JC29 (Medicine) - Seizure and LOC Flashcards
1
Q
4 major disease entities that cause sudden LOC +
A
Syncope
Seizure
Pseudo-seizure
Toxic/ Metabolic coma
2
Q
Syncope +
- Pathophysiology/ Mechanism
- S/S, Precipitating factors
- Subtypes
A
Pathophysiology/ Mechanism: Generalized hypoperfusion to the brain
Features
- Brief lightheadedness
- LOC < 1 min, Fast recovery with no confusion
- Precipitated by pain, emotion or standing position (vasovagal)
- S/S: darkening of vision, tinnitus, hyperventilation, distal tingling, nausea, clamminess or sweating
Subtypes
- Neurocardiogenic: Situational, Vasovagal, Hypertensive carotid sinus syndrome
- Postural hypotension
- Cardiogenic: poor cardiac output causes
3
Q
Seizure
- Pathophysiology/ Mechanism
- Different S/S and presentations
- Causes
A
Pathophysiology/ Mechanism: abnormally excessive or synchronous activity in brain
Features: Transient altered awareness + abnormal behavior + involuntary movement
- Preceded by aura (eg. peculiar taste/smell, déjà vu feeling, auditory hallucination, anxiety, nausea, abdominal pain)
- LOC + falling + clonic movement = generalized tonic clonic
- LOC + stare blankly into space = absence
- LOC + Localized contractions = focal
- Lasts > 1 min with slow recovery
- S/S incontinence, uprolling eyeball, tongue-biting
Causes:
- Epilepsy (unprovoked)
- Provoked seizures
4
Q
Causes of provoked seizures
A
Provoked seizures:
- Drugs or toxin-related
- Metabolic, eg. hypoGly, hypoCa, hypoNa
- CNS infection
- Acute stroke or haemorrhage
- Head trauma
- Febrile convulsion in children
Provoked seizure means NOT EPILEPSY
5
Q
Pseudo-seizure
- Pathophysiology/ Mechanism
- Features
A
Mechanism - Psychogenic, non-epileptic attack
Features
- Long episodes >30 mins, rapid recovery/ emotional distress
- Precipitate by emotional triggers
- Retain awareness, only 10% LOC
- Eyes cannot be opened
6
Q
Differentiate seizures from syncope
A
Features Specific to seizure, not syncope:
- Aura
- Cyanosis
- Tongue-biting
- Post-ictal confusion, amnesia, headache
Features specific to syncope, not seizure:
- Rapid recovery
- +/- minor tongue biting
7
Q
Compare toxic and metabolic coma S/S
Causes of each type of coma
A
Toxic coma
- transient, intermittent coma
- Cause by alcohol, solvent, barbituates
Metabolic coma
- LOC
- Preceded by sweating, confusion, weakness
- Cause by insulin, fasting, anti-diabetics
8
Q
Likely causes of sudden LOC precipitated by micturition, sleep, standing, and exercise
A
→ During blood-taking, micturition - syncope
→ During sleep - seizure
→ Standing - orthostatic hypotension
→ During exercise - outflow obstruction
9
Q
Common forms of aura
A
- Peculiar taste or smell
- Feeling of déjà vu
- Feeling of jamais vu (never seen)
- Hearing of familiar music
- Feeling of fear or anxiety welling up in chest
- Visceral feelings, eg. nausea, abdominal pain
10
Q
Presentation:
Short LOC with rapid recovery
Under 1 minute
Brief, asynchronous jerking
Pallor
Light-headedness, sweating, visual darkening
Most likely dx?
A
Syncope
11
Q
Presentation:
Few minutes of LOC with slow recovery and confusion
With aura
Incontinence
Tongue-biting
Tonic-clonic movement
Most likely Dx
A
Generalized seizure
12
Q
Presentation:
Several hours episode, no LOC
Partially retain awareness
Eyes cannot be open
Preceded by emotional distress
Most likely dx?
A
Pseudo-seizure/ Psychogenic seizure
13
Q
First-line investigations for sudden LOC
A
Ix
EEG for epilepsy
ECG ± Holter monitor for arrhythmia
Tilt-table test for neurogenic syncope and orthostatic hypotension
Echocardiography for cardiomyopathy
Blood glucose for hypoglycaemia
14
Q
Physiological control of consciousness
- Define consciousness
- Components of consciousness
- Areas of brain involved
A
Consciousness: state of awareness of self and surrounding
Components:
□ Arousal: state of being ‘awake’ → from ascending reticular formation + thalamus
□ Awareness: cognitive and affective mental function (i.e. the ‘content’) → from anterior cingulate and precuneus
Dependent on:
□ Reticular activating system (RAS) in brainstem, hypothalamus, thalamus
□ Cerebral hemisphere
15
Q
Reticular activating system (RAS)
- Location in brain
- Function
- EEG patterns in wakefulness and sleep
- Physiological mechanisms
A
Location: Upper brainstem and medial thalamus
Function: Maintain cerebral cortex in state of wakeful consciousness
EEG pattern:
- Awake/ REM sleep = desynchronized waves
- Non-REM sleep = Regular spindles
Mechanisms:
- Thalamic relay neurons from brain stem to thalamus > activate cortical pyramidal neurons > control level of consciousness
- Tonic mode: thalamic neurons fire and activate cortex in desynchronized way > maintain wakefulness/ REM sleep
- Burst mode: thalamic neurons fire and active cortex in synchronous way > non-REM sleep
16
Q
Coma
- Definition
- GCS cut-off
- Critical brain structure involved
A
Coma: severe impairment of arousal ± awareness
Definition: GCS ≤8 (E≤1, V≤2, M≤5)
- Diffuse bilateral cortical/ hemispheric damage
- Direct damage/suppression of RAS or its projections)
- Suppression of reticulo-cerebral function: drugs, toxins, metabolic causes
17
Q
Intracranial causes of coma
A
□ Traumatic: diffuse white matter injury, haematoma
□ Vascular: SAH, ICH, cerebral infarct with ↑ICP, brainstem infarct/haemorrhage
□ Neoplastic: tumour with oedema
□ Infective: meningitis, abscess, encephalitis
□ Others: epilepsy, hydrocephalus
18
Q
Extracranial causes of coma
A
□ Metabolic: electrolyte imbalances, liver/renal failure, endocrine disorders
□ Drugs/toxins: sedatives, anticonvulsants, anaesthetics, alcohol, heavy metals, CO…
□ Vascular occlusion: vertebral artery disease, bilateral carotid disease
□ Cardiorespiratory insufficiency
□ Psychiatric: hysteria, catatonia
19
Q
Structural causes of coma
A
- Bilateral internal carotid artery occlusion
- Bilateral anterior cerebral artery occlusion
- Basilar occlusion
- Subarachnoid hemorrhage
- Thalamic hemorrhage
- Pontine hemorrhage
- Trauma - contusion, concussion
- Hydrocephalus
- Midline brainstem tumor
20
Q
List disorders of conscioussness
A
Coma
Stupor - baseline unresponsiveness, only aroused by vigorous stimuli
Persistent Vegetative State (PVS)
Akinetic Mutism and Abulia
Inattention
21
Q
Persistent vegetative state
Definition
Area of brain involved
Common causes
Prognosis
A
Definition
- Awake but unresponsive state
- No cognitive neurological function but retain non-cognitive function (cardiac, respiration, vascular)
- Head and neck movement may persist
- No meaningful response to external and internal environment
Area:
- Extensive cortical gray or subcortical white matter lesion
- Preservation of brainstem function
Common causes: Cardiac arrest and head trauma
Prognosis: Regaining mental function after months of PVS is almost zero
22
Q
Define akinetic mutism and abulia
A
Akinetic mutism:
- Partially or fully awake, able to form impression and think
- Immobile and mute
- Damage in medial thalamic nuclei, frontal lobes or hydrocephalus
Abulia: (mild akinetic mutism)
- Mental and physical slowness, diminished ability to initiate activity
23
Q
GCS scale
A
24
Q
Conditions that mimic coma
A
- PVS
- Locked-in syndrome - Alert, aware, quadriplegic with lower cranial nerve palsy due to bilateral ventral pontine syndrome)
- Akinetic mutism and abulia
- Catatonia - appear awake with eyes open, hypomobile and mute syndrome with major psychosis
- Pseudocoma - awake, eye cannot be opened, emotional distress
25
Conditions that mimic epileptic seizures
1. **Hyperventilation** - Anxiety, peripheral cyanosis, hand paresthesia, carpopedal spasm
2. **Migraine**
3. **Panic attack** - intense dread or fear, inability to breathe, no LOC, autonomic features
4. **Psychogenic seizures** - motionless with forceful eye closure, thrashing limb movement and pelvic thrusting
5. **Syncope**
6. **Transient global amnesia** - Hours of isolated amnesic syndrome, no confusion, no negative features
7. **Transient ischemic attack** - predominant negative features: weakness, loss of sensation…etc
26
Diagnostic criteria of epilepsy
2 or more seizures NOT PROVOKED by illnesses or circumstances, occur 24 hours apart
_OR_
Single unprovoked seizure if recurrence risk is high
_OR_
Diagnosis of an epilepsy syndrome
27
Causes of Epilepsy
Epilepsy = unprovoked seizure
1. Idiopathic (62%) - genetic mutations in cellular and synaptic proteins and ion channels
2. Stroke (9%)
3. Head trauma (9%)
4. Alcohol (6%)
5. Neurodegenerative diseases (4%)
6. Static encephalopathy (3.5%) - e.g. hepatic or uremic encephalopathy
7. Brain tumor (3%)
8. Infection (2%)
9. Autoimmune - NMDAR autoantibodies encephalitis
28
Clinical Classification of Seizures
Partial (focal, local) seizures
* Simple partial seizure (SPS) - normal consciousness
* Complex partial seizure - impaired consciousness
* Partial seizure secondarily generalized
Generalized seizures
* Myoclonic seizure
* Absence seizure
* Clonic seizure
* Tonic-clonic seizure
* Tonic seizure
* Atonic/ Astatic seizure
29
epilepsy syndrome
* Definition
* How to classify which syndrome?
* Main Classes
Syndrome with predisposition to **Recurrent, Unprovoked seizures**
Classification according to:
1. Types of seizure
2. Any neurological and developmental abnormalities
3. EEG findings
Main classes:
1. Generalized epilepsy syndrome (Genetic) - seizure begin simultaneously in both cerebral hemispheres
2. Partial/ Localized-related epilepsy syndrome (CNS lesions) - seizure originate in 1 or more localized foci
30
General Mechanism of seizure
Abnormal/ excessive synchronous electrical activity in brain
High spread and neuronal recruitment due to:
* Enhanced connectivity
* Enhanced excitatory transmission
* Failure of inhibitory mechanisms
* Changes in intrinsic neuronal properties
31
Specific mechanisms of Epilepsy (unprovoked seizure)
Generalized epilepsies asso. with mutations of:
* Ion-channels
* Neurotransmitter receptors
* Synaptic support protein
* mTOR pathway regulators
* Chromatin remodeling and transcription regulators
Mostly complex inheritance patterns, some Mendelian inheritance of single gene mutation
32
Generalized epilepsy with febrile seizures plus (GEFS+)
Definition
Associated mutations
syndromic autosomal dominant disorder, can exhibit numerous epilepsy phenotypes (e.g. absence, myoclonic, atonic, afebrile GTCS)
Usually present in childhood, most disappear by adulthood
Mutation in voltage-gated Na Channel B1 subunit (SCN1B), SCN1A, and GABRG2 genes \> high depolarization rate and hyperexcitability
33
List some epilepsy syndrome asso. with single gene mutations
Generalized epilepsy with febrile seizures plus (GEFS+) - SCN1A, SCN1B, SCN2A, GABRG2
Benign familial neonatal convulsions - KCNQ2, KCNQ3
Autosomal dominant nocturnal frontal lobe epilepsy - CHRNA4, CHRNB2
Childhood absence epilepsy and febrile seizures - GABRG2
Autosomal dominant partial epilepsy with auditory features - LGI2
34
Complex partial seizures
Cause
S/S
Cause: Temporal Lobe Epilepsy (TLE)
Onset S/S:
* Olfactory/ gustatory hallucinations
* Epigastric sensation
* Psychiatric symptoms: deja vu/ jamais vu
* Stare blankly
Progress to LOC with S/S:
* Unintelligible speech, lip smacking
* Picking at clothes
* Automatism: coordinated involuntary motor activity during clouded consciousness e.g. screaming, crying, laughing
35
Partial Seizure
Causes
Most common type and brain areas involved
Causes: Most common seizure in adults
* Head trauma
* Stroke
* Tumor
Mesial temporal lobe epilepsy (mTLE)
* Complex partial seizure from mesial temporal lobe
* Common lesion: hippocampal sclerosis
* Areas involved: mesial temporal lobe structures: hippocampus, amygdala, parahippocampal cortex
36
Investigations for epilepsy
1. Neurological exam
2. Skin lesions in neurocutaneous syndromes - Neurofibromatosis, Tuberous sclerosis
3. For unprovoked first seizure:
* EEG
* MRI for structural lesions
* Blood: CBC, electrolyte, L/RFT, Ammonia
* Substance abuse screen
37
Investigations for epilepsy (+)
1. Neurological exam
2. Skin lesions in neurocutaneous syndromes - Neurofibromatosis, Tuberous sclerosis
3. For unprovoked first seizure:
* EEG
* MRI for structural lesions
* Blood: CBC, electrolyte, L/RFT, Ammonia
* Substance abuse screen
38
EEG for Dx of epilepsy (-)
Pros and Cons
Pros:
* Epileptiform EEG patterns (spikes and sharp waves) help Dx and Classification of seizure
* Video EEG monitoring possible to find epileptogenic focus (ictal EEG)
Cons:
* Abnormal EEG only in 50% of unprovoked first seizure
* Interictal EEG abnormalities cannot Dx epilepsy
* Normal EEG cannot exclude epilepsy
* Sleep deprivation is confounding factor of abnormal EEG
39
Epilepsy management options
Indications
**Lifestyle modification**
* Avoid potentially **dangerous activities:** Driving, power equipment, hiking, swimming, cooking over fire..etc
**Neuromodulation therapy**
* Electrical pulses to brain/ nerves to enhance rhythmic pulses against seizure generation
* e.g. Vagus nerve stimulation
**Pharmacological - Anti-epileptic drugs**
* Indicated for recurrent seizure dx by EEG or known seizure cause
* Broad-spectrum or narrow-spectrum AED
**Surgery**
* Refractory to AED after 2nd, 3rd line - Drug-resistant epilepsy
40
2 major categories of anti-epileptic drugs and examples
Broad-spectrum AED
* Valproate
* Lamotrigine
* Levetiracetam
* Topiramate
* Perampanel
Narrow-spectrum AED
* Carbamazepine, Oxcarbazepine
* Phenytoin
* Lacosamide
* Gabapentin, Pregabalin
41
Indication and contraindication of narrow-spectrum AED
Indication:
**Focal/ Localized epilepsy with Partial and secondarily generalized seizures**
C/I:
Some types of Idiopathic generalized epilepsy syndrome: Absence epilepsy and Myoclonic seizures
42
AEDs for absence seizure only
Ethosuximide
43
AED for focal seizures only
**Narrow AED**\*
Carbamazepine, Oxcarbazepine
Gabapentin, Pregabalin
Lacosamide
Phenytoin
44
**First-line AED for All focal and most generalized seizures (+)**
BDZs
## Footnote
**Levetiracetam**
**Perampanel**
**Topiramte**
**Sodium Valproate**
45
Valproate (-)
* Indication
* MoA
* Metabolism
* S/E
* C/I
Indication: Primary GTCS, absence and myoclonic seizures, 2nd line for partial seizures
MoA: Voltage-dependent blockade of Na channels
Metabolism: Protein-bound, T½ 7-17h, Liver metabolism
S/E: Tremor, weight gain, sedation, pancreatitis, BM suppression, thrombocytopenia, urea cycle dysfunction (increase NH3)
C/I: Teratogenic! Children, female of child-bearing age
46
Phenytoin (-)
* Indication
* MoA
* Metabolism
* S/E
Indication: GTCS, Partial seizure
MoA: Voltage-dependent blockade of Na channels
Metabolism: Hepatic CYP450, Protein bound, diseases can change unbound fraction, disproportionate serum amount after saturation
S/E: Dose-related neuro-toxicity, Hypersensitive skin reactions, Gingival Hyperplasia and Coarse facial feature, Hirsutism, Hypocalcemia, Megaloblastic anaemia
47
Carbamazepine (-)
* Indication
* MoA
* Metabolism
* S/E
* C/I
Indication: GTCS, Partial seizure
MoA: Prevent repetitive firing in depolarized neurons through blocking Na channels
Metabolism: hepatic, need increasing dose over time
S/E: Significant D/D interaction with lots of drugs, Dose-related neurotoxicity, Allergic morbilliform rash, SJS, Reversible leukopenia, HypoNa, Toxic hepatitis, Orofacial dyskinesia, Arrhythmia
C/I: Absence and myoclonic seizure
48
Lamotrigine (-)
* Indication
* MoA
* Metabolism
* S/E
Indication: GTCS, Partial seizure, 1st line for Elderly
MoA: Anti-folate activity (inhibit dihydrofolate reductase) + Inhibit voltage-dependent Na channels
Metabolism: Protein-bound, hepatic metabolism, Urine excretion, T½ 30h, No D/D interaction with other AED
S/E: Rash, drowsiness, dizziness, unsteady gait, headache, tremor, nausea
49
Levetiracetam
* Indication +
* MoA
* Metabolism
* S/E
Indication: adjunct for **ALL partial seizure +/- secondary generalized seizure**
MoA: Bind to synaptic vesicle protein SV2A \> modulate exocytotic function of presynaptic neuron
Metabolism: Enzymatic hydrolysis, urine excretion, No D/D interactions with any AED or cardiac drugs
S/E: Hyperactivity, Somnolence, Asthenia, Dizziness, Infection
50
Reasons for cautionary use of AED on women and children
1. **Valproate (high risk):** Teratogenic, PCOS, Anovulation, Hyperandrogenism
2. AED use increase **Fetal Malformation, Poor cognitive outcomes** (Low IQ)
3. Lamotrigine interacts with OC pills
51
Which AED to use in pregnant women?
All AEDs have risk
Lowest risk = Lamotrigine, **Levetiracetam**
52
Epilepsy surgery
* Indications
* Types
* Complications
Indication:
* Drug-resistant AED (refractory to 2 or more AED)
* TLE (most common drug-resistant AED)
Types:
* Standard **anterior temporal lobectomy**
* Selective **amygalo-hippocampectomy**
* Laser Interstitial Thermal Therapy
* **Steotactic Radiosurgery**
Complications:
* short-term memory loss (dominant temporal lobe surgery)
* Infection
* Visual field defects
* CN palsies
* Hemiparesis
* Death
53
Status Epilepticus
* Definition
* Subtypes (-)
* Causes
* Prognosis (-)
Definition: **Prolonged (\>5 mins) or repeated seizure** without full recovery of consciousness between attacks
Subtypes:
* Convulsive status epilepticus (generalized tonic clonic) - most common
* Non-convulsive status epilepticus (absence)
* Complex partial Status Epilepticus
Causes:
* **Acute cerebral insult:** CNS infection, Neurotoxins, Autoimmune encephalitis
* **Rapid withdrawal of AED**
Prognosis: 3-20% mortality
54
Status Epilepticus
Treatment and monitoring
Medical Emergency!
* **ABC**: airway protection, oxygen, intubation with ventilation, IV fluid, BP
* Observe **vitals**
* **ECG**
* **EEG**
* Terminate seizure: **IV AED**
* Look for underlying **causes**: AED withdrawal? CNS infection? Neurotoxins? Autoimmune encephalitis?
55
Status Epilepticus
Drug options and indications
**IV AEDs:**
* Phenytoin , Valproate, Levetiracetam, Lacosamidem, Perampanel
**Anesthesia and hypnotics:**
* Phenobarbital (caution respiratory arrest)
* **Propofol**
* Thiopental
* Midazolam (refractory to IV AED)
56
Drug options for non-convulsive Status Epilepticus
* Lorazepam
* Diazepam
* **IV Valproate**
* **Levetiracetam**
57
Acute confusion/ Delirium
## Footnote
Diagnostic criteria
Dx criteria (DSM-IV)
At least 2 of:
* **Perceptual disturbance** (misinterpretation, illusion, hallucination)
* **Incoherent speech**
* Disturbance of **sleep-wake cycle**
* Increased or decreased **psychomotor** activity
58
List all mental function impairments in Acute confusion state (-)
Memory
Perception
Comprehension
Problem-solving
Language
Praxis
Visuospatial function
Emotional behavior
59
Delirium
* Definition
* Prognosis
* S/S
**Definition: Acute Confusion state with acute decline in attention and cognition**
Mortality rate 1-year = 35-40%
S/S:
* Acute onset with fluctuating course
* **Inattention**
* **Disorganized thinking**
* Altered level of **consciousness**
* Cognitive deficits
* Perceptual illusions/ **hallucinations**
* **Psychomotor** disturbance: hyperactive/ hypoactive/ mixed
* Altered **sleep**
* **Emotional** disturbances
60
Why is delirium underdiagnosed -
Features causing under-diagnosis
* Fluctuating S/S
* Overlap with dementia
* No formal system for cognitive assessment
* Underappreciation of clinical consequences and significance/ importance
61
Delirium -
Pathogenesis
Areas of brain involved
Diffuse slowing of cortical background activity, Generalized disruption of higher cortical functions
Disturbances in brain chemistry: Cholinergic deficiency, Dopaminergic excess, Cytokines breakdown BBB, Chronic hypercortisolism
Areas involved:
* Prefrontal cortex
* Subcortical structures
* Thalamus
* Basal ganglia
* Frontal and temporoparietal cortex
* Fusiform cortex
* Lingual gyri
62
Approach for Delirium
* Formal cognitive testing with **MMSE**
* Determine acuity of mental state changes
* Look for **underlying causes:** esp. Dementia (major RF)
* Review **medication** and alcohol abuse
* (EEG and neuroimaging have low yield)
Investigations:
Basic **Blood** baseline, glucose, ketone
**ABG** for respiratory failure
**LP**
**Septic** workup with blood culture
63
Precipitating factors for Delirium
64
Conditions that lead to delirium
**Drugs**: sedatives, hypnotics, narcotics, anticholinergics, alcohol or drug withdrawal
**Primary neurological diseases:** Stroke, Intracranial bleed, meningitis or encephalitis
**Intercurrent illness**: Infection, AMI, DKA, Hypoxia, Shock, Fever, Anemia, Dehydration, Starvation, Metabolic derangement
**Surgeries**
**Hospital environment:** use of physical restraints, use of bladder catheter, admit to ICU
**Psychological**: Stress, sleep deprivation, chronic pain
65
Prevention of delirium
1. **Orientation** and therapeutic activities for cognitive impairment
2. Early **mobilization**
3. Use non-pharmacological Tx
4. **Improve sleep**
5. **Hydration**
6. Better **communication** if visual or hearing impairment
66
Management of Delirium
1. Find **underlying cause**
2. **Supportive**
* ABC, hydration, nutrition
* **No immobilization,** Prevent DVT, pressure sores
* **Avoid restraints**
* Provide **calm environment** with orientating things (clock, calendars, pictures)
* Frequent **communication** with staff
* **Improve sleep/** normal sleep
* Coordinated drug schedule, vitals assessments, procedures
3**. Prevent complications**
4. Treat behavioral symptoms: **Antipsychotics, Antidepressants, BDZ**
67
List 4 drugs for delirium
Indication
Only for behavior symptoms with harm to self or others
**Antipsychotics** - **Haloperidol** (1st line)
**Atypical antipsychotic** - **Riseperidone**, Olanzapine, Quetiapine
**BDZ** - Lorazepam (2nd line)
**Antidepressant** - Trazodone
68
Brain Death
Clinical Criteria
1. **Coma**
2. No spontaneous respiration**/ absolute apnea** (CO2 tension above 60 mmHg)
3. **No brainstem reflexes** (pupillary, oculocephalic, corneal, gag)
4. **No reversible causes of CNS depression** (drug, hypothermia, electrolyte disturbance)
5. Electrocerebral silence - **Isoelectric EEG** signal with no cerebrocortical function
