Shared Decision-making in Autoimmune Neurology: Making Decisions in the Face of Uncertainty.

PURPOSE OF REVIEW: In this article, the author explores the use of shared decision making (SDM) in the management of the preference-sensitive condition, neural autoantibody-mediated syndromes. RECENT FINDINGS: The field of autoimmune neurology lacks trials and often data to support therapeutic decisions. Treatment choices need to be made acutely, lacking crucial laboratory information and with uncertainty regarding treatment response and prognosis. This lack of data does not necessitate indecision in a population where delayed treatment may lead to poor outcomes. Over the past several decades, SDM has emerged as a model of communication enabling clinicians and their patients to explore current knowledge in the context of a patient's values and goals to arrive at joint decision, even when data are lacking. SUMMARY: SDM is a tool autoimmune neurologists should use to develop individualized treatment plans based on the patient's clinical presentation contextualized within specific values and preferences.

Rosai-Dorfman Disease: A Less Common Cause of Leptomeningeal and Nerve Root Enhancement.

A 46-year-old male experienced progressive neurocognitive decline, weight loss, intermittent headaches, and weakness over 6 months. Magnetic resonance imaging of the brain revealed hydrocephalus and the spinal cord imaging showed diffuse leptomeningeal enhancement with prominent nerve root involvement. Intradural biopsy of lumbar arachnoid tissue found mixed inflammatory infiltrate consisting predominantly of histiocytes, S100 and CD68 positivity, and lymphocytophagocytosis (emperipolesis) consistent with extranodal Rosai-Dorfman disease. Rosai-Dorfman disease, a non-Langerhans cell histocytic disorder, can mimic the appearance of neurosarcoidosis and leptomeningeal carcinomatosis and should remain on the differential of a patient presenting with diffuse leptomeningeal enhancement, a common occurrence on a neurohospitalist service.

Inflammatory Manifestations of Systemic Diseases in the Central Nervous System.

PURPOSE OF REVIEW: This review presents the current recommended therapeutic interventions for inflammatory disease in the central nervous system (CNS) secondary to systemic diseases of immune dysregulation. Treatment recommendations for CNS inflammation associated with rheumatologic conditions, immune-related adverse effects from immune checkpoint inhibitors (ICIs), and demyelinating disease from tumor necrosis factor-α (anti-TNFs) are explored. Additional therapeutic options for inflammation related to postviral syndromes and genetic immunodeficiencies are also discussed. RECENT FINDINGS: In addition to treatment of mild, moderate, and severe CNS rheumatologic disease as guided by the European League Against Rheumatism (EULAR), early consideration of rituximab for severe IgG4-related disease and induction with anti-TNF therapy for severe neurosarcoidosis should be considered. Although often not first line, treatment options for CNS inflammatory diseases based on disease mechanism are emerging, including tocilizumab for Behcet's disease, natalizumab for ICI associated autoimmune encephalitis, and abatacept for treatment of infiltrative disease secondary to CTLA-4 deficiency. Hematopoietic stem cell treatments represent highly efficacious but risky options for autoimmunity related to genetic immunodeficiency. SUMMARY: While early high dose steroids remains first line therapy for most CNS inflammatory conditions, a rapidly expanding arsenal of immune targeted therapies offers clinicians tailored disease specific options for treatment.

Anti-Yo Mediated Paraneoplastic Cerebellar Degeneration Associated with Pseudobulbar Affect in a Patient with Breast Cancer.

Paraneoplastic cerebellar degeneration (PCD) is a rare anti-Yo mediated paraneoplastic syndromes rarely that is infrequently associated with breast cancer. We present a case of a 52-year-old female presenting with diplopia, gait instability, dysarthria, dysphagia, nystagmus, and, most notably, new onset paroxysmal episodes of uncontrollable crying concerning for pseudobulbar affect (PBA). Serologic testing showed anti-Yo antibodies. The patient was found to have stage IIIA breast cancer as the inciting cause of the paraneoplastic syndrome. The patient was treated with neoadjuvant chemotherapy, modified radical mastectomy, adjuvant Herceptin, and pertuzumab. She was given IVIG for paraneoplastic syndrome, antidepressants, and dextromethorphan-quinidine (Nuedexta), the first FDA-approved therapy for PBA. With multimodality therapy, she demonstrated significant improvement in neurologic and mood symptoms associated with PCD and PBA.

A KCNQ channel opener for experimental neonatal seizures and status epilepticus.

OBJECTIVE: Neonatal seizures occur frequently, are often refractory to anticonvulsants, and are associated with considerable morbidity and mortality. Genetic and electrophysiological evidence indicates that KCNQ voltage-gated potassium channels are critical regulators of neonatal brain excitability. This study tests the hypothesis that selective openers of KCNQ channels may be effective for treatment of neonatal seizures. METHODS: We induced seizures in postnatal day 10 rats with either kainic acid or flurothyl. We measured seizure activity using quantified behavioral rating and electrocorticography. We compared the efficacy of flupirtine, a selective KCNQ channel opener, with phenobarbital and diazepam, two drugs in current use for neonatal seizures. RESULTS: Unlike phenobarbital or diazepam, flupirtine prevented animals from experiencing development of status epilepticus when administered before kainate. In the flurothyl model, phenobarbital and diazepam increased latency to seizure onset, but flupirtine completely prevented seizures throughout the experiment. Flupirtine was also effective in arresting electrographic and behavioral seizures when administered after animals had developed continuous kainate-induced status epilepticus. Flupirtine caused dose-related sedation and suppressed electroencephalographic activity but did not result in respiratory suppression or result in any mortality. INTERPRETATION: Flupirtine appears more effective than either of two commonly used antiepileptic drugs, phenobarbital and diazepam, in preventing and suppressing seizures in both the kainic acid and flurothyl models of symptomatic neonatal seizures. KCNQ channel openers merit further study as potential treatments for seizures in infants and children.