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Page 60 Griffiths et al. Neuroimmunol Neuroinflammation 2020;7:51-67 I http://dx.doi.org/10.20517/2347-8659.2019.21

Table 4. Progressive MS cases defined by relative cortical grey matter lesion load
Case Sex 2yr RR Onset Prog W’chair Died Duration Pm delay Brain Seizures LLS Menin inflam
weight (g) (Y/N) (0-3)
Cortical GM High MS
MS202 F 2 35 46 47 58 23 39 1200 N Y 3
MS212 F 1 18 33 35 47 29 66 1314 N Y 3
MS214 F 2 20 31 38 51 31 20 1140 n/d N 2
MS217 F 1 42 49 50 57 15 29 1200 N Y 3
MS257 F 6 27 31 39 49 22 28 1168 Y Y 3
MS278 M 1 9 23 23 30 21 60 1402 Y Y 3
MS323 F 2 31 38 44 62 31 13 1207 Y N 1
MS360 M 1 15 40 51 55 40 18 1063 Y Y 3
MS366 F 3 42 45 53 61 19 14 1090 N Y 3
n = 9 7F:2M 2 27 38 44 55 23 31.9 1198.2 4Y:4N 7/9 3
Cortical GM Low MS
MS204 M 3 39 44 48 58 19 35 1180 N N 1
MS223 F 4 43 43 45 45 2 72 1004 Y N 1
MS224 F 1 26 35 36 59 33 27 1100 N N 1
MS226 F 5 37 51 58 64 27 27 1300 N N 0
MS253 F 3 21 23 33 37 16 24 1259 N N 2
MS258 M 2 26 35 38 46 20 44 1460 N N 1
MS293 F 2 35 42 43 53 18 44 1250 Y Y 3
MS295 F 5 56 60 62 71 15 42 1166 N N 0
MS336 F 1 30 47 51 57 27 24 1226 N Y 3
MS344 F 6 42 43 47 57 15 14 1062 N N 1
MS361 F 2 26 38 42 60 34 10 956 Y N 1
MS387 F 6 32 35 36 43 11 13 1115 N N 2
MS395 M 1 37 45 52 63 26 4 958 N N 1
n = 13 10F:3M 3 35 43 45 57 19 24.3 1161.3 3Y:10N 2/13 1
Associated clinical and pathological data of Cortical High and Cortical Low grey matter lesion MS. Sex (Female/Male), 2yr RR (number
of relapses in first two years of clinical disease), Onset (retrospectively determined age at first MS symptoms, Prog (age at which disease
became progressive), Died (age at death), Duration (time from first symptom onset to death), PM delay (post-mortem delay in hours),
Brain weight (wet brain weight), Seizures (one or more seizures recorded in the clinical notes - Yes or No), LLS [positive (Yes) or negative
(No)], Menin inflam (relative extent of meningeal inflammation). n/d, not determined, data not available. Text in bold represents median
or mean (brain weight only) values for each group. LLS: lymphoid-like structure; GM: grey matter; MS: multiple sclerosis; W'chair: age at
which they required a wheelchair

matter tissue atrophy; data not shown), did not reveal a difference between the cortical GML High and Low
MS cases [Table 4].

Clinical correlations of a high subpial cortical grey matter lesion load
There was no difference in the proportion of males to females or of any reported clinical measure (such as
the number of relapses in the first two years, the report of seizures or age of death) between cortical GML
High and Low groups [Table 4]. There was no difference between groups with regards age of disease onset (P
= 0.11), confirmed age at onset of progressive phase (P = 0.27) or disease duration (P = 0.15). Post-mortem
delay did not differ between the groups (P = 0.75; Table 4).

Leptomeningeal inflammation, lymphoid-like structures and cortical demyelination
We identified four separate “+++” rated foci of substantial leptomeningeal infiltrates in a single P1
section of Case MS217, which displayed massive cortical, and exclusively subpial, GM demyelination
(59.6% of cortical GM defined as GML; Figure 5A and B). Progressive MS cases with moderate-to-high
leptomeningeal inflammation (rated ++/+++ or +++/+++ for immune cell infiltrates) had an increased
relative cortical GML area compared with those cases with little-to-mild leptomeningeal infiltrates 7.8%
(range 0.8%-27.7%) vs. 26.2% (range 0.8%-60.2%), P = 0.012, Mann-Whitney U test). The relative area of
hippocampus and deep GML area (7.4%, range 0%-19.1% vs. 16.4% range 1.4%-69.2%, P = 0.159) and WML