Epilepsy Psychiatry

Study Notes

Sources: Kaplan & Sadock's Comprehensive Textbook of Psychiatry (10th ed.), Stahl's Essential Psychopharmacology (5th ed.), Trimble & Schmitz, Seizures, Affective Disorders and Anticonvulsant Drugs, Engel & Pedley, Epilepsy: A Comprehensive Textbook, Oxford Textbook of Epileptology

SECTION 1: SEIZURE CLASSIFICATION: ILAE 2017

1.1 The Three-Level Framework

The 2017 ILAE classification operates at three levels:

Swipe to compare →

1.2 Seizure Onset Classification

1.3 Focal Seizures: Detailed Classification

Focal seizure descriptors (motor):

• Automatisms: Repetitive semi-purposeful movements (lip smacking, hand fumbling)
• Atonic: Loss of muscle tone in one body part
• Clonic: Rhythmic jerking
• Epileptic spasms: Brief sustained muscle contraction
• Hyperkinetic: Pedalling, thrashing movements
• Myoclonic: Brief irregular jerks
• Tonic: Sustained increased tone

Focal seizure descriptors (non-motor):

• Autonomic: Pallor, flushing, piloerection, cardiovascular changes
• Behaviour arrest: Cessation of activity
• Cognitive: Dysphasia, deja vu, jamais vu, forced thinking
• Emotional: Fear, anxiety, joy, ictal emotions
• Sensory: Somatosensory, visual, auditory, olfactory, gustatory, vestibular
• Sensory, special: The "dreamy state" of Jackson (temporal lobe)

1.4 Generalised Seizures: Detailed

Tonic-Clonic (Grand Mal):

• Tonic phase: 10–30 seconds, rigid extension, ictal cry (forced expiration through adducted cords), cyanosis
• Clonic phase: 30–120 seconds, rhythmic jerking, gradually slowing
• Postictal: Confusion, deep sleep, headache, myalgia, Todd's paralysis possible
• EEG: 10 Hz polyspikes during tonic; spike-wave during clonic; postictal flattening

Typical Absence (Petit Mal):

• Abrupt onset and offset, 3–20 seconds
• Staring, mild automatisms (eye blinking), no postictal phase
• 3 Hz spike-wave on EEG (pathognomonic)
• Precipitated by hyperventilation (useful in clinic)
• Age: 4–12 years, remits at puberty in 60–70%

Atypical Absence:

• Slower onset/offset, longer duration
• Associated with intellectual disability, multiple seizure types
• 1.5–2.5 Hz slow spike-wave
• Associated with Lennox-Gastaut syndrome

Myoclonic Seizures:

• Brief (<0.1 sec), bilateral, synchronous muscle jerks
• No loss of consciousness
• Worst in morning (characteristic of JME)
• Polyspike-wave on EEG

Atonic Seizures (Drop Attacks):

• Sudden loss of muscle tone
• High injury risk (helmet needed)
• EEG: Burst of polyspikes followed by slow waves
• Associated with Lennox-Gastaut

Tonic Seizures:

• Sustained muscle contraction, 2–30 seconds
• Usually during sleep
• Associated with Lennox-Gastaut

1.5 Epilepsy Types and Syndromes

SECTION 2: EPILEPSY SYNDROMES RELEVANT TO PSYCHIATRY

2.1 Temporal Lobe Epilepsy (TLE)

Epidemiology:

• Most common focal epilepsy (60% of focal epilepsies)
• Onset: Any age, but peaks in childhood and adolescence
• Drug resistance: 30–40% of cases

Aetiology:

• Hippocampal sclerosis (mesial temporal lobe epilepsy, MTLE), most common structural cause
• Cortical dysplasia
• Tumours (ganglioglioma, DNET)
• Vascular malformations
• Encephalitis (especially HSV, limbic encephalitis)
• Perinatal injury, febrile convulsions (controversial causality)

Mesial TLE (MTLE), Key Features:

• Aura: Epigastric rising sensation (most common), fear, deja vu/jamais vu, olfactory/gustatory hallucinations
• Automatisms: Oral (lip smacking, chewing), manual (fumbling, picking)
• Impaired awareness during seizure
• Postictal confusion (>30 min), aphasia if dominant hemisphere
• Unilateral tonic posturing (contralateral to focus)

Lateral (Neocortical) TLE:

• Auditory hallucinations (superior temporal gyrus)
• Receptive aphasia (Wernicke's area, dominant hemisphere)
• Experiential phenomena: Forced memories, deja vu
• Rare automatisms

MRI in MTLE:

• Hippocampal sclerosis: Atrophy + T2/FLAIR hyperintensity + loss of internal architecture
• FDG-PET: Hypometabolism in ipsilateral temporal lobe (interictal)
• Wada test: For lateralisation of language and memory before surgery

Psychiatric Comorbidity in TLE:

2.2 Juvenile Myoclonic Epilepsy (JME)

Classic Triad:

1. Myoclonic jerks, worse on awakening, early morning
2. Generalised tonic-clonic seizures, often triggered by sleep deprivation
3. Absence seizures, in ~30% of patients

Features:

• Onset: 12–18 years (adolescence)
• Normal intelligence, normal neurological exam
• EEG: Generalised polyspike-wave, 4–6 Hz, frontally dominant
• Photosensitivity: 30–50%
• Strong genetic component (CACNB4, GABRA1, EFHC1 mutations)
• AED of choice: Valproate (most effective); levetiracetam, lamotrigine alternatives

Psychiatric Considerations in JME:

• Higher rates of ADHD, anxiety, depression vs. general population
• Personality profile: Impulsivity, poor self-regulation (controversial, may reflect shared neurobiology)
• Valproate: Risk of cognitive side effects, teratogenicity, significant for female patients of reproductive age
• Sleep deprivation, alcohol, stress are key triggers, lifestyle factors matter
• JME patients often have insight into triggers but struggle to modify behaviour (ADHD overlap)

2.3 Childhood Absence Epilepsy (CAE)

Features:

• Age of onset: 4–12 years
• Multiple daily absences (50–100/day)
• Normal development, normal neurological exam
• EEG: Classic 3 Hz generalised spike-wave
• Remission: 60–70% by puberty; persistent in 30–40%

Psychiatric Relevance:

• Academic difficulties secondary to frequent undetected seizures
• Attention and learning problems independent of AEDs
• Misdiagnosis: Often mistaken for daydreaming or ADHD
• AEDs: Ethosuximide (first-line for pure absence), valproate (also covers GTC), lamotrigine

2.4 West Syndrome (Infantile Spasms)

Triad:

1. Infantile spasms, brief (1–2 sec), symmetric flexion or extension, clusters on awakening
2. Hypsarrhythmia on EEG, chaotic, high-amplitude, asynchronous slow waves with superimposed multifocal spikes
3. Developmental regression, loss of previously acquired milestones

Epidemiology:

• Onset: 3–12 months (peak 4–6 months)
• Incidence: 1/4000 births

Aetiology:

• Structural (40%): Tuberous sclerosis (most common structural cause, ALWAYS think TSC in infantile spasms), cortical dysplasia, hypoxic-ischaemic injury, Down syndrome
• Genetic/metabolic (10%)
• Unknown (cryptogenic) (50%)

Treatment:

• First-line: ACTH (most evidence), vigabatrin (especially if TSC, superior response)
• Second-line: High-dose prednisolone, ketogenic diet, pyridoxine
• Early treatment = better neurodevelopmental outcome

Psychiatric Outcome:

• Autism spectrum disorder: 30–50%
• Intellectual disability: 70–80% (varies with aetiology)
• ADHD-like features: Common
• If TSC-associated: Higher psychiatric burden

2.5 Lennox-Gastaut Syndrome (LGS)

Triad:

1. Multiple seizure types, tonic (especially nocturnal), atonic (drop attacks), atypical absence; also GTC, myoclonic
2. EEG, slow spike-wave (< 2.5 Hz), generalized; also paroxysmal fast activity (> 10 Hz) during sleep
3. Intellectual disability, cognitive regression is common

Features:

• Onset: 1–7 years (peak 3–5 years)
• Preceded by West syndrome in 30%
• Drop attacks: Major safety concern; helmets required
• Tonic seizures during sleep: Characteristic, dangerous
• Drug-resistant in 90%

AEDs Used in LGS:

Psychiatric Comorbidity:

• Intellectual disability: Core feature
• Autism features: 20–30%
• Behavioural problems: Aggression, self-injury, high frequency
• ADHD: Significant overlap
• Psychiatric management: Challenging due to polypharmacy and cognitive burden

SECTION 3: TEMPORAL LOBE EPILEPSY AND PSYCHIATRIC PHENOMENA

3.1 Geschwind Syndrome (Interictal Behavioral Syndrome)

Historical Context:

Norman Geschwind (1975) described a cluster of personality and behavioural traits in patients with TLE, particularly MTLE with hippocampal pathology. The original description was based on clinical observation rather than controlled studies.

The Five Classic Features (Geschwind Syndrome):

Memory aid, 5 H's: Hypergraphia, Hyperreligiosity, Hyposexuality, "Hurts to leave" (viscosity), Heightened affect

Critical caveats:

• Not all patients with TLE show these features
• The syndrome is not specific to TLE
• Hypergraphia is the most specific feature
• Geschwind did not describe this as a psychiatric disorder, it is a personality style
• Trimble and Bear popularised the concept
• Recent research: Methodological criticisms; comparison studies show much weaker effects

3.2 Interictal Dysphoric Disorder (IDD)

Blumer's Description (2004):

Dietrich Blumer described a pattern of affective disturbance specific to epilepsy that differs from standard mood disorder classifications. It is characterised by:

Eight Core Symptoms:

Depressive-type (4):

1. Depressive mood
2. Anergia (lack of energy)
3. Pain (somatic complaints)
4. Insomnia

Labile/Irritable-type (4):

1. Fear/anxiety (episodic)
2. Euphoric moods (episodic)
3. Irritability
4. Paroxysmal affective disturbances

Key Features of IDD:

• Intermittent, not continuous
• Dysphoric in character (mixed low mood + irritability)
• Pleiotropy: Combines features of dysthymia, cyclothymia, and anxiety disorder
• Temporally related to seizure activity but not strictly peri-ictal
• Responds to SSRI + low-dose lamotrigine (anecdotally)

IDD vs. Major Depressive Disorder in Epilepsy:

3.3 Interictal Psychosis

See Section 5.2 for detailed coverage.

SECTION 4: ICTAL PSYCHIATRIC PHENOMENA

4.1 Overview of Peri-Ictal Psychiatric Phenomena

Temporal Framework:

4.2 Ictal Fear

Characteristics:

• Most common ictal emotion (60–70% of emotional seizures)
• Sudden, intense, unprovoked fear
• Duration: Seconds to 1–2 minutes
• Origin: Amygdala activation (mesial temporal focus)
• Patient retains memory of the fear if aware
• Quality: Unlike normal fear, no clear object, sudden onset, reproducible

Differential Diagnosis:

• Panic disorder: Longer duration, builds up, no EEG correlate, no stereotypy
• Generalised anxiety: Chronic, not paroxysmal
• PTSD: Triggered by stimuli, narrative content
• Pheochromocytoma: Hypertension, flushing, sweating

Clinical Implication:

Patients with TLE presenting to psychiatry with "panic attacks", especially brief, stereotyped, with no identifiable trigger, and with other TLE features, should have EEG performed.

4.3 Ictal Psychosis

Definition: Psychotic symptoms occurring during an ictal discharge, with EEG confirmation.

Features:

• Rare (< 1% of TLE patients)
• Usually brief (minutes)
• Hallucinations: Visual, auditory, olfactory more common than in schizophrenia
• Delusions: Simple, poorly formed
• Associated with continuous EEG abnormality
• Non-convulsive status epilepticus (NCSE) can present as psychosis, this is the critical clinical scenario

Ictal hallucinations by lobe:

4.4 Forced Normalisation (Landolt's Phenomenon)

Definition:

The phenomenon in which the cessation of seizures (either spontaneous or pharmacologically induced) is associated with the emergence of psychosis. The EEG, previously showing epileptiform activity, becomes paradoxically normal.

Historical Context:

• Landolt (1953): First EEG description, "forced normalisation" referring to the EEG finding
• Tellenbach (1965): "Alternative psychosis", emphasising the alternating, competitive relationship between psychosis and seizures
• The terms are sometimes used interchangeably but are distinct:
• Forced normalisation = EEG phenomenon (normalisation)
• Alternative psychosis = clinical phenomenon (psychosis when seizures remit)

Mechanism (Theoretical):

• Competing inhibitory mechanisms: Seizures may temporarily suppress psychosis-generating processes
• Dopamine hypothesis: Seizures may modulate mesolimbic dopamine; normalization removes this effect
• GABA-glutamate balance shifts
• Not fully understood

Clinical Scenario:

Patient with known TLE, previously seizure-prone, started on new AED (e.g., vigabatrin, levetiracetam). Seizures stop. Two weeks later: acute psychosis, florid hallucinations, EEG now normal.

Management:

• Reduce or discontinue the offending AED (discuss with neurologist)
• Short-term antipsychotic (lowest dose)
• Do NOT automatically increase AED dose, may worsen psychosis
• Monitor EEG during psychosis

AEDs Most Associated with Forced Normalisation:

• Vigabatrin (highest risk)
• Ethosuximide
• Lamotrigine (occasionally)
• Levetiracetam (behavioural side effects, but forced normalisation less clearly established)

SECTION 5: POSTICTAL AND INTERICTAL PSYCHOSIS

5.1 Postictal Psychosis (PIP)

Definition:

Psychosis emerging after a seizure or cluster of seizures, with a lucid interval (clear period) of 24–48 hours between seizure and psychosis onset.

Epidemiology:

• Prevalence: 7–10% of TLE patients
• More common in: Bilateral seizure foci, longer duration of epilepsy, poor seizure control

The Lucid Interval:

• Critical distinguishing feature
• Duration: Typically 24–48 hours (range: 12 hours to 7 days)
• During this period: Patient is relatively clear, may seem recovered
• Then: Acute psychosis emerges

Clinical Features of PIP:

Risk Factors for PIP:

1. Bilateral (or dual) seizure foci
2. History of febrile convulsions
3. Longer duration of epilepsy (> 10 years)
4. Male sex (some studies)
5. Temporal lobe focus
6. Prior postictal psychosis (strongest predictor)

Management of PIP:

1. Immediate: Observation, safety, supportive care
2. Antipsychotics: Low-dose haloperidol or olanzapine (avoid clozapine, lowers seizure threshold; avoid phenothiazines)
3. Benzodiazepines: For agitation
4. AED optimisation: Reduce seizure frequency to prevent recurrence
5. Psychoeducation: Family must understand lucid interval, they may think patient is fine, then decompensate

Natural History:

• Self-limiting in most cases (days to weeks)
• Risk of progression to chronic interictal psychosis with repeated episodes (~15%)
• Does not require long-term antipsychotic in most cases

5.2 Interictal Psychosis (IIP) / Schizophrenia-Like Psychosis of Epilepsy (SLPE)

Slater and Beard (1963):

Classic study describing psychosis in 69 epilepsy patients. Found psychosis resembling schizophrenia but with key differences.

Definition:

Chronic psychosis occurring in epilepsy patients, not time-locked to seizure activity (interictal), persisting for months to years.

Prevalence:

• 5–10% of TLE patients
• Risk vs. general population: 6–12x higher (depending on study)
• Most common in: MTLE, bilateral foci, long duration, poor control

Clinical Features, SLPE vs. Schizophrenia:

The "Positive Without Negative" Pattern:

This is the most testable feature of SLPE. Hallucinations and delusions are present, but the patient retains warmth, maintains relationships, and shows preserved emotional responsiveness. This "schizophreniform" picture without the typical deterioration distinguishes it.

Risk Factors for SLPE:

1. TLE (especially MTLE and bilateral TLE)
2. Long duration of epilepsy
3. Poor seizure control
4. Alien tissue lesions (ganglioglioma, hamartoma, DNET)
5. Bilateral or left-sided foci
6. Ictal fear as prominent symptom
7. History of postictal psychosis

Mechanism Hypotheses:

1. Kindling: Repeated sub-threshold stimulation → permanent neuronal changes
2. Structural: Hippocampal, amygdala, and parahippocampal atrophy → psychotic vulnerability
3. Neurotransmitter: Dopaminergic dysregulation secondary to limbic pathology
4. Shared vulnerability: Common genetic/neurodevelopmental substrate for epilepsy and psychosis

Management of SLPE:

• Antipsychotics: Atypical antipsychotics preferred
• Aripiprazole: Least proconvulsant
• Risperidone: Effective; moderate proconvulsant risk
• Olanzapine: Effective; moderate proconvulsant
• Clozapine: Avoid (highest proconvulsant risk); reserve for treatment-resistant
• Haloperidol: Useful acutely; chronic use less favoured
• Continue AEDs, do NOT reduce AEDs expecting this to help psychosis
• Monitor EEG when starting antipsychotics

Proconvulsant Risk of Antipsychotics (Low → High):

Aripiprazole < Haloperidol < Risperidone < Quetiapine < Olanzapine < Clozapine

SECTION 6: DEPRESSION IN EPILEPSY

6.1 Epidemiology and Prevalence

Prevalence:

• 20–55% of epilepsy patients (most consistent estimate: ~30%)
• Most common psychiatric comorbidity in epilepsy
• More common in:
• TLE
• Drug-resistant epilepsy
• Active seizures (vs. well-controlled)
• Left hemisphere focus (some evidence)
• Limbic involvement

The Bidirectional Relationship:

Mechanisms of Depression in Epilepsy:

6.2 Postictal Depression

• Occurs within 24–48 hours of seizure
• Duration: Hours to 1–2 days
• Features: Sadness, hopelessness, fatigue, suicidal ideation (can be dangerous)
• May be part of postictal psychiatric syndrome (postictal psychosis, agitation, mania also occur)
• Management: Short-term support; SSRI if persistent or severe

6.3 NDDI-E (Neurological Disorders Depression Inventory for Epilepsy)

Why NDDI-E and not PHQ-9?

• PHQ-9 includes somatic items that overlap with AED side effects and seizure effects (fatigue, sleep disturbance, concentration)
• NDDI-E excludes somatic items; focuses on cognitive-emotional features
• Developed and validated specifically for epilepsy populations

NDDI-E Items (6 items, each scored 1–4):

1. Everything is a struggle
2. Nothing I do is right
3. Feel guilty
4. I'd be better off dead
5. Frustrated
6. Difficulty finding pleasure

Scoring:

• Total: 6–24
• Cutoff ≥ 15: Probable major depressive disorder (sensitivity 81%, specificity 90%)
• Scores 11–14: Subclinical, monitor

GAD-7 for Anxiety:

• GAD-7 is recommended for anxiety screening in epilepsy
• Same rationale, validated and less somatic overlap than other scales

6.4 Antidepressants in Epilepsy

Proconvulsant Risk, Antidepressants:

6.5 Suicide Risk in Epilepsy

Prevalence:

• Suicide attempts: 5x higher than general population
• Completed suicide: 3–5x higher
• SUDEP (Sudden Unexpected Death in Epilepsy): 1/1000 patient-years (competing cause)

Risk Factors for Suicide in Epilepsy:

1. TLE (especially MTLE)
2. Depression (strongest modifiable risk factor)
3. Drug-resistant epilepsy
4. Young age, male sex
5. Recent diagnosis
6. Social isolation, unemployment
7. AED side effects (particularly topiramate and levetiracetam)

FDA Black Box Warning (2008):

All AEDs carry an FDA black box warning for increased suicidality. This applies to the class as a whole, not specific agents. Meta-analysis showed approximately 2x increased risk. The absolute risk is small.

SECTION 7: ANXIETY IN EPILEPSY

7.1 Prevalence and Types

Prevalence: 20–40% of epilepsy patients

Anxiety Disorders in Epilepsy:

7.2 Anticipatory Anxiety

• Fear of the next seizure, "living on the edge"
• Leads to avoidance behaviour, activity restriction
• Reduced quality of life independent of seizure frequency
• Cognitive-behavioural interventions are effective
• AED optimisation helps by reducing uncertainty

7.3 Treatment

• SSRIs/SNRIs: First-line for GAD, panic, social anxiety in epilepsy
• Buspirone: Safe; no proconvulsant risk; useful for GAD
• Benzodiazepines: Use with caution (tolerance, sedation, cognitive impairment, respiratory depression)
• CBT: Evidence-based; strongly recommended alongside pharmacotherapy
• Mindfulness-based interventions: Growing evidence

SECTION 8: ANTIEPILEPTIC DRUGS AND PSYCHIATRIC EFFECTS

8.1 Overview

Master Table, AED Psychiatric Profiles:

8.2 Valproate: Psychiatric Indications

Epilepsy uses:

• Generalised epilepsy (JME, childhood absence, idiopathic)
• Focal epilepsy (second-line)
• Lennox-Gastaut syndrome
• Status epilepticus (IV formulation)

Psychiatric uses:

• Bipolar disorder I, acute mania (first-line), maintenance
• Augmentation in schizoaffective disorder
• Impulse control disorders
• Aggression/behavioural problems in dementia, ID
• Migraine prophylaxis (neurological)

8.3 Carbamazepine: Psychiatric Considerations

• Mood stabiliser: Particularly for rapid cycling, mixed states, BD with dysphoric mania
• Drug interactions: Strong CYP3A4 inducer
• Reduces plasma levels of: Haloperidol, olanzapine, risperidone, aripiprazole, quetiapine, valproate, lamotrigine
• Oral contraceptives: Efficacy reduced (important, counsel women)
• SIADH and hyponatraemia: Especially in elderly; can cause encephalopathy
• Aplastic anaemia/agranulocytosis: Rare but potentially fatal; monitor FBC
• Oxcarbazepine: Less enzyme induction, better tolerated

8.4 Lamotrigine: Psychiatric Considerations

• Mood stabilisation: Evidence-based for bipolar depression maintenance
• NOT first-line for acute mania
• Rash: 10% mild rash; 0.1–0.3% severe (Stevens-Johnson syndrome, TEN)
• Risk reduced by slow titration
• Risk increased with: Rapid titration, concomitant valproate (doubles lamotrigine levels → double rash risk)
• Interaction with oral contraceptives: OCP reduces lamotrigine levels by ~50%; monitor doses if OCP started/stopped
• Psychosis: Rare; associated with forced normalisation in some patients

8.5 Levetiracetam: Psychiatric Side Effects

Psychiatric side effects:

• Irritability/agitation: 10–15% (dose-dependent)
• Depression: 5–10%
• Anxiety: 5–8%
• Psychosis: 0.5–2% (can be severe, acute onset)
• Associated with forced normalisation

Mechanism hypothesis: SV2A binding modulates neurotransmitter release; unclear why this produces behavioural effects in some patients.

Management:

• Dose reduction often helps
• Adjunctive pyridoxine (vitamin B6): Some evidence for reducing irritability in children; less clear in adults
• Switching to alternative AED if intolerable
• Antidepressants/antipsychotics as needed

8.6 Topiramate: Cognitive Effects

Cognitive effects:

• Word-finding difficulty: Most prominent, distressing to patients
• Processing speed: Reduced
• Working memory: Impaired
• Attention: Impaired
• Effects: Dose-dependent (much worse at > 200 mg/day)

Other notable effects:

• Weight loss (positive for some patients, negative in underweight individuals)
• Nephrolithiasis (carbonic anhydrase inhibition → alkaline urine → calcium phosphate stones)
• Oligohidrosis (reduced sweating), rare but dangerous in hot weather
• Depression and suicidality: Monitor

8.7 Phenobarbital: Depression Risk

• Oldest AED; first-line in low-income countries (cheap, available)
• Depression: Most clearly linked to phenobarbital among all AEDs
• Mechanism: GABA-A enhancement → sedation, CNS depression
• Hyperactivity in children: Paradoxical effect
• Sedation: Prominent, limits use
• Cognitive impairment: Significant with chronic use
• Tolerance: Develops to sedative effects
• Dependence: Physical dependence; withdrawal seizures if stopped abruptly

SECTION 9: AED INTERACTIONS WITH PSYCHOTROPICS

9.1 Enzyme Induction by AEDs

Strong CYP3A4 Inducers (AEDs):

• Carbamazepine
• Phenytoin
• Phenobarbital
• Primidone (metabolised to phenobarbital)

Effect on Psychotropics:

These AEDs dramatically reduce plasma levels of most antipsychotics and antidepressants. Clinical consequence: Apparent treatment resistance.

Clinical implication: When starting enzyme-inducing AEDs, anticipate need to increase psychotropic doses. When stopping them, reduce psychotropic doses (risk of toxicity).

9.2 Enzyme Inhibition by AEDs

Valproate inhibits CYP2C9, CYP2C19, and is a UGT inhibitor:

• Doubles lamotrigine levels (important, rash risk)
• Increases phenobarbital levels
• May increase levels of certain SSRIs (via CYP2C19)

9.3 Psychotropic Effects on AED Levels

9.4 Seizure Threshold and Psychotropics

Psychotropics that Lower Seizure Threshold:

SECTION 10: PSEUDOSEIZURES / PNES

10.1 Terminology

Current preferred terminology: Psychogenic Non-Epileptic Seizures (PNES) or Functional Seizures

Why terminology matters: "Pseudo" implies faking. These are not voluntary. They are genuine, disabling, and medically serious. This distinction matters in court, in medical letters, and in therapeutic relationships.

10.2 Epidemiology

• Prevalence: 2–33/100,000 (community); higher in epilepsy monitoring units
• 20–30% of patients referred to epilepsy monitoring units have PNES
• 10–30% of PNES patients also have comorbid epilepsy (dual diagnosis), critical point
• Sex: Female:male ratio ~3:1 to 7:1
• Age of onset: Bimodal, adolescence and 30s
• Misdiagnosis duration: Average 7 years before correct diagnosis

10.3 Differentiating Epileptic Seizures from PNES

Gold Standard: Video-EEG monitoring with ictal EEG recording (or absence of EEG change during typical event)

Clinical Differentiators:

Semiology features suggesting PNES:

• Pelvic thrusting (though not specific)
• Forward pelvic thrusting (more specific for PNES)
• Opisthotonus (arc de cercle)
• Bicycling leg movements
• Atypical motor features (e.g., gradual onset, build-up)
• Eye closure and resistance
• Crying during or immediately after event
• Out-of-phase limb movements
• Prolonged duration

Semiology features suggesting epilepsy:

• Stereotypy across events
• Brief duration (< 3 minutes)
• Postictal confusion
• Todd's paralysis (postictal focal weakness)
• Lateral tongue bite
• Clear postictal coma

10.4 Investigation

Note on prolactin: Not reliable enough alone. Sensitivity 60%; specificity 96% for GTC/CPS (not absence, frontal, or postictal period > 60 min). Use only as adjunct.

10.5 Psychiatric Comorbidity in PNES

10.6 Management of PNES

Step 1, Establish diagnosis definitively (Video-EEG)

Step 2, Communicating the diagnosis:

• Lead with what it IS, not what it isn't: "Your spells are a type of functional neurological disorder..."
• Do NOT say: "It's all in your head" or "There's nothing wrong with you"
• Emphasise: Real symptoms, not faking, treatable
• Acknowledge the diagnostic journey
• Explain the diagnosis as a brain-body communication problem (mind-brain framework)
• Joint consultation (neurologist + psychiatrist ideally)

Step 3, Psychiatric treatment:

• Psychotherapy: CBT with seizure-specific components (strongest evidence); trauma-focused therapy if PTSD; EMDR; psychodynamic
• Treat comorbidities: Depression, PTSD, anxiety, standard treatments
• Address iatrogenic harm: Many patients have been overmedicated with AEDs, suffered AED side effects; gradual AED withdrawal after diagnosis (if no comorbid epilepsy)
• Physiotherapy/rehabilitation: For functional neurological disorder comorbidities

Step 4, Withdrawal of AEDs (if no comorbid epilepsy):

• Gradual, not abrupt
• Done jointly with neurology
• Expect potential short-term worsening of PNES (extinction burst)
• Long-term: AED withdrawal reduces PNES burden in many patients

Prognosis:

• 30–40% remit completely with treatment
• 50% improve substantially
• Poorer prognosis: Longer duration of misdiagnosis, comorbid personality disorder, secondary gain, multiple comorbidities

SECTION 11: EEG IN PSYCHIATRY

11.1 Normal EEG Rhythms

Normal variants (not epileptiform):

• Wicket spikes: Benign temporal variant
• SREDA (subclinical rhythmic EEG discharges of adults)
• 14 and 6 Hz positive bursts
• Benign epileptiform transients of sleep (BETS/BETS)
• Hypnagogic hypersynchrony (children)

11.2 Epileptiform Discharges

11.3 EEG in Psychiatric Conditions

11.4 Indications for EEG in Psychiatry

SECTION 12: STATUS EPILEPTICUS

12.1 Definition and Classification

ILAE 2015 Operational Definitions:

Classification of SE:

12.2 Management Protocol for Convulsive SE

Time-based Protocol:

0–5 min (Stabilisation Phase):

• ABC, oxygen, IV access, glucose (check and treat if low)
• Blood: FBC, EUC, glucose, LFTs, AED levels, toxicology
• Position: Recovery position if no spinal injury concern
• Do NOT restrain

5–20 min (First-line, Benzodiazepines):

• Lorazepam IV 0.1 mg/kg (max 4 mg per dose); preferred if IV access
• Diazepam IV 0.2 mg/kg (max 10 mg)
• Midazolam IM/buccal/intranasal 10 mg, if no IV access (equivalent efficacy)
• Can repeat once after 5–10 minutes if seizure continues

20–40 min (Second-line, Non-benzodiazepine):

• Levetiracetam IV 60 mg/kg (max 4500 mg), now often first choice for second-line
• Valproate IV 40 mg/kg (max 3000 mg), avoid in hepatic disease, pregnancy, mitochondrial disease
• Phenytoin IV 20 mg/kg (max 1500 mg), fosphenytoin preferred if available; cardiac monitoring needed
• Lacosamide IV, emerging second-line option

40–60 min (Third-line, Refractory SE):

• ICU transfer
• Anaesthetic agents: Midazolam infusion, propofol, thiopental, ketamine
• EEG monitoring (continuous)
• Burst suppression target

12.3 NCSE: Psychiatric Presentation

Why NCSE Is a Psychiatric Emergency:

NCSE can present with:

• Acute onset psychosis
• Fluctuating consciousness
• Bizarre behaviour
• Mutism
• Automatic behaviour with post-event amnesia

Red Flags for NCSE in a Psychiatric Setting:

• Known epilepsy history
• Fluctuating, not continuous symptoms
• Subtle motor features (lip smacking, eye blinking, subtle facial twitching)
• Amnesia for the episode
• Impaired response to commands despite apparent wakefulness
• EEG-confirmed (required for diagnosis)

Management: IV benzodiazepine diagnostic trial; AED optimisation; treat underlying cause

SECTION 13: EPILEPSY SURGERY AND PSYCHIATRIC OUTCOMES

13.1 Surgical Options

13.2 Psychiatric Outcomes Post-Surgery

Post-ATL Psychiatric Outcomes:

Predictors of Good Post-Surgery Psychiatric Outcome:

• Absence of pre-surgical psychiatric disorder
• High baseline IQ
• Seizure freedom achieved
• Strong social support
• Younger age at surgery

Predictors of Poor Psychiatric Outcome:

• Pre-existing depression or psychosis
• History of postictal psychosis
• Bilateral foci
• Right temporal resection (some studies suggest higher depression risk)
• Failure to achieve seizure freedom

Pre-surgical psychiatric assessment:

• Mandatory in most epilepsy surgery centres
• Wada test (intracarotid amobarbital test): Assesses language lateralisation and memory function of each temporal lobe separately
• Neuropsychological assessment: Predicts post-operative cognitive change
• Structured psychiatric interview: Identifies risk factors for post-surgical psychiatric complications

SECTION 14: WOMEN WITH EPILEPSY

14.1 Teratogenicity of AEDs

Relative Teratogenicity:

Valproate-specific developmental effects:

• IQ: Children exposed to valproate in utero have ~7–9 point lower IQ on average vs. unexposed
• Autism risk: ~6x higher
• ADHD: Increased risk
• Language and verbal abilities: Specifically impaired
• These effects are independent of major structural malformations

Folic acid supplementation:

• ALL women with epilepsy on AEDs planning pregnancy: High-dose folic acid 5 mg/day (not 0.4 mg)
• Start at least 3 months before conception
• Continue through first trimester at minimum
• Reduces (but does not eliminate) NTD risk

14.2 Contraception and AEDs

14.3 Pregnancy and Epilepsy

Pre-conception counselling:

1. Confirm diagnosis, is epilepsy definite?
2. Review AED choice, switch from valproate if possible
3. High-dose folate started pre-conception
4. Consider AED monotherapy at lowest effective dose
5. Discuss risks openly, untreated seizures also harm foetus

Changes during pregnancy:

• AED levels often fall due to: Increased volume of distribution, renal clearance, decreased protein binding
• Lamotrigine: Levels fall significantly in pregnancy; increase dose with monitoring
• Levetiracetam: Levels also fall; monitor
• Seizure frequency may increase due to: Sleep deprivation, AED level changes, hormonal changes, medication non-compliance

Delivery:

• Vaginal delivery: Preferred; risk of seizures during labour is low
• IV benzodiazepines: Available for rescue
• Vitamin K: Neonates should receive at delivery (AED enzyme induction reduces neonatal vitamin K)

Breastfeeding:

• Generally encouraged
• Most AEDs: Low concentrations in breast milk
• Exceptions: Phenobarbital, lamotrigine (significant amounts), monitor baby for sedation
• Valproate, carbamazepine, levetiracetam: Relatively low breast milk levels; generally safe

14.4 Catamenial Epilepsy

Definition: Epilepsy with seizures clustering around menstrual cycle, defined as ≥2x increase in seizure frequency in specific cycle phase vs. baseline.

Three patterns (Herzog):

1. Perimenstrual (C1): Seizure cluster around menstruation (days -3 to +3)
2. Periovulatory (C2): Seizure cluster around ovulation (days 10–13)
3. Anovulatory (C3): Entire second half of cycle (days 10–28)

Mechanism: Estrogen (proconvulsant) increases; progesterone (anticonvulsant via GABA-A action) falls abruptly at menstruation

Treatment:

• Acetazolamide (carbonic anhydrase inhibitor): Perimenstrual use
• Clonazepam intermittently
• Progesterone supplementation (luteal phase support)
• OCP (continuous): Eliminates cycle variation
• Optimise baseline AED

SECTION 15: DRIVING AND EPILEPSY: INDIAN REGULATIONS

15.1 Indian Motor Vehicles Act: Epilepsy

Current Indian Regulations (Motor Vehicles Act 1988, Central Motor Vehicles Rules 1989):

• Epilepsy is a disqualifying condition for obtaining a driving licence under standard eligibility
• A person with epilepsy may be considered for driving licence if: Seizure-free for ≥ 2 years (on or off medication)
• This is different from the UK (1 year seizure-free) and many Western countries

Practical Clinical Advice:

1. Always document seizure-free dates in records
2. Counsel all patients about driving restrictions at diagnosis and at every follow-up
3. Document that counselling was given (medicolegal protection)
4. Report to licensing authority if a patient continues to drive against advice (duty to protect third parties)
5. Consider: Employment implications, alternative transport planning

15.2 Fitness to Drive: Clinical Assessment

Factors Affecting Driving Clearance:

• Type of seizure (absence vs. GTC vs. nocturnal-only)
• Seizure-free duration
• AED compliance and stability
• Occupational vs. private driving (higher standard for commercial/HGV)
• Prodromal warning (if adequate warning, some jurisdictions allow driving)

Nocturnal Seizures Only:

In many guidelines (UK, India provisions): If seizures are exclusively nocturnal for ≥ 3 years, driving may be permitted. Discuss with licensing authority.

SECTION 16: SPECIAL TOPICS

16.1 Psychiatric Disorders in Epilepsy: Summary Framework

Using the Temporal Framework (critical for MCQs):

16.2 Cognitive Impairment in Epilepsy

Sources of Cognitive Impairment:

16.3 Limbic Encephalitis: Epilepsy-Psychiatry Crossover

Types of Limbic Encephalitis:

Anti-NMDAR Encephalitis, Know this:

1. Most common autoimmune encephalitis
2. Young women; associated with ovarian teratoma (40%)
3. Sequence: Psychiatric phase → seizures → movement disorders → autonomic instability → coma
4. MRI: Often normal initially; may show FLAIR changes
5. CSF: Pleocytosis; CSF antibody more sensitive than serum
6. Treatment: Immunotherapy (steroids, IVIG, plasmapheresis) + tumour removal; antipsychotics for safety
7. Antipsychotics may worsen movement disorder phase, use cautiously

SECTION 17: QUICK REFERENCE TABLES

Table 1: Key Syndromes Summary

Table 2: AED Psychiatric Effects: Quick Reference

Table 3: Psychosis Timing in Epilepsy

Model Answers

Sources: Kaplan & Sadock 10th ed., Trimble's Neuropsychiatry of Epilepsy, Oxford Textbook of Epilepsy, Stahl's 5th ed.

Answer 1: Classify seizures according to ILAE 2017. Describe the psychiatric relevance of temporal lobe epilepsy.

Introduction

The International League Against Epilepsy (ILAE) 2017 classification revised the terminology of seizure types, abandoning older terms such as "simple partial" and "complex partial." It operates at three hierarchical levels: seizure type, epilepsy type, and epilepsy syndrome. (1 mark)

ILAE 2017 Seizure Classification (3 marks)

Level 1, Seizure Onset:

Swipe to compare →

Level 2, Epilepsy Type: Focal, Generalised, Combined focal + generalised, Unknown.

Level 3, Epilepsy Syndrome: e.g., TLE, JME, Childhood absence epilepsy, West syndrome, Lennox-Gastaut.

Temporal Lobe Epilepsy (TLE): Overview (1 mark)

TLE is the most common focal epilepsy (60% of focal epilepsies). Mesial TLE (MTLE) arising from the hippocampus, amygdala, and parahippocampal gyrus is the most psychiatrically significant variant. Aura typically includes epigastric rising, fear, deja vu/jamais vu, olfactory/gustatory hallucinations. Automatisms (oral, manual) and postictal confusion are characteristic.

Psychiatric Relevance of TLE (4 marks)

1. Depression (30–50% prevalence):

Most common psychiatric comorbidity in TLE. The relationship is bidirectional, TLE doubles depression risk, and depression is independently associated with increased seizure frequency. Mechanism involves serotonergic and limbic disruption. NDDI-E (Neurological Disorders Depression Inventory for Epilepsy) is the validated screening tool (cutoff ≥15).

2. Psychosis, Interictal (Schizophrenia-Like Psychosis of Epilepsy, SLPE):

Prevalence 5–10%. Described by Slater and Beard (1963). Key features: positive symptoms (hallucinations, delusions) WITHOUT prominent negative symptoms; preserved affect ("warmth"); no family history of schizophrenia. Develops 10–15 years after epilepsy onset on average.

3. Postictal Psychosis:

Occurs 24–48 hours after a seizure cluster (the "lucid interval" is pathognomonic). Duration: days to weeks. Features often include elevated mood, religious ideation, both visual and auditory hallucinations. Managed with low-dose antipsychotics; self-limiting in most cases.

4. Geschwind Syndrome (Interictal Personality Changes):

Cluster of personality traits: hypergraphia, hyperreligiosity, hyposexuality, viscosity (circumstantiality, "stickiness"), deepened affect. Existence as a distinct syndrome is debated but remains testable content.

5. Ictal Phenomena:

Ictal fear (most common ictal emotion, amygdala origin), ictal psychosis (rare, EEG-confirmed), forced normalisation (psychosis paradoxically emerging when seizures are controlled, Landolt, 1953).

6. Anxiety: 25–40% prevalence; includes ictal fear, anticipatory anxiety, and interictal generalised anxiety. Panic attacks must be distinguished from ictal fear (brevity, stereotypy, EEG correlation).

Clinical Implications (1 mark)

Any new-onset psychosis or atypical psychiatric presentation, especially if episodic, brief, stereotyped, associated with memory symptoms or olfactory aura, warrants EEG and neurological evaluation. Non-convulsive status epilepticus presenting as acute psychosis is a psychiatric emergency.

Answer 2: Discuss postictal psychosis: features, pathophysiology, and management.

Definition (1 mark)

Postictal psychosis (PIP) is a transient psychotic episode emerging after a cluster of seizures, characterised by a lucid interval of 24–48 hours between the seizure(s) and the onset of psychosis. It occurs in 7–10% of patients with TLE and represents one of the most clinically significant peri-ictal psychiatric syndromes.

Epidemiology (0.5 marks)

• Prevalence: 7–10% of TLE patients
• Risk factors: Bilateral seizure foci, long duration of epilepsy (>10 years), history of febrile convulsions, prior PIP episodes (strongest predictor), male sex, dominant temporal focus

Clinical Features (3 marks)

Pathophysiology (2 marks)

The mechanism of PIP is incompletely understood. Proposed mechanisms include:

1. Forced normalisation: Seizure activity may temporarily modulate limbic dopaminergic tone. When seizures cease, this modulating effect is removed, allowing dopaminergic dysregulation to emerge as psychosis. EEG normalisation during PIP supports this model.

1. Transient dopaminergic hyperactivity: Post-seizure rebound dopamine release in mesolimbic pathways.

1. GABA/glutamate shift: Postictal GABAergic inhibition followed by glutamatergic rebound → neuronal hyperexcitability in limbic circuits without convulsive threshold.

1. Structural substrate: Bilateral hippocampal and amygdala pathology in patients with bilateral foci increases risk; suggests an anatomical vulnerability.

1. Immune/inflammatory: Postictal neuroinflammation has been proposed; blood-brain barrier disruption following clusters of seizures may allow inflammatory mediators to trigger psychosis.

Management (3 marks)

Immediate:

• Safety assessment, risk to self and others
• Observation in a calm, low-stimulation environment
• Ensure family/carers aware (lucid interval phenomenon must be explained)

Pharmacological:

• Low-dose antipsychotic: Haloperidol 2–5 mg/day OR olanzapine 5–10 mg/day
• Benzodiazepine: For agitation (lorazepam 1–2 mg)
• Avoid: Clozapine (highest proconvulsant risk), high-dose typical antipsychotics
• Duration: Short-term (1–4 weeks typically sufficient)

AED Optimisation:

• Long-term reduction of seizure frequency reduces recurrence risk
• Review AED regimen; add or increase if poorly controlled

Psychoeducation:

• Explain the lucid interval, families and carers often misinterpret apparent recovery as full resolution
• Written crisis plan for future episodes

Follow-up:

• Monitor for progression to chronic interictal psychosis (~15% risk with recurrent PIP)
• Long-term antipsychotic generally NOT required after a single episode; consider prophylaxis after 2+ episodes

Prognosis (0.5 marks)

Most episodes are self-limiting within 2 weeks. With repeated episodes (3+), risk of persistent interictal psychosis rises to ~15%. Early recognition, adequate treatment, and seizure control are the primary modifiable factors.

Answer 3: Describe the schizophrenia-like psychosis of epilepsy. How does it differ from schizophrenia?

Introduction (1 mark)

Slater and Beard (1963) first systematically described a schizophrenia-like psychosis occurring in patients with epilepsy that differed from idiopathic schizophrenia in several important ways. Now termed "Interictal Psychosis" or "Schizophrenia-Like Psychosis of Epilepsy (SLPE)," it represents the most common form of chronic psychosis in epilepsy, occurring in 5–10% of temporal lobe epilepsy patients.

Epidemiology (0.5 marks)

• Prevalence in TLE: 5–10%
• Overall risk in epilepsy: 6–12x higher than general population
• Onset: Typically 10–15 years after epilepsy onset (mean age ~30–35 years)
• More common in MTLE, bilateral foci, alien tissue lesions (ganglioglioma, DNET, hamartoma)

Clinical Features of SLPE (3 marks)

Positive Symptoms (prominent):

• Auditory hallucinations, voices (similar to schizophrenia)
• Delusions, often persecutory, religious, grandiose
• Passivity phenomena (first rank symptoms may be present)

Negative Symptoms (characteristically ABSENT or mild):

• Flat affect: Rare in SLPE, affect is PRESERVED and often WARM
• Alogia: Not prominent
• Avolition/anhedonia: Mild at most
• Social withdrawal: Less severe than schizophrenia

Other Features:

• Mood congruent features may be present (elevation, dysphoria)
• Paranoid > disorganised presentations
• Preserved social functioning (relatively)
• No family history of schizophrenia
• Premorbid functioning often normal

Comparison: SLPE vs. Schizophrenia (4 marks)

Pathophysiology (1 mark)

Four mechanisms are proposed:

1. Kindling: Repeated subthreshold limbic stimulation produces permanent neuronal sensitisation leading to psychotic vulnerability
2. Structural: Hippocampal, parahippocampal, and amygdala atrophy disrupts limbic-dopamine regulation
3. Dopaminergic dysregulation: Secondary to limbic epileptiform activity
4. Shared neurodevelopmental substrate: Common vulnerability for both epilepsy and psychosis (e.g., perinatal injury, genetic factors)

Management (0.5 marks)

• Atypical antipsychotics: Aripiprazole (lowest proconvulsant risk), risperidone, olanzapine
• Continue AEDs, never reduce AED with the expectation that this will help psychosis
• Do NOT use clozapine unless treatment-resistant (highest seizure risk)
• Monitor EEG if clozapine is required

Answer 4: Discuss the role of AEDs in psychiatric disorders. Describe the psychiatric side effects of antiepileptic drugs.

Introduction (1 mark)

Antiepileptic drugs (AEDs) occupy a unique position in neuropsychopharmacology, several are used as primary treatments in psychiatric disorders (valproate, carbamazepine, lamotrigine) while others carry significant risks of inducing or worsening psychiatric symptoms. Understanding both dimensions is essential for safe practice at the neurology-psychiatry interface.

AEDs as Psychiatric Treatments (3 marks)

Valproate:

• Bipolar disorder I, acute mania: First-line (equivalent to lithium)
• Bipolar maintenance: Effective, especially for rapid cycling
• Schizoaffective disorder: Augmentation
• Impulse control disorders, aggression in intellectual disability
• Mechanism: GABAergic enhancement + sodium channel blockade + multiple downstream effects

Carbamazepine:

• Bipolar disorder: Second-line; particularly dysphoric mania, rapid cycling
• Acute mania: Less evidence than valproate/lithium but used
• Trigeminal neuralgia, PTSD augmentation
• Mechanism: Sodium channel blockade; structural resemblance to TCAs

Lamotrigine:

• Bipolar depression: Best evidence among all drugs for bipolar depression maintenance
• NOT first-line for acute mania; may precipitate mixed states
• Mechanism: Sodium + calcium channel blockade; reduces glutamatergic transmission

Clonazepam:

• Panic disorder, social anxiety (short-term)
• Acute mania (adjunct)
• Catatonia (IV lorazepam/diazepam)

Pregabalin/Gabapentin:

• Generalised anxiety disorder (pregabalin is licensed for GAD in Europe)
• Neuropathic pain comorbid with psychiatric disorders

Psychiatric Side Effects of AEDs (5 marks)

FDA 2008 Black Box Warning:

All AEDs carry a class warning for increased suicidality. Risk approximately doubles (from ~0.24% to 0.43% over study periods). The absolute risk is small but clinically relevant, monitor all patients starting AEDs for mood and suicidal ideation.

Levetiracetam, Psychiatric Effects (detailed):

Dose-dependent irritability and behavioural disinhibition in ~10% of patients. Thought to relate to SV2A binding modulating inhibitory neurotransmitter release. Adjunctive pyridoxine (Vitamin B6) has limited evidence for reducing irritability. Dose reduction or drug switch is the primary intervention.

Topiramate, Cognitive Effects (detailed):

Word-finding difficulty (anomia) is most characteristic. Processing speed and working memory also affected. Severity is dose-dependent, much less problematic at ≤100 mg/day. Labelled "Dopamax" by patients and clinicians colloquially. Cognitive testing before and after dose escalation is good practice.

Clinical Implications (1 mark)

When a patient with epilepsy presents with new psychiatric symptoms, always review:

1. Recent AED changes (new AED, dose increase)
2. AED interactions (enzyme induction reducing psychotropic levels)
3. Seizure control (improvement may trigger forced normalisation)
4. Temporal relationship (within weeks of AED change = likely AED-related)

Answer 5: Describe psychogenic non-epileptic seizures (PNES). How are they differentiated from epileptic seizures? Discuss management.

Definition and Terminology (1 mark)

Psychogenic Non-Epileptic Seizures (PNES), also termed functional seizures, are paroxysmal events resembling epileptic seizures in clinical appearance but occurring without the ictal neurophysiological changes (epileptiform EEG activity) characteristic of epilepsy. They represent a form of Functional Neurological Disorder (FND). The term "pseudoseizures" is outdated and stigmatising, it implies voluntary fabrication, which is incorrect.

Epidemiology (0.5 marks)

• Prevalence: 2–33/100,000 in community settings
• 20–30% of patients in epilepsy monitoring units have PNES
• 10–30% of PNES patients also have comorbid epilepsy
• Female:male ratio: 3:1 to 7:1
• Average delay to diagnosis: 7 years
• Average number of AEDs tried before diagnosis: 2–3

Differentiation: PNES vs. Epileptic Seizures (4 marks)

Gold standard: Video-EEG telemetry with a recorded typical event.

Semiology features strongly suggesting PNES:

• Asynchronous limb movements (arms and legs out of phase)
• Pelvic thrusting, especially forward thrusting
• Opisthotonus (arc de cercle)
• Eye closure with resistance
• Crying during or immediately after
• Gradual onset with emotional build-up
• Duration >5 minutes with preserved partial awareness

Psychiatric Comorbidity (1.5 marks)

Management (3 marks)

Step 1, Definitive Diagnosis:

Video-EEG monitoring with captured event. Do not diagnose PNES on clinical grounds alone, the consequences of misdiagnosis are severe (either undertreated epilepsy or continued AED treatment in non-epileptic patients).

Step 2, Disclosure:

Delivery of the diagnosis is the first therapeutic act. Framework:

• Lead with what it IS: "Your brain is experiencing a type of functional nervous system difficulty..."
• Do NOT say: "It's not real," "you're fine," "it's psychological" (pejorative framing)
• Frame as: Real, disabling, treatable, not deliberate
• Acknowledge diagnostic journey and prior misdiagnosis
• Involve a neurologist and psychiatrist jointly

Step 3, Psychotherapy (Primary Treatment):

• CBT: Strongest evidence; seizure-specific CBT (cognitive restructuring + behavioural experiments targeting triggers)
• Trauma-focused therapy: If PTSD is present, trauma-focused CBT, EMDR
• EMDR: Growing evidence for PNES with trauma history
• Psychodynamic therapy: For patients with poor insight into emotional triggers
• Group therapy: Reduces isolation, shame

Step 4, AED Withdrawal (if no comorbid epilepsy):

• Gradual, collaborative with neurology
• Expect short-term worsening (extinction burst), prepare patient
• Long-term: AED withdrawal generally beneficial; reduces AED side effects

Step 5, Treat Comorbidities:

• Antidepressants for depression (SSRIs first-line)
• Trauma-focused work for PTSD
• DBT skills for BPD features

Prognosis (0.5 marks)

• Seizure freedom: 30–40% with treatment
• Substantial improvement: 50%
• Poorer prognosis: Long diagnostic delay, secondary gain, comorbid personality disorder, continued AED use (maintains sick role), lack of insight

Answer 6: Write a note on forced normalisation. Describe Landolt's phenomenon with clinical implications.

Historical Background (1 mark)

Heinrich Landolt (1953), a Swiss neurologist, described a paradoxical EEG phenomenon in epilepsy patients: when seizures were controlled, either spontaneously or pharmacologically, the EEG, previously showing epileptiform activity, would normalise (become apparently normal). Simultaneously, patients would develop acute psychiatric symptoms, most commonly psychosis. He termed this "forced normalisation" (erzwungene Normalisierung in German), referring to the EEG finding.

Tellenbach (1965) described the clinical counterpart, "alternative psychosis", emphasising the competitive, alternating relationship between epileptic seizures and psychosis.

Definition (1 mark)

Forced normalisation (Landolt): The paradoxical normalisation of EEG coinciding with the emergence of acute psychiatric symptoms (most commonly psychosis) when epileptic activity is suppressed.

Alternative psychosis (Tellenbach): The clinical alternating relationship between seizures and psychosis, when one is present, the other is absent.

These terms are related but distinct: Forced normalisation is an EEG description; alternative psychosis is a clinical description of the same phenomenon.

Clinical Features (3 marks)

AEDs Most Commonly Associated (1 mark)

Pathophysiology (2 marks)

The mechanism is not fully established. Proposed models:

1. Competing inhibition: Seizure activity itself may paradoxically inhibit psychotic mechanisms (perhaps via postictal dopamine modulation). When seizures are suppressed, this inhibitory effect is removed, unmasking psychotic vulnerability.

1. Dopamine hypothesis: Seizures modulate mesolimbic dopamine tone. The anticonvulsant effect removes seizure-related dopaminergic modulation, allowing dopaminergic hyperactivity to emerge.

1. GABA enhancement: Vigabatrin increases GABA by inhibiting GABA transaminase. Excess GABAergic inhibition in limbic circuits may disrupt psychotic threshold regulation.

1. Limbic network rebalancing: Anticonvulsants shift the balance of excitation/inhibition across limbic networks; in vulnerable individuals, this rebalancing produces psychosis rather than normalcy.

Clinical Management (2 marks)

Step 1, Recognition: Clinician must know this phenomenon. Any acute psychosis emerging after seizure control (especially new AED or dose increase) should trigger assessment for forced normalisation.

Step 2, AED Reduction:

• Discuss with the treating neurologist
• Consider reducing the offending AED (especially vigabatrin, ethosuximide)
• The paradox: Allowing seizure recurrence may resolve psychosis
• Weigh seizure risk against psychiatric risk

Step 3, Antipsychotic:

• Low-dose antipsychotic for psychosis
• Avoid clozapine (increases seizure threshold paradoxically may help, but risk too high)
• Aripiprazole preferred (least proconvulsant)

Step 4, Monitor EEG:

• Serial EEG during psychotic episode
• Return of epileptiform activity often heralds resolution of psychosis

Key Clinical Principle: Do NOT automatically increase AED dose when psychosis emerges post-seizure control, this may worsen the psychiatric syndrome.

Answer 7: Discuss depression in epilepsy: prevalence, bidirectional relationship, screening, and treatment.

Introduction (0.5 marks)

Depression is the most common psychiatric comorbidity in epilepsy, affecting 20–55% of patients. It significantly impairs quality of life, often more than seizure frequency itself. The relationship between epilepsy and depression is uniquely bidirectional, reflecting shared neurobiological mechanisms.

Prevalence (0.5 marks)

• Overall in epilepsy: 20–55% (most consistent: ~30%)
• TLE specifically: 30–50%
• Drug-resistant epilepsy: Up to 55%
• Active seizures (vs. well-controlled): Higher prevalence
• Compared to general population (~10–15%): 2–4x higher

Bidirectional Relationship (3 marks)

Epilepsy → Depression:

1. Neurobiological: Limbic hyperactivity disrupts serotonergic circuits; HPA axis dysregulation; interictal hypometabolism in frontal and limbic regions
2. AED effects: Phenobarbital, topiramate, levetiracetam, zonisamide directly increase depression risk
3. Psychosocial: Driving restrictions, employment limitations, stigma, dependency, loss of autonomy
4. Peri-ictal: Postictal depression (common after GTC) and interictal dysphoric disorder

Depression → Epilepsy:

1. Meta-analyses show: Individuals with depression have RR of 1.5–2.0 for subsequently developing epilepsy
2. Shared mechanisms: Serotonergic pathways, HPA axis dysregulation, hippocampal atrophy (depression causes hippocampal volume loss, same region vulnerable in MTLE)
3. Neuroinflammation: Depression and epilepsy both associated with elevated inflammatory markers

Shared Neurobiology:

• Both involve: Serotonin, GABA, glutamate dysregulation
• Both associated with: Hippocampal atrophy, amygdala hyperactivity
• Both benefit from: Anticonvulsant mood stabilisers (lamotrigine, valproate)

Screening Tools (1.5 marks)

NDDI-E (Neurological Disorders Depression Inventory for Epilepsy):

• Validated specifically for epilepsy, avoids somatic items that overlap with AED side effects
• 6 items, each scored 1–4
• Cutoff ≥ 15: Probable MDD (sensitivity 81%, specificity 90%)
• Items: "Everything is a struggle," "Nothing I do is right," "Feel guilty," "I'd be better off dead," "Frustrated," "Difficulty finding pleasure"
• Preferred over PHQ-9 in epilepsy settings

GAD-7: Recommended for anxiety screening in epilepsy for the same reason.

Why not PHQ-9? Somatic items (sleep, fatigue, concentration, appetite) are confounded by AED side effects and postictal effects, inflates false positive rate.

Suicide Risk (1 mark)

• Suicide attempt rate: 5x higher than general population
• Completed suicide: 3–5x higher
• FDA 2008: All AEDs carry class black box warning for suicidality
• Risk factors: TLE, active depression, young male, drug-resistant epilepsy, recent diagnosis, social isolation

Treatment (3 marks)

Antidepressants:

Psychotherapy:

• CBT: Strong evidence; helps both depression and epilepsy adjustment
• IPT: Useful for interpersonal dimension of chronic illness adjustment
• Mindfulness-based CBT (MBCT): Growing evidence; particularly for relapse prevention

AED Optimisation:

• If AED is contributing (phenobarbital, topiramate, levetiracetam): Consider switching
• If seizure control is poor: Improving control often improves mood

Collaborative Care:

• Joint neuropsychiatry clinics are ideal
• Regular NDDI-E monitoring at follow-up

Interictal Dysphoric Disorder (0.5 marks)

Blumer's syndrome, intermittent dysphoria with eight symptoms (depressive: low mood, anergia, pain, insomnia; irritable: episodic fear, euphoria, irritability, paroxysmal affect). Does not map to DSM; may respond to SSRI + lamotrigine combination.

Answer 8: Discuss Women with Epilepsy (WWE): teratogenicity of AEDs, contraception, and pregnancy management.

Introduction (0.5 marks)

Women with epilepsy (WWE) face unique challenges at the intersection of reproductive health and neurological disease. Uncontrolled seizures during pregnancy carry foetal risks, while AEDs carry teratogenic risks. The clinical goal is to minimise seizure exposure and foetal drug exposure simultaneously, requiring careful pre-conception planning and ongoing monitoring.

Teratogenicity of AEDs (3.5 marks)

Background risk of major congenital malformation (MCM) in general population: ~1–2%.

Key valproate facts for exam:

• Highest structural AND neurodevelopmental teratogenicity
• Neurodevelopmental effects: Independent of structural malformations; dose-dependent
• MHRA 2018/2024: Valproate MUST NOT be used in women of childbearing potential without effective contraception and annual PREVENT review
• If valproate is absolutely necessary: Use minimum effective dose; folic acid 5 mg/day; detailed fetal anomaly scans

Folic acid:

• All WWE on AEDs planning pregnancy: 5 mg/day (high dose, not 0.4 mg)
• Start ≥ 3 months before conception
• Reduces (does not eliminate) NTD risk
• Rationale: AEDs (especially enzyme inducers and VPA) deplete folate

Contraception and AED Interactions (2 marks)

Clinical Implication: WWE on carbamazepine, phenytoin, or oxcarbazepine taking the OCP need to be counselled about reduced OCP efficacy. IUD is the most reliable option.

Pregnancy Management (3.5 marks)

Pre-conception:

1. Review diagnosis, is epilepsy definitely present?
2. Rationalise AED: Switch from valproate if at all possible; prefer monotherapy at lowest effective dose
3. High-dose folate 5 mg/day
4. Counsel re: risks of uncontrolled seizures (foetal hypoxia, placental abruption, maternal injury) AND AED teratogenicity
5. Optimise seizure control before conception, accept some AED risk for good control

During Pregnancy:

• AED levels fall (increased Vd, renal clearance), especially lamotrigine and levetiracetam
• Monitor drug levels monthly (especially LTG); increase dose to maintain pre-pregnancy levels
• Serial anomaly scans: Detailed 20-week scan; fetal echocardiography if valproate/carbamazepine
• Neurology review each trimester
• Seizure risk in 3rd trimester: Sleep deprivation, non-compliance, level changes

Delivery:

• Vaginal delivery preferred; seizure risk during labour is low (~1–3%)
• IV lorazepam or diazepam available in delivery room
• Neonatal vitamin K at birth (enzyme-inducing AEDs reduce neonatal vitamin K → haemorrhage risk)

Breastfeeding:

• Encouraged in most cases
• Safe: Valproate, carbamazepine, oxcarbazepine (low breast milk levels)
• Monitor infant: Phenobarbital (sedation), lamotrigine (moderate levels), levetiracetam (moderate levels)
• Valproate: Low breast milk levels, generally safe

Catamenial Epilepsy (1 mark)

Seizures clustering with the menstrual cycle in ≥2x increase in specific phase vs. baseline. Three patterns: perimenstrual (C1), periovulatory (C2), anovulatory (C3). Mechanism: estrogen proconvulsant, progesterone anticonvulsant (GABA-A modulation), premenstrual progesterone withdrawal triggers seizures. Treatment: intermittent acetazolamide, progesterone supplementation, continuous OCP.

Answer 9: Discuss Non-Convulsive Status Epilepticus (NCSE). Why is it relevant to psychiatry?

Definition (1 mark)

Non-Convulsive Status Epilepticus (NCSE) refers to a state of prolonged (≥10 minutes) epileptic seizure activity without major motor manifestations, manifesting primarily as altered consciousness, cognitive dysfunction, or behavioural changes. Diagnosis requires EEG confirmation. NCSE encompasses absence status epilepticus, complex partial status epilepticus (focal status with impaired awareness), and subtle generalised convulsive SE.

Psychiatric Relevance (3 marks)

NCSE is the most important differential diagnosis in a patient presenting acutely with:

• Sudden-onset psychosis
• Acute confusional state (delirium-like)
• Fluctuating consciousness
• Mutism
• Bizarre behaviour with partial recall
• Apparent dissociative states

Clinical presentations that mimic psychiatric disorders:

Red Flags for NCSE in Psychiatric Settings:

1. Known epilepsy history
2. Recent change in AED
3. Fluctuating rather than sustained symptoms
4. Subtle motor features: lip smacking, eye blinking, facial twitching
5. Amnesia for the episode
6. Impaired command-following despite apparent wakefulness

Diagnosis (2 marks)

EEG is mandatory for diagnosis. NCSE cannot be reliably diagnosed clinically.

EEG Patterns in NCSE:

Salzburg Criteria (2015): Most widely used criteria for NCSE diagnosis on EEG, requires epileptiform activity >2.5 Hz OR epileptiform activity at any frequency with clinical/EEG improvement on IV benzodiazepine.

Diagnostic therapeutic trial:

IV lorazepam 0.1 mg/kg or IV diazepam 0.2 mg/kg, if clinical and EEG improvement occurs, this confirms NCSE.

Management (3 marks)

Immediate:

• Call neurology/intensive care
• Airway protection; oxygen
• IV access; glucose check

First-line (Benzodiazepines):

• IV lorazepam 0.1 mg/kg OR diazepam 0.2 mg/kg
• Buccal/intranasal midazolam if no IV access

Second-line (if persistent at 20–40 min):

• IV levetiracetam 60 mg/kg (preferred)
• IV valproate 40 mg/kg
• IV lacosamide (emerging)

NCSE-Specific Considerations vs. Convulsive SE:

• Less urgency than convulsive SE (no immediate airway compromise or rhabdomyolysis risk)
• But prolonged NCSE causes neuronal injury, treat within 30–60 minutes
• De-escalation of treatment can be more gradual

After resolution:

• Review and optimise AED regimen
• Identify precipitant: AED non-compliance, infection, sleep deprivation, metabolic disturbance
• Monitor for postictal psychiatric syndromes (psychosis, depression, anxiety)

Key Teaching Point (1 mark)

Every psychiatric inpatient unit should have access to EEG services. The rule of thumb: any acute-onset psychiatric syndrome with altered consciousness, fluctuating course, subtle motor features, or known epilepsy history, get an EEG before attributing to a primary psychiatric cause. Missing NCSE in a psychiatric setting constitutes a serious clinical error.

Answer 10: Discuss the management of epilepsy with comorbid bipolar disorder. What are the challenges?

Introduction (1 mark)

The co-occurrence of epilepsy and bipolar disorder presents a complex therapeutic challenge. Both conditions share neurobiological substrates (limbic-monoaminergic dysregulation, ion channel dysfunction), and several AEDs double as mood stabilisers. However, the interaction of AEDs with psychiatric medications, the risk of drug-induced mood changes, and the competing demands of seizure control versus mood stabilisation create genuine clinical complexity.

Prevalence of Comorbidity (0.5 marks)

• Bipolar disorder in epilepsy: ~5–10% (vs. ~2% in general population)
• Higher in TLE, limbic epilepsy
• Bidirectional risk: History of bipolar disorder increases epilepsy risk (shared neurodevelopmental vulnerability)

Shared AEDs: Dual-Use Agents (3 marks)

Strategic approach: When a patient has both epilepsy and bipolar disorder, prioritise AEDs with dual efficacy:

• BD-I + epilepsy: Valproate is optimal (covers seizures + mania)
• BD + epilepsy depression: Lamotrigine + valproate combination (covers both depression and seizures; but doubles LTG levels, titrate slowly, halve dose)
• Rapid cycling BD + epilepsy: Valproate ± lamotrigine

Specific Challenges (4 marks)

Challenge 1, AED-Induced Mood Episodes:

• Levetiracetam: Can cause irritability, depression, mania-like agitation, problematic in BD
• Topiramate: Depression and cognitive effects worsen BD depressive phases
• Vigabatrin: Can precipitate psychosis and mania
• Carbamazepine: Generally mood-stabilising, but rarely can activate
• Management: Monitor mood carefully when initiating AEDs; prefer valproate or lamotrigine in BD patients

Challenge 2, Drug Interactions:

• Carbamazepine reduces quetiapine levels by 60–70% → apparent antipsychotic failure
• Carbamazepine reduces lamotrigine levels → loss of mood stabilisation
• Valproate doubles lamotrigine levels → risk of Stevens-Johnson syndrome if titrated too quickly
• Enzyme-inducing AEDs reduce all psychotropic levels significantly

Challenge 3, Lithium + Epilepsy:

• Lithium is NOT an AED; lowers seizure threshold at toxic levels
• Lithium toxicity (levels >1.5 mM) can cause seizures, tremor, encephalopathy
• For BD patients with epilepsy: Prefer valproate over lithium if seizure threshold is a concern

Challenge 4, Clozapine in Refractory Cases:

• If treatment-resistant BD psychosis requires clozapine: Significant seizure risk (3–5% at high doses)
• EEG monitoring recommended before and during clozapine use
• Consider prophylactic AED (valproate) when clozapine dose escalates
• Do NOT combine clozapine + carbamazepine (dual agranulocytosis risk, absolute contraindication)

Challenge 5, Suicidality:

• Both epilepsy and BD independently elevate suicide risk
• Combined: Risk is substantially higher
• All AEDs carry FDA black box warning for suicidality
• Monitor closely; NDDI-E plus mood diary

Clinical Approach: Summary (1.5 marks)

1. Establish each diagnosis independently, avoid assuming mood symptoms are entirely seizure-related
2. Monotherapy preferred, minimise drug burden; prioritise dual-use agents (valproate, lamotrigine, carbamazepine)
3. Interaction check mandatory before adding any new agent
4. Mood monitoring at each visit, NDDI-E, mood diary
5. Integrated care: Neuropsychiatrist or epilepsy psychiatry liaison is optimal; if unavailable, maintain clear communication between neurologist and psychiatrist
6. Teratogenicity counselling in women, valproate concerns apply equally to BD and epilepsy

Answers 11–15: Additional Model Answers

Answer 11: Describe the EEG findings in epilepsy. What is the role of EEG in psychiatric practice?

EEG Fundamentals (1 mark)

Electroencephalography (EEG) records electrical activity of the cerebral cortex via scalp electrodes, measuring voltage fluctuations from ionic current flows in neurons. The International 10–20 system standardises electrode placement. A standard EEG records ~20–30 minutes; prolonged (24–72 hour) and video-EEG extend diagnostic yield.

Normal EEG Rhythms (1.5 marks)

Epileptiform Findings (2.5 marks)

Role of EEG in Psychiatry (4 marks)

1. Ruling out organic cause of psychiatric presentation:

• First-episode psychosis: EEG should be performed to exclude NCSE, encephalitis, structural/metabolic causes
• Acute confusional state: EEG distinguishes delirium (diffuse slowing), NCSE (epileptiform activity), functional (normal)

2. NCSE in acute psychiatric settings:

• Any fluctuating psychiatric syndrome with altered consciousness → urgent EEG
• Finding: Continuous or near-continuous epileptiform activity → confirms NCSE → emergency treatment

3. PNES evaluation:

• Gold standard: Video-EEG telemetry with captured event
• Normal EEG during typical event confirms PNES diagnosis

4. Monitoring drug effects:

• Clozapine: EEG before and after dose escalation; epileptiform activity = risk for clinical seizure
• Lithium toxicity: Diffuse slowing, triphasic waves
• Benzodiazepines: Increased beta activity (useful to confirm ingestion)

5. Delirium:

• Diffuse slowing is the hallmark EEG change in delirium, correlates with severity
• Monitoring treatment response in ICU delirium

6. ECT:

• Pre-ECT: Rule out structural lesions in selected patients
• Post-ECT: Postictal slowing; monitoring for adequate ictal duration

7. Dementia:

• Alzheimer's: Progressive slowing; alpha power reduction
• CJD: PSWCs 1–2 Hz (pathognomonic, present in ~70%)
• Frontotemporal: Less specific changes

Limitations (1 mark)

• Normal interictal EEG does NOT exclude epilepsy (30–50% of epilepsy patients have normal routine EEG)
• Epileptiform discharges in ~1–2% of normal adults (not diagnostic alone)
• Must interpret with clinical context always
• Prolonged/ambulatory EEG significantly improves sensitivity

Answer 12: Discuss the management of status epilepticus. What are the psychiatric implications?

Definition (0.5 marks)

Status epilepticus (SE) is a seizure lasting ≥5 minutes OR two or more seizures without full recovery of consciousness between them (ILAE 2015 operational definition for convulsive SE). The functional definition (T2, when neuronal injury begins) for convulsive SE is 30 minutes.

Classification (1 mark)

Management Protocol (4 marks)

Phase 1, 0–5 min (Stabilisation):

• ABCDE assessment
• High-flow oxygen, IV access
• Glucose: Check and correct if <3 mmol/L
• Blood: FBC, EUC, glucose, AED levels, toxicology, LFTs, Ca, Mg
• Thiamine 100 mg IV if alcoholism suspected (before glucose)

Phase 2, 5–20 min (First-line: Benzodiazepines):

Phase 3, 20–40 min (Second-line: AED):

Phase 4, 40+ min (Refractory SE: ICU):

• Anaesthetic agents: Midazolam infusion, propofol, thiopentone
• Continuous EEG monitoring (target: burst suppression)
• Ventilatory support
• Identify and treat underlying cause

Psychiatric Implications (3.5 marks)

1. NCSE as Psychiatric Emergency:

As discussed, acute psychosis, confusion, mutism as SE presentations. Every psychiatrist must know this differential. Emergency EEG in acutely confused patients with known epilepsy is mandatory.

2. Post-SE Psychiatric Sequelae:

After convulsive SE, the following can emerge:

• Postictal psychosis (24–48h later, lucid interval)
• Postictal depression
• Postictal aggression (in the immediate postictal period, not purposeful)
• Cognitive decline (especially after prolonged SE or recurrent SE)

3. AED Selection in Patients with Psychiatric Comorbidity:

• Prefer levetiracetam or lacosamide as second-line in patients with mood disorders (valproate is acceptable; phenytoin less so)
• Avoid phenobarbital maintenance post-SE in depression-prone patients

4. Neurological Injury → Psychiatric Sequelae:

Prolonged SE causes hippocampal neuronal loss → subsequent development of TLE → full psychiatric spectrum of TLE. This trajectory (SE → TLE → depression/psychosis) is well-described and justifies aggressive SE management.

5. Psychiatric Medications and SE:

Clozapine, chlorpromazine, TCAs, lithium toxicity, all can precipitate SE. When SE occurs in a psychiatric patient, review all medications for proconvulsant potential.

1 mark: Correctly note that the psychiatric team's role in SE is primarily: (a) recognition when presenting as psychiatric symptoms, (b) managing post-SE psychiatric sequelae, (c) ensuring ongoing AED optimisation in patients with psychiatric comorbidity.

Answer 13: Describe Lennox-Gastaut syndrome. What are its psychiatric implications?

Definition and Triad (1 mark)

Lennox-Gastaut syndrome (LGS) is a severe, age-related epileptic encephalopathy defined by three features: (1) multiple seizure types, (2) characteristic EEG pattern, and (3) cognitive/developmental impairment. It is one of the most challenging epilepsy syndromes to manage, with near-universal drug resistance.

Epidemiology and Aetiology (1 mark)

• Onset: 1–7 years; peak 3–5 years
• Preceded by West syndrome in 30%
• Structural causes: Cortical dysplasia, hypoxic-ischaemic injury, tuberous sclerosis, metabolic disorders
• Cryptogenic: 30–35%

Clinical Features: The Triad (3 marks)

1. Multiple Seizure Types:

2. EEG Features:

• Interictal: Slow spike-and-wave complexes < 2.5 Hz (typically 1.5–2 Hz), defines LGS EEG
• Sleep EEG: Paroxysmal fast activity (>10 Hz, 10–25 Hz "recruiting rhythm") during NREM sleep, highly specific
• Background: Diffuse slowing

3. Cognitive/Developmental Impairment:

• Intellectual disability: Present in >80%
• Progressive deterioration in many
• Regression common after LGS onset

Psychiatric Implications (4 marks)

1. Intellectual Disability and Adaptive Functioning:

• Ranges from mild to profound ID
• Requires educational placement, occupational therapy, structured daily routines
• Psychiatric assessment must be adapted for level of cognitive functioning, standard questionnaires may not apply

2. Behavioural Problems:

• Prevalence: 50–80% of LGS patients exhibit significant behavioural problems
• Types: Aggression, self-injurious behaviour, hyperactivity, stereotypies, non-compliance
• Management: Behavioural analysis, environmental modification, judicious use of medication
• Medications for aggression in ID: Risperidone, aripiprazole (evidence in ID/autism)

3. Autism Spectrum Disorder:

• ASD features: 20–30% of LGS
• Overlapping with tuberous sclerosis (when TSC is the aetiology, ASD rate is higher, 40–50%)
• ASD evaluation: Developmental history, CARS or ADOS adapted for level of function

4. ADHD Features:

• Hyperactivity, impulsivity, attention difficulties common
• May reflect frontal lobe dysfunction secondary to seizure activity
• AED polypharmacy (especially benzodiazepines, topiramate) worsens cognitive and attentional symptoms

5. AED-Related Psychiatric Effects in LGS:

• Clobazam: Sedation, paradoxical disinhibition (especially in ID patients)
• Topiramate: Cognitive effects worsening baseline ID
• Valproate: Sedation; preferred due to mood stabilisation properties
• Rufinamide: Generally well tolerated psychiatrically
• Cannabidiol (CBD): Emerging evidence; psychiatric side effects, somnolence, decreased appetite

6. Parental/Family Psychiatric Impact:

• Caregivers of LGS patients: High rates of depression (up to 60%), anxiety, burnout
• Respite care access, caregiver support groups, psychiatric monitoring of parents, part of comprehensive management

7. Quality of Life:

• Severely impaired in both patients and families
• Drop attacks are the feature most associated with poor QoL (physical danger, social restriction)
• Helmet use is necessary but stigmatising

Answer 14: Discuss the psychiatric aspects of West syndrome and infantile spasms.

Definition (1 mark)

West syndrome is an age-related epileptic encephalopathy of infancy, characterised by a classic triad: (1) epileptic (infantile) spasms, (2) hypsarrhythmia on EEG, and (3) developmental regression or arrest. It is the most common epileptic encephalopathy in infancy and one of the most psychiatrically significant, given its strong association with autism spectrum disorder and intellectual disability.

Epidemiology (0.5 marks)

• Incidence: ~1/4000 live births
• Age of onset: 3–12 months; peak 4–6 months
• Male slightly predominant

Aetiology (1 mark)

Tuberous sclerosis (TSC) is the most common identifiable structural cause, always examine for TSC features (ash leaf macules, shagreen patches, adenoma sebaceum, cardiac rhabdomyoma).

Clinical Features (1.5 marks)

Infantile Spasms:

• Brief (1–2 seconds), symmetric contractions
• Flexion, extension, or mixed
• Occur in clusters, most prominent on waking
• Child may appear to startle or "scrunch up"
• Often preceded by a cry or giggle

Hypsarrhythmia (EEG):

• Chaotic, high-amplitude
• Asynchronous slow waves with multifocal spikes superimposed
• No organised background activity
• Pathognomonic for West syndrome

Developmental Regression:

• Loss of previously acquired milestones (smile, eye contact, reaching)
• Often noted by parents as "baby seems different"
• Regression is the most clinically alarming feature

Treatment (1 mark)

Early treatment = better neurodevelopmental outcome. Every 1-week delay increases ASD risk.

Psychiatric Implications (4.5 marks)

1. Autism Spectrum Disorder (ASD):

• Prevalence of ASD in West syndrome: 30–50% overall; up to 60% in TSC-associated cases
• ASD features may emerge after seizure onset, often as developmental regression
• Mechanism: Epileptiform activity in limbic and association cortices disrupts critical periods of social-communicative brain development
• Diagnosis: Developmental surveillance at all follow-up appointments; formal ASD evaluation at 18–24 months
• Management: ABA, speech therapy, occupational therapy, structured educational programme

2. Intellectual Disability:

• 70–80% of West syndrome survivors have ID (ranges from mild to profound)
• Extent of ID correlates with: Underlying aetiology (TSC = better than anoxic injury), EEG duration of hypsarrhythmia, age at seizure onset, treatment latency
• Cryptogenic West syndrome: Better cognitive outcome (~50% normal or near-normal)

3. ADHD Features:

• Inattention, hyperactivity, impulsivity common in survivors
• May reflect frontal lobe involvement or medication effects (ACTH, steroids in early life)

4. Behavioural Disturbance:

• Irritability, sleep disturbance, self-injurious behaviour, all more common in TSC-associated cases
• ASD + seizures = complex behavioural management challenge

5. Impact on Caregivers:

• West syndrome diagnosis triggers significant parental crisis
• Parents require: Clear, compassionate communication; prognostic counselling; early referral to developmental services
• Parental depression: ~50–60% in first year after diagnosis
• Family counselling, social work input, essential components of management

6. Tuberous Sclerosis Complex (TSC), Special Case:

TSC-associated West syndrome warrants mention as a separate entity:

• Earlier vigabatrin treatment (pre-symptomatic in some guidelines) reduces ASD risk
• Everolimus (mTOR inhibitor): Reduces tuber burden and some cognitive effects
• Psychiatric manifestations in TSC beyond ASD: Anxiety, OCD, ADHD, aggression

Answer 15: Discuss the ILAE-defined epilepsy syndromes relevant to psychiatry. Compare their psychiatric profiles.

Introduction (1 mark)

Epilepsy syndromes are defined constellations of seizure types, EEG patterns, age of onset, aetiology, and natural history. For psychiatric practice, five syndromes are particularly relevant: Childhood Absence Epilepsy (CAE), Juvenile Myoclonic Epilepsy (JME), West syndrome, Lennox-Gastaut Syndrome (LGS), and Temporal Lobe Epilepsy (TLE). Each carries a distinct psychiatric profile.

Syndrome Profiles (5 marks)

Key Differentiating Points (2 marks)

CAE vs. ADHD: CAE is the critical differential for inattentive ADHD in children. Brief, frequent staring spells with no postictal phase = CAE until proven otherwise. Hyperventilation test in clinic: Induces typical absences. EEG confirms. Ethosuximide resolves both seizures and "attention problems."

JME lifestyle significance: JME is one of the few epilepsies where lifestyle modification is as important as medication. Sleep deprivation, alcohol, photic stimulation (common in adolescent social contexts) trigger seizures. Psychiatric input for sleep hygiene, impulse control, and substance use counselling is directly therapeutic.

LGS behavioural burden: LGS generates the highest caregiver psychiatric burden of all syndromes. Psychiatric support for families is not optional, depression and burnout in caregivers directly affects patient safety and treatment adherence.

TLE psychiatric depth: No other epilepsy syndrome generates as diverse or as clinically significant psychiatric comorbidity as TLE. Every psychiatrist working in a hospital setting will encounter TLE patients with depression, psychosis, or PNES, often simultaneously.

Clinical Synthesis (2 marks)

Psychiatric approach by syndrome priority:

1. TLE, Screen for depression (NDDI-E), psychosis, anxiety at every visit; joint neuropsychiatry input
2. West/LGS, Prioritise developmental assessment, ASD screening, caregiver psychiatric support
3. JME, Lifestyle counselling, mood monitoring, valproate teratogenicity counselling in women
4. CAE, Misdiagnosis awareness; once treated, most psychiatric issues resolve with seizure control

Mnemonics & Memory Tricks

15+ mnemonics covering all high-yield topics in Epilepsy & Psychiatry

MNEMONIC 1: Geschwind Syndrome: "5 H's of TLE Personality"

H H H H H

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MNEMONIC 2: Postictal Psychosis Key Features: "LUCID"

L U C I D

MNEMONIC 3: SLPE vs Schizophrenia: "PAWNS"

Schizophrenia-Like Psychosis of Epilepsy has PAWNS (not schizophrenia's full deck)

MNEMONIC 4: ILAE 2017: Focal Seizure Descriptors, "SAME ACE"

Motor descriptors: SAME ACE

Non-motor: Autonomic, Behaviour arrest, Cognitive, Emotional, Sensory

MNEMONIC 5: West Syndrome Triad: "HIRS"

H I R S (Hypsarrhythmia In Regressing Spasms)

MNEMONIC 6: Lennox-Gastaut: "DATS"

LGS = D A T S

MNEMONIC 7: NDDI-E Items: "EVERYTHING FEELS LIKE A GUILTY STRUGGLE"

Six items of NDDI-E (Neurological Disorders Depression Inventory for Epilepsy):

GDNFEP, "Guilty Dead Nothing Frustrated Everything Pleasure"

Cutoff: ≥15 out of 24 = probable MDD (6 items × max 4 = 24)

MNEMONIC 8: AED Proconvulsant Risk for Antipsychotics: "A ROQC" (Low to High)

A → R → O → Q → C (Aripiprazole → Risperidone → Olanzapine → Quetiapine → Clozapine)

Memory: "A Royal Orchestra Quite Carefully", least to most risky

MNEMONIC 9: Antidepressants to AVOID in Epilepsy: "BBC" (Bad For Brain Convulsions)

B B C

Safe alternatives: SSRIs (sertraline, escitalopram), SNRIs, mirtazapine

MNEMONIC 10: Enzyme-Inducing AEDs: "CORP"

C O R P = AEDs that induce CYP3A4 (reduce psychotropic levels)

Clinical consequence: Reduce levels of all antipsychotics and many antidepressants by 40–70%. When adding CORP drugs, expect apparent drug failure, increase psychotropic dose.

MNEMONIC 11: Teratogenicity Hierarchy: "VERY BAD PILL, LAMOTRIGINE OK"

Teratogenicity: High → Low

Folic acid: 5 mg/day for all WWE on AEDs, start 3 months pre-conception

MNEMONIC 12: Status Epilepticus Management: "BEAT IT"

B E A T I T (Time-based Protocol)

MNEMONIC 13: JME Classic Triad + Triggers: "MAG + SAS"

Triad: MAG (Myoclonic + Absence + Grand mal)

Triggers: SAS (Sleep deprivation + Alcohol + Stress/Sunlight)

MNEMONIC 14: Catamenial Epilepsy Patterns: "C1 C2 C3 = Period, Ovulation, Whole Luteal"

Three Herzog Patterns:

Memory: "C1 = (C)ycle start, C2 = (C)entre, C3 = (C)lose (whole closing half)"

MNEMONIC 15: PNES vs. Epilepsy Differentiators: "CLOSE EYES CRY LONG"

Features suggesting PNES:

MNEMONIC 16: Ictal Emotions by Structure: "FAJ" (Fear-Amygdala-Joy)

Also: Anger (temporal-frontal), Sadness (temporal), Disgust (basal ganglia-insula)

MNEMONIC 17: AED Psychiatric Uses: "VaLCa" (Valproate, Lamotrigine, Carbamazepine)

VaLCa = The three AEDs with established psychiatric indications

The rest of the AEDs (levetiracetam, topiramate, gabapentin, phenobarbital) are NOT primary psychiatric treatments. Pregabalin = licensed for GAD in Europe only.

MNEMONIC 18: Forced Normalisation: "LANDOLT'S PARADOX"

Simple memory sentence:

MNEMONIC 19: Blumer's Interictal Dysphoric Disorder: "DEAF + PFIE"

Eight symptoms in two groups:

Depressive group (DEAF):

Labile/Irritable group (PFIE):

MNEMONIC 20: Normal EEG Rhythms: "All Brains Think Deeply"

A B T D (Alpha, Beta, Theta, Delta: fast to slow)

"All Brains Think Deeply", Alpha → Beta → Theta → Delta (decreasing frequency)

High-Yield Comparisons

10 high-yield comparison tables for exam revision

Table 1: Epileptic Seizures vs. PNES (Psychogenic Non-Epileptic Seizures)

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Table 2: Ictal vs. Postictal vs. Interictal Psychosis

Table 3: TLE (Temporal Lobe Epilepsy) vs. FLE (Frontal Lobe Epilepsy)

Table 4: Interictal Dysphoric Disorder (IDD) vs. Major Depressive Disorder in Epilepsy

Table 5: AED Psychiatric Profiles: Benefit vs. Risk

Table 6: Postictal Psychosis vs. Forced Normalisation vs. Interictal Psychosis

Table 7: Childhood Absence Epilepsy vs. Juvenile Myoclonic Epilepsy

Table 8: West Syndrome vs. Lennox-Gastaut Syndrome

Table 9: Schizophrenia vs. Schizophrenia-Like Psychosis of Epilepsy (SLPE)

Table 10: Valproate vs. Lamotrigine: Psychiatric and Reproductive Comparison

PYQ Frequency Analysis

Analysis based on PG exams MD Psychiatry Paper IV question patterns, PG theory papers, and PG exams PG entrance patterns. Covers 17+ years of available data.

SECTION 1: Master Frequency Table

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SECTION 2: Tier 1 Topics: Highest Priority

Topic 1: Postictal Psychosis

Estimated appearances: 4–6 times in 17 years

Why it's Tier 1: Combines clinical psychiatry (psychosis management), neuropsychiatry (peri-ictal phenomena), and pharmacology (antipsychotics in epilepsy). Examiners love it because it tests integration.

How it's been asked:

• "Describe postictal psychosis. Discuss its management." (10 marks)
• "Write a short note on postictal psychosis." (5 marks)
• "What is the lucid interval? Discuss its clinical significance." (5 marks)
• Part of: "Classify psychiatric phenomena in epilepsy."

What the marking key expects:

1. Definition with lucid interval prominently stated
2. Epidemiology (7–10% TLE)
3. Clinical features table (mood, hallucinations, EEG, duration)
4. Risk factors (bilateral foci, prior PIP)
5. Pathophysiology (forced normalisation/dopamine)
6. Management (antipsychotic choice, aripiprazole/olanzapine, avoid clozapine; AED optimisation; psychoeducation)
7. Prognosis (15% risk of chronic interictal psychosis with recurrence)

Topic 2: PNES / Psychogenic Non-Epileptic Seizures

Estimated appearances: 4–6 times in 17 years

Why it's Tier 1: Tests clinical differentiation skill, psychiatric formulation, and management of a medically complex patient. Also tests awareness of FND framework.

How it's been asked:

• "Compare epileptic seizures with pseudoseizures." (10 marks)
• "Discuss the management of PNES." (10 marks)
• "What is the gold standard for diagnosing PNES? Discuss clinical features." (5–10 marks)
• "Write a short note on psychogenic non-epileptic seizures." (5 marks)

What the marking key expects:

1. Definition and preferred terminology (PNES, functional seizures, not pseudoseizures)
2. Epidemiology (20–30% of EMU referrals; 7-year diagnostic delay)
3. Clinical differentiation table (semiology, EEG, postictal, eye position)
4. Gold standard = Video-EEG with captured event
5. Psychiatric comorbidity profile (depression, PTSD, BPD)
6. Disclosure framework (what to say, what NOT to say)
7. Management (CBT first-line; treat comorbidities; AED withdrawal)
8. Prognosis

Topic 3: AEDs as Mood Stabilisers

Estimated appearances: 4–5 times in 17 years

Why it's Tier 1: Bridges neurology and psychiatry pharmacology. Extremely practical. Also connects to teratogenicity and drug interactions.

How it's been asked:

• "Discuss the role of anticonvulsants in psychiatry." (10 marks)
• "Write about valproate as a mood stabiliser." (5–10 marks)
• "Compare valproate and lamotrigine in bipolar disorder." (10 marks)
• "Discuss carbamazepine in psychiatry." (5 marks)

Key content points:

• Valproate: BD-I mania first-line; mechanism; teratogenicity; PREVENT
• Carbamazepine: BD (especially rapid cycling, dysphoric); enzyme induction
• Lamotrigine: Bipolar depression (best evidence); rash; OCP interaction
• The three together: VaLCa (Valproate + Lamotrigine + Carbamazepine)

Topic 4: Psychiatric Side Effects of AEDs

Estimated appearances: 4–5 times in 17 years

Why it's Tier 1: Pure pharmacology with direct clinical application. Every resident will encounter this.

How it's been asked:

• "Discuss the psychiatric side effects of antiepileptic drugs." (10 marks)
• "Write a note on levetiracetam and its psychiatric effects." (5 marks)
• "What are the cognitive effects of topiramate?" (5 marks)
• "Discuss phenobarbital and depression." (5 marks)

The examiner's three key drugs:

1. Levetiracetam, irritability/aggression/psychosis (10%)
2. Topiramate, cognitive impairment ("Dopamax"), word-finding
3. Phenobarbital, depression (worst AED for depression)

Plus: Valproate teratogenicity, vigabatrin forced normalisation, FDA black box for all AEDs.

Topic 5: Depression in Epilepsy

Estimated appearances: 3–4 times in 17 years

How it's been asked:

• "Discuss depression in epilepsy." (10 marks)
• "Write a note on NDDI-E." (5 marks)
• "What is the bidirectional relationship between epilepsy and depression?" (5 marks)

Key content requirements:

• Bidirectional relationship (both increase risk of the other, shared neurobiology)
• Prevalence 30–50% in TLE
• NDDI-E (6 items, cutoff ≥15, preferred over PHQ-9 in epilepsy)
• Antidepressants in epilepsy: SSRIs safe; bupropion contraindicated; TCAs avoid
• Suicide risk (5× higher)
• FDA 2008 AED suicidality warning

Topic 6: SLPE / Interictal Psychosis

Estimated appearances: 3–4 times in 17 years

How it's been asked:

• "Describe schizophrenia-like psychosis of epilepsy." (10 marks)
• "How does interictal psychosis differ from schizophrenia?" (10 marks)
• "Write a note on Slater and Beard (1963)." (5 marks)

Non-negotiable content:

• Slater & Beard 1963, cite this
• "Positive without negative" pattern
• Preserved affect (warmth), most distinctive
• No family history of schizophrenia
• Appears 10–15 years after epilepsy onset

SECTION 3: Tier 2 Topics: Important, Appear Regularly

Topic 7: Forced Normalisation / Landolt

How asked: "Write a short note on forced normalisation." (5 marks)

Must include: Landolt 1953; EEG normalisation when seizures stop; alternative psychosis (Tellenbach); AEDs implicated (vigabatrin, ethosuximide); management (reduce AED + antipsychotic); clinical implication (do NOT increase AED).

Topic 8: ILAE Seizure Classification

How asked: "Classify seizures according to ILAE 2017." (5 marks, or as part of a 10-mark TLE question)

Must include: Three levels (seizure type, epilepsy type, syndrome); focal (aware/impaired/bilateral), generalised (motor/non-motor), unknown; replace old terms with new.

Topic 9: Temporal Lobe Epilepsy and Psychiatry

How asked: "Discuss the psychiatric relevance of temporal lobe epilepsy." (10 marks)

Must include: MTLE features; aura types; psychiatric comorbidities (depression 30–50%, anxiety 25–40%, psychosis 5–10%); Geschwind syndrome; ictal fear; peri-ictal psychoses; PNES overlap.

Topic 10: Women with Epilepsy / Teratogenicity

How asked: "Discuss management of epilepsy in pregnancy." / "Write about teratogenicity of AEDs." (10 marks, 5 marks)

Must include: Valproate hierarchy; lamotrigine preferred; folic acid 5 mg; OCP interactions; pregnancy AED level monitoring; fetal anomaly scans; breastfeeding guidance.

Topic 11: EEG in Psychiatry

How asked: "Discuss the role of EEG in psychiatric practice." (5–10 marks)

Must include: Normal rhythms (table); epileptiform patterns; delirium (diffuse slowing); NCSE; PNES (video-EEG); clozapine monitoring; CJD (PSWCs); drug effects (benzodiazepine → beta).

Topic 12: Status Epilepticus

How asked: "Outline the management of status epilepticus." (5–10 marks)

Must include: ILAE 2015 definition (≥5 min); time-based protocol; benzodiazepines first (doses); second-line (LEV, VPA, phenytoin); refractory (ICU, anaesthetic); psychiatric relevance (NCSE).

Topic 13: West Syndrome and LGS

How asked: Usually "short note" (5 marks each)

West, must include: Triad (spasms + hypsarrhythmia + regression); age (3–12 months); ACTH/vigabatrin; ASD and ID outcomes.

LGS, must include: Triad (multiple seizure types + slow SWD <2.5 Hz + ID); tonic seizures hallmark; drop attacks; drug resistance; psychiatric burden.

SECTION 4: Tier 3 Topics: Lower Frequency, Include if Time Permits

SECTION 5: Question Pattern Analysis by Year-Type

Common Long Answer (10-mark) Patterns

Common Short Note (5-mark) Patterns

SECTION 6: High-Yield Facts That Appear as MCQs or One-Liners

SECTION 7: Predicted High-Probability Questions for 2026 Exit Exam

SECTION 8: Topics to COMBINE in Answers

Some topics appear individually but are better answered together, mentioning them in a related answer earns extra marks.

Revision note: Cross-reference with D2-ModelAnswers.md for fully written-out versions of the top predicted questions.

Quick Review

30 rapid-fire question-answer pairs covering all high-yield Epilepsy & Psychiatry topics

RAPID-FIRE Q&A: ALL 30 PAIRS

Q1

What is the pathognomonic feature that distinguishes postictal psychosis from other peri-ictal psychoses?

Q2

Slater and Beard (1963) described schizophrenia-like psychosis of epilepsy. What are the TWO most important features that distinguish it from schizophrenia?

Q3

What is forced normalisation? Who described it and when?

Q4

Which AED carries the highest risk of inducing forced normalisation?

Q5

What is the gold standard for diagnosing PNES?

Q6

Name the 6 items of the NDDI-E and its cutoff score for probable MDD.

Q7

Why is NDDI-E preferred over PHQ-9 for screening depression in epilepsy?

Q8

Describe the bidirectional relationship between epilepsy and depression.

Q9

Which antidepressant is contraindicated in epilepsy and why?

Q10

Rank the following antipsychotics from LOWEST to HIGHEST proconvulsant risk: Clozapine, Risperidone, Aripiprazole, Olanzapine, Quetiapine.

Q11

Why is clozapine + carbamazepine absolutely contraindicated?

Q12

What are the five features of Geschwind syndrome?

Q13

What is the ILAE 2017 replacement for "complex partial seizure"?

Q14

Describe the classic triad of West syndrome and its first-line treatments.

Q15

What is the EEG hallmark of Lennox-Gastaut syndrome?

Q16

What is the JME classic triad and its most important seizure trigger?

Q17

What is the teratogenic risk profile of valproate?

Q18

How does an oral contraceptive pill (OCP) interact with lamotrigine?

Q19

What is the Indian regulatory requirement for driving after epilepsy?

Q20

Describe the 3 Hz spike-wave discharge, what condition is it pathognomonic of?

Q21

What is the most common form of autoimmune encephalitis and how does it present psychiatrically?

Q22

What is the ILAE 2015 operational definition of convulsive status epilepticus?

Q23

Name the second-line AEDs for status epilepticus with doses.

Q24

What is Interictal Dysphoric Disorder (IDD)? Name its 8 symptoms.

Q25

What is NCSE and why is it a psychiatric emergency?

Q26

Describe the three patterns of catamenial epilepsy (Herzog classification).

Q27

What psychiatric sequelae can occur after epilepsy surgery (anterior temporal lobectomy)?

Q28

What are the psychiatric comorbidities of tuberous sclerosis complex (TSC)?

Q29

Classify EEG rhythms from fastest to slowest and state one clinical association for each.

Q30

Summarise the management of PNES in 6 steps.

BONUS: 10 One-Line Facts for Last-Minute Revision

Cross-reference: D1 (Study Notes) for depth · D2 (Model Answers) for written practice · D3 (Mnemonics) for retrieval cues · D4 (Comparisons) for differential tables · PYQ Analysis for question prediction