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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5203_Библиотеки_им_академика_М_И_Перельмана.pdf
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the United States followed in August 2009. In 2010, vigabatrin was recommended
as a rst-line therapy for infantile spasms associated with tuberous sclerosis. Acting
as an analog of GABA, vigabatrin exhibits specicity in binding to GABA aminotransferase, irreversibly increasing the GABA concentration in the brain and thereby
exerting an antiepileptic effect. In 2023, Tierradentric-Garcia and colleagues
employed magnetic resonance technology to investigate the effects of vigabatrin on
brain damage in epilepsy patients [568]; in 2024, Kuchenbuch M etal. summarized
the results of the use of vigabatrin in the treatment of infantile spasm, deepening
people’s understanding of the use of vigabatrin in the treatment of epilepsy [569].
Observational Research ontheTreatment ofEpilepsy
From 2012 to 2018, the National Infantile Spasm Association conducted a prospective study at 23U.S. centers to compare the efcacy of various initial treatments for
infantile spasms in children aged 2–24months. Zachary M.Grinspan etal. utilized
propensity score weighting and in-center correlation generalized estimation equations to address treatment selection bias. The study revealed the following failure
rates without treatment: adrenocorticotropin (ACTH) 88/190 (46%), oral steroids
42/95 (44%), vigabatrin 32/87 (37%), and nonstandard treatment 4/51 (8%).
Transitioning from use of oral steroids to that of ACTH was not predicted to impact
remission rates (44% observed, estimated 44% [95% condence interval 34–54%]).
However, switching from nonstandard therapy to ACTH therapy was estimated to
increase the response rate from 8% to 39% (17–67%), and transitioning to oral steroid therapy was expected to increase the response rate from 8% to 38% (15–68%).
Although statistically insignicant, switching from vigabatrin to ACTH (29–42%
[15–75%]), from vigabatrin to oral steroids (29–42% [28–57%]), and from nonstandard treatment to vigabatrin (8–20% [6–50%]) demonstrated substantial estimated
effects. Notably, among patients treated with vigabatrin, those with tuberous sclerosis (TSC) exhibited a greater response rate than did the other patients (62% vs. 29%;
p < 0.05). The researchers concluded that use of ACTH and oral steroids offer
advantages over nonstandard treatment for initial infantile spasm therapy. Although
the estimated effectiveness of vigabatrin fell between that of ACTH/oral steroids
and that of nonstandard treatment, the statistical condence in the sample was inadequate. Vigabatrin showed optimal efcacy against TSC.This study provides Class
III evidence indicating that use of ACTH or oral steroids outperforms nonstandard
treatment for children with new-onset infantile spasms [570].
Addition ofTreatment forRefractory Epilepsy
In a study conducted by Taylor N.Gatson etal., the terms “vigabatrin” and “sabril”
were utilized to search English literature spanning from 1999 to 2023, in an aim to
identify relevant studies and review articles. The objective of this study was to
examine the pharmacokinetics, efcacy, and adverse reactions associated with
sabril and its role in treating refractory focal involuntary seizures in adults. A
double- blinded, placebo-controlled multicenter study conducted in 2000 involving
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90 adult patients revealed that 48% of those treated with vigabatrin experienced a
50% or greater reduction in the frequency of complex partial seizures, compared to
26% of those receiving placebo. The study also revealed that vigabatrin was well
tolerated by 72.4% of patients and had common side effects, including drowsiness,
dizziness, headache, and fatigue. Subsequent studies have highlighted the signicant risk of visual eld loss associated with vigabatrin, suggesting that it may only
be an option for refractory patients. Despite these potential risks, studies have indicated that adult patients tend to continue with long-term vigabatrin use. Vigabatrin
serves as an adjunctive treatment for patients aged at least 10years with intractable
complex partial seizures who are unresponsive to alternative therapies. Numerous
clinical trials have demonstrated its efcacy in reducing seizure frequency when
used alongside existing treatments. However, cautious monitoring for adverse reactions, particularly during prolonged use, is imperative, with discontinuation recommended upon the occurrence of serious side effects [571].
Treatment ofEpilepsy Syndrome
West syndrome is a prevalent form of epilepsy in infants and young children, often
leading to signicant neurodevelopmental challenges. A panel of pediatric neurologists and epileptologists led by SUVASINI SHARMA and colleagues collaborated
to establish guidelines for the management of West syndrome. Through focused
group discussions supplemented by email and phone interactions, the experts
reached a consensus based on the reviewed evidence. When uncertainties arose, the
Delphi consensus method was employed. The nalized guidelines underwent expert
review for approval. The diagnosis of West syndrome relies on clinical identication through history or home video observation of spasms, coupled with EEG ndings indicating arrhythmia or variants. Brain magnetic resonance imaging is the
preferred neuroimaging modality, with the use of additional tests, such as genetic
and metabolic screenings, contingent upon clinical and radiological results.
Hormone therapy, involving either corticotropin or oral steroids, is recommended
for patients with conditions other than tuberous sclerosis, while vigabatrin is preferred for patients with tuberous sclerosis. Studies have shown comparable efcacy
and adverse reaction proles for adrenocorticotropin and high-dose prednisolone in
West syndrome treatment. Second-line options include ASMs (vigabatrin, sodium
valproate, topiramate, zonisamide, nitrazepam, and clobazam), ketogenic diet therapy, and epilepsy surgery [572].
In a related study by Ramantani G etal., a literature review spanning from 2014
to July 2020 was conducted to update infantile spasm (ISS) management practices.
Their recommendations build upon evidence from previous guidelines and current
research ndings. Early electroencephalogram (EEG) assessment is advised when
ISS is suspected, followed by immediate initiation of treatment upon conrmation.
The response to rst-line therapy should be evaluated clinically and via EEG after
14days. First-line therapy consists of hormone-based monotherapy (adrenocorticotropin or prednisolone) or a combination of hormones and vigabatrin. Vigabatrin is
recommended for children with tuberous sclerosis or contraindications to hormone
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therapy. If rst-line treatments fail, second-line options, including ketogenic diet
therapy, sulthiame, topiramate, valproic acid, zonisamide, or benzodiazepines,
should be considered. Early evaluation for epilepsy surgery is recommended for
refractory patients, especially those with focal brain injury. Additionally, providing
comprehensive information to parents about the disease, medication efcacy,
adverse effects, and available support options is crucial, as is regular follow-up care
[573]. Xu, Z etal. conducted a systematic review and meta-analysis to assess the
efcacy of vigabatrin (VGB) in treating infantile epileptic spasm syndrome (IESS).
The authors systematically searched the PubMed, Embase, Web of Science,
MEDLINE, and Cochrane Library databases for reports of relevant randomized
controlled trials (RCTs) and observational studies (OSs) investigating VGB for
IESS.The primary outcome of this meta-analysis was the cessation of epileptic
spasms (ES). Their analysis included ve RCTs and nine OSs comparing the efcacy of VGB and hormonal monotherapy for IESS.A meta-analysis of the ve
RCTs revealed that hormonal monotherapy was signicantly more effective than
VGB monotherapy in patients with newly diagnosed IESS (OR = 0.37, 95%
CI=0.20–0.67). The results from the meta-analyses of the nine OSs were consistent
with those of the RCTs (OR = 0.61, 95% CI = 0.43–0.85). VGB demonstrated
greater efcacy in patients with tuberous sclerosis complex (TSC) than in those
with other etiologies (5 OS, OR=5.59, 95% CI=2.17–14.41). However, there was
no signicant difference in the effectiveness of VGB combined with hormone therapy compared to that of hormone monotherapy for IESS (two RCTs, OR=0.75,
95% CI=0.09–6.45). The researchers concluded that hormonal monotherapy was
superior to VGB monotherapy for non-TSC-associated IESS, whereas VGB was
preferred for patients with IESS due to TSC.Additionally, combining VGB with
hormone therapy did not signicantly improve the control rate of ES compared to
hormone monotherapy [574].
Application ofVigabatrin inSpecial Epileptic Populations
Katarzyna Kotulska etal. conducted a multicenter study involving 94 infants with
tuberous sclerosis complex (TSC) who were monitored with monthly video electroencephalography (EEG) and who received vigabatrin as routine antiepileptic therapy. Treatment commenced either after the rst EEG or clinical seizure or as
prophylaxis when epileptiform EEG activity was detected before a seizure. In a
randomized controlled trial (RCT) conducted at six sites, participants were randomly assigned to treatment or control groups at a 1:1 ratio. At four sites, the treatment distribution was xed, constituting an open-label trial (OLT). Subjects were
followed until 2years of age, with the primary endpoint being the time to the rst
clinical episode. The present study revealed that 54 subjects exhibited epileptiform
EEG abnormalities before experiencing seizures. Compared with conventional
treatment, prophylactic treatment signicantly prolonged the time to the rst clinical attack. At 24 months, pooled analyses indicated that preventive treatment
reduced the risk of clinical seizures, drug-resistant seizures, and infantile spasms.
No adverse events were associated with preventive treatment. Researchers have
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concluded that prophylactic use of the antiseizure medication vigabatrin is safe and
has the potential to alter the natural course of TSC-related seizures, thus mitigating
the risk and severity of epilepsy [575]. In a study by Sufang Lin etal., the efcacy
and safety of vigabatrin in treating focal epilepsy associated with tuberous sclerosis
were evaluated. The review included patients with focal epilepsy and tuberous sclerosis treated with vigabatrin over an 8-year period at a children’s epilepsy center.
Among the 85 patients, 20 (23.5%) achieved seizure freedom at 12months, 45
(52.9%) achieved a favorable response (≥50% reduction in seizures), and 20
(23.5%) were unresponsive to treatment. Patients who became seizure-free had a
greater median age at seizure onset than did those in the responsive and nonresponsive groups. Additionally, fewer patients in the seizure-free group exhibited the largest nodular calcications, although the presence of nodular calcications did not
differ signicantly between the groups. In children with tuberous sclerosis, vigabatrin was more likely to result in seizure freedom in those with focal seizures beginning in infancy and without calcications within the largest tubercles [576].
Epileptic spasm is a devastating form of early infantile epileptic encephalopathy
(EIEE) with multiple etiologies. Early diagnosis and shorter treatment preparation
times are critical for terminating seizures and optimizing neurodevelopmental outcomes. Genetic testing has become an integral part of epilepsy treatment, directly
guiding management and family planning and playing a role in the discovery of new
targeted treatments. Neuronal Differentiation Factor 2 (NEUROD2) variants have
recently been found to be the cause of neurodevelopmental disorders (NDDs) and
EIEE with unique characteristics. Kullasate Sakpichaisakul etal. described a case
of a Southeast Asian female infant who presented with systemic developmental
delays and epileptic spasms shortly after birth. Whole exome sequencing identied
a novel de novo heterozygotic pathogenic NEUROD2 variant, p.E130Q.Pretreatment
EEG showed multifocal independent spikes primarily in two posterior brain regions,
which signicantly improved with vigabatrin and high-dose prednisolone treatment. However, several relapses occurred after the discontinuation of ASMs.The
researchers suggested that the epileptic spasms associated with the novel NEUROD2
pathogenic variant responded well to combination therapy with vigabatrin and highdose prednisolone, indicating the potential benets of using such a regimen for
treating NEUROD2-associated neurodevelopmental disorder syndrome [577].
Among children with infantile spasm syndrome (ISS), those with trisomy 21
(T21) and those with normal development and no clear cause at the time of onset
(previously called “idiopathic”) are expected to have relatively favorable outcomes. Anita N.Datta etal. aimed to determine differences in treatment response,
recurrence, and subsequent epilepsy between two groups of children with infantile spasms (ISs) treated with vigabatrin as rst-line therapy. The study revealed
no signicant differences in age of onset, sex distribution, or treatment lag
between the two groups. However, the T21 group required a greater average number of antiepileptic treatments, experienced more relapses, and had a greater risk
of subsequent seizures than did the control group. These ndings suggest that
vigabatrin may be less advantageous than steroids as a rst-line treatment for T21
and ISS patients [578].
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Viral encephalitis (VE) or bacterial meningoencephalitis (BME) in early childhood can cause brain damage and neurological sequelae, including seizures.
Postencephalitic epilepsy (PEE), characterized by epileptic spasms (ESs), is a rare
but serious condition. There is an urgent need to develop new methods to assess the
characteristics of these children and select appropriate treatments. Lin Wan et al.
conducted an observational study of 20 patients with postencephalitic epilepsy
(PEE) characterized by epileptic spasms (ES) following viral encephalitis (VE) or
bacterial meningoencephalitis (BME). Patients were followed for more than
12months and their prognoses were analyzed. The study revealed that children with
PEE with ES were more likely to develop drug-resistant epilepsy (DRE), and the
prognosis was worse for VE patients than for BME patients. Further research is
needed to evaluate the efcacy of treatments such as adrenocorticotropin (ACTH),
a ketogenic diet (KD), vigabatrin, and vagus nerve stimulation (VNS) therapy in
these patients [579].
The Efcacy andSafety ofVigabatrin asthePreferred Treatment forEpilepsy
The use of vigabatrin in the treatment of patients with infantile spasm (IS) and
tuberous sclerosis (TSC) has been extensively studied. Infantile spasm (IS) is an
epileptic encephalopathy with a generally poor prognosis, with most patients
exhibiting psychomotor delay or intractable epilepsy. However, early and
aggressive treatment is associated with better response rates and outcomes,
especially in patients with idiopathic IS.Dina Amin Saleh etal. conducted a
retrospective chart review to investigate the different treatment modalities and
outcomes of patients diagnosed with IS at a pediatric neurology clinic in Abu
Dhabi, United Arab Emirates. The authors analyzed the medical history, demographics, etiology, neurodiagnostic tests, treatment modalities, and outcomes of
patients diagnosed with IS between September 2014 and September 2019. Three
treatment modalities were identied as rst-line options: prednisolone (UKISS),
ASMs, and vigabatrin. The study revealed that complete response rates to vigabatrin as a rst-line therapy showed the greatest statistical signicance. Patients
with idiopathic IS responded to treatment similarly to patients with symptomatic IS.In patients who showed partial or no response to rst-line therapy, an
additional response to second-line therapy was noted with the prednisolone
UKISS regimen and vigabatrin. None of the patients received adrenocorticotropin therapy. All patients with desirable outcomes had idiopathic IS and did not
develop symptoms. The researchers concluded that more than one-third of
patients showed poor treatment response when they did not receive treatment
according to currently available options. This highlights the need for a unied
treatment program that considers the availability of medications, expertise, and
diagnostic tests outside major tertiary care centers in the region [580]. Fahad A
Bashiri etal. conducted a retrospective medical record review to evaluate neurodevelopmental and epileptic outcomes in children with infantile spasms (ISs)
at King Khalid University Hospital (KKUH) in Riyadh, Saudi Arabia. Patients
who were diagnosed with IS according to the International League against
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Epilepsy (ILAE) criteria between January 2000 and December 2017 were
included. Patients who were lost to follow-up or were not treated at KKUH were
excluded. A total of 53 patients with IS were included in the study and classied
into unknown, cryptogenic, and symptomatic types. The majority had symptoms (71.7%). The etiological type and treatment delay were found to be signicant predictors of motor and cognitive outcomes but were not predictors of
seizure control. Patients with unknown IS who were diagnosed earlier had better
neurodevelopmental outcomes. Treatment with vigabatrin in combination with
adrenocorticotropin (ACTH) or prednisolone resulted in better seizure control
than monotherapy or other combination therapies [581].
An article by M.Kuchenbuch etal. emphasized signicant advancements in the
treatment of TSC-related epilepsy in children. A European controlled trial involving
94 infants with TSC demonstrated that early treatment with vigabatrin before the
onset of seizures can prevent infantile spasms and reduce the risk and severity of
subsequent seizures over a 2-year follow-up period. This underscores the importance of proactive management strategies in improving outcomes for children with
TSC-associated epilepsy [582].
In clinical drug application, adverse reactions to drugs are the focus of our attention in addition to drug efcacy. Vigabatrin (VGB) is a second-generation antiseizure medication that is effective in the treatment of infantile spasms and focal
epilepsy, mainly in patients with tuberous sclerosis (TSC). However, reports of
adverse events related to VGB use, including VGB-related visual eld loss and
brain abnormalities in neuroimaging, have raised concerns about the wider use of
VGB, thus signicantly limiting its application. Weronika Golec etal. conducted a
review focused on summarizing recent treatment guidelines and the use of VGB in
focal seizures, particularly in patients with tuberous sclerosis complex (TSC). They
also discussed new applications of VGB to improve treatment for patients with TSC
and reviewed current views on potential VGB-related toxicity and safety [583].
Although vigabatrin (VGB) is approved as a monotherapy for pediatric patients
with infantile spasm (IS), the duration of use of VGB should be limited due to the
risk of retinal and neurotoxicity, but the optimal duration of treatment is unclear.
Béatrice Desnous et al. aimed to determine the risk of spasticity recurrence in
patients assessed as good responders to VGB therapy. They focused on infants with
IS who were treated with VGB as rst-line therapy and who did not exhibit clinical
spasms or arrhythmias after 4weeks of treatment. These infants were divided into
two groups based on the duration of VGB treatment: a 6-month treatment group and
a >6-month treatment group. The study revealed no recurrence of spasticity in either
group. Additionally, in the 6-month treatment group, no other seizure types were
observed in patients with nonidentied etiology (NIE). Furthermore, between 6 and
9months after initiating VGB therapy, only 5 of 37 patients developed advanced
epilepsy in the form of focal seizures, with 3 of 30 patients in the 6-month treatment
group and 2 of 7 patients in the extended treatment group falling into this category.
These ndings suggest that a brief 6-month course of VGB may sufce for the treatment and prevention of IS; particularly noteworthy is the absence of spasticity
recurrence in NIE children [584].
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It is crucial to assess any child experiencing appetite and weight issues due to the
potential inuences of these factors on their growth and development due to various
factors associated with epilepsy. Antiseizure medications (ASMs) can have side
effects, some of which may impact appetite, thereby affecting normal growth and
weight gain in children. Buraniqi E etal. systematically reviewed studies on the
effects of ASM use on children’s appetite and weight. They found that certain
ASMs, such as oxcarbazepine, eslicarbazepine, lamotrigine, levetiracetam, lacosamide, CBZ, vigabatrin, and clobazam, have minimal impacts on weight and appetite. However, some ASMs may inuence both appetite and weight, potentially
increasing the risk of related ailments and reducing adherence to treatment regimens [80].
The association between ASMs and suicidal tendencies remains contentious,
necessitating further analysis of additional datasets to comprehend this intricate
relationship. Leppien EE etal. conducted a study utilizing the U.S.Food and Drug
Administration Adverse Event Reporting System (FAERS) database to compare the
safety proles of new and traditional ASMs concerning suicidal tendencies. They
identied four new ASMs (lacosamide, clobazam, brivaracetam, and vigabatrin)
associated with signicantly lower rates of suicide attempts than traditional ASMs,
while perampanel was associated with notably higher rates. This case–control study,
spanning a decade and including 6309 FDA adverse event reports of suicidal tendencies, enhances the understanding of the safety proles of novel ASMs [585].
Evidence-Based Medical Research
In tuberous sclerosis (TSC), a prevalent genetic contributor to epilepsy, infantile
epileptic spasticity syndrome (IESS) typically manifests as the initial neurological
hallmark, progressively transitioning into refractory epilepsy. Vigabatrin (VGB)
commonly serves as the primary therapeutic option for patients with TSC with IESS
in clinical settings. Giovanni Prezioso etal. conducted a systematic review aimed at
gathering and analyzing data concerning the efcacy of VGB in treating TSC with
IESS, aiming to evaluate the robustness of the evidence available in the literature.
The authors’ ndings indicate that although all examined studies reported a favorable impact of VGB in TSC patients with IESS, exhibiting a superior response rate
compared to IESS patients without TSC, the limited evidence base and substantial
heterogeneity in ndings do not justify rm treatment recommendations [586].
Effects onEEG andCognitive Function
Vigabatrin (VGB) is a potent and selective inhibitor of gamma-aminobutyric aminotransferase (GABA-T) and is a nonconventional medication approved for treating
individuals with intractable epilepsy. However, its impact on epilepsy development
and its potential correlation with cognitive function postepilepsy onset remain
obscure. Using a Li-pilocarpine-induced seizure model, Ming-Chi Lai etal. investigated the effects of VGB on epileptogenesis and neuronal impairment in Sprague–
Dawley rats following status epilepticus. Cognitive assessment was conducted
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using the inhibitory avoidance test. Research has revealed that VGB can impede
epilepsy onset by mitigating spontaneous recurrent seizures, hippocampal neuron
deterioration, and chronic mossy ber sprouting. Nonetheless, VGB failed to preserve cognitive function. These ndings underscore the imperative of delving deeper
into the role of VGB in both the genesis and management of epilepsy within clinical
settings [587].
Side Effects
Side effects such as imaging abnormalities and visual eld defects may occur during the use of vigabatrin.
Vigabatrin (VGB) is an effective antiseizure medication for the treatment of West
syndrome. It acts by irreversibly inhibiting gamma-aminobutyric acid (GABA)
transaminase and increasing central GABA levels. Vigabatrin-associated brain
abnormalities on magnetic resonance imaging (VABAMs), a side effect of VGB,
have only been described in children, but the pathophysiology of this effect is
unknown. Ikeda Azusa etal. evaluated the relationship between VGB and GABA
levels in the brain and the association between VABAMs and GABA.Researchers
speculate that elevated levels of GABA in the brain are observed in VABAM
patients, suggesting that GABA is involved in the pathogenesis of this condition. In
particular, it is characterized by a signicant increase in free GABA levels in cerebrospinal uid. Although the increase in the GABA-to-creatine ratio and phosphocreatine (Cr) peak ratio (GABA/Cr) is mild, it may help in the early identication of
patients at risk for VABAM [588]. Gabriela Reyes Valenzuela et al. conducted a
retrospective analysis of clinical and EEG epilepsy data from 288 WS patients identied between 2014 and 2020. They assessed the efcacy of a ketogenic diet, valproate, levetiracetam, or topiramate in treating these patients. Vigabatrin (VGB)
treatment in children with West syndrome (WS) led to characteristic MRI changes,
with most cases being asymptomatic. However, some patients experienced dyskinesia and acute encephalopathy. Of the 288 WS patients who underwent VGB, 44
displayed MRI ndings consistent with VGB-related brain abnormalities. The
median age at diagnosis was 6.29months (range 2weeks to 11months). The etiology of VGB-associated brain abnormalities on MRI was unknown in 22 patients
(52.27%), genetic factors in 7 patients (15.9%), genetic structure in three patients
(6.8%), structural malformation in 3 patients (6.8%), and acquired structure in eight
patients (18.2%). Twenty-ve of the 44 patients had asymptomatic brain abnormalities on MRI related to vigabatrin. Among the infants, 10 (22.7%) experienced worsening movement disorders, while nine (21.4%) exhibited progressive psychomotor
deterioration linked to encephalopathy signs and symptoms. The researchers
observed dose-dependent MRI abnormalities in infants treated with VGB, with
potential risk factors including age below 11 months and higher VGB doses
(>165mg/kg/day). Typically, these brain abnormalities resolved after discontinuing
VGB, often within 3months [589]. Chellamani Harini etal. investigated additional
hippocampal signal abnormalities in infant patients showing typical vigabatrinrelated MRI changes. Among the 55 patients, 26 (47%) exhibited typical
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vigabatrin- related MRI changes, with six showing additional signal abnormalities
in the hippocampus. Follow-up revealed parallel hippocampal signal changes in
four patients, while two patients showed good clinical outcomes without MRI follow-up. There were no differences in clinical parameters, including seizure status,
between patients with and without additional hippocampal signaling changes. One
patient displayed unilateral thalamic/pedalus signal abnormalities alongside typical
vigabatrin changes. Researchers have proposed that typical vigabatrin-related hippocampal changes may occur under appropriate exposure circumstances [590].
Yong Xu etal. investigated the potential risk factors and frequency of vigabatrinassociated brain abnormalities on magnetic resonance imaging (VABAMs), building upon prior research showing the association of VGB exposure with such
abnormalities. They also scrutinized whether diffusion-weighted imaging (DWI)
should be a standard MRI sequence for children undergoing VGB treatment. This
study focused on infants with infantile spasms (ISs) receiving VGB therapy.
Participants were categorized into VABAM and non-VABAM groups based on
VABAM occurrence. Clinical data and drug exposure information were compiled.
This study revealed a VABAM incidence of 32.5%, surpassing most previous
reports. Furthermore, the peak VGB dosage was conrmed to be a risk factor for
VABAM.The ndings suggested that VABAMs could manifest even with standard
VGB dosages (i.e., 50–150 mg/kg/day). Consequently, researchers advocate for
routine MRI assessments, even when administering typical VGB doses [591].
Vigabatrin therapy is frequently prescribed for infants diagnosed with tuberous
sclerosis, particularly in cases of epilepsy. However, it can induce bilateral symmetric
sequence changes in deep brain matter and the brain stem on MRI.These abnormalities typically manifest in infancy, are reversible, and may or may not present symptoms. Joseph Franklin Craft etal. highlighted a patient with typical neuroimaging
ndings, emphasizing the importance of recognizing these patterns to prevent unnecessary follow-up tests. The decision to continue or discontinue vigabatrin therapy
should take into consideration the potential risk of extrapyramidal symptoms [592].
Jonsson H etal. conducted a study to assess visual elds using Goldmann or
Octopus perimetry and peripapillary retinal nerve ber layer (RNFL) thickness with
spectral-domain optical coherence tomography (OCT) during school age or adolescence. They aimed to investigate the prevalence of vigabatrin-attributed visual eld
defects (VAVFDs) in infantile spasms and the utility of OCT in detecting vigabatrinrelated injury. Of the 88 patients who were exposed to vigabatrin in infancy, 28
underwent formal visual eld testing. Two patients had structural visual eld
defects, four had mild VAVFDs, and one had severe VAVFDs. The duration of vigabatrin treatment was signicantly longer in the VAVFD group than in the normal
visual eld group. Three patients with VAVFDs exhibited RNFL thinning on
OCT.The study concluded that the incidence of VAVFDs after infancy was low but
increased with treatment duration. Further research is needed to identify susceptible
infants and determine the role of OCT in diagnosis [593]. Loretta Giuliano etal.
conducted a systematic review of 5164 studies, including 67, ve of which involved
adult patients. They found that ASM side effects, including retinal toxicity, were
more common in girls, with a greater risk observed in boys treated with vigabatrin.
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Sex differences in ASM side effects are understudied and may be underestimated,
highlighting the need for systematic evaluation of sex as a determinant variable in
clinical studies to better understand drug responses [594].
Drug-induced liver injury (DILI) is a risk factor associated with ASMs, especially older-generation ASMs. Brad K.Kamitaki et al. sought to quantify recent
reports of DILI attributed to old and new generation ASMs and investigate newly
marketed ASM hepatotoxicity using the FDA Adverse Event Reporting System
(FAERS) database. They analyzed over 2.6million adverse event reports of DILI
from July 1, 2018, to March 31, 2020, uncovering 2175 cases attributed to ASM;
these included mostly severe reactions, including death, hospitalization, disability,
and other life-threatening outcomes. Older and newer-generation ASMs were implicated in DILI, but no cases were reported for vigabatrin, tiagabine, or runamide,
suggesting minimal correlation with DILI for most new-generation ASMs [182].
Basic Research
Vigabatrin (VGB) is the primary choice for managing drug-resistant epilepsy and
infantile spasms, although its use often triggers ataxia, tremors, and abnormal gait,
indicating potential cerebellar involvement. Marwa Abd El-Kader etal. conducted a
groundbreaking study aiming to explore, for the rst time, the role of necrosis and
apoptosis in VGB-induced cerebellar cell loss and the potential protective effect of
combined omega-3 and vitamin B12 supplementation. Their research involved 50
adult male Sprague–Dawley rats (160–200g) divided into ve groups receiving various treatments administered intragastrically daily for 4weeks. The results revealed
that VGB-induced damage to the cerebellar cortex and white matter was dose dependent, indicating the occurrence of apoptosis and necrotic death mechanisms. Notably,
supplementation with both B12 and omega-3 PUFAs has the potential to ameliorate
or mitigate VGB-induced neurotoxicity. These ndings underscore the importance of
recommending dietary B12 and omega-3 supplements when prescribing VGB [595].
In another study on the use of vigabatrin, an antiepileptic agent that irreversibly
inhibits GABA transaminase activity, male C57Bl/6J mice received continuous
infusions of various doses (0, 40, or 80mg/kg/day) for 12days. The study design
involved pooling retinas, eyes (excluding retinas), whole brains, and plasma from
n= 24 animals per dosage group, yielding eight triplicates per treatment group.
Analysis revealed the distribution of active (S)-(+) VGB to the retina, indicating the
involvement of a stereospecic transporter whose identication may unveil new
therapeutic strategies to mitigate VGB’s well-documented retinal toxicity and
broaden its clinical utility [596].
Other Research
Vigabatrin (VGB), an unconventional antiseizure medication (ASM), has shown
promise in treating brain tumors, yet its impact on ion channels in glioma cells
remains unclear. Te-Yu Hung etal. utilized patch-clamp technology to investigate
the effect of VGB on ion currents in the glioblastoma multiforme cell line