prognosis: what happens in transient epileptic amnesia ... · • kapur n, young a, bateman d,...

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Prognosis: What happens in T ransient Epileptic Amnesia: over TIME? Dr Sharon Savage [email protected] TEA Day, June 2018

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Page 1: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

Prognosis:

What happens in Transient

Epileptic Amnesia:

over TIME?

Dr Sharon Savage

[email protected]

TEA Day, June 2018

Page 2: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

At onset, most commonly….

(Butler et al., 2007)

Page 3: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

Common memory difficulties

Certain life events

Routes/ places

new information

(Hoefeijzers et al., 2013)

Page 4: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

TEA short-term outcome:

Short-term (6-24 months after commencing medication):

good seizure control (Butler et al., 2007)

stable intellectual abilities (Del Felice et al., 2014)

Some improvements in memory for new information (Midorikawa& Kawamura, 2008; Razavi et al., 2010)

Improved memory for recent life events (Mosbah et al., 2014)

Page 5: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

Medium to longer-term outcome?

Research to-date:

5-yr follow-up: stable (Kapur, 1989)

16-yr follow-up: risk of Alzheimer’s Disease? (Cretin et al., 2014)

Page 6: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

Aims

to investigate outcomes of TEAover 10 (or in some cases 20years)

Follow up with people seen through TIME

Collect medical info

Repeat cognitive assessment

Page 7: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

Participants

Zeman et al 1998 cohort (C1)

9 men; 1 woman

Age of onset: 49 – 78 years (average = 63 years)

Seizures well controlled on medication (80%)

Butler et al 2007 cohort (C2) - additional 42 people

27 men; 15 women

Age of onset: 44 – 77 years (average = 62 years)

Seizures well controlled on medication (96%)

Page 8: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

Method: Medical history

Summaries from GP

Seizure and medication history

Record of cognitive problems (e.g. memory, planning)

Cause of death, where applicable

Page 9: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

Method: Cognitive ability

Standard memory tests

Story recall

Visual recall (geometric figure)

Recognition test (words and faces)

Standard cognitive tests

General ability (IQ)

Visual skills (drawing)

General knowledge (picture naming)

Executive function (problem solving)

Page 10: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

Results - Clinical outcome

Page 11: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

(Zeman et al 1998) (Butler et al., 2007)

(Savage et al 2016; Seizure)

• Seizures: controlled (7 with medication; 1 not)• Cause of death: ruptured aneurysm• Dementia: None diagnosed

Page 12: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

(Zeman et al 1998) (Butler et al., 2007)

(Savage et al 2016; Seizure)

Seizures: 20% of people had at least 1 more seizure.

Life expectancy: did not appear reduced (average= 82 years)

Causes of death: pneumonia, cancer

Dementia: 6 cases (AD cases: 8.6%)

Page 13: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

(Zeman et al 1998) (Butler et al., 2007)

(Savage et al 2016; Seizure)

Seizures: 2 had at least 1 more seizure.

Causes of death: pneumonia, cancer,heart failure (all aged in 80s)

Dementia: 1 case

Page 14: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

Participants – Cognitive outcome

Demographics TEA-BL (n=50)

TEA-10yr (n=19)

TEA-20yr (n=3)

Average age 66yrs 75yrs 83yrs Sex (M : F) 34 : 16 15 : 4 2 : 1

People with TEA Similar people but without TEA

Page 15: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

-2.5

-2

-1.5

-1

-0.5

0

0.5

1

1.5

2

LM1 LM2 RCFT 30'recall

RMT-W RMT-F

Z s

core

Memory tests: initial and 10-yr results BL z-score

10yr z-score

Story-Imm Story-Delay Figure-Delay Words Faces

TEA participants compared with IQ and age matched controls

Cognitive ability

(21% below) (26% below) (0% below) (26% below) (16% below)

Page 16: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

-2

-1.5

-1

-0.5

0

0.5

1

1.5

2

GNT FAS Animals WCSTcategories

Z s

core

Other cognitive tests BL z-score

10yr z-score

Naming Problem solving – Words Problem solving-sorting

TEA participants compared with IQ and age matched controls

Cognitive ability

(5% below) (11-17% below) (0% below)

Page 17: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

Comparison with matched adults

Mild memory difficulties are common in TEA (green bars)

And often persist over time (blue bars)

For some individuals: stable or improvements;

in others: declines

In other intellectual abilities, people with TEA generally performin keeping with their peers and do not show declines over a 10-year period

Page 18: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

0

5

10

15

20

25

30

35

40

45

50

LM1 (/25) LM2 (/25) RCFT 30'recall (/36)

RMT-W (/50) RMT-F (/50)

Raw

score

TEA 1 TEA 2

TEA 3 HC

Memory at 20-year follow up

Memory tests

Immediate Story Delayed Story Delayed Figure Recognise Words Recognise Faces(out of 25) (out of 25) (out of 36) (out of 50) (out of 50)

Page 19: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

So what did we learn overall?

Seizures generally remain well controlled, but some adjustmentsto medication may be required from time to time

Memory difficulties commonly persist in TEA

For some: stable or some improvement over 10-20 years;

in others: some declines

BUT: compared with matched community participants, peoplewith TEA generally perform in keeping with their peers

Across the two cohorts, prevalence of Alzheimer’s Disease(8.6%) was similar to population data (9.7%)

Page 20: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

Adam ZemanChris ButlerFraser Milton

Thanks to the TIME research team:

Acknowledgements

to the families involved

to the funding bodies

Page 21: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

Thank you for listening

Comments or questions?

Page 22: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

• Butler CR et al. The syndrome of transient epileptic amnesia. Ann Neurol. 2007 Jun 1;61(6):587–98.

• Cretin B, et al. Can the syndrome of transient epileptic amnesia be the first feature of Alzheimer’s disease? Seizure. 2014 Nov;23(10):918–20

• Del Felice A, et al. Transient epileptic amnesia mistaken for mild cognitive impairment? A high-density EEG study. Epilepsy Behav EB. 2014 Jul;36:41–6.

• Hoefeijzers, S. et al. Accelerated Long-term Forgetting in Transient Epileptic Amnesia: an acquisition or consolidation deficit? Neuropsychologia, 2013;51:1549-1555.

• Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up. Cortex. 1989 Sep;25(3):387–402

• Mosbah A, et al. Clinical, neuropsychological, and metabolic characteristics of transient epileptic amnesia syndrome. Epilepsia. 2014 May 1;55(5):699–706.

• Manes F et al. Autobiographical amnesia and accelerated forgetting in transient epileptic amnesia. J Neurol Neurosurg Psychiatry. 2005 Jan 10;76(10):1387–91.

References

Page 23: Prognosis: What happens in Transient Epileptic Amnesia ... · • Kapur N, Young A, Bateman D, Kennedy P. Focal Retrograde Amnesia: A Long Term Clinical and Neuropsychological Follow-Up

• Midorikawa A, Kawamura M. Recovery of Long-Term Anterograde Amnesia, but Not Retrograde Amnesia, after Initiation of an Anti-Epileptic Drug in a Case of Transient Epileptic Amnesia. Neurocase. 2008 May 15;13(5–6):385–9.

• Razavi M, Barrash J, Paradiso S. A longitudinal study of transient epileptic amnesia. Cogn Behav Neurol. 2010;23(2):142–5.

• Savage, S et al. (in press). The evolution of accelerated long-term forgetting: Evidence from the TIME study. Cortex

• Savage, S et al. (2016) Transient Epileptic Amnesia over twenty years: long-term follow-up of a case series with three detailed reports. Seizure, 43, 48-55

• Zeman AZJ, Boniface SJ, Hodges JR. Transient epileptic amnesia: a description of the clinical and neuropsychological features in 10 cases and a review of the literature. J Neurol Neurosurg Psychiatry 1998;64:435–43.

References