Epilepsy and Seizures Flashcards
What is a seizure? What can they be caused by?
A seizure is a transient occurrence of signs or symptoms due to abnormal, unsynchronized neuronal activity in the brain. It is a sudden clinical event, that occurs with a clear beginning and end.
They can occur at any age, have variable recurrence and can have multiple etiologies.
A seizure can be a manifestation of CNS injury : CNS disorder (vascular disorders, head injuries, hypoxia), metabolic disorder (hypo/hyperglycemia, hypo/hypernatremia), toxic disorder (alcohol withdrawal syndrome, cocaine), infectious diseases.
A previous seizure increases the chances of having another one, especially if the cause remains : missed medication intake, altered drug absorption, pharmacokinetic interactions, sleep deprivation, alcohol intake.
Semiology of seizures?
Semiology of seizure focuses on how different parts of the brain contribute to specific signs and symptoms during a seizure. This can help identify the epileptogenic zone.
- It is important to recall initial symptoms and details as they can provide important clues to the epileptogenic zone.
- Patterns of seizure spread often start with face jerks and the progress to the upper and then lower limbs.
- Lobe specific seizure.
- The temporal lobe generates cognitive and emotional symptoms such as Deja vu, can cause auditory or olfactory hallucinations and is associated to automatisms such as lip smacking, chewing.
- The occipital lobe may cause visual hallucinations that vary in complexity.
International classification of siezures 1981 and the new ILAE classification of 2017?
The international classification of seizures 1981 is old but still used.
- Partial seizures that can be :
- Simple (no loss of consciousness) and can be sensory, motor, psychic, autonomic.
- Complex (with impaired consciousness) and can be with/without aura and with/without automatisms.
- Generalized seizure (wide area of brain) and can be tonic-clonic, atonic, myoclonic.
The new ILAE classification isn’t based on :
- Onset :
- Focal, starts from specific point in the cortex.
- Generalized, both hemispheres affected since beginning.
- Unknown.
- Motor involvement.
- Awareness.
What is an absence seizure?
Absence Seizure is a type of generalized seizure most commonly seen in children, though it can occasionally occur in young adults. It’s essential to differentiate it from “minor seizures” because, in absence seizures, there are no jerks or tonic-clonic movements.
Pathophysiology: Thought to be due to abnormal interactions between the cortex and the thalamus, leading to sudden, synchronized discharges across the brain.
Clinical Presentation : the child suddenly stops an activity (like reading or drawing), becomes unresponsive, and exhibits a “blank stare” or behavioral arrest. There may be some minor movements such as slight blinking or muscle twitching. Unlike other generalized seizures, the patient recovers immediately.
What is epilepsy?
Epilepsy is a brain disorder characterized by a long-term predisposition to generate epileptic seizures. Historically, the diagnosis of epilepsy required at least two unprovoked seizures occurring more than 24 hours apart. This definition arose from the observation that the risk of a second seizure following a single event was about 30%, but it rose to around 70% after a second event, indicating a stronger likelihood of recurrent seizures.
The modern approach to epilepsy diagnosis doesn’t always require two seizures. A single seizure can be enough for diagnosis if risk factors indicate a high likelihood of recurrence, equivalent to the risk seen after two unprovoked seizures. Risk factors include imaging abnormalities, epileptiform discharges on EEG, nocturnal seizures. Also depends on the lifestyle and occupation.
Classification of epilepsy?
Seizure classification is based on the onset of the seizure, which refers to the initial area of the brain where abnormal activity begins, rather than how the seizure evolves over time.
- Focal seizures —> activity spreads from a specific locus.
- Generalized forms of—> sudden involvement of all the cortex.
- Combined forms —> generally associated with encephalopathies.
- Unknown.
What are the main causes of epilepsy, and how is understanding its etiology important for treatment?
Epilepsy can have various causes:
- generalized epilepsies are often genetic, linked to polygenic familiarity, with abnormal thalamus-cortex interactions leading to widespread cortical involvement.
- Combined epilepsies are secondary to conditions like developmental delays or encephalopathies. Emerging evidence highlights immunological (autoimmune-related) and metabolic factors as additional causes.
Understanding etiology is essential for assessing recurrence risks and disease progression, but current treatments (anti-seizure medications) address symptoms, not the root causes, making research into these mechanisms critical for future therapies.
What is epileptic syndrome? How are they distinguished?
It is a specific set of seizure types and EEG with imaging that tends to have age dependent features, triggers and prognosis.
Until 2022 they were distinguished binary : self limited, syndromes with a spontaneous resolution and often age related and pharmacoresistant/catastrophic, do not show spontaneous resolution.
Later ILAE published many papers regarding the classification. What is impirnat to understand is that these syndromes are a spectrum. So as a patient ages they can move across this spectrum from a benign phenotype to a malignant one. This is because epilepsy is polygenic.
Childhood absence epilepsy?
Childhood Absence Epilepsy (CAE) is a common type of generalized genetic epilepsy affecting children and young adults. It is characterized by absence seizures, brief episodes lasting 3-10 seconds, often triggered by hyperventilation. These seizures can be self-triggered by children as they may perceive them as pleasurable. The EEG typically shows generalized 3 Hz spike-and-wave discharges. Prognosis is generally good, but in some cases, CAE can progress to other genetic epilepsies.
What is Status Epilepticus, and why is it a medical emergency?
Status Epilepticus (SE) is defined by recurrent seizures without recovery between episodes, seizures lasting longer than 5 minutes, or non-convulsive seizures exceeding 20 minutes. It is a medical emergency because prolonged seizures can cause neuronal death, brain network damage, and increase the risk of developing epilepsy. SE is categorized by two critical time points:
• T1: The time (e.g., 5 minutes for tonic-clonic SE) after which a seizure is unlikely to stop spontaneously, requiring urgent intervention.
• T2: The maximum time (e.g., 30 minutes for tonic-clonic SE) before which the seizure state must be resolved to prevent critical complications.
Tonic-clonic SE progresses from an initial compensatory phase (increased CO2, blood pressure, blood sugar, and lactate) to a decompensation phase, leading to respiratory collapse, rhabdomyolysis, kidney failure, and multi-organ failure if untreated. Immediate medical intervention is essential.
What is Non-Convulsive Status Epilepticus (NCSE),
Non-Convulsive Status Epilepticus (NCSE) is characterized by a lack of involuntary movements and varying levels of consciousness impairment, making it harder to diagnose, especially in patients with preexisting neurological conditions (e.g., post-stroke). Diagnosis requires an EEG and follows the Salzburg criteria, unlike convulsive SE, which can be diagnosed clinically.
How is Status Epilepticus (SE) classified and managed?
Stage 1: Early SE, treated with benzodiazepines.
Stage 2: Established SE, occurs after failure of first-line benzodiazepine treatment.
Stage 3: Refractory SE, continuous SE after failure of second-line treatments.
Stage 4: Super Refractory SE, persists despite anesthetic treatment for over 24 hours, requiring ICU admission for general anesthesia.
Research shows that third-line anesthetic treatments may worsen outcomes unless there is a motor component justifying aggressive intervention.
Epidemiology and Prognosis:
• SE is more common in older populations or those with underlying conditions. • Mortality risk is 2-4%, with higher rates in cases with hypoxic-anoxic causes. • For adults with a first SE episode, mortality is approximately 20%, and 40% develop subsequent epilepsy. • Cognitive consequences are generally minimal, but up to 50% of survivors may have disabling neurological deficits.
What is New Onset Refractory Status Epilepticus (NORSE), and how is it evaluated and managed?
New Onset Refractory Status Epilepticus (NORSE) is a rare clinical condition characterized by the sudden onset of refractory status epilepticus in patients without preexisting epilepsy or significant neurological disorders. It lacks a clear acute structural, toxic, or metabolic cause. NORSE often presents as super-refractory status epilepticus, though this is not required for diagnosis.
Key features : associated with viral infections, autoimmune disorders, though causal roles of antibodies and viruses remains unclear.
Diagnostic work up includes imaging, CSF analysis and toxicology/bloodwork.
NORSE remains a challenging condition requiring a multidisciplinary diagnostic and therapeutic approach.
What is Febrile Infection-Related Epilepsy Syndrome (FIRES), and how is it managed?
Febrile Infection-Related Epilepsy Syndrome (FIRES) is a severe subcategory of New Onset Refractory Status Epilepticus (NORSE) that occurs following a febrile infection, which starts between two weeks and 24 hours prior to the onset of refractory status epilepticus (RSE). It affects children more commonly, though it can occur at any age and has a male prevalence. The pathophysiology may involve immune activation, potentially exacerbating or triggering the condition.
Treatment strategies :
First line —> corticosteroids, IV IG and plasmapheresis.
Second line —> tacrolimus, rituximab, cyclophosphamide and anakinra.
How is a seizure diagnosed in an emergency setting, and what are the steps taken to determine its cause and nature?
In the emergency room (ER), the initial challenge is confirming whether an event is indeed a seizure. The differential diagnosis includes conditions like syncope, transient ischemic attacks (TIA), transient global amnesia (TGA), psychogenic non-epileptic seizures (PNES), sleep disorders, movement disorders such as dystonia, and others such as migraine and benign paroxysmal positional vertigo.
After confirming a seizure we must determine the type, asses consciousness impairment and identify if the event was a single seizure, a cluster or SE.
We must create a detailed medical history of the patient to better understand the onset.
Finally potential causes need to be examined such as CNS disorders, metabolic disorders, toxic disorder and infectious diseases.
Diagnostic tests : CT scan, blood test, ECG, EEG, lumbar puncture, MRI and toxicology panel.
What are the distinctions and genetic factors involved in early-onset and late-onset epilepsy?
Early-onset epilepsy often has a genetic basis, with some types showing clear Mendelian inheritance, while others may involve common genetic risk factors, including single nucleotide polymorphisms (SNPs). Moreover, the infantile brain is more susceptible to hyperexcitation due to the initially excitatory nature of GABA receptors, which are the primary inhibitory receptors in the brain. During early development, these receptors are excitatory, leaving the major inhibitory system undeveloped until later in life, thus increasing the likelihood of hyperexcitability in young children.
In contrast, late-onset epilepsy is often secondary to other underlying conditions such as strokes, tumors, or vascular problems. The peak occurrence of epilepsy in later life usually stems from these secondary causes.
What is epileptogenesis, and why is understanding this process critical for the development of effective epilepsy treatments?
Epileptogenesis is the process by which a normal brain becomes capable of generating spontaneous seizures. This transformation typically follows an initial brain insult, such as a traumatic injury, stroke, or tumor growth, which disrupts normal neural activity. The process involves an immediate response with gene activation changes, followed by a slow response including transcriptional changes and inflammation, and eventually leads to neural circuit plasticity involving neurogenesis and gliosis. These changes decrease the threshold for neuronal excitability, facilitating the onset of epilepsy.
What are the limitations of current anti-seizure medications in treating epilepsy, and what are the implications of drug resistance in epilepsy treatment?
Current anti-seizure medications primarily focus on reducing the frequency, duration, and extent of seizure activity but do not address the initial causes of epilepsy or repair damage caused by seizures. These medications aim to prevent further damage by reducing seizure-induced ischemia, which can exacerbate the condition. However, they do not intervene in the process of epileptogenesis—the development of an epileptic condition.
A significant challenge in epilepsy treatment is drug resistance. Many patients do not respond to the first anti-epileptic drug tried; only about 50% see improvement. This response rate might increase to two-thirds when two or three different drugs are used, but additional drugs do not significantly enhance the response rate. This highlights the inefficacy of adding more medications once resistance to initial treatments is evident.
What are the primary targets of current epilepsy drugs?
- Glutamatergic Transmission : Drugs may attempt to block glutamate receptors to reduce excitatory neurotransmission. However, due to glutamate’s critical role in normal brain function, this approach has limited applications.
- Sodium (Na+) Channels : Many antiepileptic drugs target Na+ channels to inhibit the propagation of hyperactivity in neurons. These drugs, such as carbamazepine, lamotrigine, and topiramate, are designed to bind to the channels and prevent them from reactivating too quickly after inactivation, thus selectively dampening hyperactive neurons.
- Calcium (Ca2+) Channels : Particularly T-type Ca2+ channels in the thalamus, these are crucial for controlling thalamic relay mechanisms that contribute to the spread of seizure activity. Drugs like ethosuximide specifically target these channels, making them effective in treating certain types of epilepsy, such as absence epilepsy.
- GABAergic Transmission: Enhancing the inhibitory effects of GABA is another strategy used by several antiepileptic drugs. Benzodiazepines, barbiturates, and others like topiramate increase the sensitivity of GABA receptors or the availability of GABA in the synaptic cleft. This helps restore balance between excitation and inhibition but can also lead to tolerance and sedative side effects.
What are some alternative approaches to treating pharmaco-resistant epilepsy, and how do they function?
- Surgical approaches : Surgery typically involves removing parts of the brain where seizures originate. Advances in medical imaging and surgical techniques now allow for more precise targeting of these epileptic foci.
- Gene therapy : Still largely experimental, gene therapy for epilepsy has shown promise in animal models.
- Cannabidiol : Cannabidiol, derived from cannabis, has been approved for treating severe infantile forms of epilepsy, such as Lennox-Gastaut syndrome and Dravet syndrome.
What are the pharmacological properties, uses, and risks associated with phenobarbital, particularly in the context of epilepsy treatment?
Phenobarbital is a barbiturate that has been used historically as both an anxiolytic and an anticonvulsant. Its primary mechanisms include the modulation of GABA_A receptors and inhibition of Ca^2+ channels, which contribute to its anticonvulsant effects.
It is effective in controlling seizures at low dosages and is relatively low in cost.
Risk and side effects : overdosing can suppress CNS leading to death, it can interact with some other drugs, common side effects include sedation, nystagmus and megaloblastic anemia.
Due to its side the use has declined.
What are the therapeutic effects and pharmacological characteristics of phenytoin in the treatment of epilepsy?
Phenytoin, also known as diphenylhydantoin, is a longstanding anticonvulsant drug primarily used to treat various kinds of tonic-clonic seizures, though it is not effective for absence seizures. I
Phenytoin functions as a use-dependent inhibitor of sodium channels, meaning it preferentially binds to and inhibits the function of these channels when they are frequently active.
Side effects are many such as CNS effects, dermatological, GI, hematological.
Due to its narrow therapeutic index careful monitoring of blood levels is crucial.
What are the pharmacological effects, therapeutic uses, and potential side effects of carbamazepine?
Carbamazepine is a widely used medication that serves multiple roles, primarily as an anticonvulsant and mood stabilizer. It is known for its effectiveness in controlling certain types of seizures and mood disorders due to its various mechanisms of action on neuronal ion channels and intracellular signaling.
- Na+ Channels: Carbamazepine primarily works by slowing the rate of recovery of sodium channels from inactivation, which reduces the ability of neurons to fire repetitively and excessively.
Effective in the treatment of partial seizures and generalized tonic clonic seizures, used as a mood stabilizer in bipolar disorder and used for neuropathic pain.
Side effects include : neurological effects, hypersensitivity reaction and water retention.
What are the therapeutic effects, mechanisms of action, and potential side effects of valproic acid in the treatment of epilepsy and mood disorders?
Valproic acid is a versatile medication widely used in the management of epilepsy, particularly in infantile forms, and as a mood stabilizer in psychiatric disorders. Its broad spectrum of activity and relative lack of sedative effects make it especially suitable for use in children.
It enhances GABAergic activity primarily by inhibiting GABA transaminase, which breaks down GABA. This results in increased GABA levels in the brain, enhancing its inhibitory effects on neuronal firing.
It also slows the recovery rate of sodium channels from inactivation and inhibits T-type calcium channels, contributing to its anticonvulsant properties.
Side effects include GI, neurological, dermatological, liver toxicity.
