Perivenous lesion location on 7 T T2*-weighted imaging is predictive of the presence of demyelination. Optimization of this imaging technique at lower magnetic resonance field strengths would offer benefit for the diagnosis of MS.

Background: Substantial grey matter (GM) demyelination occurs in both the cerebral cortex and spinal cord in multiple sclerosis (MS). GM demyelination also occurs in the cerebellar cortex and the deep GM nuclei of the brain. However, no study has made a direct ''within subject'' comparison of the extent of GM pathology between these regions. Aim: To examine the extent and pattern of GM demyelination in the motor cortex, cingulate gyrus, cerebellum, thalamus and spinal cord in MS. Methods: Postmortem study using material from 14 MS cases and three controls. Sections were taken from the five predetermined areas and stained for proteolipid protein. The extent of GM and white matter (WM) demyelination was assessed in each region. Results and conclusion: Overall, 28.8% of the GM was demyelinated compared with 15.6% of the WM (p,0.001), with demyelination being greater in the GM than in the WM at each of the anatomical sites. There was substantial variation in the extent of demyelination between the different CNS regions. GM demyelination was most extensive in the spinal cord and cerebellum while WM demyelination was most prominent in the spinal cord.The factors influencing plaque topography in multiple sclerosis (MS) are not fully understood. The majority of white matter (WM) plaques occur in a perivenular distribution, with areas containing a high density of small veins and venules-such as the periventricular WM, leucocortical junction and the WM tracts of the brainstem and spinal cordshowing a preponderance for demyelination. 1 While it has been recognised that MS also involves grey matter (GM) structures, the conventional myelin stains used in these studies grossly underestimate the true extent of this GM pathology. [2][3][4] In comparison, myelin protein immunohistochemistry is more sensitive for detecting GM demyelination, demonstrating extensive demyelination in the cerebral cortex and spinal cord GM in MS.4-6 However, it is unclear whether GM demyelination is more prominent in the spinal cord, the cerebral cortex or other GM structures; comparisons between studies are likely to be confounded by differences in MS subtype, disease duration, age, gender, etc. Therefore, in this study, we used autopsy material to quantify GM and WM demyelination in the cerebral cortex, cerebellum, spinal cord and thalamus, allowing us to make ''within subject'' comparisons of the extent of demyelination in these regions. MATERIALS AND METHODS Clinical materialFormalin fixed, paraffin embedded autopsy material was obtained from 14 pathologically confirmed MS cases and three controls (MS Brain Bank, London, UK). Patients with MS (one man, 13 women) were aged 44-81 years (mean 56.6, median 56) with disease durations of 6-32 years (mean 23.7, median 22). Eleven cases had secondary progressive MS (SPMS), two primary progressive MS (PPMS) and one relapsing remitting MS (RRMS). The controls (two women aged 69 and 78 years, one man aged 35 years) had no clinical or pathological evidence of neurological disease. The local research...

Growing evidence suggests that axonal degeneration rather than demyelination is the pathological substrate underlying chronic, irreversible disability in multiple sclerosis. However, direct evidence linking clinical disability measured in vivo with corresponding post-mortem measures of axonal pathology is lacking. Our objective in this study was to investigate the relationship between motor disability accumulated by patients with multiple sclerosis during life and the degree of axonal loss observed in their descending motor tracts after death. Human spinal cord derived at autopsy from 45 patients with multiple sclerosis was investigated. The medical records of each patient were reviewed by a multiple sclerosis neurologist to determine the degree of motor disability reached before death. Spinal cord sections were stained immunohistochemically. The degree of demyelination and the number of surviving corticospinal tract axons were measured in each patient. Patients who had accumulated higher levels of motor disability prior to death demonstrated fewer surviving corticospinal axons. Motor disability did not correlate with degree of demyelination. This study provides for the first time, direct clinico-pathological evidence that axonal loss is the pathological substrate of established disability in multiple sclerosis.

No abstract

The extent and pattern of gray matter (GM) demyelination in the spinal cord in multiple sclerosis (MS) has not been examined in detail. Human autopsy material was obtained from 36 MS cases and 12 controls. Transverse sections were taken from five levels of the spinal cord (upper cervical, lower cervical, upper thoracic, lower thoracic and lumbar levels) and the extent of GM and white matter (WM) demyelination evaluated using proteolipid protein immunohistochemistry (IHC). The proportion of the GM that was demyelinated (33%) was significantly greater than the proportion of demyelinated WM (20%) (P < 0.0001). Similarly, demyelination was more extensive in the GM than in the WM at each of the five cord levels. The extent of GM demyelination was not significantly different between the five cord levels while WM demyelination was greatest at the upper cervical level. Morphologically, the borders of a proportion of the GM plaques show a strict respect for the GM/WM boundary. We demonstrate that extensive demyelination occurs in the GM of the spinal cord in MS. Myelin protein IHC reveals a novel pattern of residual plaque morphology challenging previous work suggesting that MS plaques display a total disregard for anatomical boundaries.

Standard-Nutzungsbedingungen:Die Dokumente auf EconStor dürfen zu eigenen wissenschaftlichen Zwecken und zum Privatgebrauch gespeichert und kopiert werden.Sie dürfen die Dokumente nicht für öffentliche oder kommerzielle Zwecke vervielfältigen, öffentlich ausstellen, öffentlich zugänglich machen, vertreiben oder anderweitig nutzen.Sofern die Verfasser die Dokumente unter Open-Content-Lizenzen (insbesondere CC-Lizenzen) zur Verfügung gestellt haben sollten, gelten abweichend von diesen Nutzungsbedingungen die in der dort genannten Lizenz gewährten Nutzungsrechte. It does so using a unique dataset of 300 NGOs in Uganda with corresponding beneficiary assessments. Investigating NGO dishonesty with regards to financial transparency and community participation, the study finds a high incidence of misrepresentation among NGOs. Terms of use: Documents inResults from a Heckman probit model suggest that the determinants of misrepresentation differ according to the subject matter: the threat of being caught reduces the likelihood of dishonesty about financial transparency, while a desire to 'save face' to maintain a good reputation appears to be the main motivator of a misrepresentation of community. consultation. The analysis provides tentative indications that NGOs with antagonistic relations with the government may be more likely to hide information and be dishonest. It also lends some support to the view that excessive and unrealistic donor demands may be an obstacle to openness and transparency. The findings of this work caution against an overly naïve and simplistic view of NGOs, and specifically, an overreliance on reported information when regulating, monitoring or surveying NGOs.

In this paper, we revisit the contested issue of the impact of agricultural extension on farm production. We exploit two features of the data available to us: its longitudinal nature and explicit measures of farmer ability. We find that after controlling for innate productivity characteristics and farmer ability either using household fixed effects estimation, or by including a measure of farmer ability and village fixed effects, access to agricultural extension services, defined as receiving one or two visits per agricultural year, raises the value of crop production by about 15 per cent. This parameter estimate is statistically significant. However, we also find variability in these parameter estimates across individual crop years, with the impact being markedly different in drought and non-drought years. Collectively, these results suggest that although access to farm-level extension visits does increase productivity even after controlling for innate productivity characteristics and farmer ability, results from single-year cross-sectional studies should be treated with caution

The objective of this study was to assess neuronal pathology in the spinal cord in multiple sclerosis (MS), both within myelinated and demyelinated tissue. Autopsy material was obtained from 38 MS cases and 21 controls. Transverse sections were taken from three spinal cord levels and stained using Luxol Fast Blue/Cresyl Violet and myelin protein immunohistochemistry. Measurements of neuronal number and size were made for all neurons within the anterior horns of the gray matter. Neurons were classified as motoneurons or interneurons according to size criteria. In comparison with controls, both motoneuron and interneuron number were reduced in MS cases at the upper cervical (interneuron P = 0.0549; motoneuron P = 0.0073) and upper thoracic (interneuron P = 0.0507; motoneuron P = 0.0144), but not the lumbar level. Interneuron cross-sectional area was reduced in MS cases at all levels (upper cervical, P = 0.0000; upper thoracic, P = 0.0002; lumbar, P = 0.0337). Neuronal loss appears to be predominantly related to local gray matter plaques, whereas interneuron atrophy occurs in both myelinated and demyelinated areas.