imitators of epilepsy - mc.vanderbilt.edu of... · epilepsy differential diagnosis - the...
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Imitators of Epilepsy
Nabil J. Azar, M.D. Vanderbilt University Medical Center
Nashville, Tennessee
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Disclosure
I have no financial relationships to disclose that are relative to the content of my
presentation.
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Epilepsy differential diagnosis - The differential diagnosis of epileptic seizures is very
broad, partly because the symptomatology of epileptic seizures is varied, depending on the eloquent cortical areas activated by the epileptic activity.
- There is a great amount of diseases which can produce
focal neurological symptoms and signs, occurring repeatedly in a paroxysmal way, not unlike epileptic seizures, and which can be mistaken for epilepsy.
- To make a definite diagnosis of epilepsy, it is necessary
to demonstrate the abnormal ictal activity associated with the recurrent attacks.
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Outline
• Physiologic non-epileptic imitators:
- Cardiovascular - Syncope - Migraine - Sleep disorders - Movement disorders - Endocrine
• Non-physiologic nonepileptic imitators:
- Psychiatric - Convulsive
psychogenic attacks - Nonconvulsive
psychogenic attacks
• Paroxysmal disorders in infants and children
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Imitators of epilepsy in infants Sleep:
- Head banging: duration of 15-30 min in transition to sleep, until the age of 1 - Benign neonatal myoclonus: usually not stimulus-induced, stops upon awakening - Infant apnea: ? related to sudden infant death syndrome
Wakefulness: - Jitteriness: mostly stimulus induced - Benign myoclonus of early infancy - Spasmodic torticollis : idiopathic or related to GE reflux (Sandifer syndrome) - Spasmus nutans: head nodding, head tilt and nystagmus, outgrown by age of 5-8 - Hyperexplexia or startle disease: rare familial disorder with variable prognosis - Shuddering attacks: excessive shivering , ? familial, outgrown by age of 10 - Pallid syncope: due to transient asystole (tonic contractions)
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Imitators of epilepsy in children Sleep:
- Myoclonus - Hypnagogic paroxysmal dystonia - Parasomnias: nightmares or terrors or sleep walking
Wakefulness:
- Cyanotic breath holding spells: precipitated by fear or mild injury - Tics: disappear in sleep, may be complex (Tourette’s syndrome) - Recurrent abdominal pain: vomiting, palor, often with headaches
(15 % will have epilepsy) - Confusional migraines: lasting for hours - Munchausen syndrome by proxy
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Cerebrovascular imitators • Transient ischemic attacks (TIA) - vertebrobasilar > anterior circulation • Transient global amnesia (TGA):
- confusion and amnesia - vascular>migrainous>epileptic
• Drop attacks: with/without loss of conscioussness or postictal state - compressive brainstem vascular disturbances - cervical cord diseases - colloid cysts
Hodges J. WB Saunders 1991
Lesser R. et al. Epilepsia 1985
Meissner I. Neurology 1985
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Syncope: common features • Sudden • Unpredictable • Recurrent loss of consciousness • Common disorder (10%) • “Convulsive ” myoclonus • Stereotyped • Witness panic • Potential serious injury • High morbidity and mortality
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Factors causing syncope
• Decreased cardiac output: • Asystole • Tachy-arrhythmias • Brady-arrhythmias • Heart failure
• Decreased blood volume • Decreased total peripheral resistance • Hypotension • Any combination of the above
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Classification of syncope types by precipitating cause:
• Reflex or vasovagal syncope (common faint): loss of vasomotor tone
• Respiratory syncope: rise in intrathoracic pressure impairing cardiac venous return (coughing, weight lifting)
• Cardiac syncope: • rhythm abnormalities • Obstruction of cardiac output
• Vascular: hypotension • Areflexic or paralytic: neuropathic, drugs,
trauma
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Signs and Symptoms: seizure vs. syncope
• Common, light headedness, sweating, pallor, dimming vision
• Gradual onset and progression
• Depressed pulse, respiration and heart rate
• Usually occurs in upright position or upon exertion
• Motionless or limited clonic or myoclonic
• Usually prompt • Less common
• Less common, very brief aura
• Sudden and quick
• Rapid heart rate, elevated blood pressure
• Occurs in any position • Prominent tonic, clonic or
myoclnic, automatism • Slow • More common
Syncope Seizure
Prodrome:
Onset:
Vital functions:
Position:
Motor activity:
Recovery:
Incontinence:
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Syncope-induced myoclonus
• Incidence: up to 90 % of all syncopal attacks
• More common in younger adults • Multifocal > unifocal • Unilateral or bilateral • No prognostication for recovery except in
anoxic injury
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Diagnosis of syncope
Diagnostic testing: • Long-term video-EEG monitoring • Routine EEG • ECG / holter monitoring • Tilt table test / orthostatic blood pressure • Carotid ultrasound
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Migraines and epilepsy
• Common neurological disorders • Could trigger each other • Coexists in about 25 % of patients Relationship between migraine and epilepsy?
Overlap syndromes: - Benign occipital epilepsy - Migrainous and convulsive hemiplegia - Mitochondrial encephalopathy
Barolin G. Epilepsia 1966
Panayiotoupoulos C. Neurology 1980
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Migraine and epilepsy: common features • GI upset • Flushing and autonomic symptoms • Vertiginous disequilibrium • Complex visual hallucinations • Uncinate (smell/taste) auras • Paroxysmal and transient focal neurological deficits • Provoked by hormonal changes • Occasional CSF abnormalities • Abnormal EEG during attacks (slow activity, sharply
contoured waves, posterior sharps for hours or days) • Response to “anticonvulsants” • Comorbidities: anxiety and depression • Positive family history
Anderman E. et al. Butterworths 1987
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Migraine and epilepsy: distinguishing features
Favor migraines: • Recurrent headaches • Photophobia • Scotoma • Simple visual
hallucination • Provoked by diet • Response to anti-migraine
medications • Gradual onset • Prolonged duration • Absence of postictal state
Favor epilepsy: • Partial motor
manifestations • Generalized tonic-clonic
events • Nocturnal occurrence • Photic/HV provocation • Response to
“anticonvulsants” • Sudden onset • Short duration • Presence of postictal state
Rapoport A. Neurology 1992
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Atypical migraines
• Acephalgic migraine: controversial • Basilar artery migraine: vertigo, ataxia,
change in level of consciousness • Hemiplegic migraine • Postictal migraine “epileptic cephalgia” • Migraine-triggered seizures • Cluster headaches (autonomic
manifestations…)
Niedermeyer E. Clin Electroencephalogr 1993 Bickerstaff E. Lancet 1961
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Sleep conditions imitating epilepsy
• REM behavior disorder • Nightmares • Night terror • Sleep walking (somnanbulance) • Period leg movements of sleep • Bruxism • Cataplexy • Sleep paralysis • Daytime sleep attacks
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Parasominas vs frontal lobe seizures
Carreno M. Seminars in Neurology 2008
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Movement disorders and epilepsy • Chorea and athetosis • Ballismus • Paroxysmal ataxia • Dystonia • Tics and Tourette’s syndrome • Paroxysmal dystonic choreoathetosis (min-hours, not precipitated by
mvt) • Paroxysmal kinesigenic choreoathetosis (sec-min, precipitated by mvt) • Blepharospam • Hemifacial spasm • Tardive dyskinesia • Akathisia • Cramps and spasms • Stiff person • Myoclonus • Asterxis • Tremor • Startle disease (hyperekplexia) • Restless leg syndrome
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Paroxysmal choreoathethosis
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Myoclonus • Physiologic: Hypnic jerks,
sleep-related, cough-induced, exercise or anxiety related…
• Essential: hereditary or sporadic…
• Infectious: SSPE, CJD, postviral…
• Metabolic: uremic, hepatic, alcohol-related, toxic (AEDs, l-dopa etc)…
• Neoplastic: basal ganglia…
• Cerebrovascular: CVA, anoxic..
• Degenerative d/s: Wilson’s, HVZ, Alzheimer, Huntington, PD…
• Storage diseases: Gaucher, Tay-Sachs…
• Epileptic: - Non-progressive:
idiopathic or symptomatic - Progressive: progressive
myoclonic epilepsies
Fahn S. et al. Adv Neurol 1986
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Movement disorder side effects of AEDs
• Phenytoin: dystonia, asterexis, chorea, dyskinesia, ballismus
• Phenobarbital: dystonia, tics • Carbamazepine: orofacial dyskinesia,
myoclonus, dystonia • Valproate: asterexis, tremor (parkinsonism) • Ethosuximide: dyskinesia • Lamotrigine: Oculogyric crisis
Karas B. et al. Neurology 1983 Chadwick D. et al. J Neurol Neurosurg Psych 1976 Joyce R. et al. Neurology 1980
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Endocrine imitators of epilepsy • Hypoglycemia (double vision, confusion, odd behavior,
slurred speech, tremor, weakness, vertigo, anxiety, ataxia, palpitation….true seizures)
• Hyperglycemia (altered consciousness but very gradual…true focal seizures)
• Hyponatremia / hepernatremia • Hypocalcemia: mental status changes, carpopodeal spasm • Hyperthyroidism (Hashimoto’s) / hypothyroidism • Pheochromocytoma/paragangliomas (syncope, flushing,
epigastric sensation) • Carcinoid (serotonin releasing tumors) • Mastocytosis (mainly histamine release) • Acute porphyria (heme synthesis disturbances)
The majority of the above conditions may also provoke epileptic seizures
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Vertigo and epilepsy
• Dizziness is nonspecific and seldom associated with epilepsy
• Dizziness is very common in patients with epilepsy (AED side effects)
• Vertigo: - Peripheral: BPPV, Menier’s, acoustic
neuroma… - Central: CVA, migraine, MS…
Hughes J. et al. Dis Nerv System 1983
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Psychiatric imitators of epilepsy
• Coversion disorder • Delirium • Panic disorders • Dissociative disorders (alteration in
memory, behavior or identity) • Schizophrenia • Delusional disorders • Mutism • Mania • Major depressive episode
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Delirium and epilepsy: common features • Critically-ill patients in whom non-convulsive status
epilepticus is often under diagnosed • Fluctuating consciousness, inappropriate behavior and
subtle motor manifestations (absence, complex partial seizures)
• Similar causes: intoxication (including AEDs), organ failure, electrolytes imbalance, CVA, intracranial infections…
• Preictal, ictal and postictal delirium
The electrographic distinction maybe challenging because of nonspecific EEG patterns that could be interpreted as
encephalopathic, postictal or ictal.
Lipowski Z. Oxford Press 1990
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Ictal fear vs. panic attack
Carreno M. Seminars in Neurology 2008
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Psychosis and epilepsy • Ictal psychosis • Postictal psychosis: may be delayed 1-7 days • Interictal psychosis: - Prolonged or brief - “Forced normalization” - Not correlated with seizure frequency or epilepsy duration - May develop at anytime • Chronic psychosis in epilepsy “epileptic schizophrenia”:
unknown relationship especially that these two disorders are thought to be antagonistic (ECT)
• Geschwind syndrome: in patients with temporal lobe epilepsy, characterized by sexual behavioural disorders, hyper-religiosity, hypergraphia and viscosity (interictal>ictal)
• ECT and seizures
McKenna P. et al. Am J. Psychiat 1985
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Psychogenic Seizures - Patterns
• Generalized motor activity 66 • Migratory motor activity 93 • Unilateral motor activity 13 • Altered responsiveness only 12 • Collapse 8
Moore D. et al. J. Epilepsy 1998
192 patients with confirmed diagnosis of psychogenic nonepileptic seizures: witnesses survey
89 %
11 %
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Frontal lobe complex partial seizures
• Stereotyped pattern • Frequent seizures, often in clusters • Brief seizures, under 1 minute • Bizarre attacks that appear hysterical • Prominent motor automatisms, usually complex • Aggressive sexual automatisms • Vocalizations, with variable complexity • Short postictal period, rapid clearing • Complex partial status epilepticus common
Williamson J. et al. Annals of Neurology 1995
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Hypermotor seizure
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Coexistence of psychogenic and epileptic seizures
• 50-58 %: including staring or unresponsive spells.
• 30-45 %: based on clinical impression.
• 18-20 %: confirmed by long-term video-EEG.
• 16-20 %: confirmed by long-term video-EEG.
Holmes M. et al. Epilepsia 1993
Cohen B. et al. Seizure 1997
Lesser T. Epilepsy & Behavior 2004
Sutter M. et al. Epilepsia 2002
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Discriminating ictal features of nonepileptic seizures
1- Out of phase upper extremity movements 2- Out of phase lower extremity movements 3- No vocalization, or vocalization at onset 4- Forward pelvic thrusting 5- Absence of whole body rigidity 6- Side to side head movements
Gates J. et al. Arch Neurology 1985
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Psychogenic monepileptic attacks: red flags
• Multiple types of attacks • Changing types of attacks • Prolonged and repetitive attacks • Atypical auras (headache, numbness, chest
tightness, dizziness…) • Variable degree of responsiveness • Variable degree of awareness and memory • Poor response to antiepileptic drugs • Beware of : - “pseudosleep” - “pseudo-pseudoseizures” - pelvic thrusting
Bendabis S. et al. Epilepsy Research 2005
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Distinguishing ictal features
Azar N. et al. Epilepsia 2008
GTC PNES FLHS Eyes open 91 % (p<0.05) 27 % 67 %
Vocalization 54 % 62 % 41 % Asynchronous
movement 9 % 96 % (p<0.01) 90 % (p<0.05)
Side to side head/body
5 % 63 % (p<0.05)
76 % (p<0.01)
Mean ictal duration (sec)
42 185 (p<0.05)
34
GTC: generalized tonic-clonic seizures, PNES: psychogenic nonepileptic seizures, FLHS: frontal lobe hypermotor seizures
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Postictal breathing pattern Epileptic: - Deep - Loud with snoring - Regular - Prolonged inspiratory
and expiratory phases - Duration 1-5 minutes
Nonepileptic: - Shallow - Quiet - Irregular with brief pauses - Short inspiratory and
expiratory phases - Duration 1< minute
p < 0.001 for all features
Azar N. et al. Epilepsia 2008
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Postictal breathing- epileptic
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Postictal breathing- nonepileptic
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Injury and incontinence
Epileptic seizures: - 38 patients - 48 % tongue biting - 54 % urinary incontinence - 48 % injuries - Burns, bone fracture more
common (p<0.05)
Nonepileptic seizures: - 73 patients - 44 % tongue biting - 45 % urinary incontinence - 40 % injuries - Suicide attempts more
common (p<0.05)
Peguero E. et al. Epilepsia 1995
Telephone survey to witnesses and families
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Facial muscle involvement
• Open eyes recorded in 90 % of epileptic events in the tonic phase
• Forceful eye closure recorded in 60 % of nonepileptic events
• Tongue biting on the side reported in 54 % of patients with epileptic seizures
• Tongue biting at the tip reported in 44 % of patients with nonepileptic seizures
DeToledo J. et al. Neurology 1996
Video-EEG review and witnesses’ survey of: - 654 epileptic events observed in 257 patients
- 457 nonepileptic events observed in 159 patients
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Nonepileptic seizures: suggestive features • Atypical auras • Pre-ictal behavior changes • Gradual onset • “Pseudo-sleep” at onset • Eye closure during
unresponsiveness • Eye fluttering • Discontinuous seizure activity • Gradual cessation • Non-physiologic progression • Absence of postictal state • High seizure frequency • Excessive variability in seizure
manifestations • Funny vocalization
• Resistance to eye opening • Prolonged duration • Occurrence during clinic visit • Suggestibility • Precipitation of typical attacks
by suggestion • Attacks only in the presence of
others • Vocalizations consisting of
gagging, retching, gasping, screaming, crying or moaning
• Emotional display during events
• Emotional triggers • Retained consciousness and
recollection of events with bilateral jerking activity
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Questions 1:
• In neonates, which of the following seizure imitators includes abnormal eye movements? • A- Hyperekplexia • B- Spasmus nutans • C- Sandifer’s syndrome • D- Pallid syncope
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Questions 2:
• Which of the following is most likely to occur with syncope? • A- Multifocal myoclonus • B- Urine incontinence • C- Postictal confusion • D- Prolonged postictal state
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Questions 3:
• All is true about frontal lobe seizures except: • A- Often nocturnal • B- Tend to cluster • C- Rarely include motor manifestations • D- Brief in duration
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Questions 4:
• Which is least likely to occur in psychogenic nonepileptic seizures? • A- Ictal eye closure • B- Side-to-side movements • C- Stertorous post-ictal breathing • D- Asynchronous movements