Transcript Epilepsy Tissue Bank Institute of Neurology

Epilepsy Tissue Bank
Institute of Neurology
Jan 2013
Epilepsy Tissue Bank at IoN
• Epilepsy is a common neurological disease. There
is currently no Epilepsy Tissue Bank in the UK as
a resource for donors or researchers
• Aim to build on existing tissue archives at IoN and
promote collection to patient donors / relatives /
pathologists / Coroners in UK.
• Further research into epilepsy, its causes and
prevention, particularly SUDEP.
Epilepsy Tissue Bank: Tissue holdings
SURGICAL AND POST MORTEM TISSUES
Whole brains
Frozen tissue
FFPE
PFF
EM
Surgical tissues
• Epilepsy surgical programme at NHNN since 1992
• Mainly lobectomy specimens
• Currently > 600 samples available for use in
research
RESECTIVE EPILEPSY SURGERY
Focal/partial epilepsy syndromes
1. Structural abnormality
Anterior temporal lobectomies &
hippocampectomies
Lesionectomies
2. EEG abnormality
Lobectomies
Corticetomies
Frontal > temporal
TEMPORAL LOBE SURGERY
Tissue in Epilepsy Bank
‘en-bloc resection’
Surgical suture
marks middle
temporal gyrus
1.
2.
3.
4.
5.
POLE
Temporal
lobectomy
Fresh weight
~12g
4.5cm
Hippocampus
~2.5cm
WEIGH/VOLUMES
ORIENTATE,
PHOTOGRAPH
FREEZE
SAMPLES
(STG,MTG, ITG,
HIPPOCAMPUS)
EM
PARA
FORMALDEHYDE
FIXED SAMPLES :
Hippocampal Body
Pes hippocampus
Parahippocampal
Gyrus
Amygdala (CUSAs)
Temporal Lobe
Number of cases
RANGE OF EPILEPSY PATHOLOGIES
GFAP
NeuN
HIPPOCAMPAL SCLEROSIS
CORTICAL MALFORMATIONS
Studies
Advantages of epilepsy
surgical tissue for research
studies
• Ample, fresh tissue
available
• Optimal preservation
• Short fixation times
• Standardised regions
(Brodmann areas)
collected in each case
• Detailed pre-operative
clinical, MRI correlation (&
psychometry / functional
imaging)
Gene expression
Single cell
electrophysiology
(patch clamp
recording)
Proteomics
Cell culture
IHC
MRI-correlations
Disadvantages
Patients by definition have
refractory epilepsy all on
multiple AED
No controls
9.4T
POST MORTEM WHOLE BRAINS ~160
Collected since 1980
PATHOLOGIES
SYNDROMES
Partial epilepsy
Symptomatic focal
Temporal lobe
epilepsy
Admitted before 1972
(n=66)
Admitted in and after 1972
(n=56)
Gender (female)
Age of onset
Intellectual disabilities
Genetic cause
Potential genetic cause
Causal structural abnormalities
20 (30%)
6.5 (median)
5 (8%)
2 (3%)
8 (12%)
25 (44%)
5.0 (median)
19 (34%)
9 (16%)
17 (30%)
Hi ppoca mpa l s cl eros i s
30 (45%)
25 (45%)
6 (9%)
14 (14%)
12 (18%)
2 (3%)
6 (9%)
1 (2%)
0 (0%)
1 (2%)
2 (3%)
0 (0%)
3 (5%)
12 (21%)
2 (4%)
4 (7%)
0 (0%)
5 (9%)
0 (0%)
1 (2%)
1 (2%)
12 (21%)
14 (21%)
25 (38%)
27 (41%)
1 (2%)
11 (17%)
3 (median)
29 (52%)
16 (28%)
11 (20%)
6 (11%)
16 (29%)
6 (median)
Hi ppoca mpa l s cl eros i s pl us
Cortica l devel oppment ma l forma tion
Post-traumatic
Tra uma
Stroke
Lesion-related
epilepsy
Gl oba l hypoxi a
Degenerative disease
Va s cul a r
Idiopathic
generalised
Dravets
Tumour
Infl a mma tory
Generalised epilepsy
Seizure frequency
>1 s ei zure per week
1-4 s ei zures per month
PME
<1 s ei zure per month
Multiple seizure types (≥4)
Episodes of status epilepticus
Number of drugs tried
Majority of cases
from Epilepsy
Society,
Chalfont.
Advantage :
Detailed clinical
documentation
Disadvantage :
Selection bias of
severe epilepsy
cases
PM tissue sampling
protocols include
Temporal (T1, pole)
Frontal (cingulate, watershed, pole,
basal)
Any lesion
Hippocampus (both sides, two
levels) with parahippocampal gyrus
Amygdala,
Thalamus (Level AV nucleus)
Basal ganglia
Cerebellum (anterior and posterior
lobe)
Brainstem (midbrain pons and
medulla)
Essential blocks / Desirable blocks
In epilepsy, both hemispheres need to be sampled
as disease (causal and acquired) can be unihemispheric
Freeze samples for research , further investigation
as appropriate and where possible
Royal College of Pathologists UK, Guidelines on Autopsy Practice (Scenario 6: Deaths
associated with epilepsy) 2006
Aims of Epilepsy Tissue Bank
Development of PM collection
• Reverse current trends in acquisition of cases
• Collection of both common and rarer epilepsies e.g.
genetic epilepsies as SCN1A mutations
• Categorise and phenotype/genotype cases both clinically
and pathologically according to up to date International
League Against Epilepsy (ILAE) criteria
• Standard sampling protocols (frozen sample sets)
• Collections of SUDEP cases
SUDEP : Sudden and Unexpected death in
epilepsy
• Epilepsy death register :https://www.sudep.org
• Incidence ~500 /year UK
• Current hurdles – collection of material
60 SUDEP cases
Survey of hospital pathologists
Epilepsy Tissue Bank
Current position & Aims
Promotion of bank to all
stakeholders.
Epilepsy Tissue
Bank Within
Division Of
Neuropathology
Support & Management
structure
Continued internal and
external research
collaborations.
Potential users:
Primarily for Epilepsy
research
(Control tissue for other
neurological diseases)
Link with other UK and
European Epilepsy BB
collections
http://www.ucl.ac.uk/ion/divisions/neuropathology/memberdetails/mt
Maria Thom
Consultant in Neuropathology
Division of Neuropathology, National Hospital of Neurology and
Neurosurgery, Queen Square, London
Reader, Department of Clinical and Experimental Epilepsy, UCL,
Institute of Neurology
[email protected]