Focal Dyscognitive Seizures Research Articles

Musicogenic Epilepsy: Clinical Features, Pathophysiology, and Review of Literature

AbstractMusicogenic epilepsy is a special type of reflex epilepsy characterized by recurring seizures in response to hearing-specific musical triggers. Clinical features include focal dyscognitive seizures with typical temporal lobe semiology, normal structural brain imaging, functional imaging abnormalities in wide regions of the brain responsible for emotional and musical processing, variable locations of seizure onset within the temporal lobe, and in refractory cases good response to surgery. Musicogenic epilepsy is poorly understood from a pathophysiological standpoint and thus reflects the complexity of brain networks responsible for auditory, emotional, and cognitive functions.

P.133 Expanding the phenotype of TRNT1 mutations to include Leigh syndrome

Background: Children with biallelic mutations in TRNT1 have multi-organ involvement with congenital sideroblastic anemia, -B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) as well as seizures, ataxia and sensorineural hearing loss. The TRNT1 gene encodes the CCA-adding enzyme essential for maturation of both nuclear and mitochondrial transfer RNAs accounting for phenotypic pleitropy. Neurodegenerative Leigh syndrome has not been previously reported. Methods:Case summary: A Portuguese boy presented with global developmental delay, 2 episodes of infantile Leigh encephalopathy at 8 mo and 4 yr responsive to high-dose steroids, slow neurodegeneration of cognitive, language and motor functions with optic atrophy, pigmentary retinopathy, spasticity, dystonia, and focal dyscognitive seizures, pancytopenia, transfusion dependent sideroblastic anemia, recurrent febrile infections (pulmonary, gastrointestinal), hypernatremia, with tracheostomy dependence at age 5 yr, malabsorption and TPN dependence at 9 yr, and survival to early adulthood. Neuroimaging showed symmetric hemorrhagic lesions in the thalamus, brain stem (periaqueductal grey) and cerebellum consistent with Leigh syndrome but no lactate peak on MRS. Results: Whole exome sequencing identified a homozygous missense pathogenic variant in TRNT1, c.668T>C (p.I223T) in the affected individual. Conclusions: This report expands the neurological phenotype of TRNT1 mutations and highlights the importance of considering this gene in the evaluation of Leigh syndrome.

Paroxysmal nonepileptic events in children with epilepsy

ObjectiveThe aim of this study was to clarify the characteristics of paroxysmal nonepileptic events (PNEs) suspected as being epileptic seizures by families of children with epilepsy. MethodsThe video-EEG (vEEG) recordings of habitual paroxysmal events in children with epilepsy at Nagoya University Hospital between October 2006 and January 2016 were reviewed. Based on the doctor’s suspicion before the vEEG, the PNEs were divided into two groups that included PNEs suspected as epileptic seizures and PNEs suspected as PNEs. PNEs in the former group were classified based on the suspected seizure type. ResultsOf 886 habitual paroxysmal events, vEEG confirmed that 83 events (68 children) were PNEs. The median age of the 68 children was 3.2 years. Concurrent epilepsies included focal epilepsies (n=33), infantile spasms (n=16), and other types (n=19). The most common types of PNEs were sleep myoclonus (n=11), followed by stereotypies (n=9), awake myoclonus (n=8), paroxysmal ocular deviations (PODs, n=8), and tonic posturing (n=8). Even after direct observation or video viewing, the doctors suspected epileptic seizures in all three of the PODs and two of the tonic posturing children. Before the vEEG, however, the accurate visual information led to the speculation that the four psychogenic and two sleep myoclonus events were all PNEs. Myoclonus, stereotypies, and head drops were often misdiagnosed as epileptic spasms, while PODs and tonic posturing were often misdiagnosed as focal seizures with motor components. Additionally, staring and motion arrest during a drowsy state were often misdiagnosed as focal dyscognitive seizures. Seven of eight patients with PODs had epileptic spasms that were concurrent with epileptic seizures. A diffuse cerebral lesion or reduced visual acuity was seen in seven patients with PODs. ConclusionWe re-emphasize that vEEG is essential for accurate diagnosis and provides evidence for listing POD in the differential diagnosis of oculomotor paroxysmal events.

Pure endoscopic management of epileptogenic hypothalamic hamartomas.

Hypothalamic hamartomas (HH) are rare congenital malformations located in the region of the tuber cinereum and third ventricle. Their usual clinical presentation is characterized by gelastic/dacrystic seizures which often become pharmaco-resistant and progress to secondary focal/generalized intractable epilepsy causing mostly in children cognitive and behavioral problems (particularly in cases of progressive epileptic encephalopathy) and precocious puberty. Whereas gelastic seizures can be surgically controlled either by resection of the lesion or disconnection (tissue-destructive) procedures, aimed at functionally prevent the spreading of the epileptic burst; generalized seizures tend to respond better to HH excision rather than isolated neocortical resections, which generally fail to control them. Prospective analysis of 14 consecutive patients harboring HH treated in an 8-year period; 12 patients had unilateral and two bilateral HH. All patients were managed by pure endoscopic excision of the HH. The mean operative time was 48min and mean hospital stay was 2days; perioperative blood loss was negligible in all cases. Two patients showed a transient diabetes insipidus (DI); no transient or permanent postoperative neurological deficit or memory impairment was recorded. Complete HH excision was achieved in 10/14 patients. At a mean follow-up of 48months, no wound infection, meningitis, postoperative hydrocephalus, and/or mortality were recorded in this series of patients. Eight patients became seizure free (Engel class I), 2 other experienced worthwhile improvement of disabling seizures (Engel class II); 2 patients were cured from gelastic attacks while still experiencing focal dyscognitive seizures; and 2, having bilateral HH (both undergoing unilateral HH excision), did not experience significant improvement and required later on a temporal lobectomy coupled to amygdalohyppocampectomy. Overall, the followings resulted to be predictive factors for better outcomes in terms of seizure control: (1) cases of unilateral, Delalande class B, HH, (2) shorter history of epilepsy. Endoscopic resection of HH proved, in our series, to be effective in achieving complete control or in reducing the frequency of seizures. Furthermore, this approach has confirmed its minimally invasive nature with a very low morbidity rate: of note, it allowed to better preserve short-term memory and hypothalamic function.

Epilepsy in ring chromosome 20 syndrome

ObjectiveRing chromosome 20 syndrome is characterized by severe, drug resistant childhood onset epilepsy, often accompanied by cognitive impairment. We characterized the electro-clinical phenotype and the long-term course of epilepsy in a large series. MethodsWe reviewed the electro-clinical phenotype of 25 patients (aged 8–59 years), and assessed the relationship between epilepsy severity and clinical and/or genetic variables. We also searched for reports of patients diagnosed with r(20) syndrome in the literature, included those whose clinical information was sufficiently accurate, and compared their clinical features with the ones of our patients. ResultsEpilepsy exhibited an age dependent course. When seizure onset occurred in childhood (21 patients), terrifying hallucinations associated with focal motor seizures, often sleep-related (8 patients), or dyscognitive seizures (13 patients), were prominent features, often evolving into epileptic encephalopathy associated with non-convulsive status epilepticus (11 patients). In the long-term, progressive stabilization of drug resistant epilepsy associated with non-convulsive status epilepticus, focal seizures with motor and autonomic features, and eyelid myoclonia were noticed. Epilepsy onset in adolescence (3 patients) was accompanied by a milder developmental course, dyscognitive seizures and non-convulsive status epilepticus, and no cognitive decline. Only three older patients became seizure free (>5 years) We found statistically significant correlations between age at epilepsy onset and cognitive level. Although in the study cohort the relationship between r(20) ratio, age at epilepsy onset and cognitive level was non-statistically significant, it reached significance evaluating the larger cohort of patients previously published. SignificanceIn ring(20) syndrome, epilepsy has an age dependent course and a worse outcome when age at seizure onset is earlier. The r(20) ratio and severity of cognitive impairment appear to be directly related to each other and inversely correlated with the age at epilepsy onset.

Commentary: The return of consciousness to epilepsy seizure classification.

Commentary: The return of consciousness to epilepsy seizure classification.

An unusual cause of seizures

A 59-year-old woman presented following a transient episode of confusion. She had temporal lobe epilepsy, well controlled on sodium valproate; she had been seizure free for 14 years. She had...

Genetic analysis of PHOX2B in sudden unexpected death in epilepsy cases.

To determine the contribution of sequence variations in PHOX2B to sudden unexpected death in epilepsy (SUDEP). Patients who died of SUDEP were identified in 2 major Australian cohorts, the Epilepsy Genetics research program in Melbourne and postmortem cases at the Department of Forensic Medicine in Sydney. Coding exons of the PHOX2B gene were sequenced and a fluorescent sizing assay was used to measure the PHOX2B polyalanine repeat sequence. Sequencing of 68 cases of SUDEP identified a 15-nucleotide deletion in the PHOX2B polyalanine repeat region in one case, a 16-year-old adolescent with focal dyscognitive seizures from age 5 years. This deletion was verified using a fluorescent sizing assay. Two synonymous variants were identified in 4 cases, but no PHOX2B polyalanine repeat expansion alleles or point mutations were found. The absence of PHOX2B polyalanine repeat expansion alleles or point mutations in 68 Australian cases of SUDEP, with one deletion of uncertain significance, shows that PHOX2B mutations are not a common risk factor for SUDEP.

Limited role for routine EEG in the assessment of staring in children with autism spectrum disorder

AimThe assessment of staring episodes in children with autism spectrum disorder (ASD) is difficult due to the range of diagnostic possibilities, the increased frequency of epileptiform activity on electroencephalogram (EEG),...

Commentary: Consciousness of epilepsy.

Words matter. We should be conscious of their impact. Or would it be better to say we should be aware of their impact? The articles by Lüders et al.1 and accompanying commentary by Blumenfeld and Meador2 provide thoughtful analyses of the inadequacies of a simple concept of consciousness to characterize seizures. No fewer than five varieties of alterations of consciousness are needed to span the behaviors commonly seen during seizures. With such a large range, how practical is consciousness as a descriptor? Consciousness is beyond dispute as an important aspect of human experience and as an area for scientific study, but seizure classifiers need to be definable and detectable in a simple, replicable way. Consciousness is neither of these. What are the alternatives? One approach is to define focal seizures as a single large category, with no formal subdivisions, as proposed by the 2010 International League Against Epilepsy (ILAE) Commission.3 This takes consciousness out of the picture, except as an optional descriptor. A second approach is to define a subcategory called “focal dyscognitive seizures,” as was done by Blume et al.4 and the 2001 ILAE Glossary task force. As pointed out by Blumenfeld and Meador,2 focal dyscognitive is understandable, but not equivalent to common current use of the term complex partial. Dyscognitive does not imply loss of consciousness. A more practical approach would be to base seizure classification on measurable behaviors, such as memory, responsiveness, and awareness, as well as specific motor, sensory, autonomic, and cognitive malfunctions. Numerous studies of consciousness use awareness, memory, responsiveness5 or orientation, language, visual processing, motor praxis, sensorimotor responses, and visual tracking6 as testable surrogates for the level of consciousness, although not to the exclusion of subjective phenomena. While awake, it is possible to be conscious and unresponsive or conscious and amnestic, but probably not conscious and unaware of the external world. Professor Blumenfeld commented that “An altered level of consciousness, evidenced by decreased overall arousal and responsiveness [italics added], is the defining feature of complex partial seizures.”7 Given that arousal, awareness, and responsiveness comprise the defining features, and consciousness can be measured only via surrogates and subjective reports, why propose, as Blumenfeld and Meador do in their commentary, “Focal Aware Conscious Seizures,” instead of “Focal Aware Seizures.” This is not the place to propose a specific classification, but only to argue that a seizure classification should be based on measurable behaviors and simple subjective perceptions, such as numbness. We can decide whether someone should be driving based on awareness, responsiveness, and sensorimotor abilities during a seizure. Specification of details of consciousness is not required. Einstein advised us that “Everything should be made as simple as possible, but no simpler,”8 Consciousness does not simplify classification of seizures. I have no conflicts of interest to disclose. I confirm that I have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Dr. Robert S. Fisher is the Maslah Saul MD Professor of Neurology & Neurological Sciences at Stanford University in Stanford, California.

Refractory status epilepticus treated with trigeminal nerve stimulation

Refractory status epilepticus (RSE) is a neurologic emergency associated with significant morbidity and mortality. Alternative therapies are needed for patients who do not respond to more traditional therapies for RSE. We report on a patient with RSE treated with external trigeminal nerve stimulation (eTNS). On admission, the patient was experiencing consecutive focal dyscognitive seizures with secondary generalization without recovery in between. His seizures remained refractory to multiple therapies, including IV lorazepam, valproic acid, levetiracetam, phenobarbital, and midazolam. Although a burst suppression pattern was achieved with a continuous pentobarbital infusion, seizures returned following attempts to taper it. Given his beneficial response to eTNS during a previous clinical trial, eTNS was initiated. Four days after starting eTNS, the pentobarbital infusion was finally weaned, and his EEG revealed no further seizures. The patient's mental status improved and he was ultimately discharged with only moderately severe disability. Our case demonstrates that eTNS may have antiseizure effects in RSE. Given our patient's quick response, such benefit may have arisen from EEG-desynchronization. If confirmed in larger studies, eTNS could one day be considered along with other adjuvant treatments for RSE.