Nonconvulsive Epileptic Seizures Research Articles

Cerebral hemorrhagic infarction was diagnosed subsequently after high-amplitude slow waves detected on processed electroencephalogram during sedation: a case report

BackgroundContinuous electroencephalogram (EEG) monitoring is useful for assessing the level of sedation and detecting non-convulsive epileptic seizures and cerebral ischemia in the intensive care unit. This report describes a case of cerebral hemorrhagic infarction diagnosed after the detection of high-amplitude slow waves on processed EEG during sedation.Case presentationA 68-year-old man who underwent cardiac surgery was sedated in the intensive care unit following an invasive procedure. High-amplitude slow waves appeared on processed EEG monitoring before the detection of anisocoria. Computed tomography revealed a cerebral hemorrhagic infarction.ConclusionsIn the management of critically ill patients, continuous EEG monitoring with forehead electrodes may be useful in the early detection of brain lesions.

Diagnostic Procedure and Therapeutic Approaches in Nonconvulsive Status Epilepticus (NCSE)

Nonconvulsive epileptic seizures are major type of seizures of all patients with predominantly focal epilepsy. However, this problem is still insufficiently studied, the literature presents a few data on the diagnosis and treatment of nonconvulsive status epilepticus (NCSE). NCSE is a prolonged seizure, not accompanied by severe motor presentation. Such attacks occur much more often than previously thought. NCSE is divided into focal NCSE (complex partial status epilepticus), and generalized NCSE, often referred as absence status. The absence status divides into a typical absence status (presents with suppression of consciousness of various depths, myoclonic twitching of the eyelids, impoverishment of speech production and hallucinations), atypical absence status (presents with retardation of mental processes and eyelid myoclonus) and late absence status (long-term disorientation accompanied by cognitive deficiency and presents mainly in elderly patients). According to the available sources, more than 30% of patients in the intensive care units with impaired consciousness of unclear genesis are patients with NCSE. Use of antiepileptic drugs for intravenous administration opens better opportunities in the treatment of patients with status epilepticus and NCSE.

Nonconvulsive epileptic seizure monitoring with incremental learning

Nonconvulsive epileptic seizures (NCSz) and nonconvulsive status epilepticus (NCSE) are two neurological entities associated with increment in morbidity and mortality in critically ill patients. In a previous work, we introduced a method which accurately detected NCSz in EEG data (referred here as ‘Batch method’). However, this approach was less effective when the EEG features identified at the beginning of the recording changed over time. Such pattern drift is an issue that causes failures of automated seizure detection methods. This paper presents a support vector machine (SVM)-based incremental learning method for NCSz detection that for the first time addresses the seizure evolution in EEG records from patients with epileptic disorders and from ICU having NCSz. To implement the incremental learning SVM, three methodologies are tested. These approaches differ in the way they reduce the set of potentially available support vectors that are used to build the decision function of the classifier. To evaluate the suitability of the three incremental learning approaches proposed here for NCSz detection, first, a comparative study between the three methods is performed. Secondly, the incremental learning approach with the best performance is compared with the Batch method and three other batch methods from the literature. From this comparison, the incremental learning method based on maximum relevance minimum redundancy (MRMR_IL) obtained the best results. MRMR_IL method proved to be an effective tool for NCSz detection in a real-time setting, achieving sensitivity and accuracy values above 99%.

Immune Profile in Blood Following Non-convulsive Epileptic Seizures in Rats.

Non-convulsive status epilepticus (NCSE) is a prolonged epileptic seizure with subtle symptoms that may delay clinical diagnosis. Emerging experimental evidence shows brain pathology and epilepsy development following NCSE. New diagnostic/prognostic tools are therefore needed for earlier and better stratification of treatment. Here we examined whether NCSE initiates a peripheral immune response in blood serum from rats that experienced electrically-induced NCSE. ELISA analysis showed an acute transient increase in serum protein levels including interleukin-6 6 h post-NCSE, similar to the immune reaction in the brain. At 4 weeks post-NCSE, when 75% of rats subjected to NCSE had also developed spontaneous seizures, several immune proteins were altered. In particular, markers associated with microglia, macrophages and antigen presenting cells, such as CD68, MHCII, and galectin-3, were increased and the T-cell marker CD4 was decreased in serum compared to both non-stimulated controls and NCSE rats without spontaneous seizures, without correlation to interictal epileptiform activity. Analyses of serum following intracerebral injection of lipopolysaccharide (LPS) showed an acute increase in interleukin-6, but at 4 weeks unaltered levels of MHCII and galectin-3, an increase in CD8 and CD11b and a decrease in CD68. None of the increased serum protein levels after NCSE or LPS could be confirmed in spleen tissue. Our data identifies the possibility to detect peripheral changes in serum protein levels following NCSE, which may be related to the development of subsequent spontaneous seizures.

Novel features for capturing temporal variations of rhythmic limb movement to distinguish convulsive epileptic and psychogenic nonepileptic seizures.

To investigate the characteristics of motor manifestation during convulsive epileptic and psychogenic nonepileptic seizures (PNES), captured using a wrist-worn accelerometer (ACM) device. The main goal was to find quantitative ACM features that can differentiate between convulsive epileptic and convulsive PNES. In this study, motor data were recorded using wrist-worn ACM-based devices. A total of 83 clinical events were recorded: 39 generalized tonic-clonic seizures (GTCS) from 12 patients with epilepsy, and 44 convulsive PNES from 7 patients (one patient had both GTCS and PNES). The temporal variations in the ACM traces corresponding to 39 GTCS and 44 convulsive PNES events were extracted using Poincaré maps. Two new indices-tonic index (TI) and dispersion decay index (DDI)-were used to quantify the Poincaré-derived temporal variations for every GTCS and convulsive PNES event. The TI and DDI of Poincaré-derived temporal variations for GTCS events were higher in comparison to convulsive PNES events (P < 0.001). The onset and the subsiding patterns captured by TI and DDI differentiated between epileptic and convulsive nonepileptic seizures. An automated classifier built using TI and DDI of Poincaré-derived temporal variations could correctly differentiate 42 (sensitivity: 95.45%) of 44 convulsive PNES events and 37 (specificity: 94.87%) of 39 GTCS events. A blinded review of the Poincaré-derived temporal variations in GTCS and convulsive PNES by epileptologists differentiated 26 (sensitivity: 70.27%) of 44 PNES events and 33 (specificity: 86.84%) of 39 GTCS events correctly. In addition to quantifying the motor manifestation mechanism of GTCS and convulsive PNES, the proposed approach also has diagnostic significance. The new ACM features incorporate clinical characteristics of GTCS and PNES, thus providing an accurate, low-cost, and practical alternative to differential diagnosis of PNES.

Impact of strain, sex, and estrous cycle on gamma butyrolactone-evoked absence seizures in rats

Childhood absence epilepsy (CAE) is the most common pediatric epilepsy syndrome and is characterized by typical absence seizures (AS). AS are non-convulsive epileptic seizures characterized by a sudden loss of awareness and bilaterally generalized synchronous 2.5–4 Hz spike and slow-wave discharges (SWD). Gamma butyrolactone (GBL) is an acute pharmacological model of AS and induces bilaterally synchronous SWDs and behavioral arrest. Despite the long use of this model, little is known about its strain and sex-dependent features. We compared the dose-response profile of GBL-evoked SWDs in three rat strains (Long Evans, Sprague-Dawley, and Wistar), and examined the modulatory effects of estrous cycle on SWDs in female Wistar rats. We evaluated the number of seizures, the cumulative time seizing, and the average seizure duration as a function of dose, strain, and sex/estrous phase. Long Evans rats displayed the greatest sensitivity to GBL, followed by Wistar rats, and then by Sprague-Dawley rats. GBL-evoked SWDs were modulated by estrous cycle in female rats, with the lowest sensitivity to GBL occurring during metestrus. Wistar rats showed the greatest variability as a function of dose, and the least variability within dose; these features make this strain desirable for interventional studies. Moreover, our finding that the SWD response to GBL differs as a function of estrous cycle underscores the importance of cycle monitoring in studies examining female animals using this model. Together, these strain and sex-dependent findings provide guidance for future studies.

Detection of convulsive seizures using surface electromyography.

Bilateral (generalized) tonic-clonic seizures (TCS) increase the risk of sudden unexpected death in epilepsy (SUDEP), especially when patients are unattended. In sleep, TCS often remain unnoticed, which can result in suboptimal treatment decisions. There is a need for automated detection of these major epileptic seizures, using wearable devices. Quantitative surface electromyography (EMG) changes are specific for TCS and characterized by a dynamic evolution of low- and high-frequency signal components. Algorithms targeting increase in high-frequencyEMG signals constitute biomarkers of TCS; they can be used both for seizure detection and for differentiating TCS from convulsive nonepileptic seizures. Two large-scale, blinded, prospective studies demonstrated the accuracy of wearable EMG devices for detecting TCS with high sensitivity (76%-100%). The rate of false alarms (0.7-2.5/24h) needs further improvement. This article summarizes the pathophysiology of muscle activation during convulsive seizures and reviews the published evidence on the accuracy of EMG-based seizure detection.

Acute management of early post-traumatic epilepsy in patients with mild to moderate traumatic brain injury

BackgroundContinuous electroencephalography (EEG) monitoring for up to 24 h has been suggested to detect non-convulsive epileptic seizures during the acute phase of severe traumatic brain injury (T...

Quantitative analysis of surface electromyography: Biomarkers for convulsive seizures.

Muscle activity during seizures is in electroencephalographical (EEG) praxis often considered an irritating artefact. This article discusses ways by surface electromyography (EMG) to turn it into a valuable tool of epileptology. Muscles are in direct synaptic contact with motor neurons. Therefore, EMG signals provide direct information about the electric activity in the motor cortex. Qualitative analysis of EMG has traditionally been a part of the long-term video-EEG recordings. Recent development in quantitative analysis of EMG signals yielded valuable information on the pathomechanisms of convulsive seizures, demonstrating that it was different from maximal voluntary contraction, and different from convulsive psychogenic non-epileptic seizures. Furthermore, the tonic phase of the generalised tonic-clonic seizures (GTCS) proved to have different quantitative features than tonic seizures. The high temporal resolution of EMG allowed detailed characterisation of temporal dynamics of the GTCS, suggesting that the same inhibitory mechanisms that try to prevent the build-up of the seizure activity, contribute to ending the seizure. These findings have clinical implications: the quantitative EMG features provided the pathophysiologic substrate for developing neurophysiologic biomarkers that accurately identify GTCS. This proved to be efficient both for seizure detection and for objective, automated distinction between convulsive and non-convulsive epileptic seizures.

Posttraumatic seizures and epilepsy in adult rats after controlled cortical impact

Posttraumatic epilepsy (PTE) has been modeled with different techniques of experimental traumatic brain injury (TBI) using mice and rats at various ages. We hypothesized that the technique of controlled cortical impact (CCI) could be used to establish a model of PTE in young adult rats. A total of 156 male Sprague-Dawley rats of 2–3 months of age (128 CCI-injured and 28 controls) was used for monitoring and/or anatomical studies. Provoked class 3–5 seizures were recorded by video monitoring in 7/57 (12.3%) animals in the week immediately following CCI of the right parietal cortex; none of the 7 animals demonstrated subsequent spontaneous convulsive seizures. Monitoring with video and/or video-EEG was performed on 128 animals at various time points 8–619 days beyond one week following CCI during which 26 (20.3%) demonstrated nonconvulsive or convulsive epileptic seizures. Nonconvulsive epileptic seizures of >10s were demonstrated in 7/40 (17.5%) animals implanted with 2 or 3 depth electrodes and usually characterized by an initial change in behavior (head raising or animal alerting) followed by motor arrest during an ictal discharge that consisted of high-amplitude spikes or spike-waves with frequencies ranging between 1 and 2Hz. Class 3–5 epileptic seizures were recorded by video monitoring in 17/88 (19%) and by video-EEG in 2/40 (5%) CCI-injured animals. Ninety of 156 (58%) animals (79 CCI-injured, 13 controls) underwent transcardial perfusion for gross and microscopic studies. CCI caused severe brain tissue loss and cavitation of the ipsilateral cerebral hemisphere associated with cell loss in the hippocampal CA1 and CA3 regions, hilus, and dentate granule cells, and thalamus. All Timm-stained CCI-injured brains demonstrated ipsilateral hippocampal mossy fiber sprouting in the inner molecular layer. These results indicate that the CCI model of TBI in adult rats can be used to study the structure–function relationships that underlie epileptogenesis and PTE.

Continuous EEG monitoring in adults in the intensive care unit (ICU)

Continuous EEG monitoring in the ICU is different from planned EEG due to the rather urgent nature of the indications, explaining the fact that recording is started in certain cases by the clinical team in charge of the patient's care. Close collaboration between neurophysiology teams and intensive care teams is essential. Continuous EEG monitoring can be facilitated by quantified analysis systems. This kind of analysis is based on certain signal characteristics, such as amplitude or frequency content, but raw EEG data should always be interpreted if possible, since artefacts can sometimes impair quantified EEG analysis. It is preferable to work within a tele-EEG network, so that the neurophysiologist has the possibility to give an interpretation on call. Continuous EEG monitoring is thus useful in the diagnosis of non-convulsive epileptic seizures or purely electrical discharges and in the monitoring of status epilepticus when consciousness disorders persist after initial treatment. A number of other indications are currently under evaluation.

Postictal serum creatine kinase for the differential diagnosis of epileptic seizures and psychogenic non-epileptic seizures: a systematic review.

The aim of this review was to evaluate the sensitivity and specificity of postictal creatine kinase (CK) levels in the differential diagnosis of epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES). A systematic search was conducted for studies that evaluated postictal CK levels in patients with ES (all types) and PNES. Sensitivity and specificity with 95% confidence intervals were determined for each study, taking into account: (a) the upper limits adopted; and (b) the 95.7th percentile values, which are recently proposed practical upper reference limits for CK activity. Four studies, comprising a total of 343 events (248 ES and 95 PNES), were available for analysis. Most patients (47/78, 60%) with ES considered had primarily or secondarily generalized tonic-clonic seizures. The sensitivity of increased postictal CK levels for ES ranged from 14.6 to 87.5, whereas specificity ranged from 85.0 to 100.0. At the 95.7th percentile threshold, sensitivity ranged from 14.6 to 62.5 and specificity was 100.0. The limited number of studies available, their small sample size, and lack of individual event data prevented further stratification analysis by seizure type. Despite the clinical heterogeneity and the limitations of the included studies, increased postictal CK levels are highly specific for the diagnosis of ES, although no definite conclusion on its role in differentiating between convulsive and non-convulsive ES can be drawn. Postictal serum CK levels can provide valuable retrospective information at the later stages of the differential diagnosis of ES and PNES. Due to low sensitivity, normal postictal CK levels do not exclude ES.

Effects of linoleic acid on generalized convulsive and nonconvulsive epileptic seizures.

To comparatively investigate the effects of linoleic acid on convulsive and nonconvulsive epileptic seizures. Rats were divided into 3 groups: convulsive epileptic rats receiving only pentylentetrazole (PTZ) injections (group 1), convulsive epileptic rats receiving PTZ and linoleic acid (group 2), and Wistar Albino Glaxo rats from Rijswijk with genetic absence epilepsy receiving linoleic acid (group 3). The duration and severity of convulsive activity were determined in groups in which convulsive seizures were induced by PTZ. In group 3, intravenous linoleic acid was administered after 1-h baseline electroencephalography (EEG) recordings. The EEG recordings were analyzed. When groups 1 and 2 were compared, the delay in onset of minor seizures and the decrease in the number of rats developing major seizures were found statistically significant. When the mean spike-wave discharge number and duration values for the rats in group 3 were compared to baseline values, a statistically significant increase was found in the 1st and 6th hours and there was no significant difference in the 24th hour. While our study shows that linoleic acid may be effective in the treatment of generalized convulsive epilepsy along with conventional antiepileptic drugs used in epilepsy treatment, it reports that linoleic acid is not appropriate in the treatment of nonconvulsive epilepsies.

Poster #74 CAN D2/3 BLOCKADE IMPROVE BASIC INFORMATION PROCESSING IN FIRST EPISODE SCHIZOPHRENIA?

Muscle activity during seizures is in electroencephalographical (EEG) praxis often considered an irritating artefact. This article discusses ways by surface electromyography (EMG) to turn it into a valuable tool of epileptology.Muscles are in direct synaptic contact with motor neurons. Therefore, EMG signals provide direct information about the electric activity in the motor cortex. Qualitative analysis of EMG has traditionally been a part of the long-term video-EEG recordings.Recent development in quantitative analysis of EMG signals yielded valuable information on the pathomechanisms of convulsive seizures, demonstrating that it was different from maximal voluntary contraction, and different from convulsive psychogenic non-epileptic seizures. Furthermore, the tonic phase of the generalised tonic–clonic seizures (GTCS) proved to have different quantitative features than tonic seizures. The high temporal resolution of EMG allowed detailed characterisation of temporal dynamics of the GTCS, suggesting that the same inhibitory mechanisms that try to prevent the build-up of the seizure activity, contribute to ending the seizure.These findings have clinical implications: the quantitative EMG features provided the pathophysiologic substrate for developing neurophysiologic biomarkers that accurately identify GTCS. This proved to be efficient both for seizure detection and for objective, automated distinction between convulsive and non-convulsive epileptic seizures.

A structured questionnaire predicts if convulsions are epileptic or nonepileptic

Objective Therapy for convulsive seizures is usually initiated on the basis of clinical assessment, without video/EEG confirmation, but a nonepileptic origin may eventually be demonstrated. This study evaluates the diagnostic value of a witness-questionnaire in distinguishing between convulsive epileptic seizures (CES) and convulsive nonepileptic seizures (CNES). Methods We prospectively identified all adult patients admitted for video/EEG evaluation of convulsive attacks and interviewed the “best” witness using 12 questions on ictal and postictal features. Results Video/EEG diagnosed CES in 19 and CNES in 26 patients. The predictive accuracy of the questionnaire was 84.4%. Six features were strong predictors of CNES diagnosis: ictal eye closure, presence of side-to-side movements, prolonged seizure duration, and three postictal breathing features (not loud, shallow, no snoring). Conclusion A structured witness questionnaire distinguishes CES and CNES and will help in selecting patients for early video/EEG evaluation and rapid initiation of appropriate therapy.

Diagnosing Pseudoseizures: Don't Hold Your Breath

Postictal Breathing Pattern Distinguishes Epileptic from Nonepileptic Convulsive Seizures. Azar NJ, Tayah TF, Wang L, Song Y, Abou-Khalil BW. Epilepsia 2008;49(1):132–137. PURPOSE: To examine postictal breathing pattern in generalized convulsive nonepileptic seizures (GCNES) and generalized tonic–clonic seizures (GTCS) and evaluate this feature as a discriminating sign. METHODS: We reviewed the postictal breathing pattern seizures in 23 generalized tonic–clonic seizures in 15 consecutive patients with epilepsy and 24 convulsive nonepileptic seizures in 16 consecutive patients with pure psychogenic seizures. We also analyzed 21 frontal lobe hypermotor seizures (FLHS) in 9 patients with frontal lobe epilepsy. RESULTS: The breathing after GTCS was deep with prolonged inspiratory and expiratory phases, regular, and loud (except for two short seizures). The breathing after GCNES was characterized by increased respiratory rate or hyperpnea with short inspiratory and expiratory phases, as can be noted after exercise. The breathing was often irregular, with brief pauses. The altered breathing lasted longer after GTCS. The two groups differed significantly in loudness of postictal respiration, postictal snoring (only with GTCS), respiratory rate (faster for the GCNES group), and duration of altered breathing (longer after GTCS) (p &lt; 0.00001 for all features). FLHS shared postictal breathing features of GCNES, but had other distinguishing features. CONCLUSIONS: The postictal breathing pattern can help differentiate generalized tonic–clonic seizures from nonepileptic psychogenic seizures with generalized motor activity and may be helpful to the practitioner obtaining a seizure history in the clinic setting or witnessing a seizure.

Postictal Breathing Pattern Distinguishes Epileptic from Nonepileptic Convulsive Seizures

To examine postictal breathing pattern in generalized convulsive nonepileptic seizures (GCNES) and generalized tonic-clonic seizures (GTCS) and evaluate this feature as a discriminating sign. We reviewed the postictal breathing pattern seizures in 23 generalized tonic-clonic seizures in 15 consecutive patients with epilepsy and 24 convulsive nonepileptic seizures in 16 consecutive patients with pure psychogenic seizures. We also analyzed 21 frontal lobe hypermotor seizures (FLHS) in 9 patients with frontal lobe epilepsy. The breathing after GTCS was deep with prolonged inspiratory and expiratory phases, regular, and loud (except for two short seizures). The breathing after GCNES was characterized by increased respiratory rate or hyperpnea with short inspiratory and expiratory phases, as can be noted after exercise. The breathing was often irregular, with brief pauses. The altered breathing lasted longer after GTCS. The two groups differed significantly in loudness of postictal respiration, postictal snoring (only with GTCS), respiratory rate (faster for the GCNES group), and duration of altered breathing (longer after GTCS) (p < 0.00001 for all features). FLHS shared postictal breathing features of GCNES, but had other distinguishing features. The postictal breathing pattern can help differentiate generalized tonic-clonic seizures from nonepileptic psychogenic seizures with generalized motor activity and may be helpful to the practitioner obtaining a seizure history in the clinic setting or witnessing a seizure.

Deep Layer Somatosensory Cortical Neurons Initiate Spike-and-Wave Discharges in a Genetic Model of Absence Seizures

Typical absence has long been considered as the prototypic form of generalized nonconvulsive epileptic seizures. Recent investigations in patients and animal models suggest that absence seizures could originate from restricted regions of the cerebral cortex. However, the cellular and local network processes of seizure initiation remain unknown. Here, we show that absence seizures in Genetic Absence Epilepsy Rats from Strasbourg, a well established genetic model of this disease, arise from the facial somatosensory cortex. Using in vivo intracellular recordings, we found that epileptic discharges are initiated in layer 5/6 neurons of this cortical region. These neurons, which show a distinctive hyperactivity associated with a membrane depolarization, lead the firing of distant cortical cells during the epileptic discharge. Consistent with their ictogenic properties, neurons from this "focus" exhibit interictal and preictal oscillations that are converted into epileptic pattern. These results confirm and extend the "focal hypothesis" of absence epilepsy and provide a cellular scenario for the initiation and generalization of absence seizures.

Transient global amnesia may be caused by cerebral vein thrombosis

Transient global amnesia (TGA) is a disorder of unknown aetiology, characterized by sudden loss of anterograde memory, in the absence other neurological signs or symptoms, followed by complete recovery in less than 24h. Precipitating actions such as strenuous physical activity or valsalva-like manoeuvres are frequently reported. Since first described in 1958, by Fisher and Adams, the possible pathophysiology has undergone much speculation. Nonconvulsive epileptic seizures, migraine, paradoxical embolism thorough a patent foramen ovale, and transient ischemic attacks have been proposed as potential mechanisms. One of the latest hypotheses is that venous congestion causes either ischemia or induces spreading depression in the medial temporal lobes. It has been demonstrated that retrograde flow in the internal jugular veins occurs more frequently during valsalva manoeuvres in TGA patients than in controls, supporting a dysfunctional venous circulation as part of the pathogenesis. However, earlier hypotheses typically fail to explain the relatively low recurrence rate of TGA, lack of comorbidity and the relation to precipitating events. If cerebral venous hypertension was the solely cause of TGA it would presumably be much more common with very high recurrence rates among those predisposed of the condition. Structural changes observed in MRI and SPECT studies along with reports of mild cognitive impairment lasting much longer than the amnestic episodes, indicate that TGA is less transient and perhaps somewhat less benign than earlier believed. Many cases of TGA seem to be associated with factors of increased risk of cerebral venous thrombosis, such as polycythemia, antiphospholipid antibodies, venous hypertension, female sex and more. We suggest that most cases of TGA may be due to small thrombi in the deep cerebral venous system. Small venous thrombi may difficult to visualize even when using modern imaging technology. Further studies of TGA patients with for example blood analysis of D-dimer together with MR venography or CT venography could be done to evaluate this new hypothesis.

The epileptology of Théodore Herpin (1799-1865).

The Frenchman, Théodore Herpin (1799-1865), in Des Accès Incomplets d'Epilepsie, published posthumously in 1867, provided a very detailed account of a wide range of the possible manifestations of nonconvulsive epileptic seizures. However, he did not note the presence of absence seizures in any of his 300 patients who had experienced, at least in some of their attacks, what he considered were incomplete manifestations of epilepsy, the word "epilepsy" being taken to refer to full generalized tonic-clonic seizures. In the one patient, Herpin recognized that all epileptic seizures, whether complete or incomplete, began in the same way, and deduced that they must originate in the same place in that patient's brain. He did not develop the latter idea further. His observations, and his interpretation of them, seem to have preceded John Hughlings Jackson's independent development of similar concepts, but Jackson's more extensive intellectual exploration of the implications of his observations made him a more important figure than Herpin in the history of epileptology.