Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study.

INTRODUCTION: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.

Multiple sclerosis or "inflammatory CADASIL?": Case Report and review of the literature.

BACKGROUND: Multiple sclerosis (MS) and CADASIL presenting together is exceedingly rare. As more cases of "inflammatory" CADASIL emerge, diagnostic challenges for clinicians increase. We report an individual with MS and CADASIL presenting with cognitive decline at age 25. She presented with gadolinium enhancing lesions on MRI and inflammatory cerebrospinal fluid raising the question of whether these patients should be given a diagnosis of "inflammatory CADASIL" or both MS and CADASIL. METHODS: A literature review was conducted on reports of inflammatory CADASIL or MS and CADASIL, clinical presentations including spinal cord lesions and CSF inflammatory markers. RESULTS: Nine cases in the literature of individuals with CADASIL and inflammatory presentations were found with treatment varying from intravenous steroids to MS immunomodulatory therapy. CONCLUSIONS: If individuals with CADASIL present with immune mediated inflammatory components they may benefit from immunomodulatory therapy. This is discussed with a review of the inflammatory CADASIL/MS cases in the literature and report of a case.

Chemotactic selection with insulin, di-iodotyrosine and histamine alters the phagocytotic responsiveness of Tetrahymena.

Chemotactic selection is a method by which populations of cells exposed to ligands can be isolated and subsequently cultivated. We used Tetrahymena pyriformis GL cultures selected by chemotactic selection to insulin (10 nM), histamine (0.1 nM) and di-iodotyrosine (T2, 10 nM) to study the phagocytotic capacity under the induction of selector hormones. Our results show a long-lasting link between chemotactically selected cultures and phagocytotic activity. Cells selected to histamine produced the highest phagocytotic activity upon a second exposure to the selector hormone. T2 selection was also strongly effective, however, the phagocytosis stimulation was not specific to the hormone given later. Insulin selected sub-populations had different phagocytotic responses to the control substance itself, whereas histamine selected sub-populations seem to be heterogeneous in the phagocytotic response to histamine. For insulin, the increased endocytotic or metabolic activity was demonstrated by the lack of non-phagocytotic cells. These experiments call attention to the evolutionary role of selection in the later developing receptor-hormone relationship.

Chemotactic selection of Tetrahymena pyriformis GL induced with histamine, di-iodotyrosine or insulin.

It has been hypothesized that in phylogeny the encounter between potential signalling molecules and the continously changing cell membrane could result in the formation of a ligand specific receptor. This chemical (hormonal) imprinting is then transmitted to the progeny generations. It is, however, very difficult to know whether the selection of cells with receptor-like patterns or amplification of complete receptor-like patterns led to the formation of the receptor-hormone complex. The new technique of 'chemotactic selection provides a physiological response-guided selection of cells. It also enables the testing of subpopulations with the characteristic selector ligand. We show here that of three chemotactic ligands (histamine, di-iodotyrosine (T2) and human insulin), insulin and T2 selected subpopulations express a significantly high chemotactic response. Since the control medium has a selector capacity itself, we introduced a chemotactic selection coefficient (Chsel) which facilitates the comparison of all groups. Using this factor we found that insulin (Chsel = 1.57), functions as a strong selector and T2 (Chsel = 0.98), was a weak selector. Morphometric evaluation of the cells showed a good correlation between chemotactic responsiveness and morphometric characteristics of subpopulations selected with insulin and histamine. T2 data suggest that the long lasting responsiveness is not general, but might be subpopulation specific.