How to use spinal cord magnetic resonance imaging in the McDonald diagnostic criteria for multiple sclerosis

However, the significance of pathological changes in relation to the clinical symptoms can be evaluated only by examining a larger pathologically derived sample. The main strength of our study lies in our selection of all cases with S pathology regardless of their clinical phenotype. Several brain banks, including ours, have reported Lewy bodies in controls of their autopsy series before and after the era of S. Even in the best circumstances, the clinical documentation has been poor. In our retrospective study, we included only cases with high-quality and recent (a maximum of 1 year before death) clinical documentation which ultimately led to the exclusion of 30% of our original Spositive cohort. The majority of included cases had been examined by a neurologist and were diagnosed with a neurodegenerative disorder (30%) or with some other neurological disorders (40%), mostly cerebrovascular diseases. Most of these patients were evaluated more than once, and the interval between the clinical examination and death ranged from 5 days to 12 months. Certainly, the interval was not several years or decades as implied by Papapetropoulos and Mash. Thus, we feel confident that no full-blown parkinsonian syndrome or dementia would have remained undetected. Furthermore, we paid particularly careful attention to the analysis of neurologically unimpaired cases (the remaining 30%). Nearly all of these subjects had visited a general physician just before death or had been under a continuous clinical follow-up because of some chronic terminal illness such as neoplasia. Admittedly, even though we excluded all cases that had not been clinically evaluated within approximately 1 year, some of these individuals might have developed subtle extrapyramidal signs or mild cognitive impairment between the last clinical examination and time of death. There is really no way that this possibility can be avoided, even in the prospective analyses, because in most studies the subjects are usually evaluated once yearly. We fully agree that the diagnosis of clinical syndrome of dementia with Lewy bodies demands an extensive follow-up by a specialist. In fact, because of the difficulty to retrospectively assess the fluctuating course and the visual hallucinations associated with this syndrome, we decided to evaluate S pathology in relation to symptoms, extrapyramidal symptoms, and cognitive impairment, and not to particular disease entity. As mentioned by Drs Papapetropoulos and Mash, in our study design the evaluating neurologists were blinded to the neuropathological findings. Similarly, the neuropathologist was blinded to the clinical findings when sampling the cases for this study. The goal was not to delineate the clinicopathological diagnosis but rather to compare the clinical and neuropathological reality when dealing with S-positive inclusions. There is also evidence from both in vitro and transgenic animal model studies to indicate that the aggregation of S to inclusions is not crucial for cell death. In summary, we are not claiming that the process of S aggregation itself is not involved in the neuronal dysfunction. However, our results are in line with many biophysical studies that have proposed that the actual “death signal” is emitted during much earlier stages and that the inclusion formation could well represent a protective mechanism on the part of surviving cells.