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Advanced Neurology Seizures and CKD

lower seizure thresholds when administered to patients in advanced CKD [121,122] . In patients with small-vessel
on dialysis . Withdrawal of benzodiazepines and vasculitis, more aggressive control of disease activity with
[55]
amphetamines needs to be carefully managed [112] . newer agents, such as biologic immunosuppressives, may
Stopping the dialysis treatment is indicated in both be indicated to reduce the risks of sustaining ischemic and
DDS and air embolism-induced seizures. In DDS, hemorrhagic injury [123,124] .
subsequent dialysis should be phased, incremental, and For those receiving dialysis, control of cardiovascular
closely monitored. If air-embolization is suspected, then risk factors and careful consideration of prophylactic
the patient should be placed in the head down and left anti-platelet and anticoagulation measures are important.
lateral decubitus position, pending transfer to intensive Ischemic stroke presents 4–10 times more frequently in
care [75,79,113] . dialysis patients compared to the general population [125] .
Adequacy of dialysis needs to be maintained to minimize
Post-transplant immunosuppression regimes should
be regularly reviewed and adjusted to minimize adverse coagulopathy and uremic platelet dysfunction, which
are believed to be involved in subdural hematoma and
risks of TMA (short-term), CNS infections (short-term), intracerebral hemorrhage [126,127] . Controlling hypertension
and lymphoma (longer-term) developing with these is also important [128] .
medications. Thrombotic syndromes are mostly observed
in the first 2 months following kidney transplantation 4. AED options for the treatment of seizures
and primarily caused by immunosuppressive treatments in CKD
including CNIs, rapamycin inhibitors, and anti-CD3
monoclonal antibodies [110,111,114] . Meticulous monitoring of AEDs may be recommended for CKD patients who
CNI toxicity (e.g., cyclosporine and tacrolimus toxicity) is have experienced unprovoked or multiple provoked
[16]
important, as this is a significant cause of seizures developing seizures, depending on the risk of seizure recurrence .
post-transplantation [85,115,116] . Monitoring requires a holistic It is encouraging that the choice of AEDs has increased
evaluation of each individual’s clinical progression whilst over recent decades. Many AEDs (i.e., those of a newer
on CNIs. Serum levels are not necessarily valid indicators of generation) undergo renal clearance [129,130] . There appears to
neurotoxicity, since symptoms may develop at therapeutic be a common misconception that the etiology of a seizure is
levels . Prompt correction of hypomagnesemia, which the major determinant of AED selection for an individual.
[55]
may occur more frequently with regular CNI use, is In fact, age, comorbidities, concurrent medications, seizure
recommended [106] . Dosing and frequency of other seizure- type (e.g., focal or primary/secondary generalized, including
inducing medications administered post-transplant, such tonic-clonic, absence, myoclonic, and atonic seizures),
as rituximab, mTOR inhibitors (i.e., sirolimus), intravenous eGFR progression, history of renal adverse reactions,
immunoglobulin, and high-dose methylprednisolone and patient lifestyle/medication preferences play more
treatment also need to be monitored closely in transplanted important roles in AED-related treatment decisions [9,16,55] .
populations . Treatment of post-transplant infections In most instances, AED(s) are started in patients at risk
[55]
with carbapenems, quinolones, cefepime, and penicillin of further unprovoked seizures, while simultaneously
should be undertaken with caution in patients at high investigating the cause of the index seizure(s).
risk of seizures [117,118] . Early identification with imaging There are important principles to recognize when
and referral for multi-disciplinary discussion (involving managing AED prescriptions for CKD patients presenting
oncology and hematology specialties) is indicated for with seizure(s). If a parent drug or active metabolite is
suspected cases of CNS lymphoma [119,120] . excreted substantially in the urine, dose reduction of the
Supportive care for seizures induced by renal TMAs AED is likely to be required [9,130] . What defines substantial
(e.g., TTP, HUS, and aHUS) includes aggressive blood within this context remains subject to discussion. United
pressure control with ACE inhibitors or angiotensin States (US)-based recommendations suggest 30% as a
[9]
inhibitors, plasma exchange, and eculizumab. Specialist cutoff to consider AED dose reduction . For kidney
liaison is advised and intensive care may be required [114] . failure patients receiving HD, dialyzability of an AED
depends on its protein binding properties and molecular
3.8. Non-antiepileptic treatment of cerebrovascular size . Therefore, clearance of an AED by HD may require
[9]
event-inducing seizures post-HD dosing . Highly protein-bound AEDs include
[9]
There are strategies that can be considered to prevent phenytoin and valproic acid [130,131] .
ischemic or hemorrhagic strokes in patients with The apparent volume of distribution increases in
advanced CKD. Adjustment of anticoagulation may be uremic states [131] . This phenomenon is primarily caused
required, given the increased risk of cerebral hemorrhage by hypoalbuminemia, but the accumulation of drug

https://doi.org/10.36922/an.314
Volume 2 Issue 2 (2023) olume 2 Issue 2 (2023)
V 9 9 https://doi.org/10.36922/an.314