Clinical and electroencephalographical follow-up study of early myoclonic encephalopathy

We report a clinico-electroencephalographical follow-up study on a male patient with early myoclonic encephalopathy. Frequent massive and fragmentary myoclonic seizures, and myoclonic-clonic seizures were the initial symptoms at the age of 3 days. EEG revealed a suppression-burst pattern at the onset in which burst phases often coincided with myoclonic seizures. Subsequently, non-epileptic erratic myoclonus, various partial seizures and flexor spasms were observed. The partial seizures ceased at around 4 months of age, while the non-epileptic myoclonus and flexor spasms have persisted beyond the age of 6 months. The EEG pattern evolved into atypical hypsarhythmia at two months of age. No specific biochemical or neuroradiological findings were disclosed. His neuropsychiatric development was arrested from the onset. These observations suggest that early myoclonic encephalopathy is an independent epileptic syndrome and that it might be different from early-infantile epileptic encephalopathy described by Ohtahara.     

Clinical features of early myoclonic encephalopathy caused by a CDKL5 mutation

BackgroundCDKL5 deficiency is caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene and clinically manifests often in females as drug-resistant intractable epilepsy and severe psychomotor retardation.Case reportWe report the case of a girl with a CDKL5 mutation born at 39 weeks without neonatal asphyxia. She developed epilepsy at age 1 month with myoclonus of the face and limbs, and non-rhythmic and irregular opsoclonus. She developed tonic seizures and epileptic spasms at 6 months of age and was diagnosed with symptomatic West syndrome and underwent adrenocorticotropic hormone therapy but her seizures were refractory. At the age of 4, she was introduced to our hospital and development was at 2 months of age. We diagnosed her with early myoclonic encephalopathy (EME) due to the remaining suppression-burst pattern observed on an electroencephalogram and her symptoms since onset were mainly myoclonus. At 14 years of age, mutational analysis revealed a CDKL5 mutation (c.380A > G:p.His127Arg). She was diagnosed with epileptic encephalopathy exhibiting clinical features of early myoclonic epilepsy caused by CDKL5 deficiency.ConclusionsEarly onset epilepsy with severe psychomotor retardation without a known etiology may be caused by a mutation in CDKL5. More research investigating a genotype-phenotype correlation of CDKL5 mutations is necessary because clinical severity may be associated with the location and type of mutations.     

Early myoclonic encephalopathy, early infantile epileptic encephalopathy, and benign and severe infantile myoclonic epilepsies: a critical review and personal contributions

Nosological confusion within the epilepsies with myoclonic manifestations occurring in early life has led several epileptologists to separate more rigorously true myoclonic seizures from pseudomyoclonic ones and to identify clusters of homogeneous parameters that may lead to the formulation of syndromatic groupings. In recent years, four neonatal, infantile, and early myoclonic syndromes have been proposed: early myoclonic encephalopathy (EME), early infantile epileptic encephalopathy (EIEE), benign infantile myoclonic epilepsy (BIME), and severe infantile myoclonic epilepsy (SIME). These are reviewed critically, historically, and in the context of personal observations. The author's conclusions are that there is some justification to support, provisionally, a nosological place for the EME syndrome, that a nosologically separate position for the EIEE syndrome appears less firm, and that it seems safer to consider it at this time as an early variant of the West syndrome. From personal observations it appears that BIME and SIME, while justifiably constituting recognizable entities, may best be combined into a single syndrome of "infantile myoclonic epilepsy following febrile convulsions," with variable clinical outcomes.     

Reversible myoclonic encephalopathy revealing the AIDS-dementia complex

A 40-year-old HIV-positive right handed homosexual man was admitted for progressive mental deterioration coexisting with permanent segmental middle-amplitude arrhythmic, asynchronous and asymmetrical myoclonic jerks. EEG showed fronto-central bursts of rhythmic triphasic 1.5–2 Hz sharp waves similar to the characteristics periodic pattern of Jakob-Creutzfeldt disease. Biological procedures were negative, thus eliminating a metabolic encephalopathy. Dramatic neurological improvement occurred shortly after initiation of i.v. and then oral zidovudine which produced perfect EEG normalisation. This unusual electroclinical presentation of the AIDS-dementia complex underlines the fact that this affection may present a diagnostic challenge, particularly in individuals in whom HIV infection is unknown.     

Schinzel-Giedion syndrome: a further cause of early myoclonic encephalopathy and vacuolating myelinopathy

Here, we report a male child with Schinzel-Giedion syndrome associated with intramyelinic edema detected on brain magnetic resonance imaging (MRI) and persistent suppression-burst pattern on electroencephalography (EEG) with erratic myoclonus of the extremities and face. Similar to nonketotic hyperglycinemia, Schinzel-Giedion syndrome may be recognized as another causative genetic disease of early myoclonic encephalopathy and vacuolating myelinopathy.     

A neurodegenerative disorder with early myoclonic encephalopathy, retinal pigmentary degeneration and nephronophthisis

A female case of developmental arrest, early-onset seizures, retinal pigmentary degeneration, progressive central nervous symptoms and peripheral neuropathy, associated with progressive renal dysfunction, anemia and nephrotic syndrome, was presented. Her epileptic syndrome was possibly an early myoclonic encephalopathy, though neonatal seizures were not evident. Serial cranial MRIs showed progressive brain atrophy and a white matter change. Neuropathological examination revealed a neurodegenerative disease mainly involving the white matter with olivopontocerebellar degeneration. She also had the nephronophthisis-medullary cystic disease complex and an early stage of focal segmental glomerulosclerosis. Her grandaunts had renal diseases, one of whom died of renal failure in adolescence, and her father showed cerebellar symptoms since the middle age. All possible metabolic studies were negative. This case is similar to Senior-Loken syndrome, but distinct in terms of the severe and progressive neurological symptoms, suggestive of a new malignant syndrome with some inherent metabolic derangement affecting both the nervous system and the kidneys.     

Ohtahara syndrome: with special reference to its developmental aspects for differentiating from early myoclonic encephalopathy

Ohtahara syndrome (OS) is well known as a peculiar early onset epileptic syndrome with serious prognosis. The outline of OS, mainly in relation to the evolution with age, and differentiation from related conditions, particularly early myoclonic encephalopathy (EME) were mentioned. RESULTS: Etiologically, structural brain lesions are most probable in OS, and non-structural/metabolic disorders in EME. Clinically, tonic spasms are the main seizures in OS, while myoclonia and frequent partial motor seizures in EME. Another difference is noted in EEG findings: suppression-bursts (SB) are consistently observed in both waking and sleeping states in OS, but suppression-bursts become more apparent in sleep in EME. The course observation clarifies differences between both syndromes; SBs evolve to hypsarrhythmia around 3-4 months of age, and sometimes further to diffuse slow spike-waves in OS. In contrast, in EME suppression-bursts may persist up to late childhood after a transient evolution to hypsarryhtmia in the middle to late infancy. Transition between syndromes is also specific; OS evolves to West syndrome, and further to Lennox-Gastaut syndrome with age, but EME persists long without such evolution excepting a transient phase of West syndrome. CONCLUSION: These clinicoelectrical characteristics and differential points strongly indicate the efficiency of the developmental study to delineate both syndromes.     

A case of early myoclonic encephalopathy with intractable seizures successfully treated with high-dose phenobarbital

BackgroundEarly myoclonic encephalopathy (EME) is an epileptic syndrome that develops in neonates, commonly within 1 month of birth. The condition is characterized by irregular, partial, and asynchronous myoclonus. The seizures in EME are generally refractory to antiepileptic drugs and no effective treatment for EME has been established. We encountered a case of EME in which oral high-dose phenobarbital therapy effectively alleviated seizures.Case reportA male infant developed erratic myoclonus in the face and limbs, exhibited upward gaze and facial flushing 20–30 times a day since 1 week of age. Electroencephalogram (EEG) showed a burst-suppression pattern, and considering the clinical features, EME was diagnosed. Valproate and vitamin B6 treatments were initiated; however, they were not effective. At day 58 after birth, oral high-dose phenobarbital therapy was introduced which resulted in the suppression of seizures to one or two per week and disappearance of the burst-suppression pattern on EEG.ConclusionOral high-dose phenobarbital treatment may be suitable for controlling seizures in EME.     

Neuropathology of early-infantile epileptic encephalopathy with suppression-bursts; comparison with those of early myoclonic encephalopathy and West syndrome.

For the critical lesions and pathomechanism of early-infantile epileptic encephalopathy (EIEE) with suppression-bursts, we investigated the brains of EIEE, early myoclonic encephalopathy (EME), and West syndrome (WS) patients using immunohistochemical technique and neuropathological examination. We could compare with the results of these diseases.The EIEE patients had the most severe lesions, which were in the putamen, thalamus, hippocampus as well as the tegmentum of the brainstem. Among the syndromes, EIEE brains showed the most expanded lesions. Tyrosine hydroxylase-immunopositive cells and fibers were not demonstrated in EIEE, but were detected in WS. Reduced tyrosine hydroxylase immunoexpression in the EIEE brains was in the putamen, globus pallidus, and substantia nigra. Tryptophan hydroxylase immunoreactivity was reduced in the three epileptic syndromes, but especially in EIEE. Reduced expression of tyrosine hydroxylase and tryptophan hydroxylase may demonstrate dysfunction of the catecholaminergic and serotonergic neurons. From this study, the lesions in EIEE were widespread, including in the lower brainstem and cerebellum, compared with in EME and WS. Dysfunction of the catecholaminergic and serotonergic systems could be suggested. These characteristic changes may lead to the pathophysiology of EIEE.     

Display of prolonged EEG recordings

An interactive minicomputer system for displaying, storing and providing hard copy output of prolonged EEG recordings has been described. Perhaps the most significant feature of the system is the versatility gained by using a minicomputer. The routines developed initially solely for the display and storage of the EEG have recently been readily modified to control a different playback unit. They also form an integral part of a software package being written to set up a data base for prolonged EEG recordings and also for the study of artefacts in ambulatory recordings.     

Independent component approach to the analysis of EEG recordings at early stages of depressive disorders

ObjectiveA modern approach for blind source separation of electrical activity represented by Independent Components Analysis (ICA) was used for QEEG analysis in depression.MethodsThe spectral characteristics of the resting EEG in 111 adults in the early stages of depression and 526 non-depressed subjects were compared between groups of patients and healthy controls using a combination of ICA and sLORETA methods.ResultsComparison of the power of independent components in depressed patients and healthy controls have revealed significant differences between groups for three frequency bands: theta (4–7.5 Hz), alpha (7.5–14 Hz), and beta (14–20 Hz) both in Eyes closed and Eyes open conditions. An increase in slow (theta and alpha) activity in depressed patients at parietal and occipital sites may reflect a decreased cortical activation in these brain regions, and a diffuse enhancement of beta power may correlate with anxiety symptoms playing an important role on the onset of depressive disorder.ConclusionsICA approach used in the present study allowed us to localize the EEG spectra differences between the two groups.SignificanceA relatively rare approach which uses the ICA spectra for comparison of the quantitative parameters of EEG in different groups of patients/subjects allows to improve an accuracy of measurement.     

Simultaneous intracerebral EEG recordings of early auditory thalamic and cortical activity in human

We describe documented simultaneous intracerebral auditory evoked potentials from the auditory cortex and medial geniculate body (MGB) of a human patient. The MGB response lasted > 300 ms, with an initial negativity at 13.5 ms (N13), two positive peaks P21 and P29, and two broader negativities N50 and N200. P21 and N50 amplitudes were strongest for lowest tone frequencies, suggesting possible MGB tonotopic organization. Thalamic peaks were strongly interlaced with cortical activities recorded in Heschl's gyri before 30 ms: N13 preceded the first cortical component by 3.5 ms, then P21 and P29 preceded and lagged, respectively, the following two cortical polarity reversals by 1.5-2 ms. This study provides new functional data on the human MGB, and supports a more complex than simply relay-like role of the thalamus in sound perception.     

Ordinal pattern based similarity analysis for EEG recordings

ObjectiveOrdinal patterns analysis such as permutation entropy of the EEG series has been found to usefully track brain dynamics and has been applied to detect changes in the dynamics of EEG data. In order to further investigate hidden nonlinear dynamical characteristics in EEG data for differentiating brain states, this paper proposes a novel dissimilarity measure based on the ordinal pattern distributions of EEG series.MethodsGiven a segment of EEG series, we first map this series into a phase space, then calculate the ordinal sequences and the distribution of these ordinal patterns. Finally, the dissimilarity between two EEG series can be qualified via a simple distance measure. A neural mass model was proposed to simulate EEG data and test the performance of the dissimilarity measure based on the ordinal patterns distribution. Furthermore, this measure was then applied to analyze EEG data from 24 Genetic Absence Epilepsy Rats from Strasbourg (GAERS), with the aim of distinguishing between interictal, preictal and ictal states.ResultsThe dissimilarity measure of a pair of EEG signals within the same group and across different groups was calculated, respectively. As expected, the dissimilarity measures during different brain states were higher than internal dissimilarity measures. When applied to the preictal detection of absence seizures, the proposed dissimilarity measure successfully detected the preictal state prior to their onset in 109 out of 168 seizures (64.9%).ConclusionsOur results showed that dissimilarity measures between EEG segments during the same brain state were significant smaller that those during different states. This suggested that the dissimilarity measure, based on the ordinal patterns in the time series, could be used to detect changes in the dynamics of EEG data. Moreover, our results suggested that ordinal patterns in the EEG might be a potential characteristic of brain dynamics.SignificanceThis dissimilarity measure is a promising method to reveal dynamic changes in EEG, for example as occur in the transition of epileptic seizures. This method is simple and fast, so might be applied in designing an automated closed-loop seizure prevention system for absence epilepsy.     

Evaluation of serial EEG recordings and auditory brainstem responses in the early preterm infants]

EEGs were recorded serially throughout the neonatal period and auditory brainstem responses (ABRs) in the late neonatal period in 105 preterm infants with the gestational age of less than 33 weeks and birth weights of less than 1,750g in order to study the relation between abnormal findings and neurological outcome. A study of serial EEG recordings revealed that a disorganized pattern following severe depression of background EEG activities was closely associated with deep white matter injuries detected by ultrasonography and that infants showing such features are likely to suffer from cerebral palsy. On the other hand, a dysmature pattern was often observed following prolonged mild depression, although no abnormalities were apparent on ultrasonography. This EEG pattern was more often associated with mental impairment. Any findings of ABRs were not associated with adverse outcome. We conclude that serial EEG recordings during the neonatal period in preterm infants are useful in clarifying the extent and nature of brain injury as well as future developmental problems.     

A patient with early myoclonic encephalopathy (EME) with a de novo KCNQ2 mutation

Background

The potassium voltage-gated channel subfamily Q member 2 (KCNQ2) gene has been reported to be associated with various types of epilepsy, including benign familial neonatal seizure (BFNS), early infantile epileptic encephalopathy (EIEE), and unclassified early onset encephalopathies. We herein report a patient with early myoclonic encephalopathy (EME) caused by a KCNQ2 mutation.

Vigabatrin caused rapidly progressive deterioration in two cases with early myoclonic encephalopathy associated with nonketotic hyperglycinemia

Vigabatrin, a structural analogue of gamma-aminobutyric acid (GABA), is used for the treatment of generalized and partial seizures in infants. The drug inhibits the GABA transaminase and elevates the GABA concentration in the brain. Here we present the vigabatrin experience in two patients with early myoclonic encephalopathy owing to nonketotic hyperglycinemia (glycine encephalopathy). Both patients had early infantile seizures characterized by fragmentary myoclonic jerks associated with burst-suppression pattern on electroencephalography. Nonketotic hyperglycinemia was diagnosed with elevated cerebrospinal fluid and plasma glycine levels. The seizures were initially thought to be infantile spasms, and vigabatrin (50 mg /kg/day) was started for the treatment of seizures. Rapidly progressive deterioration was noticed after a few days. Acute encephalopathy associated with sleepiness and respiratory failure developed. Vigabatrin produced acute encephalopathy, which regressed in a few days after vigabatrin was stopped in the first patient. However, in the second case, despite the discontinuation of vigabatrin, there was no recovery of general conditions. Our observations in two cases indicate the risk of using vigabatrin in patients with nonketotic hyperglycinemia. The elevated GABA concentration in the brain can enhance the encephalopathy, together with the elevated levels of glycine. (J Child Neurol 2006;21:82-84).