Adversive Seizures Research Articles

Clinical report: a rare co-occurrence of tuberous sclerosis complex and Rett syndrome in a girl with mental retardation, epilepsy and autism

SummaryIntroduction.There are some genetic disorders with combination of mental retardation, epilepsy and autism in which the abnormal mammalian Target of Rapamycin (m-TOR) signaling is implicated. The most important of them is tuberous sclerosis complex (TSC), but the disturbances of the m-TOR pathway can also be detected in Rett syndrome (RS), Fragile X syndrome and Down syndrome. We describe the rare case of co-occurrence of TSC and RS.Case study.The female child was born at term by normal delivery after a non-complicated pregnancy. Family history was negative for epilepsy and mental retardation. The neonatal period was uneventful and psychomotor development was normal before the child became 1.5 years old. At the age of 18 months the girl developed hand-wringing stereotypes, facial hypotonia, ataxia and gait apraxia. She lost eye-to-eye contact and verbal contact with relatives, and became indifferent to the surrounding environment. When she was 2 years old, focal adversive seizures started which were readily controlled with carbamazepine. Cerebral cortical and subcortical tubers, cerebral white-matter radial migration lines and subependymal nodules on brain MRI together with hypomelanotic macules suggested the presence of TSC. Diagnosis was confirmed at age of 3 years by a heterozygous mutation c.5161-2A>G inTSC2gene on chromosome 16p13. But the rude regression of psychomotor development and speech, autistic features alongside with characteristic hand-wringing stereotypes were unexplained until at age of 4.5 years RS was diagnosed by finding a heterozygous missense mutation in exon 4 of theMECP2gene c.455C>T, resulting in a P152R substitution in the methyl-binding domain of the protein. At age of 5 the patient is not able to walk independently and has no expressive speech, she is autistic, has ataxia, limb rigidity, hyperreflexia, lack of purposeful hand movements, verbal and motor stereotypies.Discussion.The presence of two mutations (one characteristic forTSC2and one – characteristic for RS) significantly worsened the developmental and motor delay and autistic features in our patient. Dysregulation of m-TOR way is well established in TSC and recently described in RS, Down syndrome and Fragile X syndrome.

PP01.7 – 2726: A novel description of a homozygous partial deletion of RBFOX1 gene causing epileptic encephalopathy, severe intellectual disability and progressive post-natal microcephaly

Objective Partial deletions of the gene encoding the neuronal splicing regulator RBFOX1 have been reported in a range of neurodevelopmental diseases, including idiopathic generalized epilepsy, Rolandic epilepsy (RE), Autosomal dominant lateral temporal epilepsy (ADLTE) or idiopathic generalized epilepsy (IGE). Patients often exhibit severe co-morbid neuro-developmental disorders such as intellectual disability (ID) and Autism spectrum disorders (ASD) or microcephaly. Heterozygous RBFOX1 knockout mouse models demonstrate deregulated splicing, disrupting genes involved in synaptic transmission and membrane excitability leading to increased susceptibility for seizure events. All patients reported so far have a hemizygous deletion/mutation and the transmitting parents in most cases were asymptomatic. We report a female toddler, that first presented with adversive seizures at four months of age, progressing to intractable epilepsy. EEG demonstrated generalized spike & wave activity. Currently at the age of thirty months she has profound ID and progressive post-natal microcephaly. Extensive diagnostic workup was uninformative – including whole exome sequencing (WES) for known epilepsy mutations. Brain MRI demonstrated non-specific findings. Her parents are first cousins of Arab origin. Ten family members are noted for epilepsy, intellectual disability of different severities and autism, however none has the same severe presentation as the patient. Methods and results Chromosomal micro-array analysis (CMA) revealed a 426 KB homozygous deletion in chromosome 16p13.3 at the 5' UTR end of the RBFOX1 gene. The asymptomatic parents are heterozygous for the deletion. Conclusion This is the first case of a homozygous partial deletion of the RBFOX1 gene in a toddler suffering from epileptic encephalopathy with profound ID and progressive postnatal microcephaly detected by CMA. Our case strengthens the association of partial RBFOX1 deletions in neurodevelopmental diseases and extends the RBFOX1-related phenotypic spectrum.

English

Moyamoya disease is a rare cerebrovascular disease characterized by progressive occlusive cerebral arteritis affecting the distal internal carotid arteries near the circle of Willis. A collateral circulation develops around the blocked vessels which appear as a puff of smoke. Incidence is variable depending on the geographical location. The clinical features of Moyamoya disease are recurrent transient ischemic attacks (TIAs), strokes, sensorimotor paralysis, convulsions and/or migraine-like headaches. Magnetic resonance imaging (MRI) and MR Angiogram (MRA) should be performed for the diagnosis and follow-up of Moyamoya disease. Neurosurgical proceures like Encephalo myo synangiosis (EMS), multiple burr holes and some direct procedures are useful to reestablish new circulation after a few weeks. The long term outlook for patients with treated Moyamoya seems to be good. Once major stroke or bleeding take place, even with treatment, the patient may be left with permanent loss of function. So it is very important to treat this condition promptly. Herewith, we are reporting a 15 month old child with history of right focal adversive seizures, 34 events a month followed by post ictal drowsiness. Imaging studies revealed a vascular insult with infarct in the left fronto parietal lobes as well as multiple infarcts in other regions of the brain. MR Angio Brain revealed Moya moya disease. Child was successfully managed by prompt referral to Neurosurgical Centre where he underwent EMS and he is under their follow up.

Adversive seizures associated with periodic lateralised epileptiform discharges (PLEDs) after left orbital contusion

We report a patient who presented with adversive seizures associated with periodic lateralised epileptiform discharges (PLEDs), a month after head trauma. The PLEDs predominantly involving the left frontal contacts became more frequent at the onset of adversive seizures during EEG. Brain MRI demonstrated a contusion scar in the left orbital cortex with reduced diffusion, not only around this orbital lesion but also in the ipsilateral anteromedial thalamus. Single photon emission computed tomography revealed focal cerebral hyperperfusion in the left medial orbitofrontal region, basal ganglia, and thalamus. The abnormal metabolism involving the thalamus and striatum could be associated with the ipsilateral orbital contusion and might have been caused by cortical-subcortical, trans-synaptic hyperactivity. Further studies are warranted to determine the role of subcortical structures in the generation of PLEDs and adversive seizures. [Published with video sequences].

Magnetoencephalogram in a Postoperative Case With a Large Skull Defect

We present a patient in whom magnetoencephalograms were successfully performed in presurgical and postsurgical evaluations. A 12-year-old boy with congenital porencephaly was admitted with refractory adversive seizures and frontal absence seizures. Ictal magnetoencephalographic dipoles with frontal absence seizures were located in the left frontal lobe, anterior to the porencephalic cyst, and concordant with the same area detected by intraoperative electrocorticography. A partial cortical excision was performed, and the patient's cranial bone flap was removed because of an epidural abscess. The frontal absences then disappeared. The magnetoencephalogram revealed that secondary bilateral synchrony of focal discharges from the lesion may have caused the generalized seizures in this patient. Because of residual partial seizures, second and third magnetoencephalograms were performed, and we detected residual spike dipoles clustering in the area posterior to the cavity of cortical excision and anterior to the porencephalic cyst. Another excision of the area between the cavity and frontal edge of the cyst was performed, and seizure frequency diminished dramatically. In this case, despite the failure of dipole estimation by electroencephalogram in the context of a large bone defect, the magnetoencephalogram was useful in detecting the residual epileptogenic zone after failed epilepsy surgery.

Clinical and electroencephalographic findings in early and late onset benign childhood epilepsy with occipital paroxysms

Twenty-six patients were studied who had the clinical and electroencephalographic features of benign childhood epilepsy with occipital paroxysms (BCEOP) as defined by the Commission of the International League Against Epilepsy (ILAE). Twelve patients were characterized as having early-onset benign childhood occipital seizures (EBOS) susceptible syndrome, as described by Panayiotopoulos, and 14 patients had late onset childhood idiopathic occipital seizures (LOS). Patients with symptomatic epilepsy and whose EEGs exhibited occipital spikes were excluded. The age of onset of the EBOS group ranged from 2.6 to 9.4 years (mean: 4.9±1.7 years ), which was significantly younger than the LOS group (range: 4-12 years, mean:8.4±2.5 years). Both sexes were equally affected. The patients in the EBOS group had less frequent and longer seizures, ictal vomiting, more frequent deviation of the eyes, adversive seizures and more frequent nocturnal and secondary generalized seizures ( P<0.05). By comparison, patients in the LOS group had a higher incidence of seizures, shorter duration of seizures and more frequent diurnal onset ( P<0.01); also, although not statistically significant, the LOS group had more frequent visual hallucinations and headaches. The EEG topography in both groups showed at either side of occipital area typical paroxysms that were unilateral or bilaterally synchronous. Neither group had dipoles according to scalp voltage mapping. The clinical prognoses were favorable for both groups. To distinguish EBOS from LOS, detailed description of the age of onset, motor symptoms, visual symptoms, presence of eye deviation and diurnal or nocturnal occurrence are essential.

Meningioangiomatosis: a case report and review of the literature

A case of cerebral meningioangiomatosis in an adult man without any stigmata of neurofibromatosis is reported. A 22-year-old man with no previous neurological history, presented with adversive seizures; clinical examination and electroencephalogram were normal. CT showed nodular calcified masses in the left frontal lobe and in the left posterior parietal area. A craniotomy was performed and the frontal lesion was excised. Histological examination showed a predominantly intracerebral tumour involving both grey and white matter, with a complex picture of variable cellularity, dense calcification and prominent perivascular arrangements of reticulin-rich spindle cell fascicles with palisade formation widely involving the brain tissue. Immunohistochemistry for S100 protein varied between different parts of the tumour; there was focal positivity for S100 protein and smooth muscle actin in the lesion with no reaction for GFAP or EMA. Immunostaining for Factor 8-related antigen highlighted the perivascular arrangement of lesional cells and demonstrated an increase in the number of small vessels in other areas. Electron microscopy of the main mass showed elongated spindle cells with formation of pericellular basal lamina. The literature on meningioangiomatosis was reviewed. The evidence for meningeal, perivascular neural plexus or pericyte origin does not appear to be well founded.The present case further illustrates the difficulty in identifying an exact histogenetic cell and probably reflects an origin from a primitive perivascular mesenchymal cell.

Frontal Lobe Epilepsy of Childhood Onset

Summary: We retrospectively studied long‐term clinical profiles of 38 patients with cryptogenic or symptomatic frontal lobe epilepsy (FLE) of childhood onset. More patients in our patient population had FLE than temporal lobe epilepsy (TLE). Etiology of symptomatic FLE included tuberous sclerosis, cortical dysplasia, intracranial hemorrhage, perinatal asphyxia, and hemiconvulsion‐hemiplegia‐epilepsy syndrome. In 6 patients, magnetic resonance imaging (MN) showed no abnormality, but positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) showed glucose hypometabolism in the frontal lobe. The seizures were characterized by postural seizures, focal tonic or clonic seizures, complex gestural automatism, eye deviation, and adversive seizures. Seizure prognosis was poor. Only 13 patients (35%) became seizure‐free for 2 years. Poor prognostic factors for seizures included intelligence deficits, seizure clustering, and aura.

Infantile spasms in one member of a family with benign familial neonatal convulsions.

Seven members of two generations experienced benign familial neonatal convulsions (BFNC) in the neonatal period and/or early infancy. All but 1 family member had a good prognosis. One family member with infantile spasms (IS) was delivered by cesarean section at 37 weeks gestation. Birth weight (2,562 g) was slightly lower than that of other family members. At age 20 days, adversive seizures started. At age 1 month, 10 days, she developed complex partial seizures (CPS) and IS. Interictal EEG showed hypsarrhythmia. Biochemical investigations and head magnetic resonance imaging (MRI) scan showed no abnormalities. Treatment with valproate (VPA) and carbamazepine (CBZ) stopped the seizures, and she had no seizures after age 3 months. Psychomotor development was moderately delayed at 8 months. This is the first reported case of a severe epilepsy, IS, in association with BFNC.

Drop attacks: an ominous change in the evolution of partial epilepsy.

We studied 16 patients with partial epilepsy and drop attacks. The drop attacks appeared 1 to 29 years after onset of epilepsy; 15 patients had these attacks weekly or daily, despite therapy. After the appearance of drop attacks, 6 patients had severe mental disorders, and social life was disrupted in 13. There was a high rate of adversive seizures, atypical absences, and diffuse spike-wave discharges in the EEG, electroclinical features that suggest a frontal origin of epilepsy. Drop attacks are ominous because they occur so frequently, resist therapy, are physically dangerous, and portend personality change.

Alumina cream-induced epilepsy in cats. III. Wakefulness-sleep modulation of multiple unit activity in the reticular formation

Quantitative changes in tonic and phasic multiple unit activities (MUA) of the mesencephalic (MRF) and pontine reticular formations (PRF), pyramidal tract (PT) and neck muscles (EMG) during wakefulness (W), slow wave sleep (SWS) and paradoxical sleep (PS) were determined in alumina cream-induced epileptic cats showing two types of EEG/EMG seizures: type B characterized by continuous isolated EEG spikes and EMG jerks (epilepsia partialis continua) and type C characterized by episodic tonic-clonic EEG spikes and EMG jerks (adversive seizures). 1. (1) Tonic PT, MRF and PRF MUA were large during W and PS and low during SWS while EMG MUA was large during W, low during SWS and almost abolished during PS. PT and EMG MUA significantly decreased while MRF and PRF MUA did not change when cats shifted from W to SWS. PT, MRF and PRF MUA significantly increased while EMG MUA decreased from SWS to PS. PRF MUA significantly increased and EMG MUA significantly decreased while PT and MRF MUA did not change from W to PS. 2. (2) During W, type B phasic PT, MRF, PRF and EMG MUA significantly increased time-locked to the onset of isolated EEG spikes. During SWS and PS, PT, MRF and PRF MUA significantly increased while EMG MUA remained unchanged at the onset of EEG spikes. Type B phasic PT MUA significantly decreased when cats shifted from W and PS to SWS, EMG MUA decreased from W to SWS and PS while MRF and PRF did not change systematically through different wakefulness-sleep state shifts. 3. (3) During W, type C phasic PT, MRF and PRF MUA significantly increased 1 sec before while EMG MUA increased 1 sec after the onset of EEG tonic-clonic discharges. During PS, PT, MRF and PRF MUA significantly increased 5-4 sec before, decreased 2–3 sec after and increased 5–6 sec after while EMG MUA remained low and unchanged until it significantly increased 4 sec after the onset of tonic-clonic EEG discharges. PT MUA significantly increased 3 sec before, PRF MUA decreased 3 sec after and EMG MUA decreased 1–4 sec after the onset of tonic-clonic EEG discharges when cats shifted from W and SWS to PS.

Unilateral pupillary dilatation during adversive seizures.

A patient had adversive seizures accompanied by unilateral pupillary dilatation. Neuropathologic examination showed a contusion involving the middle frontal gyrus contralateral to the pupil that dilated during the seizure. The clinical features and the location of this lesion (presumably the epileptogenic focus) correlate well with experimental studies in which pupillary changes have been observed during stimulation of the cerebral cortex. Unilateral mydriasis associated with contraversion of the eyes during seizures may have value in localizing epileptogenic foci.

Frontal epileptogenic foci and their clinical correlations

Out of 10,000 consecutive EEG records only 30 cases with frontal epileptogenic foci were revealed. This is in striking contrast to the high frequency of epileptogenic foci localized in the temporal region. The reason for this is discussed. Electroencephalographic seizure discharges were recorded in ten patients, with no accompanying clinical phenomena in seven of these cases. The seizure discharges occurred spontaneously in five of these seven patients. Etiological factors were known in 27 patients. More than half of them suffered from the after-effects of severe open head injuries with fracture of the skull in the frontal region. In no case was there evidence of a birth injury or closed head injury later in life. Neuro-surgical intervention was performed on nineteen patients. In eight cases the reason for operation was frontal epileptogenic activity in combination with frequent epileptic seizures. Clinically six patients had never experienced any epileptic seizures. Among the remaining 24 patients, fourteen presented adversive seizures, ten somatic-motor, three somatic-sensory, and three patientshad an initial “rising epigastric aura”. Finally five patients presented no initial focal phenomena. Two of them suffered from grand mal with initial unconsciousness, and three from brief losses of consciousness. In these three patients, a bilateral synchronous spike-and-wave activity was recorded in addition to the frontal epileptogenic activity, suggesting an affection of the diencephalon in these cases.