Faculty Bibliography

BACKGROUND:Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia. METHODS:We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS:Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy. CONCLUSIONS:Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.

Desmopressin, a synthetic vasopressin analog, is used to treat central diabetes insipidus, hemostatic disorders such as von Willebrand's disease, and nocturnal enuresis. We present the case of a 69-year-old man who developed severe hyponatremia during treatment with intranasal desmopressin at 10 µg twice daily for chronic polyuria and nocturia thought to be due to central diabetes insipidus. After 5 months of therapy, the patient noticed progressive fatigue, anorexia, dizziness, weakness, light-headedness, decreased concentration, and new-onset falls. At 6 months of therapy, the patient was brought to the emergency department for altered mental status and was found to be severely hyponatremic with a serum sodium level of 96 mmol/L, down from a value of 134 mmol/L at the initiation of therapy. The intranasal desmopressin was discontinued and the patient was admitted to the intensive care unit where the hyponatremia was slowly corrected over the next week to 132 mmol/L, never increasing by more than 8 mmol/L a day, with careful fluid management. This included infusion of over 11 L of 5% dextrose to account for a high urine output, which peaked at 7.4 L in 1 day. However, while the recommended rate for sodium correction was followed, the patient's magnetic resonance imaging of the brain obtained after discharge displayed evidence of central pontine myelinolysis. Despite this finding, the patient eventually returned to his baseline mental status with no permanent neurologic deficits.

INTRODUCTION: Intravascular lymphoma (IVL) is a rare subtype of large B cell lymphoma (LBCL) in which growth of neoplastic cells occurs within blood vessels. Half of IVL cases are diagnosed on autopsy due to myriad clinical presentations and lack of established diagnostic approaches. We present a case of IVL that manifested as fatal refractory lactic acidosis. CASE PRESENTATION: A 71 year old female with a history of hypertension presented with generalized fatigue, abdominal pain, and unintentional 10lb weight loss over 3 months. Age appropriate cancer screening was negative. An outpatient abdominal CT scan revealed acute right portal vein thrombosis (PVT), and an isolated 1.8cm pancreatic tail lesion with no lymphadenopathy. Initial vital signs were unremarkable and examination with only mild abdominal distention. Workup revealed new mild anemia Hgb 10.7 g/dL, CO2 12mmol/L, anion gap of 20mmol/L, platelets 76,000/uL, and mild elevation of AST 110 U/L and ALT 73 U/L. Venous blood gas showed pH 7.2, PCO2 36mmHg, HCO3 13mmol/L, and lactate 10.5mmol/L. Heparin was initiated for PVT and empiric blood cultures ultimately grew Weisella confusa, an enteric lactobacillus seen in immmuncompromised hosts, with urine culture growing E.coli and E.faecalis. Biopsy of the pancreatic lesion showed high grade LBCL; bone marrow was negative. She received IV fluids, appropriate antiobiotic therapy, and empiric vasopressor therapy to target higher mean arterial pressures but lactatemia persisted. "Tumor lysis labs" such as lactate dehydrogenase and uric acid were markedly elevated. She was intubated for impending respiratory failure and developed progressive multiorgan failure. Her family eventually decided to palliatively withdraw care and the patient expired. DISCUSSION: Lack of signficant tumor burden on imaging confused interpreting this patients refractory lactic acidosis. Autopsy revealed high grade lymphoma involving nearly all organs and vessels. Her lactic acidosis was likely due to a combination of factors including widespread tumor burden, high cell turnover (Fig.1), and tissue infarction by neoplastic thrombi (Fig. 2). CONCLUSIONS: Diagnosis of IVL is elusive and, unfortunately, often post mortem. Clincal presentaion can include rapidly progressive mutliorgan failure. It is important to recognize this high grade lymphoma as a potential cause of refractory lactic acidosis