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Imitators of Epilepsy

Nabil J. Azar, M.D. Vanderbilt University Medical Center

Nashville, Tennessee

Disclosure

I have no financial relationships to disclose that are relative to the content of my

presentation.

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.

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

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)

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

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

Syncope: common features • Sudden • Unpredictable • Recurrent loss of consciousness • Common disorder (10%) • “Convulsive ” myoclonus • Stereotyped • Witness panic • Potential serious injury • High morbidity and mortality

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

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

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:

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

Diagnosis of syncope

Diagnostic testing: • Long-term video-EEG monitoring • Routine EEG • ECG / holter monitoring • Tilt table test / orthostatic blood pressure • Carotid ultrasound

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

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

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

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

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

Parasominas vs frontal lobe seizures

Carreno M. Seminars in Neurology 2008

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

Paroxysmal choreoathethosis

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

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

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

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

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

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

Ictal fear vs. panic attack

Carreno M. Seminars in Neurology 2008

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

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 %

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

Hypermotor seizure

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

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

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

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

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

Postictal breathing- epileptic

Postictal breathing- nonepileptic

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

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

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

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

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

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

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