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Advanced Neurology Seizures and CKD

potentially neurotoxic and pro-inflammatory . Instability Studies have shown that lowering extracellular
[31]
of acid-base homeostasis may be further exacerbated by concentrations of calcium and/or magnesium results in
the build-up of anions such as chloride and phosphate . depolarization of neuronal membranes, thereby increasing
[32]
These pathophysiological insults arising may eventually excitability and likelihood of epileptiform activity [46,47] .
lead to breakdown of the normal blood-brain barrier Magnesium has a membrane-stabilizing effect.
[33]
function, resulting in seizure activity . Hypomagnesemia inhibits sodium and potassium-ATPase
activity and encourages greater interaction between
Eclamptic seizures may occur in pregnancy with AKI.
Those with pre-existing CKD are at greater risk [34,35] . magnesium and NMDA receptors; this further exaggerates
dysregulation of potassium levels and predisposes the
Placental hypoperfusion is thought to be a key feature in neuronal membrane to further instability [48,49] . Disruption
the development of eclampsia . This is typically associated to the mineral metabolic pathways involving calcium,
[36]
with increased sensitivity of the maternal vasculature parathyroid hormone, phosphate, and Vitamin D is
to agents causing constriction of small arteries, thereby commonly seen in CKD and is recognized to result in
leading to reduced blood flow to multiple organs [36,37] . CKD neurological effects, although its causative role in seizures
and hypertension may predispose to vascular dysfunction requires further investigation . The role of parathyroid
[50]
before pregnancy; therefore, further insults from placental hormone is potentially interesting as it can cross the
hypoperfusion increase the risk of pre-eclampsia [36-38] . This blood-brain barrier and facilitate calcium influx, leading
may progress to full-blown eclampsia if not appropriately to cortical excitability [51,52] .
managed.
Iatrogenic hypocalcemia in CKD is also a known risk.
Other pathophysiological mechanisms which impede
placental blood flow in pregnancy include the activation of Individuals receiving plasma exchange may experience
hypocalcemia, arising from chelation caused by sodium
coagulation cascade resulting in microthrombi formation, citrate . In the hemodialysis (HD) cohort, patients may
[53]
and increased vascular permeability resulting in shift become symptomatically hypocalcemic because of reduction
of extracellular fluid from blood circulation to cellular in ionized calcium caused by over-rapid correction of
interstitial spaces . The effects of these pathophysiological acidosis .
[39]
[54]
mechanisms are systemic, affecting the kidneys, lungs, and
liver, often before cerebral dysfunction . 2.4. Seizures caused by hypo/hyperglycemia
[40]
2.3. Seizures caused by electrolyte disturbances Diabetic kidney disease is the most prevalent cause of
CKD progressing to established kidney failure. These
Electrolyte disturbances, usually involving sodium, patients usually receive glycemic-lowering medications,
potassium and calcium, play a major role in causing as part of their diabetes mellitus management, which can
disruption to membrane depolarization, thereby resulting potentially result in significant hypoglycemia . Iatrogenic
[55]
in seizure activity. hypoglycemia may lead to increased net transport of
Dysregulation of serum sodium concentration is sodium and potassium into the brain, resulting in the
usually caused by abnormalities in water homeostasis, rise of brain osmolality [56,57] . Clinicians should be aware
resulting in abnormal alterations to the relative ratio of contraindications and/or dose adjustments of these
of sodium: body water . Hyponatremia is the most commonly prescribed classes of glycemic-lowering
[41]
common cause of seizure associated with electrolyte medications. First-generation sulfonylureas should be
disturbance [16,42] . A relative excess of body water in avoided in the setting of CKD, whilst cautious use of second-
[58]
relation to sodium is observed in hyponatremia-induced generation sulfonylureas is reasonable . Metformin
seizures . The initial neurological response to acute and glucagon-like peptide 1 (GLP-1) agonists are not
[43]
hyponatremia is an increased interstitial pressure in the recommended when eGFR < 30 mL/min/1.73 m 2[58] . Dose
brain, causing shunting of extracellular fluid and solutes adjustments for dipeptidyl peptidase-4 (DPP-4) inhibitors
[58]
from the interstitial spaces into cerebrospinal fluid (CSF), are indicated for advancing CKD .
and hence into the systemic circulation . An efflux of Seizures may also result from poorly controlled
[43]
sodium, potassium, and chloride from brain cells follows diabetes. Non-ketotic hyperglycemia resulting in focal
thisand the rapid decrease in tonicity overwhelms volume motor seizures is not uncommon in the elderly, although

regulatory mechanisms in the CNS, leading to cerebral the causative mechanisms remain unclear .
[59]
[43]
edema . Affected individuals are incapable of correcting
acute abnormalities resulting from hyponatremia; the size 2.5. Seizures caused by uncontrolled hypertension
of the osmolar gradient correlates with the likelihood of Hypertension is common in CKD patients. The regulation
developing an acute seizure [44,45] . of blood pressure is an intricate and integrated homeostatic

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