Paroxysmal Epileptiform Discharges Research Articles

A short note in a long-standing discussion on the utility of EEG in patients with headache

Headache, especially migraine, has long been associated with epilepsy, based on the common clinical features, pathophysiological mechanisms and therapeutic options of these disorders. Epilepsy and headache can exist independently in the same patient or correlate in different ways. The utility of routine electroencephalogram (EEG) in patients with headache is to exclude a possible ictal origin when atypical symptoms exist. However, EEG abnormalities in migraine have been reported by a number of authors over the years. Herein, we report a case of a patient with migraine and paroxysmal epileptiform discharges (EDs) in the EEG, in an effort to contribute to the investigation of association between headache and abnormal EEG findings.

Characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations

BackgroundThe characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations (KABUK1) have not yet been well documented. This is the first review to explore this. Materials & methodsWe enrolled 14 patients with KABUK1, whose median age was 13.6years (range=4.1–21.3years). Their medical records from October 1981 to May 2016 were retrospectively analyzed. ResultsEpilepsy was present in 5 (36%) patients. Four of these patients presented with nonsense mutations and one with missense mutations. None presented with brain abnormalities. Four patients presented with annual or monthly focal seizures, of which three evolved to bilateral convulsive seizures. Median onset age of focal epilepsy was 11.8years (range=9.5–12.8years). One presented with monthly myoclonic seizures from age 11.2, whose mother with no other KABUK1 features, had focal epilepsy. The cumulative incidence of epilepsy related to KABUK1 up until age 13 was 45%. Interictal electroencephalogram revealed focal paroxysmal epileptiform discharges (in frontal, central, and parietal regions) in three patients, diffuse high-voltage spike-and-waves in one patient, and normal sleep record in one patient. Myoclonic seizures were rapidly controlled by levetiracetam. In contrast, focal seizures were not controlled in the early period of antiepileptic therapy. ConclusionThis long-term follow-up of patients with KABUK1 revealed a higher prevalence of epilepsy than previously reported. The age of epilepsy onset and rate of focal seizures evolving to bilateral convulsive seizures in KABUK1 were also higher than previously reported in patients with clinically diagnosed Kabuki syndrome. Although seizure outcome is reported to be favorable in Kabuki syndrome, focal seizures in patients with KABUK1 were not immediately responsive to medication.

Todd's Paralysis: A Crucial Entity Masquerading Stroke in the Emergency Department

A 73-year-old female with history of hypertension, left parietal ischemic stroke (leading to sequela of slight paralysis in her right extremities), and symptomatic epilepsy presented with right-sided weakness after a 5-min-long, convulsive right-sided seizure. Due to the post-seizure right-sided paralysis, the patient was referred to our center with a provisional diagnosis of acute stroke. However, interrogation of patient history revealed that the patient had been taking aspirin 300 mg and phenytoin 2 × 100 mg regularly before her presentation. At admission to our emergency department, the patient was evaluated as oriented and cooperated; however, motor examination showed paralysis on her right side (3-/5, Medical Research Council [MRC] scale). Cranial magnetic resonance imaging (MRI) performed 5 h after the seizure revealed widespread cortical diffusion restriction in the left hemisphere, which did not correspond to any vascular territory (Figure 1). Taking together the clinical manifestations and neuroimaging findings, the diagnosis was established as Todd's paralysis and antiepileptic therapy was increased to phenytoin 3 × 100 mg and levetiracetam 3 × 500 mg. Routine electroencephalography showed paroxysmal epileptiform discharges in the left hemisphere. In the following days, the patient's weakness gradually improved and the evaluation on day 4 showed recovery back to her premorbid status (4+/5, MRC). The cranial MRI performed concurrently showed total normalization of the diffusion sequences (Figure 2). Figure 2(A) Diffusion weighted imaging showing total normalization of the diffusion restriction (arrows). (B) Fluid-attenuated inversion recovery sequences showing left parietal sequela ishemic lesion (arrows). View Large Image Figure Viewer Download Hi-res image

Jeavons syndrome existing as occipital cortex initiating generalized epilepsy

Jeavons syndrome (JS) is one of the underreported epileptic syndromes characterized by eyelid myoclonia (EM), eye closure-induced seizures/electroencephalography (EEG) paroxysms, and photosensitivity. JS has been proposed as idiopathic generalized epilepsy (IGE) because of normal posterior dominant background activity and paroxysmal generalized ictal epileptiform discharges (EDs). However, we noticed subtle occipital EDs preceding EM and interictal posterior EDs using digital video-EEG. We studied clinical and EEG findings in JS to determine the specific occipital lobe relation to this "eye closure-induced" reflex IGE. We identified 12 children who met the diagnostic criteria of JS from January 2004 to April 2009 at the Hospital for Sick Children, Toronto, Canada. All patients had EM captured by video-EEG. We reviewed and described ictal EEG patterns, interictal abnormalities, and demographics, clinical, and neuroimaging findings. All patients but one were female (92%). Age at seizure onset ranged from 1.5 to 9 years, with a mean age of 4.9 years. Six patients (50%) were previously diagnosed as having absence epilepsy and 10 patients were on antiepileptic medications. All 12 patients had normal posterior dominant alpha rhythm, reactive to eye opening and closure. Spiky posterior alpha activity was noted with sustained eye closure in six patients (50%). Interictally, there were generalized EDs found in 10 patients (83%); four of them also had focal interictal EDs over the posterior head region. Eleven patients (92%) had evidence of focal posterior ictal EDs. EM and/or paroxysmal EDs were induced by photic stimulation in 9 (75%) and hyperventilation in 7 (58%). We observed two neurophysiologic findings in JS: (1) focal interictal EDs from posterior head region; and (2) predominant focal posterior ictal EDs preceding generalized EDs. Further clinical observations of seizures induced by eye closure, photic stimulation, and hyperventilation along with EEG paroxysms would raise the possibility of the occipital cortex initiating generalized epilepsy network involving the brainstem, and thalamocortical and transcortical pathways in JS.

Scn1a missense mutation causes limbic hyperexcitability and vulnerability to experimental febrile seizures

Mutations of the voltage-gated sodium (Na v) channel subunit SCN1A have been implicated in the pathogenesis of human febrile seizures including generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy in infancy (SMEI). Hyperthermia-induced seizure-susceptible (Hiss) rats are the novel rat model carrying a missense mutation (N1417H) of Scn1a, which is located in the third pore-forming region of the Na v1.1 channel. Here, we conducted behavioral and neurochemical studies to clarify the functional relevance of the Scn1a mutation in vivo and the mechanism underlying the vulnerability to hyperthermic seizures. Hiss rats showed markedly high susceptibility to hyperthermic seizures (mainly generalized clonic seizures) which were synchronously associated with paroxysmal epileptiform discharges. Immunohistochemical analysis of brain Fos expression revealed that hyperthermic seizures induced a widespread elevation of Fos-immunoreactivity in the cerebral cortices including the motor area, piriform, and insular cortex. In the subcortical regions, hyperthermic seizures enhanced Fos expression region—specifically in the limbic and paralimbic regions (e.g., hippocampus, amygdala, and perirhinal–entorhinal cortex) without affecting other brain regions (e.g., basal ganglia, diencephalon, and lower brainstem), suggesting a primary involvement of limbic system in the induction of hyperthermic seizures. In addition, Hiss rats showed a significantly lower threshold than the control animals in inducing epileptiform discharges in response to local stimulation of the hippocampus (hippocampal afterdischarges). Furthermore, hyperthermic seizures in Hiss rats were significantly alleviated by the antiepileptic drugs, diazepam and sodium valproate, while phenytoin or ethosuximide were ineffective. The present findings support the notion that Hiss rats are useful as a novel rat model of febrile seizures and suggest that hyperexcitability of limbic neurons associated with Scn1a missense mutation plays a crucial role in the pathogenesis of febrile seizures.

Epileptiform discharges augmented during sleep: Is it a trait with diverse clinical presentation according to age of expression?

Sleep has long been viewed as a negative phenomenon; however, it is now clear that it is a period of intense brain activity involving higher cortical functions. Overall, sleep affects every aspect of a child's development, particularly higher cognitive functions. The seizure threshold is often affected by changes in the level of arousal, and many interictal EEG abnormalities are activated by sleep. Epileptiform discharges augmented during sleep are described in number of epileptic syndromes characterized by infrequent clinical seizures but significant cognitive deterioration, the prototype of which is the syndrome of continuous spike-wave discharges during sleep (CSWS). In this article the conditions sharing the same EEG feature of paroxysmal epileptiform discharges augmented during sleep and their overlap will be highlighted arguing whether these disorders may be clinical presentations of same trait when expressed at different stages of brain maturity, as well as the controversies in definition and management of cases without clinical seizures.

The Electrocortical Effects of Enflurane: Experiment and Theory

High concentrations of enflurane will induce a characteristic electroencephalogram pattern consisting of periods of suppression alternating with large short paroxysmal epileptiform discharges (PEDs). In this study, we compared a theoretical computer model of this activity with real local field potential (LFP) data obtained from anesthetized rats. After implantation of a high-density 8 x 8 electrode array in the visual cortex, the patterns of LFP and multiunit spike activity were recorded in rats during 0.5, 1.0, 1.5, and 2.0 minimum alveolar anesthetic concentration (MAC) enflurane anesthesia. These recordings were compared with computer simulations from a mean field model of neocortical dynamics. The neuronal effect of increasing enflurane concentration was simulated by prolonging the decay time constant of the inhibitory postsynaptic potential (IPSP). The amplitude of the excitatory postsynaptic potential (EPSP) was modulated, inverse to the neocortical firing rate. In the anesthetized rats, increasing enflurane concentrations consistently caused the appearance of suppression pattern (>1.5 MAC) in the LFP recordings. The mean rate of multiunit spike activity decreased from 2.54/s (0.5 MAC) to 0.19/s (2.0 MAC). At high MAC, the majority of the multiunit action potential events became synchronous with the PED. In the theoretical model, prolongation of the IPSP decay time and activity-dependent EPSP modulation resulted in output that was similar in morphology to that obtained from the experimental data. The propensity for rhythmic seizure-like activity in the model could be determined by analysis of the eigenvalues of the equations. It is possible to use a mean field theory of neocortical dynamics to replicate the PED pattern observed in LFPs in rats under enflurane anesthesia. This pattern requires a combination of a moderately increased total area under the IPSP, prolonged IPSP decay time, and also activity-dependent modulation of EPSP amplitude.

Epileptic Discharges in a Mammillary Body of a Patient with Refractory Epilepsy

Objectives. To document epileptiform discharges recorded within a mammillary body (MB) of a patient with chronic refractory epilepsy (CRE). Materials and Methods. A 37-year-old man, whose epilepsy was not controlled by medication or vagus nerve stimulation, was enrolled in a study of the effects of deep brain stimulation of the MB and mammillothalamic tract (MTT) in CRE. Surface and deep EEG recordings were obtained for 3 days before implantation of the macroelectrodes and for 4 days after implantation of the macroelectrodes but before implantation of the stimulator battery. Results. Paroxysmal epileptiform discharges were recorded in the right MB while other surface and deep recordings, in particular from the right MTT, were silent. When these discharges were longer than 100 sec, they spread to the right MTT area and then to the left MB and MTT area. Simultaneously, the patient became agitated and confused. Conclusions. This original observation indicates that subcortical neuronal structures, such as the MB, may sustain epileptiform discharges in humans.

Deep EEG Recordings of the Mammillary Body in Epilepsy Patients

To our knowledge, the epileptic and nonepileptic electroencephalographic (EEG) discharges recorded within the human mammillary body (MB) and mammillothalamic tract (MTT) areas have never been published. Herein, we present the EEG recordings from these structures in patients with refractory epilepsy (RE). Three men (ages 41-43 years) were enrolled in a clinical trial for deep brain stimulation (DBS) of MB-MTT in RE. Previous evaluations had demonstrated a low likelihood of successful response to medication or resective surgery. DBS macroelectrodes were bilaterally implanted within the MB-MTT under general anesthesia and their location checked by magnetic resonance imaging (MRI). We obtained a surface-depth EEG for a 2- to 4-day period, including monitoring of the cardiorespiratory and mnemonic functions. The background pattern of EEG recorded from MB-MTT was low-amplitude (usually <25 microv for MB and <20 microv for MTT) waves with a variable combination of theta-beta rhythms. In two patients, pseudoperiodic slow spikes were unilaterally recorded with or without clinical signs. For one patient, several focal ictal discharges were recorded in the right MB without scalp EEG changes. The analysis of our depth EEG revealed that the theta-beta pattern represents the predominant physiologic profile of MB. Paroxysmal epileptiform discharges can be observed in human MB. These data supplement those available from animal observations.

Pattern‐sensitive Epilepsy: Electroclinical Characteristics, Natural History, and Delineation of the Epileptic Syndrome

To elucidate the electroclinical features and long-term outcome of patients with pattern-sensitive epilepsy. We reviewed the clinical and electroencephalographic (EEG) findings of 73 (43 female and 30 male) patients in whom pattern-sensitive epilepsy was diagnosed at Mayo Clinic (Rochester, Minnesota, U.S.A.) from 1950 through 1999. We contacted patients and their relatives by letter or telephone to obtain the latest seizure and quality-of-life outcomes. The median age at onset of seizures was 12.8 years (range, 0.6-32.9 years). Most patients had absence, myoclonic, or generalized tonic-clonic seizures. Interictal epileptiform discharges in the EEG were detected in 61 (83.6%) patients and were generalized in 54 (74%). Paroxysmal epileptiform discharges in the EEG elicited with standard patterns were all generalized in two thirds of patients but were restricted to the posterior head region in one-third. Eight (11%) patients did not exhibit photosensitivity. Television was the most common precipitant [30 patients (41%)]. Twenty-nine patients gave a clear history of one or more seizures precipitated while viewing environmental patterns such as window screens, garments, tablecloths, and ceiling tiles; the rest of the patients admitted that they preferred to avoid looking at patterned objects because these objects made them uncomfortable. The electroclinical features suggested juvenile myoclonic epilepsy in 14 patients, progressive myoclonus epilepsy in three, progressive familial cerebellar ataxia with myoclonus in two, and severe myoclonic epilepsy of infancy in one. During a median follow-up period of 15.7 years, 25 (45.5%) of 55 patients who were followed up for > or =5 years achieved complete seizure remission. The median age at remission was 24.4 years. The absence of progressive neurologic disease was correlated significantly with remission; a family history of seizures showed a trend in favor of remission. More than two thirds of the patients did not consider the seizures an impediment to their family life or to educational and occupational achievements. Although pattern sensitivity as a trait occurs in various epileptic syndromes, pattern-sensitive epilepsy is a readily distinguishable subtype of the visually provoked reflex epilepsies. In our opinion, the location and extent of the excitable region or regions within the visual cortex concerned with different attributes of visual function dictate susceptibility to a specific trigger (intermittent light, pattern, or color) or closely related multiple triggers and the resultant electroclinical phenomenon.

Reflex epilepsy and reflex seizures of the visual system: a clinical review

ABSTRACT Reflex epilepsy of the visual system is charecterised by seizures precipitated by visual stimuli. EEG responses to intermittent photic stimulation depend on the age and sex of the subject and on how stimulation is performed: abnormalities are commonest in children and adolescents, especially girls. Only generalised paroxysmal epileptiform discharges are clearly linked to epilepsy. Abnormal responses may occur in asymptomatic subjects, especially children. Photosensitivity has an important genetic component. Some patients are sensitive to patterns, suggesting an occipital trigger for these events. Myoclonus and generalised convulsive and nonconvulsive seizures may be triggered by visual stimuli. Partial seizures occur less often and can be confused with migraine. Although usually idiopathic, photosensitive epilepsy may occur in degenerative diseases and some patients with photosensitive partial seizures have brain lesions. Sunlight and video screens, including television, video games, and computer displays, are the commonest environmental triggers of photosensitive seizures. Outbreaks of triggered seizures have occurred when certain flashing or patterned images have been broadcast. There are regulations to prevent this in some countries only. Pure photosensitive epilepsy has a good prognosis. There is a role for treatment with and without antiepileptic drugs, but photosensitivity usually does not disappear spontaneously, and then typically in the third decade.

EEG during MR imaging: differentiation of movement artifact from paroxysmal cortical activity.

It is possible to record scalp EEG during the acquisition of gradient-echo/echo-planar MR images or MR spectra without significant degradation of the MR data. [1] Functional MR imaging or spectroscopy with simultaneous EEG recording allows the study of hemodynamic and metabolic changes in vivo in human subjects during cognitive tasks in normal subjects and in patients with paroxysmal epileptiform discharges or ictal events. [2] EEG registration in the MR scanner, however, is very susceptible to a variety of artifacts, particularly patient head movement and ballistocardiogram; the latter is related to head and body movements produced during systole. Despite having the head securely restrained, very small movements of the head produce high-amplitude, paroxysmal bursts on EEG that are impossible to differentiate from paroxysmal cortical epileptiform activity. This artifact results from currents produced by small movements of the EEG electrodes and wires …

Paroxysmal epileptiform discharges in temporal lobe slices after prolonged exposure to low magnesium are resistant to clinically used anticonvulsants.

Lowering of extracellular Mg2+ results in various forms of epileptiform activity in different parts of temporal lobe slices [5,22] which contain neocortical areas such as areas Te2 or Te3, the entorhinal cortex (EC), subiculum, hippocampal areas CA1 to CA3 and the dentate gyrus [5,11]. In the EC, the subiculum and Te2/Te3 seizure-like events (SLEs) with tonic and clonic electrographic discharge patterns, negative slow field potentials and ionic changes comparable to those during tonic-clonic seizures in intact animals were observed. After 30 to 120 min of recurrent seizure activity (80 +/- 37 min) the seizure-like events (SLEs) developed into a state of late recurrent discharges (LRDs). Since previous studies had shown that the LRDs do not respond to valproic acid in contrast to a blocking effect of this drug on SLEs, we investigated the effects of the clinically employed anticonvulsants phenytoin, carbamazepine, phenobarbital, midazolam and ethosuximide on LRDs. All these agents were unable to block the LRDs in the EC, subiculum and Te2/Te3. This was found true both for concentrations which can block SLEs and for higher concentrations. Thus we conclude that this activity may represent a model of difficult to treat status epilepticus.