Epilepsy

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Epilepsy

  1. 1. EPILEPSY
  2. 2. Essentials of Diagnosis • Recurrent seizures. • Characteristic electroencephalographic changes accompany seizures. • Mental status abnormalities or focal neurologic symptoms may persist for hours postictally.
  3. 3. General Considerations The term "epilepsy" denotes any disorder characterized by recurrent unprovoked seizures. A seizure is a transient disturbance of cerebral function due to an abnormal paroxysmal neuronal discharge in the brain.  Epilepsy is common, affecting approximately 0.5% of the population in the United States
  4. 4. Etiology Genetic Epilepsy This category encompasses a broad range of disorders, for which the age at onset ranges from the neonatal period to adolescence or even later in life. Monogenic disorders tend to exhibit an autosomal dominant pattern of inheritance, and where the mutation is known, the responsible gene often encodes a neuronal ion channel.
  5. 5. Structural/Metabolic Epilepsy There are many causes for recurrent seizures Metabolic disorders Withdrawal from alcohol or drugs.  Uremia and Hypoglycemia or hyperglycemia Since these seizures are provoked by a readily reversible cause, this would not be considered epilepsy
  6. 6. Trauma An important cause of seizures at any age especially in young adults.  Posttraumatic epilepsy is more likely to develop if the dura mater was penetrated and generally becomes manifest within 2 years following the injury.  However, seizures developing in the first week after head injury do not necessarily imply that future attacks will occur. There is no clear evidence that prophylactic anticonvulsant drug treatment reduces the incidence of posttraumatic epilepsy.
  7. 7. Tumors and other space-occupying lesions Neoplasms may lead to seizures at any age Especially important cause of seizures in middle and later life Seizures are commonly the initial symptoms of the tumor often are focal in character. They are most likely to occur with structural lesions involving the frontal, parietal, or temporal regions.  Tumors must be excluded by imaging studies (MRI preferred over CT) in all patients with onset of seizures after 30 years of age, focal seizures or signs, or a progressive seizure disorder.
  8. 8. Vascular diseases Become increasingly frequent causes of seizures with advancing age Are the most common cause of seizures with onset at age 60 years or older
  9. 9. Degenerative disorders Alzheimer disease and other degenerative disorders are a cause of seizures in later life.
  10. 10. Infectious diseases Must be considered in all age groups  potentially reversible causes of seizures. Seizures may occur with an acute infective or inflammatory illness Bacterial meningitis or herpes encephalitis  or in patients with more longstanding or chronic disorders, such as neurosyphilis or cerebral cysticercosis.  In patients with AIDS, they may result from central nervous system toxoplasmosis, cryptococcal meningitis, secondary viral encephalitis, or other infective complications. Seizures are a common sequela of supratentorial brain abscess, developing most frequently in the first year after treatment.
  11. 11. Unknown In many cases, the cause of epilepsy cannot be determined.
  12. 12. Pediatric age groups Congenital abnormalities and perinatal injuries may result in seizures presenting in infancy or childhood.
  13. 13. Classification of Seizures The International League Against Epilepsy distinguishes seizures affecting only part of the brain (focal seizures) from those that are generalized.
  14. 14. Seizure classification. Seizure Type Key Features Focal seizures Other Associated Features Involvement of only a restricted part of brain; may evolve to a bilateral, convulsive seizure Without Observable focal motor or autonomic impairment of symptoms, or subjective sensory or consciousness psychic symptoms may occur With impairment Above symptoms may precede, of consciousness accompany, or follow the period of altered responsiveness Generalized Diffuse involvement of brain at seizures onset Absence (petit mal) Consciousness impaired briefly; May have clonic, tonic, or atonic (ie, patient often unaware of attacks loss of postural tone) components; autonomic components (eg, enuresis); or accompanying automatisms Almost always begin in childhood and frequently cease by age 20 Atypical absences May be more gradual in onset More marked changes in tone may and termination than typical occur absence Myoclonic Single or multiple myoclonic jerks Tonic-clonic Tonic phase: Sudden loss of May be accompanied by tongue biting, consciousness, with rigidity and incontinence, or aspiration; commonly arrest of respiration, lasting < 1 followed by postictal confusion minute (grand mal) variable in duration Clonic phase: Jerking occurs, usually for < 2–3 minutes Flaccid coma: Variable duration Status epilepticus Repeated seizures without recovery between them; a fixed and enduring epileptic condition lasting ≥ 30 minutes
  15. 15. Focal Seizures The initial clinical and EEG manifestations of partial seizures indicate that only a restricted part of one cerebral hemisphere has been activated. The ictal manifestations depend on the area of the brain involved  Focal seizures sometimes involve impairment of consciousness and may evolve to convulsive seizures, in a process previously called secondary generalization.
  16. 16. Without impairment of consciousness  Seizures may be manifested by focal motor symptoms (convulsive jerking)  Somatosensory symptoms (eg, paresthesias or tingling) that spread (or “march”) to different parts of the limb or body depending on their cortical representation  Were previously described as “simple partial” seizures  In other instances, special sensory symptoms (eg, light flashes or buzzing) indicate involvement of visual, auditory, olfactory, or gustatory regions of the brain  There may be autonomic symptoms or signs (eg, abnormal epigastric sensations, sweating, flushing, pupillary dilation).  The sole manifestations of some seizures are phenomena such as dysphasia, dysmnesic symptoms (eg, déjà vu, jamais vu), affective disturbances, illusions, or structured hallucinations, but such symptoms are usually accompanied by impairment of consciousness.
  17. 17.  With impairment of consciousness  Impaired consciousness or responsiveness may be preceded, accompanied, or followed by the various symptoms mentioned above  Automatisms may occur.  Such dyscognitive seizures were previously called "complex partial" seizures.
  18. 18.  Generalized Seizures  There are several different varieties of generalized seizures  In some circumstances, seizures cannot be classified because of incomplete information or because they do not fit into any category.
  19. 19.  Absence seizures  These are characterized by impairment of consciousness, sometimes with mild clonic, tonic, or atonic components (ie, reduction or loss of postural tone), autonomic components (eg, enuresis)  Or accompanying automatisms  Onset and termination of attacks are abrupt  If attacks occur during conversation, the patient may miss a few words or may break off in midsentence for a few seconds  The impairment of external awareness is so brief that the patient is unaware of it  Absence ("petit mal") seizures almost always begin in childhood and frequently cease by the age of 20 years or are then replaced by other forms of generalized seizure  Electroencephalographically, such attacks are associated with bursts of bilaterally synchronous and symmetric 3-Hz spike-and-wave activity  A normal background in the electroencephalogram and normal or above-normal intelligence imply a good prognosis for the ultimate cessation of these seizures.
  20. 20.  Atypical absence seizures  There may be more marked changes in tone, or attacks may have a more gradual onset and termination than in typical absence seizures.  They commonly occur in patients with multiple seizure types  May be accompanied by developmental delay or mental retardation  Are associated with slower spike-wave discharges than those in typical absence attacks.
  21. 21.  Myoclonic seizures  Myoclonic seizures consist of single or multiple myoclonic jerks. Tonic-clonic ("grand mal") seizures  In these seizures, which are characterized by sudden loss of consciousness  the patient becomes rigid and falls to the ground  respiration is arrested.  This tonic phase, which usually lasts for < 1 minute, is followed by a clonic phase in which there is jerking of the body musculature that may last for 2 or 3 minutes  followed by a stage of flaccid coma  During the seizure, the tongue or lips may be bitten, urinary or fecal incontinence may occur  the patient may be injured.  Immediately after the seizure, the patient may recover consciousness, drift into sleep, have a further convulsion without recovery of consciousness between the attacks (status epilepticus),  or after recovering consciousness have a further convulsion (serial seizures).  In other cases, patients will behave in an abnormal fashion in the immediate postictal period, without subsequent awareness or memory of events (postepileptic automatism).  Headache, disorientation, confusion, drowsiness, nausea, soreness of the muscles, or some combination of these symptoms commonly occurs postictally.  Tonic, clonic, or atonic seizures Loss of consciousness may occur with either the tonic or clonic accompaniments described above, especially in children. Atonic seizures (epileptic drop attacks) have also been described.
  22. 22. Clinical Findings  Symptoms and Signs  Nonspecific changes such as headache, mood alterations, lethargy, and myoclonic jerking alert some patients to an impending seizure hours before it occurs.  These prodromal symptoms are distinct from the aura; the aura that may precede a generalized seizure by a few seconds or minutes is itself a part of the attack and it arises locally from a restricted part of the brain  In most patients, seizures occur unpredictably at any time and without any relationship to posture or ongoing activities  Occasionally, however, they occur at a particular time (eg, during sleep) or in relation to external precipitants such as lack of sleep, missed meals, emotional stress, menstruation, alcohol ingestion (or alcohol withdrawalbelow), or use of certain drugs  Fever and nonspecific infections may also precipitate seizures in epileptic patients.  In a few patients, seizures are provoked by specific stimuli such as flashing lights or a flickering television set (photosensitive epilepsy), music, or reading.  Clinical examination     No abnormality between seizures in patients with idiopathic epilepsy In the immediate postictal period, extensor plantar responses may be seen The presence of lateralized or focal signs postictally suggests that seizures may have a focal origin In patients with symptomatic epilepsy, the findings on examination will reflect the underlying cause.
  23. 23. Imaging  MRI is indicated for patients with focal neurologic symptoms or signs, focal seizures, or electroencephalographic findings of a focal disturbance  some clinicians routinely order MRI for all patients with new-onset seizure disorders.  CT is generally less sensitive than MRI to small structural brain abnormalities but may be used when MRI is contraindicated (eg, in a patient with a metallic implant).  Such studies should be performed in patients with clinical evidence of a progressive disorder and in those with new onset of seizures after the age of 20 years because of the possibility of an underlying neoplasm.
  24. 24.  Laboratory and Other Studies  Initial investigations should include complete blood count  serum glucose, electrolytes, creatinine, calcium, magnesium  liver function tests to exclude various causes of seizures and to provide a baseline for subsequent monitoring of long-term effects of treatment  A lumbar puncture may be necessary when any sign of infection is present or in the evaluation of new-onset seizures in the acute setting  Electroencephalography may support the clinical diagnosis of epilepsy (by demonstrating paroxysmal abnormalities containing spikes or sharp waves), provide a guide to prognosis, and help classify the seizure disorder.  Classification of the disorder is important for determining the most appropriate anticonvulsant drug with which to start treatment  For example, absence and focal seizures with impairment of consciousness may be difficult to distinguish clinically, but the electroencephalographic findings and treatment of choice differ in these two conditions.  Finally, by localizing the epileptogenic source, the electroencephalographic findings are important in evaluating candidates for surgical treatment.
  25. 25.  Differential Diagnosis  The distinction between the various disorders likely to be confused with generalized seizures is usually made on the basis of the history.  The importance of obtaining an eyewitness account of the attacks cannot be overemphasized.
  26. 26.  Differential Diagnosis of Focal Seizures  Transient ischemic attacks  These attacks are distinguished from seizures by their longer duration, lack of spread, and symptoms  Level of consciousness, which is unaltered, does not distinguish them  There is a loss of motor or sensory function (eg, weakness or numbness) with transient ischemic attacks, whereas positive symptoms (eg, convulsive jerking or paresthesias) characterizes seizures.
  27. 27.  Rage attacks  Rage attacks are usually situational  lead to goal-directed aggressive behavior
  28. 28. Panic attacks  These may be hard to distinguish from focal seizures unless there is evidence of an anxiety disorder between attacks  attacks have a clear relationship to external circumstances.
  29. 29.  Differential Diagnosis of Generalized Seizures  Syncope  Syncopal episodes usually occur in relation to postural change, emotional stress, instrumentation, pain, or straining  They are typically preceded by pallor, sweating, nausea, and malaise and lead to loss of consciousness accompanied by flaccidity; recovery occurs rapidly with recumbency, and there is no postictal headache or confusion  In some instances, however, motor accompaniments and urinary incontinence may simulate a seizure.
  30. 30.  Cardiac disease  Cerebral hypoperfusion due to a disturbance of cardiac rhythm should be suspected in patients with known cardiac or vascular disease or in elderly patients who present with episodic loss of consciousness  Prodromal symptoms are typically absent  Repeated Holter monitoring may be necessary to establish the diagnosis  Monitoring initiated by the patient ("event monitor") may be valuable if the disturbances of consciousness are rare  A relationship of attacks to physical activity and the finding of a systolic murmur are suggestive of aortic stenosis
  31. 31.  Brainstem ischemia  Loss of consciousness is preceded or accompanied by other brainstem signs  Basilar artery migraine and vertebrobasilar vascular disease are discussed elsewhere in this chapter
  32. 32.  Psychogenic nonepileptic seizure (PNES)         Simulates an epileptic seizure PNES may occur due to a conversion disorder or malingering Many patients also have true seizures or a family history of epilepsy. Although a PNES tends to occur at times of emotional stress, this may also be the case with true seizures. Clinically, the attacks superficially resemble tonic-clonic seizures, but there may be obvious preparation before a PNES. Moreover, there is usually no tonic phase; instead, there may be an asynchronous thrashing of the limbs, which increases if restraints are imposed and rarely leads to injury. Consciousness may be normal or “lost,” but in the latter context the occurrence of goaldirected behavior or of shouting, swearing, etc, indicates that it is feigned. Postictally, there are no changes in behavior or neurologic findings. Often, clinical observation is insufficient to discriminate epileptic from nonepileptic seizures. Video electroencephalographic monitoring may be helpful: epileptic seizures, especially those involving altered consciousness, commonly involve scalp electroencephalographic signs that coincide with a behavioral spell, whereas a PNES does not The serum level of prolactin has been found to increase dramatically between 15 and 30 minutes after a tonic-clonic convulsion in most patients, whereas it is unchanged after a PNES. Serum creatine kinase levels also increase after a convulsion but not a PNES.
  33. 33.  Treatment  General Measures For patients with epilepsy, drug treatment is prescribed with the goal of preventing further attacks and is usually continued until there have been no seizures for at least 2 years Epileptic patients should be advised to avoid situations that could be dangerous or life-threatening if further seizures should occur. Legislation may require clinicians to report to the state authorities any patients with seizures or other episodic disturbances of consciousness; driving cessation for 6 months or as legislated is appropriate following an unprovoked seizure.
  34. 34.  Choice of medication  Drug selection depends on seizure type  The dose of the selected drug is gradually increased until seizures are controlled or side effects prevent further increases  If seizures continue despite treatment at the maximal tolerated dose, a second drug is added and the dose increased depending on tolerance; the first drug is then gradually withdrawn  In treatment of focal seizures, the success rate is higher with carbamazepine, phenytoin, or valproic acid than with phenobarbital or primidone. Gabapentin, topiramate, lamotrigine, oxcarbazepine, levetiracetam, zonisamide, lacosamide, ezogabine, vigabatrin, and tiagabine are newer antiepileptic drugs used to treat focal seizures. Felbamate is also effective for such seizures but, because it may cause aplastic anemia or fulminant hepatic failure, should be used only in selected patients unresponsive to other measures. Rufinamide is currently approved only for seizures in patients with LennoxGastaut syndrome, but it may be effective against seizures in a broader range of refractory patients. For generalized or unclassified seizures, valproate is better tolerated than topiramate and more efficacious than lamotrigine and is thus preferred for many patients; however, the teratogenic potential of valproate makes its use undesirable in women of childbearing age. All antiepileptics are potentially teratogenic, although the teratogenicity of the newer antiseizure medications is less clear. Nevertheless, antiepileptic medication must be given to pregnant women with epilepsy to prevent seizures, which can pose serious risk to the fetus from trauma, hypoxia, or other factors. In most patients with seizures of a single type, satisfactory control can be achieved with a single anticonvulsant drug. Treatment with two drugs may further reduce seizure frequency or severity but usually only at the cost of greater toxicity. Treatment with more than two drugs is almost always unhelpful unless the

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