SEIZURES AND EPILEPSY : part 2

CLASSIFICATION OF SEIZURES

        

Determining the type of seizure that has occurred is essential for focusing the diagnostic approach on particular etiologies, selecting the appropriate therapy, and providing potentially vital information regarding prognosis. In 1981, the International League Against Epilepsy (ILAE) published a modified version of the International Classification of Epileptic Seizures that has continued to be a useful classification system (Table 348-1). This system is based on the clinical features of seizures and associated electroencephalographic findings. Other potentiallydistinctive features such as etiologyor cellular substrate are not considered in this classification system, although this will undoubtedlychange in the future as more is learned about the pathophysiologic mechanisms that underlie specific seizure types.

                        A fundamental principle is that seizures maybe either partial (synonymous with focal) or generalized. Partial seizures are those in which the seizure activityis restricted to discrete areas of the cerebral cortex.

                                 Generalized seizures involve diffuse regions of the brain simultaneously. Partial seizures are usually associated with structural abnormalities of the brain. In contrast, generalized seizures mayresult from cellular, biochemical, or structural abnormalities that have a more widespread distribution.

PARTIAL SEIZURES

                                      Partial seizures occur within discrete regions of the brain. If consciousness is fullypreserved during the seizure, the clinical manifestations are considered relativelysimple and the seizure is termed a simple partial seizure. If consciousness is impaired, the symptomatology is more complex and the seizure is termed a complex partial seizure. An important additional subgroup comprises those seizures that begin as partial seizures and then spread diffuselythroughout the cortex, i.e., partial seizures with secondary generalization.

                           Simple Partial Seizures Simple partial seizures cause motor, sensory,autonomic, or psychic symptoms without an obvious alteration in consciousness. For example, a patient having a partial motor seizure arising from the right primarymotor cortex in the vicinitycontrolling hand movement will note the onset of involuntarymovements of the contralateral, left hand. These movements are typically clonic (i.e., repetitive,flexion/extension movements) at a frequencyof 2 to 3 Hz; pure tonic posturing maybe seen as well. Since the cortical region controlling hand movement is immediatelyadjacent to the region for facial expression, the seizure mayalso cause abnormal movements of the face synchronous with the movements of the hand. The electroencephalogram (EEG) recorded with scalp electrodes during the seizure (i.e., an ictal EEG) mayshow abnormal discharges in a verylimited region over

the appropriate area of cerebral cortex if the seizure focus involves the cerebral convexity. Seizure activity occurring within deeper brain structures is often not recorded bythe standard EEG, however, and mayrequire intracranial electrodes for its detection.

                    Three additional features of partial motor seizures are worth noting.First, in some patients the abnormal motor movements maybegin in a veryrestricted region such as the fingers and graduallyprogress (over seconds to minutes) to include a larger portion of the extremity. This phenomenon, described byHughlings Jackson and known as a “Jacksonian march,” represents the spread of seizure activityover a progressivelylarger region of motor cortex. Second, patients mayexperience a

localized paresis (Todd’s paralysis) for minutes to many hours in the involved region following the seizure. Third, in rare instances the seizure maycontinue for hours or days. This condition, termed epilepsia partialis continua, is often refractoryto medical therapy.

                       Simple partial seizures mayalso manifest as changes in somaticsensation (e.g., paresthesias), vision (flashing lights or formed hallucinations), equilibrium (sensation of falling or vertigo), or autonomic function (flushing, sweating, piloerection). Simple partial seizures arising from the temporal or frontal cortex mayalso cause alterations in hearing, olfaction, or higher cortical function (psychic symptoms).

                 This includes the sensation of unusual, intense odors (e.g., burningrubber or kerosene) or sounds (crude or highlycomplex sounds), or an epigastric sensation that arises from the stomach or chest to the head.Some patients describe odd, internal feelings such as fear, a sense ofimpending change, detachment, depersonalization, deja ` vu, or illusions that objects are growing smaller (micropsia) or larger (macropsia). When such symptoms precede a complex partial or secondarily gen-

eralized seizure, these simple partial seizures serve as a warning, or aura.

                               Complex Partial Seizures Complex partial seizures are characterized by focal seizure activityaccompanied bya transient impairment of the

patient’s abilityto maintain normal contact with the environment. The patient is unable to respond appropriatelyto visual or verbal commands during the seizure and has impaired recollection or awareness of the ictal phase. The seizures frequentlybegin with an aura (i.e., a simple partial seizure) that is stereotypic for the patient. The start of the ictal phase is often a sudden behavioral arrest or motionless stare, which marks the onset of the period of amnesia. The behavioral arrest is usuallyaccompanied by automatisms, which are involuntary, automatic behaviors that have a wide range of manifestations. Automatisms mayconsist of verybasic behaviors such as chewing, lip smacking, swallowing, or “picking” movements of the hands, or more elaborate behaviors such as a displayof emotion or running. The patient is typically confused following the seizure, and the transition to full recoveryof consciousness mayrange from seconds up to an hour.

                           Examination immediatelyfollowing the seizure mayshow an anterograde amnesia or, in cases involving the dominant hemisphere, a postictal aphasia.

                                 The routine, interictal (i.e., between seizures) EEG in patients with complex partial seizures is often normal or mayshow brief discharges termed epileptiform spikes,or sharp waves. Since complex partial seizures can arise from the medial temporal lobe or inferior frontal lobe,i.e., regions distant from the scalp, the EEG recorded during the seizure maybe nonlocalizing. However, the seizure focus is often detected using sphenoidal or surgicallyplaced intracranial electrodes.

The range of potential clinical behaviors linked to complex partial seizures is so broad that extreme caution is advised before concluding that stereotypic episodes of bizarre or atypical behavior are not due to seizure activity. In such cases additional, detailed EEG studies may be helpful.

                           Partial Seizures with Secondary Generalization Partial seizures can spread to involve both cerebral hemispheres and produce a generalized seizure, usuallyof the tonic-clonic variety(discussed below). Secondary generalization is observed frequentlyfollowing simple partial seizures, especiallythose with a focus in the frontal lobe, but mayalso be associated with partial seizures occurring elsewhere n the brain. A partial seizure with secondarygeneralization is often difficult to distin-

guish from a primarilygeneralized tonic-clonic seizure, since bystanders tend to emphasize the more dramatic, generalized convulsive phase of the seizure and overlook the more subtle, focal symptoms present at onset. In some cases, the focal onset of the seizure becomes apparent onlywhen a careful historyidentifies a preceding aura (i.e., simple partial seizure). Often, however, the focal onset is not clinically evident and maybe established onlythrough careful EEG analysis.

Nonetheless, distinguishing between these two entities is extremely important, as there maybe substantial differences in the evaluation and treatment of partial versus generalized seizure disorders.

GENERALIZED SEIZURES

                                     Bydefinition, generalized seizures arise from both cerebral hemispheres simultaneously. However, it is currently impossible to exclude entirelythe existence of a focal region of abnormal activitythat initiates the seizure prior to rapid secondarygeneralization. For this reason, generalized seizures maybe practically defined as bilateral clinical and electrographic events without any detectable focal onset. Fortunately, several types of generalized seizures have distinctive features that facilitate clinical diagnosis.Absence Seizures (Petit Mal) Absence seizures are characterized bysudden, brief lapses of consciousness without loss of postural control. The seizure typically lasts for only seconds, consciousness returns as suddenlyas it was lost, and there is no postictal confusion. Although the brief loss of consciousness maybe clinicallyinapparent or the sole manifestation of the seizure discharge, absence seizures are usually accompanied bysubtle, bilateral motor signs such as rapid blinking of the eyelids, chewing movements, or small-amplitude, clonic movements of the hands.

                                         Absence seizures usuallybegin in childhood (ages 4 to 8) or early adolescence and are the main seizure type in 15 to 20% of children with epilepsy. The seizures can occur hundreds of times per day, but the child maybe unaware of or unable to conveytheir existence. The patient maybe constantlypiecing together experiences that have been interrupted bythe seizures. Since the clinical signs of the seizures are subtle, especiallyto new parents, it is not surprising that the first clue to absence epilepsyis often unexplained “daydreaming” and a decline

in school performance recognized bya teacher. The electrophysiologic hallmark of typical absence seizures is a generalized, symmetric, 3-Hz spike-and-wave discharge that begins and ends suddenly, superimposed on a normal EEG background. Pe-

riods of spike-and-wave discharges lasting more than a few seconds usuallycorrelate with clinical signs, but the EEG often shows many more brief bursts of abnormal cortical activitythan were suspected clinically. Hyperventilation tends to provoke these electrographic discharges and even the seizures themselves and is routinelyused when recording the EEG.

                                        Typical absence seizures are often associated with generalized, tonic-clonic seizures, but patients usuallyhave no other neurologic

problems and respond well to treatment with specific anticonvulsants.Although estimates vary, 60 to 70% of such patients will have a spontaneous remission during adolescence. 

SEIZURES AND EPILEPSY : part 1

A seizure (from the Latin sacire, “to take possession of”) is a paroxysmal event due to abnormal, excessive, hypersynchronous discharges from an aggregate of central nervous system (CNS) neurons. Depending on the distribution of discharges, this abnormal CNS activitycan have various manifestations, ranging from dramatic convulsive activityto experiential phenomena not readilydiscernible byan observer.Although a varietyof factors influence the incidence and prevalence of seizures, 5 to 10% of the population will have at least one seizure,
with the highest incidence occurring in earlychildhood and late adult-hood.
                              The meaning of the term seizure needs to be carefullydistinguished from that of epilepsy. epilepsy describes a condition in which a person has recurrent seizures due to a chronic, underlying process. This definition implies that a person with a single seizure, or recurrent seizures due to correctable or avoidable circumstances, does not necessarily have epilepsy. Epilepsy refers to a clinical phenomenon rather than a
single disease entity, since there are many forms and causes of epilepsy. However, among the many causes of epilepsy there are various epilepsy syndromes in which the clinical and pathologic characteristics are distinctive and suggest a specific underlying etiology.
                                            Using the definition of epilepsyas two or more unprovoked seizures, the incidence of epilepsyis 0.3 to 0.5% in different populations throughout the world, and the prevalence of epilepsyhas beenestimated at 5 to 10 persons per 1000.

Humans share similar behavior as mice with similar anxiety related gene abnormality

Studying animals in behavioral experiments has been a cornerstone of psychological research, but whether the observations are relevant for human behavior has been unclear. Weill Cornell Medical College researchers have identified an alteration to the DNA of a gene that imparts similar anxiety-related behavior in both humans and mice, demonstrating that laboratory animals can be accurately used to study these human behaviors.
The findings may help researchers develop new clinical strategies to treat humans with anxiety disorders, such as phobias and post-traumatic stress disorder (PTSD).
Results from the study, funded by the National Institutes of Health, are published January 15 in the journal Science.
"We found that humans and mice who had the same human genetic alteration also had greater difficulty in extinguishing an anxious-like response to adverse stimuli," explains Dr. B.J. Casey, co-senior author of the study and professor of psychology in psychiatry from The Sackler Institute for Developmental Psychobiology at Weill Cornell Medical College.
The researchers observed common behavioral responses between humans and mice that possess an alteration in the brain-derived neurotrophic factor (BDNF) gene. The mice were genetically altered -- meaning that they had a human genetic variation inserted within their genome.
To make their comparison, the researchers paired a harmless stimulus with an aversive one, which elicits an anxious-like response, known as conditioned fear. Following fear learning, exposure to numerous presentations of the harmless stimulus alone, in the absence of the aversive stimulus, normally leads to subjects extinguishing this fear response. That is, a subject should eventually stop having an anxious response towards the harmless stimulus.
"But both the mice and humans found to have the alternation in the BDNF gene took significantly longer to 'get over' the innocuous stimuli and stop having a conditioned fear response," explains Dr. Fatima Soliman, lead author of the study, who is currently a Tri-Institutional MD-PhD student, and has completed her Ph.D. in the labs of Drs. B.J. Casey and Francis S. Lee.
In addition to the observational testing, the researchers also performed brain scans using functional magnetic resonance imaging (fMRI), on the human participants, to see if brain function differed between people with the abnormal BDNF gene and those with normal BDNF genes.
They found that a circuit in the brain involving the frontal cortex and amygdala -- responsible for learning about cues that signal safety and danger -- was altered in people with the abnormality, when compared with control participants who did not have the abnormality.
"Testing for this gene may one day help doctors make more informed decisions for treatment of anxiety disorders," explains Dr. Francis S. Lee, co-senior author of the study and associate professor of psychiatry and pharmacology at Weill Cornell Medical College.
Therapists use exposure therapy -- a type of behavior therapy in which the patient confronts a feared situation, object, thought, or memory -- to treat individuals who experience stress and anxiety due to certain situations. Sometimes, exposure therapy involves reliving a traumatic experience in a controlled, therapeutic environment and is based on principles of extinction learning. The goal is to reduce the distress, physical or emotional, felt in situations that trigger negative emotion. Exposure therapy is often used for the treatment of anxiety, phobias and PTSD.
"Exposure therapy may still work for patients with this gene abnormality, but a positive test for the BDNF genetic variant may let doctors know that exposure therapy may take longer, and that the use of newer drugs may be necessary to accelerate extinction learning," explains Dr. Soliman.
Co-authors of the study include Dr. Charles Glatt, Dr. Kevin Bath, Dr. Liat Levita, Rebecca Jones, Siobhan Pattwell, Dr. Deqiang Jing, Dr. Nim Tottenham, Dr. Dima Amso, Dr. Leah Somerville, Dr. Henning Voss, Dr. Douglas Ballon, Dr. Conor Liston, Theresa Teslovich and Tracey Van Kempen, all from Weill Cornell; and Dr. Gary Glover, from Stanford University, Stanford, Calif.