Epileptic Encephalopathies: An Overview Sonia Khan 1 ,* and Raidah Al Baradie 2 Epilepsy Res Treat. 2012; 2012: 403592. Published online 2012 November 20. doi: 10.1155/2012/403592 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508533/ Epileptic encephalopathies are an epileptic condition characterized by epileptiform abnormalities associated with progressive cerebral dysfunction. In the classification of the International League Against Epilepsy eight age-related epileptic encephalopathy syndromes are recognized. These syndromes include early myoclonic encephalopathy and Ohtahara syndrome in the neonatal period, West syndrome and Dravet syndrome in infancy, myoclonic status in nonprogressive encephalopathies, and Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and epilepsy with continuous spike waves during slow wave sleep in childhood and adolescences. Other epileptic syndromes such as migrating partial seizures in infancy and severe epilepsy with multiple independent spike foci may be reasonably added. In this paper, we provide an overview of epileptic encephalopathies including clinical neurophysiological features, cognitive deterioration, and management options especially that these conditions are generally refractory to standard antiepileptic drugs. Epileptic encephalopathy is defined as a condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function, but this definition may be ambiguous [1 ]. The report of the International League Against Epilepsy (ILAE) Task Force on classification and terminology includes 8 syndromes under epileptic encephalopathies: early myoclonic encephalopathy, Ohtahara
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Epileptic Encephalopathies: An OverviewSonia Khan 1 ,* and Raidah Al Baradie 2
Epilepsy Res Treat. 2012; 2012: 403592.
Published online 2012 November 20. doi: 10.1155/2012/403592
Epileptic encephalopathies are an epileptic condition characterized by
epileptiform abnormalities associated with progressive cerebral
dysfunction. In the classification of the International League Against
Epilepsy eight age-related epileptic encephalopathy syndromes are
recognized. These syndromes include early myoclonic encephalopathy and
Ohtahara syndrome in the neonatal period, West syndrome and Dravet
syndrome in infancy, myoclonic status in nonprogressive encephalopathies,
and Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and epilepsy
with continuous spike waves during slow wave sleep in childhood and
adolescences. Other epileptic syndromes such as migrating partial seizures
in infancy and severe epilepsy with multiple independent spike foci may be
reasonably added. In this paper, we provide an overview of epileptic
encephalopathies including clinical neurophysiological features, cognitive
deterioration, and management options especially that these conditions
are generally refractory to standard antiepileptic drugs.
Epileptic encephalopathy is defined as a condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function, but this definition may be ambiguous [1]. The report of the International League Against Epilepsy (ILAE) Task Force on classification and terminology includes 8 syndromes under epileptic encephalopathies: early myoclonic encephalopathy, Ohtahara syndrome, West syndrome, Dravet syndrome, myoclonic status in nonprogressive encephalopathies, Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and epilepsy with continuous spike waves during slow-wave sleep [1]. To these syndromes, the migrating partial seizures in infancy and severe epilepsy with multiple independent spike foci may be reasonably added [2].
A common feature is that these disorders are usually refractory to standard antiepileptic drugs (AEDs) [3]. As a result, more aggressive use of AEDs considered effective in suppressing interictal epileptiform discharges (e.g., benzodiazepines, valproic acid, and lamotrigine), immunomodulatory therapies (e.g., corticosteroids, intravenous immunoglobulin (IVIG), and plasmapheresis), ketogenic diet, and surgical options is often considered [3]. In this paper, epileptic encephalopathies will be dealt with in the following concept: a particular group of usually age-related and extremely intractable epilepsies with characteristic generalized minor seizures and massive epileptic EEG abnormalities, both of which cause stagnation or deterioration in mental and cognitive functions in addition to the preexisting developmental deficit due to organic brain damage [1–3].
Early Infantile Epileptic Encephalopathy (Ohtahara Syndrome)
Ohtahara syndrome is the earliest form of the age-dependent neonatal epileptic encephalopathies and was first described by Ohtahara and colleagues in 1976 [4]. It is often defined as “Early Infantile Epileptic Encephalopathy (EIEE) with burst-suppression” or “early myoclonic encephalopathy (EME)” [4]. Symptoms appear within the first 3 months of birth and usually within the first 10 days. Often symptoms will appear with the first few hours after birth, and in some cases mothers have felt possible seizures activity in utero. Onset is acute in previously normal children [4]. Main seizure pattern is tonic spasms; other patterns include tonic/clonic, clonic, myoclonic, atonic, absences, partial, complex partial (with or without secondary generalization), gelastics, and Jacksonians. Seizures can appear in clusters or singly and patterns are likely to change with time. It is not uncommon for patterns to reappear at a later stage [4]. EEG pattern is characterized as burst suppression during both waking and sleeping states. This means that the EEG (electroencephalogram) tends to show periods of very little electrical brain activity followed by a burst of high spiky activity before returning to very low activity again. Sometimes, one side of the brain seems to be affected more than the other [5]. Seizures are intractable; although in some cases they can be improved through treatment. In general prognosis is poor with severe psychomotor retardation and significant learning difficulties. Frequently cases will progress to West syndrome or partial epilepsy (usually during infancy). Later a much smaller number develops to Lennox-Gastaut syndrome. Psychomotor development may be slightly better if the infants do not develop West or Lennox-Gastaut syndrome. Half of the children are likely
to die in infancy or childhood [5, 6]. Although the disorder in incurable, much can be done to improve the lives not only of the children but also of the families. Seizure control is the main aim and will be attempted either through optimized dosages of anticonvulsants such as vigabatrin (Topamax), Dilantin, Zonegran, and Phenobarbitone, or through steroid therapies using ACTH and Prednisone. AEDs can be taken in either mono- or polytherapies. The quest for seizure control can be a slow and frustrating process. There is also the possibility of utilizing such treatments as the ketogenic diet, the VNS, or more invasive surgery, such as a partial resection or complete hemispherectomy. Physiotherapy and occupational therapies can help improve motor skills, while hippotherapy can help improve general mobility, strength, and endurance [7].
Lennox-Gastaut Syndrome LGS
Childhood epileptic encephalopathy, or Lennox-Gastaut syndrome (LGS), is a devastating pediatric epilepsy syndrome constituting 1–4% of childhood epilepsies. The syndrome is characterized by multiple seizure types; mental retardation or regression; abnormal findings on electroencephalogram (EEG), with paroxysms of fast activity and generalized slow spike and wave discharges (1.5–2 Hz) (Figure 4). The most common seizure types are tonic-axial, atonic, and absence seizures, but myoclonic, generalized tonic-clonic, and partial seizures can be observed (see clinical presentation). An EEG is an essential part of the workup for LGS. Neuroimaging is an important part of the search for an underlying etiology. LGS can be classified according to its suspected etiology as either idiopathic or symptomatic. Patients may be considered to have idiopathic LGS if normal psychomotor development occurred prior to the onset of symptoms, no underlying disorders or definite presumptive causes are present, and no neurologic or neuroradiologic abnormalities are found. In contrast, symptomatic LGS is diagnosed if a likely cause can be identified as being responsible for the syndrome. Population-based studies have found that 70–78% of patients with LGS have symptomatic LGS. Underlying pathologies in these cases include encephalitis and/or meningitis, tuberous sclerosis, brain malformations (e.g., cortical dysplasias), birth injury, hypoxia-ischemia injury, frontal lobe lesions and trauma. Overall, LGS accounts for 1–4% of patients with childhood epilepsy but 10% of patients with onset of epilepsy when younger than 5 years. The prevalence of LGS in Atlanta, GA, USA, was reported as 0.26 per 1000 live births. LGS is more common in boys than in girls. The
prevalence is 0.1 per 1000 population for boys, versus 0.02 per 1000 population for girls (relative risk, 5.31). The mean age at epilepsy onset is 26–28 months (range, 1 d to 14 y). The peak age at epilepsy onset is older in patients with LGS of an identifiable etiology than in those whose LGS has no identifiable etiology. The difference in age of onset between the group of patients with LGS and a history of West syndrome (infantile spasm) and those with LGS without West syndrome is not significant. The average age at diagnosis of LGS in Japan was 6 years (range, 2–15 y). Epidemiologic studies in industrialized countries (e.g., Spain, Estonia, Italy, and Finland) have demonstrated that the proportion of epileptic patients with LGS seems relatively consistent across the populations studied and similar to that in the United States. The prevalence of LGS is 0.1–0.28 per 1000 population in Europe. The annual incidence of LGS in childhood is approximately 2 per 100,000 children. Among children with intellectual disability, 7% have LGS, while 16.3% of institutionalized patients with intellectual disability have LGS. Long-term prognosis overall is unfavorable but variable in LGS. Longitudinal studies have found that a minority of patients with LGS eventually could work normally, but 47–76% still had typical characteristics (mental retardation, treatment-resistant seizures) many years after onset and required significant help (e.g., home care, institutionalization). A variety of therapeutic approaches are used in LGS, ranging from conventional antiepileptic agents to diet and surgery. Unfortunately, much of the evidence supporting these approaches is not robust, and treatment is often ineffective. The medical treatment options for patients with LGS can be divided into the following 3 major groups: The medical treatment options for patients with LGS include the use of antiepileptic drugs such as valproic acid and benzodiazepines such as clonazepam, nitrazepam and clobazam, vigabatrin, zonisamide, lamotrigine, topiramate and rufinamide proven effective by double-blind placebo-controlled studies (e.g., lamotrigine, topiramate, felbamate, and rufinamide). The ketogenic diet may be useful in patients with LGS refractory to medical treatment. Surgical options for LGS include corpus callosotomy, vagus nerve stimulation, and focal cortical resection [18–21].
Lennox-Gastaut Syndromeby Edwin Trevathan, M.D., M.P.H.Dr. Trevathan is Associate Professor of Neurology & Pediatrics at Washington University School of Medicine and Director of the Pediatric Epilepsy Center at St. Louis Children's Hospital .
markedly asymmetric hypsarrhythmic pattern with virtually complete interhemispheric
asynchrony of a suppression-burst-like background.[88]
The hypsarrhythmic pattern is a maturational pattern most commonly
expressed between the ages of 4 and 12 months. As the infant grows older,
beyond the age of 2 years, it is rare to encounter typical hypsarrhythmia,
although infantile spasms may still continue. Hypsarrhythmia is replaced by
different EEG patterns such as a diffusely slow tracing, slow spike wave
discharges as seen with Lennox-Gastaut syndrome, IMSD, and, rarely, a
normal tracing.
Adrenocorticotrophic hormone therapy often has a dramatic effect on
infantile spasms as well as the hypsarrhythmic EEG pattern, which may
virtually disappear in a matter of a few days to a few weeks after initiation of
therapy. However, despite these clinical and EEG improvements, the long-
term neurocognitive development remains subnormal.
Lennox-Gastaut syndrome (childhood epileptic encephalopathy) is another
common form of SGE manifesting in early childhood with developmental
delay, neurocognitive deficits, and frequent generalized seizures including
tonic seizures. The EEG shows generalized, slow spike wave discharges
(1.5 to 2.5 Hz) superimposed on abnormally slow background activity (Fig.
24).[89,90] It is important to distinguish these EEG findings from those seen with
primary generalized epilepsy where the background activity is normal for age
and the generalized spike wave discharges are usually of faster frequency (3
to 5 Hz). Although appearing widespread and bilaterally synchronous, the
slow spike wave activity is usually higher in amplitude over the anterior head
regions (in 90% of patients); less commonly the amplitude is highest over
the occipital areas. The duration of the paroxysms varies widely from
isolated complexes to almost continuous slow spike wave activity, commonly
without an identified behavioral or awareness change. Hence, the slow spike
wave activity in Lennox-Gastaut syndrome is considered an interictal
pattern, although it must be understood that subtle changes of behavior in
retarded and uncooperative children are hard to recognize.
Figure 24 EEG of a 16-year-old child with mental retardation and tonic seizures, showing slow spike wave activity superimposed on a slow background.
When one encounters prolonged episodes of slow spike wave activity lasting
several seconds to minutes, the interpretative challenge is to decide if these
electrographic events represent an ictal pattern (atypical absences or
nonconvulsive status) or they simply represent more pronounced interictal
pattern. A history of similar long episodes of slow spike wave activity in one
or more previous EEGs would support an interictal finding. Also, giving a
small dose of lorazepam intravenously will have no affect on an interictal
pattern but will usually abort an ictal pattern, at least temporarily.
If a tonic seizure is recorded during the EEG of a patient with Lennox-
Gastaut syndrome, the characteristic finding is an electrodecrement or
"flattening" lasting several seconds. In addition, high-frequency rhythmic
activity in the alpha-beta frequency range commonly occurs during the
electrodecrement.
Another distinctive EEG pattern of a symptomatic generalized epilepsy
syndrome is IMSD characterized by the presence of three or more
independent and noncontiguous foci of spike or spike wave activity with at
least one focus in one hemisphere (Fig. 25).[91,92] As expected, the
background activity is invariably disorganized and slow in frequency.
Figure 25 EEG of a 7-month-old child, showing independent multifocal spike discharges.
Figure 25.
EEG of a 7-month-old child, showing independent multifocal spike discharges.
There is a close correlation between the three EEG patterns of
hypsarrhythmia, slow spike wave, and IMSD associated with SGE. All of
them are associated with diffuse or multifocal cerebral abnormalities and
have similar clinical correlates of mental retardation, multiple and medically
intractable seizure types, and a high incidence of neurologic deficits.[91] Furthermore, serial studies over time may show a change of one pattern
to the other in the same patient. Also, in the same EEG study, more than
one of these patterns may coexist (e.g., IMSD during wakefulness and slow
spike wave activity during sleep). It is very well known that at least 20% of
infants with hypsarrhythmia may show slow spike wave usually by the
second to fourth year of life. Both of these patterns may further change to
IMSD in early childhood. Thus, these three EEG patterns have a common
physiopathologic basis and are probably dependent more on cerebral
maturation than on a particular kind of cerebral pathologic process.[91]Hypsarrhythmia is usually seen in the later half of the first year of life in
response to a cerebral insult prenatally, perinatally, or in the immediate
postnatal period. It rarely results from cerebral insults after the second year
of life. The slow spike wave pattern associated with Lennox-Gastaut
syndrome is commonly observed between the ages of 2 and 5 years. The
IMSD pattern is seen commonly throughout the first decade of life.
A unique EEG pattern of GPFA is seen predominantly during sleep
consisting of high-frequency, 12 to 25 Hz repetitive spike discharges
occurring synchronously over both hemispheres (Fig. 26).[93] It is associated
most commonly with SGE (usually Lennox-Gastaut syndrome) but it may
rarely occur also with PGE or in patients with focal seizures, particularly with
a frontal lobe focus. This EEG pattern is usually not associated with an
obvious clinical change, although subtle tonic seizures (opening of eyes and
jaw, eye deviation upward) may be missed. In rare patients with PGE and 3
Hz generalized spike wave, the awake EEG may appear rather benign but
the presence of GPFA during sleep is a warning that more severe
encephalopathy may be present. In such patients, motor seizures are
common and the disorder is likely to persist in adulthood.[94]
Figure 26 EEG of an 11-year-old patient with Lennox-Gastaut syndrome, showing generalized paroxysmal fast activity (B).
When one encounters prolonged episodes of slow spike wave activity lasting
several seconds to minutes, the interpretative challenge is to decide if these
electrographic events represent an ictal pattern (atypical absences or
nonconvulsive status) or they simply represent more pronounced interictal
pattern. A history of similar long episodes of slow spike wave activity in one
or more previous EEGs would support an interictal finding. Also, giving a
small dose of lorazepam intravenously will have no affect on an interictal
pattern but will usually abort an ictal pattern, at least temporarily.
If a tonic seizure is recorded during the EEG of a patient with Lennox-
Gastaut syndrome, the characteristic finding is an electrodecrement or
"flattening" lasting several seconds. In addition, high-frequency rhythmic
activity in the alpha-beta frequency range commonly occurs during the
electrodecrement.
EG IN STATUS EPILEPTICUSStatus epilepticus (SE) is usually defined as continuous seizure activity persisting for more than 30 minutes or more than one sequential seizure without full recovery of consciousness between seizures. A very common reason for ordering an emergency EEG is for the diagnosis and management of SE. A simplified classification of SE includes: (1) generalized convulsive status, characterized by motor seizures with loss of consciousness; (2) simple partial or focal status, characterized by focal motor seizures repeating frequently or epilepsia partialis continua with the patient remaining fully conscious; and (3) nonconvulsive status (NCSE) characterized by a variable alteration of consciousness with minimal or no motor activity.
NCSE poses many challenging nosologic, diagnostic, and therapeutic problems. NCSE includes: (1) absence status, occurring in the setting of generalized epilepsy (idiopathic or symptomatic) and (2) complex partial status associated with focal or partial epilepsy of frontal or temporal onset. In both types, the patient may present with mental status alteration (e.g., slowness in behavior and mentation, confusion, and, rarely, stupor or coma). Then, there are patients who after treatment of generalized convulsive status continue to be obtunded or comatose and show epileptiform discharges in their EEG. These patients are often designated as having "subtle" SE or lumped under NCSE.
It is relatively easy to diagnose NCSE associated with focal epilepsy when there are frequent electrographic focal seizures with an ictal EEG pattern that evolves over time with change in the amplitude, frequency, and spatial distribution. However, it is quite common for the ictal EEG pattern associated with complex partial status associated with focal epilepsy to be generalized spikes or sharp waves repeating at 1 to 6 Hz frequency. Such a generalized EEG pattern is similar to that seen in typical absence status associated with idiopathic generalized epilepsy (absence
epilepsy) and atypical absence status in children with secondary generalized epilepsy of the Lennox-Gastaut type. To complicate the situation even further, patients with Lennox-Gastaut syndrome interictally have generalized 1.0 to 3.0 cps spike wave discharges that may be very frequent, and one needs to decide if they represent an ictal pattern (hence atypical absence status) or simply represent a prominent interictal pattern. Some waxing or waning of such generalized epileptiform discharges may not help in the distinction because this may be simply related to state changes.
Some helpful criteria are proposed by Young et al[122] in patients who show almost continuously occurring generalized, nonevolving epileptiform discharges in their EEGs, including repetitive generalized or focal epileptiform discharges (spikes, sharp waves, and spike waves) that repeat at a rate faster than three per second, very likely represent an ictal pattern. Such repetitive discharges at a frequency slower than three per second are likely to be ictal if significant clinical and/or EEG improvement is demonstrated following small doses of intravenous lorazepam or diazepam. Rhythmic sinusoidal waves of any frequency (ranging from β to δ frequency) may represent an ictal pattern if there is an evolving pattern at the onset (increasing amplitude and/or decreasing frequency) or a decrement pattern at the termination (decremental amplitude or frequency) or postdischarge slowing or voltage attenuation.
In a patient with obtundation or mental status change of recent onset, an EEG is indicated to rule out NCSE. If repetitive generalized epileptiform discharges are recorded in the EEG, 1 to 2 mg of lorazepam or 5 to 10 mg of diazepam are injected intravenously while the EEG is running. A marked clinical improvement of obtundation and disappearance of generalized paroxysmal activity in the EEG would strongly support the diagnosis of NCSE (Figs. [36] and [37]). Such a rewarding experience is most common in typical absence status and less common in other forms of NCSE.
Reviewing the previous EEG and obtaining follow-up EEG studies also provide a helpful distinction between ictal and interictal basis for the repetitive generalized spike wave discharges seen in children with Lennox-Gastaut syndrome. A period of frequent repetitive generalized spike wave discharges associated with clinical deterioration of mental status is more likely an episode of atypical absence status, particularly if the previous EEGs or follow-up EEGs display dramatically fewer epileptiform abnormalities.
"Subtle" SE commonly includes patients who had a known episode of convulsive or generalized tonic-clonic status, brought under control by intravenous antiepileptic therapy (e.g., phenytoin, lorazepam, and barbiturates), but continue to remain obtunded or comatose without significant motor activity. EEG of such patients often show repetitive discharges, which may include lateralized periodic discharges (e.g., PLEDs or BiIPLEDS) or generalized periodic discharges (PEDs). Some epileptologists[123] are of the opinion that progressive sequential EEG changes occur during generalized convulsive SE with an "intermediary" pattern of PEDs and PLEDs (unilateral or bilateral) before disappearance of all paroxysmal EEG activities, and that the presence of these "intermediary" EEG patterns necessitate further aggressive therapeutic measures (e.g., inducing pentobarbital coma, etc.). Such views are not universal. Many, on the other hand, consider PED and PLED patterns observed during the course of convulsive status not an ictal pattern but suggestive of a severe epileptic encephalopathy reflective of a neuronal dysfunction from underlying brain damage.[124]
Refractory SE is usually treated by continuous intravenous anesthesia maintained by pentobarbital, propofol, or medazolam. The dose is regulated such as to control all clear-cut clinical or electrographic seizures and to maintain a suppression-burst pattern in the EEG. Therefore, continuous bedside EEG is monitored. There is no consensus as to the duration of
"burst" and "flat" periods for optimal dosing. Most consider that establishing and maintaining any degree of suppression-burst pattern is adequate.
One final note of caution is that focal motor seizures including epilepsia partialis continua may not show ictal changes in the EEG because of the limited size of neuronal tissue involved during the epileptic seizure or because the ictal pattern in the EEG may be obscured by artifacts. Careful review of the EEG using different montages (especially a transverse bipolar montage going through the midline electrodes) and use of appropriate muscle filters may reveal a low-amplitude ictal pattern.
West syndrome usually occurs in the first year of life and consists of the triad of infantile spasms, developmental deterioration, and a hypsarrhythmia pattern on EEG [11]. The epileptic spasms are brief, generalized seizures involving extension and/or flexion axially, and of the extremities. An individual spasm lasts for seconds, often longer than typical myoclonic seizures, though not as long as most tonic seizures. The spasms may be subtle and may be isolated at onset, typically clustering later in the course. Several clusters per day, particularly in drowsiness, are characteristic [11, 12]. Hypsarrhythmia, the typical interictal EEG finding, consists of a disorganized pattern with asynchronous, very high amplitude slowing and frequent multifocal spike and sharp wave discharges (Figure 2). The ictal EEG typically reveals a generalized slow wave followed by a diffuse voltage attenuation (electro-decrement) (Figure 3), which may associate with a spasm or be only electrographic (without clinical correlation) [12]. No clear etiology is found in approximately 40% of cases. There is a broad range of potential causes, including cerebral
malformations, infection, hemorrhage, hypoxic-ischemic injury, metabolic disorders, and genetic conditions, such as Down syndrome [12, 13]. Variation in studying methodologies prohibits a clear recommendation for first line treatment; however, ACTH and vigabatrin are usually used in practice. Corticosteroids may be less efficacious than ACTH, although they are effective. Vigabatrin may be more efficacious in tuberous sclerosis. Other agents that are efficacious include valproate, levetiracetam, topiramate, zonisamide, lamotrigine, and benzodiazepines [11]. The ketogenic diet is helpful in most cases [12]. Focal cortical resection or hemispherectomy may be considered for cases that are lesional and medically intractable [11–13]. Development remains unaffected only in a minority. Most children experience slowing, plateauing, or regression of their developmental trajectory. The developmental prognosis partially depends on the etiology. No specific AED has been shown to affect long-term developmental outcome. An extensive literature review revealed that 16% had normal development, and 47% had continued seizures at an average followup of 31 months. When classified by etiology, normal development was described in 51% of cryptogenic cases versus only 6% of symptomatic cases. Approximately 17% of cases evolved into Lennox-Gastaut syndrome [12].
Figure 2Hypsarrhythmia, the typical interictal EEG finding, consists of a disorganized pattern with asynchronous, very high amplitude slowing and frequent multifocal spike and sharp wave discharges (arrows).
Figure 3The ictal EEG in West syndrome typically reveals a generalized slow wave followed by diffuse voltage attenuation (electrodecrement), which may associate with a spasm or be only electrographic without clinical correlate (arrows).
Electroencefalograma durante la fase REM del sueño. El diagnóstico de síndrome de West se realiza mediante la detección de hipsarritmias en el EEG, desapareciendo estas durante esta fase del sueño.
Epilepsy in adult patients with Down syndrome: a clinical-video EEG studyEpileptic
Disorders. Volume 13, Number 2, 125-32, Juin 2011Aglaia Vignoli, Elena Zambrelli, Valentina Chiesa, Miriam Savini, Francesca La Briola, Elena Gardella, Maria Paola Canevini
Medicine » Medical Genetics » "Genetics and Etiology of Down Syndrome", book edited by Subrata Dey, ISBN 978-953-307-631-7, Published: August 29, 2011 under CC BY-NC-SA 3.0 license
1. Introduction
Down syndrome (DS) is associated with many neurological complications including cognitive deficits,
early-onset dementia -which resembles Alzheimer’s disease- and seizures. Although seizures and
epilepsy were not mentioned in the original description of DS (Down, 1886) the prevalence of seizures
in individuals with DS is now known to be higher than in the general population, but lower than in
patients with some other types of mental retardation (Corbett et al., 1975). Reported rates of epilepsy in
DS range from 1 to 13% (see table 1) (Tatsumo et al., 1984). Individual series are difficult to compare
because of differences in inclusion criteria and study populations. The increased seizure susceptibility in
DS has been attributed to inherent structural and molecular anomalies of the brain or to associated
medical complications, such as cardiovascular abnormalities and recurrent infections.
Medical interventions in DS have resulted in increased longevity, with estimated life expectancy of
people with DS in developed countries increasing from an average of 12 years in the 1940s to an average
of 57,8 years for women and 61,1 years for men (Bittles et al., 2007). Epilepsy onset in people with
DS is age-specific; therefore, because certain complications will arise in childhood and
others in adulthood, their occurrence is relevant to paediatric and adult neurologists. This
chapter will provide a critical overview of epilepsy in DS.
Authors No. of patients Percentage (%)
Romano et al. 113 13.00
Pueschel et al. 405 8.10
Stafstrom et al. 737 6.40
TABLE 1.
Reported incidence of seizures in patients with Down syndrome in the 1990s
Video de Lennox-Gastaut Syndrome con caso de una mujer de 34 años y encefalogramahttp://www.youtube.com/watch?v=Ek7EO6U5enE
IMAGEN LENNOX EEG
Electroencephalograms (EEGs) from a patient with Lennox-Gastaut syndrome. A, EEG showing slow spike-wave complexes typical of the Lennox-Gastaut syndrome. Although the EEG is severely abnormal in these patients they are fully conscious and able to talk. B, The same patient with a seizure has the first 2 seconds of nonepileptiform EEG followed by bursts of generalized spike wave complexes that evolve to low-voltage fast activity and a tonic seizure. This is one of the seizure types that is typical of the Lennox-Gastaut syndrome, which often includes generalized tonic-clonic seizures, atypical absences, and even partial seizures.
Electroencephalograms (EEGs) from a patient with Lennox‐Gastaut syndrome. A, EEG showing slow spike‐wave complexes typical of the Lennox‐Gastaut syndrome. While the EEG is severely abnormal in these patients they are fully conscious and able to talk. B, The same patient with a seizure has the first 2 seconds of nonepileptiform EEG followed by bursts of generalized spike and wave complexes that evolve to low voltage fast activity and a tonic seizure. This is one of the seizure types that is typical of the Lennox‐Gastaut syndrome, which often includes generalized tonic‐clonic seizures, atypical absences, and even partial seizures.
Electroencephalograms (EEGs) from a patient with Lennox-Gastaut syndrome. A, EEG showing slow spike-wave complexes typical of the Lennox-Gastaut syndrome. Although the EEG is severely abnormal in these patients they are fully conscious and able to talk. B, The same patient with a seizure has the first 2 seconds of nonepileptiform EEG followed by bursts of generalized spike wave complexes that evolve to low-voltage fast activity and a tonic seizure. This is one of the seizure types that is typical of the Lennox-Gastaut syndrome, which often includes generalized tonic-clonic seizures, atypical absences, and even partial seizures.
Electroencephalograms (EEGs) from a patient with Lennox-Gastaut syndrome. A, EEG showing slow spike-wave complexes typical of the Lennox-Gastaut syndrome. Although the EEG is severely abnormal in these patients they are fully conscious and able to talk. B, The same patient with a seizure has the first 2 seconds of nonepileptiform EEG followed by bursts of generalized spike wave complexes that evolve to low-voltage fast activity and a tonic seizure. This is one of the seizure types that is typical of the Lennox-Gastaut syndrome, which often includes generalized tonic-clonic seizures, atypical absences, and even partial seizures.