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

2. 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

3. 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

4. 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

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

6. Diagnosis and management of nonepileptic events
Stop

7. 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:

8. Diagnosis and management of nonepileptic events
Stop

9. Diagnosis and management of nonepileptic events
Stop

10. Diagnosis and management of nonepileptic events
Look

11. Diagnosis and management of nonepileptic events
Look
Epileptic seizure
PNES

12. Diagnosis and management of nonepileptic events
Secondary generalised epileptic seizure

13. Diagnosis and management of nonepileptic events
PNES

14. 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:

15. 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
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:

16. 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

17. 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

18. 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

19. Diagnosis and management of nonepileptic events
Look

20. Diagnosis and management of nonepileptic events
Listen
Shukla: Psychiatric Manifestations in TLE: a controlled study Br J Psychiatry 1979;135:
Fiordelli: Epilepsy and psychiatric disturbance: a cross-sectional study. Br J Psychiatry 1993;163:
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:

21. 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

22. 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:

23. 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:

24. 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:

25. 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.

26. 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.

27. 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.

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

29. 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= Neurologists: n= Patients with DS: n=40
Whitehead K, Kandler R, Reuber M. Patients‘ and neurologists‘ perception of epilepsy and psychogenic nonepileptic seizures. Epilepsia 2013; 54:

30. 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:

31. 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%

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