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Advanced Neurology Seizures and CKD

reduced significantly with the reduction in aluminum- to be 5–30 times higher than in those without kidney
contaminated dialysate and the phasing out of aluminum- disease [96,97] . Seizures following these cerebrovascular events
based phosphate binders . are not uncommon, and depend on factors such as severity,
[82]
Seizure onset following kidney transplantation size of infarct, hemorrhagic transformation, and site
[98]
is predominantly caused by complications of (cortical as opposed to subcortical) . Subdural hematomas
immunosuppressant use, thrombotic syndromes, and the and intracerebral hemorrhages are more common
development of post-transplant infections and malignancies. amongst those receiving HD, because of anticoagulation,
[99,100]
Calcineurin inhibitor (CNI) medications such as cyclosporine coagulopathy, and uremic platelet dysfunction .
and tacrolimus have the potential to exhibit several neurotoxic Cerebrovascular event-inducing seizures are believed
side effects including cerebellar ataxia, postural tremor, and to arise following a cascade of events arising from the area
peripheral neuropathy, as well as induce seizure activity [85,86] . of cerebral insult. Reduced blood flow in the brain causes
The risks of seizure activity are increased in the presence of further global cerebral hypoperfusion and disruption
other comorbidities, including electrolyte abnormalities (for of intracranial pressure autoregulation processes [101] .
example, tacrolimus may exacerbate hypomagnesemia) and Following the accumulation of sodium and calcium,
PRES . Other medications prescribed as part of a post- seizure thresholds are lowered by depolarization of
[86]
transplant immunosuppression regime (rituximab, mTOR transmembrane potentials and other calcium-medicated
inhibitors, intravenous immunoglobulin, and high-dose effects [101] . Glutamate released as a consequence of cell
methylprednisolone therapy) may also have neurotoxic death contributes to further intracranial metabolic
effects, but less frequently than CNIs . dysfunction, which also reduces the seizure threshold [101] .
[87]
Thrombotic microangiopathy (TMA) syndromes,
which occur following kidney transplantation, include 3. Non-AED treatment strategies to prevent
thrombotic thrombocytopenic purpura (TTP), hemolytic and manage seizures in CKD
uremic syndrome (HUS), and atypical HUS. Neurological When managing a CKD patient who is at increased
complications, including seizures, can be associated with risk of seizures, the clinician should address potential
TMA . metabolic and/or physiological factors, before considering
[88]
[9]
Because of the requirement for regular AED prescription . In scenarios where seizure has
immunosuppression, kidney transplant patients are more occurred, non-AED alongside AED treatment (if this is
susceptible to CNS infections. Meningitis, encephalitis, indicated) reduces the risk of further seizure episodes [9,16] .
myelitis, and brain abscess are uncommon during the early We describe potential non-AED treatment strategies
post-operative periods, but the risks increase with time and for the various etiologies of CKD-associated seizures
the burden of immunosuppression, especially involving (Table 2) [55,57,59,71,75,78,79,102-128] .
opportunistic infections (human immunodeficiency virus, 3.1. Uremic encephalopathy
hepatitis C, herpes simplex virus, cytomegalovirus, Epstein-
Barr virus, parvovirus, Mycobacterium tuberculosis, Listeria Prevention or initial management of uremic encephalopathy
monocytogenes, Cryptococcus neoformans, Pneumocystis should focus on addressing any severe and untreated
jirovecii, and Mucor spp.) [89,90] . These infections may also uremia. Gradually incremental dialysis treatments, or
contribute to the onset of TMAs . Malignancies, such as hemofiltration on the intensive care unit, may be indicated
[91]
CNS lymphoma, also increase in frequency with long-term if seizures follow the onset of uremic encephalopathy [102] .
immunosuppression. CNS lymphoma is the most common Neurological symptoms may take days or even weeks to
cause of CNS-related malignancy in kidney transplant abate following initiation of dialysis [102] .
recipients [92,93] . Primary CNS lymphoma has been noted to
develop as early as 3-month postoperatively . The tumor 3.2. AKI-on-CKD seizures
[94]
itself, depending on size, location, and rate of progression, Preventive measures and management strategies for
can cause focal damage, infiltration of surrounding cerebral AKI-on-CKD seizures differ according to the etiology
structures, and/or hydrocephalus due to obstruction of of kidney dysfunction leading to the seizure. Serum
CSF flow, all of which lead to raised intracranial pressure electrolytes (K , Ca . Mg ) and glucose levels should be
2+
2+
+
[95]
and the risk of seizures . checked. Intravenous glucose, electrolyte supplementation,
and/or thiamine may be indicated during AKI
2.8. Cerebrovascular event-inducing seizures management . Close monitoring for pre-eclampsia in
[78]
The incidence of cerebrovascular events (i.e., ischemic and pregnant CKD patients is essential, to prevent the onset and
hemorrhagic strokes) in CKD patients has been reported exacerbation of eclamptic seizures alongside consideration
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