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Review article
Side effects of phenobarbital in epilepsy: a systematic review
Ling-Li Zhang, Li-Nan Zeng, You-Ping Li
the development of better tolerated new generation AEDs, phenobarbital is still widely used particularly in developing countries because of its low cost. The purpose of this review was to:
<i>(i)</i> investigate whether phenobarbital can be safely used as an antiepileptic drug and
<i>(ii)</i> determine the questions which need to be addressed in order to comprehensively and adequately evaluate the safety of phenobarbital for the treatment of epilepsy.
<i>Methods</i>. The literature was searched using the Cochrane Central Register of randomised controlled trials (1800-2009), Medline (1966-2009), Embase (1966-2009) and three Chinese databases.
<i>Results</i>. Twenty studies were finally included in this systematic review. The determination of adverse effects of combined antiepileptic drugs (AEDs) from different studies was complicated by numerous factors including study design, different descriptions of adverse events and a lack of standardised data collection. These factors may also have been responsible for the heterogeneity present in the meta-analysis. The data did not demonstrate any evidence of association between phenobarbital and a higher risk of adverse events. However, phenobarbital appeared to be associated with a higher rate of adverse drug reaction related withdrawal (ADR-related withdraw), compared to carbamazepine, valproic acid and phenytoin. This may have been due to a concern for possible adverse effects of phenobarbital.
<i>Conclusions.</i> Phenobarbital was associated with a higher rate of drug withdrawal although there was no evidence to suggest that phenobarbital caused more adverse events compared to carbamazepine, valproic acid or phenytoin. However, in the case of pregnant women, it is important for clinicians to evaluate the benefits and risks of phenobarbital administration before making a final recommendation. Furthermore, unified scales for the assessment of cognitive function should be applied for future studies particularly in children.
Invited editorial comment
Original articles
Lessons learned from a comparison of language localisation using fMRI and electrocortical mapping: case studies of neocortical epilepsy patients
Kwang Ki Kim, Michael D Privitera, Jerzy P Szaflarski
MRI (fMRI) has been utilised for language and other cortical function localisation. We describe language localisation in two patients using both ECM and fMRI. Co-registration of fMRI and ECM revealed that although two fMRI tasks localised multiple language areas, the verb generation task had an advantage over the semantic decision/tone decision task in that there was a clear overlap between the language areas identified by the verb generation task and ECM. In addition to the language areas detected by ECM, fMRI showed other language-related areas that may be important for post-operative language outcome. Therefore, fMRI may provide additional and complementary information to ECM in presurgical evaluation of patients with epilepsy. The correlation between fMRI and ECM may depend on the language testing methods utilised during the procedures.
Montreal Cognitive Assessment in cryptogenic epilepsy patients with normal Mini-Mental State Examination scores
Kanitpong Phabphal, Janyapon Kanjanasatien
to the Mini-Mental State Examination (MMSE) score. We tested our hypothesis that the prevalence of mild cognitive impairment and associated patient correlation factors might be increased (score < 26) according to the MoCA, in spite of a normal MMSE score, and that cognitive impairment might occur in a range of domains of the MoCA. Eighty-five patients participated in this study. The mean MoCA score was 22.44 (± 4.32). In spite of a normal MMSE score, which was an inclusion criterion, cognitive impairment was detected in 60% patients based on the MoCA score. The variable that correlated with a higher risk of cognitive impairment was the number of antiepileptic drugs (polytherapy: OR 2.71; CI 1.03-7.15). The mean scores of visuospatial and executive function, naming ability, attention, language, abstraction, delayed recall and orientation among patients with mild cognitive impairment were significantly lower than those of patients with normal cognitive function. These findings suggest that mild cognitive impairment in cryptogenic epileptic patients is common. We suggest using MoCA as a screening test for patients with epilepsy.
Vagus nerve stimulation: effectiveness and tolerability in 64 paediatric patients with refractory epilepsies
Ricardo O Cersósimo, Marcelo Bartuluchi, Sebastian Fortini, Alejandra Soraru, Hugo Pomata, Roberto H Caraballo
<i>Materials and methods</i>. Sixty-four patients (34 male and 30 female) implanted with VNS for refractory epilepsy were analysed. Electroclinical features were compatible with Lennox-Gastaut syndrome in 46 patients, focal epilepsies in 10 patients, Dravet syndrome in three patients, epilepsy with myoclonic-astatic seizures in three patients, and West syndrome in two. The NeuroCybernetic Prosthesis (NCP) system (Cyberonics, Webster, TX, USA) was employed and the following stimulation parameters were used: output current of 1 to 2.5mA, signal frequency of 30Hz, signal pulse width of 500μs, and signal “on” and “off” times of 30 seconds and 5 minutes, respectively.
<i>Results</i>. Of 46 patients with LGS, 30 cases showed a significant improvement in seizure control, with a reduction in seizure frequency of at least 50%. Ten patients with focal epilepsy, three patients with myoclonic-astatic seizures, two patients with Dravet, and two patients with West showed a significant improvement in seizure control, with a reduction in seizure frequency of at least 50%. A good clinical response was evident early and efficacy progressively improved with the duration of treatment up to 36 months. In a significant number of patients, reduced seizure severity and shorter recovery time and hospital stay were also observed. VNS was well tolerated in all patients.
<i>Conclusion</i>. VNS is an effective and well-tolerated treatment for paediatric patients with refractory epilepsies, improving quality of life and neuropsychological performance.
Reflex seizures in Rett syndrome
Ana Roche Martínez, M Itziar Alonso Colmenero, Andreia Gomes Pereira, Francesc X Sanmartí Vilaplana, Judith Armstrong Morón, Mercé Pineda Marfa
is common in Rett syndrome patients (up to 70%), but to the authors’ knowledge, no pressure or eating-triggered seizures have yet been reported in Rett children. We describe three epileptic Rett patients with reflex seizures, triggered by food intake or proprioception. One patient with congenital Rett Sd. developed infantile epileptic spasms at around seven months and two patients with classic Rett Sd. presented with generalised tonic-clonic seizures at around five years. Reflex seizures appeared when the patients were teenagers. The congenital-Rett patient presented eating-triggered seizures at the beginning of almost every meal, demonstrated by EEG recording. Both classic Rett patients showed self-provoked pressure -triggered attacks, influenced by stress or excitement. Non-triggered seizures were controlled with carbamazepine or valproate, but reflex seizures did not respond to antiepileptic drugs. Risperidone partially improved self-provoked seizures. When reflex seizures are suspected, reproducing the trigger during EEG recording is fundamental; however, self-provoked seizures depend largely on the patient's will. Optimal therapy (though not always possible) consists of avoiding the trigger. Stress modifiers such as risperidone may help control self-provoked seizures.
Analysis of acylcarnitine levels by tandem mass spectrometry in epileptic children receiving valproate and oxcarbazepine
Ali Cansu, Ayse Serdaroglu, Gursel Biberoglu, Leyla Tumer, Tugba Luleci Hirfanoglu, Fatih Suheyl Ezgu, Alev Hasanoglu
in children with epilepsy. A total of 56 children with idiopathic partial or generalised epilepsy were included in the study. Patients were assigned to receive either VPA or OXC monotherapy. Free carnitine (C0) and acylcarnitine profiles of the patients were investigated using tandem mass spectrometry at baseline and at six and 18 months after commencement of therapy. For patients receiving VPA or OXC monotherapy, there were no significant differences in plasma levels of C0, compared with baseline, at six and 18 months (
<i>p</i>>0.05). Treatment with VPA for six and 18 months correlated with a significant increase in 3-hydroxy-isovalerylcarnitine (C5-OH) (six months: +23%; 18 months: +73%), and significant decreases in the following acylcarnitines: C6-acylcarnitine (six months: -60%; 18 months: -66%), C14-acylcarnitine (six months: -25%; 18 months: -38%), C16-acylcarnitine (six months: -73%; 18 months: -73%), and C18:1-OH-acylcarnitine (six months: -60%; 18 months: -70%), compared with baseline (
<i>p</i><0.05). In patients receiving OXC monotherapy, on the other hand, plasma concentrations (μmol/L) of acylcarnitines (from C2 to C18:1-OH) fell within the normal reference range. The results of this study indicate that there are significant biochemical changes in acylcarnitines in ambulatory children on VPA monotherapy but these are not clinically significant. OXC monotherapy had no effect on acylcarnitine metabolism in ambulatory children.
Seizures as a manifestation of multiple sclerosis
Jeffrey L Sponsler, Anastasia C Kendrick-Adey
seizure.</p><p>To present a case report of seizure as the initial symptom of MS, to quantify the occurrence of seizures among MS patients, and to classify patients according to when seizures occur relative to onset of MS.</p><p>The medical history of patients presenting with MS and seizure in our clinic was examined. In addition, 25 scientific papers were reviewed and the number and characteristics of patients with MS and seizure recorded. Data from the literature review and from our own clinical series were combined and examined.</p><p>Of the MS patients, 1.95% experienced seizures at any time during life. Patients experiencing seizures before MS diagnosis were classified into three categories: (a) 25 (7.3% of patients with MS and seizures) with seizure as the initial presentation of MS; (b) 27 (7.9%) with seizures appearing with other signs and symptoms of MS; and (c) 68 (20%) with seizures occurring years or an unknown period of time before MS onset. Seizure occurring as a symptom of MS relapse was found in 29 patients.</p><p>The prevalence of seizures among MS patients was higher than that in the general population, indicating a relationship between seizures and MS. Seizures occurred before MS diagnosis in a small percentage of patients.</p>
Early-onset childhood absence epilepsy: is it a distinct entity?
Pue Farooque, Jatinder Goraya, Ignacio Valencia, Karen S Carvalho, H Huntley Hardison, Agustin Legido, Divya S Khurana
reviewed the electroencephalography laboratory database and paediatric neurology clinic records (from January 2000 to June 2009) at our institution in order to identify patients with absence seizures beginning before age three. Information was collected for age, gender, neurodevelopment, antiepileptic drugs (AEDs) used, seizure control, follow-up, and side effects. Of 12 patients identified, mean age at onset was 20.5 months (range: 11 months to two years; follow-up: six months to 11 years). Seven of 12 patients had normal neurodevelopment and five had speech delay. Four patients were seizure-free without AEDs, three were seizure-free with a single AED, and five still had seizures with multiple AEDs. Three patients had recurrences after medication withdrawal. Other previously published series have identified better seizure control than that reported here, however, 16% of the 130 patients so far documented are reported to have poorly controlled epilepsy, indicating that early-onset CAE is not a homogeneous condition. The debate as to whether early-onset CAE is a distinct epilepsy syndrome therefore continues. We believe that early-onset CAE may be a distinct epilepsy syndrome, with some features that overlap with those of typical CAE, as well as unique distinguishing features. Large prospective multicentric studies would be necessary to definitely resolve this matter.
Clinical commentary
Early-onset absence epilepsy at eight months of age
Yu Kobayashi, Noriyuki Akasaka, Tsukasa Ohashi, Shinji Saitoh, Yuko Tomonoh, Shinichi Hirose, Jun Tohyama
year of life is very rare. We report a girl with intractable absence seizures with onset at age eight months. Her seizures were characterised by loss of responsiveness, with eyes drifting upwards and some myoclonic jerks of the upper and lower limbs. These symptoms were accompanied by bilaterally symmetric high-amplitude 2-2.5 Hz generalised spike-and-wave discharges on the electroencephalogram. Her seizures were refractory to conventional antiepileptic drugs; treatment with adrenocorticotropic hormone was transiently effective. Comprehensive metabolic screening, cytogenetic, and genetic analysis did not determine an underlying cause of her condition. Patients with intractable, very early-onset absence epilepsy with a myoclonic component have an unfavourable outcome and may be classified under a new epileptic syndrome, such as
<i>“early infantile absence epilepsy”</i>.
Clinical commentaries
Limited resection of focal cortical dysplasia and associated epileptogenic cortex may lead to positive surgical outcome
Kyriakos Garganis, Vasileios Kokkinos, Basilios Zountsas
zone. Presurgical fMRI of the sensorimotor areas showed haemodynamic responses over the posterior border of the lesion and ictal EEG-fMRI revealed activation of both the primary sensorimotor strip and premotor lesion area. Almost continuous 1-2 Hz interictal spiking was recorded during a chronic ECoG study over the primary sensorimotor cortex. Following partial resection of the lesion, an acute ECoG revealed marked reduction of epileptic activity over the sensorimotor area. Post-operatively, seizure control was significantly improved (class IV ILAE outcome). Although partial FCD resections predict a worse postoperative outcome, individual patients may still respond favourably. The type of lesion, resected portion, and histopathology may be included among factors related to successful outcome.
Intracranial localisation of ictal urinary urge epileptogenic zone to the non-dominant temporal lobe
Khatuna Gurgenashvili, Shavonne L Massey, Mitzie Grant, Joseph Piatt Jr, Agustin Legido, Ignacio Valencia
has been established using scalp video-EEG monitoring or functional imaging. We report the case of a 19-year-old girl with refractory epilepsy and ictal urinary urge arising from the non-dominant temporal lobe, confirmed by invasive, subdural EEG monitoring. Since undergoing a temporal lobectomy two and a half years ago, the patient has not experienced ictal urinary urge. To our knowledge, this is the first report demonstrating localisation of ictal urinary urge epileptogenic zone to the non-dominant temporal lobe by invasive intracranial monitoring.
Mirth and laughter elicited during brain stimulation
Guadalupe Fernández-Baca Vaca, Hans O Lüders, Maysaa Merhi Basha, Jonathan P Miller
was consistently produced during stimulation of the left inferior frontal gyrus (opercular part) using stereotactically placed depth electrodes. A review of the literature shows that cortical sites that produce mirth when stimulated are located in the dominant hemisphere close to language areas or cortical negative motor areas.
Coexistence of two distinct benign EEG variants in the same subject
Francesco Brigo, Paolo Manganotti, Antonio Fiaschi, Luigi Giuseppe Bongiovanni
significance that occur without any correlation with epilepsy. Each of these patterns has been described to occur alone and in the literature there are no previous reports of co-occurrence of the two distinct benign EEG variants in the same patient. We describe the coexistence of RTTD and SREDA in EEG recordings from the same subject. Although the coexistence of two distinct EEG variants in the same patient is a rarity, these patterns are not so infrequently encountered when present alone and should thus be promptly recognised in order to avoid misdiagnosis of epilepsy due to an over-interpretation of normal sharp patterns.
Serial EEG and MRI changes in status epilepticus-induced excitotoxic neuronal necrosis
Fehim Arman, Dilaver Kaya, Alp Dincer, Aydin Sav, M. Necmettin Pamir
woman presented with right hemiplegia and aphasia following a generalised tonic-clonic status epilepticus of two hours duration. Accompanying serial MRI with advanced imaging techniques, EEG and histopathology of the cortical tissue of the patient were all compatible with excitotoxic neuronal necrosis. In this histopathologically-proven rare case of status epilepticus-induced excitotoxic neuronal injury, the observation of delayed cortical laminar necrosis on MRI, together with paroxysmal lateralised epileptiform discharges on the EEG, suggests that these changes may be an early sign of impending and ongoing excitotoxic neuronal injury and delayed cell death caused by glutamate release due to excessive neuronal firing in status epilepticus.
aPTT prolongation and skin eruption possibly associated with lamotrigine monotherapy in a paediatric patient
Jung Sook Yeom, Ji Sook Park, Ji Hyun Seo, Eun Sil Park, Jae Young Lim, Chan-Hoo Park, Hyang Ok Woo, Hee-Shang Youn
months after initiating lamotrigine treatment with dose increment. Two weeks after lamotrigine withdrawal, the skin eruption disappeared and aPTT normalised. To our knowledge, this is the first report of aPTT prolongation possibly due to factor inhibitors associated with lamotrigine monotherapy.
Letter to the editor
Seizure or migraine? The eternal dilemma
Vincenzo Belcastro, Pasquale Striano, Pasquale Parisi
