A meditation on medications, among other things

This third issue of Neurology® Neuroimmunology & Neuroinflammation incorporates a number of fascinating and informative clinical reports, including a presentation of prion disease as hyperacusis from Merkler et al. as well as a case of NMDA receptor antibody disease associated with bilateral sensorineural hearing loss from Taraschenko et al. In the case reported by Merkler et al., central auditory processing is the suspected pathophysiology, while the data from Taraschenko et al. suggest that the cochlear apparatus was directly targeted by pathogenic autoantibodies. Together the 2 cases illustrate how much neurophysiology can be gleaned from thoughtful study of these unusual patients. We also present a transient episode of autoimmune autonomic ganglionopathy (AAG) from Baker et al. This case illustrates the clinical and scientific importance of case reports. Individuals with AAG harbor autoantibodies to ganglionic acetylcholine receptors, producing (usually) modest autonomic insufficiency syndromes. This case of transient symptoms in a neonate born to a patient with AAG confirms that the antibodies are directly pathogenic and also alerts clinicians to the potential for this complication of the disorder. FernándezFournier et al. report a careful study of cervical myelitis in a young girl, with onset only 3 days after human papillomavirus immunization. The extremely short interval between immunization and neuroinflammation, along with the presence of CSF oligoclonal immunoglobulin M, are consistent with the possibility that a preexisting autoimmune diathesis was present. This challenges the research community to identify markers of the few individuals (insufficient numbers to exceed background in surveys) who may be at risk for expressing inflammatory complications of prophylactic immunization. Another clinical study, from Morgello et al., addresses the complex relationships between vascular disease and chronic viral infection (in this case HIV with or without hepatitis C virus [HCV]). It has been clear for some time that HIV infection carries a risk of vascular disease, possibly related to a persistent inflammatory reaction. In this incisive study, Morgello et al. focus on small vessel cerebral disease and show that coinfection withHCV is an identifiable and substantial (20% of variance) risk factor. The methodology using multivariate analysis is hypothesis-raising rather than hypothesis-testing, but the findings will be of considerable public health and scientific utility. Wang et al. describe a case of Lyme neuroborreliosis that is interesting because of its geography: this US patient manifested a syndrome of cranial polyneuritis and spinal radiculitis that would be familiar to non-US physicians but is quite atypical in the United States. The reasons for these differences are speculative (different Borrelia species? genetic or environmental host factors?), but the report will educate US physicians caring for such patients. Two benchtop clinical research studies appear in this issue. In one, Williams et al. show that CCR2 chemokine receptor expression on a monocyte subpopulation often termed “intermediate” (CD14/ CD16) may provide a suggestive indicator for cognitive impairment in HIV1 individuals. The findings integrate cognitive and laboratory investigation to yield data that may help to understand why some HIV1 persons develop cognitive impairment as well as to identify those at increased risk. Thomas et al. also focus on a subset of mononuclear phagocytes, a newly described dendritic cell subset (termed “6-sulfo LacNAc1 dendritic cells” or “slan-DCs”) whose P selectin glycoprotein ligand 1 is decorated with 6-sulfo N-acetyl-D-lactosamine rather than more common modifications. These cells have been proposed to drive pathogenic T-cell responses in other human conditions. Here the analysis is extended to include multiple sclerosis (MS) by examination of blood, CSF, and brain lesion cells. In addition, effects of several immunomodulatory MS treatments are examined. The data underline how little we securely know of the specific cellular interactions that produce neuroimmunologic diseases.