Transient focal cortical hypometabolism in idiopathic West syndrome

Positron emission tomography (PET) using ¹⁸F-labeled 2-deoxy- -glucose was performed serially in 5 infants with idiopathic West syndrome. While tonic spasms persisted, 2 infants had hypometabolism in the bilateral temporo-parieto-occipital regions, which disappeared after cessation of spasms. In 2 other infants, PET revealed focal hypometabolism in the temporal region a few months after the disappearance of tonic spasms, but subsequent PET studies were normal. PET can detect transient metabolic abnormalities of the cerebral cortex which may be associated with the pathophysiology of West syndrome.     

Cortical Hypometabolism and Delayed Myelination in West Syndrome

Summary: Purpose: We examined the relation between cortical hypometabolism and delayed myelination in patients with West syndrome (WS).
Methods: Serial positron emission tomography (PET) with [^18F]fluorodeoxyglucose ([^18F]FDG) and magnetic resonance imaging (MRI) were performed in 18 patients with WS, first at the onset of epileptic spasms and later at age 10 months. The age at onset of seizures ranged from 2 to 7 months. Ten patients were diagnosed as having cryptogenic WS and 8 as having symptomatic WS.
Results: Cortical hypometabolism was detected in many patients at onset of epilepsy, but disappeared later, whereas delayed myelination tended to become evident with age. PET showed diffuse or focal cortical hypometabolism in 12 patients at onset, but in only 6 patients at age 10 months. MRI showed delayed myelination in only 2 patients at onset of epilepsy, but the number of patients with delayed myelination increased to 12 at age 10 months. Delayed myelination was more often present in patients with cortical hypometabolism. Delayed myelination was noted in 11 (85%) of 13 patients with cortical hypometabolism on first or second PET scans, but in only 1 (20%) of 5 patients who did not show PET abnormalities. Hypometabolism on the first or second PET scan was positively correlated with delayed myelination at age 10 months.
Conclusions: In patients with WS, assessing myelination with MRI again at age 8–10 months is important even when MRI at the onset of epilepsy appears normal. Serial MRI and PET scans disclose more detailed pathophysiology of WS.     

Surgical treatment of West syndrome.

The discovery of focal or multifocal cortical lesions using magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning in the majority of infants with West syndrome has led to a surgical approach in the treatment of some patients with intractable infantile spasms. The locations of these lesions should be concordant with localization of focal ictal and/or interictal electroencephalographic (EEG) abnormalities prior to proceeding with cortical resection. When a single lesion is present on the MRI or PET, and there is good correlation with EEG localization, surgical treatment is generally quite favorable in terms of both seizure control and cognitive development. Interictal glucose metabolism PET scans in children with intractable cryptogenic infantile spasms show unifocal cortical hypometabolism in about 20% of cases. In the majority, however, multifocal asymmetric hypometabolism is suggestive of multifocal underlying lesions, possibly multifocal cortical dysplasia. When the pattern of glucose hypometabolism is symmetric, a lesional etiology is less likely, thus neurometabolic or neurogenetic disorders should be considered. Therefore, the pattern of glucose hypometabolism on PET in infants with intractable cryptogenic spasms is a useful guide to decide whether a medical or surgical approach should be undertaken. In order to achieve the best cognitive outcome with surgery, it is important to resect the entire 'nociferous' area rather than just the seizure focus. Our research with new PET imaging probes has attempted to provide a comprehensive evaluation of the epileptogenic zone including the 'nociferous' cortex. We have used [(11)C]flumazenil (FMZ), which labels gamma aminobutyric acid(A) (GABA(A)) receptors, and have found this to be particularly useful in showing: (i) decreased receptor binding with medial temporal involvement thus indicating resection of medial temporal structures, (ii) the peri-lesional epileptogenic zone surrounding MRI lesions, (iii) the seizure onset zone in MRI-negative cases, and (iv) potential secondary epileptic foci. Another recently developed PET probe, alpha[(11)C]methyl-L-tryptophan (AMT) which is a precursor for the serotonin and the kynurenine metabolism pathways, is capable of differentiating between epileptogenic and non-epileptogenic tubers in patients with tuberous sclerosis complex and intractable epilepsy (including infantile spasms). Subsequently, we have applied AMT PET in patients with multifocal cortical dysplasia to determine the predominant seizure focus, and the results have been promising with regard to seizure control but not cognitive development. Thus, the introduction of newer more specific PET probes for epilepsy has led to improved and more accurate localization of seizure foci that should ultimately improve outcome of epilepsy surgery in West syndrome.     

Delayed myelination at the onset of cryptogenic West syndrome

To evaluate the prognostic value of delayed myelination at the onset of cryptogenic West syndrome, the relationship between the seizure or developmental outcome and myelination was examined. Cranial magnetic resonance imaging studies were performed in nine cryptogenic cases. Infantile spasms were controlled in all patients, but three cases showed a mild developmental delay at 2 years after onset. Delayed myelination was observed in three cases (33.3%) on T(1)-weighted images and in two cases (22.2%) on T(2)-weighted images. In the present study, neither the seizure outcome nor developmental status was positively correlated with the existence of delayed myelination at the onset of cryptogenic West syndrome.     

Infantile spasms: I. PET identifies focal cortical dysgenesis in cryptogenic cases for surgical treatment

Positron emission tomography (PET) of local cerebral glucose metabolism in 13 children with infantile spasms of undetermined cause (cryptogenic spasms) revealed unilateral hypometabolism involving the parieto-occipito-temporal region in 5 female infants. Cranial computed tomography showed normal findings in all infants. Magnetic resonance imaging (MRI) demonstrated a normal appearance in 4 of the 5 infants; in 1 infant, MRI revealed a subtle abnormality consisting of poor demarcation between occipital gray and white matter. Surface electroencephalography (EEG) in 4 showed hypsarrythmia at some time in the patients' courses, but at other times showed localized or lateralized abnormalities corresponding to areas of PET-detected hypometabolism. Because of poor seizure control, 4 infants underwent surgical removal of the cortical focus guided by intraoperative electrocorticography and were seizure free postoperatively. Neuropathological examination of resected tissue in each showed microscopic cortical dysplasia. Our findings indicate that in infants with cryptogenic spasms, PET can effectively identify those due to unsuspected focal cortical dysplasia, for which resective surgery offers improved prognosis.     

Infantile spasms in remission may reemerge as intractable epileptic spasms

BACKGROUND: West syndrome consists of infantile spasms with hypsarrhythmia and is perceived as a disorder of infants. METHODS: We describe 10 patients with West syndrome with spasms that remitted, started again, and persisted (followed up for 8-25 years). RESULTS: In all, West syndrome developed at younger than 17 months (five cryptogenic, six symptomatic). With initial treatment, spasms completely stopped for 4.5 months to 6 years, when epileptic spasms returned. Recurrent spasms were typical with brief arm extension, eye elevation, and head drop without falling. Spasms lasted 2-6 s in rhythmic strings over 20- to 60-min periods and occurred daily throughout follow-up. Persistent spasms were particularly troublesome, because of incontinence in one and postictal confusion in several. During the string of spasms, most refused to interact, and several would wander off. Up to 15 antiepileptic drugs did not render any patient spasm free. Only two had persistent spasms as the only seizure type; six also had intractable complex partial seizures, and three had occasional grand mal convulsions. Interictal EEGs showed multifocal spikes. Ictal recordings in six showed electrodecremental events. CONCLUSIONS: Recurrent spasms after remission of West syndrome represent an extremely resistant, distressing form of epilepsy. The onset of West syndrome is age related, but it does not reliably vanish.     

Epidemiological and clinical studies of West syndrome in Miyagi Prefecture, Japan

We performed a retrospective epidemiological study of West syndrome (WS) in Miyagi prefecture over a 3-year period (2000 -2003). Twenty-two children (6 boys, 16 girls) developed WS. The incidence of WS was 3.4/10,000 live births. It agreed with the incidence of previous report in Japan. The mean age at onset of spasms was 6.5 months (range 1 - 17 months). Thirteen patients (59%) had symptomatic WS; of these, eight patients had prenatal causes and five had perinatal causes. There were no familial cases, although four patients had family history that included neurological diseases. Periventricular leukomalacia was found in four of nine patients with abnormal magnetic resonance imagings (MRI) . Early seizure outcome was good in twenty-one patients (95%). Six patients (29%) had seizure recurrence. There were no significant differences between symptomatic WS and cryptogenic WS in terms of seizure recurrence and persistent EEG abnormalities. The Five patients (20%) with developmental quotients (DQ) more than 70 were all cryptogenic WS, while patients with DQ less than 70 were significantly frequent in symptomatic WS as compared with cryptogenic WS.     

The perfusion defect seen with SPECT in West syndrome is not correlated with seizure prognosis or developmental outcome

We used interictal single photon emission computed tomography (SPECT) on 40 patients with West syndrome to determine whether cortical perfusion abnormalities are closely related to the development of West syndrome and whether they are correlated with the long-term seizure prognosis or the developmental outcome. Localized cortical perfusion abnormalities were seen in 24 patients (60%), while 15 patients (38%) were classified as normal. The remaining patient showed hyperperfusion of the basal ganglia bilaterally. Of 24 patients with localized perfusion abnormalities, unifocal cortical hypoperfusion was present in 11, multifocal hypoperfusion in 10, multiple cortical hypo- and hyperperfusion in one, hyperperfusion of the bilateral frontal cortices and brain stem in one, and focal hyperperfusion in the residual frontal cortex in one. For statistical analysis, we focused on 26 patients (cryptogenic; 10, symptomatic; 16), who were followed for more than 2 years after the onset of tonic spasms (mean 5.0 years). The results showed that focal cortical perfusion abnormalities were not correlated with the long-term seizure prognosis, the developmental outcome, or the response to ACTH therapy. In agreement with previous reports, the results of interictal SPECT suggested that focal cortical lesions play an important role in the development of West syndrome. However, statistical analysis showed that the existence of cortical dysfunction as defined by SPECT did not predict the seizure prognosis or the developmental outcome.     

Long-term cognitive outcomes of a cohort of children with cryptogenic infantile spasms treated with high-dose adrenocorticotropic hormone

PURPOSE: To evaluate the outcome of children with cryptogenic infantile spasms treated with high-dose synthetic adrenocorticotropic hormone (ACTH) and the relation between early treatment, within 1 month of onset, and outcome. METHODS: We assessed the long-term cognitive and seizure outcomes of 37 patients with cryptogenic infantile spasms (onset, age 3 to 9 months) receiving standardized treatment regimen of high-dose tetracosactide depot, 1 mg IM every 48 h for 2 weeks, with a subsequent 8- to 10-week slow taper and followed by oral prednisone, 10 mg/day for a month, with a subsequent slow taper for 5 months or until the infant reached the age of 1 year, whichever came later. Development was assessed before treatment. Seizure outcomes were followed up prospectively. Cognitive outcomes were determined after 6 to 21 years and analyzed in relation to treatment lag and pretreatment regression. RESULTS: Twenty-two infants were treated within 1 month of onset of infantile spasms, and 15 after 1 to 6.5 months. Normal cognitive outcome was found in all 22 (100%) patients of the early-treatment group, and in 40% of the late-treatment group. Normal cognitive outcome was found in all 25 (100%) patients who had no or only mild mental deterioration at presentation, including four in the late-treatment group but in only three of the 12 patients who had had marked or severe deterioration before treatment. CONCLUSIONS: Early treatment of cryptogenic infantile spasms with a high-dose ACTH protocol is associated with favorable long-term cognitive outcomes. Once major developmental regression lasts for a month or more, the prognosis for normal cognitive outcome is poor. Further studies are needed on the optimal treatment regimen for this disorder.     

Infantile spasms: III. Prognostic implications of bitemporal hypometabolism on positron emission tomography

Positron emission tomography (PET) of brain glucose utilization is highly sensitive in detecting focal cortical abnormalities in patients with infantile spasms even when the computed tomographic (CT) and magnetic resonance imaging (MRI) scans are normal. Of 110 infants with spasms evaluated for potential surgical intervention during an 8-year period, we encountered 18 infants (7 males, 11 females; age range, 10 mo to 5 yr) with a common metabolic pattern on positron emission tomography (PET) consisting of bilateral hypometabolism in the temporal lobes. CT and MRI scans did not reveal any focal abnormalities in the 18 infants. Video-electroencephalographic monitoring indicated either bilateral or multifocal epileptogenicity, or failed to show any epileptic focus, so that none of the 18 infants were considered candidates for resective surgery. These patients were then enrolled in a prospective study aimed at determining long-term outcome in the presence of bilateral temporal PET hypometabolism. Analysis of outcome in 14 of the 18 subjects (follow-up period, 10 mo to 10 yr 5 mo; mean, 3 yr 11 mo ± 2 yr 4 mo [SD]) revealed the following: (1) all had severe developmental delay and had failed to gain significant milestones; (2) language development had been minimal or absent; (3) 10 of the 14 met the DSM-IV criteria for autistic disorder. Our findings indicate that patients with infantile spasms and bitemporal glucose hypometabolism on PET comprise a relatively homogeneous group and are typically not candidates for cortical resection. The long-term outcome of these infants is particularly poor and the majority are autistic.     

Epidemiological and clinical study of West syndrome in Nagasaki Prefecture, Japan

To determine the occurrence, outcome, and prognostic factors of West syndrome (WS), we performed a retrospective epidemiological study of WS occurred in 47 children (26 boys and 21 girls) in Nagasaki prefecture during a recent 10-year period from 1989 to 1998. The incidence of WS was 3.1/10,000 live births. The mean age at onset of spasm is 6.3 months (range: 2 to 12 months). Thirty-nine patients (83%) had symptomatic WS, in which the prenatal causes (patients) were most frequent, followed by low-birth weight infants (patients), perinatal (patients) and postnatal (patients). The brain CT was performed in 37 patients, and revealed congenital brain malformations (9 patients), destructive brain disorders (12 patients), and no structural abnormalities (16 patients). The seizure outcome was worse in the symptomatic WS than in the cryptogenic WS; seizure/disappeared in 39% of the former and in 75% of the latter/developmental delay before the onset of WS, relapse of WS and persistence of seizures were associated with poor seizure outcomes. Among the remaining seizures at the time of this surveillance, a tonic seizure was most frequently observed, followed by the partial seizures. Lennox-Gastaut syndrome was observed in 2 patients only. Epileptic discharge in the latest interictal EEG were diffuse in 4.3%, focal or multifocal in 60.7%, and absent in 35%, suggesting that many patients with WS had cortical epileptogenic foci. The developmental outcome was very poor in both the symptomatic and cryptogenic WS. The mean DQ in all the patients was 25, and only 4 patients (11%) had a normal DQ (> 75). DQ was lower in patients with congenital brain malformations than in those with destructive brain disorders.     

Infantile spasms: diagnosis and assessment of treatment response by video-EEG

The purpose of this study was to investigate early electroclinical manifestations and evaluate treatment responses by video-EEG in infants with newly diagnosed spasms. Spasms were recorded in 44 infants (27 males, 17 females) before adequate treatment. Mean ages at onset of spasms and at first video-EEG were 5.3 months (range 0.9 to 9 months) and 5.9 months (range 2.4 to 11.5 months) respectively. Thirteen infants had cryptogenic and 31 had symptomatic aetiology. First treatment was vigabatrin in 36 infants. All infants were followed until 12 months of age or death. Treatment response in the first months of therapy was assessed by repeated video-EEG studies in 23 infants. On the first video-EEG, 34 infants had typical symmetric motor spasms, three infants showed asymmetric or asynchronous behaviour, and seven infants had only subtle spasms. Interictal EEG showed hypsarrhythmia in 27 infants and multifocal spikes with normal or nearly normal background in 17 infants. Subtle spasms, asymmetric or asynchronous spasms, and asymmetric ictal or interictal EEG abnormalities were associated with symptomatic aetiology and poor cognitive and seizure outcome at 12 months. Serial video-EEG recordings showed a transition from motor to subtle spasms during the first 2 weeks of vigabatrin therapy in four infants and only subtle spasms in two therapy-resistant infants at 12 months. Cessation of spasms usually preceded disappearance of hypsarrhythmia or multifocal spikes, but persistence of multifocal spikes over several weeks was always associated with existing spasms. Transition of hypsarrhythmia into multifocal spikes was observed during vigabatrin therapy even in infants with intractable spasms. Initial diagnosis of infantile spasms requires video-EEG studies especially in infants with symptomatic aetiology who may show only subtle spasms. Video-EEG is the only reliable method for assessing treatment response as spasms and interictal EEG abnormalities are modified by treatment and may become subtle.     

West syndrome and other infantile epileptic encephalopathies--Indian hospital experience.

Children with infantile epileptic encephalopathies comprising 3.5% of the Pediatric Neurology Clinic registrations in a tertiary care hospital were retrospectively analyzed. Data were retrieved from case records and analyzed for seizure semiology, prenatal and perinatal insults, developmental status and relevant investigations. The various therapeutic modalities and their influence on spasm frequency, long-term development and final seizure status were compared. The two primary outcome variables analyzed included final seizure status and developmental outcome. Of the 94 infantile epileptic encephalopathies, West syndrome was the commonest (55.3%), of which two thirds were symptomatic. Etiological factors were prenatal in 66.6% and perinatal in 33.3%. The initial response to ACTH was good in 54.5% with subsequent relapse in 27.8% and for prednisolone was 52.9 and 44.4%, respectively, compared to 25.3% spasms control with conventional antiepileptic drugs. Disease category of infantile epileptic encephalopathies evolved in 4, i.e. early myoclonic encephalopathy to West syndrome 1, early infantile epileptic encephalopathy to West syndrome 1, West syndrome to Lennox-Gastaut syndrome 2. Psychomotor retardation was seen in 88.2%, with 16.1% having normal development at onset of spasms. Microcephaly was associated with delayed development but did not influence final seizure outcome. Final seizure outcome was poor in children with delayed development at onset (adjusted odds ratio [OR]=4), delay in diagnosis >12 months (OR=2.27) and in children with Lennox-Gastaut syndrome (OR=4.75). ACTH/prednisolone and antiepileptic treatment versus antiepileptics alone showed a good final seizure response in 36.6% versus 20%. Development on follow up was delayed in children with initial psychomotor retardation (OR=23.4) and abnormal electroencephalogram (OR=7.46). Perinatal factors constituted one third of symptomatic West syndrome. The use of ACTH/corticosteroids resulted in good initial spasm control though final seizure outcome and development were unaffected. Prednisolone had similar response to ACTH in spasm control but higher subsequent relapse rate. Vigabatrin was useful though often unaffordable. The identification of a neurometabolic etiology, though uncommon, has significant therapy implications. Delay in diagnosis was common and negatively influenced final seizure outcome.     

West syndrome and other infantile epileptic encephalopathies--Indian hospital experience

Children with infantile epileptic encephalopathies comprising 3.5% of the Pediatric Neurology Clinic registrations in a tertiary care hospital were retrospectively analyzed. Data were retrieved from case records and analyzed for seizure semiology, prenatal and perinatal insults, developmental status and relevant investigations. The various therapeutic modalities and their influence on spasm frequency, long-term development and final seizure status were compared. The two primary outcome variables analyzed included final seizure status and developmental outcome. Of the 94 infantile epileptic encephalopathies, West syndrome was the commonest (55.3%), of which two thirds were symptomatic. Etiological factors were prenatal in 66.6% and perinatal in 33.3%. The initial response to ACTH was good in 54.5% with subsequent relapse in 27.8% and for prednisolone was 52.9 and 44.4%, respectively, compared to 25.3% spasms control with conventional antiepileptic drugs. Disease category of infantile epileptic encephalopathies evolved in 4, i.e. early myoclonic encephalopathy to West syndrome 1, early infantile epileptic encephalopathy to West syndrome 1, West syndrome to Lennox-Gastaut syndrome 2. Psychomotor retardation was seen in 88.2%, with 16.1% having normal development at onset of spasms. Microcephaly was associated with delayed development but did not influence final seizure outcome. Final seizure outcome was poor in children with delayed development at onset (adjusted odds ratio [OR] = 4), delay in diagnosis >12 months (OR = 2.27) and in children with Lennox-Gastaut syndrome (OR = 4.75). ACTH/prednisolone and antiepileptic treatment versus antiepileptics alone showed a good final seizure response in 36.6% versus 20%. Development on follow up was delayed in children with initial psychomotor retardation (OR = 23.4) and abnormal electroencephalogram (OR = 7.46). Perinatal factors constituted one third of symptomatic West syndrome. The use of ACTH/corticosteroids resulted in good initial spasm control though final seizure outcome and development were unaffected. Prednisolone had similar response to ACTH in spasm control but higher subsequent relapse rate. Vigabatrin was useful though often unaffordable. The identification of a neurometabolic etiology, though uncommon, has significant therapy implications. Delay in diagnosis was common and negatively influenced final seizure outcome.     

Profile of West syndrome in North Indian children

To study the profile of West syndrome (WS) in North Indian Children, 165 cases of WS were analyzed. Details of seizure semiology, prenatal and perinatal events, developmental milestones, treatment received, physical and neurological examination and investigations were recorded. The response of seizures to various therapeutic modalities and the final developmental status were taken as primary outcome variables. Analysis was done to find the factors influencing these outcome variables. The age of onset of infantile spasms ranged from 1 to 19 (mean 6.1 +/- 3.4) months. Age at presentation ranged from 1.5 months to 4.5 years (mean 14.7 +/- 11.4 months); 74% had flexor spasms. Other types of seizures were associated in 31 children. Antenatal problems and adverse perinatal events were reported in 26.7 and 59.4%, respectively. Developmental delay was recognized in 69.7% prior to and in 27.9% after onset of spasms. Microcephaly was seen in 72.7%. Interictal EEG showed hypsarrhythmia in 44; generalized spike and slow waves in 31% and burst suppression in 7%. Computed tomography scan done in 94 cases showed cerebral atrophy in 15%, infarcts in 8%, tubers in 7%, developmental malformations in 5%. Magnetic resonance imaging done in 77 cases showed periventricular T2WI white matter hyper intensities in 33.8% and cerebral atrophy in 21%. Prednisolone and ACTH were used in 57 and 35 cases, respectively. Complete control of seizures was seen in 49 and 46% cases. No significant difference in seizure control or developmental outcome was found in the two groups. Overall, 42.4, 30.9 and 16% children showed complete, partial and no control of seizures. After therapy, developmental improvement was seen in 55.8% and no change in 23.6% cases. The type of spasms had no correlation with the other parameters including etiology, seizure or developmental outcome. An early age of onset correlated with presence of antenatal problems (P < 0.05). Seizure control and developmental improvement correlated significantly (P < 0.005). Developmental outcome was better in cryptogenic as compared to symptomatic cases (P < 0.05). No other significant correlations were found. In India WS is often diagnosed late because of lack of awareness. Adverse perinatal events are important etiological factors. Non-affordability of ACTH and Vigabatrin prompts the use of prednisolone in most cases.     

Levetiracetam monotherapy in newly diagnosed cryptogenic West syndrome

The combination of axial spasms in clusters, hypsarrhythmia, and psychomotor delay beginning in the first year of life defines West syndrome. Adrenocorticotrophic hormone remains the choice of treatment for many neurologists. Recent controlled studies support vigabatrin as first-line therapy, and open-label studies suggest that topiramate, lamotrigine, and zonisamide may be useful in treating spasms. Studies regarding the efficacy and safety of such treatments often come from small, uncontrolled trials and are often inconclusive. Levetiracetam is effective for treating localization-related epilepsy, but it is uncertain whether it is effective for treating West syndrome. To evaluate the efficacy of levetiracetam monotherapy in newly diagnosed cryptogenic West syndrome, levetiracetam was used initially in the treatment of five patients with cryptogenic West syndrome. On admission, levetiracetam (30 mg/kg) tablets were crushed and administered via nasogastric tube. Two patients were seizure free, two patients experienced a 50% reduction in seizure frequency, and one patient had no improvement in seizure frequency. There were no relapses in the two patients at 6 months after the cessation of seizures. It appears that levetiracetam may be effective in the initial treatment of selected patients with cryptogenic West syndrome.     

Development of visual attention in West syndrome

PURPOSE: To study prospectively the evolution of visual attention in children with West syndrome to evaluate its development before the onset of spasms, its possible deterioration as a consequence of epileptic disorders, and its outcome at the age of 2 years, and the possible relation between the impairment of visual attention and cognitive development. METHODS: Infants with symptomatic West syndrome were examined before the onset of spasms and until age 24 +/- 2 months. Visual attention study (through a clinical observation and the fixation-shift test), cognitive assessment, and complete clinical examination including brain magnetic resonance imaging were performed. RESULTS: A maturation defect of fixation shift skills was generally observed in infants with West syndrome. In some cases, the impaired visual-attention abilities paralleled a cognitive deterioration, even months before the onset of spasms. During the acute stage of West syndrome, infants lost the previously acquired visual and cognitive abilities, with a typical fluctuation of arousal. Usually at 2 years, there was a persistent defective visual attention detected with the fixation-shift test. CONCLUSIONS: The parallel defect of visual attention and of cognitive competencies is a constant finding in infants with West syndrome; these can precede the clinical onset of epileptic spasms. The severity and persistence of visual inattention might be explained by the age of visual maturation, corresponding to the usual onset of West syndrome.     

Predicting Favorable Outcome in Idiopathic West Syndrome

Summary: Among 45 patients with cryptogenic West Syndrome (WS) we report 30 with a favorable outcome consisting of normal psychomotor development and cessation of epilepsy with at least 2 years follow-up (mean 4 years 7 months). These favorable patients could be recognized from onset by (a) absence of significant mental regression with a preserved visual function; (b) absence of focal interictal EEG abnormalities after intravenous diazepam; and (c) reappearance of hypsarrhythmia between consecutive spasms of a cluster. The latter criterion requires EEG recording of a series of spasms. The favorable outcome in these patients suggests that they had no cortical brain lesions. This new type of idiopathic epilepsy referred to as idiopathic West syndrome has important prognostic, therapeutic, and etiologic implications.     

The effect of lead time to treatment and of age of onset on developmental outcome at 4 years in infantile spasms: evidence from the United Kingdom Infantile Spasms Study

Purpose: Infantile spasms is a severe infantile seizure disorder. Several factors affect developmental outcome, especially the underlying etiology of the spasms. Treatment also affects outcome. Both age at onset of spasms and lead time to treatment (the time from onset of spasms to start of treatment) may be important. We investigated these factors. Methods: Developmental assessment using Vineland Adaptive Behaviour Scales (VABS) at 4 years of age in infants enrolled in the United Kingdom Infantile Spasms Study. Date of or age at onset of spasms was obtained prospectively. Lead time to treatment was then categorized into five categories. The effects of lead time to treatment, age of onset of spasms, etiology, and treatment on developmental outcome were investigated using multiple linear regression. Key Findings: Age of onset ranged (77 infants) from <1 to 10 months (mean 5.2, standard deviation 2.1). Lead time to treatment was 7 days or less in 11, 8–14 days in 16, 15 days to 1 month in 8, 1–2 months in 15, >2 months in 21 and not known in 6. Each month of reduction in age at onset of spasms was associated with a 3.1 [95% confidence interval (CI) 0.64–5.5, p = 0.03] decrease, and each increase in category of lead time duration associated with a 3.9 (95% CI 7.3–0.4, p = 0.014) decrease in VABS, respectively. There was a significant interaction between treatment allocation and etiology with the benefit in VABS in those allocated steroid therapy being in children with no identified etiology (coefficient 29.9, p = 0.004). Significance: Both prompt diagnosis and prompt treatment of infantile spasms may help prevent subsequent developmental delay. Younger infants may be more at risk from the epileptic encephalopathy than older infants.     

Epilepsy in the first year of life: a review.

The prevalence of epilepsy is highest during the first year of life. Approximately 50% of patients with seizure onset between 1 and 12 months of age suffer from West syndrome. The rest have one of 12 well-delineated epilepsy syndromes, or in most cases have what are classified as generalized or partial seizures. The outcome of infants with partial seizures is significantly worse than that of patients with generalized seizures. This is true not only for symptomatic partial seizures but also for a subgroup of infants with cryptogenic partial seizures.