ABSTRACT
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an underdiagnosed disease that has been described thus far only in case series. Patients, the majority of which are females, develop neuropsychiatric symptoms that can often be misdiagnosed as purely psychiatric illness. Although teratomas are nearly pathognomonic for anti-NMDAR encephalitis, these are less common in children and males. This case illustrates some common features of anti-NMDAR encephalitis and some of the challenges in diagnosis.
Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis/blood , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnosis , Nerve Tissue Proteins/blood , Receptors, N-Methyl-D-Aspartate/blood , Adolescent , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/complications , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/drug therapy , Delayed Diagnosis , Electroencephalography , Emergency Service, Hospital , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Methylprednisolone/therapeutic use , Neuroprotective Agents/therapeutic use , Psychotic Disorders/etiology , Seizures/etiologyABSTRACT
LAR-like receptor protein tyrosine phosphatases (RPTPs), which are abundantly expressed in the nervous systems of most if not all bilaterian animals thus far examined, have been implicated in regulating a variety of critical neuronal processes. These include neuronal pathfinding, adhesion and synaptogenesis during development and, in adult mammals, neuronal regeneration. Here we explored a possible role of a LAR-like RPTP (HmLAR1) in response to mechanical trauma in the adult nervous system of the medicinal leech. In situ hybridization and QPCR analyses of HmLAR1 expression in individual segmental ganglia revealed a significant up-regulation in receptor expression following CNS injury, both in situ and following a period in vitro. Furthermore, we observed up-regulation in the expression of the leech homologue of the Abelson tyrosine kinase, a putative signaling partner to LAR receptors, but not among other tyrosine kinases. The effects on neuronal regeneration were assayed by comparing growth across a nerve crush by projections of individual dorsal P neurons (P(D)) following single-cell injection of interfering RNAs against the receptor or control RNAs. Receptor RNAi led to a significant reduction in HmLAR1 expression by the injected cells and resulted in a significant decrease in sprouting and regenerative growth at the crush site relative to controls. These studies extend the role of the HmLARs from leech neuronal development to adult neuronal regeneration and provide a platform to investigate neuronal regeneration and gene regulation at the single cell level.
