Handbook of Genetic Counseling/Epilepsy and Seizures

Epilepsy and Seizures

Background

 * Epilepsies
 * Group of disorders characterized by chronic, recurrent changes in neurologic function
 * Caused by abnormalities in electrical activity of brain
 * An individual with isolated, nonrecurrent seizures who are otherwise healthy do not have epilepsy
 * Prevalence is 0.5-1.0% in general population
 * Seizures
 * An episode of neurologic dysfunction
 * Convulsive seizures are accompanied by motor manifestations or other changes in neurologic function
 * Sensory
 * Cognitive
 * Emotional
 * Classification is based on electroencephalographic pattern, clinical seizure type, and clinical context
 * Age of patient
 * Type of seizure
 * Presence of neurologic lesions

Classifications and Clinical Findings

 * Partial or focal seizures
 * Begin with activation of neurons in only one part of the brain
 * Specific clinical symptoms depend on area of brain involved
 * Potential causes
 * Birth injury
 * Postnatal trauma
 * Tumor
 * Abscess
 * Infarction
 * Vascular malformation
 * Structural abnormality
 * Two subclassifications
 * Simple if no alteration in consciousness
 * Complex if lose awareness of the environment
 * Simple partial seizures
 * Recurrent contractions of muscles of one part of body without loss of consciousness
 * May remain confined to one area of body or spread to surrounding parts
 * May cause sensory symptoms (hallucinations) or psychic symptoms (unwarranted emotions)
 * Complex partial seizures
 * Episodic changes in behavior causing a loss of conscious contact with environment
 * May begin with illusions, hallucinations, feeling of déjà vu, or unusual smell
 * May see lip smacking, swallowing, walking aimlessly, automatisms, or unconscious performance of highly skilled activities
 * When seizure ends, individual experiences amnesia
 * Secondary generalization of partial seizures
 * Progression of partial seizure to loss of consciousness and convulsive motor activity
 * May happen after a few seconds or a few minutes
 * Primary generalized seizures
 * Tonic-clonic (Grand mal)
 * Usually begin without warning
 * Cause sudden loss of consciousness, tonic contraction of muscles, loss of posture control, and cry as respiratory muscles contract
 * Individual may sustain injury when they fall to the floor
 * May suffer cyanosis if respiration inhibited
 * Clonic period of rhythmic contractions of all four limbs that lasts for variable period of time
 * Headaches, drowsiness, amnesia, incontinence, and tongue biting may occur
 * Tonic seizures
 * Sudden occurrence of rigid posturing of limbs and torso
 * Not followed by clonic phase and shorter in duration
 * Absence seizures (petit mal)
 * Sudden cessation of ongoing conscious activity
 * No convulsive muscular activity or loss of postural control
 * So brief they may not be apparent but may cause lapse of consciousness or awareness accompanied by minor motor manifestations
 * Usually begin in children 6-14
 * Often appear neurologically normal
 * Usually sensitive to antiepileptic drugs
 * 1/3 outgrow disorder, 1/3 continue to have only absence seizures, 1/3 have tonic-clonic seizures
 * Atypical absence
 * Similar to absence seizures by coexist with other forms of seizures
 * Occur in children with underlying neurologic dysfunction
 * Resistant to medication
 * Myoclonic seizures
 * Sudden, brief, single or repetitive muscle contractions involving one body part or entire body
 * May occur alone or with other types
 * Symptom of medical conditions
 * Uremia
 * Hepatic failure
 * Creutzfeldt-Jakob Disease
 * Subacute leukoencephalopathies
 * Lafora body disease
 * Juvenile Myoclonic Epilepsy (JME)
 * Atonic seizures
 * Brief loss of posture and consciousness
 * No muscular contraction
 * Usually occur in children
 * Infantile spasms or hypsarrhthmia
 * Occur in infants birth to 12 months
 * All signs of seizures disappear from ages 3-5
 * Suffer other types of generalized seizures later in life
 * Contractions of neck, torso, and both arms
 * Usually occur in children with neurological disease
 * Tuberous sclerosis
 * Anoxic encephalopathy
 * 90% of these children develop mental retardation
 * Febrile seizures
 * Controversial definition, prognosis, treatment, pathophysiology
 * Associated with fever but no evidence of intracranial infection or other cause
 * Usually occur from 3 months to 5 years of age
 * 2-6% go on to develop epilepsy
 * Estimated to occur in 2-5% of all Caucasian children
 * Family history reported in 7-58% of all children with these seizures
 * 8-15%% of first degree relatives may also be affected
 * Multifactorial inheritance
 * Recurrence risks for children of affected proband
 * 18.5% if only proband affected
 * 36.5% if proband and one parent affected
 * 45% if proband and both parents affected

Genetic Etiology

 * Genetic influences may be chromosomal, dominant or recessive autosomal, X-linked, or multifactorial
 * Environmentally induced seizures carry low recurrence risk for other family members

Differential Diagnosis

 * Syncope
 * Fainting or a sudden loss of consciousness not involving convulsions
 * If origin unknown, patient should undergo cardiovascular evaluation, EEG with sleep recording, and prolonged ambulatory EEG monitoring
 * Transient ischemic attacks and migraines
 * Transient alteration in neurologic function without loss of consciousness
 * Can undergo MRI or CT scan, carotid studies, and EEG precedures
 * Antiepileptic drugs may help migraines
 * Pseudoseizures and "hysterical seizures"
 * Patients may appear emotionally disturbed and receive psychiatric treatment
 * Normal EEG but may have activity in deep temporal lobe not detected
 * May be eliminated or reduced by suggestion

Treatment and Management Options

 * Eliminate cause, suppress expression, and deal with psychosocial consequences
 * May be treated by correcting metabolic disturbance, hormonal disruptions, etc.
 * Pharmacologic control
 * Goal is to prevent seizures without interfering with cognitive function
 * Many patients are resistant to medication
 * Teratogenic
 * Neurosurgical treatment
 * Remove structural lesion and nearby diseased part of brain (e.g. - tumor)
 * May not help eliminate psychological disturbances that may occur

Psychosocial Issues

 * Anxiety over potential future development of epilepsy
 * Complications associated with pregnancy
 * Difficulty assessing exact recurrence risks
 * Frustration if unknown etiology or explanation
 * Social stigma associated with neurological disorders
 * Fear of potential seizures at school, in public, etc.