Pathophysiology II - Exam 4 - Seizure Disorders ⚡️

what is a seizure?

acute neurological event

- clinical manifestation of abnormal excessive or synchronous neuronal firing in the brain

- various types!

what is epilepsy?

the occurrence of 2+ seizures separated by 24+ hours

- not provoked by a reversible cause

what is a provoked seizure? provide examples

patient is NOT predisposed to seizures once the provoking factor is removed or treated; ex:

- drug overdose or withdrawal (alcohol, barbiturates, benzodiazepines, antiepileptics)

- acute neurologic illness

- systemic illness

- febrile seizures

define ictal, post-ictal, and inter-ictal

- ictal: of/pertaining to seizures

- post-ictal: the immediate period after a seizure; the patient may not have returned to baseline yet

- inter-ictal: time between seizures

what are the common comorbidities of seizure disorders?

related to disease MANAGEMENT:

- depression

- anxiety

related to SEIZURE D/O:

- neurodevelopmental delay

- cognitive impairment

what are the psychosocial (social factors and individual thought and behavior) issues associated with seizure disorder?

depends on degree of disease control!

- higher incidence of suicide

- difficulty maintaining employment

- driving

- pregnancy, contraception, and breastfeeding complications (anti-epileptics are associated with birth defects; prevented with folic acid!)

how does the prevalence of epilepsy change with age?

bimodal distribution

- newborns and young children

- >65 yo

what is the prognosis for epilepsy?

overall good, but epileptic patients have a 2-3x higher risk of mortality

- sudden unexplained death in epilepsy (SUDEP)

what are the 6 categories of epilepsy etiology?

NOT mutually-exclusive... can have several!

- genetic

- structural

- infectious

- metabolic

- immune

- unknown

describe the presentation of genetic epilepsies; provide examples

present in childhood (acquired at birth)

- associated with molecular abnormalities, often involving Na+ and Ca2+ channels

- ex: Dravet syndrome, childhood absence epilepsy, juvenile myoclonic epilepsy

describe the presentation of structural epilepsies; provide examples

acquired or genetic

- abnormalities are visible on neuroimaging

- ex: posttraumatic epilepsy, Hx of stroke

describe the presentation of infectious epilepsies; which infections are EXCLUDED from this classification?

acquired

- secondary to infection

- most common etiology globally (but not in the US)

- NOT due to acute meningitis or encephalitis (these are considered provoked!)

describe the presentation of metabolic, immune, and unknown epilepsies; provide examples

less common and not well understood

- metabolic: Lafora disease (disorder of glycogen metabolism)

- immune: anti-NMDA R encephalitis

- unknown: no identifiable cause; could be secondary to as-yet-unidentified genetic, metabolic, immune, or other causes

what are the risk factors of seizure disorders?

- premature birth and small birth weight

- perinatal anoxia (decreased blood flow to the brain during birth)

- PMH alcohol withdrawal seizures

- PMH febrile seizures

- FH of seizures

what are the common triggers of seizure disorders?

- hyperventilation

- photo-stimulation

- physical/emotional stress

- sleep deprivation

- sensory stimulation

- hormone changes

withdrawal from what medications are associated with drug-related epilepsy?

- benzodiazepines

- barbiturates

- antiepileptic drugs

- alcohol

what medications are associated with drug-related epilepsy?

- phenothiazines

- beta-lactam ABX

- theophylline

- illicit drugs

- alcohol

- antidepressants

- flumazenil

- busulfan

- meperidine

what are the key pathophysiological factors involved in seizure development?

result from neuronal hyperexcitability AND hyper-synchronization

- a small group of hyperexcitable neurons fire abnormally in synchrony

- this excess excitability spreads due to a breakdown of normal membrane conductance and inhibitory currents, leading to local (focal) and then wider spread (both hemispheres) of seizure activity

what are the primary mechanisms of hyperexcitability?

- alteration in the number, type, and biophysical properties of ion channels

- alterations in vesicle trafficking and NT release

- alterations in NT uptake and metabolism

- others

what factors promote the synchronization of hyperexcitability during seizure propagation?

- intrinsic organization of some brain structures promote epileptiform activity

- modifications in ratio and function of inhibitory circuits can promote seizures

■ large groups of interconnected neurons can become synchronously inhibited, then excited in abnormal conditions

■ neuronal sprouting and reorganization in damaged tissue increase chronic seizure risk

what generalized seizure types are categorized as motor seizures? as non-motor seizures?

motor

- atonic

- clonic

- tonic

- tonic-clonic

- myoclonic

non-motor

- absence

how are focal onset seizures classified?

based on awareness during the seizure and the earliest motor or non-motor sign

- aware: cognitively-intact; aware of self and environment

- impaired awareness: loss of consciousness

appearance varies from person to person and depends on the neurons impacted!

what questions are used to classify the state of awareness during a focal onset seizure?

- can they appropriately answer questions during the event?

- do they lose awareness at any time during the seizure?

T/F: motor manifestations of seizures are unilateral

TRUE

motor manifestations of seizures - what are automatism and atonic seizures?

- automatism: repetitive motion

- atonic: loss of muscle tone; limp

motor manifestations of seizures - what are clonic and myoclonic seizures?

- clonic: rhythmic jerking/twitching

- myoclonic: arrhythmic jerking/twitching

motor manifestations of seizures - what are tonic, spastic, and hyperkinetic seizures?

- tonic: extension, flexion, or stiffness of the limbs

- spastic: 'classic', convulsive seizure

- hyperkinetic: drastic thrashing

non-motor manifestations of seizures - what are common cognitive and emotional manifestations?

- cognitive: language or thinking issues; de ja vu!

- emotional: any inappropriate extreme emotion

non-motor manifestations of seizures - what are common sensory, autonomic, and behavioral arrest manifestations?

- sensory: numbness, tingling, hearing or tasting things, vertigo

- autonomic: salivating, sweating

- behavioral arrest: staring, freezing

T/F: focal onset seizures always remain in their initial hemisphere of the brain

FALSE

- can spread to both hemispheres

- Sx are often tonic-clonic

- hard to distinguish from general onset seizures!

what portions of the brain do general seizures occur and what are the characteristics of Sx?

arise in both hemispheres

- motor manifestations are bilateral and symmetrical

what are absence seizures? describe their characteristics

brief, sudden loss of consciousness

- short duration (2-30 secs), but can happen hundreds of times per day

- unaware of the environment / unresponsive

- minimal post-ictal confusion

- NO motor manifestations

- spontaneous remission in 70% of cases

describe the manifestations and their location for myoclonic seizures; do individuals experiencing these seizures often lose consciousness?

sudden, brief muscle contractions

- isolated or rapidly repetitive; "jerks"

- bilateral and either generalized or only observed in one part of the body

- NOT associated with alteration of consciousness

describe the manifestations and their location for generalized tonic-clonic seizures; do individuals experiencing these seizures often lose consciousness?

sudden, sharp bilateral tonic contraction of the muscles with a subsequent period of rigidity and clonic movements

- impaired breathing

- contraction of expiration muscles and larynx (may make groaning sounds)

- jaw muscle contraction

- increased sympathetic tone (increased HR and BP)

- loss of sphincter control (incontinence)

- loss of consciousness

describe the Sx observed in the post-ictal phase of generalized tonic-clonic seizures

can last for a few to 30 mins

- unresponsive, muscular flaccidity, excessive salivation

- drowsiness

- confusion

- HA, fatigue, muscle aches

the longer the seizure, the longer the post-ictal phase!

describe the manifestations of atonic seizures

brief, sudden loss of muscle tone

- head or limb drop

- collapse (all limbs affected)

how are seizure disorders diagnosed?

relies on patient/caregiver reports

- NO lab tests or objective signs inter-ictally

imaging tests

- electroencephalograms (EEGs): identify where in the brain the seizures are occurring

- MRI: may display finding SUGGESTIVE of seizures

- CT: identify CNS disease, which may predispose a patient to seizures

what is status epilepticus?

seizures that lasts >5 mins OR are recurrent without the return of consciousness

- neurologic emergency

- associated with brain damage and death

- (treated with LARGE doses of benzodiazepines, but may result in ventilation use)

what is non-convulsive status epilepticus?

ongoing seizure activity without outward signs of seizure (still can be damaging to brain)

- if a seizure lasts a long time, the patient will eventually stop having tonic-clonic manifestations and will APPEAR to be in the post-ictal phase, but is actually STILL SEIZING!

what ages and races experience the highest incidence of status epilepticus?

- non-white people

- <1 and >60 yo

what are some possible etiologies of status epilepticus with NO structural lesions?

- low anti-epileptic drug levels (MAIN CAUSE)

- infection

- metabolic issues (hyper-/hypo-glycemia)

- alcohol abuse or withdrawal

- drug-related

- unknown

what are some possible etiologies of status epilepticus WITH structural lesions?

- anoxia/hypoxia

- CNS tumor

- stroke (hemorrhagic stroke-related seizures typically occur within the first 7 days, while ischemic stroke-related seizures occur later)

- trauma

- drug overdose

- congenital malformations

what are the most common etiologies of status epilepticus observed in infants and young children?

infants

- withdrawal seizures (due to maternal substance abuse)

- pyridoxine deficiency

- acute encephalitis

- metabolic disorders

young children

- fever

- viral illness

what are the most common etiologies of status epilepticus observed in adults?

- CVA (strokes)

- rapid anticonvulsant withdrawal (important to taper!)

- low anticonvulsant levels

- drug abuse/withdrawal

how long does it take for neuronal destruction to occur due to status epilepticus?

30-60 mins

patients with status epilepticus frequently develop _______________; what are the associated consequences?

epilepsy

- less likely to experience seizure remission

- associated with acquired intellectual disability, neurological and memory deficits, and cognitive dysfunction

how does the death rate due to status epilepticus change with age? what influences these rates?

increases with age

- influenced by time to treatment initiation and duration of the seizure

describe the pathogenesis of status epilepticus

quick succession of seizures OR strong proconvulsant stimulus that overwhelms the brain's inhibitory mechanisms

describe the clinical presentation of status epilepticus

- altered consciousness

- muscle contractions, spasms, extensor or flexor posturing (over time, these become less apparent)

- secondary injuries (falls, bites tongue, cognitive impairment)

how is status epilepticus diagnosed?

- EEG

- must determine the cause!

■ labs

■ vital signs

■ lumbar puncture

■ neuroimaging