Focal Seizures Induced by Paraneoplastic Syndrome Leading to a Diagnosis of Small Cell Lung Carcinoma.

Paraneoplastic neurological disorders are a rare complication of multiple neoplasms, such as lung, testis, and breast, and can be associated with positive antibody anti-Hu (anti-neuronal nuclear antibody type 1 or ANNA-1), anti-Ta, anti-Ma, and uncharacterized antibody, or be antibody-negative. Early treatment of the underlying tumor is the most likely modality that will lead to regression of the paraneoplastic neurological symptoms. Here, we present a case of a 73-year-old female with new-onset seizure activity from ANNA-1 encephalitis found to have undiagnosed small cell lung cancer to highlight the need for further workup for malignancy.

Human Herpes Virus-6 (HHV-6) infectious encephalitis in an immunocompetent adult.

Human herpesvirus 6 (HHV-6) is one of the most prevalent childhood viruses. HHV-6 reactivation in allogeneic hematopoietic cell transplant recipients and solid organ transplant recipients is well described in medical literature. We present a case of HHV-6 reactivation causing encephalitis, which is rare in immunocompetent adults.

Systemic Lymphoma Masquerading as Multiple Sclerosis Relapse.

Multiple sclerosis (MS) is a chronic immune-mediated central nervous system disease that can affect both the brain and spinal cord. Given that MS can occur at any location in the brain or spinal cord and can lead to a variety of symptoms, this can lead to difficulty in diagnosing MS versus other conditions mimicking MS. Here we present a case of a 69-year-old female with a history of relapsing-remitting MS diagnosed in 2002 and melanoma status post-excision who exhibited progressive neurological decline over eight weeks characterized by right internuclear ophthalmoplegia, bilateral ataxia, and left hemiparesis sparing the face. Mimics of MS can include various inflammatory, neoplastic, infectious, metabolic, and genetic disorders. The diagnosis of MS-mimicking diseases can be especially challenging for someone with a known history of MS. A biopsy should be considered for new lesions seen on imaging if acute immunotherapies have no response to the clinical patient's symptoms. Given the wide variety of symptoms that can present with MS, it is important to keep a broad range of differential diagnoses when considering MS, even in those with a known history of MS.

5'ValCAC tRNA fragment generated as part of a protective angiogenin response provides prognostic value in amyotrophic lateral sclerosis.

Loss-of-function mutations in the ribonuclease angiogenin are associated with amyotrophic lateral sclerosis. Angiogenin has been shown to cleave transfer RNAs during stress to produce 'transfer-derived stress-induced RNAs'. Stress-induced tRNA cleavage is preserved from single-celled organisms to humans indicating it represents part of a highly conserved stress response. However, to date, the role of tRNA cleavage in amyotrophic lateral sclerosis remains to be fully elucidated. To this end, we performed small RNA sequencing on a human astrocytoma cell line to identify the complete repertoire of tRNA fragments generated by angiogenin. We found that only a specific subset of tRNAs is cleaved by angiogenin and identified 5'ValCAC transfer-derived stress-induced RNA to be secreted from neural cells. 5'ValCAC was quantified in spinal cord and serum from SOD1G93A amyotrophic lateral sclerosis mouse models where we found it to be significantly elevated at symptom onset correlating with increased angiogenin expression, imbalanced protein translation initiation factors and slower disease progression. In amyotrophic lateral sclerosis patient serum samples, we found 5'ValCAC to be significantly higher in patients with slow disease progression, and interestingly, we find 5'ValCAC to hold prognostic value for amyotrophic lateral sclerosis patients. Here, we report that angiogenin cleaves a specific subset of tRNAs and provide evidence for 5'ValCAC as a prognostic biomarker in amyotrophic lateral sclerosis. We propose that increased serum 5'ValCAC levels indicate an enhanced angiogenin-mediated stress response within motor neurons that correlates with increased survival. These data suggest that the previously reported beneficial effects of angiogenin in SOD1G93A mice may result from elevated levels of 5'ValCAC transfer RNA fragment.

Human-derived neural progenitors functionally replace astrocytes in adult mice.

Astrocytes are integral components of the homeostatic neural network as well as active participants in pathogenesis of and recovery from nearly all neurological conditions. Evolutionarily, compared with lower vertebrates and nonhuman primates, humans have an increased astrocyte-to-neuron ratio; however, a lack of effective models has hindered the study of the complex roles of human astrocytes in intact adult animals. Here, we demonstrated that after transplantation into the cervical spinal cords of adult mice with severe combined immunodeficiency (SCID), human pluripotent stem cell-derived (PSC-derived) neural progenitors migrate a long distance and differentiate to astrocytes that nearly replace their mouse counterparts over a 9-month period. The human PSC-derived astrocytes formed networks through their processes, encircled endogenous neurons, and extended end feet that wrapped around blood vessels without altering locomotion behaviors, suggesting structural, and potentially functional, integration into the adult mouse spinal cord. Furthermore, in SCID mice transplanted with neural progenitors derived from induced PSCs from patients with ALS, astrocytes were generated and distributed to a similar degree as that seen in mice transplanted with healthy progenitors; however, these mice exhibited motor deficit, highlighting functional integration of the human-derived astrocytes. Together, these results indicate that this chimeric animal model has potential for further investigating the roles of human astrocytes in disease pathogenesis and repair.