Unusual Variants of Infantile Spasms Jane
F. Donat, MD; Francis S.
Wright,
MD
Abstract
During evaluation of video-electroencephalograms (EEGs) performed in our laboratory, we identified 11 patients who had unusual repetitive movements that appeared to be variants of infantile spasms. Movements included yawning, facial grimacing, eye movements, and transient focal motor activity. These symptoms coincided with generalized attenuation, slow-wave transients, or other EEG ictal changes characteristic of infantile spasms. The background EEGs showed true or modified hypsarrhythmia. This series of patients shows that infantile spasms may be extremely subtle and clinically atypical. Patients who have these variants may or may not also have typical infantile spasms. In some patients, the seizures appear to be time-related or medication-induced modifications of more typical infantile spasms. (J Child Neurol 1991;6:313-318).
usual clinical symptoms of infantile spasms have been well characterized in earlier studies by analysis of video-electroencephalographic (EEG) data. Typical infantile spasms involve abrupt flexion or extension movements of the extremities, trunk, and neck. Contractions of the facial
The
muscles, eye opening
or
closure, upward eye roll-
nystagmoid eye movements associated. 1-4 be Large series and review artimay cles concerning infantile spasm patients have mentioned that fragmentary variants of these seizures may occur in some infantile spasm patients. 1-3,5-7 Previous authors have emphasized that these seizures may be extremely subtle and may be missed during history taking and even during video-EEG evaluation, unless specifically looked for. 2,5,6 Infantile spasm fragments that have been documented include head nodding, shoulder shrugging, and abdominal contractions. 1-3 Infantile spasms characteristically occur in a series that crescendos and then decrescendos, and these fragmentary forms may oc2 cur at the onset and offset of the series.2 ing, eyelid fluttering,
or
Received Dec 18, 1990. Received revised April 9, 1991. Acfor publication April 10, 1991. From the Department of Pediatrics, Children’s Hospital, Ohio State University School of Medicine, Columbus, OH Presented in part in abstract form at the Child Neurology Society annual meeting, San Antonio, Texas, October 13, 1989 (Ann
cepted
Neurol 1989;26:470). Address correspondence to Dr J.F. Donat, Children’s Hospital, 700 Children’sDrive, Columbus, OH 43205.
Points that are important for the clinical diagnosis of infantile spasms but that have not been clarified in earlier reports include whether fragmentary forms occur in a series without typical infantile spasms and whether fragmentary forms occur as the only form of infantile spasms in some patients. Nodding spasms have been reported to occur in series. 1,8 Holmes stated that eye movements could occur independently from infantile spasms and precede the
of infantile spasms by weeks.9 Whether the occurrence of fragmentary forms has any usefulness in predicting prognosis or outcome of treatment has not been commented on previwho said that their sigously, except by Lombroso, nificance was uncertain.55 In this report, we describe fragmentary variants of infantile spasms that have not previously been reported, we describe their occurrence as series of seizures that did not include typical infantile spasms, and we describe their occurrence both in patients who did and who did not also have typical infantile spasms. We also discuss the physical similarities and differences between fragmentary and typical infantile spasms in patients who had both, recount when during the history of infantile spasms the variants were recorded, and describe how the variants in some patients appear to be modifications that result from the effects of time or treatment on typical infantile spasms.
development
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found in seven patients and no associated disorders identified in four patients (Table 1). Neurologic examination was normal in two patients and showed developmental delay in seven patients, spastic hemiparesis in one patient, and spastic quad-
Patients and Methods The 11 patients who had the infantile spasm
variants were all referred to the EEG laboratory because of possible seizures and had video-EEGs performed to document the seizure type before initiation of treatment. The 11 patients constitute 13% of all patients who had initial diagnoses of infantile spasms documented by video-EEGs performed during the 39-month period from March 1987 through May 1990. All EEGs were obtained on 21-channel Nihon-Kohden EEG machines with simultaneous time-locked videotape recording. Four patients had routine-length recordings (50 minutes). Three patients had 3- to 7-hour recordings. Four patients had routine-length recordings plus 24-hour remote
were
riparesis in one patient.
Electroencephalograms All 11 patients had their first video-EEG evaluations 2 days to 6 weeks after the onset of clinical seizures. Interictal EEGs showed hypsarrhythmia in eight patients (Figure 1) and modified hypsarrhythmia in three patients.l° Ictal EEGs in all patients consisted of a generalized decrement in cerebral activity. In some instances, this was preceded by an initial generalized sharp- or slow-wave transient (Figure 2) and/or accompanied by low-voltage &dquo;fast&dquo; activity. These findings were identical to EEG findings in patients who have typical infantile spasms .2,3
telemetry recordings (Telefactor, ConshoEight patients also had video-EEGs per-
video-EEG cable
hocken, PA).
two or more later dates to
follow-up response to of these eight patients had routine-length recordings, three of the eight had 3- to 6-hour recordings, and one patient had a routine-length recording plus a 24hour remote video-EEG cable telemetry recording. formed
on
treatment. Four
Patients were included who met the following criteria: the interictal EEG showed hypsarrhythmia or modified hypsarrhythmial°; the variants consisted of movements of very brief duration (similar to the duration of typical infantile spasms) that involved a limited body area or restricted group of muscles; the variants occurred alone in a series that did not include typical infantile spasms; and each seizure was associated with an ictal EEG change identical to the one that accompanies typical infantile spasms.2,3
Characteristics of the Infantile Spasm Variants Each of the variants occurred in a series that did not include typical infantile spasms. Each series consisted of at least three seizures, and each seizure in the series was separated by 5 to 30 seconds. The longest series lasted 6 minutes. Descriptions of the variants are included in Table 2.
Results Patients The 11 patients ranged in age from 3 to 9 months at the time of the EEG that showed the infantile spasm variants, with a mean age of 6 months. There were five girls and six boys. Symptomatic causes were TABLE 1 Timing and Outcome of Infantile _
,
-
-
-.
--
-
-
Infantile Spasm Variant Found on First EEG In seven patients, the infantile spasm variants
Spasm Variants --
-
.
~
-
V infantile spasm variants; T typical infantile spasms; N seizures resolved on medication. *EEG performed 1 day to 3 months after first EEG. tDetailed follow-up not available. tpatient 10 had two successive variants (see text). =
=
were
the first video-EEG evaluation, which present was obtained at the time of diagnosis of infantile spasms (Table 1). Three of these patients had no history of typical infantile spasms. Patient 1 died of a on
=
no
seizures recorded; R
314
Downloaded from jcn.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 21, 2015
’
..
=
FIGURE 1 EEG showed tient 3).
hypsarrhythmia
in
a
9-month-old
girl (pa-
brain disease a few weeks later. Patients 2 and 3 (Figure 3) were reported to be seizure free on adrenocorticotropic hormone (ACTH), but EEG and detailed clinical follow-up were not available. Patient 4 had a history of typical infantile spasms that spontaneously resolved 2 weeks before
degenerative
the time of the video-EEG evaluation that demonstrated the variants of upward eye rolling. Patient 5, whose variants consisted of elevation of one arm, had a contralateral porencephalic cyst on computed tomographic (CT) brain scan as a result of neonatal asphyxia. This patient later developed bilaterally symmetrical typical infantile spasms, which were recorded on video-EEG 3 weeks later. Patients 6 and 7 had typical infantile spasms, as well as the variants, present on the first EEG. Patient 6 had the variants (upward eye deviation) only in sleep; the variants appeared to be fragments of the typical infantile spasms that the patient had while awake. The variants found in patient 7 consisted of ocular adduction (Figure 4). It was uncertain whether these eye movements were present during the series of typical infantile spasms because the eyes were difficult to see during the whole body movements of the typical infantile spasms. Following treatment with clonazepam, this patient had only the variants present on a follow-up EEG 2 months later; this EEG also showed improvement in the hypsarrhythmia pattern to a multifocal spike-and-wave pattern. ACTH was then started and resulted in resolution of the seizures and of the epileptiform EEG pattern. The other three patients for whom clinical and EEG follow-up were available had resolution of the infantile spasm variants as well as the typical infantile spasms during treatment with ACTH (patient 4)11 or valproic acid (patients 5 and 6).12
FIGURE 2 Infantile spasm variants
(eye opening and upward eye deviation) in a 4-month-old girl (patient 2) were accompanied by ictal EEG changes that included generalized slow-wave transients followed by decrements. 315
Downloaded from jcn.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 21, 2015
TABLE 2 Infantile Spasm Variants in 11 Patients
*Eye
movements consisted of
movement,
or
burst of
upward or downward or adduction nystagmoid eye movements or eyelid flut-
ter.
tOne
patient tone patient
had upward eye rolling and facial grimace. had facial grimace and lateral head jerk.
Infantile Spasm Variant Found on Later EEG Four patients had typical infantile spasms present the first video-EEG evaluation and the variants present on video-EEGs performed 1 day (patient 9) or 1 to 3 months later (patients 8, 10, and 11) (Table 1). Patient 8 had both typical and variant infantile spasms present on the later EEG. In this patient, the variants, which consisted of a mouth opening or yawning movement, did not appear to be fragments of the patient’s typical flexor infantile spasms. The ictal EEG changes also differed: the typical infantile spasms were each associated with a generalized slow-wave transient, but the variants were each associated with a generalized
FIGURE 4 Adduction of the eyes was an infantile spasm variant in 5-month-old boy (patient 7).
a
on
FIGURE 3 Upward eye rolling was an infantile spasm variant in 9-month-old girl (patient 3).
a
decrement.
Both types of infantile spasms reincrease in dose of ACTH. Patient 9 sponded had the variants (facial grimace) but no longer had typical infantile spasms on a video-EEG performed for the purpose of a pyridoxine injection 1 day after the first EEG and after two doses of ACTH; the parents of this patient noted the grimace to be part of the generalized infantile spasms, which had disappeared. These episodes subsequently stopped. Patient 10, who had a neonatal cerebral infarct and asymmetrical hypsarrhythmia, had asymmetrical extensor infantile spasms that included a lateral head jerk and facial grimace on the first video-EEG. Variants that consisted of a lateral head jerk and grimace were recorded on video-EEG 1 month later, after treatment with valproic acid, and variants that consisted only of the grimace were recorded on video-EEG 2 weeks after that (Figure 5). At this time, clonazepam was added and the seizures stopped.l3 Patient 11 had resolution of hypsarrhythmia and typical infantile spasms documented on a video-EEG performed 1 month after beginning ACTH treatment. However, ACTH was stopped 6 weeks later because of side effects. Two weeks later, variants (eye opening) were recorded on videoEEG at a time when the EEG still showed no interictal epileptiform activity and the parents had noticed no seizures. Treatment with valproic acid was begun, but typical infantile spasms and hypsarrhythmia were again recorded on an EEG 2 months later. Clonazepam was added and the seizures resolved. to
an
316
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FIGURE 5 Facial grimace was one of two successive infantile spasm variants in a 9-month-old girl (patient 10).
Discussion In most of our patients, the infantile spasm variants appeared to be fragments or limited expressions of more typical infantile spasms. In some of these patients, the variants coexisted with typical infantile spasms and probably represented natural variability in physical expression of infantile spasms. However, in some patients, the variants may have resulted from a change in level of consciousness, time, or medication that modified the clinical expression of the infantile spasms. The effect of level of consciousness was seen in patient 6, who had typical infantile spasms in the waking state but had variants during sleep that consisted of only part of the typical infantile spasm. Time appeared to modify typical infantile spasms in patient 4, who, by history, had generalized infantile spasms that resolved spontaneously 2 weeks before our video-EEG demonstrated the variants, and by patient 5, who developed typical infantile spasms 3 weeks after the variants were recorded. These spontaneous changes suggest that the variants were a stage in the natural evolution of the infantile spasms. Of particular interest are the two patients whose variants appeared to be modifications that resulted from treatment of typical infantile spasms. Increasingly restricted variant forms were recorded in patient 10 on two occasions during treatment before the seizures ceased. In patient 11, the variants were recorded on a video-EEG that was obtained after ACTH given for typical infantile spasms was stopped because of side effects. This was at a time
when the parents thought the seizures were gone and before the interictal EEG showed a recurrence of the hypsarrhythmia pattern. These variants may have been an undetected residual type of infantile spasms that persisted after treatment with ACTH, or they may have heralded the recurrence of infantile spasms after ACTH was stopped. Patient 7 demonstrated a possible difference in therapeutic response between variants and typical infantile spasms: both types of infantile spasms initially coexisted, but only the variants persisted after treatment with clonazepam. The variants then resolved after treatment with ACTH. In other patients, the infantile spasm variants appeared to be separate types of infantile spasms that were not fragments of typical infantile spasms. In patient 8, the infantile spasm variants appeared to be a type of infantile spasms that was different both clinically and electrographically from the same patient’s typical infantile spasms, although both types responded to the same treatment. In patients 1, 2, and 3, the infantile spasm variants occurred with no previous or subsequent history of typical infantile spasms; unfortunately, due to death or lack of follow-up, video-EEG documentation of the subsequent course was not possible. Also, these patients were treated for infantile spasms after the videoEEGs demonstrated the seizures to be infantile spasm variants, and therefore the natural history was altered. The seizures in these patients were diagnostic dilemmas because the clinical descriptions of the seizures did not fit recognized seizure types. This series of patients demonstrates how extremely subtle and clinically atypical infantile spasm variants can be. It is reasonable to assume that the clinical significance of the variants is as great as that of typical infantile spasms.6 Failure to recognize or detect fragmentary variants may account for some of the patients reported to have hypsarrhythmia and electrodecremental episodes without clinical infantile spasms. 2,14 It can also result in underreporting of the number of infantile spasms in patients undergoing treatment, as cautioned by Kellaway et a1.2 In addition, our experience suggests that medications may modify typical infantile spasms into fragmentary variants and that failure to detect these seizures can result in the erroneous conclusion that seizures have stopped when they have only been modified by medication. Infantile spasm variants themselves do not appear to affect prognosis. However, their presence could result in a poorer outcome for infantile spasm patients because of failure to recognize and treat them. In our patients, the variants ap-
317
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group of medications infantile spasms, includtypical and ing ACTH, valproic acid, clonazepam, although in several patients, a different medication or increase in dose was necessary. We suggest that clinicians who diagnose and treat patients who have infantile spasms or who have EEGs that show hypsarrhythmia need to be aware of the wide variety and subtlety of variant infantile spasms. Parents should be educated to watch for residual fragments during treatment of infantile spasms. As a result of our experience with these patients, we now obtain video-EEG evaluations in all infants with undiagnosed serial or clustering episodes, however atypical the descriptions may be for infantile spasms. We also routinely perform follow-up video-EEGs during treatment of infantile spasm patients.
peared that
to
respond
we use
to the
same
3.
to treat
References New York, Raven Press,
1.
Lacy JR, Penry JK: Infantile Spasms. 1976, pp 9-17.
2.
Kellaway P, Hrachovy RA, Frost JD Jr, Zion T: Precise characterization and quantification of infantile spasms. Ann Neurol 1979;6:214-218.
4.
King DW, Dyken PR, Spinks IL Jr, Murvin AJ: Infantile spasms: Ictal phenomena. Pediatr Neurol 1985;1:213-218. Nolte R, Christen H-J, Doerrer J: Preliminary report of a multicenter study on the West syndrome. Brain Dev 1988;10:236-242.
5. Lombroso CT: A prospective study of infantile spasms: Clinical and therapeutic correlations. Epilepsia 1983;24:135-158. 6. Aicardi J: Epilepsy in Children. New York, Raven Press, 1986, International Review of Child Neurology Series, pp 17-38. 7. Westmoreland BF, Gomez MR: Infantile spasms (West syndrome), in Luders H, Lesser RP (eds): Epilepsy: Electroclinical Syndromes. New York, Springer-Verlag, 1987, pp 49-70. 8. Jeavons PM, Bower BD: Infantile Spasms. A Review of the Literature and a Study of 112 Cases. London, Spastics Society and Heinemann, 1964, Clinics in Developmental Medicine No. 15, pp 8-25. 9. Holmes GL: Diagnosis and Management of Seizures in Children. Philadelphia, WB Saunders, 1987, p 213. 10. Hrachovy RA, Frost JD Jr, Kellaway P: Hypsarrhythmia: Variations on the theme. Epilepsia 1984;25:317-325. 11. Snead OC III, Benton JW Jr, Hosey LC, et al: Treatment of infantile spasms with high-dose ACTH: Efficacy and plasma levels of ACTH and cortisol. Neurology 1989;39:1027-1031. 12. Bachman DS: Use of valproic acid in treatment of infantile spasms. Arch Neurol 1982;39:49-52. 13. Lo W, Donat J, Wright F: Apparent synergism between valproic acid and clonazepam in the treatment of infantile spasms. Ann Neurol 1989;26:470. 14. Donat J, Wright FS: Sleep, epilepsy, and the EEG in infancy
and
childhood.J Child Neurol 1989;4:84-94.
318
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F. Donat, MD; Francis S.
Wright,
MD
Abstract
During evaluation of video-electroencephalograms (EEGs) performed in our laboratory, we identified 11 patients who had unusual repetitive movements that appeared to be variants of infantile spasms. Movements included yawning, facial grimacing, eye movements, and transient focal motor activity. These symptoms coincided with generalized attenuation, slow-wave transients, or other EEG ictal changes characteristic of infantile spasms. The background EEGs showed true or modified hypsarrhythmia. This series of patients shows that infantile spasms may be extremely subtle and clinically atypical. Patients who have these variants may or may not also have typical infantile spasms. In some patients, the seizures appear to be time-related or medication-induced modifications of more typical infantile spasms. (J Child Neurol 1991;6:313-318).
usual clinical symptoms of infantile spasms have been well characterized in earlier studies by analysis of video-electroencephalographic (EEG) data. Typical infantile spasms involve abrupt flexion or extension movements of the extremities, trunk, and neck. Contractions of the facial
The
muscles, eye opening
or
closure, upward eye roll-
nystagmoid eye movements associated. 1-4 be Large series and review artimay cles concerning infantile spasm patients have mentioned that fragmentary variants of these seizures may occur in some infantile spasm patients. 1-3,5-7 Previous authors have emphasized that these seizures may be extremely subtle and may be missed during history taking and even during video-EEG evaluation, unless specifically looked for. 2,5,6 Infantile spasm fragments that have been documented include head nodding, shoulder shrugging, and abdominal contractions. 1-3 Infantile spasms characteristically occur in a series that crescendos and then decrescendos, and these fragmentary forms may oc2 cur at the onset and offset of the series.2 ing, eyelid fluttering,
or
Received Dec 18, 1990. Received revised April 9, 1991. Acfor publication April 10, 1991. From the Department of Pediatrics, Children’s Hospital, Ohio State University School of Medicine, Columbus, OH Presented in part in abstract form at the Child Neurology Society annual meeting, San Antonio, Texas, October 13, 1989 (Ann
cepted
Neurol 1989;26:470). Address correspondence to Dr J.F. Donat, Children’s Hospital, 700 Children’sDrive, Columbus, OH 43205.
Points that are important for the clinical diagnosis of infantile spasms but that have not been clarified in earlier reports include whether fragmentary forms occur in a series without typical infantile spasms and whether fragmentary forms occur as the only form of infantile spasms in some patients. Nodding spasms have been reported to occur in series. 1,8 Holmes stated that eye movements could occur independently from infantile spasms and precede the
of infantile spasms by weeks.9 Whether the occurrence of fragmentary forms has any usefulness in predicting prognosis or outcome of treatment has not been commented on previwho said that their sigously, except by Lombroso, nificance was uncertain.55 In this report, we describe fragmentary variants of infantile spasms that have not previously been reported, we describe their occurrence as series of seizures that did not include typical infantile spasms, and we describe their occurrence both in patients who did and who did not also have typical infantile spasms. We also discuss the physical similarities and differences between fragmentary and typical infantile spasms in patients who had both, recount when during the history of infantile spasms the variants were recorded, and describe how the variants in some patients appear to be modifications that result from the effects of time or treatment on typical infantile spasms.
development
313
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found in seven patients and no associated disorders identified in four patients (Table 1). Neurologic examination was normal in two patients and showed developmental delay in seven patients, spastic hemiparesis in one patient, and spastic quad-
Patients and Methods The 11 patients who had the infantile spasm
variants were all referred to the EEG laboratory because of possible seizures and had video-EEGs performed to document the seizure type before initiation of treatment. The 11 patients constitute 13% of all patients who had initial diagnoses of infantile spasms documented by video-EEGs performed during the 39-month period from March 1987 through May 1990. All EEGs were obtained on 21-channel Nihon-Kohden EEG machines with simultaneous time-locked videotape recording. Four patients had routine-length recordings (50 minutes). Three patients had 3- to 7-hour recordings. Four patients had routine-length recordings plus 24-hour remote
were
riparesis in one patient.
Electroencephalograms All 11 patients had their first video-EEG evaluations 2 days to 6 weeks after the onset of clinical seizures. Interictal EEGs showed hypsarrhythmia in eight patients (Figure 1) and modified hypsarrhythmia in three patients.l° Ictal EEGs in all patients consisted of a generalized decrement in cerebral activity. In some instances, this was preceded by an initial generalized sharp- or slow-wave transient (Figure 2) and/or accompanied by low-voltage &dquo;fast&dquo; activity. These findings were identical to EEG findings in patients who have typical infantile spasms .2,3
telemetry recordings (Telefactor, ConshoEight patients also had video-EEGs per-
video-EEG cable
hocken, PA).
two or more later dates to
follow-up response to of these eight patients had routine-length recordings, three of the eight had 3- to 6-hour recordings, and one patient had a routine-length recording plus a 24hour remote video-EEG cable telemetry recording. formed
on
treatment. Four
Patients were included who met the following criteria: the interictal EEG showed hypsarrhythmia or modified hypsarrhythmial°; the variants consisted of movements of very brief duration (similar to the duration of typical infantile spasms) that involved a limited body area or restricted group of muscles; the variants occurred alone in a series that did not include typical infantile spasms; and each seizure was associated with an ictal EEG change identical to the one that accompanies typical infantile spasms.2,3
Characteristics of the Infantile Spasm Variants Each of the variants occurred in a series that did not include typical infantile spasms. Each series consisted of at least three seizures, and each seizure in the series was separated by 5 to 30 seconds. The longest series lasted 6 minutes. Descriptions of the variants are included in Table 2.
Results Patients The 11 patients ranged in age from 3 to 9 months at the time of the EEG that showed the infantile spasm variants, with a mean age of 6 months. There were five girls and six boys. Symptomatic causes were TABLE 1 Timing and Outcome of Infantile _
,
-
-
-.
--
-
-
Infantile Spasm Variant Found on First EEG In seven patients, the infantile spasm variants
Spasm Variants --
-
.
~
-
V infantile spasm variants; T typical infantile spasms; N seizures resolved on medication. *EEG performed 1 day to 3 months after first EEG. tDetailed follow-up not available. tpatient 10 had two successive variants (see text). =
=
were
the first video-EEG evaluation, which present was obtained at the time of diagnosis of infantile spasms (Table 1). Three of these patients had no history of typical infantile spasms. Patient 1 died of a on
=
no
seizures recorded; R
314
Downloaded from jcn.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 21, 2015
’
..
=
FIGURE 1 EEG showed tient 3).
hypsarrhythmia
in
a
9-month-old
girl (pa-
brain disease a few weeks later. Patients 2 and 3 (Figure 3) were reported to be seizure free on adrenocorticotropic hormone (ACTH), but EEG and detailed clinical follow-up were not available. Patient 4 had a history of typical infantile spasms that spontaneously resolved 2 weeks before
degenerative
the time of the video-EEG evaluation that demonstrated the variants of upward eye rolling. Patient 5, whose variants consisted of elevation of one arm, had a contralateral porencephalic cyst on computed tomographic (CT) brain scan as a result of neonatal asphyxia. This patient later developed bilaterally symmetrical typical infantile spasms, which were recorded on video-EEG 3 weeks later. Patients 6 and 7 had typical infantile spasms, as well as the variants, present on the first EEG. Patient 6 had the variants (upward eye deviation) only in sleep; the variants appeared to be fragments of the typical infantile spasms that the patient had while awake. The variants found in patient 7 consisted of ocular adduction (Figure 4). It was uncertain whether these eye movements were present during the series of typical infantile spasms because the eyes were difficult to see during the whole body movements of the typical infantile spasms. Following treatment with clonazepam, this patient had only the variants present on a follow-up EEG 2 months later; this EEG also showed improvement in the hypsarrhythmia pattern to a multifocal spike-and-wave pattern. ACTH was then started and resulted in resolution of the seizures and of the epileptiform EEG pattern. The other three patients for whom clinical and EEG follow-up were available had resolution of the infantile spasm variants as well as the typical infantile spasms during treatment with ACTH (patient 4)11 or valproic acid (patients 5 and 6).12
FIGURE 2 Infantile spasm variants
(eye opening and upward eye deviation) in a 4-month-old girl (patient 2) were accompanied by ictal EEG changes that included generalized slow-wave transients followed by decrements. 315
Downloaded from jcn.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 21, 2015
TABLE 2 Infantile Spasm Variants in 11 Patients
*Eye
movements consisted of
movement,
or
burst of
upward or downward or adduction nystagmoid eye movements or eyelid flut-
ter.
tOne
patient tone patient
had upward eye rolling and facial grimace. had facial grimace and lateral head jerk.
Infantile Spasm Variant Found on Later EEG Four patients had typical infantile spasms present the first video-EEG evaluation and the variants present on video-EEGs performed 1 day (patient 9) or 1 to 3 months later (patients 8, 10, and 11) (Table 1). Patient 8 had both typical and variant infantile spasms present on the later EEG. In this patient, the variants, which consisted of a mouth opening or yawning movement, did not appear to be fragments of the patient’s typical flexor infantile spasms. The ictal EEG changes also differed: the typical infantile spasms were each associated with a generalized slow-wave transient, but the variants were each associated with a generalized
FIGURE 4 Adduction of the eyes was an infantile spasm variant in 5-month-old boy (patient 7).
a
on
FIGURE 3 Upward eye rolling was an infantile spasm variant in 9-month-old girl (patient 3).
a
decrement.
Both types of infantile spasms reincrease in dose of ACTH. Patient 9 sponded had the variants (facial grimace) but no longer had typical infantile spasms on a video-EEG performed for the purpose of a pyridoxine injection 1 day after the first EEG and after two doses of ACTH; the parents of this patient noted the grimace to be part of the generalized infantile spasms, which had disappeared. These episodes subsequently stopped. Patient 10, who had a neonatal cerebral infarct and asymmetrical hypsarrhythmia, had asymmetrical extensor infantile spasms that included a lateral head jerk and facial grimace on the first video-EEG. Variants that consisted of a lateral head jerk and grimace were recorded on video-EEG 1 month later, after treatment with valproic acid, and variants that consisted only of the grimace were recorded on video-EEG 2 weeks after that (Figure 5). At this time, clonazepam was added and the seizures stopped.l3 Patient 11 had resolution of hypsarrhythmia and typical infantile spasms documented on a video-EEG performed 1 month after beginning ACTH treatment. However, ACTH was stopped 6 weeks later because of side effects. Two weeks later, variants (eye opening) were recorded on videoEEG at a time when the EEG still showed no interictal epileptiform activity and the parents had noticed no seizures. Treatment with valproic acid was begun, but typical infantile spasms and hypsarrhythmia were again recorded on an EEG 2 months later. Clonazepam was added and the seizures resolved. to
an
316
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FIGURE 5 Facial grimace was one of two successive infantile spasm variants in a 9-month-old girl (patient 10).
Discussion In most of our patients, the infantile spasm variants appeared to be fragments or limited expressions of more typical infantile spasms. In some of these patients, the variants coexisted with typical infantile spasms and probably represented natural variability in physical expression of infantile spasms. However, in some patients, the variants may have resulted from a change in level of consciousness, time, or medication that modified the clinical expression of the infantile spasms. The effect of level of consciousness was seen in patient 6, who had typical infantile spasms in the waking state but had variants during sleep that consisted of only part of the typical infantile spasm. Time appeared to modify typical infantile spasms in patient 4, who, by history, had generalized infantile spasms that resolved spontaneously 2 weeks before our video-EEG demonstrated the variants, and by patient 5, who developed typical infantile spasms 3 weeks after the variants were recorded. These spontaneous changes suggest that the variants were a stage in the natural evolution of the infantile spasms. Of particular interest are the two patients whose variants appeared to be modifications that resulted from treatment of typical infantile spasms. Increasingly restricted variant forms were recorded in patient 10 on two occasions during treatment before the seizures ceased. In patient 11, the variants were recorded on a video-EEG that was obtained after ACTH given for typical infantile spasms was stopped because of side effects. This was at a time
when the parents thought the seizures were gone and before the interictal EEG showed a recurrence of the hypsarrhythmia pattern. These variants may have been an undetected residual type of infantile spasms that persisted after treatment with ACTH, or they may have heralded the recurrence of infantile spasms after ACTH was stopped. Patient 7 demonstrated a possible difference in therapeutic response between variants and typical infantile spasms: both types of infantile spasms initially coexisted, but only the variants persisted after treatment with clonazepam. The variants then resolved after treatment with ACTH. In other patients, the infantile spasm variants appeared to be separate types of infantile spasms that were not fragments of typical infantile spasms. In patient 8, the infantile spasm variants appeared to be a type of infantile spasms that was different both clinically and electrographically from the same patient’s typical infantile spasms, although both types responded to the same treatment. In patients 1, 2, and 3, the infantile spasm variants occurred with no previous or subsequent history of typical infantile spasms; unfortunately, due to death or lack of follow-up, video-EEG documentation of the subsequent course was not possible. Also, these patients were treated for infantile spasms after the videoEEGs demonstrated the seizures to be infantile spasm variants, and therefore the natural history was altered. The seizures in these patients were diagnostic dilemmas because the clinical descriptions of the seizures did not fit recognized seizure types. This series of patients demonstrates how extremely subtle and clinically atypical infantile spasm variants can be. It is reasonable to assume that the clinical significance of the variants is as great as that of typical infantile spasms.6 Failure to recognize or detect fragmentary variants may account for some of the patients reported to have hypsarrhythmia and electrodecremental episodes without clinical infantile spasms. 2,14 It can also result in underreporting of the number of infantile spasms in patients undergoing treatment, as cautioned by Kellaway et a1.2 In addition, our experience suggests that medications may modify typical infantile spasms into fragmentary variants and that failure to detect these seizures can result in the erroneous conclusion that seizures have stopped when they have only been modified by medication. Infantile spasm variants themselves do not appear to affect prognosis. However, their presence could result in a poorer outcome for infantile spasm patients because of failure to recognize and treat them. In our patients, the variants ap-
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group of medications infantile spasms, includtypical and ing ACTH, valproic acid, clonazepam, although in several patients, a different medication or increase in dose was necessary. We suggest that clinicians who diagnose and treat patients who have infantile spasms or who have EEGs that show hypsarrhythmia need to be aware of the wide variety and subtlety of variant infantile spasms. Parents should be educated to watch for residual fragments during treatment of infantile spasms. As a result of our experience with these patients, we now obtain video-EEG evaluations in all infants with undiagnosed serial or clustering episodes, however atypical the descriptions may be for infantile spasms. We also routinely perform follow-up video-EEGs during treatment of infantile spasm patients.
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