Diagnosis and management of nonepileptic events Professor Markus Reuber Honorary Consultant Neurologist Quebec, 15.10.2016 Academic Neurology Unit University of Sheffield Royal Hallamshire Hospital, Sheffield, UK Markus.Reuber@sth.nhs.uk

Faculty / presenter disclosure Faculty: Markus Reuber Relationships with commercial interests: Grants / Research Support: UCB Pharma Speakers Bureau / Honoraria: Eisai Livanova Consulting Fees: - none Other: none

Epilepsy T.I.A. Migraine Cataplexy Dissociative seizure Hypoglycaemia Diagnosis and management of nonepileptic events Differential diagnosis Paroxysmal neurological disorders Epilepsy Migraine Neurovasogenic syncope Benign paroxysmal positional vertigo Hypoglycaemia Dystonia Cataplexy T.I.A. Parasomnia Hyper- ventilation Dissociative seizure Cardiogenic syncope

Diagnosis and management of nonepileptic events Differential diagnosis Differential diagnosis of Transient Loss of Consciousness TLOC Secondary disturbance of brain function Primary disturbance of brain function Epileptic seizures Psychogenic nonepileptic seizures Genetic generalised epilepsy Structural / metabolic epilepsy Unclassifiable epilepsy Neurovasogenic syncope Cardiac syncope Reuber M, Grünewald R. The first seizure – is it epilepsy? In Panayiotopolous, C.P. (ed): The educational kit on epilepsies, Vol. 3, Newly identified epileptic seizures: diagnosis, procedures and management. Oxford: Medicinae, 2007: 66-71

Diagnosis and management of nonepileptic events Diagnostic process Stop, look, listen

Diagnosis and management of nonepileptic events Stop

Diagnosis and management of nonepileptic events Stop Manifestation and diagnosis N N=313 Mean delay: 7.2 years ¾ female Age (years) Reuber M, Fernández G, Bauer J, Helmstaedter C, Elger CE. Diagnostic delay in psychogenic nonepileptic seizures. Neurology 2002;58:493-495

Diagnosis and management of nonepileptic events Stop

Diagnosis and management of nonepileptic events Stop

Diagnosis and management of nonepileptic events Look Markus.Reuber@sth.nhs.uk

Diagnosis and management of nonepileptic events Look Epileptic seizure PNES

Diagnosis and management of nonepileptic events Secondary generalised epileptic seizure

Diagnosis and management of nonepileptic events PNES

Diagnosis and management of nonepileptic events Look Different movement patterns in GTCS and convulsive DS Vinton A et al. „Convulsive nonepileptic seizure have a distinctive pattern of rhythmic movement artefact distinguishing them from convulsive epileptic seizures. Epilepsia 2004;45:1344-1350.

Diagnosis and management of nonepileptic events Look PNES manifestations: different semiological categories Identified 22 „signs“ in 145 DS from 52 patients Multiple correspondence analysis, hierarchical cluster analysis 61.5% of patients: one type of attack. Others: up to 4 types of attack 46% additional „confirmed“ epilepsy - 22 clinical variables collected for each seizure: duration of seizure (<1 min, 1-5 min, >5 min), prodromes (dizziness, feeling of strangeness, abdominal pain.), modality of onset and end (sudden or progressive), responsiveness (interactions with observer through verbal answers, execution of instructions), dystonic movements, tremor, myoclonus, focal signs (one limb, head, halfbody, two lower or two upper limbs), axial extension, axial immobility, closed eyes, side-to-side head shaking, one-sided rotation of the head, face asymmetry, movements of the mouth (chewing, protraction of the tongue), vocalisation, hyperventilation and vegetative signs (sweating, flushes, pallor), sensory manifestations (paraesthesias), hypermotor primitive gestural activity (looking oriented to a purpose,ie, hiding one’s face, punching, grasping), variation of symptom intensity (eg, tremor fluctuating between high and low amplitude or frequency) and postictal state (defined as the abnormal condition occurring between the end of an attack and return to baseline condition). Hubsch et al. Clinical classification of psychogenic nonepileptic seizures based on video-EEG analysis and automatic clustering. J Neurol Neurosurg Psychiatry 2011;82:955-960. Markus.Reuber@sth.nhs.uk

Diagnosis and management of nonepileptic events Look Observation: Body motor activity Observation Epilepsy NES Duration 0.5-2 min Often >2min Undulating activity Rare Common Ophisthotonus Occasional Pelvic thrusting Shaking Clonus Tremor

Diagnosis and management of nonepileptic events Look Observation: Head and face Observation Epilepsy NEA Eyes / mouth Typically open Often closed Side-to-side head movement Rare Occasional Tongue biting Uncommon Ictal crying Vocalisation Occasionally formed

Diagnosis and management of nonepileptic events Look Ictal examination Observation Epilepsy NES Resisted eye-opening Very rare Common Retained light reflex Unusual Reactive during attack Occasional Worse after iv anticonvulsants Reorientation May be slow Too rapid/slow

Diagnosis and management of nonepileptic events Look Markus.Reuber@sth.nhs.uk

Diagnosis and management of nonepileptic events Listen Shukla: Psychiatric Manifestations in TLE: a controlled study Br J Psychiatry 1979;135:411-417 Fiordelli: Epilepsy and psychiatric disturbance: a cross-sectional study. Br J Psychiatry 1993;163:446-450 Manchanda Psychiatric disorders in candidates for epilepsy surgery. JNNP 1996;61:82-89 Ettinger Prevalence of depression in persons with epilepsy and associated finding from epilepsy impact project. Epilepsia 2002;43(suppl 7):120 (huge study, community and asthma controls) Swinkels WAM et al. Prevalence of psychopathology in Dutch inpatients. Epilepsy Behav 2001;2:441-447. Markus.Reuber@sth.nhs.uk

Diagnosis and management of nonepileptic events Listen Differentiation of epileptic and dissociative Seizures Limitation Feature in the history suggestive of DS Little differentiating value No ictal injury, no seizures from (apparant) sleep, no incontinence, no tongue biting, pelvic thrusting Differentiate but not noticed / described reliably Long duration, closed eyes (tonic-clonic like attacks), closed mouth ( tonic phase), no cyanosis Differentiate but not commonly reported Pre-ictal anxiety symptoms, ictal crying, ictal weeping, vocalisation during tonic-clonic phase Differentiate but require expert observation Unusually rapid or slow recovery, variation in amplitude but not frequency of motor activity, ictal reactivity, tremor rather than clonus

Diagnosis and management of nonepileptic events Listen Subjective seizure symptoms: Paroxysmal Event Profile (PEP) Key: 1=always 2= frequently 3=sometimes 4=rarely 5=never Reuber et al. Value of patient-reported symptoms in the diagnosis of transient loss of consciousness . Neurology 2016, 87; 6: 625-633.

Diagnosis and management of nonepileptic events Listen Subjective seizure symptoms: Paroxysmal Event Profile (PEP) Factor Typical item EvS EvN NvS Feeling overpowered My attacks build up gradually When I feel an attack coming I try to fight it E>S N>E N>S Sensory experience I feel hot and cold in my attacks In my attacks my vision goes dim E<S E<N N=S Disconnection In my attacks I see things which are not really there During my attacks I feel as if I am two different people Catastrophic experience During my attacks I am frightened I am going to die During my attacks I am frightened I might go crazy Amnesia Afterwards I have no idea I have had an attack After my attacks I feel very confused E=N Correct Classification 91% 84% 94% Reuber et al. Value of patient-reported symptoms in the diagnosis of transient loss of consciousness . Neurology 2016, 87; 6: 625-633.

Diagnosis and management of nonepileptic events Listen History-taking: interactional observations Feature Epilepsy Dissociative seizures Seizure topic Volunteered (focus on symptoms) May need prompting (“focussing resistance“), focus on situations / consequences) Seizure symptoms Volunteered, detailed Avoided (“detailing block“) Formulation work Extensive Practically absent Gaps in consciousness Exact description Little description Schwabe M, Reuber M, Schöndienst M, Gülich E. Listening to people with seizures: How can Conversation Analysis help in the differential diagnosis of seizure disorders. Communication and Medicine, 2008;5:59-72. Reuber M et al. Using interactional and linguistic analysis to distinguish between epileptic and psychogenic non-epileptic seizures: a prospective blinded multi-rater study. Epilepsy and Behavior, 2009;16:139-144.

Diagnosis and management of nonepileptic events Listen Conversational diagnostic features in routine clinical practice 1. The patient readily focuses on seizure symptoms 2. In response to questions the patient readily elaborates seizure descriptions 3. The patient provide detailed seizure descriptions 4. The patients focuses more on symptoms than circumstances / consequences 5. Seizure descriptions are characterised by formulation effort 6. The interview was challenging for me Jenkins, L et al. Neurologists can identify diagnostic linguistic features during routine seizure clinic interactions. Manuscript in preparation 2015.

Diagnosis and management of nonepileptic events Listen Conversational diagnostic features in routine clinical practice Jenkins, L et al. Neurologists can identify diagnostic linguistic features during routine seizure clinic interactions. Manuscript in preparation 2015.

Diagnosis and management of nonepileptic events Listen Conversational diagnostic features in routine clinical practice Summated scale: Sensitivity: 77% Specificity: 85% Jenkins, L et al. Neurologists can identify diagnostic linguistic features during routine seizure clinic interactions. Manuscript in preparation 2015.

Diagnosis and management of nonepileptic events Listen But I have them when I am just watching TV

Diagnosis and management of nonepileptic events Listen Attribution of epilepsy and NEE by neurologists and patients Cause of epilepsy Cause of nonepileptic events Patients with epilepsy: n=34 Neurologists: n=45 Patients with DS: n=40 Whitehead K, Kandler R, Reuber M. Patients‘ and neurologists‘ perception of epilepsy and psychogenic nonepileptic seizures. Epilepsia 2013; 54:708-17. Markus.Reuber@sth.nhs.uk

Diagnosis and management of nonepileptic events Don’t! Don’t rely on interictal tests PNES (n=206) Epilepsy (& PNES) (N=123) Epileptiform EEG abnormality 8.7% 70.7% MRI abnormality 9.7% 60.2% Neuropsychological test abnormality (>2SD) 52.8% Any abnormality 22.3% 91.9% Reuber et al. Evidence of brain abnormality in patients with PNES. Epilepsy Behav 2002;3:249-254

Diagnosis and management of nonepileptic events Don’t! Treat for epilepsy because they probably have mixed seizures Study Group Prospective Diagnosis Prevalence Cohen RJ 1982 57 IP yes clinical 12% Lesser R 1983 50 IP/OP no EEG (+interictal) 10% Krumholz 1983 34 IP 37% Gates JR 1985 25 IP v-EEG / (clinical) 20% (56%) Lempert 1990 8% (22%) Leis 1992 47 IP v-EEG (+interictal) 23% Betts 1992 128 IP 36% Devinsky 1996 99 IP No v-EEG (clinical) 20% (32%) Sigurdardottir 1998 14 IP/OP v-EEG 50% Benbadis 2001 32 IP 9% Reuber 2002 313 IP/OP 32%

Diagnosis and management of nonepileptic events Diagnostic process Stop, look, listen