What are the clinical manifestations and treatment options for a condition like epilepsy?

Clinical Manifestations of Epilepsy

Epilepsy manifests as recurrent unprovoked seizures with characteristic clinical features that vary by seizure type, and approximately one-third of patients experience neuropsychiatric comorbidities including behavioral disturbances, cognitive impairment, and mood disorders. 1, 2

Core Clinical Manifestations

Seizure Types and Presentations

Generalized convulsive seizures present with generalized movements and unresponsiveness reflecting excessive synchronous cortical electrical activity 1:

• Tonic-clonic seizures: Prolonged tonic-clonic movements with onset coinciding with loss of consciousness, often with tongue biting, blue face, and post-ictal confusion lasting more than a few minutes 1
• Myoclonic seizures: Brief, massive synchronous jerks of arms and/or legs, occurring in 18-25% of certain epilepsy populations 1
• Absence seizures: Altered rather than lost consciousness without falls, primarily in children 1

Partial (focal) onset seizures originate from a specific brain region 1, 3:

• May present with hemilateral clonic movements, automatisms (chewing, lip smacking, frothing), or auras (rising abdominal sensation, unusual smells) 1
• Can secondarily generalize to involve the entire brain 1

Distinguishing Features from Syncope

Key clinical findings that indicate seizure rather than syncope 1:

• During the event: Tonic-clonic movements are prolonged and coincide with loss of consciousness (versus brief asynchronous movements after falling in syncope) 1
• Before the event: Epileptic aura versus pre-syncopal lightheadedness 1
• After the event: Prolonged confusion (>few minutes), aching muscles, or post-ictal focal deficits indicate seizure 1
• Timing of movements: In epilepsy, clonic movements occur before the fall; in syncope, movements occur after slumping to the floor due to brain ischemia 1

Neuropsychiatric Manifestations

Central nervous system adverse manifestations occur commonly 4:

• Somnolence and fatigue: Reported in 14.8% of adult patients and 22.8% of pediatric patients 4
• Behavioral abnormalities: Aggression, agitation, anger, anxiety, depression, emotional lability, hostility, and irritability occur in 13.3% of adults and 37% of pediatric patients 4
• Psychotic symptoms: Occur in 0.7% of patients, typically within the first week of treatment 4
• Coordination difficulties: Ataxia, abnormal gait, or incoordination in 3.4% of patients 4

Post-Cardiac Arrest Seizures

Seizures are common after cardiac arrest, occurring in approximately one-third of comatose patients after return of spontaneous circulation 1:

• Myoclonus is most common (18-25%), followed by focal or generalized tonic-clonic seizures 1
• Post-anoxic status epilepticus detected in 23-31% using continuous EEG monitoring 1
• Clinical seizures may be masked by sedation, requiring EEG for detection 1

Treatment Approach

Acute Seizure Management

For status epilepticus after benzodiazepine failure, three agents show equivalent efficacy 1:

• Levetiracetam, fosphenytoin, or valproate administered intravenously over 10 minutes all achieve seizure cessation in approximately 45-47% of patients at 60 minutes 1
• No significant difference in efficacy between these three agents (stopped early for futility to find most effective treatment) 1
• Median time to seizure termination: valproate 7.0 minutes, levetiracetam 10.5 minutes, fosphenytoin 11.7 minutes 1

For post-cardiac arrest seizures, treat with sodium valproate, levetiracetam, phenytoin, benzodiazepines, propofol, or a barbiturate 1:

• Myoclonus is particularly difficult to treat; phenytoin is often ineffective 1
• Propofol is effective to suppress post-anoxic myoclonus 1
• Clonazepam, sodium valproate, and levetiracetam are antimyoclonic drugs that may be effective 1
• Routine seizure prophylaxis is not recommended due to risk of adverse effects and poor response among patients with clinical seizures 1

Chronic Epilepsy Management

Antiepileptic drug (AED) selection depends on seizure type 3, 2:

• For partial onset seizures in adults: Initiate levetiracetam 1000 mg/day (500 mg BID), increase by 1000 mg/day every 2 weeks to maximum 3000 mg/day 4
• For partial onset seizures in children 4-16 years: Start 20 mg/kg/day (10 mg/kg BID), increase by 20 mg/kg every 2 weeks to recommended 60 mg/kg/day 4
• For generalized seizures: Valproate, lamotrigine, and topiramate are preferentially effective 3
• For myoclonic seizures (juvenile myoclonic epilepsy): Levetiracetam 1000 mg/day, increase to 3000 mg/day over 4 weeks 4

Approximately two-thirds of patients achieve seizure control with medication 2, 5:

• If trials of more than two AEDs fail to control seizures, refer to epilepsy center for surgical evaluation 3
• Epilepsy surgery renders 60-70% of patients with temporal lobe epilepsy free of disabling seizures 3

Monitoring and Prognostication

EEG monitoring is critical in specific scenarios 1:

• Use intermittent EEG to detect epileptic activity in patients with clinical seizure manifestations 1
• Consider continuous EEG for diagnosed status epilepticus and monitoring treatment effects 1
• Emergent EEG is indicated for suspected nonconvulsive status epilepticus, subtle convulsive status epilepticus, patients receiving long-acting paralytics, or drug-induced coma 1
• 25% of patients with generalized convulsive status epilepticus have continuing electrical seizures when convulsive movements cease 1

Neuroimaging recommendations 1:

• MRI of the brain is usually appropriate for most clinical scenarios involving seizures and epilepsy 1
• Non-contrast CT of the head is usually appropriate emergently to diagnose or exclude emergent scenarios 1
• Emergent neuroimaging should be performed for post-ictal focal deficits that don't quickly resolve or failure to return to baseline within several hours 1

Common Pitfalls

Critical diagnostic errors to avoid 1:

• Mistaking syncopal movements (brief, asynchronous, occurring after fall) for epileptic seizures 1
• Missing nonconvulsive status epilepticus in patients with persistent altered consciousness after apparent seizure termination 1
• Failing to distinguish epileptic from non-epileptic myoclonus (majority of myoclonus is non-epileptic) 1
• Overlooking psychogenic nonepileptic seizures (10% of enrolled patients in major trials) 1

Treatment considerations 1, 4:

• Behavioral symptoms and psychotic episodes typically occur within first 4 weeks of treatment, requiring close monitoring 4
• Myoclonus and electrographic seizure activity relate to poor prognosis, but individual patients may survive with good outcome 1
• Prolonged observation may be necessary after treatment of seizures before prognostication 1