CPLL – NEUROPATHOLOGY PROTOCOL

Name / Case No.
Date of Birth
d / d / m / m / y / y / y / Y
Age
Sex: 1=> Female; 2=> Male
Postmortem interval (hrs.)
1

C

Gross Examination
1. Total brain weight: / Grams
1 = > Fresh 2=> Fixed
a. Formalin-fixed hemisphere:
1=>Right 2=> Left 9=> DK
b. Brainstem
1=>Right 2=> Left 9=> DK
c. Cerebellum
1=>Right 2=> Left 9=> DK
2. Major gross abnormalities of meninges?
0=> No 1=> Yes 9=> DK
If Yes, describe presence of haemorrhage, neoplasm, inflammation, fibrosis or thickening:
3. Gross evidence of brain atrophy:
0=> No 1=> Yes 9=> DK
If No, skip to 4
Normal / Mild / Mod / Sev / DK
0 / 1 / 3 / 5 / 9
4.
b. Location of widened sulci:
Normal / Mild / Mod / Sev / DK
Frontal / 0 / 1 / 3 / 5 / 9
Parietal / 0 / 1 / 3 / 5 / 9
Temporal / 0 / 1 / 3 / 5 / 9
Hippocampus / 0 / 1 / 3 / 5 / 9
Occipital / 0 / 1 / 3 / 5 / 9
Cerebellar / 0 / 1 / 3 / 5 / 9
c. Unusual sulcal or ventricular features?
0=> No 1=> Yes 9=> DK
If Yes, describe:
4. / a. Pallor of substantia nigra?
0=> No 1=> Yes 9=> DK
b. Pallor of locus coeruleus?
0=> No 1=> Yes 9=> DK
5. Other non-vascular gross CNS lesions present (e.g. cancer, infection, congenital anomaly)?
0=> No 1=> Yes 9=> DK
If Yes, describe:
5

D

Cerebral Vascular Disease: Gross Findings

1. / Cerebral vessels
a.  Atherosclerosis
0 = > None
1 = > Mild
3 = > Moderate
5 = > Severe
9 = > DK
b. Significant obstruction (> 50% compromise of lumen) of large or cerebral vessels?
(circle of Willis and major branches)
0=> No 1=> Yes 9=> DK
If yes, describe and give size and location of vessels:
(Rt.) middle cerebral-50%, (Rt.) anterior cerebral -90%, (Rt) posterior cerebral-80%, (Lt) anterior cerebral-70%, (Lt) posterior cerebral-95%, Lt MCA not available
c. Gross evidence of other vascular lesions such as aneurysms, A-V malformations, etc?
0=> No 1=> Yes 9=> DK
If yes, describe:
2. / parenchymal vascular lesions (gross)
0=> No 1=> Yes 9=> DK
If No, skip to section E
3. / Indicate type of parenchymal vascular lesions present:
No / Yes / DK
0 / 1 / 9 / Infarct(s)
0 / 1 / 9 / Lacuna(s)
0 / 1 / 9 / Haemorrhage
6
a) Infarcts (> 10 mm diameter)
0=> No 1=> Yes 9=> DK
Number of lesions:
Largest size(s) mm: / X
Anatomical and arterial distributions(s)
No / Yes / DK
0 / 1 / 9 / Anterior Cerebral
0 / 1 / 9 / Middle Cerebral
0 / 1 / 9 / Posterior Cerebral
0 / 1 / 9 / Vertebro-Basilar
0 / 1 / 9 / Watershed – junction of anterior-middle cerebral arteries
0 / 1 / 9 / Watershed – junction of middle-posterior cerebral arteries
0 / 1 / 9 / Watershed – Other (specify: / )
b) Lacunas (cystic infarct < 10 mm diameter)
0=> No 1=> Yes 9=> DK
Frequency (Number of Lacunas)
Location / None / 1-4 / 5-9 / 10 or more
Basal ganglia and/or thalamus / 0 / 1 / 3 / 5
Cerebral white matter / 0 / 1 / 3 / 5
Brainstem / 0 / 1 / 3 / 5
Other (specify) / 0 / 1 / 3 / 5
c. Other infarcts (< 10 mm diameter)
0=> No 1=> Yes 9=> DK
Frequency
Location / None / 1-4 / 5-9 / 10 or more
Basal ganglia and/or thalamus / 0 / 1 / 3 / 5
Cerebral white matter / 0 / 1 / 3 / 5
Brainstem / 0 / 1 / 3 / 5
Other (specify) / 0 / 1 / 3 / 5
7
d. Haemorrhages (parenchymal)
0=> No 1=> Yes 9=> DK
Enter approximate NUMBER in each size class
small
(< 5mm diam)
Medium
(6-10 mm)
Large
(> 10mm)
Describe the LOCATION of the haemorrhages using the codes:
0=> No 1=> Yes 9=> DK
Small / Medium / large
Cortex
Cerebral white matter
Deep grey (basal ganglia, thalamus)
Brainstem
Cerebellum
8

E

Microscopic Vascular Findings
1. / Cerebral vessels
a. Atherosclerosis / 0=> No 1=> Yes 9=> DK
b. Arteriolosclerosis / 0=> No 1=> Yes 9=> DK
c. V-R space extension / 0=> No 1=> Yes 9=> DK
If yes, describe
Cortex
White matter
Deep grey
0=> No 1=> Yes 9=> DK
d. Perivascular gliosis
0=> No 1=> Yes 9=> DK
Location
1=> White matter 2=> Deep grey 5=> Both 9=> DK
e. Other microscopic vascular disease (e.g. vascular malformation, vasculitis)
0=> No 1=> Yes 9=> DK
If Yes, describe:
2. / Vascular lesions
0=> No 1=> Yes 9=> DK
If No, skip to G
a. Microinfarcts detected microscopically?
0=> No 1=> Yes 9=> DK
If No, skip to b
First column: / 0=> No 1=> Yes 9=> DK
Second column: / 1=> Grey 2=> White 3=> grey and white
Area / W/G
Hippocampus, ERC
Temporal
Frontal
Parietal
Occipital
Deep grey
9
b. White matter pallor
0=> No 1=> Yes 9=> DK
If Yes, describe location
No / Yes / DK
Occipital / 0 / 1 / 9
Parietal / 0 / 1 / 9
Frontal / 0 / 1 / 9
Temporal / 0 / 1 / 9
Deep White / 0 / 1 / 9
10
G
Microscopic Evaluation of Hippocampus,
Neocortex and Selected Regions
1. / Complete the tables below. For each anatomical region, indicate the presence or severity of microscopic abnormalities using the specified codes
0=> None 1=> Sparse 3=> Moderate

For items 1-3

5=> Frequent/Severe 9=> NA
Hippocampus / Entorhinal Cortex
1. / Plaques
a) neuritic plaques
b) amyloid deposits
2. / Neurofibrillary tangles
3. / Vascular Amyloid
Parenchymal
Meningeal
Associated Haemorrhages

For items 4-8

/ 0=> Absent 1=> Present 9=> NA
For items 9 and 10 / 0=> Absent
3=> 3 to 5 neurons
containing inclusions / 1=> 1 or 2
Neurons containing
inclusions
5=> more than
5 neurons con-
taining inclusions
Hippocampus / Entorhinal Cortex
4. / Granulovacuolar degeneration
5. / Hirano bodies
6. / Severe neuronal loss
7. / Severe gliosis
8. / Other (describe)
9. / Pick bodies
10. / Lewy bodies
11. / Ubiquitin pos. dots
12. / Ubiquitin inclusions
11
For items 1-3 / 0=> None 1=> Sparse 3=> Moderate
5=> Frequent/severe 9=> NA
Frontal / Temporal / Parietal / Occipital (Primary Visual Cortex) (Optional)
1. / Plaques
a) neuritic plaques
b) amyloid deposits
2. / Neurofibrillary tangles
3. / Vascular Amyloid
Parenchymal
Meningeal
Associated Haemorrhages

For items 4-6

/ 0=> Absent 1=> Present 9=> NA
For items 7 and 8
/ 0=> No inclusions 1=> 1 or 2
neurons containing
inclusions
3=> 3 to 5 neurons 5=> more than
containing inclusions 5 neurons con-
taining inclusions
Frontal / Temporal / Parietal / Occipital (Primary Visual Cortex) (Optional)
4. / Severe neuronal loss
5. / Severe gliosis
6. / Other (describe)
7. / Pick bodies
8. / Lewy bodies
9. / Ubiquitin pos. dots
10. / Ubiquitin inclusions
12
The following table is optional with the exception of the substantia nigra. For each anatomical region, indicate the presence or severity of microscopic abnormalities using he indicated codes.

For items 1-4

/ 0=> None 1=> Sparse 3=> Moderate
5=> Frequent/severe 9=> NA

For items 5-7

/ 0=> None 1=> 1 or 2 per section
3=> 3 to 5 per section 5=> More than 5 per section
Sub Nigra / N Basalis / D Raphe N / L Coerul / D Vagus N
1. Neuronal loss
2. Gliosis
3. Pigment incontinence
4. Other (describe)
5. Lewy bodies
6. Tangles
7. Plaques
Cerebellum: / Agonal changes
0=> No
1=> Yes
9=> DK
13
H

Assessment of Neurohistological Findings

a. CERAD-AD score
(age vs. neuritic plaques)
0=> None
1=> Uncertain evidence of AD
3=> Suggestion of AD
5=> Indicative of AD
b. Braak Staging
NTF / Amyloid Plaques
01234569 / 01239
14

I

Neuropathological Diagnoses, blind to clinical information,

with regard to dementia

0=> No; 1=> Yes; 9=> DK
1. / Normal brain, clinically insignificant change
2. / Alzheimer-type pathology
a) cortical
b) subcortical
c) brainstem
3. / Lewy body-type pathology
a) cortical
b) subcortical
c) brainstem
4. / Vascular disease
a) Large vessel disease
i) Multiple large infarcts
ii) Single large infarct (non strategic)
iii) Strategic infarct
b) Small vessel disease
i) Multiple small infarcts
ii) Multiple small infarcts, including strategic area
iii) White matter ischaemia
iv) V-R space expansion
c) Haemorrhage
i) Intra-cerebral
ii) extra-cerebral
iii) Other (specify)
5. / Pick’s disease (with Pick bodies)
6. / :Lobar atrophy (without Pick bodies)
7. / CJD, spongiform encephalopathy
8. / Huntington’s disease
9. / Leukoencephalopathy – specify:
Tumour
10. / Primary – specify:
11. / Secondary – specify
12. / Other – specify:
Rank order of pathological findings, which in the opinion of the neuropathologist contribute to clinical symptomatology. Rank in order of significance. If deemed to be approximately equal, more than one may be ranked together.
Rank / Diagnosis
15