Infantile spasms associated with a histamine H1 antagonist

Some anti-allergic agents act as histamine H1 antagonists and induce seizure discharges in epileptic patients. Of these agents, ketotifen has an especially potent effect. We have experienced 2 cases of 4-month-old boys who developed infantile spasms 8 to 10 days after ketotifen administration. They showed almost the same clinical course with regard to their age, the interval between ketotifen administration and the onset of seizures, their symptoms and EEG abnormalities. These cases suggest that the administration of ketotifen to young infants may be hazardous with regard to inducing infantile spasms.     

Infantile spasms

Infantile spasms are a seizure disorder in young infants with diverse etiologies, suggesting that they arise from any disturbance of central nervous system function during susceptible periods of development. The prognosis for normal intellectual and neurologic development parallels that of the underlying etiology. Early and appropriate treatment with ACTH may lead to seizure control in a majority of patients. The treating physician must anticipate the side effects of this modality.     

Infantile spasms in tuberous sclerosis complex.

The high incidence of infantile spasms (IS) and hypsarrhythmia in tuberous sclerosis complex (TSC) has long been emphasized but it is now clear that infants with TSC show clinical and EEG differences from those with classical West syndrome. Seizures at onset are mainly characterized by partial motor seizures and IS. Subtle partial seizures may be present in the early neonatal period and may precede the onset of IS. Visual recording techniques have led to significant progress in the classification of seizures associated with TSC, demonstrating that they have a focal or multifocal origin in the vast majority of cases. In most cases, an awake interictal EEG shows focal or independent multifocal spike and slow-wave activity at onset and later a pseudo-hypsarrhythmic pattern. Ictal EEG starts with focal spikes originating from the posterotemporal, or occipital regions followed by a generalized irregular slow transient and an abrupt diffuse flattening. Although the pathophysiological mechanisms responsible for the coexistence of partial seizures and IS are still unclear, IS associated with TSC may be the result of a rapid secondary generalization. The presence of IS due to TSC is strongly predicted by the cortical tuber count, while the age of onset of seizures and the age of occurrence of EEG foci depend on the localization of cortical tubers with an earlier expression of the parieto-occipital than of the frontal regions. Early recognition of these distinctive features appears worthwhile for therapeutic and prognostic implications. Despite the efficacy of vigabatrin the prognosis of IS is generally poor. Studies using combined topographic mapping of EEG, magnetic resonance imaging and positron emission tomography may provide new strategies for selecting candidates suitable for surgery.     

Infantile spasms: ictal phenomena

Ictal phenomena were studied during three separate six-hour video/polygraphic recording sessions in 10 patients with infantile spasms; 1,079 spasms occurred. Frequency during wakefulness (7.7 spasms/hour) was greater than that during sleep (2.5 spasms/hour); 46.6% of spasms occurred in clusters. Spasms were composed of one or more of three phases: a myoclonic contraction, a tonic contraction, and/or an arrest of activity. The most common types were myoclonic-tonic (40.3%) and myoclonic alone (36.3%). When classified by postural motor phenomena, 41.6% were "flexor", 16.3% "extensor", 39.0% "mixed", and 3.1% "arrest" alone. Electrographic monitoring revealed that myoclonic contractions were associated with an initial paroxysmal event. Tonic contractions and arrests were usually associated with suppression of electroencephalographic activity with or without rhythmic activity. Knowledge of these clinical and electrographic features is important for diagnosis and evaluation of proposed treatments.     

Infantile spasms: West syndrome

West syndrome is an epileptic syndrome with a devastating clinical course. In recent years, anatomic and functional neuroimaging studies have helped to diagnose the cause of the spasms in most children, but with little progress in improving the poor developmental outcome associated with this syndrome. This article cites 4 seminal observations regarding the clinical presentation, diagnosis, and treatment of infantile spasms.     

Infantile spasms and pigmentary mosaicism

We present a 3‐year‐old boy with pigmentary mosaicism and persistent intractable infantile spasms due to mosaicism of chromosome 7. Getting the diagnosis of pigmentary mosaicism in a child with infantile spasms may not be easy, as most diagnostic work‐up is done in infancy, at a time when skin manifestations can be subtle. We stress the need for a meticulous search for an etiology in cases of infantile spasms. Diagnostic work‐up should include a dermatologic evaluation with skin biopsies for fibroblast culture (and karyotyping) from abnormal pigmented skin areas.     

Infantile spasms in COFS syndrome

Cerebro-oculo-facial-skeletal (COFS) syndrome is a rare, autosomal recessive syndrome characterized by microcephaly, microphthalmia and/or cataracts, neurogenic arthrogryposis, and multiple congenital anomalies. A term female infant with COFS syndrome who developed infantile spasms at the age of 3 months is reported. The patient had a good response to intramuscular ACTH with disappearance of infantile spasms and resolution of the hypsarrhythmic pattern on electroencephalography succeeded by a slow, synchronous pattern. Modified hypsarrhythmia returned after ACTH therapy was discontinued. Infantile spasms have not previously been reported in association with COFS syndrome and are a potentially treatable aspect of the disease. This patient may add to the clinical spectrum of COFS syndrome or may have a variant.     

Infantile spasms and Lennox-Gastaut syndrome

Infantile spasms and Lennox-Gastaut syndrome are rare but are important to child neurologists because of the intractable nature of the seizures and the serious neurologic comorbidities. New antiepileptic drugs offer more alternatives for treating both infantile spasms and Lennox-Gastaut syndrome. Selected children with infantile spasms are candidates for epilepsy surgery. Vagus nerve stimulation, corpus callosotomy, and the ketogenic diet are all options for selected children with Lennox-Gastaut syndrome. The epidemiology, clinical manifestations of the seizures, electroencephalographic characteristics, prognosis, and treatment options are reviewed for infantile spasms and Lennox-Gastaut syndrome. Additional therapies are needed for both infantile spasms and Lennox-Gastaut syndrome as many children fail to achieve adequate seizure control in spite of newer treatments.     

Infantile spasms in patients with neurofibromatosis type 1

The authors report two patients with neurofibromatosis type 1 who were affected by infantile spasms. The infantile spasms were severe and unresponsive to anticonvulsant treatment. The authors maintain that infantile spasms may belong to the clinical features of neurofibromatosis type 1.     

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.     

Infantile spasms: A U.S. consensus report

The diagnosis, evaluation, and management of infantile spasms (IS) continue to pose significant challenges to the treating physician. Although an evidence‐based practice guideline with full literature review was published in 2004, diversity in IS evaluation and treatment remains and highlights the need for further consensus to optimize outcomes in IS. For this purpose, a working group committed to the diagnosis, treatment, and establishment of a continuum of care for patients with IS and their families—the Infantile Spasms Working Group (ISWG)—was convened. The ISWG participated in a workshop for which the key objectives were to review the state of our understanding of IS, assess the scientific evidence regarding efficacy of currently available therapeutic options, and arrive at a consensus on protocols for diagnostic workup and management of IS that can serve as a guide to help specialists and general pediatricians optimally manage infants with IS. The overall goal of the workshop was to improve IS outcomes by assisting treating physicians with early recognition and diagnosis of IS, initiation of short duration therapy with a first‐line treatment, timely electroencephalography (EEG) evaluation of treatment to evaluate effectiveness, and, if indicated, prompt treatment modification. Differences of opinion among ISWG members occurred in areas where data were lacking; however, this article represents a consensus of the U.S. approach to the diagnostic evaluation and treatment of IS.     

Infantile spasms. Comparative trial of nitrazepam and corticotropin

Fifty-two patients were enrolled in a four-week randomized multicenter study comparing nitrazepam and corticotropin in the treatment of infantile spasms. The drugs' efficacy was evaluated in 48 patients, all less than 2 years of age. Both treatments resulted in a statistically significant reduction in spasm frequency from that at baseline, but the difference between treatments was not significant. The number of patients who experienced side effects was similar in the two treatment groups, but the adverse effects encountered among the patients treated with corticotropin were qualitatively more severe and required the discontinuation of treatment in six patients.     

Infantile spasms provoked by partial seizures

A case of infantile spasms that were persistently preceded by a partial seizure is presented. The absence of normal interhemispheric communication through the corpus callosum excludes rapid secondary generalization via this route as a possible explanation for bilateral spasms. A mechanism implicating the brainstem as the common source of infantile spasms and their characteristic hypsarrhythmic EEG pattern is discussed.     

Infantile spasms: A prognostic evaluation

Background:Few papers address the comprehensive prognosis in infantile spasms and look into the seizure profile and psychomotor outcome.Objective:We aimed to follow up children with infantile spasms to study: a) the etiology, demographics, semiology, electroencephalogram (EEG), and radiological pattern; b) seizure control, psychomotor development, and EEG resolution with treatment; c) the effects of various factors on the control of spasms, resolution of EEG changes, and psychomotor development at 3-year follow-up.Results:Of the children followed up, 51% were seizure-free and 37% had a normal EEG at the 3-year follow-up. Autistic features were seen in 74% of the children. Only 22.7% among the seizure-free (11.6% of the total) children had normal vision and hearing, speech with narration, writing skills, gross and fine motor development, and no autism or hyperactivity. On multivariate analysis, two factors could predict bad seizure outcome — the occurrence of other seizures in addition to infantile spasms and no response to 28 days of adrenocorticotropic hormone (ACTH). No predictor could be identified for abnormal psychomotor development.

Discussion and Conclusion:

In our study, we could demonstrate two factors that predict seizure freedom. The cognitive outcome and seizure control in this group of children are comparable to the existing literature. However, the cognitive outcome revealed by our study and the survey of the literature are discouraging.     

Infantile spasms: therapy and outcome

Up-to date information about corticotropin (ACTH) in the treatment of infantile spasms and evaluation of the long-term outcome was provided to answer questions about (1) the efficacy of doses of ACTH in comparison with other drugs, especially with vigabatrin, and the efficacy in patients with tuberous sclerosis; (2) tolerability; and (3) long-term outcome. In two studies, high doses were not more effective than low doses but were more effective in another study. In the follow-up of the studies, there was no difference. In an open, randomized, prospective study, the efficacy and relapse rates of ACTH and vigabatrin treatment did not differ significantly. The high response rates in tuberous sclerosis complex were similar. Both drugs had severe side effects. In the long-term follow-up of 20 to 35 years, one third of the patients died, the intellectual outcome of the remaining patients was normal or slightly subnormal, and one quarter and one third of the patients were seizure free. ACTH should be the first choice for treatment of infantile spasms. The side effects of ACTH, unlike those of vigabatrin, are well known, treatable, and reversible. However, an open, prospective study to compare the efficacy, relapse rate, and long-term outcome of treatment with ACTH and vigabatrin is urgently needed. The frequency of visual field defects after vigabatrin therapy should be evaluated.     

Joubert's syndrome associated with congenital ocular fibrosis and histidinemia

We describe a 16-month-old girl with Joubert's syndrome (JS), congenital ocular fibrosis, and histidinemia. Abnormal respiration, ptosis, and minimal eye movements were observed in the neonatal period. Intraoperative examination of the eyes later demonstrated severely restricted eye movements and abnormal insertions and fibrosis of the extraocular muscles. Computed tomography of the head revealed absence of the corpus callosum and brain stem. Histidine levels were elevated in the blood, urine, and cerebrospinal fluid. The patient was ataxic and developmentally delayed. To our knowledge, the association of JS with congenital ocular fibrosis has not previously been described. This report indicates that jerky eye movements are not an invariable finding in JS.     

Infantile spasms. A retrospective study of 105 cases]

This paper is a summary of our observations on 105 cases of infantile spasms. The age of onset was around six months after birth, but the patients came for treatment mainly about one year after onset. Fever of unknown cause, asphyxia, birth injury, infection of the central nervous system, tuberous sclerosis, phenylketonuria and recent immunization etc. were possible etiology. Clinically, it is characterized by head nodding, mental retardation, myoclonic jerks and various neurologic deficits. EEG findings showed classical or modified arrhythmia or other epileptiform patterns. About one third of 22 cases examined had abnormal brain stem auditory evoked potentials. Among 42 patients who underwent CT scanning before ACTH treatment, 18 were normal and 7 abnormal; during ACTH treatment 3 normal and 4 abnormal; after completion of treatment, 4 normal and 6 abnormal, suggesting no further atrophy of the brain. Examination of trace elements of the hair by proton-induced X-ray emission (PIXE) method in 23 patients revealed a significant difference in lead, calcium and zinc contents between patients and 101 controls, but no statistical difference in iron and copper contents between the two groups. Sodium valproate, prednisone and ACTH appear to be effective in the treatment of infantile spasms. Eight patients fully recovered, and they can go to school without difficulty. Many patients derived various degrees of improvement of the satisfaction of their parents. Two patients were still amended and often attacked by myoclonus. The effects, side effects of these drugs, and the possible pathogenesis were discussed.