Focal Spasms Research Articles

Study of retinal changes among patients presenting with pregnancy induced hypertension

Study of retinal changes among patients presenting with pregnancy induced hypertension - IJCEO- Print ISSN No: - 2395-1443 Online ISSN No:- 2395-1451 Article DOI No:- 10.18231/j.ijceo.2019.101, Indian Journal of Clinical and Experimental Ophthalmology-Indian J Clin Exp Ophthalmol

Genetic and clinical features of SCN8A developmental and epileptic encephalopathy

ObjectiveWe aim to delineate the genetic and clinical features of SCN8A developmental and epileptic encephalopathy. MethodsNine patients with SCN8A developmental and epileptic encephalopathy were included in this study. Genetic and clinical features and effectiveness of sodium channel blockers were assessed in patients who were confirmed with SCN8A mutations. ResultsThe onset of seizures ranged from the neonatal period to 18 months of age. Seizure types were diverse and predominantly involved focal seizures or spasms. The most common initial epilepsy syndrome was West syndrome in four patients, followed by neonatal-onset focal seizures in three patients and unclassified focal epilepsy in two patients. Electroencephalograms (EEGs) showed slow and disorganized background and epileptiform abnormalities with occipital predominance. Six patients presented intractable seizures including one patient with recurrent nonconvulsive status epilepticus. Sodium channel blockers were effective in seven patients among eight patients given them. All patients showed developmental delay or regression. Severe hypotonia or ataxia was also presented in some patients. Microcephaly was also characteristic. De novo missense mutations in SCN8A were found in the inactivation gate, C-terminal, loop 2, and transmembrane segments (S1, 4, 5, and 6). There was no correlation between the location of the mutation in the protein and phenotype or response to sodium channel blockers. ConclusionSCN8A developmental and epileptic encephalopathy presents intractable seizures including spasms, focal seizures, neonatal status epilepticus, and nonconvulsive status epilepticus. Sodium channel blockers were effective irrelevant to the location of the mutation in the protein.

Neuroimaging of Early Life Epilepsy.

We assessed the adherence to neuroimaging guidelines and the diagnostically relevant yield of neuroimaging in newly presenting early life epilepsy (ELE). There were 775 children with a new diagnosis of epilepsy (<3 years old at onset) who were recruited through the ELE study at 17 US pediatric epilepsy centers (2012-2015) and managed prospectively for 1 year. The data were analyzed to assess the proportion of children who underwent neuroimaging, the type of neuroimaging, and abnormalities. Of 725 children (93.5%) with neuroimaging, 714 had an MRI (87% with seizure protocols) and 11 had computed tomography or ultrasound only. Etiologically relevant abnormalities were present in 290 individuals (40%) and included: an acquired injury in 97 (13.4%), malformations of cortical development in 56 (7.7%), and other diffuse disorders of brain development in 51 (7.0%). Neuroimaging was abnormal in 160 of 262 (61%) children with abnormal development at diagnosis versus 113 of 463 (24%) children with typical development. Neuroimaging abnormalities were most common in association with focal seizure semiology (40%), spasms (47%), or unclear semiology (42%). In children without spasms or focal semiology with typical development, 29 of 185 (16%) had imaging abnormalities. Pathogenic genetic variants were identified in 53 of 121 (44%) children with abnormal neuroimaging in whom genetic testing was performed. Structural abnormalities occur commonly in ELE, and adherence to neuroimaging guidelines is high at US pediatric epilepsy centers. These data support the universal adoption of imaging guidelines because the yield is substantially high, even in the lowest risk group.

Early epileptic encephalopathy associated with SCN2A mutations: clinical and genetic description of eight novel patients

Background. A large number of single gene disorders with seizures in clinical picture has been described. Among them, a special place is held by early-onset epileptic encephalopathies (EEE) – a genetically diverse group of disorders characterized by manifestation of seizures in the first 2 years of life and severe progressing course. Currently, 58 genetic variants of EEE has been identified. The objective is to analyze the incidence, clinical and genetic characteristic of type II EEE in a sample of patients from Russia identified by whole exome sequencing using next generation sequencing. Materials and methods. The patient sample included 67 children (35 boys and 32 girls) with ages varying from 4 months to 10 years. All patients underwent neurological examination using the standard techniques. Monitoring of electroencephalography (EEG) was performed in accordance with the International 10–20 system. For magnetic resonance imaging, tomographs with magnetic induction of 1.5 and 3.0 T were used. The identified changes were confirmed by Sanger sequencing using DNA from the patients and their parents. Results. In total, 67 patients with EEE were diagnosed, 8 of which had causational mutations in the SCN2A gene: p.Leu1611Pro (c.4832T>C), p.Cys728* (c.2184C>A), p.Arg607* (c.1819C>T), p.Val1325Ile (c.623T>C), p.Leu419Met (c.1255T>A), p.Asp1487Glu (c.4461C>A), p.Val208Ala (c.3973G>A), p.Gln1211Lys (c.3631G>A). Analysis of parent DNA had shown that all mutations appeared de novo. At the time of disease onset, all patients had multiregional epileptiform activity per EEG. Focal seizures, myoclonic seizures, and epileptic spasms were the most common types of seizures in the patients. The majority of patients (5/8) had diffuse muscular hypotonia. All patients had pronounced mental deficiency. All patients received more than 2 therapy regimens (including hormonal therapy and ketogenic diet) but full remission wasn’t obtained. In some patients, partial positive dynamic was registered with hormonal therapy and sodium channel blockers. Various mutations in the SCN2A gene caused a similar clinical picture but had different functional significance which determined the effectiveness of anti-epileptic therapy. Conclusion. Identification of the mutated genes causing EEE and further study of their function are important for selection of therapeutic approach to epilepsy treatment.

Ictal signs in tuberous sclerosis complex: Clinical and video-EEG features in a large series of recorded seizures

Epilepsy is the most common neurological symptom in tuberous sclerosis complex (TSC), occurring in 72–85% of affected individuals. Despite the large number of patients reported, their electroclinical phenotype has been rarely described. We analyzed seizure semiology through ictal video-electroencephalography (V-EEG) recordings in a large series of patients. In this multicenter study, we reviewed V-EEGs of 51 patients: ictal recordings were analyzed in correlation with their clinical variables.The median age of epilepsy onset was six months (one day–16 years), with onset in the first year of life in 71% patients (36/51), in 10 of them during the neonatal period. Sixty-five percent of patients (33/51) experienced epileptic spasms in their life, with late-onset (>two years) in five; 42% of the epileptic spasms persisted after age two years, despite the onset in the first year of life.We identified four different electroclinical subsets: focal epilepsy (35%, 18/51), Lennox–Gastaut Syndrome evolution (27%, 14/51), focal seizures with persisting spasms (33%, 17/51), and spasms only (4%, 2/51).We reviewed 45 focal seizures, 13 clusters of epileptic spasms, and seven generalized seizures. In 12 patients, we recorded different seizure types. In 71% of the focal seizures (32/45), the ictal pattern was focal without diffusion. In 38% of the patients (5/13) epileptic spasms were related to typical diffuse slow wave pattern associated with superimposed fast activity, with focal predominance.Focal seizures and focal spasms resulted as the most frequent seizure types in TSC. Seizure onset was variable but showing a predominant involvement of the frontocentral regions (40%). Discrete clinical signs characterized the seizures, and behavioral arrest was the predominant first clinical objective sign. Epileptic spasms were a typical presentation at all ages, frequently asymmetrical and associated with lateralizing features, especially in older patients.

Effectiveness of total corpus callosotomy for diffuse bilateral polymicrogyria: Report of three pediatric cases

PurposePolymicrogyria, a malformation of the cerebral cortex, frequently causes epilepsy. Diffuse bilateral polymicrogyria (DBP) is related to poor epilepsy prognosis, but most patients with DBP are not good candidates for resective epilepsy surgery and effectiveness of corpus callosotomy (CC), a palliative surgery, for patients without resective epileptogenic cortices, has not been established in DBP. Because CC might be effective against DBP-related epilepsy, we conducted total CC in three pediatric DBP cases. MethodsCase 1. A girl developed epilepsy at 3 months of age, with focal versive seizures and epileptic spasms. The electroencephalogram (EEG) showed a suppression-burst pattern. Total CC was performed at 6 months of age.Case 2. A female infant developed epilepsy on the day of birth, exhibiting epileptic spasms, generalized tonic-clonic seizures, and eye-deviating seizures. She had a history of clusters of tonic seizures. Total CC was performed at 1 year and 2 months of age. After CC, the epileptic focus of the tonic seizures was identified; a secondary resective surgery was conducted.Case 3. A girl developed multiple types of seizures at 3 years of age. Frequent atypical absence status was refractory to antiepileptic drugs. Total CC was conducted at 8 years of age. ResultsCase 1: Frequencies of both seizure types decreased. The background EEG changed to continuous high-voltage slow waves.Case 2: Clusters of tonic seizures were well-controlled.Case 3: Atypical absence seizures completely disappeared. ConclusionCC could be effective for patients with DBP, whose habitual seizures include epileptic spasms and absence seizures.

Direct central nervous system effects of botulinum neurotoxin

Local intramuscular injections of botulinum neurotoxin type A (BoNT/A) are effective in the treatment of focal dystonias, muscle spasms, and spasticity. However, not all clinical effects of BoNT/A may be explained by its action at peripheral nerve terminals. For example, the therapeutic benefit may exceed the duration of the peripheral neuroparalysis induced by the neurotoxin. In cellular and animal models, evidence demonstrates retrograde transport of catalytically active BoNT/A in projection neurons. This process of long-range trafficking is followed by transcytosis and action at second-order synapses. In humans, several physiological changes have been described following intramuscular delivery of BoNT/A. In particular, clinical studies have documented a decrease in Renshaw cell-mediated inhibition (i.e., recurrent inhibition), which may be important therapeutically for normalizing uncoordinated movements and overflow of muscle activity. In this review, we present data obtained in animal and experimental models that support direct central actions of BoNT/A mediated via retrograde axonal trafficking. We also discuss the reorganization of central circuitry induced by BoNT/A in patients, and the potential contribution of these effects to the therapeutic efficacy of the neurotoxin.

Refractory spasms of focal onset—A potentially curable disease that should lead to rapid surgical evaluation

PurposeInfantile spasms (IS) can occur as the only seizure type in children with surgically amenable epilepsies. Although early surgery has shown positive effects, little is known regarding outcomes. MethodsWe retrospectively reviewed all children with IS referred to our tertiary center between 2002 and 2014 and try to define factors of outcome. ResultsSixty-eight children with focal onset seizures were referred: twenty children with a hemispheric implication and 48 with one or more lobes involved. The age of onset was significantly earlier in the hemispheric population (8.0 versus 16.7 months in the focal population). There was no difference in the age of onset between anterior and posterior onset zones, as we could expect regarding the maturation gradient. The epilepsy began earlier in life in tuberous sclerosis than in DNET. Only three children of the 48 non-hemispheric patients had a normal MRI at the time of the surgery. Temporal lobe was involved only in a third of the population. More than 86% of the patients were operated on. Patients with hemispheric lesions were operated on younger (2.6 years+/− 2.1 years) compared to 4.6+/− 3.5 years in the whole population. The most frequent etiologies were in descending order: dysplasia, ganglioglioma or dysembryoplastic tumours and tuberous sclerosis. The global seizure outcome was favorable (Engel 1a) in 74.6% of the patients, and 87.9% if the delay between the first seizure and the surgery was less than 36 months. It fell to 64.7% if the delay exceeded 50 months. ConclusionSpasms of focal onset have a similar postsurgical outcome as other seizure types so surgery may be an excellent option for treating selected patients with focal infantile spasms. Volume and type but not topography of the lesion influence the age of onset. MRI is very helpful to locate the pathology in the pediatric population, since only a small portion had a normal MRI.

Botulinum Toxin Treatment in Multiple Sclerosis—a Review

Purpose of review The purpose of this review is to provide updated information on the role of botulinum neurotoxin (BoNT) therapy in multiple sclerosis (MS). This review aims to answer which symptoms of multiple sclerosis may be amenable to BoNT therapy. Recent findings We searched the literature on the efficacy of BoNTs for treatment of MS symptoms up to April 1st 2017 via the Yale University Library's search engine including but not limited to Pub Med and Ovis SP. The level of efficacy was defined according to the assessment's criteria set forth by the Subcommittee on Guideline Development of the American Academy of Neurology. Significant efficacy was found for two indications based on the available blinded studies (class I and II) and has been suggested for several others through open-label clinical trials. Summary There is level A evidence (effective- two or more class I) that injection of BoNT-A into the bladder's detrusor muscle improves MS-related neurogenic detrusor overactivity (NDO) and MS-related overactive (OA) bladder. There is level B evidence (probably effective- two class II studies) for utility of intramuscular BoNT-A injections for spasticity of multiple sclerosis. Emerging data based on retrospective class IV studies demonstrates that intramuscular injection of BoNTs may help other symptoms of MS such as focal tonic spasms, focal myokymia, spastic dysphagia, and double vision in internuclear ophthalmoplegia. There is no data on MS-related trigeminal neuralgia and sialorrhea, two conditions which have been shown to respond to BoNT therapy in non-MS population.

Treatment of Focal Status Epilepticus plus Epileptic Spasms with Leukotomy in an Infant with TSC 1 Mutation: A Case Study

ABSTRACTBackground: Focal status epilepticus and catastrophic epilepsy are not rare in infants. Epilepsy surgery can be safely done in selected infants to cure epilepsy.Patient description: We report on an infant who began having drug-resistant status epilepticus at 2 weeks of age and developed epileptic spasms. We discuss in detail how the clinical and electroencephalographic data were used to reach a consensus for epilepsy surgery and why a particular surgical approach was preferred over other alternatives.Method: Presurgical evaluation consisted of 32-channel scalp video EEG using the standard 10–20 system of electrodes, 3-Tesla brain magnetic resonance imaging, and 18 F-fluorodeoxyglucose positron emission tomography. The surgery consisted of resection of the extensive epileptogenic lesion, in addition to disconnection of the left frontal lobe anterior to the motor strip.Result: The infant underwent epilepsy surgery at three months of age. At two-year follow up, she remained seizure free, with no focal motor deficit and the epileptic encephalopathy resolved. The disconnected left frontal lobe shows epileptiform discharges restricted to the disconnected tissue.Conclusion: We highlight the importance of epilepsy surgery in selected infants to achieve seizure freedom and to reverse epileptic encephalopathy. In the process, we demonstrate how epileptic spasms, although clinically and electrographically generalized, resolved after disconnecting the epileptogenic zone.

P40 – 2775: Unusual presentation in a child with a mutation in GRIN2A

Introduction Mutations in the gene GRIN2A have been reported as an etiology for epilepsy in case of ESES. We here present an unusual presentation in an infant carrying a mutation in GRIN2A, expanding the phenotypic spectrum associated with mutations in this gene. Case report An 8 month-old infant presented with severe development delay and a very extensive range of different electrical and clinical seizures including focal clonic seizures, spasms (generalized or unilateral), stereotyped behaviour, and tonic seizures since the age of 2 months. Seizures were refractory to multiple anti-epileptic drugs. Massive parallel sequencing with a gene panel for epileptic encephalopathies revealed a mutation in GRIN2A, which occurred de novo. In the recent literature, only 2 cases with the same clinical presentation have been reported so far. Conclusion In case of severe epilepsy in infancy, it is important to extend the spectrum of the genes to be studied. Mutations in GRIN2A are not only associated with ESES but must also be explored in case of epileptic encephalopathy with a great diversity of seizures in infancy

The phenotypic spectrum of SCN8A encephalopathy.

SCN8A encodes the sodium channel voltage-gated α8-subunit (Nav1.6). SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. We aimed to delineate the phenotype associated with SCN8A mutations. We used high-throughput sequence analysis of the SCN8A gene in 683 patients with a range of epileptic encephalopathies. In addition, we ascertained cases with SCN8A mutations from other centers. A detailed clinical history was obtained together with a review of EEG and imaging data. Seventeen patients with de novo heterozygous mutations of SCN8A were studied. Seizure onset occurred at a mean age of 5 months (range: 1 day to 18 months); in general, seizures were not triggered by fever. Fifteen of 17 patients had multiple seizure types including focal, tonic, clonic, myoclonic and absence seizures, and epileptic spasms; seizures were refractory to antiepileptic therapy. Development was normal in 12 patients and slowed after seizure onset, often with regression; 5 patients had delayed development from birth. All patients developed intellectual disability, ranging from mild to severe. Motor manifestations were prominent including hypotonia, dystonia, hyperreflexia, and ataxia. EEG findings comprised moderate to severe background slowing with focal or multifocal epileptiform discharges. SCN8A encephalopathy presents in infancy with multiple seizure types including focal seizures and spasms in some cases. Outcome is often poor and includes hypotonia and movement disorders. The majority of mutations arise de novo, although we observed a single case of somatic mosaicism in an unaffected parent.

Focal seizures versus epileptic spasms in children with focal cortical dysplasia and epilepsy onset in the first year

Focal cortical dysplasia (FCD) has been recognized as one of the most frequent causes of drug resistant epilepsy, especially in children. In infancy, onset of FCD-related epilepsy is substantially characterized by epileptic spasms (ES) or focal seizures. Which elements pertaining to the FCD are responsible for the onset of one type of seizure over the other is still unclear. Purpose of our study was to compare the characteristics of FCDs in terms of lateralization and site in patients with epileptic spasms versus patients with focal seizures. We retrospectively reviewed data from 41 patients with FCD related epilepsy with onset during the first 14 months of life. Seizure semeiology and drug resistance were analyzed, as were age at onset and FCD site and lateralization. Twenty-one children had focal seizures, 11 had ES and nine had focal seizures followed by ES. Mean age at onset was respectively 8.2, 5.1 and 1.8 months. Drug resistance was present in respectively 38.5%, 34.6% and 26.9% of children. Among patients with only ES, 90.9% had an exclusively frontal FCD localization, versus 42.9% of patients with focal seizures and 11.1% of patients with focal seizures followed by ES. FCD lateralization was right sided respectively in 47.6%, 81.8% and 66.7% of patients. Frontal lobe localization of FCDs was closely associated with ES (p=0.001). Moreover we also found that patients with focal seizures followed by ES had a significantly earlier age at onset compared to patients with focal seizures only (p<0.001). The association between ES and right-sided FCD lateralization, even if numerically suggestive, did not reach statistical significance (p=0.16). There was no significant association between seizure type and drug resistance (p=0.08).

Surgery for posterior quadrantic cortical dysplasia. A review.

Posterior quadrant dysplastic lesions represent 3-15% of multilobar cortical developmental pathologies, 3-5% of all the indications to surgery for epilepsy resistant to medical treatment. The objective of this study is to review the pertinent literature related to the presurgical clinical, neurophysiological, and neuroradiological evaluation of children affected by posterior quadrant dysplasia in order to discuss the intraoperative management and the different surgical techniques that have been proposed to treat this condition as well as factors related with postsurgical seizure outcome. Seizures appear most commonly in infants and rapidly progress to a catastrophic course. They are mostly represented by focal seizures and spasms. Surface interictal video-EEG is characterized by background flattening and paroxysmal discharges prevalent on the affected side but not unusually extending to the controlateral hemisphere. The last occasionally shows an independent irritative activity in spite of the absence of further visible structural abnormalities. Most of the patients have visual field or visual attention deficits at diagnosis. Resective as well as disconnective surgical procedures have been proposed for the management of this condition, none of them having shown clear advantages in terms of seizure outcome and complications. Intraoperative electrocorticography (EcoG) and sensorimotor monitoring have been successfully used to improve the localization of the epileptic focus and reduce surgical complication rates. Undistincted lesion borders, independent controlateral ictal or/and interictal EEG activity, and incomplete resections/disconnections are among the main factors that have resulted to be associated with a worse seizure outcome.

Early-Onset Focal Seizures and Spasms—Is it Surgical?

Early-Onset Focal Seizures and Spasms—Is it Surgical?

Clinical manifestations of hysteria: an epistemological perspective or how historical dynamics illuminate current practice.

Hysteria has generated the most heated debates among physicians, from antiquity to the present day. It has been long confused with neuroses and neurological pathologies such as Parkinson's disease and epilepsy, principally associated with women and sexual disorders. The clinical manifestations must first be seen in their historical context, as interpretation varies according to the time period. Recently, the Diagnostic and Statistical Manual of Mental Disorders by the American Psychiatric Association marked a break in the consensus that previously seemed to apply to the concept of hysteria and approach to the clinical manifestations. The clinical manifestations of hysteria are numerous and multifaceted, comprising 3 main classifications: paroxysms, attacks, and acute manifestations; long-lasting functional syndromes, and visceral events. Each main classification can be subdivided into several subgroups. The first main group of paroxysms, attacks, and acute manifestations includes major hysterical attacks, such as prodrome, trance and epileptic states, minor hysterical attacks such as syncope and tetany, twilight states, paroxysmal amnesia, and cataleptic attacks. The second group includes focal hysterical symptoms, paralyses, contractures and spasms, anesthesia, and sensory disorders. Visceral manifestations can be subdivided into spasms, pain, and general and trophic disorders. The diversity of the symptoms of hysteria and its changing clinical presentation calls into question the same hysterical attacks and the same symptoms, which have had only a few differences for over 2,000 years. A new definition of hysteria should be proposed, in that it is a phenomenon that is not pathological, but physiological and expressional.

SUCCESSFUL MANAGEMENT OF ACUTE-ONSET TORTICOLLIS IN A GIRAFFE (GIRAFFA CAMELOPARDALIS RETICULATA)

A 2-yr-old male reticulated giraffe (Giraffa camelopardalis reticulata) presented with severe midcervical segmental torticollis upon arrival as an incoming shipment. Despite initial medical management, the giraffe developed marked neck sensitivity, focal muscle spasms, and decreased cervical range of motion. Using operant conditioning to assist patient positioning and tolerance to cervical manipulation, a series of manually applied chiropractic treatments were applied to the affected cervical vertebrae in an effort to restore normal cervical mobility. Laser therapy and cervical range of motion exercises were also used to reduce cervical muscle hypertonicity. The combined application of these nontraditional therapies produced marked clinical improvement. This case highlights the potential benefits of combining traditional medical management with chiropractic treatment and physical therapy techniques for management of severe acute-onset torticollis in a giraffe.

Cortical contribution to scalp EEG gamma rhythms associated with epileptic spasms

The cortical contribution for the generation of gamma rhythms detected from scalp ictal EEG was studied in unique cases of epileptic spasms and a review of the related literature was conducted. Ictal scalp gamma rhythms were investigated through time–frequency analysis in two cases with a combination of focal seizures and spasms and another case with spasms associated with cortical dysplasia. In the two patients with combined seizures, the scalp distribution of ictal gamma rhythms was related to that of focal seizure activity. In the third patient, an asymmetric distribution of the ictal scalp gamma rhythms was transiently revealed in correspondence to the dysplasic cortex during hormonal treatment. Therefore, the dominant region of scalp gamma rhythms may correspond to the epileptogenic cortical area. The current findings have reinforced the possibility of the cortical generation of ictal scalp gamma rhythms associated with spasms. The detection of high frequencies through scalp EEG is a technical challenge, however, and the clinical significance of scalp gamma rhythms may not be the same as that of invasively recorded high frequencies. Further studies on the pathophysiological mechanisms related to the generation of spasms involving high frequencies are necessary in the future, and the development of animal models of spasms will play an important role in this regard.

Focal facial spasms associated with benign parotid hypertrophy

A Caucasian 47 years-old man, without previous diseases, suddenly developed clonic and, sometimes, tonic involuntary contractions of the right orbicular oris muscle. Even a smile could elicitate the spasms. Neurologic examination was unre-markable, but a right parotid enlargement was noticed. Magnetic resonance imaging (MRI) disclosed a parotid tumour which was initially considered to be an adenoma. The macroscopic aspect of the VII nerve with all its branches was normal and the hys-topathological study disclosed only a benign parotid hypertro-phy. After the surgery, the patient obtained a partial relief in his focal spasms. The Figure disclosed the local of surgery. The pa-tient gave an informed consent for this publication.

Functional imaging correlates of fronto-temporal dysfunction in Morvan’s syndrome

A previously well 66-year-old man presented with a 1-month history of focal involuntary spasms of his arms and then his left leg, culminating in two generalised convulsions. He also complained...