Neurology: Seizure & Epilepsy (PDF)

**OUTLINE** I. **Introduction** II. **Seizure** III. **Epilepsy** a. Risk of Epilepsy After 2 Seizures b. Resolved Epilepsy IV. **Seizure vs. Epilepsy** V. **Basic Pathology of Seizures and Epilepsy** c. Excitatory Transmission d. Inhibitory Transmission VI. **Common...

**OUTLINE** I. **Introduction** II. **Seizure** III. **Epilepsy** a. Risk of Epilepsy After 2 Seizures b. Resolved Epilepsy IV. **Seizure vs. Epilepsy** V. **Basic Pathology of Seizures and Epilepsy** c. Excitatory Transmission d. Inhibitory Transmission VI. **Common Etiologies of Seizures in Children** VII. **Conditions Also Presenting with Seizures** VIII. **Approach to Diagnosis** IX. **New Definition and Classification** e. Seizure Confirmation f. Basic Version X. **Basic Pathophysiology of Seizures and Epilepsy** XI. **Epilepsy Diagnosis** g. Definition of Terms h. Abbreviation for the Most Important Seizure Types i. Common Descriptors of Behaviors During and After Seizure XII. **Epilepsy Classification** j. 2017 ILAE Epilepsy Classification k. Seizure Type Identification l. Criteria for Syndrome Classification XIII. **2022 ILAE Epilepsy Classsification** m. Childhood Absence Classification n. Juveneile Myoclonic Classification o. Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS) XIV. **Developmental / Epileptic Encephalopathy** p. Infactile Epileptic Spasms Control XV. **Other Relevant Conditions PRE** q. Neonatal Seizures r. Febrile Seizures s. Status Epilepticus XVI. **Approach to Seizure** t. Evaluation After 1^st^ Seizure u. Electroencephalography v. Neuroimaging Procedure w. Majore Issues in Epilepsy x. Management of Epilepsy XVII. **Anti-Seizure Medication** XVIII. **Status Epilepticus Management** +-----------------------+-----------------------+-----------------------+ | **LEGEND** | | | +=======================+=======================+=======================+ | ⭐ | 🖊️ | 📖 | | | | | | Must | Lecture | Book | | | | | | Know | *\[lec\]* | *\[bk\]* | +-----------------------+-----------------------+-----------------------+ OBJECTIVES {#objectives.ListParagraph.TransOutline} ========== At the end of this lecture, the future Bedan must be able to: - Discuss the definition of seizure vs. epilepsy - What is the pathophysiology of seizure - Classification of Seizure Types - Classification of Epilepsies - Discuss special conditions -- febrile seizures, neonatal seizures INTRODUCTION {#introduction.TransOutline} ============ Figure 1. Impact of seizure 🖊️*According to WHO, the burden of epilepsy is high and is often neglected in public health agendas.* - 🖊️*Epilepsy is one of the most common neurological diseases affecting more than 50 million people of all ages around the world.* - The risk for premature death with people with epilepsy is 3-6x greater than the general population. - Roughly half of the people with epilepsy have at least one other health condition like: - Physical disability like cerebral palsy - Neurologic developmental disorder like autism - 🖊️ *Psychiatric conditions such as depression and anxiety make seizures worse and reduce the quality of life*. - *🖋Epilepsy has significant applications. In terms of health care needs and terms of productivity at work, the projected prevalence rate of epilepsies is \~7.6 per 1,000 persons.* - Majority of people with epilepsy (80%) live in low- and middle-income countries like the Philippines and majority of them (75%) do not receive adequate treatment. - The cause of the treatment gap is due to the **lack of trained staff, poor access to anti-seizure medication, societal misconceptions** about epilepsies, **poverty**, and the **low prioritization** for the treatment of epilepsy in the public health. - It also carries stigma and discrimination impacting their function in the family, work, and social standing. - Epilepsy is one of the most common neurologic diseases in children. - 1 in 150 children is diagnosed with epilepsy during the first 10 yrs of life, with the highest incidence rate observed during infancy. - No available data on lifelong highest incidence rate and active case of epilepsy in the PH. - *"We are still in the process of creating a database for Px with epilepsy"* - Estimated prevalence is 9/1000 persons-years-990,000 Filipinos are living with epilepsy - ️"*\~1/3 of these are children \< 15yrs old"* - *️"Much larger today, nasa around 1M Filipinos na ata."* - Large epilepsy treatment gap - Reasons: - Limited \# of physician's confident in Dx and Tx. - Limited access to medications-most pronounced in geographically isolated & financially disadvantaged areas. - ️ *"Recently with the passing of the PH mental health law in 2018, we are now mandated to discuss epilepsy in all lvls of education esp. In medical school."* SEIZURE {#seizure.TransOutline} ======= - **Transient & reversible** alteration of behavior caused by a paroxysmal, abnormal, & excessive (hypersynchronous) neuronal discharge. - 🖊️ *Biglang tumaas yung kuryente sa brain. In other words, it is only temporary. It can go back to normal or back to baseline.* - An event of **cerebral origin** - **Sudden & transitory abnormal phenomena** (motor, sensory, autonomic / behavioral) - Transient dysfunction of [one part or all the brain] EPILEPSY {#epilepsy.TransOutline} ======== - A **disease of the brain** characterized by an [enduring predisposition to develop seizures.] - 🖋Seizure disorder yung tawag ng older physicians [but they are not equivalent.] - 🖋"Ang seizure disorder kasi ay any condition presenting with seizures" - Practical (or operational) definition: - **At least 2 unprovoked (or reflex) seizures occurring \> 24H apart.** - Used clinically - 🖊️ ***unprovoked*** *meaning there is [no cause or exocranial infection]; no provoking factors such as dec. Electrolytes like hyponatremia.* - *️ it can be a **reflex seizure provoked by certain stimuli** such as lights, reading, music, and it should always be constant with the stimulus.* - **1 unprovoked (or reflex) seizure** & w/ risk factors for ↑ seizure risk recurrence (\~60%) occurring over the next 10 years. - *🖋 Based on FMHx, Dx workups, & certain factors* - Diagnosis of an epilepsy syndrome: - *🖋 Epilepsy syndrome is a set of conditions wherein a patient is age-dependent, has certain EEG & seizure characteristics* RISK OF EPILEPSY AFTER 2 SEIZURES {#risk-of-epilepsy-after-2-seizures.TransSubtopic1} ---------------------------------  - **Figure 2**. Risk of recurrence vs. age - *🖋 In a prospective study wherein, they follow people with having 2 or more seizures, they noted that after 2^nd^ seizure within the next 6-12month period, the risk of occurrence is reaching \~60%* - 🖋 Ito ung reason kung bakit sila nag-adapt ng 60% as the lower end of the CI for recurrence risk of seizures - After 2 unprovoked seizures, by the 60^th^ month the risk is 73% (Mataas na seizure recurrence risk nila for the next 5 yrs.) RESOLVED EPILEPSY {#resolved-epilepsy.TransSubtopic1} ----------------- - Individuals who had an age-dependent epilepsy syndrome but are now past the applicable age. - Those who have **remained seizure-free for the last 10yrs, w/ no seizure medicines for the last 5 yrs.** - 🖋 Read this journal suggest ni doc = A qr code on a white background Description automatically generated SEIZURE VS. EPILEPSY {#seizure-vs.-epilepsy.TransOutline} ==================== - **Seizure** is the [most common **symptom**] of the disease. - **Epilepsy** is the [**disease** associated with spontaneously recurring seizures.] - Seizure disorder is [not synonymous] to epilepsy. - Seizure disorder is vague. - It may include other conditions such as febrile seizures, acute symptomatic seizures. - DO NOT USE AS DIAGNOSIS BASIC PATHOLOGY OF SEIZURES AND EPILEPSY {#basic-pathology-of-seizures-and-epilepsy.TransOutline} ======================================== - 3 PHYSIOLOGIC REQS FOR SEIZURES TO OCCUR: - **Population of pathologically excitable neurons (HYPEREXCITABILITY)** - **↑ excitatory (glutaminergic) activity through recurrent connections to spread the discharge.** - 🖋 *Meaning, mas tumaas din yung release ng glutamate sa brain that can propagate the discharge of the neighboring nearby neuron.* - **↓ in activity of the normally inhibitory GABAergic projections (HYPERSYNCHRONY)**  Figure 3. Balance of seizure and control - *🖋 If EPSPs (Excitatory post synaptic potential), meaning [↑ Na+ influx, ↑Ca2+ ions,] which causes paroxysmal depolarization, recruits enough \# of neurons, & progresses & bypasses the inhibitor GABAergic projections, it causes a seizure.* - Seizure is controlled by increase of IPSPs (Inhibitory post synaptic potential), K+ efflux, Cl- influx, & acidic profile inhibits seizure propagation. - 🖋 **ketogenic diet** influences this mechanism EXCITATORY TRANSMISSION {#excitatory-transmission.TransSubtopic1} ----------------------- {#section.TransSub-subtopic2} {#section-1.TransSub-subtopic2} **Figure 4.** Excitatory transmission in the presynaptic and postsynaptic - **GLUTAMATE** = Main excitatory neurotransmitter - Attaches to 2 post-synaptic receptors: a. **Non-NMDA** (kainate & amino-3-isoxazole propionic acid or AMPA) i. Responsible for **"Fast" excitatory postsynaptic potential (EPSP)** 1. *🖋Causes Na+ influx at postsynaptic* b. **NMDA** (N-methyl-D-aspartate) Slower ii. Requires **glycine**; receptor has a Mg ion blocking pore opening. iii. Has prolonged sustained EPSP 2. *🖋 Play important role in learning, memory, & neuronal plasticity* INHIBITORY TRANSMISSION {#inhibitory-transmission.TransSubtopic1} ----------------------- {#section-2.TransSub-subtopic2}  {#section-3.TransSub-subtopic2} --------------------- **Figure 5**. Inhibitory Transmission in the presynaptic & postsynaptic - **GABA** = Main inhibitory neurotransmitter - Influx of Ca2+ → depolarization → release GABA into the synaptic cleft → binds to its receptors (GABA) → Cl- ions enter the neuron - Cl- influx ↑ the negative charge inside the postsynaptic neuron → hyperpolarization - 🖋 *Kapag nag decrease itong activity na ito, magkakaroon ng seizure.* - The resultant change in membrane potential is called an inhibitory postsynaptic potential (IPSP) - 🖋 GABA is synthesized from glutamate in the presynaptic neuron by the action of the enzyme glutamate decarboxylase & requires vit. B6 as a cofactor. COMMON ETIOLOGIES OF SEIZURES IN CHILDREN {#common-etiologies-of-seizures-in-children.TransOutline} ========================================= - *🖋 Metabolic etiologies can cause acute seizures & can cause epilepsy later* - *🖋 The most common cause of acquired epilepsy in children in the PH is birth injury which causes **hypoxic ischemic encephalopathy*** - ***🖋** Accidental / non-accidental head trauma can cause **acute asymptomatic seizures*** - If there is brain injury because of the head trauma, then it can also lead later to epilepsies - *🖋* *Shigella gastroenteritis can trigger acute asymptomatic seizures.* - *🖋 The most common in the toxic/drug is the **acute withdrawal of seizure medications (AED)*** - *🖋The most common manifestation of meningitis or meningoencephalitis in any patient is usually seizures.* - Because it irritates the cortical region **Table 1**. Common Etiologies of Seizures In Children CONDITIONS ALSO PRESENTING WITH SEIZURES {#conditions-also-presenting-with-seizures.TransOutline} ======================================== - *🖋* These conditions are not considered as epilepsy - Febrile seizures in children aged **0.5 - 6years old**. - Acute Symptomatic Seizures - Drug (Alcohol withdrawal, adverse drug rxns) - Metabolic (Na+, Ca2+, Mg2+, Glucose, Oxygen, Renal HTN) - Post-traumatic seizures - Seizures within the 1^st^ week of infection/stroke - Convulsive syncope - *🖋Paroxysmal event that mimics seizure. These are fainting spells that can present with convulsive-like episodes.* - The differentiating factor is the ABSENCE OF SYMPTOMS AFTER the event APPROACH TO DIAGNOSIS {#approach-to-diagnosis.TransOutline} ===================== - *🖋 First of all, **we need to confirm if it is really a seizure / not.** Remember may tinatawag na pseudoseizures or yung paroxysmal non-epileptic events which may look like epileptic seizures but they are actually secondary to psychiatric condition. If we are convinced that is a seizure, ask ourselves what the seizure type is.* - *Later, **we classify** them according to focal, general\...etc.* - *We are looking for the [etiology / what is the cause of epilepsies]* - *Subspecialists / who are well-versed for the diagnoisis of epilepsy, we try to diagnose an **epilepsy syndrome**.* - *We [investigate the seizures & patient factors for a clinical pattern]. Why is that?* - *Because, they have certain [prognostic factors & management implications]*  {#section-4.TransSub-subtopic2} **Figure 7:** Clinical algorithm for epilepsy - *🖋 It is very important to take note of the [medical Hx, the PE and NE]* - Blood tests = confirm if there are acute symptomatic seizures - EEG & brain imaging - If ang diagnosis is "could be epilepsy" & 1^st^ seizure, check whether the patient has low/high risk for a 2^nd^ seizure. - **Low risk** = [review] risk factors, pros & cons of treatment - **High risk / presenting w/ 2^nd^ seizure** = [Begin treatment w/ antiseizure medication.] - PNES (Psychogenic Non-epileptic seizure): If they look like they're having seizures, but the EEG is completely normal, - Associated w/ **anxiety** disorder - Treated acc to the underlying psychiatric condition NEW DEFNITION AND CLASSIFICATION {#new-defnition-and-classification.TransOutline} ================================ - *🖋* 2014: Fisher -- Practical Definition of Epilepsy - *🖋* 2017: Fisher -- Operational Classification of Seizure types - *🖋* 2017: Scheffer -- ILAE Classification of the epilepsies SEIZURE CONFIRMATION {#seizure-confirmation.TransSubtopic1} -------------------- - 🖊️ **Clinical history** - Important to emphasize that all patients with seizures that a detailed clinical history is often needed to **differentiate** a **non-epileptic** from **epileptic** seizures in children. - 🖊️ **"Constellation of Symptoms"** (e.g. Ask for eye movement, body movement, affectation of one or both sides, alteration of awareness, presence or absence of other symptoms, duration, and other postictal symptoms) - Onset (How did it start?) - Presence or absence of awareness - 1st Prominent feature (What the eyewitness will provide to you) - 🖊 **Stereotyped pattern with recurring features and evolution** then you can confirm that this is a real epileptic seizure  **Figure 8**. Seizure confirmation BASIC VERSION {#basic-version.TransSubtopic1} ------------- **Figure 9**. Basic version of ILAE seizure type classification - 🖊️ For non-experienced clinicians and medical students - ⭐️ **Focal seizures** - Important to differentiate presence of **awareness** throughout the event - Motor onset (clonic and tonic movements) - Non-motor onset (Blank staring episodes) - *🖊️ Important yung word na onset so pag nag history taking ang tatanungin nyo ay "paano po nagsimula yung seizure? Nakita nyo po ba paano nagsimula?"* - Can evolve into a focal to bilateral tonic-clonic seizure - **Generalized onset** we usually [do not quantify the presence or absence of awareness] because we already [assume that there is absence or impaired awareness] during the seizure. - We [must quantify] if the most prominent feature is a [motor or a nonmotor component.] - *Difficult to note kasi minsan di alam ni eyewitness kung ano yung prominent feature or nagpapanic na sila* - **Unknown onset** if the eyewitness reports [cannot point out or have difficulty] - *🖊️ Pero pwede mong sabihin na may motor component (tonic-clonic) kasi yun yung nakita nila or nagsimula na nakatulala lang yung pasyente, you can say that it is an unknown onset with a non-motor component* - *🖊️Kung medyo [malabo ang description] ng pasyente or eyewitnesses, but it looks the same in all events, pwede muna natin ilagay **temporarily as seizure unclassified*** **BASIC PATHOPHYSIOLOGY OF SEIZURES AND EPILEPSY**  **Figure 10**. Pathophysiology of Focal Seizures - *🖊️ Usually coming from **one part** of the brain, starting from 3 and 4 and it can spread later to the **contralateral side** becoming a **focal to bilateral tonic clonic seizure**.* - *🖊️ From one focus it can spread to the **contralateral hemisphere** through the **thalamocortical network** or through the connections from the **corpus callosum**.* - **Ipsilateral**: focal seizure; **Contralateral**: focal and bilateral tonic-clonic seizure **Figure 11**. Pathophysiology of Generalized seizures - *🖊️ They begin **simultaneously** in **both hemispheres**.* - *🖊️ There is a **characteristic spike wave pattern** in the EEG generated by interactions between the cortex and the thalamus which rapidly spreads via the corpus callosum contributing to the rapid bilateral synchrony of the discharges.* - *🖊️ There is one type of **thalamic neuron** (blue one), is a GABAergic inhibitor that has **intrinsic oscillatory properties**.* - It can fire burst of action potential with specific calcium channels allowing the modulation of the ongoing **excitatory** corticothalamic activity. - Once stimulated, it gives the characteristic spike wave pattern seen on EEG. - [Equal spread] A. **OLD TERMS TO AVOID ⭐** - Complex Partial -- now as **focal impaired awareness seizure** - Simple Partial -- renamed as **focal aware seizure** - Localization-related - **vague** and is **not readily understandable** - Secondarily generalized tonic-clonic is now **focal to bilateral tonic-clonic seizure** - Psychic seizures and dyscognitive seizures are no longer used in literature B. **EXPANDED VERSION**  **Figure 12**. Expanded version of ILAE seizure type classification - 🖊️ Instead of using the basic names of for example focal motor onset, we can use the expanded version to name the seizure as **focal clonic seizure**. - 🖊️ Generalized non-motor seizures are generally called **absences** due to the **presence of blank staring episodes.** - 🖊️ If eyewitnesses are unsure about the onset, you could call it as an unknown onset seizure depending on your observations, for example if the patient came in in active tonic-clonic seizure you can temporarily classify it as **tonic-clonic seizure with an unknown onset.** - 🖊️ If not clear but you are sure that it is a seizure, it can temporarily be called as an **unclassified seizure.** - ***Notes from discussion ⭐*** - Atonic seizures and epileptic spasms would not have level of awareness specified - Pedalling grouped in hyperkinetic rather than automatisms (arbitrary) - Cognitive seizures: (🖊️ sa mga behavioral arrest, non-motor onset) - Impaired language - Other cognitive domains - Positive features e.g. déjà vu, hallucinations, perceptual distortions - Emotional seizures: anxiety, fear, joy, etc. - 🖊️ we have to be very cognizant of this because this can also be the initial features for non-epileptic events or yung mga RULES FOR CLASSIFYING SEIZURES {#rules-for-classifying-seizures.TransSubtopic1} ------------------------------ - Onset: - Decide whether seizure onset is focal or generalized, using an 80% confidence level, Otherwise, onset is unknown. - Awareness: - For focal seizures, decide whether to classify by degree of awareness or to omit awareness as a classifier. - Impaired awareness at any point: - A focal seizure is a focal impaired awareness seizure if awareness is impaired at any point during the seizure - 🖊️ A focal impaired awareness seizure is usually longer and can be followed by motor component after. The features are usually more prominent - 🖊️ Versus absences which are usually brief and recurrent most of the time, mabibilis lang sila - Onset predominates: - Classify a focal seizure by its first prominent sign or symptom - Do not count transient behavior arrest - Optional terms: - Terms such as motor or nonmotor may be omitted when the seizure type is otherwise unambiguous (clearly recognizable) - Additional descriptors: - After classifying seizure type based on initial manifestations, it is encouraged to add descriptions of other signs and symptoms, suggested descriptors or free text. These do not alter the seizure type - Example: focal emotional seizure with tonic right arm activity and hyperventilation - **Bilateral vs. generalized**: - Use the term "bilateral" for tonic-clonic seizures that propagate to both hemispheres and "generalized" for seizures that apparently originate simultaneously in both - **Atypical absence**: if it has slow onset or offset, marked changes in tone or EEG spike-waves at less than 3 per second - 🖊️ It is very difficult to differentiate a focal impaired awareness seizures from atypical absences. Ang kailangan naming dyan ay isang EEG recording' - **Clonic vs. myoclonic:** clonic refers to sustain rhythmical jerking and myoclonic to a regular unsustained jerking - **Eyelid myoclonia:** absence with eyelid myoclonia refers to forced upward jerking of the eyelids during an absence seizure - 🖊️ Parang nagbeautiful eyes **EPILEPSY DIAGNOSIS** - 🖊️ Clinical History - Precipitating Factors - Age - Position (Where it happened) - Activity - Was the patient asleep? Awake? Playing? - Intercurrent illness - Medications - 🖊️ Predisposing Factors - Past Medical History - Recent illness or neurological symptoms - Family History - Febrile seizures - Epilepsy - Developmental Problems **Figure 13**. 2017 Algorithm for Classification of Epilepsy - 🖊️ This is a multi-level classification designed to classify epilepsy in different clinical environments. - ⭐ The starting point of epilepsy classification is the **seizure type**; this is the **most important**. - 🖊️ If you're unable to get this from the start, then the diagnosis would become much more difficult. - 🖊️ Level 1 (Seizure type) is already enough if you have a diagnosis of the seizure, but you can move on to the next levels if the patient's seizures would reoccur (Epilepsy type). - ⭐ If unsure, you can classify the episode as unknown but always pay attention to the etiology - Structural - Genetic - Infectious - Metabolic - Immune - Unknown - 🖊️ We try to avoid using the term seizure disorder because this term encompasses all the etiologies that can cause seizure like symptomatic seizure, febrile seizure and the like; not helpful in management - 🖊️ At all levels, you should consider the other comorbidities of the epilepsy such as the presence or absence of intellectual disability, neurodevelopmental conditions such as autism spectrum disorder or ADHD A. **DEFINITION OF TERMS** - 🖊️ **Clonic** -- regularly repetitive jerking of similar muscle groups - 🖊️ **Tonic** -- sustained muscle contraction lasting for few seconds to minutes. - Sometimes need medications. - 🖊️ **Tonic-Clonic** - sequence of tonic followed by clonic phase.  **Figure 14**. First video - A child exhibiting seizure. () - 🖊️ Seizure Type: - Focal impaired awareness (MOTOR) Seizure (Basic) - Focal clon ic seizure (Expanded) - Omit level of awareness - ⭐ Features: - **IMPAIRED AWARENESS** - ⭐ **PROMINENT FEATURE: HEAD JERKING** - Head jerking and left shoulder jerking - Left eye clonic awareness - 🖊️ Usually only affects one side of the body **Figure 15**. A child exhibiting generalized motor seizure. - 🖊️ Seizure Type: - Generalized Motor Seizure (Basic) - Generalized Tonic-Clonic Seizure (Expanded) - ⭐ Features: - Sudden Generalized stiffening - Followed by bilateral clonic arm movements - Notice the head version to one side  **Figure 16**. Patient exhibiting focal to bilateral tonic-clonic seizure - 🖊️ Seizure Type: - FOCAL TO BILATERAL TONIC-CLONIC SEIZURE - ⭐ Features: - Blank Staring - Bimanual automatism - Head version to the right - Bilateral tonic flexion of arms and legs - Bilateral clonic movements **OTHER DEFINITION OF TERMS** - 🖊️ **Myoclonic** - Sudden, brief (\