- Email: [email protected]
Focal and Multifocal Seizures
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Focal and Multifocal Seizures Douglas R. Nordli, Jr.
An expanded version of this chapter is available on www.expertconsult.com. See inside cover for registration details.
INTRODUCTION Focal seizures originate in one region of the brain, where they may stay confined or spread to other areas. Focal seizures were previously referred to as partial, but this term created confusion when translated into other languages, and the International League Against Epilepsy (ILAE) has recommended that it no longer be used. If a discrete area of eloquent cortex is involved, the first manifestation may be an aura—something that only the patient can describe. If the seizure propagates into bilaterally distributed networks, the patient will likely become unaware of subsequent phases of the seizure. In the past this was referred to as the complex phase of the seizure. Other terms, including dialeptic and dyscognitive, have been used to describe some alteration of awareness and cognition. The simple term unaware might also suffice. Further diffuse spread of the ictus can result in secondary generalization with manifestations that are nearly identical to those of a generalized tonic-clonic seizure. When only the last portion of the seizure is witnessed, it may be impossible to discern if the onset was focal or generalized unless the patient can recall early declarative features. Multifocal seizures arise from multiple locations and are not simply a composite of the individual focal seizures, but may be reflective of different underlying processes and therefore may respond differently to medications. Both focal and multifocal types have been underrecognized in children, but modern epidemiologic studies show that focal epilepsies account for about 60% of all seizure disorders (Berg et al., 1999). The behavioral manifestations of focal seizures relate not only to the region of the brain involved during the ictal discharge, but also to the maturation of the nervous system and the integrity of the pathways necessary for clinical expression.
TYPES OF FOCAL SEIZURES IN CHILDREN The ILAE Commission on Classification proposed a classification of seizures in 1981 (ILAE, 1981). This scheme was widely used for almost three decades and divided focal seizures into simple partial, complex partial, and partial with secondary generalization. Subsequently, another ILAE commission on classification proposed a substantial revision (Berg et al., 2010; Vendrame et al., 2011). In this revision, the term focal replaced the previous term partial, and the obligatory separation of partial seizures into simple, complex, and secondary generalized was discarded. This created some consternation, even though the committee proposed that descriptors, albeit slightly wordy, should still be used in the full characterization of seizures. In adolescents and adults who can communicate normally, it may be useful to subdivide seizures by alteration of awareness. In the ILAE 2010 document, examples of such descriptors were given, including “without impairment of consciousness or awareness,” “with impairment of consciousness or awareness,” and “evolving to bilateral convulsive seizure.” The
reader will note that these terms roughly equate to the older terminology delineating simple, complex, and secondary generalized seizures.
Alteration of Consciousness Classifications that emphasize alteration of consciousness have substantial limitations in pediatrics. It may be very difficult or even impossible to accurately determine alteration of consciousness in the preschool child, even when children have the ability to communicate normally (Nordli, Kuroda, & Hirsch, 2001). In preverbal infants it is all but impossible. Simply because a child does not appear to alert to verbal or visual cues does not necessarily imply alteration of consciousness. Well-known examples are the focal seizures seen in children with rolandic epilepsy. An eye-witness will commonly infer that consciousness was altered in some daytime events because the child did not respond normally, but when one interviews the child, one realizes that awareness was completely preserved throughout the entire event, and the inability to speak was secondary to a selective anarthria. If classification schemes using awareness as the first branch point are widely adopted, another category of “awareness uncertain” may be a convenient way to approach the seizures in younger patients or those with limited ability to communicate.
Semiologic Classification Schemes Lüders and colleagues (1998) developed a classification system for seizures that has been used in many major epilepsy centers in a wide variety of countries. Others have proposed a similarly simplified semiologic classification system for use in the very young (Nordli et al., 1997). Neither of these schemes has yet been endorsed by the ILAE. Although seizures may sometimes be broadly classified using the most prominent and early feature of the seizure, the various combinations of features, patterns, and time course of the seizure cannot be adequately summarized in a single word or phrase. Nothing can replace a thorough and meticulous description of the seizure. Indeed, the historic narrative of the seizure, as described or observed by parents, is the single most helpful piece of information allowing proper diagnosis of the seizure disorder and should be recorded, as accurately as possible, with few or no editorial comments. Still, certain features can be identified that increase the likelihood that a described event was a focal seizure, and these same features can be used to characterize the early and prominent features of the majority of pediatric focal seizures. This semiologic approach is simple, demonstrates good interobserver reliability (Nordli et al., 1997), and has a certain degree of sincerity in that it does not infer more than is possible from the clinical manifestations alone. The early manifestations are the most important because they are the closest to the source of the ictus and therefore provide the best localizing information. There is no doubt that the path the ictus takes may have a major influence on the degree of disability induced by
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the seizure and therefore is not trivial, but the clinical analysis of the complex patterns seen during ictal progression is complicated, and it is important to keep in mind that some features of seizures may not be the direct manifestation of electrical stimulation of the telencephalon, but may be a result of disinhibition of deeper structures or networks. This may be particularly important when evaluating the semiology of frontal lobe seizures. Tassinari and colleagues (2005) make the point that some automatic motor movements may originate from deep structures that are preprogrammed motor movements (central pattern generators), remarkably conserved across species. Recent imaging work has indeed
implicated deeper gray-matter and brainstem circuits in the generation of tonic postures, spasms, and atonia. Accordingly, clinical features alone cannot always allow one to correctly diagnose a focal seizure. Rather, “focal seizure” is actually an electroclinical diagnosis. It usually is made following consideration of multiple factors related to the patient and the clinical event, but may require electroencephalogram (EEG) confirmation, particularly in the very young. To summarize, experience using video EEG monitoring suggests that certain clinical features tend to have focal ictal EEG correlates (Figure 67-1), and these may be used as a way to categorize focal seizures in pediatrics, including the very young, although
Fp1–F7 F7–T3 T3–T5 T5–O1
150 µV 1 sec
Fp2–F8 F8–T4 T4–T6 T6–O2
A
Fp1–F7 F7–T3 T3–T5 T5–O1
500 µV 1 sec
Fp2–F8 F8–T4 T4–T6 T6–O2
B Fp1–F3 F3–C3 C3–P3 P3–O1
400 µV 2 sec
Fp2–F4 F4–C4 C4–P4 P4–O2
C Figure 67-1. Typical interictal findings on electroencephalogram (EEG) in children with focal seizures. A, This EEG from a child with benign rolandic epilepsy of childhood (BREC) shows focal stereotypic spikes appearing on a normal background. Notice that each spike closely resembles the others in morphology and location, as is typical of idiopathic localization-related epilepsies. B, By contrast, this EEG from a child with an epileptogenic focal structural lesion in the left temporal region demonstrates pleomorphic spikes and background slowing in the same region. C, EEGs from children with multifocal seizures often show multifocal interictal epileptiform discharges.
Focal and Multifocal Seizures TABLE 67-1 A Simple Semiologic Categorization of Pediatric Seizures Focal
Generalized Aura Autonomic
Clonic Myoclonic
Elementary motor
Focal clonic Focal myoclonic Focal tonic Versive
Tonic Tonic-clonic Epileptic spasms Myoclonic-atonic
Complex motor
Automotor Epileptic spasms with asymmetry Gelastic Hypermotor
Myoclonic-tonic Absence
Negative
Dialeptic/ dyscognitive Behavioral arrest/ hypomotor
Negative
Atypical absence Myoclonic absence Absence with eyelid myoclonia Atonic
confirmation sometimes requires electroencephalographic data (Table 67-1).
Auras Auras are special sensory or psychogenic phenomena that are perceived only by the patient. They occur in a variety of forms and have important localizing value. Although the concurrent ictal EEG often does not reveal clear electrographic expression in most patients, auras are believed by most authorities to be the manifestation of discrete focal seizures. When a somatosensory aura is specific and an ictal EEG correlate is present, the ictal discharge is often low-voltage fast activity localized over the corresponding region of the sensory homunculus. Other auras arising from limbic structures often are “indescribable,” or may have a fearful quality or include a feeling of epigastric discomfort. These discharges arise from subcortical structures, so the EEG may reveal little to no change, other than ipsilateral diffuse delta activity or a rhythmic theta-alpha pattern in the anterior to midtemporal region, particularly when the onset of activity is mesial temporal in location. Auras are supportive of the diagnosis of a focal seizure, especially when having certain clinical characteristics strongly localizing to a particular cortical area, although recent studies have reported the presence of auras in generalized seizures as well.
Autonomic Rarely, the only manifestation of a focal seizure is through the autonomic nervous system. Some examples include an increase in heart rate, oxygen desaturation, pallor, and piloerection in one region of the body.
Automotor Limb automatisms are semipurposeful movements, such as rubbing or fumbling of the hands, or picking at the air, that may be seen in focal seizures. Oral automatisms, such as lip smacking, can occur with generalized absence seizures, but unilateral limb automatisms suggest a focal process. Well-developed distal limb automatisms are rarely seen in infants but become more common above age 6 years. When
533
unilateral, automatisms are another helpful sign, indicating the presence of a focal seizure, and are typically seen ipsilateral to the epileptic focus in older children and adults. Most often automatisms are probably coupled with some alteration of cognition, but this is not invariably the case. In infants and young children rigorous assessment of cognition is sometimes impossible.
Behavioral Arrest or Hypomotor In some infants and young children, the most conspicuous feature of a focal seizure may be the sudden, abrupt cessation of ongoing activity or a marked change in demeanor, as indicated by subtle but distinct changes in facial expression. Parents easily identify these features because they represent a clear paroxysmal alteration in the child’s behavior. Parents are particularly well attuned to the nature of their child’s habitual behavior, but these behavioral changes may be challenging for a person unacquainted with the child to identify on videotape. In the preverbal child, and in many children with special needs, it is impossible to ascertain alteration of consciousness reliably. Alteration of consciousness cannot be unambiguously inferred from behavior (e.g., daydreaming in school). To assess consciousness accurately, test items must be given and recall tested after the seizure. In children, this often is not possible, so the simple description of a behavioral arrest is more reliably used, rather than trying to infer if the patient was unaware during the seizure. Behavioral arrest seizures also have been described as hypomotor seizures. This description refers to a sudden reduction in the motor activity of the child. The electrographic ictal accompaniment often emanates from the temporal lobe or posterior quadrant and may be composed of monotonous rhythmic delta or theta-alpha patterns with an electrographic “crescendo” appearance, or low-voltage fast discharges that subsequently evolve to other rhythms (Figure 67-2). In children above age 3 years, behavioral arrest may accompany both focal and generalized seizures (absence seizures), so in isolation it is not a reliable indicator of a focal seizure; however, because absence seizures rarely occur in children less than 2.5 years of age, it is likely to be the correlate of a focal seizure in this age group.
Clonus or Myoclonus—Focal Hand or arm clonus (clonic seizure) or myoclonus is another reliable feature of focal epilepsy. This activity is easily recognized as ictal by the repetitive nature of the jerking in the case of clonus or the sudden isolated jerk of myoclonus. Clonic seizures can sometimes be distinguished from jitteriness or tremor by the inability to suppress the motion by passive restraint. Clonus is usually accompanied by runs of rhythmic spike discharges in the contralateral rolandic region, and it is a reliable indicator of a focal seizure. The EEG correlate of myoclonias is most often spikes or spike-wave discharges in the contralateral hemisphere.
Dialeptic or Dyscognitive Dialeptic or dyscognitive seizures are those in which the main manifestation is an alteration of consciousness. The term dialeptic was coined as a purely descriptive one, without the need to infer whether the underlying EEG correlate was focal or generalized (Lüders et al., 1998). Another largely synonymous term is dyscognitive (Berg et al., 2010), but because there are many aspects to consciousness and cognition, one could argue that a simpler option would be simply to state that the patient was unaware. In the author’s personal experience,
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Fp1–F3 F3–C3 C3–P3 P3–O1 150 µV 1 sec Fp2–F4 F4–C4 C4–P4 P4–O2
A
Fp1–F3 F3–C3 C3–P3 P3–O1
200 µV 1 sec
Fp2–F4 F4–C4 C4–P4 P4–O2
B Fp1–F3 F3–C3 C3–P3 P3–O1
400 µV 2 sec
Fp2–F4 F4–C4 C4–P4 P4–O2
C Figure 67-2. Common infantile ictal patterns on electroencephalogram (EEG) in focal seizures. A, EEG during a behavioral arrest seizure shows an ictal discharge in the left temporal region. Notice the rhythmic buildup of fast activity. Ictal discharges usually have an evolution in frequency, amplitude, and spatial distribution (like a crescendo in music). B, During a clonic seizure involving the left arm, the EEG demonstrates an ictal correlate consisting of repetitive spikes in the right central region. Notice that the ictal discharge remains very localized. C, EEG obtained during a versive seizure with eyes deviating to the right, or the same side as for the ictal discharge, shows a fast ictal pattern superimposed on some rhythmic slowing in the right posterior head region.
it is rare to diagnose pure dialeptic seizures of focal origin in infants and young children. Because consciousness and ongoing cognition are very difficult to assess in the young and because children tend to be more active when awake, the most conspicuous manifestation of a focal seizure with dialeptic features often tends to be an arrest of movement (hypomotor). There are times, however, when there is a constellation of features, including subtle posture, brief body movements, and slight version, that makes it difficult to segregate the seizure into one simple category, and if consciousness can be verified to be abnormal, as is often the case with older children or adolescents, than the terms dialeptic or dyscognitive can be used.
Epileptic Spasms With Asymmetric Features Spasms can be recognized by their tendency to recur in clusters, many times in an almost periodic fashion, with a fairly constant interval between successive individual spasms. Spasms have a quick or myoclonic component at the start, followed by a brief sustained posture (tonic phase), followed in turn by a relaxation. Spasms that are asymmetric, that occur in a child with hemiparesis or other focal pathology, or that are associated with marked interhemispheric asymmetries on EEG could be considered to be a form of focal seizures in that they may have a focal telencephalic trigger. In about 25% of patients with spasms, clear electrographic focal seizures can be detected before, during, or after the cluster. The EEG accompaniment of spasms often contains diffuse electrodecrements, even if they are preceded by clear focal seizures.
Gelastic Gelastic seizures are rarely seen but important to recognize because of their association with hypothalamic hamartomas. They may also be seen with lesions in the frontal lobe. They are characterized by brief epochs of “mirthless” laughter and may have subtle surface EEG correlates.
Hypermotor Hypermotor seizures usually involve a complex series of large movements, resulting in a violent appearance of the event. Although they have been noted to arise from the mesial frontal supplementary sensorimotor area, or other regions of the frontal lobe in adults, they may also be seen in temporal lobe seizures in children. Temporal lobe seizures in very young infants may show prominent coarse motor manifestations, but these tend to decrease with advancing age (Ray and Kotagal, 2005).
Tonic Tonic postures, both symmetric and asymmetric, are seen with focal seizures. It is surprising to observe how often symmetric tonic postures can occur as a manifestation of a focal seizure in infants, and also how unreliable asymmetries of tonic postures can be in localizing ictal onsets. It is possible that these tonic postures are generated in deeper brainstem or subcortical structures and are not direct manifestations of the ictal discharges. This finding would explain why some asymmetric tonic postures can be reversed by passive turning of the head during a seizure, in a fashion similar to the tonic neck reflex elicited in the newborn. As the child matures, symmetric tonic
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postures are seen less frequently as a manifestation of a focal epilepsy. Instead, tonic postures become more asymmetric and show more lateralizing features.
Versive Pronounced and sustained lateral version of the eyes (as in a so-called versive seizure) is rarely encountered as an ictal manifestation in infants or young children. When present, version is another indicator of a focal seizure. In contrast with older children and adults, in whom the electrographic discharge often is best developed in the contralateral frontotemporal region, the ictal discharge in infants is more often in the ipsilateral occipital lobe.
Ontogeny of Focal Seizures The clinical expression of focal and multifocal seizures changes with age, in a more or less predictable fashion. Features that occur with more regularity with increasing age include aura, limb automatisms, dystonic posture, secondary generalization, and unresponsiveness. In contrast, the frequency of asymmetric clonus and symmetric tonic posturing decreases with age (Hamer et al., 1999; Acharya et al., 1997)
EVALUATION AND MANAGEMENT Although it is important to distinguish focal seizures from their generalized counterparts, this simple segregation is not sufficient to guide treatment. A broader understanding of the epilepsy syndrome, category of epilepsy, and etiology is even more important. A good example is Dravet syndrome. Infants with this condition will often have hemiconvulsive events early in their course, even though the EEG features may indicate a more multifocal process (Figure 67-3). If one focused only on the seizure type, one might correctly diagnose focal seizures and be tempted to select drugs that modulate the sodium channel (e.g., carbamazepine or phenytoin), but these medications may actually worsen the underlying sodium channel dysfunction causing the epilepsy and might very well make the patient worse. If a precise epilepsy syndrome cannot be established, it may be helpful to consider the development of the child and the interictal EEG. If the child is developing normally and the EEG background is normal, then in most circumstances the EEG spikes should be rather stereotyped. If all of this is true for the particular case, it is most likely that one is dealing either with a familial epilepsy or a self-limited epilepsy, such as rolandic epilepsy or Panayiotopoulos syndrome. If the child shows slowed development and the EEG background is slow, then a diffuse or multifocal encepha lopathy needs to be considered. In this case the spikes will usually be multifocal and pleomorphic. A wide variety of conditions may cause this presentation, including metabolic disorders (Chapter 76) and de novo mutations. If these circumstances broader-spectrum agents will usually be more effective. The reader is referred to Chapter 77 focusing on medication. Finally, if there is focal slowing, attenuation, or both, then a structural lesion needs to be considered. In this case there will often be focal pleomorphic spikes. Imaging should be obtained, and if multiple well-chosen medications have not helped, then a surgical evaluation should be considered (see Chapter 78).
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A
B Figure 67-3. Electroencephalogram (EEG) findings in Dravet syndrome in an infant. A, In the first year of life EEGs may be normal, although posterior spikes and polyspikes are sometimes seen, as in this child at 10 months. B, Later, generalized spike and polyspike-wave discharges are noted. This is the same child 2 years later.
REFERENCES The complete list of references for this chapter is available in the e-book at www.expertconsult.com. See inside cover for registration details. SELECTED REFERENCES Acharya, J.N., Wyllie, E., Lüders, H.O., et al., 1997. Seizure symptomatology in infants with localization-related epilepsy. Neurology 48, 189. Berg, A.T., Berkovic, S.F., Brodie, M.J., et al., 2010. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005– 2009. Epilepsia 51 (4), 676–685. Berg, A.T., Shinnar, S., Levy, S.R., et al., 1999. Newly diagnosed epilepsy in children: presentation at diagnosis. Epilepsia 40, 445. Hamer, H.M., Wyllie, E., Lüders, H.O., et al., 1999. Symptomatology of epileptic seizures in the first three years of life. Epilepsia 40, 837. International League against Epilepsy, 1981. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 22, 489. Lüders, H., Acharya, J., Baumgartner, C., et al., 1998. Semiological Seizure Classification. Epilepsia 39, 1006. Nordli, D.R., Kuroda, M.M., Hirsch, L.J., 2001. The ontogeny of partial seizures in infants and young children. Epilepsia 42, 986. Nordli, D.R. Jr., Bazil, C.W., Scheuer, M.L., et al., 1997. Recognition and classification of seizures in infants. Epilepsia 38 (5), 553. Ray, A., Kotagal, P., 2005. Temporal lobe epilepsy in children: overview of clinical semiology. Epileptic Disord. 7 (4), 299–307.
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Tassinari, C.A., Rubboli, G., Gardella, E., et al., 2005. Central pattern generators for a common semiology in fronto-limbic seizures and in parasomnias. A neuroethologic approach. Neurol. Sci. 26 (Suppl. 3), s225–s232. [Epub 2005/12/07]. Vendrame, M., Zarowski, M., Alexopoulos, A.V., et al., 2011. Localization of pediatric seizure semiology. Clin. Neurophysiol. 122, 1924.
E-BOOK FIGURES AND TABLES The following figures and tables are available in the e-book at www.expertconsult.com. See inside cover for registration details. Fig. 67-4 This EEG shows the highly stereotyped epileptiform discharges seen in a 3-year-old child with Panayiotopoulos syndrome. Fig. 67-5 Magnetic resonance image showing left mesial temporal sclerosis in an 8-year-old girl. Box 67-1 Seizure Semiology Indicating a Focal Seizure Box 67-2 International Classification of Seizures Box 67-3 Further Descriptions of Focal Seizures Box 67-4 Electroclinical Syndromes Categorized by Age at Onset (Eponyms Traditionally Associated with Syndromes Are Provided When Appropriate) Table 67-2 A Categorization of the Epilepsies Based Upon Prominent EEG Characteristics Table 67-3 Practical Guide to Antiseizure Medicines
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Focal and Multifocal Seizures Douglas R. Nordli, Jr.
An expanded version of this chapter is available on www.expertconsult.com. See inside cover for registration details.
INTRODUCTION Focal seizures originate in one region of the brain, where they may stay confined or spread to other areas. Focal seizures were previously referred to as partial, but this term created confusion when translated into other languages, and the International League Against Epilepsy (ILAE) has recommended that it no longer be used. If a discrete area of eloquent cortex is involved, the first manifestation may be an aura—something that only the patient can describe. If the seizure propagates into bilaterally distributed networks, the patient will likely become unaware of subsequent phases of the seizure. In the past this was referred to as the complex phase of the seizure. Other terms, including dialeptic and dyscognitive, have been used to describe some alteration of awareness and cognition. The simple term unaware might also suffice. Further diffuse spread of the ictus can result in secondary generalization with manifestations that are nearly identical to those of a generalized tonic-clonic seizure. When only the last portion of the seizure is witnessed, it may be impossible to discern if the onset was focal or generalized unless the patient can recall early declarative features. Multifocal seizures arise from multiple locations and are not simply a composite of the individual focal seizures, but may be reflective of different underlying processes and therefore may respond differently to medications. Both focal and multifocal types have been underrecognized in children, but modern epidemiologic studies show that focal epilepsies account for about 60% of all seizure disorders (Berg et al., 1999). The behavioral manifestations of focal seizures relate not only to the region of the brain involved during the ictal discharge, but also to the maturation of the nervous system and the integrity of the pathways necessary for clinical expression.
TYPES OF FOCAL SEIZURES IN CHILDREN The ILAE Commission on Classification proposed a classification of seizures in 1981 (ILAE, 1981). This scheme was widely used for almost three decades and divided focal seizures into simple partial, complex partial, and partial with secondary generalization. Subsequently, another ILAE commission on classification proposed a substantial revision (Berg et al., 2010; Vendrame et al., 2011). In this revision, the term focal replaced the previous term partial, and the obligatory separation of partial seizures into simple, complex, and secondary generalized was discarded. This created some consternation, even though the committee proposed that descriptors, albeit slightly wordy, should still be used in the full characterization of seizures. In adolescents and adults who can communicate normally, it may be useful to subdivide seizures by alteration of awareness. In the ILAE 2010 document, examples of such descriptors were given, including “without impairment of consciousness or awareness,” “with impairment of consciousness or awareness,” and “evolving to bilateral convulsive seizure.” The
reader will note that these terms roughly equate to the older terminology delineating simple, complex, and secondary generalized seizures.
Alteration of Consciousness Classifications that emphasize alteration of consciousness have substantial limitations in pediatrics. It may be very difficult or even impossible to accurately determine alteration of consciousness in the preschool child, even when children have the ability to communicate normally (Nordli, Kuroda, & Hirsch, 2001). In preverbal infants it is all but impossible. Simply because a child does not appear to alert to verbal or visual cues does not necessarily imply alteration of consciousness. Well-known examples are the focal seizures seen in children with rolandic epilepsy. An eye-witness will commonly infer that consciousness was altered in some daytime events because the child did not respond normally, but when one interviews the child, one realizes that awareness was completely preserved throughout the entire event, and the inability to speak was secondary to a selective anarthria. If classification schemes using awareness as the first branch point are widely adopted, another category of “awareness uncertain” may be a convenient way to approach the seizures in younger patients or those with limited ability to communicate.
Semiologic Classification Schemes Lüders and colleagues (1998) developed a classification system for seizures that has been used in many major epilepsy centers in a wide variety of countries. Others have proposed a similarly simplified semiologic classification system for use in the very young (Nordli et al., 1997). Neither of these schemes has yet been endorsed by the ILAE. Although seizures may sometimes be broadly classified using the most prominent and early feature of the seizure, the various combinations of features, patterns, and time course of the seizure cannot be adequately summarized in a single word or phrase. Nothing can replace a thorough and meticulous description of the seizure. Indeed, the historic narrative of the seizure, as described or observed by parents, is the single most helpful piece of information allowing proper diagnosis of the seizure disorder and should be recorded, as accurately as possible, with few or no editorial comments. Still, certain features can be identified that increase the likelihood that a described event was a focal seizure, and these same features can be used to characterize the early and prominent features of the majority of pediatric focal seizures. This semiologic approach is simple, demonstrates good interobserver reliability (Nordli et al., 1997), and has a certain degree of sincerity in that it does not infer more than is possible from the clinical manifestations alone. The early manifestations are the most important because they are the closest to the source of the ictus and therefore provide the best localizing information. There is no doubt that the path the ictus takes may have a major influence on the degree of disability induced by
531
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the seizure and therefore is not trivial, but the clinical analysis of the complex patterns seen during ictal progression is complicated, and it is important to keep in mind that some features of seizures may not be the direct manifestation of electrical stimulation of the telencephalon, but may be a result of disinhibition of deeper structures or networks. This may be particularly important when evaluating the semiology of frontal lobe seizures. Tassinari and colleagues (2005) make the point that some automatic motor movements may originate from deep structures that are preprogrammed motor movements (central pattern generators), remarkably conserved across species. Recent imaging work has indeed
implicated deeper gray-matter and brainstem circuits in the generation of tonic postures, spasms, and atonia. Accordingly, clinical features alone cannot always allow one to correctly diagnose a focal seizure. Rather, “focal seizure” is actually an electroclinical diagnosis. It usually is made following consideration of multiple factors related to the patient and the clinical event, but may require electroencephalogram (EEG) confirmation, particularly in the very young. To summarize, experience using video EEG monitoring suggests that certain clinical features tend to have focal ictal EEG correlates (Figure 67-1), and these may be used as a way to categorize focal seizures in pediatrics, including the very young, although
Fp1–F7 F7–T3 T3–T5 T5–O1
150 µV 1 sec
Fp2–F8 F8–T4 T4–T6 T6–O2
A
Fp1–F7 F7–T3 T3–T5 T5–O1
500 µV 1 sec
Fp2–F8 F8–T4 T4–T6 T6–O2
B Fp1–F3 F3–C3 C3–P3 P3–O1
400 µV 2 sec
Fp2–F4 F4–C4 C4–P4 P4–O2
C Figure 67-1. Typical interictal findings on electroencephalogram (EEG) in children with focal seizures. A, This EEG from a child with benign rolandic epilepsy of childhood (BREC) shows focal stereotypic spikes appearing on a normal background. Notice that each spike closely resembles the others in morphology and location, as is typical of idiopathic localization-related epilepsies. B, By contrast, this EEG from a child with an epileptogenic focal structural lesion in the left temporal region demonstrates pleomorphic spikes and background slowing in the same region. C, EEGs from children with multifocal seizures often show multifocal interictal epileptiform discharges.
Focal and Multifocal Seizures TABLE 67-1 A Simple Semiologic Categorization of Pediatric Seizures Focal
Generalized Aura Autonomic
Clonic Myoclonic
Elementary motor
Focal clonic Focal myoclonic Focal tonic Versive
Tonic Tonic-clonic Epileptic spasms Myoclonic-atonic
Complex motor
Automotor Epileptic spasms with asymmetry Gelastic Hypermotor
Myoclonic-tonic Absence
Negative
Dialeptic/ dyscognitive Behavioral arrest/ hypomotor
Negative
Atypical absence Myoclonic absence Absence with eyelid myoclonia Atonic
confirmation sometimes requires electroencephalographic data (Table 67-1).
Auras Auras are special sensory or psychogenic phenomena that are perceived only by the patient. They occur in a variety of forms and have important localizing value. Although the concurrent ictal EEG often does not reveal clear electrographic expression in most patients, auras are believed by most authorities to be the manifestation of discrete focal seizures. When a somatosensory aura is specific and an ictal EEG correlate is present, the ictal discharge is often low-voltage fast activity localized over the corresponding region of the sensory homunculus. Other auras arising from limbic structures often are “indescribable,” or may have a fearful quality or include a feeling of epigastric discomfort. These discharges arise from subcortical structures, so the EEG may reveal little to no change, other than ipsilateral diffuse delta activity or a rhythmic theta-alpha pattern in the anterior to midtemporal region, particularly when the onset of activity is mesial temporal in location. Auras are supportive of the diagnosis of a focal seizure, especially when having certain clinical characteristics strongly localizing to a particular cortical area, although recent studies have reported the presence of auras in generalized seizures as well.
Autonomic Rarely, the only manifestation of a focal seizure is through the autonomic nervous system. Some examples include an increase in heart rate, oxygen desaturation, pallor, and piloerection in one region of the body.
Automotor Limb automatisms are semipurposeful movements, such as rubbing or fumbling of the hands, or picking at the air, that may be seen in focal seizures. Oral automatisms, such as lip smacking, can occur with generalized absence seizures, but unilateral limb automatisms suggest a focal process. Well-developed distal limb automatisms are rarely seen in infants but become more common above age 6 years. When
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unilateral, automatisms are another helpful sign, indicating the presence of a focal seizure, and are typically seen ipsilateral to the epileptic focus in older children and adults. Most often automatisms are probably coupled with some alteration of cognition, but this is not invariably the case. In infants and young children rigorous assessment of cognition is sometimes impossible.
Behavioral Arrest or Hypomotor In some infants and young children, the most conspicuous feature of a focal seizure may be the sudden, abrupt cessation of ongoing activity or a marked change in demeanor, as indicated by subtle but distinct changes in facial expression. Parents easily identify these features because they represent a clear paroxysmal alteration in the child’s behavior. Parents are particularly well attuned to the nature of their child’s habitual behavior, but these behavioral changes may be challenging for a person unacquainted with the child to identify on videotape. In the preverbal child, and in many children with special needs, it is impossible to ascertain alteration of consciousness reliably. Alteration of consciousness cannot be unambiguously inferred from behavior (e.g., daydreaming in school). To assess consciousness accurately, test items must be given and recall tested after the seizure. In children, this often is not possible, so the simple description of a behavioral arrest is more reliably used, rather than trying to infer if the patient was unaware during the seizure. Behavioral arrest seizures also have been described as hypomotor seizures. This description refers to a sudden reduction in the motor activity of the child. The electrographic ictal accompaniment often emanates from the temporal lobe or posterior quadrant and may be composed of monotonous rhythmic delta or theta-alpha patterns with an electrographic “crescendo” appearance, or low-voltage fast discharges that subsequently evolve to other rhythms (Figure 67-2). In children above age 3 years, behavioral arrest may accompany both focal and generalized seizures (absence seizures), so in isolation it is not a reliable indicator of a focal seizure; however, because absence seizures rarely occur in children less than 2.5 years of age, it is likely to be the correlate of a focal seizure in this age group.
Clonus or Myoclonus—Focal Hand or arm clonus (clonic seizure) or myoclonus is another reliable feature of focal epilepsy. This activity is easily recognized as ictal by the repetitive nature of the jerking in the case of clonus or the sudden isolated jerk of myoclonus. Clonic seizures can sometimes be distinguished from jitteriness or tremor by the inability to suppress the motion by passive restraint. Clonus is usually accompanied by runs of rhythmic spike discharges in the contralateral rolandic region, and it is a reliable indicator of a focal seizure. The EEG correlate of myoclonias is most often spikes or spike-wave discharges in the contralateral hemisphere.
Dialeptic or Dyscognitive Dialeptic or dyscognitive seizures are those in which the main manifestation is an alteration of consciousness. The term dialeptic was coined as a purely descriptive one, without the need to infer whether the underlying EEG correlate was focal or generalized (Lüders et al., 1998). Another largely synonymous term is dyscognitive (Berg et al., 2010), but because there are many aspects to consciousness and cognition, one could argue that a simpler option would be simply to state that the patient was unaware. In the author’s personal experience,
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Fp1–F3 F3–C3 C3–P3 P3–O1 150 µV 1 sec Fp2–F4 F4–C4 C4–P4 P4–O2
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B Fp1–F3 F3–C3 C3–P3 P3–O1
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C Figure 67-2. Common infantile ictal patterns on electroencephalogram (EEG) in focal seizures. A, EEG during a behavioral arrest seizure shows an ictal discharge in the left temporal region. Notice the rhythmic buildup of fast activity. Ictal discharges usually have an evolution in frequency, amplitude, and spatial distribution (like a crescendo in music). B, During a clonic seizure involving the left arm, the EEG demonstrates an ictal correlate consisting of repetitive spikes in the right central region. Notice that the ictal discharge remains very localized. C, EEG obtained during a versive seizure with eyes deviating to the right, or the same side as for the ictal discharge, shows a fast ictal pattern superimposed on some rhythmic slowing in the right posterior head region.
it is rare to diagnose pure dialeptic seizures of focal origin in infants and young children. Because consciousness and ongoing cognition are very difficult to assess in the young and because children tend to be more active when awake, the most conspicuous manifestation of a focal seizure with dialeptic features often tends to be an arrest of movement (hypomotor). There are times, however, when there is a constellation of features, including subtle posture, brief body movements, and slight version, that makes it difficult to segregate the seizure into one simple category, and if consciousness can be verified to be abnormal, as is often the case with older children or adolescents, than the terms dialeptic or dyscognitive can be used.
Epileptic Spasms With Asymmetric Features Spasms can be recognized by their tendency to recur in clusters, many times in an almost periodic fashion, with a fairly constant interval between successive individual spasms. Spasms have a quick or myoclonic component at the start, followed by a brief sustained posture (tonic phase), followed in turn by a relaxation. Spasms that are asymmetric, that occur in a child with hemiparesis or other focal pathology, or that are associated with marked interhemispheric asymmetries on EEG could be considered to be a form of focal seizures in that they may have a focal telencephalic trigger. In about 25% of patients with spasms, clear electrographic focal seizures can be detected before, during, or after the cluster. The EEG accompaniment of spasms often contains diffuse electrodecrements, even if they are preceded by clear focal seizures.
Gelastic Gelastic seizures are rarely seen but important to recognize because of their association with hypothalamic hamartomas. They may also be seen with lesions in the frontal lobe. They are characterized by brief epochs of “mirthless” laughter and may have subtle surface EEG correlates.
Hypermotor Hypermotor seizures usually involve a complex series of large movements, resulting in a violent appearance of the event. Although they have been noted to arise from the mesial frontal supplementary sensorimotor area, or other regions of the frontal lobe in adults, they may also be seen in temporal lobe seizures in children. Temporal lobe seizures in very young infants may show prominent coarse motor manifestations, but these tend to decrease with advancing age (Ray and Kotagal, 2005).
Tonic Tonic postures, both symmetric and asymmetric, are seen with focal seizures. It is surprising to observe how often symmetric tonic postures can occur as a manifestation of a focal seizure in infants, and also how unreliable asymmetries of tonic postures can be in localizing ictal onsets. It is possible that these tonic postures are generated in deeper brainstem or subcortical structures and are not direct manifestations of the ictal discharges. This finding would explain why some asymmetric tonic postures can be reversed by passive turning of the head during a seizure, in a fashion similar to the tonic neck reflex elicited in the newborn. As the child matures, symmetric tonic
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postures are seen less frequently as a manifestation of a focal epilepsy. Instead, tonic postures become more asymmetric and show more lateralizing features.
Versive Pronounced and sustained lateral version of the eyes (as in a so-called versive seizure) is rarely encountered as an ictal manifestation in infants or young children. When present, version is another indicator of a focal seizure. In contrast with older children and adults, in whom the electrographic discharge often is best developed in the contralateral frontotemporal region, the ictal discharge in infants is more often in the ipsilateral occipital lobe.
Ontogeny of Focal Seizures The clinical expression of focal and multifocal seizures changes with age, in a more or less predictable fashion. Features that occur with more regularity with increasing age include aura, limb automatisms, dystonic posture, secondary generalization, and unresponsiveness. In contrast, the frequency of asymmetric clonus and symmetric tonic posturing decreases with age (Hamer et al., 1999; Acharya et al., 1997)
EVALUATION AND MANAGEMENT Although it is important to distinguish focal seizures from their generalized counterparts, this simple segregation is not sufficient to guide treatment. A broader understanding of the epilepsy syndrome, category of epilepsy, and etiology is even more important. A good example is Dravet syndrome. Infants with this condition will often have hemiconvulsive events early in their course, even though the EEG features may indicate a more multifocal process (Figure 67-3). If one focused only on the seizure type, one might correctly diagnose focal seizures and be tempted to select drugs that modulate the sodium channel (e.g., carbamazepine or phenytoin), but these medications may actually worsen the underlying sodium channel dysfunction causing the epilepsy and might very well make the patient worse. If a precise epilepsy syndrome cannot be established, it may be helpful to consider the development of the child and the interictal EEG. If the child is developing normally and the EEG background is normal, then in most circumstances the EEG spikes should be rather stereotyped. If all of this is true for the particular case, it is most likely that one is dealing either with a familial epilepsy or a self-limited epilepsy, such as rolandic epilepsy or Panayiotopoulos syndrome. If the child shows slowed development and the EEG background is slow, then a diffuse or multifocal encepha lopathy needs to be considered. In this case the spikes will usually be multifocal and pleomorphic. A wide variety of conditions may cause this presentation, including metabolic disorders (Chapter 76) and de novo mutations. If these circumstances broader-spectrum agents will usually be more effective. The reader is referred to Chapter 77 focusing on medication. Finally, if there is focal slowing, attenuation, or both, then a structural lesion needs to be considered. In this case there will often be focal pleomorphic spikes. Imaging should be obtained, and if multiple well-chosen medications have not helped, then a surgical evaluation should be considered (see Chapter 78).
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A
B Figure 67-3. Electroencephalogram (EEG) findings in Dravet syndrome in an infant. A, In the first year of life EEGs may be normal, although posterior spikes and polyspikes are sometimes seen, as in this child at 10 months. B, Later, generalized spike and polyspike-wave discharges are noted. This is the same child 2 years later.
REFERENCES The complete list of references for this chapter is available in the e-book at www.expertconsult.com. See inside cover for registration details. SELECTED REFERENCES Acharya, J.N., Wyllie, E., Lüders, H.O., et al., 1997. Seizure symptomatology in infants with localization-related epilepsy. Neurology 48, 189. Berg, A.T., Berkovic, S.F., Brodie, M.J., et al., 2010. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005– 2009. Epilepsia 51 (4), 676–685. Berg, A.T., Shinnar, S., Levy, S.R., et al., 1999. Newly diagnosed epilepsy in children: presentation at diagnosis. Epilepsia 40, 445. Hamer, H.M., Wyllie, E., Lüders, H.O., et al., 1999. Symptomatology of epileptic seizures in the first three years of life. Epilepsia 40, 837. International League against Epilepsy, 1981. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 22, 489. Lüders, H., Acharya, J., Baumgartner, C., et al., 1998. Semiological Seizure Classification. Epilepsia 39, 1006. Nordli, D.R., Kuroda, M.M., Hirsch, L.J., 2001. The ontogeny of partial seizures in infants and young children. Epilepsia 42, 986. Nordli, D.R. Jr., Bazil, C.W., Scheuer, M.L., et al., 1997. Recognition and classification of seizures in infants. Epilepsia 38 (5), 553. Ray, A., Kotagal, P., 2005. Temporal lobe epilepsy in children: overview of clinical semiology. Epileptic Disord. 7 (4), 299–307.
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Tassinari, C.A., Rubboli, G., Gardella, E., et al., 2005. Central pattern generators for a common semiology in fronto-limbic seizures and in parasomnias. A neuroethologic approach. Neurol. Sci. 26 (Suppl. 3), s225–s232. [Epub 2005/12/07]. Vendrame, M., Zarowski, M., Alexopoulos, A.V., et al., 2011. Localization of pediatric seizure semiology. Clin. Neurophysiol. 122, 1924.
E-BOOK FIGURES AND TABLES The following figures and tables are available in the e-book at www.expertconsult.com. See inside cover for registration details. Fig. 67-4 This EEG shows the highly stereotyped epileptiform discharges seen in a 3-year-old child with Panayiotopoulos syndrome. Fig. 67-5 Magnetic resonance image showing left mesial temporal sclerosis in an 8-year-old girl. Box 67-1 Seizure Semiology Indicating a Focal Seizure Box 67-2 International Classification of Seizures Box 67-3 Further Descriptions of Focal Seizures Box 67-4 Electroclinical Syndromes Categorized by Age at Onset (Eponyms Traditionally Associated with Syndromes Are Provided When Appropriate) Table 67-2 A Categorization of the Epilepsies Based Upon Prominent EEG Characteristics Table 67-3 Practical Guide to Antiseizure Medicines
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