Benign spasms of infancy: a mimicker of infantile epileptic disorders*

Benign spasms of infancy (BSI), previously described as benign non‐epileptic infantile spasms or benign myoclonus of early infancy, are non‐epileptic movements manifesting during the first year of life and spontaneously resolving in the second year of life. BSI are characterized by spasms typically lasting 1–2 seconds, involving, to varying degrees, the head, neck, trunk, shoulders and upper extremities. Ictal and interictal EEG recordings are normal. BSI are not associated with developmental regression and do not require treatment. Distinction between BSI and infantile epileptic disorders, such as epileptic spasms or myoclonic epilepsy of infancy, can be challenging given the clinical similarities. Moreover, interictal EEGs can be normal in all conditions. Epileptic spasms and myoclonic epilepsy require timely treatment to improve neurodevelopmental outcomes. We describe a six‐month‐old infant presenting with spasm‐like movements. His paroxysms as well as a positive family history for epileptic spasms were in keeping with a likely diagnosis of West syndrome. Surprisingly, ictal video‐EEG did not reveal epileptiform activity, and suggested a diagnosis of BSI. We emphasize that ictal video‐EEG is the gold standard for classification of infantile paroxysms as epileptic or non‐epileptic, thereby avoiding over‐treatment for BSI and facilitating timely targeted treatment of infantile epilepsies. [Published with video sequences]     

Atonic elements combined or uncombined with epileptic spasms in infantile spasms

Objective

To study the atonic elements combined or uncombined with epileptic spasms in infantile spasms.

Ambulatory 24-hour EEG recording in epileptic infantile spasms

Twenty-four h cassette recording (MEDILOG 9000) where obtained in 22 untreated infants (23 records) with a West syndrome (idiopathic: n = 12, symptomatic: n = 10). All these infants had had a 3 h polygraphic recording. Tracings were visually analyzed for sleep stages. Electro-clinical seizures and infraclinical discharges were listed according to their type and the stage of vigilance. Two hundred twenty-eight critical events were recorded in 22 cassette recordings: isolated spasms, clusters of spasms, partial or generalized discharges followed or not by clusters of spasms. Sixty per cent of these fits occurred during wakefulness, 27% during non REM sleep, 13% during awakening and none during REM sleep. Partial discharges, followed or not by clusters of spasms, were only present in cases with unfavourable outcome. In benign spasms the hypsarrhythmic pattern was present between spasms in each cluster, but not in cases with unfavourable outcome. Compared with 3 h polygraphic recordings, 24 h cassette recordings gave supplementary data on the presence, type and timing of seizures in 16 of out 22 cases.     

Benign myoclonus of early infancy or benign non-epileptic infantile spasms

Lombroso and Fejerman (1983) described a syndrome which shares with West syndrome the clinical features of flexion spasm with onset in early infancy. However the syndrome differs from West syndrome in the absence of mental and psycho-motor involvement and having a normal EEG during wakefulness and sleep. We report four cases of these benign spasms of early infancy with polygraphic recording of the spasms providing the following information: the spasms are clinically similar to those often observed in West syndrome; namely they are characterized by a short (2-4 sec.) tonic contraction, there are no significant changes of the EEG concomitant to the spasm, series of spasms can occur not only during the daytime but also during sleep and immediately after awakening. Differential diagnosis is discussed with West syndrome and benign myoclonic epilepsy in infancy and with non-epileptic syndromes. The authors propose to name this syndrome: Benign Non-Epileptic Infantile Spasms.     

Surgery for symptomatic infant-onset epileptic encephalopathy with and without infantile spasms

Children undergoing surgery with infant-onset epilepsy were classified into those with medically refractory infantile spasms (IS), successfully treated IS, and no IS history, and the groups were compared for pre- and postsurgery clinical and Vineland Adaptive Behavior Scale (VABS) developmental quotients (DQ). Children without an IS history were older at surgery and had longer epilepsy durations than those with IS despite similar substrates, surgeries, and seizure frequencies. In all groups, better postsurgery VABS-DQ scores were associated with early surgical intervention indicating that infant-onset epilepsy patients with or without IS are at risk for seizure-induced encephalopathy.     

Infantile epileptic encephalopathy with hypsarrhythmia (infantile spasms/West syndrome).

Infantile spasms is a unique disorder peculiar to infancy and early childhood. In this article, the clinical manifestations and electroencephalographic features of the disorder are described. The possible pathophysiologic mechanisms underlying infantile spasms and the relation of this disorder to other childhood encephalopathies are discussed. Finally, the treatment of patients with infantile spasms and their long-term outcome are briefly reviewed.     

Neuropathology of the brainstem in age-dependent epileptic encephalopathy--especially of cases with infantile spasms

Twenty-two autopsy cases with developmental disabilities with history of infantile spasms were studied with special regard to brainstem lesions. Eleven out of 22 cases were considered to be of prenatal origin, ten cases were perinatal and one case had suffered from acute encephalopathy at six months of age. Some common pathological findings were noticed throughout the cases despite their various etiologies; small size of the brainstem tegmentum, spongy state in and around the central tegmental tract, localized periaqueductal glial scar. Control study on another autopsy series of 76 cases with developmental disabilities showed a close connection between these findings in the brainstem tegmentum and history of infantile spasms.     

Vigabatrin for infantile spasms

We reviewed 20 infants receiving vigabatrin for infantile spasms. Patients were not enrolled in a formal study. All families obtained the medication abroad. Age at initiation of vigabatrin ranged from 1 to 48 months; nine infants had received prior treatment with various antiepileptic medications. Patients were begun on the lowest practical dose of 125-250 mg/day, with gradual daily increments to a target of 100 mg/kg/day, but maintained at the lowest effective dosage. Video electroencephalogram was obtained to document resolution of spasms and hypsarrhythmia. Of 20 infants, 12 responded with cessation of spasms and resolution of hypsarrhythmia, at doses of 25-135 mg/kg/day (median = 58 mg/kg/day). Partial responses were observed in six patients, whereas two had no response at 111 and 125 mg/kg/day. Additional new seizure types developed in three infants after initial response to vigabatrin. Increasing the vigabatrin did not have any clinical benefit. Vigabatrin is an effective, well-tolerated treatment for infantile spasms. The response is dose-independent, suggesting that starting at a low dose and gradually increasing, rather than beginning with an arbitrary 100 mg/kg/day dose is advantageous.     

Treatment of infantile spasms

Although the syndrome of infantile spasms has been known for 150 years and its treatment described since 1958, controversy still surrounds the appropriate therapy for this devastating disorder. The rationale, dosage, and side effects of ACTH treatment of infantile spasms is described. The recommended treatment regimen is placed in the context of the literature on the therapy of spasms and its relation to outcome.     

Benign familial neonatal convulsions in a family with one member with infantile spasms]

A pedigree of benign familial neonatal convulsions (BFNC) was reported. Seven members of two generations experienced convulsions in the neonatal period and/or in early infancy. All of these members except one had a good prognosis. One member who had infantile spasms was uneventfully delivered at 37 weeks of gestation, with a birth weight of 2,562 g and, without trouble during pregnancy. At the age of 20 days, she began to have adversive seizures. Later, she developed complex partial seizures and infantile spasms at 1 month and 10 days of age. Interictal EEG showed hypsarrhythmia. Biochemical investigations and MRI of the head revealed no abnormality. Treatment with sodium valproate and carbamazepine succeeded in stopping the seizures and she had no seizures after 3 months. But her psychomotor development was moderately delayed at 8 months. No case with severe epilepsy such as infantile spasms has been reported in the previous literature on BFNC. From our experience, early treatment and careful follow-up are considered to be important for BFNC.     

Hypothalamic hamartoma and infantile spasms

PURPOSE: A small number of patients with hypothalamic hamartoma (HH) present with infantile spasms (IS) as an initial or early seizure type. We describe the clinical features of IS associated with HH. METHODS: Our series of patients with HH and epilepsy was reviewed to identify cases with a history of IS. The clinical features and neuroradiological findings in this study group were compared to a control group of patients with HH and refractory epilepsy, but without a history of IS. RESULTS: We identified six patients with HH and a history of IS in this series (n = 122, 4.9%). Five of the six are male. Four of the six patients (67%) developed IS as their first seizure type. The mean age for onset of IS was 6.2 months (range 4-9 months). Results of electroencephalographic (EEG) study at the time of IS diagnosis showed hypsarrhythmia in two (33%). Five patients were treated with adrenocorticotropic hormone (ACTH), and four of the five (80%) responded with control of IS. However, these patients developed other seizure types, and were ultimately refractory to medical management. Aside from the IS, no significant differences in clinical and imaging features were determined between the study group and the control group. CONCLUSIONS: HH should be included in the differential diagnosis for infants presenting with IS. These patients may have hypsarrhythmia on initial EEG, and may respond to ACTH treatment with improvement of IS. However, all became refractory with other seizure types, more commonly seen in HH patients. Focal pathologies associated with IS may be subcortical, as well as cortical, in nature. We have not identified any predictive features for the occurrence of IS in the HH population.     

Neuroradiological aspects of infantile spasms

With the modern noninvasive brain imaging methods, cerebral lesions of different types and degrees can frequently be determined in infants with West syndrome. In CT examinations preceding the spasms and the ACTH therapy, "idiopathic" forms of infantile spasms were rare. The CT findings consistent with perinatal or postnatal encephalopathy were more frequent than those found with embryonic or fetal lesions alone. The fact that pathognomonic changes cannot be determined, may reflect the low specificity of CT diagnosis in infants with chronic CNS diseases. A slight and mostly transient enlargement of CSF spaces during ACTH therapy is a probable side-effect of the medication. In infants with persistent or progressive enlargement of the CSF spaces, however, this alteration appears to be mainly due to pre-existing brain damage. CT examinations of infants with West syndrome should be performed because prognostic information may be obtained and in a few cases operations to drain CSF may be necessary.     

Focal lesions in infantile spasms

Among 174 cases of infantile spasms examined by CT-scan between January 80 and December 85, 17 (9.8%) had a focal lesion without microcephaly. It consisted of an angioma (1 case), a cortical dysplasia (1 case) and porencephalic lesions (15 cases). In 11 cases with porencephaly, an acute event had occurred between 28 weeks of gestation and 3 months of life. In 7 cases, the lesion extended to the major part of one hemisphere. In the 10 others, it was localized either to the rolandic or to the temporo-occipital regions. In all the cases, the lesion concerned at least one of these areas. It involved the cortex in 15 cases but in the 2 others it seemed to only concern the white matter. The lesion was on the left in 14 cases. After steroids, the epilepsy recurred in 6 cases of which 5 involved the frontal lobe (P less than 0.05). This study seems to show that it is mainly the rolandic and the temporo-occipital areas that favour the occurrence of infantile spasms, whereas extension to the frontal area is responsible of a later partial epilepsy.     

The latest on infantile spasms

PURPOSE OF REVIEW: This article reviews the most significant advances in the field of infantile spasm during the past year, with emphasis on best practise for treatment, and on some new etiological genetic and metabolic causes for the spasms, and new advances in the knowledge of tuberous sclerosis. RECENT FINDINGS: Up-to-date information comparing corticotrophin, oral steroids and vigabatrin shows that hormonal treatment is the most effective therapy in the short term. In a recent randomized trial, large doses of prednisolone were as effective as corticotrophin. There are insufficient data to recommend any treatment schedule for infantile spasms. Vigabatrin is the choice for infants with tuberous sclerosis. Visual field defects in (older) children seem to be as common as in adults. In animals, vigabatrin can induce apoptosis of the neurons in the developing brain. New rare factors associated with infantile spasms are mitochondrial diseases, mutations of the Aristales-related homeobax gene and posterior quadrantic dysplasia syndrome. The outcome in children with tuberous sclerosis and infantile spasms is better understood. SUMMARY: The accurate determination of etiology is now becoming increasingly possible. There is still a lack of consensus about the treatment of first choice for infantile spasms. However, recent data show that hormonal treatment is the most effective therapy in the short term. Frequency of visual field defects in children treated with vigabatrin should be studied in addition to the long-term outcome in general. Advances in our understanding of brain maturation, etiologies, mechanisms and genetics underlying catastrophic epilepsy may facilitate more effective pharmacologic interventions.     

Sleep characteristics in infantile spasms

Sleep staging was performed on 32 patients with infantile spasms. All patients demonstrated significantly less total sleep time and lower percentage of REM time than the expected normal values for age. Seventeen were treated with ACTH or prednisone. There was no increase in total sleep time in those who received hormone therapy, whether or not it was successful. However, the percentage of REM time increased significantly in patients who responded to therapy; this increase occurred concurrently with clinical and electroencephalographic improvement. There was no significant change in REM-sleep values in patients who did not respond.     

Evoked potentials in infantile spasms

In infants and toddlers (N = 8) with infantile spasms, visual and somatosensory evoked potentials (VEP, SEP) were recorded during the course of the illness. During hypsarrhythmia the pattern evoked potential was missing (7/8) or grossly abnormal (1/8), indicating functional amaurosis. Flash evoked responses were normal in 50% even during the EEG-status, showing the superiority of pattern versus flash evoked potentials for visual functions in infancy. The alterations were reversible after successful treatment. Early SEP-components remained normal even during the bioelectrical status but later cortical components were altered in a reversible manner. The results show the objective state of functional sensory block during the EEG-status and underline the necessity of quick and effective treatment to avoid delayed visual maturation.     

Symptomatology of infantile spasms.

Epileptic spasms in West syndrome consist of a brief phasic contraction followed by a gradually relaxing tonic component, associated with typical ictal electroencephalographic (EEG) patterns. Three different EEG patterns are associated with a clinical spasm: fast wave bursts, high voltage slow waves (HVS), and desynchronization, occurring in this order. HVS are consistently seen and correspond to a clinical spasm, but usually preceded by fast wave bursts, which may be associated with an inhibition of muscle activity. Epileptic spasms can be classified into: symmetric spasms, asymmetric/asynchronous spasms, focal spasms, spasms with partial seizures, subtle spasms, spasms preceded by brief atonia, or subclinical spasms. Although clinical spasms are usually symmetric, ictal fast waves are always localized, and the following slow waves are not bilaterally synchronous and generalized, suggesting a focal cortical origin of spasms.