Acute encephalopathy and myoclonic status induced by vigabatrin monotherapy]

Vigabatrin (VGB) is a new antiepileptic drug useful in refractOry partial seizures. Psychosis as a secondary effect of VGB is well known. This drug may even induce new epileptic seizures. We report a 69-year-old hypertensive patient with multiple cerebral infarcts. She was diagnosed as having late onset symptomatic partial epilepsy (complex partial seizures and generalized secondary motor partial seizures). She had been receiving VGB 3 g/day in monotherapy. She came to the emergency room in a psychotic state with new epileptic seizures. We performed an EEG and video during the ictal phase. The patient was awake, conscious and partially oriented. The video showed generalized myoclonic jerks involving facial and limb muscles, separated by non-convulsive intervals lasting three minutes. The EEG showed spike and wave discharges over a diffuse slow-wave background activity. The patient was conscious throughout the recording. The electroclinical picture was considered as an encephalopathy-associated generalized myoclonic status. VGB was replaced by phenytoin. Two weeks later, and after a clinical improvement, a new recording showed the disappearance of signs of encephalopathy and the myoclonic status. Epileptic seizures induced by VGB are well reported. Several pathogenic mechanisms have been suggested. In our case the myoclonic status was related to a non-dose dependent encephalopathy induced by VGB. The electroclinical improvement after withdrawal of the drug supports this possibility.     

Penicillin epilepsy in the rabbit

The effects of penicillin perfusion were studied in 16 rabbits with chronically implanted electrodes in the sensorimotor and in the visual cortex of both hemispheres. In 14 rabbits, at an average dose of 1,279,966 IU/kg, penicillin caused the appearance of generalized spikes or polyspikes accompanied by massive myoclonic jerks. Sometimes massive myoclonic jerks without EEG epileptic activity were seen. In one animal only spinal myoclonic activity without EEG epileptic abnormalities occurred. Three of these rabbits developed, after a mean penicillin dose of 2,193,174 IU/kg, generalized seizures accompanied on the EEG by bilateral and synchronous discharges of spike or polyspike and wave complexes. The effect of penicillin was tested also in a group of four rabbits in which a small cortical vascular lesion was made, and in another group of four animals with electrodes implanted into the hippocampus.Rabbits with a vascular lesion and those with hippocampal electrodes developed a focal epilepsy at a mean dose of 1,286,804 IU/kg. In the rabbits with the cortical lesion, the seizures started always from the site of the lesion. In the group of animals with the hippocampal electrodes, the seizures could begin, even in the same rabbit, from the hippocampus or from the cortex over the implanted electrode. Penicillin in the rabbit produces a predominantly myoclonic form of seizure disorder and only rarely organized generalized seizures similar to those observed in the cat. Under circumstances in which a local breakdown of the blood-brain barrier has been created, it induces focal seizure discharges that become often secondarily generalized.     

Instruction manual for the ILAE 2017 operational classification of seizure types

This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. Illustration of the classification is enacted by tables, a glossary of relevant terms, mapping of old to new terms, suggested abbreviations, and examples. Basic and extended versions of the classification are available, depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categories of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can further be optionally characterized by whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it a focal impaired awareness seizure. Focal seizures are further optionally characterized by motor onset signs and symptoms: atonic, automatisms, clonic, epileptic spasms, or hyperkinetic, myoclonic, or tonic activity. Nonmotor‐onset seizures can manifest as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which might then progress to other signs and symptoms. Focal seizures can become bilateral tonic–clonic. Generalized seizures engage bilateral networks from onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic–atonic, myoclonic–tonic–clonic, tonic, or tonic–clonic. Nonmotor (absence) seizures are typical or atypical, or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown onset may have features that can still be classified as motor, nonmotor, tonic–clonic, epileptic spasms, or behavior arrest. This “users’ manual” for the ILAE 2017 seizure classification will assist the adoption of the new system.     

Anleitung („instruction manual“) zur Anwendung der operationalen Klassifikation von Anfallsformen der ILAE 2017

This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. The classification is illustrated by tables, a glossary of relevant terms, a table mapping old to new terms, recommended abbreviations and examples. Basic and extended versions of the classification are available depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categorization of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can be further optionally characterized with respect to whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it classified as a focal impaired awareness seizure. Focal seizures can be further optionally characterized by the first motor signs and symptoms as atonic, automatisms, clonic, epileptic spasms, hyperkinetic, myoclonic or tonic activity. Nonmotor onset seizures can be manifested as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which can then further progress to other signs and symptoms. Focal seizures can become bilateral tonic–clonic seizures. Generalized seizures include an early involvement of bilateral networks from the onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic–atonic, myoclonic–tonic–clonic, tonic or tonic–clonic manifestatíons. Nonmotor (absence) seizures are typical or atypical or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown origin may have features that can still be classified as motor, nonmotor, tonic–clonic, epileptic spasms or behavior arrest. This users’ manual for the ILAE 2017 seizure classification can assist the acceptance of the new system.     

Idiopathic Generalized Epilepsies Imitating Focal Epilepsies

Summary:  Classification of epileptic seizures and epilepsy syndromes as either focal or generalized is a fundamental and early part in the diagnostic process and is generally fairly easily accomplished. However, in patients with idiopathic generalized epilepsies, seizure and EEG features may suggest, particularly to the unwary, the occurrence of focal rather than generalized seizures. Misinterpretation of typical absence seizures as focal seizures, especially as temporal lobe seizures and of myoclonic seizures as focal clonic seizures, is a relatively common error and focal features during generalized tonic–clonic seizures may also be quite common. Sequences of seizures in idiopathic generalized epilepsies (such as absences or jerks followed by generalized tonic–clonic seizures) may also cause confusion. Versive and circling seizures are seizure types whose ictal semiology is clearly focal; nevertheless such seizures are described in idiopathic generalized epilepsies accompanied by generalized EEG discharges. The occurrence of focal EEG abnormalities in certain idiopathic generalized epilepsy syndromes is common. This is best known in juvenile myoclonic epilepsy.     

Epileptic negative myoclonus induced by carbamazepine in a child with BECTS. Benign childhood epilepsy with centrotemporal spikes.

A 7-year-old female with benign childhood epilepsy with centrotemporal spikes developed epileptic negative myoclonus (ENM) seizures during carbamazepine (CBZ) treatment. She had experienced nocturnal partial seizures since 5 years of age. Interictal electroencephalography demonstrated typical rolandic discharges. Valproate was first initiated at 6 years of age, but the seizures were uncontrollable. Carbamazepine was added and valproate withdrawn. The frequency of partial seizures did not decrease. Moreover, she had brief episodes of tone loss in each or both arms and eye blinking several weeks after CBZ introduction. Unilateral loss of arm tone corresponded to spike-and-wave discharges in the contralateral centrotemporal region, and a loss of tone in arms was associated with bilateral synchronous discharges. Eye blinking was also related to bilateral synchronous discharges and classified as a myoclonic seizure. The ENM and myoclonic seizures disappeared soon after CBZ withdrawal. Therefore the authors concluded that CBZ induced the ENM and myoclonic seizures in this patient. CBZ sometimes induces generalized seizures in the treatment of partial epilepsy and generalized epilepsy. CBZ-induced ENM seizures should be considered when a brief lapse of tone appears during CBZ treatment.     

Overlap cases of eyelid myoclonia with absences and juvenile myoclonic epilepsy.

Eyelid myoclonia with absences (EMA) and juvenile myoclonic epilepsy (JME) are two separate epileptic syndromes included in the new classification of epilepsies and epileptic syndromes by ILAE in 2001. Both are idiopathic generalized epilepsies with their clinical onset in the first two decades. EMA is characterized by eyelid myoclonia associated with absences and photosensitivity. Self-induced seizures are frequently seen in EMA. It can be associated with mildly mental retardation and resistance to treatment. JME includes three types of generalized seizures: typical absences, myoclonic jerks and generalized tonic-clonic seizures. The myoclonic jerks occur almost exclusively on awakening, involve preferently the upper extremities, may rarely affect the lower extremities or the entire body. More severe attacks may be accompanied by a fall. The myoclonic jerks occur rarely in EMA. They are usually mild and are freqently restricted to the upper extremities. Generalized tonic-clonic seizures, photosensitivity and generalized polyspike-wave discharges provoked by eye closure are features of both epileptic syndromes. In this study, we describe four female patients with eyelid myoclonia associated with absences, myoclonic jerks causing falling down and rare generalized tonic-clonic seizures. All patients had good school performance and total seizure control under sodium valproate treatment. Their EEGs show generalized polyspike-wave discharges with a frequency of 3.5-6Hz always appearing a few seconds after eye closure and photoparoxysmal response. These patients show the characterictics of both epileptic syndromes. It is clinically important to make a syndromic diagnosis for an optimum advise on treatment, lifestyle restrictions and prognosis. In this study, we have gathered evidence that EMA and JME are dynamic syndromes that tend to evolve into one another.     

Neonatal seizures with tonic clonic sequences and poor developmental outcome

Seizures consisting of a tonic followed by a clonic phase have rarely been described in neonates and are not included in the current classifications of neonatal seizures. Our video archive of 105 neonates with seizures or suspected seizures revealed six neonates with such tonic clonic or tonic myoclonic sequences. Two of those neonates had pyridoxine dependent seizures. The other four neonates had drug refractory seizures and demonstrated similarities in electro-clinical pattern, clinical course and outcome. Their seizures started with tonic posturing and after 10-20s tonic posturing was superimposed by focal or multifocal cloni or myocloni. Ictal EEG started with voltage attenuation followed by bilateral or alternating focal epileptic discharges. The interictal EEG was abnormal. One child died, while the other three children became seizure free but had severe motor delay and mental retardation. In one of those three children, a de novo missense mutation was detected in the voltage gated potassium channel gene KCNQ2, indicating a genetic relationship between drug refractory neonatal seizures of unknown etiology with tonic clonic or myoclonic sequences and the well-known syndrome of benign familial neonatal convulsions (BFNC).     

Electroencephalographic and pathophysiologic features of rat parenteral panicillin epilepsy

A multifocal epileptic pattern with secondary generalization, clinically characterized by mild myoclonic jerks, was evoked in the rat by the i.p. injection of 600,000 to 1,200,000 IU/kg penicillin. The development of clonic or tonic-clonic seizures was sometimes observed at that dose. Smaller doses of penicillin sometimes evoked focal spikes or bilateral synchronous bursts of atypical spike and wave complexes accompanied by vigilance reduction. Occasional and late involvement of thalamic structures in producing the paroxysmal activity was observed also with the largest doses. Diffuse bilateral application of a dilute penicillin solution (250 to 1,000 IU/hemisphere) produced EEG patterns which were very similar to those evoked by i.p. administration. Because of the larger doses of parenteral penicillin required to evoke epileptic activity compared with the cat model, both a more effective rat blood-brain barrier and/or a lesser sensitivity of rat cortex to the epileptogenic action of penicillin are suggested. In addition, other dissimilarities exist between epilepsies in the rat and cat after parenterally administered penicillin. Topical administration of the antibiotic to the thalamus did not induce any paroxysmal pattern, whereas epileptic responses were recorded when penicillin was topically applied to the hippocampus. No electroclinical pattern resembling the human epileptic syndrome was observed. Our data emphasize also in this model the primary role of the cortex in the genesis of the penicillin-induced epileptic activity.     

Video-Polygraphic Analysis of Myoclonic Seizures in Juvenile Myoclonic Epilepsy

Summary: We studied myoclonic seizures (MS) in 5 patients with juvenile myoclonic epilepsy (JME) using video polygraphic recordings to investigate the clinical characteristics of MS in this epileptic syndrome. The total number of MS analyzed was 302 (range 27–125, mean 60) seizures per patient. MS occurred either singly or repetitively (37 vs. 63%) and corresponded to generalized bilaterally synchronous single or multispike-and-wave complexes at 3–5 Hz. Video analysis of the myoclonic jerks demonstrated that either distal or proximal muscle involvement predominated. In the former, there was mild bilateral flexion and some external rotation of the forearms. In the latter, flexion of both arms at the elbow, flexion and abduction of the thighs, and extension of the back was observed. Asymmetry of MS was noted in 4 of 5 patients. Facial involvement of MS occurred infrequently in 2 patients. When the patients kept both arms outstretched, the arms dropped or there was sudden interruption of ongoing electromyographic (EMG) potentials immediately after myoclonic jerks (postmyoclonic inhibition) in all patients. One should inquire about these clinical characteristics of MS in JME when taking a thorough history in patients with primary generalized tonic-clonic seizures (GTC).     

Periodic lateralized frontal epileptiform discharges with ipsilateral epilepsia partialis continua

PURPOSE: Lateralized clonic jerks of the extremities during epileptic seizures usually arise from the contralateral rolandic cortex. In our exceptional case one-sided extremity twitches related to epileptiform activity in the ipsilateral frontal lobe. METHODS: Case study with clinical-electroencephalographic correlation. RESULTS: A 47-year-old man suffered destruction of most of his right cerebral hemisphere, including the perirolandic region. Epilepsia partialis continua (EPC) ensued, with clonic jerks of the proximal right upper and lower limbs temporally related to periodic lateralized epileptiform discharges (PLEDs) from the parasagittal region of the right frontal lobe with a variable time interval over 100 ms. Sectioning of the subcortical callosal and projection connections of the frontal lobe abolished the clonic jerks. CONCLUSIONS: We propose the ipsilateral EPC arose from projections from the supplementary motor region to the medullary reticular formation to account for the long and variable latency between PLEDs and jerks.     

Correlation between electrocorticographic and motor phenomena induced by pentamethylenetetrazol during ontogenesis in rats

Motor and electrocorticographic (ECoG) phenomena induced by pentamethylenetetrazol (PTZ) were directly compared in adult as well as in young rats (age groups of 7, 12, and 18 days). The technique for implantation of cortical electrodes was elaborated in young rats. Myoclonic jerks were elicited by PTZ in all age groups studied. In adult animals they were accompanied by isolated spikes and/or spike-and-wave complexes, whereas in 7-day-old rats there was a poor correlation between ECoG abnormalities and myoclonic jerks. With increasing age an improved correlation between ECoG abnormalities and behavioral changes were noted. After further injections of PTZ, rats had generalized tonic-clonic motor seizures. Ictal ECoG activity usually started in one cortical region in 7-day-old rats and became progressively generalized whereas in older rats generalized electrical discharges accompanied the motor seizures from onset. The clonic phase of motor seizures was not always accompanied by specific ECoG changes in young rats. At all ages the correlation between ECoG activity and individual phases of the generalized tonic-clonic seizures was poor.     

The New Classification of Seizures by the International League Against Epilepsy 2017

Purpose of Review

This review presents the newly developed International League Against Epilepsy (ILAE) 2017 classification of seizure types.

Recent Findings

The fundamental distinction is between seizures that begin focally in one hemisphere of the brain, generalized onset seizures that apparently originate in both hemispheres, and seizures of unknown onset. Focal seizures optionally can be subclassified according to whether awareness (a surrogate marker for consciousness) is intact or impaired. The next level of classification for focal seizures is motor (with subgroups automatisms, atonic, clonic, epileptic spasms, hyperkinetic, myoclonic, tonic), non-motor (with subgroups autonomic, behavior arrest, cognitive, emotional, sensory), and focal to bilateral tonic-clonic. Generalized seizures are categorized as motor (tonic-clonic, clonic, tonic, myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, epileptic spasms) and non-motor/absence (typical, atypical, myoclonic, eyelid myoclonia).

Summary

The classification allows new types of focal seizures and a few new generalized seizures, and clarifies terms used to name seizures.

     

Adult-onset autosomal dominant myoclonic epilepsy: report of a family with an overlooked epileptic syndrome.

OBJECTIVE: Myoclonic epilepsy is a common epileptic syndrome with high genetic contribution. We described a pedigree in which 10 individuals presented with a non-progressive, adult-onset myoclonic epilepsy. MATERIALS AND METHODS: The pedigree was constructed and analyzed. Six affected members were studied with clinical grounds, mental status, neurophysiology, video-electroencephalographic (EEG), brain magnetic resonance imaging (MRI) and mutational analysis of GABRA1 (GABRA1A, which endoces the alpha1 subunit of the gamma-aminobutyric acid receptor subtype A). Clinical and EEG data were collected from six unaffected members. RESULTS: Autosomal dominant hereditary was shown. The age of seizure onset was approximately 40. All the individuals had myoclonic seizures and a normal cognitive level. Bilateral symmetric jerks of the shoulders, arms or legs featured the myoclonic seizure. Ictally, the consciousness was not affected. The ictal EEG demonstrated bilateral spikes-and-waves. The occurrence of myoclonic seizures was not associated with sleepiness. Rare generalized tonic-clonic seizures occurred in two individuals. No absence or accompanying involuntary movements were observed. A lower dose of valproic acid (200-500 mg/D) (clonazepam 0.5 mg/D in a patient) was required to stop the myoclonic seizures. CONCLUSIONS: The clinical features of late adult-onset autosomal dominant myoclonic epilepsy are similar to juvenile myoclonic epilepsy (JME), which is a common generalized epileptic syndrome with a significant hereditary component. But the age of onset, rare association of other seizure patterns, and non-relation of seizure onset to sleepiness suggest that this may be a distinct familial epileptic syndrome different from recognized familial myoclonic epilepsies.     

Rotatory seizures in juvenile myoclonic epilepsy

Rotatory seizures have been reported in association with focal intracranial lesions. This type of seizure was also described in patients with primary generalized epilepsies. To our knowledge, there is only one previous publication denoted an association between juvenile myoclonic epilepsy (JME) and rotatory seizures. We present two female patients with JME and rotatory seizures together. The onset of myoclonic jerks and generalized tonic clonic (GTC) seizures was in their midteens. Their interictal EEGs showed bilateral symmetric spike and polyspike wave discharges. The rotatory seizures of the patients started at age of 26 and 33 years, respectively. In one of the patients, turning to the left was followed by three or four complete turns, after then, she had GTC seizures. The other patient has turned to the right with only one or two turns and sometimes continued with GTC seizures. Neuroradiologic investigations including brain CT, MRI, and SPECT were performed. Response to valproate therapy of rotatory seizures was good. We believe that rotatory seizures are rarely seen in JME patients, and this causes false diagnosis which lead unsuitable drug choice.     

Epileptic phenomena in bismuth toxic encephalopathy.

Seventy patients admitted to hospital with bismuth encephalopathy had repeated clinical and EEG examinations. All the patients exhibited myoclonic jerks, but no paroxysmal features ever appeared on EEG. Computed tomography showed cortical hyperdensities. Seizures were observed in 22 patients, but epileptic EEG patterns appeared only when the bismuth blood level was below 1500 microgram/1. It is suggested that a high cortical intracellular bismuth concentration induces a "cortical inhibition" which causes suppression of physiological electrical brain activity, the absence of EEG paroxysmal phenomena during myoclonic jerks, and explains the rarity of epileptic seizures.     

Clinical and EEG studies of symptomatic focal epilepsy in 7 patients with colpocephaly

The clinical observations of seven patients with epileptic seizures and colpocephaly were summarized. The ages at the time of onset of the seizures were usually under 1 year, and the frequency of seizures in the late-onset cases was lower than that in the early-onset cases. The seizures were characterized by vomiting, eye deviation, versive seizures, and focal motor seizures. Interictal electroencephalograms showed either unilateral or synchronous bilateral spikes (and wave) or slowing of the basic activity in the occipital area. The basic activity slowed down in all of the cases. Epileptic seizures accompanied with colpocephaly may derive from epileptic foci in the occipital and posterior temporal region, which is structurally abnormal. Ongoing convulsions ceased after the intravenous administration of diazepam. In addition, the oral antiepileptics clobazam and clorazepate proved to be effective for the treatment of refractory cases.     

Reflex Epilepsy Induced by Calculation Using a "Soroban," a Japanese Traditional Calculator

We report three cases of reflex epilepsy with myoclonic jerks of the right arm and fingers precipitated by calculation using a Soroban. An EEG spike-wave complex with left central prevalence was induced. Various types of stimulation were used to induce epileptic discharges, and a simultaneous mental task requiring a high degree of concentration and complicated and delicate finger movements was necessary to induce the epileptic discharges. Comparison of our cases with previously reported reflex epilepsy induced by higher mental activity led to the assumption that the neural mechanism inducing seizures in our cases is similar to that of writing epilepsy. Valproate was effective in reducing epileptic discharges, and all patients became seizure-free.     

Absences in juvenile myoclonic epilepsy: a clinical and video-electroencephalographic study

We report a prospective clinical and electroencephalographic study of 19 patients with juvenile myoclonic epilepsy and absence seizures. Absences began 1 to 9 (4.5 +/- 2.5) years before myoclonic jerks and generalized tonic-clonic seizures. Clinical manifestations during the absence ictus showed great variation, ranging from subtle or no overt features to severe impairment of consciousness, and severity was age related. Simple and complex absence seizures can occur in the same patient. The electroencephalographic features were distinct, with many interictal discharges, fragmentation of the paroxysms, and frequent polyspikes of varying numbers and amplitude for each spike-slow wave component. The combined clinical-electroencephalographic manifestations were characteristic and allow differentiation of absences in juvenile myoclonic epilepsy from typical absence seizures in other epileptic syndromes.     

Pre- and post-dormitum epilepsies: idiopathic generalized epilepsies

Epilepsy and sleep have a profound bidirectional influence. Idiopathic generalized epilepsy (IGE) comprises a fascinating group of syndromes that constitute nearly one-third of all epilepsies. These syndromes are genetically determined and affect otherwise normal people of both sexes and all races. IGE manifests with typical absences, myoclonic jerks, and generalized tonic-clonic seizures, alone or in varying combinations and severity. IGE syndromes are typically modulated by the sleep-wake cycle, and particularly by the sleep-wake transition process, both in terms of the occurrence of seizures and interictal epileptiform discharges (IED), with pronounced susceptibility to sleep deprivation. IGE analysis from the point of view of arousal modulation enhances the concept of a biological continuum existing among IGE syndromes. At the same time, this analysis broaches the problem of syndromic diagnosis and identification of the factors influencing the phenotypic expression of some epileptic phenomena over the course of life with potential bidirectional influences between epileptic manifestations and sleep-wake processes.