A 79-Year-Old Woman With Worsening Headaches and Pachymeningeal Enhancement: A Case Report From the National Multiple Sclerosis Society Case Conference Proceedings.

A 79-year-old woman presented with subacutely worsening headaches and right arm weakness. MRI showed diffuse pachymeningeal enhancement. Serologic workup revealed elevated erythrocyte sedimentation rate and C-reactive protein. CSF demonstrated elevated opening pressure, a lymphocytic pleocytosis, and elevated protein. We discuss our differential diagnosis and distinguish between 2 overlapping clinical entities.

Relapsing Anti-GAD65-Associated Encephalitis Responsive to Thymoma Resection, Radiation, and Immunomodulatory Therapy.

Herein we describe a case of relapsing anti-GAD65-associated encephalitis which was responsive to the combination of thymoma resection, external beam radiotherapy, and immunomodulatory therapy. The case illustrates the value of remaining vigilant for the possibility of paraneoplastic syndromes in the context of anti-GAD65 antibodies and thymoma. It also illustrates that tumor-directed therapies may offer additional benefit beyond immunomodulatory therapy alone.

Large Mitochondrial DNA Deletions in HIV Sensory Neuropathy.

OBJECTIVE: The primary objective of this study was to evaluate the correlation of large mitochondrial DNA (mtDNA) deletions in skin samples of people with HIV (PWH) with measures of neuropathy and prior exposure to therapy. We hypothesized that deletions would be associated with neuropathy. As secondary objectives, we determined the correlation of deletion burden with demographic data and neuropathy measures. METHODS: In this retrospective cohort study, we measured the accumulation of large mtDNA deletions in skin biopsies from PWH recruited as part of the AIDS Clinical Trials Group (ACTG). Our cohort includes individuals with and without sensory neuropathy, as well as individuals with normal or abnormal skin biopsies. Skin biopsies, sural and peroneal nerve conduction studies, total neuropathy score, and deletion burden scores were measured, along with baseline demographic data such as age, CD4+ cell count, viral counts, and prior nucleoside reverse transcriptase inhibitor exposures. RESULTS: Sixty-seven PWH were enrolled in the study. The mean age of the cohort (n = 67) was 44 years (SD 6.8, range 32-65 years), and 9 participants were female. The mean CD4+ T-cell count was 168 cells/mm3 (SD 97 cells/mm3, range 1-416 cells/mm3) and mean viral load was 51,129 copies/mL (SD 114,586 copies/mL, range 147-657,775 copies/mL). We determined that there was a correlation between the total mtDNA deletion and intraepidermal nerve fiber density (IENFD) (r = -0.344, p = 0.04) and sural nerve amplitude (r = -0.359, p = 0.004). CONCLUSIONS: Both IENFD and sural nerve amplitude statistically correlate with mitochondrial mutation burden in PWH, specifically in those with HIV-associated sensory neuropathy as assessed by skin biopsy.

Sudden Sensorineural Hearing and Vestibular Loss in a Case of Relapsing Polychondritis.

OBJECTIVES: To report a case of profound bilateral sensorineural hearing and vestibular loss from relapsing polychondritis and hearing outcomes after cochlear implantation. METHODS: Case report and literature review. RESULTS: A 43 year-old woman developed sudden loss of hearing and balance that progressed over several weeks to bilateral, profound hearing and vestibular loss. Steroid treatments were ineffective. She underwent vestibular physical therapy and left cochlear implantation. About 10 months after her initial presentation, she developed erythema, warmth, swelling, and pain of the left auricle sparing the lobule, flattening of the bridge of her nose, and right ankle swelling, warmth, and skin erythema. A biopsy of the left auricle revealed histopathologic findings consistent with relapsing polychondritis. She was treated with high dose prednisolone. The ear inflammation resolved, however, despite excellent auditory response to pure tone thresholds, the patient reported no improvement in speech perception after cochlear implantation. CONCLUSIONS: Relapsing polychondritis can present with rapidly progressive, profound loss of hearing and vestibular function. Hearing outcomes after cochlear implantation can include poor speech discrimination despite good pure tone detection thresholds.

Neurological manifestations associated with COVID-19: a review and a call for action.

While the epidemic of Coronavirus disease 2019 (COVID-19) continues to spread globally, more and more evidences are collected about the presence of neurological manifestations and symptoms associated with it. A systematic review has been performed of papers published until 5 April 2020. 29 papers related to neurological manifestations associated with COVID-19 were examined. The results show presence of central and peripheral nervous system manifestations related to coronavirus. Neurological manifestations, or NeuroCOVID, are part of the COVID-19 clinical picture, but questions remain regarding the frequency and severity of CNS symptoms, the mechanism of action underlying neurological symptoms, and the relationship of symptoms with the course and severity of COVID-19. Further clinical, epidemiological, and basic science research is urgently needed to understand and address neurological sequalae of COVID-19. Concomitant risk factors or determinants (e.g. demographic factors, comorbidities, or available biomarkers) that may predispose a person with COVID-19 to neurological manifestations also need to be identified. The review shows that although more and more papers are reporting neurological manifestations associated with COVID-19; however, many items remain unclear and this uncertainty calls for a global action that requires close coordination and open-data sharing between hospitals, academic institutions and the fast establishment of harmonised research priorities and research consortia to face the NeuroCOVID-19 complications.

Chronic inflammation mediates brain injury in HIV infection: relevance for cure strategies.

PURPOSE OF REVIEW: Chronic inflammation is a major component of HIV infection, the effects of which can be devastating in the central nervous system (CNS). Protecting the brain is, therefore, critical as efforts proceed to cure HIV infection by reactivating latent viral reservoirs and driving immune responses. We review the clinical presentation and pathology findings of inflammatory processes in the CNS in patients managed with ART and the drivers of these processes. RECENT FINDINGS: Chronic inflammation is associated with increased mortality and morbidity and HIV infection increases the risk for chronic diseases, especially cognitive impairment. Latent viral reservoirs, including microglia and tissue macrophages, contribute to inflammation in the CNS. Inflammation is generated and maintained through residual viral replication, dysregulation of infected cells, continuously produced viral proteins and positive feedback loops of chronic inflammation. Novel therapeutics and lifestyle changes may help to protect the CNS from immune-mediated damage. SUMMARY: As therapies are developed to cure HIV, it is important to protect the CNS from additional immune-mediated damage. Adjunctive therapies to restore glial function, reduce neuroinflammation and systemic inflammation, and inhibit expression of viral proteins are needed.

Clinician-rated measures for distal symmetrical axonal polyneuropathy: ACTTION systematic review.

Distal symmetrical axonal polyneuropathy (DSP) is due to injury to peripheral sensory, motor, and autonomic nerve fibers, resulting in distal predominant sensory loss, pain, and gait instability. DSP occurs as a complication of multiple medical conditions including diabetes or HIV, or following exposure to various toxins such as chemotherapy. It affects at least 10% of the United States population. Few treatments for DSP are approved by regulatory agencies. Reliable and responsive outcome measures are integral to developing new DSP treatments. Multiple clinician-rated measures that incorporate neuropathy signs exist, however, it is not clear which of these measures performs best for various DSP phenotypes. This systematic review summarizes the content of 18 published measures of DSP identified using PubMed and from personal archives of the authors. The relative percentage of scoring dedicated to motor, reflex, large and small fiber sensory, and autonomic domains varied considerably among measures. The most common neurologic examination items included in the scales were (1) vibration perception (n = 18, 100%), (2) reflexes (n = 16, 89%), (3) pinprick perception (n = 14, 78%), (4) muscle strength (n = 11, 61%), (5) touch-pressure perception (n = 9, 50%), and (6) joint position perception (n = 8, 44%). This review can be used to inform decisions regarding which of the available clinician-rated sign outcome measures would be most appropriate for use in a particular DSP population, based on the domains most affected by that neuropathy or on the domains most likely to be affected by a particular experimental therapy.