Epilepsy With Myoclonic Atonic Seizures: An Electroclinical Study of 69 Patients

Epilepsy with myoclonic-atonic seizures is characterized by myoclonic-atonic, absence, tonic-clonic, and eventually tonic seizures, appearing in previously normal children at ages 18-60 months. We analyzed the electroclinical features, treatment, and outcome of 69 patients with myoclonic-atonic seizures; these patients were followed between 1990 and 2012 at the Juan P. Garrahan Pediatric Hospital, Buenos Aires, Argentina. No structural or metabolic etiology was identified. Based on the electroclinical features and evolution, two groups could be distinguished. The first group of 39 patients with myoclonic and myoclonic-atonic seizures with or without generalized tonic-clonic seizures and absences associated with generalized spike- and polyspike-and-wave paroxysms had excellent prognoses. The second group of 30 patients had myoclonic jerks and myoclonic-atonic seizures associated with other seizure types including tonic seizures; some had myoclonic status epilepticus and cognitive deterioration. The interictal EEG showed frequent generalized spike- and polyspike-and-wave paroxysms. In 16 patients, the seizures remitted within 3.6 years. The two groups were distinguished in retrospect, when enough time had elapsed to evaluate cognitive deterioration and different seizure types. In conclusion, epilepsy with myoclonic atonic seizures is an epileptic syndrome with a broad clinical spectrum and variable prognosis.     

MRI volumetry shows increased anterior thalamic volumes in patients with absence seizures

The interaction between thalamus and cortex appears to be critical to the pathophysiology of idiopathic generalized epilepsies (IGEs). The objective of this study was to investigate thalamic volumes of a group of patients with IGEs using high-resolution MRI. Thalamic segmentation was performed by the same rater, who was unaware of the diagnosis. Thalamic volumes were divided into anterior half and posterior half. One hundred forty-seven patients were scanned (71 with juvenile myoclonic epilepsy, 49 with generalized tonic-clonic seizures only, and 27 with absence epilepsy). Subgroup analyses with corrections for multiple comparisons showed that, when compared with those of controls, anterior thalamic volumes were increased in patients with absence epilepsy and juvenile myoclonic epilepsy with absence seizures, but not in patients with generalized tonic-clonic seizures only and juvenile myoclonic epilepsy without absence seizures. Our results demonstrated that the anterior thalamus is structurally different in patients with IGEs and absence seizures as compared with patients with IGEs without absence seizures.     

Hashimoto encephalopathy

Hashimoto encephalopathy is a chronic relapsing steroid responsive encephalopathy characterized by antibodies against thyroid components. Etiology is still unknown. Confusion, seizures and coma are frequent reported symptoms. We present a 65-year old patient with acute onset of partial seizures and cognitive impairment. Hashimoto encephalopathy was assumed with diagnosis of Hashimoto thyroiditis and clinical syndrome. Symptoms resolved with thyroid treatment alone. Hashimoto encephalopathy should be considered in patients with unexplained encephalopathy, even when thyroid function seems to be normal.     

PRKCG mutation (SCA-14) causing a Ramsay Hunt phenotype.

Progressive myoclonic ataxia, also referred to as Ramsay Hunt syndrome, is characterized by a combination of myoclonus and cerebellar ataxia, infrequently accompanied by tonic-clonic seizures. Its differential diagnosis overlaps with progressive myoclonic epilepsy, a syndrome with myoclonus, tonic-clonic seizures, progressive ataxia and dementia. In patients with progressive myoclonic epilepsy, specific diseases can frequently be recognized, but the diagnostic yield in progressive myoclonic ataxia is much lower. We describe a patient who presented with multifocal myoclonus in his thirties and who later developed cerebellar ataxia and focal dystonia. His father was similarly affected. Genetic studies revealed a mutation in the protein kinase C gamma (PRKCG) gene, known to cause spinocerebellar ataxia type 14 (SCA-14). This case illustrates that both myoclonus and dystonia are part of the clinical spectrum in SCA-14 and that myoclonus can even be the presenting symptom. We suggest that SCA-14 should be considered in the differential diagnosis of progressive myoclonic ataxia.     

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.     

Use of topiramate in childhood generalized seizure disorders

Topiramate is a sulfamate derivative of the naturally occurring monosaccharide D-fructose. It was initially approved in the United States as adjunctive therapy for partial seizures in 1997. However, there is increasing evidence that it is effective in the treatment of generalized seizures and epilepsy syndromes. Initially, open-label studies using topiramate as add-on therapy in children with refractory generalized seizure types were performed. These showed improvement in patients with the following generalized seizure types: typical and atypical absence, atonic, myoclonic, generalized tonic-clonic, and juvenile myoclonic epilepsy. Double-blind, placebo-controlled multicentered studies in patients with refractory primary generalized tonic-clonic seizures and epilepsy syndromes were performed. The median reduction in seizure frequency for primary generalized tonic-clonic seizures was 56.7% for topiramate and 9% for placebo. Additionally, 13.6% of topiramate-treated patients were primary generalized tonic-clonic seizure free for the study period. In the topiramate-treated juvenile myoclonic epilepsy patients, primary generalized tonic-clonic seizures were reduced > 50% in 73% of patients. Open-label extension showed that primary generalized tonic-clonic seizures were reduced >50% in 63% of topiramate-treated patients for > or = 6 months, and 16% were primary generalized tonic-clonic seizure free > or = 6 months. Accumulating evidence suggests that topiramate has a broad spectrum of antiepileptic effect. Moreover, life-threatening organ toxicity has not been attributed to topiramate. Topiramate is an effective treatment for refractory generalized seizure types and epilepsy syndromes encountered in children.     

A detailed analysis of symptomatic posterior cortex seizure semiology in children younger than seven years

PURPOSE: To analyze the semiology of seizure onset and evolution in young children with posterior cortex epilepsy (PCE), compare this with adult reports, and assess age-related differences. METHODS: We videotaped and analyzed 110 seizures from 18 patients with PCE, aged 3-81 months. All had a good prognosis after posterior epileptogenic zone removal. Ictal events were categorized by behavioral, consciousness, autonomic, and sensory features, as well as motor patterns, which included myoclonic, tonic, clonic, unclassified motor seizures, and epileptic spasm. A time-scaled data sheet was developed to record each epileptic event as onset, very early, early, or late manifestation. RESULTS: Patients had a high seizure frequency with < or =100 attacks/day; one third of them showed a cluster tendency. The mean duration of seizures was 67 s. The most common seizure components were motor manifestations (with myoclonic and tonic seizures), but psychomotor (automotor), hypomotor attacks, and isolated auras also were frequently observed. Clinical seizure spread was frequent; auras and visual sensory signs were difficult to record in this age. Typical phenomena during seizures included behavioral changes, ictal vocalization, smile, flush, head nod, oculomotor features, and late-appearing oral automatisms, whereas hypermotor and secondarily generalized tonic-clonic seizures were not seen. CONCLUSIONS: Our results suggest that PCE in infants and young children is very heterogeneous but shows important age-related features. Compared with adults, children with PCE have shorter but more frequent seizures; they rarely report aura or visual sensory signs, only sporadically develop hypermotor and secondarily generalized tonic-clonic seizures, whereas ictal smile, flush, head nod, and behavioral change are typical features at this age. Because of frequent subtle ictal phenomena, long-term video-EEG monitoring is a useful diagnostic tool with infants and young children with PCE.     

Two-year efficacy of lacosamide as adjunctive therapy for generalized tonic-clonic seizures in patients with juvenile myoclonic epilepsy

ObjectiveTo report the long-term efficacy of adjunctive lacosamide therapy in patients with juvenile myoclonic epilepsy whose generalized tonic-clonic seizures were significantly reduced by treatment.MethodsA retrospective study was conducted in patients who visited the Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital and the Department of Pediatrics, National Hospital Organization Nagasaki Medical Center. Among patients who had been diagnosed with juvenile myoclonic epilepsy, those who received lacosamide as adjunctive therapy for refractory generalized tonic-clonic seizures for at least 2 years from January 2017 to December 2022, and who achieved seizure freedom or >50% seizure reduction in tonic-clonic seizures were included. The medical records and neurophysiological data of the patients were reviewed retrospectively.ResultsFour patients met the inclusion criteria. The mean age at the onset of epilepsy was 11.3 years (range 10–12), and the mean age of starting lacosamide was 17.5 years (range 16–21). All patients received two or more antiseizure medications prior to lacosamide. Three of four patients had seizure freedom for more than 2 years, and the one remaining patient had >50% seizure reduction for more than one year. Only one patient had recurrent myoclonic seizures after starting lacosamide. The mean lacosamide dose at the last visit was 425 mg/day (range 300–600).ConclusionAdjunctive lacosamide therapy might be a treatment option for juvenile myoclonic epilepsy with generalized tonic-clonic seizures, which are not responsive to standard antiseizure medications.     

Selection of drugs for the treatment of epilepsy

Antiepileptic drug selection is based on efficacy for specific seizure types and epileptic syndromes. For idiopathic generalized epilepsies with absence, tonic-clonic, and myoclonic seizures, the drug of choice is valproate. Secondary generalized epilepsies with tonic, atonic, and other seizure types are difficult to treat with any single drug or combination of drugs. The drugs of choice for absence seizures are ethosuximide and valproate. For control of tonic-clonic seizures, any of the other major antiepileptic drugs can be effective. If valproate cannot be used, carbamazepine, phenobarbital, phenytoin, or primidone is effective, but ethosuximide or a benzodiazepine needs to be added to control associated absence or myoclonic seizures. The drugs of first choice for partial epilepsies with partial and secondarily tonic-clonic seizures are carbamazepine and phenytoin. Increasing evidence suggests that valproate may be a third alternative. Phenobarbital and primidone are second choice selections because of side effects. A combination of two of these five major antiepileptic drugs may be necessary for inadequately controlled patients. Other epilepsy syndromes such as neonatal and infantile epilepsies, febrile epilepsy, and alcoholic epilepsy require specific drug treatment. For all these seizure types and epilepsy syndromes, treatment ultimately must be selected to provide maximal efficacy and minimal adverse effect for each individual patient.     

Sex difference in susceptibility to epileptic seizures in rats: importance of estrous cycle.

Sex difference in seizure susceptibility is one of the unresolved issues of epilepsy. It is known that estrogen is excitatory and progesterone is inhibitory to the central nervous system. Therefore, it is to be expected that seizure susceptibility may be associated with the estrous cycle, which should be tested in epilepsy research. Otherwise, different results in epilepsy studies could be an artifact of the estrous cycle. Reports in the literature are inconsistent about testosterone effects on seizures. In light of these considerations, sex differences in seizure susceptibility were restudied in rats. There was no significant sex difference in mean latencies to picrotoxin-induced seizures; prestrous-females had the shortest latencies to epileptic seizures compared to males and estrousfemales. With testosterone-injected rats, there was either no sex difference in latencies (to akinetic and focal seizures) or females had significantly shorter latencies than males (to status epilepticus, generalized tonic-clonic seizures, and myoclonic seizures). Testosterone-treated male rats had a significantly longer mean latency than controls for status epilepticus only; otherwise, these males showed no significant differences between mean latencies before and after testosterone (to focal, myoclonic, or generalized tonic-clonic seizures). In females, mean latencies to myoclonic seizures and status epilepticus were significantly shorter after testosterone than before. It was concluded that there is a sex difference in susceptibility to epileptic seizures in rats, provided that the estrous cycle is taken into account. Testosterone may increase and decrease seizure susceptibility in females and males, respectively. These effects may be important for understanding the mechanisms of epileptic phenomena and may provide some important clues to epilepsy treatment.     

The Seizure Prognosis of Juvenile Myoclonic Epilepsy

Abstract: Thirty-two patients with juvenile myoclonic epilepsy (JME) were studied to evaluate the seizure prognosis. The response to antiepileptic drugs ww excellent in 68%, but the patients, who had much more focal discharges on EEG and were sensitive to neuropsychological EEG activations at the beginning of treatment, had an unfavorable outcome. A combination of absence seizure alone resulted in the excellent prognosis for both absence and myoclonic seizures, and a combination of generalized tonic-clonic seizure on awakening related to rare myoclonic seizures. These findings suggest that the outcome of JME would be predicted by the EEG abnormality and the combination of the other types of seizures, which are probably determined by the pathophysiology at the beginning of treatment.     

Clinical and Neurophysiological Development of Unverricht-Lundborg Disease in Four Swedish Siblings

Four siblings aged 12-18 years with progressive myoclonus epilepsy demonstrated a subclinical stage at the age of 9-11 years, with visual blackouts and polyspike electroencephalographic (EEG) activity on photic stimulation, an early myoclonic stage at the age of 12-15 years, with increasing segmental, stimulus-sensitive myoclonus, occasional nocturnal buildup myoclonic "cascade" seizures, slowing of EEG alpha-activity, episodic 4-6 Hz bilateral sharp waves and polyspikes with myoclonias on photic stimulation, and a disabling myoclonic stage at the age of 16-18 years, with periodic generalized myoclonias, nocturnal myoclonic "cascade" seizures, ataxia, dysarthria, mental changes, intermittent wheelchair dependency, and continuous EEG slow waves with polyspikes and intense myoclonias on photic stimulation. One of the siblings died at the age of 18 years with no apparent cause of death. Treatment with antiepileptic drugs other than valproate may have contributed but none of the siblings were ever treated with phenytoin. Extensive clinical and laboratory investigations revealed no abnormalities and excluded other known possible causes of progressive myoclonus epilepsy. The diagnosis was consistent with Unverricht-Lundborg disease and rested on typical age of onset, clinical signs, EEG, and evoked response abnormalities. Buildup myoclonic seizures are typical in advanced stages of Unverricht-Lundborg disease. We have labeled these myoclonic "cascade" seizures. A typical seizure was studied with video-EEG and cardiorespiratory monitoring. Characteristics revealed were onset with continuous arrhythmic myoclonic jerks followed by intense rhythmic myoclonus with increasing muscle tone that successively reduced the amplitude of the jerks. The EEG during the whole seizure showed intense polyspike activity. Obstructive apnea was seen at the peak of the seizure. There were no cardiac dysrhythmias. Consciousness was normal or only slightly impaired. Postictal drowsiness was not observed. Myoclonic "cascade" seizures are easily confused with generalized tonic-clonic seizures.     

Adult myoclonic epilepsy: a distinct syndrome of idiopathic generalized epilepsy

The authors present 11 cases of idiopathic generalized epilepsy that began in adulthood at a mean age of 39 years. All patients had myoclonic jerks, five had absence seizures, and nine had infrequent generalized tonic-clonic seizures. A majority had a family history of seizures. EEG in all patients showed generalized epileptiform abnormalities, whereas neuroimaging and neurologic examination results were normal. This series appears to represent a previously undescribed idiopathic generalized epilepsy syndrome of adult myoclonic epilepsy.     

青少年肌阵挛性癫(癎)

青少年肌阵挛性癫是一种以晨起肌阵挛、全身强直-阵挛发作为临床特征的特发性全身性癫综合征,有时伴有失神发作。本文就青少年肌阵挛性癫的临床表现、遗传学、脑电图特点、鉴别诊断以及治疗方法进行了阐述。     

Levetiracetam in the treatment of childhood epilepsy

Epilepsy is a common pediatric neurologic disorder that is difficult to manage in a substantial portion of children. Levetiracetam (LEV) is a novel antiepileptic drug (AED) that has recently been approved as add-on treatment for various seizure types in epilepsy populations that include children: for refractory partial seizures in epilepsy patients ≥4 years old, for myoclonic seizures in juvenile myoclonic epilepsy patients ≥12 years old, and for primary generalized tonic-clonic seizures in idiopathic generalized epilepsy patients (≥6 years old with FDA approval; ≥12 years old with EMEA approval). A review of published pediatric studies indicates that the efficacy of LEV is best established for partial seizures; however, results from recent double-blind and open-label trials indicate that adjunctive LEV also controls generalized seizures – particularly myoclonic and generalized tonic-clonic – in children and adolescents with primary generalized epilepsy. LEV was well-tolerated in pediatric studies. The most common adverse events (AEs) reported were sedation related. Behavioral AEs were among the most commonly reported events in some trials; conversely, improvements in behavior and cognition were also frequently reported. LEV appears to be a safe and effective AED with unique characteristics that benefit the treatment of children with epilepsy.     

Clinical associations of occipital intermittent rhythmic delta activity

Association of occipital intermittent rhythmic delta activity with absence seizures has been well documented in the published literature. Two recent studies have also described an association with focal seizures. After obtaining approval from our Institutional Review Board, all electroencephalograms with occipital intermittent rhythmic delta activity at our institution between July 1, 2006 and December 31, 2009 were identified. Charts of these patients were reviewed to collect clinical data. A matched comparison group was assembled. Thirty-one of the patients who met criteria had evaluable clinical data. Fifteen had generalized seizures (9 absence; 2 tonic-clonic; 3 absence and tonic-clonic; 1 absence, tonic-clonic, myoclonic, and atonic). Eleven had focal seizures. One had both generalized tonic-clonic and focal seizures. Events in 1 were nonepileptic in nature. Documentation was inadequate for seizure classification in 3. There was a statistically significant difference between the study and comparison groups for absence seizures, but not for focal seizures.     

Clinical features, EEG findings and diagnostic pitfalls in juvenile myoclonic epilepsy: a series of 63 patients

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalized epileptic syndrome distinctively characterized by myoclonic jerks often associated to generalized tonic-clonic seizures (GTCS) and typical absence seizures. In spite of typical clinical and EEG profiles, JME is widely underdiagnosed. In the present study we retrospectively revised clinical and EEG data of JME patients referring to our Epilepsy Service. A diagnosis of JME could be made in 63 patients, that is 5.7% of all the epileptic patients referring to our Service and 25.9% of those suffering from an idiopathic generalized epilepsy. General features as well as modality of onset and course of the syndrome of our JME subjects were in accordance with literature. Regarding EEG findings, asymmetries were detected in 38.1% of cases. At referral to our Service only 31.7% of JME patients were correctly diagnosed. Main factors responsible for misdiagnosis were failure in eliciting a history of myoclonic jerks and misinterpretation of myoclonic jerks as simple partial seizures. EEG asymmetries were misleading in 13 patients. In conclusion, a correct JME diagnosis is strictly dependent on the knowledge of the syndrome leading the interviewer to look for and correctly interpret myoclonic jerks whereas EEG is just an ancillary diagnostic tool.     

Tonic seizures in subacute sclerosing panencephalitis: a video-illustration of two cases.

Subacute sclerosing panencephalitis is a progressive disorder which also presents with various types of seizures, mainly myoclonic jerks, atonic attacks and tonic-clonic seizures. We report two cases, documented by video-EEG that during the course of the disease also presented with tonic seizures. The differential diagnosis of non-epileptic paroxysmal events might prove to be a problem.     

Early-onset progressive encephalophathy with migrant,continuous myoclonus

Three unusual cases of focal continuous myoclonus with onset during the first months of life, lasting from dozens of minutes to hours, are reported. During disease evolution, prolonged bilateral myoclonic seizures and generalized tonic-clonic seizures occur. Subsequently, a progressive encephalopathy with hypotonia and ataxia appears. A net worsening of the neurological condition is observed after the age of 4–5 years. Cortical atrophy is shown by CCT and MRI. Neurometabolic screening is not contributory. Repeated polygraphic recordings show continuous and segmental myoclonic jerks, localized in different muscles, at frequencies ranging between 0.5–1 c/s and 6–8 c/s. Moreover action myoclonus is recorded. During the first period of disease the EEG does not show any paroxysmal activity. As to the classification, this syndrome corresponds to an early onset progressive encephalopathy of unknown origin, similar in some aspects to Alper's disease. Another problem is the interpretation of the myoclonic phenomena. Some important aspects suggest a cortical origin of the diverse myoclonic phenomena observed in these cases.