The incidences of multiple sclerosis have risen worldwide, yet neither the trigger nor efficient treatment is known. Some research is dedicated to looking for treatment by parasites, mainly by helminths. However, little is known about the effect of helminths that infect the nervous system. Therefore, we chose the neurotropic avian schistosome Trichobilharzia regenti, which strongly promotes M2 polarization and tissue repair in the central nervous system, and we tested its effect on the course of experimental autoimmune encephalomyelitis (EAE) in mice. Surprisingly, the symptoms of EAE tended to worsen after the infection with T. regenti. The infection did not stimulate tissue repair, as indicated by the similar level of demyelination. Eosinophils heavily infiltrated the infected tissue, and the microglia number increased as well. Furthermore, splenocytes from T. regenti-infected EAE mice produced more interferon (IFN)-γ than splenocytes from EAE mice after stimulation with myelin oligodendrocyte glycoprotein. Our research indicates that the combination of increased eosinophil numbers and production of IFN-γ tends to worsen the EAE symptoms. Moreover, the data highlight the importance of considering the direct effect of the parasite on the tissue, as the migrating parasite may further tissue damage and make tissue repair even more difficult.

JC virus is the etiological agent of progressive multifocal leukoencephalopathy, a white matter demyelinating disease that mostly affects immunocompromised patients. JC virus can also infect neurons and meningeal cells and cause encephalitis, meningitis and granule cell neuronopathy. We report a patient with JC virus granule cell neuronopathy, without concomitant progressive multifocal leukoencephalopathy, presenting as inaugural acquired immune deficiency syndrome-related illness. This patient’s human immunodeficiency virus infection remained undiagnosed for several months after neurological symptoms onset. We review JC virus pathophysiology, clinical manifestations, treatment and prognosis, and emphasize the importance of considering human immunodeficiency virus infection and related opportunistic infections in the differential diagnosis of new-onset isolated cerebellar disease.

Objectives: The aim of this study was to describe cognitive, academic, and psychosocial outcomes after an incident demyelinating event (acquired demyelinating syndromes, ADS) in childhood and to investigate the contribution of brain lesions and confirmed MS diagnosis on outcome. Methods: Thirty-six patients with ADS (mean age=12.2 years, SD=2.7, range: 7–16 years) underwent brain MRI scans at presentation and at 6-months follow-up. T2-weighted lesions on MRI were assessed using a binary classification. At 6-months follow-up, patients underwent neuropsychological evaluation and were compared with 42 healthy controls. Results: Cognitive, academic, and behavioral outcomes did not differ between the patients with ADS and controls. Three of 36 patients (8.3%) were identified with cognitive impairment, as determined by performance falling ≤1.5 SD below normative values on more than four independent tests in the battery. Poor performance on a visuomotor integration task was most common, observed among 6/32 patients, but this did not differ significantly from controls. Twelve of 36 patients received a diagnosis of MS within 3 years post-ADS. Patients with MS did not differ from children with monophasic ADS in terms of cognitive performance at the 6-months follow-up. Fatigue symptoms were reported in 50% of patients, irrespective of MS diagnosis. Presence of brain lesions at onset and 6 months post-incident demyelinating event did not associate with cognitive outcome. Conclusions: Children with ADS experience a favorable short-term neurocognitive outcome, even those confirmed to have MS. Longitudinal evaluations of children with monophasic ADS and MS are required to determine the possibility of late-emerging sequelae and their time course. (JINS, 2016, 22, 1050–1060)

Action potential conduction velocity increases dramatically during early development as axons become myelinated. Integral to this process is the clustering of voltage-gated Na+ (Nav) channels at regularly spaced gaps in the myelin sheath called nodes of Ranvier. We show here that some aspects of peripheral node of Ranvier formation are distinct from node formation in the CNS. For example, at CNS nodes, Nav1.2 channels are detected first, but are then replaced by Nav1.6. Similarly, during remyelination in the CNS, Nav1.2 channels are detected at newly forming nodes. By contrast, the earliest Nav-channel clusters detected during developmental myelination in the PNS have Nav1.6. Further, during PNS remyelination, Nav1.6 is detected at new nodes. Finally, we show that accumulation of the cell adhesion molecule neurofascin always precedes Nav channel clustering in the PNS. In most cases axonal neurofascin (NF-186) accumulates first, but occasionally paranodal neurofascin is detected first. We suggest there is heterogeneity in the events leading to Nav channel clustering, indicating that multiple mechanisms might contribute to node of Ranvier formation in the PNS.

To ensure rapid and efficient impulse conduction, myelinated axons establish and maintain specific protein domains. For instance, sodium (Na+) channels accumulate in the node of Ranvier; potassium (K+) channels aggregate in the juxtaparanode and neurexin/caspr/paranodin clusters in the paranode. Our understanding of the mechanisms that control the initial clustering of these proteins is limited and less is known about domain maintenance. Correlative data indicate that myelin formation and/or mature myelin-forming cells mediate formation of all three domains. Here, we test whether myelin is required for maintaining Na+ channel domains in the nodal gap by employing two demyelinating murine models: (1) cuprizone ingestion, which induces complete demyelination through oligodendrocyte toxicity; and (2) ceramide galactosyltransferase deficient mice, which undergo spontaneous adult-onset demyelination without oligodendrocyte death. Our data indicate that the myelin sheath is essential for long-term maintenance of sodium channel domains; however, oligodendrocytes, independent of myelin, provide a partial protective influence on the maintenance of nodal Na+ channel clusters. Thus, we propose that multiple mechanisms regulate the maintenance of nodal protein organization. Finally, we present evidence that following the loss of Na+ channel clusters the chronological progression of expression and reclustering of Na+ channel isoforms during the course of CNS remyelination recapitulates development.

Transplantation of cell suspensions containing olfactory ensheathing cells (OECs) has been reported to remyelinate demyelinated axons in the spinal cord with a Schwann cell (SC)-like pattern of myelination. However, questions have been raised recently as to whether OECs can form SC-like myelin. To address this issue we prepared SCs and OECs from transgenic rats in which a marker gene, human placental alkaline phosphatase (hPAP), is linked to the ubiquitously active promoter of the R26 gene. SCs were prepared from the sciatic nerve and OECs from the outer nerve-fiber layer of the olfactory bulb. Positive S100 and p75 immunostaining indicated that >95% of cells in culture displayed either SC or OEC phenotypes. Suspensions of either SCs or OECs were transplanted into an X-irradiation/ethidium bromide demyelinating lesion in the spinal cord. We observed extensive SC-like remyelination following either SC or OEC transplantation 3 weeks after injection of the cells. Alkaline phosphatase (ALP) chromagen reaction product was associated clearly with the myelin-forming cells. Thus, cell suspensions that are enriched in either SCs or OECs result in peripheral-like myelin when transplanted in vivo.

This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate into astrocytes as well oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oliodendrocyte progenitor cell line CG4) are described. These show that CG4 cells do not survive (or migrate) when transplanted into the normal adult CNS. However, if they are transplanted into CNS tissue that has previously been exposed to 40 Gy of x-irradiation then transplanted CG4 cells survive, divide and migrate over large distances. Moreover, within an x-irradiated environment, migrating transplanted CG4 cells are able to enter remotely located foci of demyelination and contribute to the remyelination of the demyelinated axons within. These studies demonstrate that although the normal adult CNS does not appear to support survival and migration of the CG4 cell line, it is possible to manipulate the environment in such a way that these nonpermissive properties of the environment can be overcome.