Clinical Spasms Research Articles

EEG-based spatiotemporal dynamics of fast ripple networks and hubs in infantile epileptic spasms.

Infantile epileptic spasms (IS) are epileptic seizures that are associated with increased risk for developmental impairments, adult epilepsies, and mortality. Here, we investigated coherence-based network dynamics in scalp EEG of infants with IS to identify frequency-dependent networks associated with spasms. We hypothesized that there is a network of increased fast ripple connectivity during the electrographic onset of clinical spasms, which is distinct from controls. We retrospectively analyzed peri-ictal and interictal EEG recordings of 14 IS patients. The data was compared with 9 age-matched controls. Wavelet phase coherence (WPC) was computed between 0.2 and 400 Hz. Frequency- and time-dependent brain networks were constructed using this coherence as the strength of connection between two EEG channels, based on graph theory principles. Connectivity was evaluated through global efficiency (GE) and channel-based closeness centrality (CC), over frequency and time. GE in the fast ripple band (251-400 Hz) was significantly greater following the onset of spasms in all patients (P < 0.05). Fast ripple networks during the first 10s from spasm onset show enhanced anteroposterior gradient in connectivity (posterior > central > anterior, Kruskal-Wallis P < 0.001), with maximum CC over the centroparietal channels in 10/14 patients. Additionally, this anteroposterior gradient in CC connectivity is observed during spasms but not during the interictal awake or asleep states of infants with IS. In controls, anteroposterior gradient in fast ripple CC was noted during arousals and wakefulness but not during sleep. There was also a simultaneous decrease in GE in the 5-8 Hz range after the onset of spasms (P < 0.05), of unclear biological significance. We identified an anteroposterior gradient in the CC connectivity of fast ripple hubs during spasms. This anteroposterior gradient observed during spasms is similar to the anteroposterior gradient in the CC connectivity observed in wakefulness or arousals in controls, suggesting that this state change is related to arousal networks.

Clinical characteristics of children with infantile epileptic spasms syndrome from a tertiary-care hospital in Dhaka, Bangladesh

BackgroundWe describe patient characteristics and response to initial treatment in a large case series of children presenting with infantile epileptic spasms syndrome to a tertiary-care hospital with a pediatric neurology service in Bangladesh. The purpose of the study was to add to the growing body of literature on infantile epileptic spasms syndrome in low- and middle-income countries. MethodsWe enrolled 212 infants with new-onset infantile epileptic spasms syndrome (IESS) at the time of initial presentation to the National Institute of Neurosciences and Hospital (NINS) in Dhaka, Bangladesh, between January 2019 and August 2021. We collected data about seizure type and frequency, etiology, medication dosage, and available neuroimaging. ResultsMedian age at initial presentation to NINS was 9 months. Developmental delay and regression prior to presentation were found in 83% and 36%, respectively. Prior to their presentation at NINS, 197 (93%) patients had received anti-seizure medication to treat spasms, of whom only 8 (4%) had received standard therapy with ACTH, prednisolone, or vigabatrin. At NINS, 207 (98%) of patients received standard therapy, most frequently ACTH in 154 (73%). Median time between seizure onset to receipt of first-line therapy was 5 months. Of the 169 patients who were seen in follow-up at average of 5 weeks, 92 (54%) reported absence of clinical epileptic spasms. No serious adverse events requiring hospitalization were reported. ConclusionsThis study highlights the long lead times to treatment for IESS in a low- and middle-income country, and the need for early referral of children with suspected epileptic spasms to epilepsy care centers.

Clinical and Electroencephalographic Pattern and Short-Term Outcome to Treatment in Infantile Spasm: A Randomized Controlled Trial

Background: Infantile spasms (epileptic spasm) is an epileptic encephalopathy with unique clinical and electrographic features, which affects children mostly in the middle of the first year of life.&#x0D; Objective: The aim of this study was to evaluate the clinical and electroencephalographic profile and short-term outcome in infantile spasm.&#x0D; Methodology: This was a randomized controlled trial study done in Department of Pediatric Neurology, National Institute of Neuroscience &amp; Hospital, Dhaka, Bangladesh. The patient of infantile spasm aged 2 months to 2 years were enrolled in the study from June 2017 to May 2018. With parent’s written informed consent, they were randomized into two groups, 25 in each. One group got ACTH only and another group got both ACTH and vigabatrin. Detailed history including seizure pattern was taken. EEG was done before and after2 -3 weeks of starting treatment. They were followed up at 8, 15, 43 days.&#x0D; Results: The mean age of onset of seizure (mean ±SD) was 7.24±4.13 (2 to 19) month on hormonal therapy and 6.84±5.89 (2 to 22) month on combination therapy. Most patient had history of perinatal birth asphyxia, developmental delay, seizure pattern was flexor spasm and EEG pattern were predominantly classical hypsarrhythmia in both groups. After treatment cessation of spasms occurred between 14 to 42 days in 72.0% in combination therapy and 44% in hormonal therapy (P value=0.045). EEG became normal in 60.0% and 32.0% patients in combination and hormonal therapy respectively (P value =0.047).&#x0D; Conclusion: In conclusion combination therapy of ACTH hormone plus vigabatrin has better than ACTH therapy alone in cessation of clinical spasms and electroencephalographic remission.&#x0D; Journal of National Institute of Neurosciences Bangladesh, July 2022;8(2):130-135

Early transient dysautonomia predicts the risk of infantile epileptic spasm syndrome onset: A prospective cohort study.

Infantile epileptic spasm syndrome (IESS) is an age-dependent epileptic encephalopathy with a significant risk of developmental regression. This study investigates the association between heart rate variability (HRV) in infants at risk of IESS and the clinical onset of IESS. Sixty neonates at risk of IESS were prospectively followed from birth to 12 months with simultaneous electroencephalogram (EEG) and electrocardiogram recordings for 60 min at every 2-month interval. HRV metrics were calculated from 5 min time-epoch during sleep including frequency domain measures, Poincare analysis including cardiac vagal index (CVI) and cardiac sympathetic index (CSI), and detrended fluctuation analysis (DFA α1, DFA α2). To assess the effect of each HRV metric at the 2-month baseline on the time until the first occurrence of either hypsarrhythmia on EEG and/or clinical spasm, univariate cox-proportional hazard models were fitted for each HRV metric. Infantile epileptic spasm syndrome was diagnosed in 20/60 (33%) of the cohort in a 12-month follow-up and 3 (5%) were lost to follow-up. The median age of developing hypsarrhythmia was 25 (7-53) weeks and clinical spasms at 24 (8-40) weeks. Three (5%) patients had clinical spasms without hypsarrhythmia, and 5 (8%) patients had hypsarrhythmia before clinical spasms at the initial presentation. The infants with high CSI (hazard ratio 2.5, 95% CI 1.2-5.2, P = 0.01) and high DFA α1 (hazard ratio 16, 95% CI 1.1-240, P = 0.04) at 2 months were more likely to develop hypsarrhythmia by the first year of age. There was a trend toward decreasing CSI and DFA α1 and increasing CVI in the first 8 months of age. Our data suggest that relative sympathetic predominance at an early age of 2 months may be a potential predictor for developing IESS. Hence, early HRV patterns may provide valuable prognostic information in children at risk of IESS allowing early detection and optimization of cognitive outcomes. Whether early intervention to restore sympathovagal balance per se would provide clinical benefit must be addressed by future studies.

Clinical seizure semiology is subtle and identification of seizures by parents is unreliable in infants with tuberous sclerosis complex.

The objectives of this study were to assess the accuracy of parental seizure detection in infants with antenatally diagnosed tuberous sclerosis complex (TSC), and to document the total seizure burden (clinical and subclinical) in those patients who met criteria for prolonged electroencephalography (EEG) recording. Consecutive infants at a single institution with antenatally diagnosed TSC who met criteria for prolonged video-EEG (vEEG) were recruited to this study. The vEEG data were reviewed and when a seizure was identified on EEG, the video and audio recording was assessed for evidence of clinical seizure and, if present, whether there was evidence of parent seizure identification. Nine infants were enrolled, for whom 674 focal seizures were identified in eight of nine patients across 24 prolonged vEEG recordings, with vEEG total duration of 634 h 49 min (average seizure frequency of 1 focal seizure/h). Only 220 of 674 (32.6%) were clinical seizures, 395 of 674 (58.6%) were subclinical seizures, and 59 of 674 seizures could not be classified. Only 63 of 220 clinical seizures (28.6%) were identified by parents, with 157 of 220 (71.4%) not identified. Thirty clusters of epileptic spasms were detected in one patient. At least one clinical epileptic spasm occurred in 2 of 30 clusters (6.7%), 24 of 30 clusters of epileptic spasms (80%) were electrographic only, and classification was uncertain for 4 of 30 clusters (13.3%). No clinical epileptic spasms were detected by parents. Clinical seizure frequency was significantly underestimated by parents for all patients. This study demonstrates that in infants with TSC who met criteria for prolonged vEEG, (1) parents significantly under recognize total clinical seizure count, (2) parents fail to identify epileptic spasms, and (3) seizure frequency is high. This highlights that epilepsy treatment decisions should not be based solely on parental clinical seizure identification. Prolonged vEEG monitoring may have an important role in the routine epilepsy care of infants with TSC, as demonstrating undetected high clinical seizure frequency may allow improved epilepsy management decisions.

Association of Time to Clinical Remission With Sustained Resolution in Children With New-Onset Infantile Spasms.

Standard therapies (adrenocorticotropic hormone [ACTH], oral steroids, or vigabatrin) fail to control infantile spasms in almost half of children. Early identification of nonresponders could enable rapid initiation of sequential therapy. We aimed to determine the time to clinical remission after appropriate infantile spasms treatment initiation and identify predictors of the time to infantile spasms treatment response. The National Infantile Spasms Consortium prospectively followed children aged 2-24 months with new-onset infantile spasms at 23 US centers (2012-2018). We included children treated with standard therapy (ACTH, oral steroids, or vigabatrin). Sustained treatment response was defined as having the last clinically recognized infantile spasms on or before treatment day 14, absence of hypsarrhythmia on EEG 2-4 weeks after treatment, and persistence of remission to day 30. We analyzed the time to treatment response and assessed clinical characteristics to predict sustained treatment response. Among 395 infants, clinical infantile spasms remission occurred in 43% (n = 171) within the first 2 weeks of treatment, of which 81% (138/171) responded within the first week of treatment. There was no difference in the median time to response across standard therapies (ACTH: median 4 days, interquartile range [IQR] 3-7; oral steroids: median 3 days, IQR 2-5; vigabatrin: median 3 days, IQR 1-6). Individuals without hypsarrhythmia on the pretreatment EEG (i.e., abnormal but not hypsarrhythmia) were more likely to have early treatment response than infants with hypsarrhythmia at infantile spasms onset (hazard ratio 2.23, 95% CI 1.39-3.57). No other clinical factors predicted early responders to therapy. Remission after first infantile spasms treatment can be identified by treatment day 7 in most children. Given the importance of early and effective treatment, these data suggest that children who do not respond to standard infantile spasms therapy within 1 week should be reassessed immediately for additional standard treatment. This approach could optimize outcomes by facilitating early sequential therapy for children with infantile spasms.

Comparison of Cosyntropin, Vigabatrin, and Combination Therapy in New-Onset Infantile Spasms in a Prospective Randomized Trial.

Objective: In a randomized trial, we aimed to evaluate the efficacy of cosyntropin injectable suspension, 1 mg/mL, compared to vigabatrin for infantile spasms syndrome. An additional arm was included to assess the efficacy of combination therapy (cosyntropin and vigabatrin) compared with cosyntropin monotherapy. Methods: Children (2 months to 2 years) with new-onset infantile spasms syndrome and hypsarhythmia were randomized into 3 arms: cosyntropin, vigabatrin, and cosyntropin and vigabatrin combined. Daily seizures and adverse events were recorded, and EEG was repeated at day 14 to assess for resolution of hypsarhythmia. The primary outcome measure was the composite of resolution of hypsarhythmia and absence of clinical spasms at day 14. Fisher exact test was used to compare outcomes. Results: 37 children were enrolled and 34 were included in the final efficacy analysis (1 withdrew prior to treatment and 2 did not return seizure diaries). Resolution of both hypsarhythmia and clinical spasms was achieved in in 9 of 12 participants (75%) treated with cosyntropin, 1/9 (11%) vigabatrin, and 5/13 (38%) cosyntropin and vigabatrin combined. The primary comparison of cosyntropin versus vigabatrin was significant (64% [95% confidence interval 21, 82], P < .01). Adverse events were reported in all 3 treatment arms: 31 (86%) had an adverse event, 7 (19%) had a serious adverse event, and 15 (42%) had an adverse event of special interest with no difference between treatment arms. Significance: This randomized trial was underpowered because of incomplete enrollment, yet it demonstrated that cosyntropin was more effective for short-term outcomes than vigabatrin as initial treatment for infantile spasms.

What is the optimal duration for vigabatrin monotherapy in patients with infantile spasms: 6 months or longer?

Vigabatrin (VGB) is approved as monotherapy for pediatric patients with Infantile Spasms (IS). Duration of VGB use should be limited because of the risk of retinal and neurotoxicity, but the optimal length of treatment is unknown. Our study aimed to determine the risk of spasms relapse after 6 months of VGB as first-line therapy in IS patients deemed VGB good responders.The participants were 44 infants with IS who demonstrated both absence of clinical spasms and hypsarrhythmia four weeks after starting VGB, obtained from two cohorts: 29 patients from a multicenter prospective cohort and 15 patients from a retrospective single-center cohort. We divided them post hoc into two groups according to the duration of VGB treatment: 6-month group (n=34) and >6-month group (n=10) and compared outcome between the two groups.No patient in either group had a relapse of spasms. For patients with non-identified etiology (NIE) in the 6 months treatment group, no other seizure types were observed. Late epilepsy, in the form of focal seizures, emerged in only 5/37 patients (3/30 in the 6-month treatment group; 2/7 in the extended treatment group); all within the first 6-9 months after VGB initiation.Our study provides substantial evidence that a shortened VGB course of 6 months could be sufficient to treat and prevent relapse of spasms in children with IS, particularly those with NIE.

Comparative Effectiveness of Initial Treatment for Infantile Spasms in a Contemporary US Cohort.

To compare the effectiveness of initial treatment for infantile spasms. The National Infantile Spasms Consortium prospectively followed up children with new-onset infantile spasms that began at age 2 to 24 months at 23 US centers (2012-2018). Freedom from treatment failure at 60 days required no second treatment for infantile spasms and no clinical spasms after 30 days of treatment initiation. We managed treatment selection bias with propensity score weighting and within-center correlation with generalized estimating equations. Freedom from treatment failure rates were as follows: adrenocorticotropic hormone (ACTH) 88 of 190 (46%), oral steroids 42 of 95 (44%), vigabatrin 32 of 87 (37%), and nonstandard therapy 4 of 51 (8%). Changing from oral steroids to ACTH was not estimated to affect response (observed 44% estimated to change to 44% [95% confidence interval 34%-54%]). Changing from nonstandard therapy to ACTH would improve response from 8% to 39% (17%-67%), and changing to oral steroids would improve response from 8% to 38% (15%-68%). There were large but not statistically significant estimated effects of changing from vigabatrin to ACTH (29% to 42% [15%-75%]), from vigabatrin to oral steroids (29% to 42% [28%-57%]), and from nonstandard therapy to vigabatrin (8% to 20% [6%-50%]). Among children treated with vigabatrin, those with tuberous sclerosis complex (TSC) responded more often than others (62% vs 29%; p < 0.05). Compared to nonstandard therapy, ACTH and oral steroids are superior for initial treatment of infantile spasms. The estimated effectiveness of vigabatrin is between that of ACTH/oral steroids and nonstandard therapy, although the sample was underpowered for statistical confidence. When used, vigabatrin worked best for TSC. This study provides Class III evidence that for children with new-onset infantile spasms, ACTH or oral steroids were superior to nonstandard therapies.

Effectiveness of corticosteroids versus adrenocorticotropic hormone for infantile spasms: a systematic review and meta-analysis.

ObjectiveTo compare the therapeutic effectiveness of oral corticosteroids with that of adrenocorticotrophic hormone for infantile spasms.MethodsPubMed, Embase, Scopus, and the Cochrane library were searched to retrieve studies published before December 2018 to identify pediatric patients with a diagnosis of infantile spasms. The interventions of oral corticosteroids and adrenocorticotrophic hormone were compared. We included only randomized controlled trials that reported the cessation of spasms as treatment response. The primary outcome was clinical spasm cessation on day 13 or 14. The secondary outcomes were the resolution of hypsarrhythmia, side effects, continued spasm control, spasm relapse rate, and subsequent epilepsy rate. Following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses, the study‐level quality assessment was conducted using the Cochrane risk‐of‐bias tool.ResultsAfter extensive review, 39 articles were included for meticulous evaluation. Five randomized controlled trials with a total of 239 individuals were eligible for further analysis. No significant difference was detected between the corticosteroids and adrenocorticotrophic hormone in the cessation of clinical spasms (odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.16 to 1.81; P = 0.32). The subgroups of high‐dose prednisolone versus adrenocorticotrophic hormone and low‐dose prednisone versus adrenocorticotrophic hormone also exhibited no significant difference. Furthermore, the two subgroups did not differ in terms of hypsarrhythmia resolution, side effects, relapse rate, or subsequent epilepsy rate.InterpretationThis meta‐analysis suggests that high‐dose prednisolone is not inferior to adrenocorticotrophic hormone and that it be considered a safe and effective alternative treatment.

The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium.

The multicenter National Infantile Spasms Consortium prospective cohort was used to compare outcomes and phenotypic features of patients with infantile spasms with and without hypsarrhythmia. Patients aged 2 months to 2 years were enrolled prospectively with new-onset infantile spasms. Treatment choice and categorization of hypsarrhythmia were determined clinically at each site. Response to therapy was defined as resolution of clinical spasms (and hypsarrhythmia if present) without relapse 3 months after initiation. Eighty-two percent of patients had hypsarrhythmia, but this was not associated with gender, mean age, preexisting developmental delay or epilepsy, etiology, or response to first-line therapy. Infants with hypsarrhythmia were more likely to receive standard treatment (adrenocorticotropic hormone, prednisolone, or vigabatrin [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4-4.7] and preexisting epilepsy reduced the likelihood of standard treatment (OR 3.2, 95% CI 1.9-5.4). Hypsarrhythmia was not a determinant of response to treatment. A logistic regression model demonstrated that later age of onset (OR 1.09 per month, 95% CI 1.03-1.15) and absence of preexisting epilepsy (OR 1.7, 95% CI 1.06-2.81) had a small impact on the likelihood of responding to the first-line treatment. However, receiving standard first-line treatment increased the likelihood of responding dramatically: vigabatrin (OR 5.2 ,95% CI 2-13.7), prednisolone (OR 8, 95% CI 3.1-20.6), and adrenocorticotropic hormone (ACTH; OR 10.2, 95% CI 4.1-25.8) . First-line treatment with standard therapy was by far the most important variable in determining likelihood of response to treatment of infantile spasms with or without hypsarrhythmia.

Infantile spasms in Down syndrome: a good response to vitamin B6

We report the results of patients with Down syndrome (DS) and West syndrome (WS) treated with vitamin B6 and discuss the mechanisms of pyridoxine in WS. Twenty patients with DS and WS were referred to our service for infantile spasms (IS) between February 1990 and December 2002. WS was diagnosed on the basis of clinical and electroencephalogram features. Thirteen patients were treated conservately while seven patients (four girls and three boy) were treated according to the new alternative treatment scheme with vitamine B6. The dose of oral pyridoxine was between 200 and 400 mg/day (25-50 mg/kg/day). Five patients initiated the treatment with vitamin B6 for IS two weeks and two patients four weeks after starting to receive antiepileptic drugs. One of them, who initially received intravenous pyridoxine 200 mg/day during three days with a partial control of IS, responded well to oral vitamin B6 400 mg/day associated to valproic acid five months later. Mean age at the beginning of pyridoxine treatment was 9.5 months, ranging from 3 to 14 months. The time between the onset of spasms and vitamin B6 administration ranged from 2 to 4 weeks. Cessation of spasms was obtained within 2 weeks of treatment in four patients. Their electroencephalograms became normal as soon as the spasms disappeared. In four patients whose spasms ceased, pyridoxine was discontinued after 24 and 30 months and clinical spasms did not recur. These four children did not experience any other type of seizure after a mean time of follow-up of 6 years (range 1-10 years) without any type of treatment. In the fifth patient, cessation of spasms was obtained within four weeks the second time she received vitamin B6, five months after the first treatment. She still receives with pyridoxine 400 mg/day (40 mg/kg/ day) after twelve months of follow up and has had no spasms since. Two patients did not respond well either to pyridoxine or to vigabatrin, adrenocorticotropic hormone, valproic acid or benzodiazepines. The patients had no adverse events during treatment with pyridoxine. We consider an oral dose of 200-400 mg/day (25-50 mg/kg/day) of pyridoxine either in monotherapy or combined with classic antiepleptic drugs to be the first choice of therapy in patients with IS and DS. Furthermore, patients who initially do not respond well to pyridoxine could be treated again and for a longer period. (J Pediatr Neurol 2004; 2(1): 15-19).

Early total corpus callosotomy in a patient with cryptogenic West syndrome

West syndrome is a generalized epileptic syndrome of infancy, that is characterized by clinical spasms and hypsarrhythmia and usually has an onset age before two years old. Children affected by West syndrome have a high risk of severe psychomotor developmental delay. Infants with West syndrome without identification of underlying neurological disorder after adequate investigations are classified as ‘‘cryptogenic’’ and usually have better prognoses than children with ‘‘symptomatic’’ West syndrome. Early seizure cessation, particularly among cryptogenic cases, may cure the disease and allow a good neurodevelopmental outcome. Corpus callosotomy was first introduced as a palliative treatment for epilepsy in 1940 and is performed in patients whose seizures are not amenable to surgical focal resection. West syndrome is often medically intractable and has features of ‘‘generalized’’ epilepsy, but corpus callosotomy has not been discussed widely as a treatment strategy. Given the catastrophic nature of West syndrome, an early indication for total corpus callosotomy may be appropriate. Here, we describe a case that was diagnosed as cryptogenic West syndrome, in which the epileptogenic focus was defined after total corpus callosotomy.

Topiramate and Adrenocorticotropic Hormone (ACTH) as Initial Treatment for Infantile Spasms

Historically, adrenocorticotropic hormone was used as a first-line treatment for infantile spasms; however, there has been increasing use of topiramate as initial therapy. Here, we report a retrospective study of adrenocorticotropic hormone (ACTH) and topiramate as initial treatment for infantile spasms. The neurology patient database at the Children's Hospital of Philadelphia was searched using the International Classification of Diseases, Ninth Revision code for infantile spasms, and 50 patients were randomly chosen for chart review. We identified 31 patients receiving either adrenocorticotropic hormone or topiramate monotherapy (adrenocorticotropic hormone n = 12, topiramate n = 19) as a first-line treatment for infantile spasms. A total of 26 patients were symptomatic and 5 cryptogenic. Six patients treated with adrenocorticotropic hormone had resolution of clinical spasms and hypsarrhythmia within a month, but 3 relapsed. Of the 19 patients treated with topiramate, 4 patients eventually, though over a period of 0, 1, 8, or 69 months, had resolution of spasms and hypsarrhythmia.

Aetiological aspects of west syndrome

West Syndrome involves epileptic encephalopathy in infants, occurring with an incidence of 5/10000 live births. Its main clinical feature are spasms that occur in clusters, which are associated with an EEG pattern called hypsarrhythmia and psychomotor retardation in most patients. West Syndrome is associated with many underlying conditions and the terms idiopathic, cryptogenic, and symptomatic are used for its aetiological subgroups. The objective of this investigation was to determine the aetiological diagnosis of patients with West Syndrome and to compare the results with other studies. In this 34-year longitudinal prospective one-centre study, 404 patients were studied. All patients exhibiting the diagnostic criteria for West Syndrome were investigated by clinical and neurological examination, EEG, ophthalmologic, psychological, metabolic, genetic, as well as neuroradiological methods, according to their particular indications. 36 (8.9%) patients had normal development, in whom infantile spasms occurred without any identifiable underlying cause, forming the idiopathic group. 51 patients (12.6%) with neurological impairment of unknown aetiology formed the cryptogenic group. The greatest number of patients (317 or 78.5%) formed the symptomatic group, in which neurological features and developmental delay preceded the onset of spasms. Disgenetic disorders and hereditary metabolic diseases were aetiological factors 44 (10.8%) patients. Prenatal and perinatal aetiological factors were revealed in one third of the patients (134 or 31%). Postnatal aetiological factors were revealed in 42 (10.2%) patients. In our study, disgenetic disorders were registered less frequently and perinatal complications more frequently than in other studies. Our results indicate the possibility of preventing West Syndrome with good quality obstetric and neonatal care, as well as the early prenatal diagnosis of brain malformations. Modern, sophisticated investigation makes the more accurate aetiological diagnosis of West Syndrome possible.

Focal cortical high-frequency oscillations trigger epileptic spasms: Confirmation by digital video subdural EEG

Objective To localize high-frequency oscillations (HFOs) on the cortex during epileptic spasms using video subdural EEG and Multiple Band Frequency Analysis (MBFA). Methods Using video subdural EEG sampled at 1 kHz, we studied a 14-year-old boy with asymmetric epileptic spasms of possible left frontal origin. We identified HFOs, then analyzed and localized their distributions by MBFA. We correlated HFO distribution to clinical spasm intensity. Results Ictal subdural EEG recorded HFOs at 60–150 Hz lasting 0.3–4 s. MBFA showed extensive but noncontiguous distribution of HFOs predominantly over the left frontal and temporal regions. HFOs began and became quasiperiodic before manifestation of clinical spasms. As clinical spasms intensified, HFOs persisted in regions where they initiated subclinically but were of higher frequency and greater power than HFOs in other regions. We performed cortical resections over the left frontal and temporal regions with predominant HFOs. Six months after surgery, the patient remained seizure free. Conclusions HFOs were present over the ictal onset zone during epileptic spasms. Periodic spasms in this patient had the characteristics of partial seizures. Significance We show that HFOs occurred over the cerebral cortex during epileptic spasms, and we suggest that these focal cortical HFOs triggered the spasms.

Infantile Spasms.

Infantile spasm is a catastrophic form of epilepsy found only in infants and young toddlers. Onset is before one year of age, with a peak incidence occurring between 4 to 7 months of age. The prevalence is difficult to calculate, but previous reviews have estimated between 1 per 2000 to 6000 live births. There are many causes of infantile spasms, including tuberous sclerosis, malformations of cortical development, hypoxic-ischemic injury, congenital infectious diseases, inborn errors of metabolism, genetic syndromes such as Aicardi's syndrome, and chromosomal abnormalities. A small percentage of patients have idiopathic infantile spasms, with no identifiable cause and premorbid normal growth and development. In order to prevent an ongoing epileptic encephalopathy with its concomitant consequences of cognitive impairment and intractable seizures, treatment should be aggressive and immediate. It is not enough to control the clinical infantile spasms. The underlying "interictal" hypsarrhythmia pattern must also be abolished if the prognosis is to be improved. Otherwise, the immature brain appears to remain hyperexcitable.

Clinical use of polysynaptic flexion reflexes in the management of spasticity with intrathecal baclofen

The aim of this study was to evaluate the clinical usefulness of lower limb flexion reflexes (FR) in the assessment of spinal excitability responsible for spontaneous or induced spasms. FR were recorded on the short head of biceps femoris, after electrical stimulation of the ipsilateral sural nerve at the ankle, in 17 spastic patients selected for chronic intrathecal administration of baclofen. The results obtained before and after treatment were compared with clinical scores commonly used to assess spasticity (Ashworth and spasm scores). Before intrathecal baclofen 15 17 patients (88%) had pathologically enhanced flexor in the lower limbs, which were associated to clinical spasms. Reflex enhancement was accompanied in 47% of cases by abnormal decrease of reflex threshold. No significant correlation appeared between the magnitude or threshold of FR in control conditions and either the hypertonia (Ashworth scale) or the number of clinical spasms per unit of time. Intrathecal baclofen attenuated flexor reflex amplitude and increased reflex threshold in all patients. Our results suggest that FR investigate the intrinsic features of the spasms (threshold, intensity and duration) not assessed clinically, and that therefore the information gathered from FR recordings is not redundant with, and adds significantly to, that obtained by clinical scales. In our experience, FR recordings appeared to be a useful tool for quantifying the benefit of antispastic treatment and might be used as an ancillary indicator to determine the minimal effective dose of intrathecal baclofen.

High-dose Corticotropin (ACTH) Versus Prednisone for Infantile Spasms: A Prospective, Randomized, Blinded Study

To compare the efficacy of corticotropin (ACTH) (150 U/m2/day) and prednosone (2 mg/kg/day) given for 2 weeks, in suppressing clinical spasms and hypsarrhythmic electroencephalogram (EEG) in infantile spasms (IS). AACTH and prednisone are standard treatments for IS. ACTH at high doses causes severe dose- and duration-dependent side effects, but may be superior to prednisone, based on retrospective or uncontrolled studies. Blinded prospecive studies have shown equal efficacy of prednisone and low-dose ACTH, and low versus high-dose ACTH. A prospective, randomized, single-blinded study. Patient population consisted of consecutive infants fulfilling entry criteria, including the presence of clinical spasms, hypsarrhythmia (or variants) during a full sleep cycle video-EEG, and no prior steroid/ACTH treatment. Response required both cessation of spasms and elimination of hypsarrhythmia by the end of the 2-week treatment period, as determined by an investigator "blinded" to treatment. Treatment of responders was tapered off over 12 days; those failing one hormone were crossed-over to the other. OF 34 eligible infants, 29 were enrolled. Median age of patients was 6 months. Twenty-two infants were "symptomatic" with known or suspected cause, and seven were cryptogenic (two normal). Of 15 infants randomized to ACTH, 13 responded by EEG and clinical criteria (86.6%); Seizures stopped in an additional infant, but EEG remained hypsarrhythmic (considered a failure). Four of the 14 patients given prednisone responded (28.6%,, with complete clinical-EEG correlation), significantly less than with ACTH, (chi2 test). Using a prospective, randomized approach, a 2-week course of high-dose ACTH is superior to 2 weeks of prednsone for treatment of IS, as assessed by both clinical and EEG criteria.

Functional Outcome and Clinical Significance of Long-term Intrathecal Baclofen Therapy for Severe Spasticity

Continuous delivery of intrathecal baclofen via an implantable pump was first used to treat severe intractable spasticity in 1985. We report the results of 70 patients fol lowed for up to five years and the effects that reduction of spasticity has had on mobil ity status, daily living activities, and satisfaction with treatment. Practical considera tions resulting from this experience and implications for patient selection and management are reported.Over the time span studied, muscle tone and spontaneous painful muscle spasms were markedly reduced and remained stable at two steps lower than prior to treatment when assessed by the Ashworth spasticity and clinical spasms scale. After six months, more than 90% of both the physicians and the patients assessed the benefit of the pro cedure as excellent or good. Patients with spasticity in lower limbs caused by spinal lesions had the best long-term success with regard to their mobility status and their daily living activities, e.g., dressing. Increased dose re...