JC29 (Medicine) - Seizure and LOC Flashcards
4 major disease entities that cause sudden LOC +
Syncope
Seizure
Pseudo-seizure
Toxic/ Metabolic coma
Syncope +
- Pathophysiology/ Mechanism
- S/S, Precipitating factors
- Subtypes
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
Seizure
- Pathophysiology/ Mechanism
- Different S/S and presentations
- Causes
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
Causes of provoked seizures
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
Pseudo-seizure
- Pathophysiology/ Mechanism
- Features
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
Differentiate seizures from syncope
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
Compare toxic and metabolic coma S/S
Causes of each type of coma
Toxic coma
- transient, intermittent coma
- Cause by alcohol, solvent, barbituates
Metabolic coma
- LOC
- Preceded by sweating, confusion, weakness
- Cause by insulin, fasting, anti-diabetics
Likely causes of sudden LOC precipitated by micturition, sleep, standing, and exercise
→ During blood-taking, micturition - syncope
→ During sleep - seizure
→ Standing - orthostatic hypotension
→ During exercise - outflow obstruction
Common forms of aura
- 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
Presentation:
Short LOC with rapid recovery
Under 1 minute
Brief, asynchronous jerking
Pallor
Light-headedness, sweating, visual darkening
Most likely dx?
Syncope
Presentation:
Few minutes of LOC with slow recovery and confusion
With aura
Incontinence
Tongue-biting
Tonic-clonic movement
Most likely Dx
Generalized seizure
Presentation:
Several hours episode, no LOC
Partially retain awareness
Eyes cannot be open
Preceded by emotional distress
Most likely dx?
Pseudo-seizure/ Psychogenic seizure
First-line investigations for sudden LOC
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
Physiological control of consciousness
- Define consciousness
- Components of consciousness
- Areas of brain involved
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
Reticular activating system (RAS)
- Location in brain
- Function
- EEG patterns in wakefulness and sleep
- Physiological mechanisms
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
Coma
- Definition
- GCS cut-off
- Critical brain structure involved
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
Intracranial causes of coma
□ 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
Extracranial causes of coma
□ 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
Structural causes of coma
- 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
List disorders of conscioussness
Coma
Stupor - baseline unresponsiveness, only aroused by vigorous stimuli
Persistent Vegetative State (PVS)
Akinetic Mutism and Abulia
Inattention
Persistent vegetative state
Definition
Area of brain involved
Common causes
Prognosis
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
Define akinetic mutism and abulia
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
GCS scale
Conditions that mimic coma
- 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
Conditions that mimic epileptic seizures
- Hyperventilation - Anxiety, peripheral cyanosis, hand paresthesia, carpopedal spasm
- Migraine
- Panic attack - intense dread or fear, inability to breathe, no LOC, autonomic features
- Psychogenic seizures - motionless with forceful eye closure, thrashing limb movement and pelvic thrusting
- Syncope
- Transient global amnesia - Hours of isolated amnesic syndrome, no confusion, no negative features
- Transient ischemic attack - predominant negative features: weakness, loss of sensation…etc
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
Causes of Epilepsy
Epilepsy = unprovoked seizure
- Idiopathic (62%) - genetic mutations in cellular and synaptic proteins and ion channels
- Stroke (9%)
- Head trauma (9%)
- Alcohol (6%)
- Neurodegenerative diseases (4%)
- Static encephalopathy (3.5%) - e.g. hepatic or uremic encephalopathy
- Brain tumor (3%)
- Infection (2%)
- Autoimmune - NMDAR autoantibodies encephalitis
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
epilepsy syndrome
- Definition
- How to classify which syndrome?
- Main Classes
Syndrome with predisposition to Recurrent, Unprovoked seizures
Classification according to:
- Types of seizure
- Any neurological and developmental abnormalities
- EEG findings
Main classes:
- Generalized epilepsy syndrome (Genetic) - seizure begin simultaneously in both cerebral hemispheres
- Partial/ Localized-related epilepsy syndrome (CNS lesions) - seizure originate in 1 or more localized foci
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
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
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
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
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
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
Investigations for epilepsy
- Neurological exam
- Skin lesions in neurocutaneous syndromes - Neurofibromatosis, Tuberous sclerosis
- For unprovoked first seizure:
- EEG
- MRI for structural lesions
- Blood: CBC, electrolyte, L/RFT, Ammonia
- Substance abuse screen
Investigations for epilepsy (+)
- Neurological exam
- Skin lesions in neurocutaneous syndromes - Neurofibromatosis, Tuberous sclerosis
- For unprovoked first seizure:
- EEG
- MRI for structural lesions
- Blood: CBC, electrolyte, L/RFT, Ammonia
- Substance abuse screen
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
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
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
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
AEDs for absence seizure only
Ethosuximide
AED for focal seizures only
Narrow AED*
Carbamazepine, Oxcarbazepine
Gabapentin, Pregabalin
Lacosamide
Phenytoin
First-line AED for All focal and most generalized seizures (+)
BDZs
Levetiracetam
Perampanel
Topiramte
Sodium Valproate
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
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
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
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
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
Reasons for cautionary use of AED on women and children
- Valproate (high risk): Teratogenic, PCOS, Anovulation, Hyperandrogenism
- AED use increase Fetal Malformation, Poor cognitive outcomes (Low IQ)
- Lamotrigine interacts with OC pills
Which AED to use in pregnant women?
All AEDs have risk
Lowest risk = Lamotrigine, Levetiracetam
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
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
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?
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)
Drug options for non-convulsive Status Epilepticus
- Lorazepam
- Diazepam
- IV Valproate
- Levetiracetam
Acute confusion/ Delirium
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
List all mental function impairments in Acute confusion state (-)
Memory
Perception
Comprehension
Problem-solving
Language
Praxis
Visuospatial function
Emotional behavior
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
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
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
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
Precipitating factors for Delirium
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
Prevention of delirium
- Orientation and therapeutic activities for cognitive impairment
- Early mobilization
- Use non-pharmacological Tx
- Improve sleep
- Hydration
- Better communication if visual or hearing impairment
Management of Delirium
- Find underlying cause
- 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
- Treat behavioral symptoms: Antipsychotics, Antidepressants, BDZ
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
Brain Death
Clinical Criteria
- Coma
- No spontaneous respiration/ absolute apnea (CO2 tension above 60 mmHg)
- No brainstem reflexes (pupillary, oculocephalic, corneal, gag)
- No reversible causes of CNS depression (drug, hypothermia, electrolyte disturbance)
- Electrocerebral silence - Isoelectric EEG signal with no cerebrocortical function
