Peculiar EEG Pattern Research Articles

PPP3CA gene-related developmental and epileptic encephalopathy: Expanding the electro-clinical phenotype

PurposeThe objective of this study is to characterize the electro-clinical phenotype of individuals affected by the rare PPP3CA gene-related developmental and epileptic encephalopathy (DEE). MethodsWe provide a detailed electro-clinical description of four previously unreported subjects, with unremarkable structural brain MRI and a normal screening for inborn errors of metabolism, who carry pathogenic variants within the regulatory domain of the PPP3CA gene, which encodes for calcineurin. We also conducted a literature review via PubMed and SCOPUS (up to December 2023) to collect all the studies reporting clinical details of subjects with PPP3CA pathogenic variants within the regulatory domain. ResultsOur in-depth investigation reveals two distinct electro-clinical phenotypes with unique interictal and ictal patterns. Pathogenic variants within the calmodulin-binding domain result in childhood-onset epilepsy with focal and generalized seizures, developmental and intellectual impairments. Pathogenic variants within the regulatory domain lead to early onset drug-resistant severe epilepsy and potentially fatal outcomes. Comparative analysis with existing literature corroborates the notion that truncating mutations, prevalent in the regulatory domain but also possible in the calmodulin-binding domain, consistently associate with more profound disabilities and drug-resistant epilepsy. ConclusionOur study emphasizes the critical role of pathogenic variants’ type and location on the severity of PPP3CA-related DEE. We also speculate, based on peculiar EEG patterns, on potential pathophysiological mechanisms involving calcineurin dysfunction and calcium homeostasis. In order to improve our understanding of this rare DEE, we need both collaborative efforts to gather larger cohorts and further experimental studies.

Bilateral and synchronous “dents de scie” spikes: A highly specific EEG pattern of young adult Dravet syndrome

BackgroundIn Dravet syndrome (DS), EEGs evolve over time. ObjectiveTo describe a peculiar EEG pattern in two adults with a de novo SCN1A gene mutation, in exon 5 (case 1) and 9 (case 2). MethodsTwo female patients underwent a prolonged video EEG (24 h) as part of their epilepsy assessment. ResultsIn both cases, the EEG showed a very peculiar and stereotypical pattern of bilateral synchronous spikes at about 5–6 Hz. This activity was present during wakefulness and highly activated at sleep onset and in NREM sleep, which could show nearly continuous spike activity. This activity dramatically decreased in REM sleep and after awakening. This pattern of “dents de scie” (sawtooth) spikes maintained the same morphology throughout the entire EEG recording. In both patients, the spikes were favored by passive eye closure. During wakefulness, the spikes could evolve into atypical absences while keeping the same “dents de scie” pattern. Neither patient had tonic or myoclonic seizures at the time of the EEG assessment. Both were moderately retarded, and neither one had a typical DS gait disorder. Previous EEG recordings of case 1 performed at 9.5 and 18.5 years showed spike-waves, but the morphology did not correspond to the EEG recording observed at 22 years. ConclusionsBoth patients have a similar electro-clinical phenotype. This “dents de scie” pattern appears to be very specific and could be pathognomonic in a subgroup of young adults with DS. Results of sleep EEG recording could be added to the diagnostic criteria for this syndrome.

A characteristic occipital epileptiform EEG pattern in ADCK3-related mitochondrial disease.

ADCK3-related disease is a mitochondrial disorder associated with an abnormality of coenzyme Q10 metabolism. Ataxia and epilepsy are common, and the phenotype overlaps with other mitochondrial encephalopathies, particularly POLG-related disease. CoQ10 supplementation may be beneficial. We have noted a remarkable epileptiform pattern in ADCK3-related encephalopathy, and since EEG studies in this rare condition are limited, we wished to assess the evolution of EEG characteristics in patients with this disorder. All EEG recordings of the four known patients from Mid-Norway were systematically reviewed. EEG graphoelements were classified according to the standardized computer-based organized reporting of EEG (SCORE) and international glossary terms. The evolution of EEG features was assessed. A total of 96 recordings spanning over 15-32 years were available, with a mean of 24 per patient (range: 17-28). Altogether, 50 digital recordings were reviewed, including four long-term and 46 selected paper segments. In three patients, EEG showed prominent bilateral asynchronous and synchronous epileptiform discharges in occipital and posterior-temporal regions. This intense activity included multiple epileptiform graphoelements, which occurred continuously, nearly continuously or in prolonged runs. The findings remained stable over many years. Although the number of patients is small, we suggest that interictal EEG findings of continuous/nearly continuous bi-occipital spike-waves may serve as a biomarker for this potentially treatable condition. This peculiar EEG pattern might help to differentiate ADCK3-related disease from the more common POLG-related disease, which is usually characterized by lateralized or focal slowing with more sporadic epileptiform elements of similar topography.

Expanding the Spectrum of EEG Periodic Discharges in Subacute Sclerosing Panencephalitis: A Case Report

Abstract Background Atypical electroencephalogram (EEG) abnormalities emerge in patients with subacute sclerosing panencephalitis (SSPE), especially in cases with an atypical clinical presentation that can lead to diagnostic difficulties. Case Report In this article, we presented a case of SSPE with an atypical onset with epileptic seizures and Parkinson's features. The neurological examination during the initial evaluation of the patient showed extrapyramidal syndrome, hyperreflexia, intention tremor, and dysmetria. Cranial magnetic resonance imaging was normal. Video EEGs were performed in wakefulness and sleep. In wakefulness, multiple brief seizures (1–1.5 seconds were recorded, consisting of gradual bending of the body forward and to the right that lacked the sudden characteristic of myoclonia. During those episodes, we recorded generalized epileptiform activity of 4 or 5 sharp waves, with higher amplitude in the anterior regions, in some of the paroxysms superimposed on a slow wave or followed by a high amplitude slow wave. The paroxysms appeared periodically every 15 to 30 seconds. However, 2 months later, the EEG showed typical periodic generalized activity of biphasic/triphasic slow waves (Radermecker complexes), accompanied by myoclonias. Conclusion We reported a peculiar EEG pattern in a patient with SSPE that consists of periodic generalized activity of sharp waves. Atypical EEG patterns can appear when the disease progresses, but initially too, before typical periodic complexes and can complicate the diagnostic process.

Metronidazole Encephalopathy EEG Features: A Case Report with Systematic Review of the Literature.

Metronidazole-induced encephalopathy (MIE) is a rare and often under-recognized iatrogenic condition. The diagnosis should be considered in metronidazole-treated patients presenting with acute encephalopathy, unprovoked seizures and cerebellar signs. While typical magnetic resonance imaging (MRI) findings strongly support the diagnosis, electroencephalography (EEG) features have been rarely reported and poorly described. We present a longitudinal EEG assessment in one patient with encephalopathy due to metronidazole toxicity who presented a peculiar EEG pattern presentation and evolution. During the acute phase of encephalopathy, the EEG showed a monomorphic, sharply contoured theta activity symmetrically represented over frontal regions with an anterior–posterior progression which evolved in parallel with clinical worsening. Together with a systematic review of the literature, we discuss whether this EEG activity may represent a distinct neurophysiological correlate of ‘cerebellar encephalopathy’.

Neonatal Seizures and Inborn Errors of Metabolism: An Update

Early identification of an underlying inborn error of metabolism in newborns with otherwise unexplained seizures may address appropriate disease-specific treatment and provide important tools about the choice of the antiepileptic drugs. Neonatal seizures usually present as prolonged or recurrent, often configuring epileptic status. Striking features of an underlying metabolic disorder include abnormal neurological examination, lethargy and/ or symptoms of acute decompensation. Ex adiuvantibus, trial with intravenous pyridoxine administration could be attempted in refractory unexplained neonatal seizures. Peculiar EEG patterns such as Suppression Burst may address diagnosis and laboratory work-up being most frequently associated to specific metabolic disorders.

Low frequency mu-like activity characterizes cortical rhythms in epilepsy due to ring chromosome 20

ObjectivesTo evaluate the spectral and spatial features of the cortical rhythms in patients affected by ring chromosome 20 – [r(20)]-syndrome. MethodsTwelve patients with [r(20)] syndrome were studied. As controls we enrolled 12 patients with idiopathic generalized epilepsy (IGE) and 12 healthy volunteers (HV). Blind source separation, spectral analyses and source reconstruction were applied in all cases in order to identify reliable spatio-temporal patterns of cortical activity. ResultsA theta–delta EEG rhythm was identified in [r(20)] patients, with spectral peak ranging between 3 and 7Hz and whose generators mapped over the sensory-motor cortices. A second peak laying at a frequency about double with respect to the first one was present in 6 cases. Analogue methodological approach in HV and IGE groups failed to show similar findings. ConclusionsEEG of [r(20)] patients reveals the existence of a highly reproducible EEG pattern arising from the sensory-motor system. SignificanceThe recognition of this peculiar EEG pattern could help the diagnostic work-up. Additionally, our findings supports the existence of a parallelism between this EEG trait and the physiological “mu” rhythm which is generate by the sensory-motor system. Such link suggests a sensory-motor system dysfunction in [r(20)] patients.

Neonatal suppression‐burst without epileptic seizures: expanding the electroclinical phenotype of STXBP1‐related, early‐onset encephalopathy

Early-onset epileptic encephalopathies (EOEEs) are characterised by epileptic seizures beginning in the first months of life, abnormal background EEG activity, and are associated with severe developmental delay and poor prognosis. Mutations and deletions in the STXBP1 gene are associated with Ohtahara syndrome, also known as "early infantile epileptic encephalopathy". We report an infant affected by EOEE with a 9q34.11 deletion that encompassed the genes STXBP1 and SPTAN1. The infant presented with neonatal encephalopathy without epileptic seizures and an EEG pattern varying from highly discontinuous to suppression-burst. This was followed by West syndrome at 2 months with atypical hypsarrhythmia and spasms, easily controlled by therapy. Our findings suggest that molecular analysis of STXBP1 should be considered for newborns affected by neonatal encephalopathy associated with a peculiar EEG pattern, even in the absence of neonatal epileptic seizures.

Periodic EEG patterns: importance of their recognition and clinical significance

Periodic electroencephalographic (EEG) patterns consist of discharges usually epileptiform in appearance, which occur at regular intervals, in critical patients. They are commonly classified as periodic lateralized epileptiform discharges (PLEDs), bilateral independent PLEDs or BIPLEDs, generalized epileptiform discharges (GPEDs) and triphasic waves. Stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) are peculiar EEG patterns, which may be present as periodic discharges. The aim of this study is to make a review of the periodic EEG patterns, emphasizing the importance of their recognition and clinical significance. The clinical significance of the periodic EEG patterns is uncertain, it is related to a variety of etiologies, and many authors suggest that these patterns are unequivocally epileptogenic in some cases. Their recognition and classification are important to establish an accurate correlation between clinical, neurological, laboratorial and neuroimaging data with the EEG results.

Electroclinical evolution in ring chromosome 20 epilepsy syndrome: A case with severe phenotypic features followed for 25 years

Intractable epilepsy and peculiar EEG patterns characterize ring chromosome 20 syndrome [r(20)], while dysmorphic features, mental retardation and behavioural disturbances are widely variable. The clinical evolution of r(20) over time is not well defined as relatively few cases have been reported. Here we describe a patient with severe clinical features followed for a 25-year period. The patient was subjected to clinical, psychometric and EEG evaluation twice a year from the age of 21 years. Cytogenetic studies, using chromosome analysis and fluorescence in situ hybridization (FISH) and several immunological investigations were performed. Ring chromosome 20 was found in 50% of examined metaphases with the deletion of subtelomeric regions 20p and 20q. Our patient presented with marked dysmorphic features, severe mental retardation, tetraparesis, dysarthria and intractable epilepsy with onset during the first year of life. During follow up, EEG findings and clinical features progressively worsened: a progressive disorganization of background EEG activity occurred and mental and motor impairment evolved. The severity of clinical expression depended on the extent of chromosomal deletion and on the haploinsufficiency of other important related genetic loci due to ring instability. The progressive worsening of both clinical and EEG features over a long period, which has also been reported by other authors, further characterized this syndrome.

Source localization of small sharp spikes: Low resolution electromagnetic tomography (LORETA) reveals two distinct cortical sources

Objective We have investigated the cortical sources and electroencephalographic (EEG) characteristics of small sharp spikes (SSS) by using statistical non-parametric mapping (SNPM) of low resolution electromagnetic tomography (LORETA). Methods We analyzed 7 SSS patterns (501 individual SSS) in 6 patients who underwent sleep EEG studies with 29 or 23 scalp electrodes. The scalp signals were averaged time-locked to the SSS peak activity and subjected to SNPM of LORETA values. Results All 7 SSS patterns (mean 72 individual SSS, range 11–200) revealed a very similar and highly characteristic transhemispheric oblique scalp voltage distribution comprising a first negative field maximum over ipsilateral lateral temporal areas, followed by a second negative field maximum over the contralateral subtemporal region approximately 30 ms later. SNPM–LORETA consistently localized the first component into the ipsilateral posterior insular region, and the second component into ipsilateral posterior mesial temporo-occipital structures. Conclusions SSS comprise an amalgam of two sequential, distinct cortical components, showing a very uniform and peculiar EEG pattern and cortical source solutions. As such, they must be clearly distinguished from interictal epileptiform discharges in patients with epilepsy. Significance The awareness of these peculiar EEG characteristics may increase our ability to differentiate SSS from interictal epileptiform activity. The finding of a posterior insular source might serve as an inspiration for new physiological considerations regarding these enigmatic waveforms.

Encefalopatia induzida por cefepime: achados clínicos e eletroencefalográficos em sete pacientes

Cefepime, a fourth-generation cephalosporin, with large antibacterial spectrum, is a commonly used antibiotic for the treatment of serious hospital infections. Its security report is considered favourable. Recently, many cases of a severe and reversible cefepime-induced encephalopathy were described. In this paper, we report seven patients with reversible cefepime-induced encephalopathy, with a peculiar EEG pattern, characterized by semiperiodic diffuse triphasic waves. We discuss the EEG abnormalities found and their association with nonconvulsive status epilepticus.

Sleep‐related, low voltage Rolandic and vertex spikes: an EEG marker of benignity in infancy‐onset focal epilepsies

ABSTRACT Although benign forms of epilepsies with onset in infancy have recently been recognized, the occurrence of seizures in an infant or very young child is very often an event of great significance and the prognosis concerning both epilepsy and neuropsychological development must be guarded. No reliable clinical or electroencephalographic (EEG) markers that can predict the outcome have been described. In a retrospective series of 10 patients, we found a peculiar EEG pattern seen across sleep stages, but not in the waking state in infants whose first seizures appeared before the age of 1 year, and which were mostly complex focal. In all cases, follow‐up showed a favourable outcome with complete seizure remission and no cognitive impairment. The specificity of these EEG changes was 100%, but the sensitivity was lower, since they were not seen in some of the infants with the same favourable outcome. We discuss the clinical similarities between our patients and those cases reported earlier by other authors as benign, non‐familial or familial focal epilepsies, in whom, however, no interictal abnormalities had been seen on the EEG. Such EEG changes are probably specific to benign, self‐limited, early onset focal epilepsies.

Does a peculiar EEG pattern exist also for FRAXE mental retardation?

Objective: FRAXE mental retardation, a recently identified rare genetic condition, is due to a mutation of the FMR2 gene, located at Xq28 region. The phenotype is non-specific and characterized by developmental delay, speech, reading and writing problems, poor adaptive skills, anxiety, aggressiveness, obsessive-compulsive disturbance, and hyperactivity. The objective of this study was to describe the characteristic EEG pattern found in one patient with FRAXE mental retardation. Methods: EEG (with photic stimulation and hand/foot tapping) and median nerve somatosensory evoked potentials were recorded in a 8-year-old male patient with FRAXE mental retardation (diagnosis confirmed by molecular genetic analysis) and speech disturbances. Results: The patient never presented seizures; however, sleep enhanced multifocal spikes were found in the EEG. Moreover, tactile stimulation of hands and feet, as well as intermittent photic stimulation, provoked the appearance of spikes. Somatosensory evoked potentials from the median nerves showed a ‘giant’ component at around 60 ms. Conclusions: Considering the rarity of both FRAXE mental retardation and tactile evoked spikes, their association in the same subject might be considered as not casual. If confirmed by future studies, these neurophysiological findings might be considered as a marker for FRAXE mental retardation.