Table 1. topology of GM pathology in MS.
Study | Studied numbers and MS type | Method | Affected GM region | Main findings |
---|---|---|---|---|
Bö et al.5 |
5 SPMS 1 PPMS |
immunohistochemistry |
Frontal cortex Parieto-occipital cortex |
The presence, distribution and extent of WM changes were independent of the extent of GM pathology |
Bö et al.7 |
10 SPMS 7 PPMS 3 RRMS, 7 NC |
immunohistochemistry |
Cingulate gyrus Superior frontal gyrus Paracentral lobule Superior temporal gyrus |
Demyelination more pronounced in cerebral cortex (especially cingulate gyrus) than in WM |
Gilmore et al.12 |
36 MS 12 NC |
immunohistochemistry |
Spinal cord: upper cervical, lower cervical, upper thoracic and lower thoracic and lumber levels. |
The proportion of GM demyelination was larger than WM demyelination at each of the five spinal cord levels |
Gilmore et al.13 |
11 SPMS 2 PPMS 1 RRMS 3 NC |
immunohistochemistry |
Motor cortex Cingulate gyrus Cerebellum Thalamus Cervical level spinal cord Thoracic level spinal cord Lumbar level spinal cord |
GM demyelination most extensive in spinal cord and cerebellum, while WM demyelination was most prominent in the spinal cord |
Kutzelnigg et al.9 |
11 AMS 6 RRMS 15 PPMS 20 SPMS 15 AD |
immunohistochemistry |
Cerebral GM and WM |
Active, focal, inflammatory lesions in the WM in patients with acute MS and RRMS, while diffuse abnormalities (with active microglia) in the WM and GM lesions were more typical in SPMS and PPMS |
Kutzelnigg et al.16 |
5 AMS 3 RRMS 19 SPMS 10 PPMS 3 chronic MS 8 NC 34 hypoxia patients |
immunohistochemistry |
Cerebellum |
Extensive cerebellar demyelination in particularly SPMS and PPMS patients. GM demyelination in cerebellum was similar to or even exceeding demyelination in the cerebral GM. |
Huitinga et al.14 |
15 SPMS 2 PPMS 14 NC |
immunohistochemistry |
hypothalamus |
Significant number of lesions in hypothalamus and adjacent structures. Both active and chronic active lesions were found in WM. Signs of demyelination in paraventricular nuclei and supraoptic nuclei |
Geurts et al.11 |
9 SPMS 7 PPMS 1 RRMS 1 chronic MS 6 NC |
immunohistochemistry |
Hippocampus |
High number of lesions, both mixed intrahippocampal-perihippocampal lesions and isolated intrahippocampal lesions |
Papadopoulos et al.17 |
38 SPMS 7 PPMS 7 NC |
immunohistochemistry |
Hippocampus |
Average demyelination 30.4%. Lesions were often chronic and subpially or subependymally located. Gross hippocampal atrophy, neuronal shrinkage and synaptic, axonal, and neuronal loss |
Dutta et al.10 |
|
Immunohistochemistry, microarray assay and western blots |
Hippocampus Motor cortex |
Demyelinated hippocampi had minimal neuronal loss but significant decreases in synaptic density and neuronal proteins essential for axonal transport, synaptic plasticity, glutamate neurotransmission, glutamate homeostasis and memory/learning |
Vercellino et al.19 |
3 RRMS 3 SPMS 6 NC |
immunohistochemistry |
Cingulate gyrus Temporal lobe Insula Frontal cortex |
Great variation in extent of GM demyelination between patients and brain regions. Cingulate gyrus most affected. Neuronal loss and signs of apoptosis in GM lesions of patients with prominent GM demyelination |
Vercellino et al.21 |
1 AMS 6 RRMS 7 SPMS 6 ALS 6 NC |
immunohistochemistry |
Thalamus Caudate Putamen Pallidum Claustrum Amygdala Hypothalamus Substantia nigra Mammilary bodies Globus pallidus |
GM lesions most often seen in thalamus and caudate, but were also present in putamen, pallidum, claustrum, amygdale, hypothalamus and substantia nigra. Most lesion were mixed GM/WM lesions and had sometimes immune cell infiltrates. Neuronal loss and atrophy seen in GM lesions and in myelinated gray matter. |
Peterson et al.18 |
50 MS 7 NC |
immunohistochemistry |
Cerebral cortex and white matter |
Cortical demyelination involving neurite transection, neuronal death by apoptosis and reduced inflammation compared with WM lesions |
Wegner et al.20 |
22 MS 17 NC |
immunohistochemistry |
Superior frontal gyrus precentral gyrus postcentral gyrus middle frontal gyrus superior temporal gyrus middle temporal gyrus |
Neocortical thinning of 10% in MS independent of GM lesions. Type I lesions show significant glial, neuronal and synaptic loss |
Kooi et al.15 |
7 SPMS 4 PPMS 3 ND MS 10 AD |
immunohistochemistry |
Hippocampus |
An unaltered activity and protein expression of acetylcholinesterase, but a decrease of activity and protein expression of acetylcholintransferase in MS |
Schmierer et al.73 |
21 MS |
MRI/immunohistochemistry |
Cerebral cortex and white matter |
36 GM lesions detected (16 type I, 0 type II, 18 type III, 2 type IV). Twenty-eight GM lesions were visible on 9.4 Tesla T2 weighted MRI (15 type I, 11 type III and 2 type IV). |
Geurts et al.44 | 5 SPMS 2 PPMS 2 ND MS |
MRI/immunohistochemistry | Cerebral cortex and white matter | A total of 98 GM lesions were found (27 type I, 12 type II, 41 type III, 10 type IV, 8 deep GM) and 70 WM lesions. T2SE MRI images only depicted 3% of the intracortical lesion, while the 3D FLAIR images showed 5%. |
AMS, acute MS or Marburg’s type of MS; SPMS, secondary progressive MS; PPMS, primary progressive MS; chronic MS, SPMS or PPMS; ND, MS subtype not determined; ALS, amyotrophic lateral sclerosis; AD, Alzheimer disease NC, non-neurological control.