Reactions 2001, p264 - 30 Mar 2024 1

Multiple drugs S

Lack of efficacy
In retrospective case series involving 2 male patients [exact ages at ADR onset not stated] were described, who exhibited lack of
efficacy during treatment with carbamazepine, phenobarbital, phenytoin, primidone, clonazepam, gabapentin, lamotrigine,
topiramate, lacosamide, valproic acid, levetiracetam, pregabalin or valproate for bilateral mesial temporal epilepsy [routes and
dosages not stated].
Case 1 : The man presented at 52 year of age was hospitalised with worsening of epilepsy highlighted by rising
epigastric sensations progressing to focal nonmotor seizures with impaired awareness (FIAS) twice per week to twice per day,
and focal to bilateral tonic-clonic (FBTC) seizures without aura occurring one to two times monthly. He had a history of viral
encephalitis, resulting in coma and convulsions at 10 months of age. He reported vagus nerve stimulator placement at 44 years of
age, which led to minor improvement in seizures.Additionally, he experienced FIAS up to three times per day, with
occasional FBTC seizures and was refractory to anti-seizure drugs (ASDs) since childhood. His medication regime
involved carbamazepine, phenobarbital, phenytoin, primidone, clonazepam, gabapentin, lamotrigine, topiramate, lacosamide and
valproic acid. On presentation, a detailed investigation was carried out which revealed left sided bilateral mesial temporal sclerosis
with temporal hypometabolism involving bilateral epileptiform discharges predominantly on the left side. A theta–delta activity was
noted in anterior bitemporal regions, along with automatisms and right dystonic posturing. He had bilateral weakness and marked
worsened perceptual reasoning than verbal skills. All findings revealed worsening of FIAS and FBTC despite treatment
with carbamazepine, phenobarbital, phenytoin, primidone, clonazepam, gabapentin, lamotrigine, topiramate, lacosamide and
valproic acid indicating lack of efficacy.Meanwhile, he was reported with previously placed depth electrodes in bilateral hippocampi
and amygdalae. His vagus nerve stimulator (VNS) was inactivated. Thus, total six FIAS were reported along with twenty subclinical
left temporal electrographic seizures. However, his clinical left temporal seizures started on day 2 of admission after his
carbamazepine, phenobarbital, phenytoin, primidone, clonazepam, gabapentin, lamotrigine, topiramate, lacosamide and valproic
acid were partially weaned, and right temporal seizures started on day 5 of admission after further titration. Thereafter, a responsive
nerve stimulator (RNS) with bilateral mesial temporal depth electrodes was implanted at 54 years of age initially leading
to decreased FBTCs frequencies but later, his clinical seizure was increased due to VNS battery depletion. However, after VNS
battery replacement, his seizures gradually subsided. On a follow-up at 58 years of age, his RNS stimulation was reprogrammed to
bilateral detection with unilateral stimulation. He was then treated with levetiracetam, which resulted in significant improvement.
Following after 1 year, he remained seizure free for 6 months and reported FIAS less than once per week.
Case 2 : The man presented with worsening of epilepsy highlighted by flushing and drooling FIAS, and severe memory
disturbance occurring every 2 days. He had a history of hypoxic brain injury secondary to narcotic drug overdose, diagnosed
at 17 years of age. Additionally, he reported persistent seizures despite his treatment with levetiracetam, lamotrigine, clonazepam,
pregabalin, valproate, and lacosamide indicating lack of efficacy. On presentation, a detailed investigation revealed bilateral
hippocampal atrophy with architecture loss. Thus, bilateral symmetric placement of one lateral temporal and three subtemporal
strips was performed. Thereafter, due to independent bitemporal seizures, an VNS was implanted at 22 years of age, leading to
improvement. Later, his seizure frequency remained consistent, leading to significant memory decline. Thus, depth electrodes were
placed in bilateral hippocampal, leading to diagnosis of bilateral independent bilateral mesial temporal seizures. Therefore, an RNS
with two bi-hippocampal leads was implanted followed by RNS treatment.Following after, placement his seizures substantially
decreased however, VNS was turned off during an office visit because of device malfunction. He requested to deactivate both the
devices due to discomfort. On a follow-up, worsening of clinical seizure was reported secondary to prior VNS deactivation. His RNS
was readjusted with increased current, leading to remarkable improvement in frequency of seizures.
Khankhanian P, et al. Combined VNS-RNS Neuromodulation for Epilepsy. Journal of Clinical Neurophysiology 39: E5-E9, No. 2, Feb 2022. Available from: URL: 10.1097/
WNP.0000000000000870 803849980