Onset Of Myoclonic Jerks Research Articles

Effect of calcium channel blocker as anticonvulsant and its potentiating effect when used along with sodium valproate in pentylenetetrazole induced seizures in Albino rats

Background: Many antiepileptic drugs were introduced for the treatment of epilepsy. Ideal antiepileptic drug should not only prevent but also correct the underlying pathophysiology without altering the normal neurotransmission. Calcium channel blockers may form such group because initiation of seizure is associated intrinsic burst firing which is triggered by large inward calcium current, so this study was done to evaluate the anticonvulsant effect of amlodipine in albino rats.Methods: A total of 42 adult albino rats were included in the study and divided into 7 groups, each containing 6 rats. Group 1 received distilled water, group 2,3 received sodium valproate 50mg/kg and 100mg/kg, group 4-6 received amlodipine 1, 2, 4mg/kg and group 7 received combination of Amlodipine 1 mg/kg and sodium valproate 50mg/kg. Pentylenetetrazole induced seizures model was done and onset of myoclonic jerks, onset of clonic convulsions and duration of clonic convulsions was studied.Results: There was a significant anticonvulsant effect in Amlodipine doses 2, 4mg/kg (p <0.001). The combination of Amlodipine (1mg/kg) and Sodium valproate (50mg/kg) also had significant anticonvulsant effect.Conclusions: Amlodipine, a calcium channel blocker has anticonvulsant effect and also potentiated the anticonvulsant effect of low dose sodium valproate.

Progression of neuropsychiatric and cognitive features due to exons 2 to 5 deletion in the epsilon-sarcoglycan gene: a case report

ABSTRACTPhysical symptoms of myoclonus dystonia due to epsilon-sarcoglycan mutations are well documented; however, the progression of neuropsychiatric and cognitive symptoms remains unclear. We present a case of a 34-year-old woman with early childhood onset of myoclonic jerks, dystonic posture and developmental delay due to exons 2 to 5 deletion in the epsilon-sarcoglycan gene. Over time, she developed neuropsychiatric symptoms. She underwent bilateral deep brain stimulation of the ventral intermediate nucleus of the thalamus for her motor symptoms, which greatly improved but she exhibited slow deterioration of her neuropsychiatric and cognitive symptoms, particularly apathy, aggression and severe executive dysfunction.

1. Benign form of Unverricht–Lundborg disease (ULD) mimicking juvenile myoclonic epilepsy (JME) in adulthood

Unverricht–Lundborg disease (ULD) (EPM1) is an autosomal recessive neurodegenerative disease with progressive myoclonus epilepsy (PME). The onset is usually between 6 and 15 years of age with myoclonus and generalized tonic-clonic seizures, variable severity and course, and variable degrees of cognitive deterioration. With good antiepileptic management, the patients can now survive into their 50’s and 60’s. The gene for this disorder was identified in 1996 as cystatin B ( CSTB ), a cysteine protease inhibitor. The most common mutation is a dodecamer repeat, although rare point mutations have also been described. To present an extended phenotype of ULD (EPM1). The proband who carried a diagnosis of juvenile myoclonus epilepsy (JME) presented with her partner for preconceptional genetic counseling. Since she had a distant family history of Unverricht–Lundborg disease on the maternal side, carrier screening for the CSTB gene was carried out for both, employing detection of the dodecamer repeat expansion and sequencing of the CSTB gene to rule out point mutations. This 30-year-old female had a single generalized tonic-clonic seizure during sleep at the age of 11 years, and onset of myoclonic jerks on awakening at around the same time, which were well-controlled by valproic acid. She carries a clinical diagnosis of JME. She was born prematurely after 25 weeks’ gestation weighing 750 grams. Developmental milestones were normal, and she was on the honor roll at school in grade X. She works as a high school teacher for behaviourally challenged children. Both paternal grandparents were of Irish origin; both maternal grandparents were French–Canadian, from the Gaspé peninsula of Quebec. Four siblings of the maternal grandmother were diagnosed clinically with ULD and were known to us; the three affected sisters died in their 20’s and 30’s, and the affected brother died at age 65. A third degree cousin of the mother had epilepsy and died at 18 years of age. A paternal uncle had a single generalized tonic-clonic seizure at the age of 7 years. A distant cousin of the paternal great grandmother was also said to have PME. CSTB testing revealed that our patient was a compound heterozygote for two mutations: an expansion of the dodecamer repeat and a splice site c.67–1G > C mutation in intron 1, predicting a deletion of the downstream exon 2 with in-frame deletion of 34 aminoacids (p.delV23_K56). This is the second most common mutation underlying EPM1, and the most common point mutation. The husband has no potential EPM1-causing sequence alterations. Although ULD is often confused with JME in the early stages of the disease, it is rare to find patients with ULD at age 30 who are as well controlled and high-functioning as this patient. Furthermore, other compound heterozygotes with the same combination of mutations have had more severe phenotypes with progressive deterioration. The reason for the milder phenotype in this individual remains unexplained, and may be due to modifying genes and/or gene–environment interactions.

Senile myoclonic epilepsy: Delineation of a common condition associated with Alzheimer's disease in Down syndrome

In Down syndrome (DS), epilepsy is frequent in all age classes and is recognized as a significant cause of additional handicap and morbidity. Longer life expectancy has led to the recognition of the high incidence of both Alzheimer's disease and seizures in elderly persons with DS. Neuropathological markers of AD are found in all DS brains and clinical symptoms of AD become apparent by the age of 60 years and above in over 50% of DS subjects. Following preliminary description of myoclonic seizures and/or myoclonic epilepsy in isolated cases or small series, we wish to report the diagnostic criteria, treatment and prognosis of a specific and recognizable form of epilepsy associated with AD in a larger group of middle-aged to elderly DS patients. This markedly under-recognized entity may indeed concern an already large and steadily increasing number of patients. We reviewed all medical records of patients with DS referred to our centers (Centre Saint Paul-Gastaut, Marseille; Epilepsy Unit, Montpellier University Hospital; Department of Neurology, Hospital General de Asturias, Oviedo) since 1995. DS had been diagnosed in all at birth, and all presented with the typical morphological changes associated with DS. We selected all cases (18) referred as adults with new onset of myoclonic jerks (MJ) and/or behavioral or cognitive deterioration (CD).

Cortical myoclonus in Janz syndrome

Objective: To evaluate the characteristics of EEG paroxysms and the relationship between EEG spikes and ictal myoclonic jerks in patients with juvenile myoclonic epilepsy (JME). Methods: Six patients with a typical form of JME entered the study and underwent computerized polygraphic recordings. In each patient, the inter-peak spike interval was measured on repeated EEG bursts, and jerk-locked back averaging was performed on ictal epochs using a time window including the 100 ms before and the 100–200 ms after the point at which the jerk-related EMG potential diverged from baseline. Results: In all cases, the myoclonic jerks were associated with polyspike waves (PSW) complexes. The frequency of repeated spikes within the PSW complex ranged from 16 to 27 Hz. Jerk-locked averaging revealed a positive-negative EEG transient with maximal amplitude on the frontal leads, which preceded the myoclonic jerk by 10.25±0.96 ms. A delay of 9.50±1.73 ms was measured between the jerk-locked positive peak detected on the frontal EEG leads of the two hemispheres; a comparable time lag was observed between the onset of myoclonic jerks in the two deltoid muscles. Conclusions: Our data suggest that the ultimate mechanism responsible for ictal myoclonic jerks in JME is largely similar to that sustaining cortical myoclonus in more severe pathological conditions such as progressive myoclonus epilepsies, despite the different pathogenic substrate and triggering mechanisms.

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.

Brain-stem auditory evoked poteivtials (BAEPs) in patients suffering from focal dystonias: a study of 16 subjects

Objective: To evaluate the characteristics of EEG paroxysms and the relationship between EEG spikes and ictal myoclonic jerks in patients with juvenile myoclonic epilepsy (JME).Methods: Six patients with a typical form of JME entered the study and underwent computerized polygraphic recordings. In each patient, the inter-peak spike interval was measured on repeated EEG bursts, and jerk-locked back averaging was performed on ictal epochs using a time window including the 100 ms before and the 100–200 ms after the point at which the jerk-related EMG potential diverged from baseline.Results: In all cases, the myoclonic jerks were associated with polyspike waves (PSW) complexes. The frequency of repeated spikes within the PSW complex ranged from 16 to 27 Hz. Jerk-locked averaging revealed a positive-negative EEG transient with maximal amplitude on the frontal leads, which preceded the myoclonic jerk by 10.25±0.96 ms. A delay of 9.50±1.73 ms was measured between the jerk-locked positive peak detected on the frontal EEG leads of the two hemispheres; a comparable time lag was observed between the onset of myoclonic jerks in the two deltoid muscles.Conclusions: Our data suggest that the ultimate mechanism responsible for ictal myoclonic jerks in JME is largely similar to that sustaining cortical myoclonus in more severe pathological conditions such as progressive myoclonus epilepsies, despite the different pathogenic substrate and triggering mechanisms.

Polysomnographic study in men with asymptomatic HIV infection

Objective: To evaluate the characteristics of EEG paroxysms and the relationship between EEG spikes and ictal myoclonic jerks in patients with juvenile myoclonic epilepsy (JME).Methods: Six patients with a typical form of JME entered the study and underwent computerized polygraphic recordings. In each patient, the inter-peak spike interval was measured on repeated EEG bursts, and jerk-locked back averaging was performed on ictal epochs using a time window including the 100 ms before and the 100–200 ms after the point at which the jerk-related EMG potential diverged from baseline.Results: In all cases, the myoclonic jerks were associated with polyspike waves (PSW) complexes. The frequency of repeated spikes within the PSW complex ranged from 16 to 27 Hz. Jerk-locked averaging revealed a positive-negative EEG transient with maximal amplitude on the frontal leads, which preceded the myoclonic jerk by 10.25±0.96 ms. A delay of 9.50±1.73 ms was measured between the jerk-locked positive peak detected on the frontal EEG leads of the two hemispheres; a comparable time lag was observed between the onset of myoclonic jerks in the two deltoid muscles.Conclusions: Our data suggest that the ultimate mechanism responsible for ictal myoclonic jerks in JME is largely similar to that sustaining cortical myoclonus in more severe pathological conditions such as progressive myoclonus epilepsies, despite the different pathogenic substrate and triggering mechanisms.

RO15-4513 but not FG-7142 reverses anticonvulsant effects of ethanol against bicuculline- and picrotoxin-induced convulsions in rats.

The reversal of anticonvulsant effect of ethanol against chemoconvulsions by RO15-4513 was investigated in rats as this novel imidazobenzodiazepine (ethyl-8 azido-5, 6-dihydro-5-methyl-6-Oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate) is reported to antagonize the acute behavioral and biochemical effects of ethanol in animals. Reversal of ethanol effects on onset of myoclonic jerks, tonic extensor phase, mortality time and percent protection against mortality were compared with not only other anticonvulsant pentobarbital but also with another inverse agonist FG-7142. Pretreatment with RO15-4513 (4 mg/kg) reversed the protective effect of ethanol against bicuculline-induced tonic extensor phase and mortality (87%). This response was sensitive to reversal by RO15-1788 (10 mg/kg). However, onset of myoclonic jerks and duration of clonus were not significantly altered. It also reversed the effect against picrotoxin but the reversal against mortality was up to 50%. As compared to ethanol, RO15-4513 reversed partially the protective effect of pentobarbital against bicuculline- and picrotoxin-induced convulsions. FG-7142 failed to reverse the protective effect of ethanol and pentobarbital against bicuculline-induced tonic extensor phase although it reversed the effect against onset and mortality. It had no effect on the protective effect against picrotoxin-induced convulsions. Both RO15-4513 and FG-7142 possessed proconvulsant effects against bicuculline but not against picrotoxin. These observations suggest that RO15-4513 has a more preferential action against ethanol effects as compared to the other inverse agonist.

Encephalopathie myoclonique precoce avec epilepsie

The authors describe the electroclinical and evolutive aspects of 4 cases (including 2 brothers) of myoclonic epileptic encephalopathy beginning between 2 days and 10 weeks of life. From the onset of myoclonic jerks, polymorphous fits (partial seizures, tonic seizures) and multifocal electrical abnormalities are associated. Repeated spasms and 'suppression-burst' patterns appear later. The neurological status deteriorates progressively, leading within a few months to decerebration posture with opisthotonus. In spite of thorough neuroradiological, biochemical, cytological to metabolic investigations, etiology remains unknown. However, the electroclinical and evolutive patterns are similar to that of metabolic diseases, especially non-ketotic hyperglycemia. The authors discuss the relations between their observations and those in the literature and the nosological problems of this particular epileptic encephalopathy of infancy.

Clinical and EEG characteristics of Juvenile Myoclonic Epilepsy

Objective : To determine the clinical and electroencephalographic characteristics of patients with Juvenile Myoclonic Epilepsy (JME). Methods: In this descriptive case series study, 60 patients of Juvenile myoclonic epilepsy (JME) were included. After detailed history clinical examination, Electroencephalography (EEG) with standard protocol was performed in all patients and was analyzed by a neurologist. Results: Out of 60 patients, 26 (43.3%) were males and 34 (56.6%) were females. Mean age at the onset of myoclonic jerks (MJ) and generalized tonic clonic seizures (GTCS) was 13.7 ± 2.12 years and 14.15 ± 1.79 years respectively. Average delay in the diagnosis was 5.2 years. Myoclonic jerks (MJ) were present in all patients, GTCS in 52 (86.6%), and absence seizures in 8 (13.33%) patients. 6 (10%) had only Myoclonic Jerks. First seizure type was MJ in 52 (86.6%) and absence in 8 (13.3%). Most common precipitating factors were sleep deprivation in 80% and fatigue in 66.6%. Family history for epilepsy was positive in 20%. Diagnosis by referring physicians was JME in only 6 (10%) patients. EEG was abnormal in 42 patients (70%) showing generalized , 4- to 6-Hz polyspike and wave in 27 (45%), generalized single spike/ sharp waves in 7 patients (11.6%), 8 (13.3%) patients had 3-Hz spike-and-wave (SW) activity in addition to the polyspike-and-wave (PSW) pattern. Independent focal EEG abnormalities were noted in 12 patients (20%). Conclusion: Many of our patients were misdiagnosed by the referring physicians and were prescribed inappropriate antiepileptic drugs. Factors causing misdiagnosis were failure to elicit history of myoclonic jerks, misinterpreting myoclonic jerks as partial seizures and misinterpretation of EEG abnormalities.