced PRES . The underlying pathogenesis of PRES gradient causing a shift in water movement in the brain) [77,78] .
[69]
remains unclear and probably depends on the etiology . An increase in intracellular brain solutes (myoinositol,
[70]
Failure of vascular autoregulation resulting in extravasation glutamine, and taurine) may also contribute toward this
and vasogenic edema in the posterior cerebral circulation osmotic disequilibrium .
[78]
appears to be a central concept in most theories of
pathogenesis [68,70] . When hypertension is not involved, Air embolism is a rare but important complication of
endogenous stimulants or exogenous toxins causing HD. Because patients are seated upright during dialysis,
cerebral endothelial dysfunction drive derangements in inappropriately infused air rises into the cerebral venous
the autoregulation response [68,70] . Activation of cerebral system, blocking the venous return and potentially leading to
[79]
vasopressin receptors is also thought to play a role in the loss of consciousness, seizure, and death . This complication
pathogenesis of PRES [68,70] . has become rare with modern dialysis machines, which have
inbuilt air detectors, but is still recognized, for example, with
2.7. Erythropoietin and medication-induced vascular access malfunction .
[80]
seizures in CKD, dialysis, and transplantation
Aluminum neurotoxicity is a rare condition associated
Anemia in CKD stems primarily from a reduction in with a chronic dialysis encephalopathy, dialysis-associated
endogenous erythropoietin production from diseased dementia, and increases seizure activity [81,82] . Aluminum
kidneys. It is a recognized complication of CKD and is affects the expression and processing of the beta-A4 (βA4)
treated with iron, Vitamin B12 and folate supplementation, precursor protein, leading to an extracellular deposition
and erythropoietin-stimulating agents (ESAs). High doses of amyloidogenic βA4 protein in senile plaques [83,84] .
of ESAs and over-rapid correction of anemia have been Aluminum-associated complications during dialysis have

V 5 5 https://doi.org/10.36922/an.314
Volume 2 Issue 2 (2023) olume 2 Issue 2 (2023)
https://doi.org/10.36922/an.314