first weeks of life and reflect a wide variety of underlying central nervous system disorders. Acute symptomatic seizures occur more often during the neonatal period than at any period of life and are associated with adverse long-term neurodevelopmental sequelae and an increased risk of post-neonatal epilepsy. The improvements of neonatal care in the last decades have changed the spectrum of insults to which the immature brain is exposed and facilitated a decrease in mortality of newborns with seizures. However, the prevalence of long-term morbidity in survivors remains unchanged. Whereas aetiology is presumed to be the main predictor of long-term outcome in neonates with seizures, there is converging evidence that specific electroencephalographic (EEG) abnormalities are related to unfavourable outcomes. Interictal EEG abnormalities, especially concerning background activity patterns, thus constitute a major indicator of disease severity and predictor of outcome, while the added value of sequential EEG assessments is so far controversial. Moreover, experimental as well as clinical studies of hypoxic-ischaemic encephalopathy support the notion that recurrent seizures may amplify injury to the developing brain beyond that associated with the underlying aetiology, thus justifying antiepileptic drug treatment. To date, unresolved issues in seizure detection and classification, in addition to the significant variation in gestational ages and brain insults of neonates, still impede clinical research of neonatal seizures. The wider use of long-term EEG or amplitude integrated EEG monitoring may prove crucial for timely neonatal seizure identification and treatment initiation, and thus ultimately improve outcome.
Veronica Birca, Tania Tayah, Jean-Marc Saint-Hilaire, Dang Khoa Nguyen
attempted to determine whether ictal swearing could help localise the epileptic focus. We review two previously published cases and report eight additional epileptic patients with ictal swearing for whom the epileptic focus was determined based on clinical, structural, electrophysiological, and surgical outcome data. Results indicated that ictal swearing occurs more commonly in male subjects and lateralises to the non-dominant hemisphere, but has poor localisation value, arising either from the frontal, parietal, temporal or occipital lobes in different patients. We discuss the significance of these findings. [
Published with video sequences]
Martin Kudr, Pavel Krsek, Bruno Maton, Stephen Malone, Alena Jahodova, Petr Jezdik, Vladimir Komarek, Ian Miller, Prasanna Jayakar, Trevor Resnick, Michael Duchowny
/p><p>We visually evaluated 98 ictal SPECT studies from 67 children treated surgically for intractable epilepsy caused by FCD. SPECT findings were classified as “non-localised”, “well-localised”, and “extensive” and compared with parameters of injected seizures (seizure type and duration, injection time, and scalp EEG ictal pattern), presence of structural pathology on MRI, type of surgery performed after SPECT study, and histological findings.</p><p>A shorter injection time and duration of injected seizure was associated with more localised SPECT hyperperfusion. SPECT findings were not significantly influenced by type of injected seizure. Widespread ictal scalp EEG patterns were associated with extensive SPECT findings. Larger zones of hyperperfusion were more common in patients with lesional MRI and patients undergoing multilobar resections. SPECT studies demonstrating good localisation were more common in patients with mild malformations of cortical development.</p><p>Early ictal SPECT radiotracer injection is crucial for successful localisation of the epileptogenic zone. Seizure duration, type of scalp EEG findings, and presence of structural pathology on MRI may influence the extent of ictal SPECT hyperperfusion, which was associated with certain types of epilepsy surgery as well as histopathological findings.</p>
Veronica Pelliccia, Roberto Mai, Stefano Francione, Francesca Gozzo, Ivana Sartori, Lino Nobili, Giorgio Lo Russo, Chiara Pizzanelli, Laura Tassi
data, presurgical ictal scalp-EEG findings are often sufficient to define the epileptogenic zone. It is widely believed that ictal scalp-EEG findings in temporal lobe epilepsy are represented by 5-9-Hz lateralised rhythmic theta activity or 2-5-Hz lateralised rhythmic delta activity. On the basis of experimental models and experience with intra-cerebral EEG recordings, the pattern of low-voltage fast activity is considered to be the electrophysiological hallmark of the epileptogenic zone. We reviewed the ictal scalp-EEG data relating to 111 seizures in 47 patients with temporal lobe epilepsy who underwent video-EEG recordings during presurgical work-up. We found that 35 patients (74.4%) showed flattening, low-voltage fast activity or fast activity as the initial EEG pattern. When visible, the rhythmic delta or theta activity followed the fast activity. Low-voltage fast activity, flattening or fast activity occurs in the majority of patients with temporal lobe epilepsy and represents the main ictal EEG pattern. Low-voltage fast activity (or similar) is also identifiable as the initial ictal EEG pattern in scalp-EEG recordings.
Renata Oliveira, Cristina Pereira, Fidjy Rodrigues, Claudia Alfaite, Paula Garcia, Conceição Robalo, Isabel Fineza, Olavo Gonçalves, Eduard Struys, Gajja Salomons, Cornelis Jakobs, Luísa Diogo
families). A clinical diagnosis of neonatal pyridoxine-dependent epilepsy was confirmed by biochemical and genetic studies. Clinical evaluation was performed and medical records were reviewed for therapy implementation and management, neurodevelopment outcome, magnetic resonance imaging, and electroencephalography. All were taking pyridoxine treatment and were seizure-free. Elevated urinary alpha-aminoadipic semialdehyde excretion was found in all patients. Antiquitin gene analysis identified a large homozygous deletion in one patient and two heterozygous mutations in the others. Treatment with pyridoxine should be attempted for all cases of infantile and childhood refractory epilepsy, as has been the case over the last 20 years. Currently, urinary alpha-aminoadipic semialdehyde is a reliable biomarker of pyridoxine-dependent epilepsy, even under pyridoxine treatment. Detection of mutations in the antiquitin gene, encoding alpha-aminoadipic semialdehyde dehydrogenase, establishes the diagnosis and allows for adequate genetic counselling.
Abdul G. Mikati, Ibrahim Abu Gheida, Alhan Shamseddine, Mohamad A Mikati, Pascale E Karam
Methods. We reviewed the clinical and electroencephalographic manifestations of two siblings with GAMT deficiency. We also performed a thorough literature review of all cases of GAMT deficiency, using the PubMed database, and compared our findings to those previously reported.
Results. One sibling presented with Lennox-Gastaut syndrome while the second had manifestations of late-onset West syndrome. Based on a literature search, we found that the clinical picture of GAMT deficiency has been described in a total of 58 cases, including our two patients, 45 of whom had at least some description of EEG and/or seizure manifestation. Epilepsy was present in 81%, with age at onset usually between 10 months and 3 years. Drug resistance was observed in approximately 45%. Initial seizures were febrile, tonic, or tonic-clonic. Drop attacks and generalised seizures were the most frequent seizure type. Absence and febrile seizures also occurred. Less frequently, focal seizures and late-onset infantile spasms (one prior case) were observed. Multifocal spikes and generalised <3-Hz-spike slow waves were common while only one prior single case report of hypsarrhythmia was described. Lennox-Gastaut syndrome was common, while progressive myoclonic epilepsy was also, less frequently, reported.
Conclusions. To our knowledge, this is the second report of the occurrence of West syndrome in GAMT deficiency. The majority of patients with GAMT deficiency have seizures and approximately half are drug-resistant. Late-onset of hypsarrhythmia and/or epileptic spasms could potentially prove to be a distinctive, albeit infrequent, feature of this treatable metabolic disorder.
Roberto Horacio Caraballo, Ricardo Oscar Cersósimo, Pablo Sebastián Fortini, Lorena Ornella, María Celeste Buompadre, Carolina Vilte, Juan Pablo Princich, Natalio Fejerman
with or without encephalopathy, with status epilepticus during sleep (ESES) or continuous spikes and waves during slow sleep (CSWS) syndrome.
Methods. From June 1990 to December 2012, 39 males and 27 females, aged 5-26 years, were studied. We did not include patients with bilateral PMG or cases with unilateral PMG associated with other cerebral lesions. The mean follow-up period was 12 years (range: 3-22 years).
Results. Mean age at epilepsy onset was 6.5 years. Focal motor seizures occurred in all cases and 25 had secondary generalised seizures. Six patients also had complex focal seizures. Interictal EEG recordings showed focal spikes in all cases. For 43 of 53 patients with epilepsy, aged 2-9.5 years, the electroclinical features changed. An increase in frequency of focal motor seizures was reported in 20 patients, negative myoclonus occurred in 32 patients, atypical absences in 25 patients, and positive myoclonus in 19 patients. All patients had a continuous symmetric or asymmetric pattern of spike-wave activity during slow-wave sleep.
Conclusion. For patients presenting with congenital hemiparesis, negative or positive myoclonus, and absences and focal motor seizures with ESES/CSWS, unilateral PMG should be considered. Brain MRI is mandatory to confirm this cortical malformation. The most commonly used treatments were clobazam, ethosuximide, and sulthiame, alone or in combination. For refractory cases, high-dose steroids were administered and surgery was performed in two patients. Outcome was relatively benign.
Takefumi Hitomi, Katsuya Kobayashi, Naoto Jingami, Tomokazu Nakagawa, Hisaji Imamura, Riki Matsumoto, Takayuki Kondo, Kazuo Chin, Ryosuke Takahashi, Akio Ikeda
associated with paternal or maternal transmission. We investigated the relationship between gender of the transmitting parent and clinical anticipation in nine BAFME families. Clinical anticipation regarding either cortical tremor or generalised seizures was observed in all 12 parent/child pairs (8 mother/child pairs and 4 father/child pairs). Moreover, a higher degree of clinical anticipation was associated with maternal transmission than with paternal transmission (
p=0.03). Although a causative gene for BAFME still remains unknown, our finding suggests that BAFME and diseases with unstable expanding repeats, including those in non-coding regions, might share a similar molecular mechanism because such diseases often show clinical anticipation with maternal transmission.
Michael Boyd, Hrayr Attarian, Jeffrey Raizer, Priya Kumthekar, Micheal P Macken, Stephan U Schuele, Elizabeth Gerard
being typical clinical manifestations. Though the literature supports auditory hallucinations as ictal phenomena, there are no reported cases of these hallucinations correlating with electrographic seizure for this disease entity. Early recognition of auditory hallucinations as seizures could alter treatment and subsequently affect short-term outcomes in these patients. We report the case of a patient with auditory hallucinations and progressive cognitive decline, as well as serological evidence of VGKC antibodies, in whom ictal hallucinations were identified by continuous video-EEG monitoring. This case highlights the subtlety of this entity, in both clinical and electrographic detection. [
Published with video sequences]
Aasef G. Shaikh
abutting ventral mesencephalon. The quickphase of the torsional nystagmus was directed towards the left side, ipsilateral to the side of compression by the hamartoma. Ipsi-lesionally directed pure torsional nystagmus in this case is attributed to the compressive lesion of ocular motor structures responsible for the neural integration of torsional and vertical eye movements, the interstitial nucleus of Cajal. [
Published with video sequences]
Vincenzo Belcastro, Roberto Horacio Caraballo, Antonino Romeo, Pasquale Striano
year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [
Published with video sequences]
José L Fernández-Torre, Miguel A Hernández-Hernández, Juan C Rodríguez-Borregán, Vicente González-Quintanilla
with intravenous cefepime. To the best of our knowledge, we report the first case, illustrated by video-EEG, of a critically ill patient receiving treatment with cefepime who developed an episode of confirmed symptomatic myoclonic status epilepticus (MSE)
. Methods. Case report and video-EEG.
Results. A 60-year-old man, who had received a liver transplant due to alcoholic cirrhosis one year ago, was admitted to our intensive care unit due to septic shock. Computed tomography revealed a prostatic abscess as cause of his sepsis. On Day 27, a respiratory infection due to
Pseudomona aeruginosa was diagnosed, and treatment with intravenous cefepime (2 g/8 hours) was initiated. On Day 32, his mental status deteriorated and he developed inattention, a reduced level of consciousness, and multifocal and generalised continuous myoclonic jerks. A video-EEG study was compatible with the diagnosis of symptomatic MSE. On Day 35, cefepime was stopped and general anaesthesia with midazolam was started in order to achieve a faster clinical improvement. We used the BIS-Vista™ monitor to guide general anaesthesia and detect potential episodes of NCSE. On Day 40, an EEG confirmed the existence of moderate diffuse encephalopathy. Finally, the patient died as a consequence of severe heart failure
. Conclusions. Cefepime may be a cause of MSE in non-anoxic comatose patients. Clinicians should be aware of this possibility when evaluating comatose patients on cephalosporin therapy in order to establish a correct diagnostic approach and accurate prognosis. [
Published with video sequences]
Viktoria Kapina, Maria-Isabel Vargas, Gabriele Wohlrab, Serge Vulliemoz, Joel Fluss, Margitta Seeck
We report the case of a girl admitted at the age of 8 years with idiopathic nephrotic syndrome. On the second day of admission, she presented with focal complex seizures and cerebral MRI showed posterior encephalopathy and no hippocampal sclerosis. MRI after one month confirmed the diagnosis of PRES. The seizures recurred and the girl developed pharmacoresistant epilepsy and was admitted to our hospital for further investigation. Cerebral MRI three years after the diagnosis of PRES showed hippocampal sclerosis which was not present on the initial MRI. We conclude that there is a triggering role of PRES in the development of hippocampal sclerosis. Hippocampal sclerosis may have resulted from seizure-associated damage, alternatively, hypertensive encephalopathy may have led to hippocampal damage
via a vascular mechanism.
María Eugenia García García, Sergio Muñiz Castrillo, Irene Garcia Morales, Daniela Di Capua Sacoto, Alberto Marcos Dolado
MRI usually reveal a high intensity signal in the medial temporal lobe and cerebrospinal fluid analysis shows mild pleocytosis and oligoclonal bands. It may occur in association with cancer, infection, or as an isolated clinical condition, often accompanying autoimmune disorders. Immune-mediated limbic encephalitis is now subclassified according to the presence and type of autoantibodies, which has significant consequences regarding the effectiveness of treatment and prognosis. Glutamic acid decarboxylase (GAD) is an enzyme that catalyses glutamic acid into gamma aminobutyric acid. Anti-GAD antibodies are associated with different neurological and non-neurological disorders, but only a few cases of limbic encephalitis associated with anti-GAD antibodies have been reported in the literature, most of them non-paraneoplastic. Here, we report the case of a young female patient with a medical history of psoriasis who developed an acute onset and chronic evolution of anterograde amnesia, associated with drug-resistant epilepsy. Brain MRI showed hyperintensity in the medial temporal lobes and the biochemical studies revealed intrathecal synthesis of anti-GAD antibodies. Screening tests for tumours were negative. Despite antiepileptic drugs, intravenous immunoglobulins and immunosuppressive treatment, the patient did not show clinical improvement and one year later, she continues to present refractory temporal epilepsy and cognitive deficits.
Daniela Di Capua, Sara García-Ptacek, Maria Eugenia García-García, Belen Abarrategui, Jesús Porta-Etessam, Irene García-Morales
anti-N-methyl-D-aspartate receptor encephalitis with atypical age and gender, and a characteristic electroencephalographic pattern that supported the diagnosis. A 66-year-old male presented with psychiatric disturbances and focal seizures with alteration of consciousness, and progressed to a state of akinetic mutism. Auxiliary tests were negative or non-specific for anti-NMDAR encephalitis. Electroencephalographic monitoring revealed a unique pattern; the extreme delta brush. The patient improved with immunotherapy and was asymptomatic at six months of follow-up. Ancillary testing was positive for anti-N-methyl-D-aspartate receptor antibodies. Extreme delta brush is a recently described electroencephalographic pattern presenting in only one third of patients with anti-N-methyl-D-aspartate receptor encephalitis. The identification of this pattern, as in our case, may guide early diagnosis and treatment of anti-N-methyl-D-aspartate receptor encephalitis.