Amiodarone-Induced Syndrome of Inappropriate Antidiuretic Hormone: A Case Report and Review of the Literature.

Amiodarone (Cordarone®, Pfizer Inc) is an antiarrhythmic medication with a well-known toxicity profile, including rare cases of hyponatremia as a result of syndrome of inappropriate antidiuretic hormone (SIADH). We report on such a case in which a patient was found to be hyponatremic after evaluation. An 88-year-old male who presented to the emergency department was found to be hyponatremic secondary to amiodarone-induced SIADH following a fall, with possible seizure and traumatic brain injury. He had a history of hypertension, paroxysmal atrial fibrillation, emphysema, myocardial infarction, benign prostatic hyperplasia, chronic kidney disease, Meniere's disease, anemia, and gastroesophageal reflux. Upon admission, his urine sodium level was elevated, and his serum sodium, urine osmolality, and anion gap were below normal. In the setting of hyponatremia, the patient's amiodarone was held: he had been taking amiodarone 200 mg once daily for nine months prior to admission. He was treated with intravenous (IV) normal saline over four days. He was fluid-restricted and his sodium levels were closely monitored every two hours. Within 19 hours, his serum sodium levels had improved. Amiodarone was restarted approximately three days later. Upon follow-up after discharge, the patient remained on amiodarone for the next two months. His serum sodium level ranged from 126 mEq/L to 131 mEq/L over a two-week period. He was supplemented with sodium chloride tablets and has been otherwise stable. Amiodarone may cause acute or chronic SIADH, with a wide range of symptoms. Seizures have not been reported in the literature but our patient had a witnessed seizure, although his electroencephalogram (EEG) was negative. Syndrome of inappropriate antidiuretic hormone can occur with any formulation of amiodarone in a dose-dependent fashion. Our patient's sodium levels stabilized within two weeks after amiodarone was resumed. The mechanism of amiodarone-induced SIADH remains unclear.

Association of Neighborhood Socioeconomic Status With Withdrawal of Life-Sustaining Therapies After Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: Mortality after intracerebral hemorrhage (ICH) is common. Neighborhood socioeconomic status (nSES) is an important social determinant of health (SDoH) that can affect clinical outcome. We hypothesize that SDoH, including nSES, contribute to differences in withdrawal of life-sustaining therapies (WLSTs) and mortality in patients with ICH. METHODS: We performed a retrospective study of patients with ICH at 3 tertiary care hospitals between January 2017 and December 2022 identified through the Get with the Guidelines Database. We collected data on age, clinical severity, race/ethnicity, median household income, insurance, marital status, religion, mortality before discharge, and WLST from the electronic medical record. We assessed for associations between SDoH and WLST, mortality, and poor discharge mRS using Mann-Whitney U tests and χ2 tests. We performed multivariable analysis using backward stepwise logistic regression. RESULTS: We identified 868 patients (median age 67 [interquartile range (IQR) 55-78] years; 43% female) with ICH. Of them, 16% were Black non-Hispanic, 17% were Asian, and 15% were of Hispanic ethnicity; 50% were on Medicare and 22% on Medicaid, and the median (IQR) household income was $81,857 ($58,669-$122,078). Mortality occurred in 17% of patients, and of them, 84% of patients had WLST. Patients from zip codes with higher median household incomes had higher incidence of WLST and mortality (p < 0.01). Black non-Hispanic race was associated with lower WLST and discharge mortality (p ≤ 0.01 for both). In multivariable analysis adjusting for age and clinical severity scores, patients who lived in zip codes with high-income levels were more likely to have WLST (adjusted odds ratio [aOR] 1.88; 95% CI 1.29-2.74) and mortality before discharge (aOR 1.5; 95% CI 1.06-2.13). DISCUSSION: SDoH, including nSES, are associated with WLST after ICH. This has important implications for the care and management of patients with ICH.

Progressive multifocal leukoencephalopathy in transplant recipients.

OBJECTIVE: Transplant recipients are at risk of developing progressive multifocal leukoencephalopathy (PML), a rare demyelinating disorder caused by oligodendrocyte destruction by JC virus. METHODS: Reports of PML following transplantation were found using PubMed Entrez (1958-July 2010). A multicenter, retrospective cohort study also identified all cases of PML among transplant recipients diagnosed at Mayo Clinic, Johns Hopkins University, Washington University, and Amsterdam Academic Medical Center. At 1 institution, the incidence of posttransplantation PML was calculated. RESULTS: A total of 69 cases (44 solid organ, 25 bone marrow) of posttransplantation PML were found including 15 from the 4 medical centers and another 54 from the literature. The median time to development of first symptoms of PML following transplantation was longer in solid organ vs bone marrow recipients (27 vs 11 months, p = 0.0005, range of <1 to >240). Median survival following symptom onset was 6.4 months in solid organ vs 19.5 months in bone marrow recipients (p = 0.068). Case fatality was 84% (95% confidence interval [CI], 70.3-92.4%) and survival beyond 1 year was 55.7% (95% CI, 41.2-67.2%). The incidence of PML among heart and/or lung transplant recipients at 1 institution was 1.24 per 1,000 posttransplantation person-years (95% CI, 0.25-3.61). No clear association was found with any 1 immunosuppressant agent. No treatment provided demonstrable therapeutic benefit. INTERPRETATION: The risk of PML exists throughout the posttransplantation period. Bone marrow recipients survive longer than solid organ recipients but may have a lower median time to first symptoms of PML. Posttransplantation PML has a higher case fatality and may have a higher incidence than reported in human immunodeficiency virus (HIV) patients on highly-active antiretroviral therapy (HAART) or multiple sclerosis patients treated with natalizumab.

The challenges with brain death determination in adult patients on extracorporeal membrane oxygenation.

BACKGROUND: To identify a reliable method of performing apnea testing as part of brain death determination in adult patients who develop loss of brainstem reflexes while receiving extracorporeal membrane oxygenation (ECMO). ECMO provides extracirculatory support to patients in cardiorespiratory failure who would otherwise be expected to die. Many studies have reported brain death as a potential complication of adult ECMO, but none have cited how apnea testing was performed in these patients. METHODS: This retrospective review identified adults 15 years or older treated with ECMO at our institution (2002-2010) and the method of determination of brain death when complete loss of brainstem reflexes occurred. RESULTS: Loss of all brainstem reflexes was identified in three cases (3/87, 3.4%). The apnea test was not performed since it was deemed "difficult," leading to withdrawal of ECMO and intensive care. Ancillary tests such as cerebral flow studies were not used because they may not document absent cerebral arterial flow due to the ischemic nature of the injury. We propose the use of an oxygenated apnea test on ECMO using continuous positive airway pressure (CPAP) through the ventilator or anesthesia bag, with an inline manometer and an end tidal CO(2) device. CONCLUSION: Apnea testing is essential in the determination of brain death, but may not be employed in ECMO-treated adult patients. Apnea testing using the above protocol may assist in better decision making for adult ECMO patients at risk of brain death.

Erythropoietin-Associated Posterior Reversible Encephalopathy Syndrome.

INTRODUCTION: This case demonstrates an underrecognized cause of posterior reversible encephalopathy syndrome (PRES). CASE REPORT: We report a 51-year-old male with a history of essential hypertension without preexisting renal impairment who presented with 3 days of occipital headache and convulsive status epilepticus in the setting of refractory hypertension. He had been receiving outpatient human recombinant erythropoietin injections for virally mediated bone marrow suppression, which worsened his baseline hypertension. Magnetic resosnance imaging (MRI) of the brain on admission showed diffuse bilateral, symmetric signal hyperintensities and patchy enhancement involving the cortex and white matter in both cerebral hemispheres. His blood pressure and seizures were successfully treated during hospital admission, with complete resolution of his neurological deficits. MRI brain performed 6 weeks from initial scan showed normalization of his prior findings. CONCLUSION: Recombinant human erythropoietin (RhEPO) may be an underrecognized cause of PRES and should be considered in patients receiving this treatment regardless of the absence or presence of renal impairment. RhEPO-mediated precipitation/exacerbation of hypertension, alterations in cerebral blood flow, and changes in endothelial integrity may underlie this association. MRI signal changes are reversible and typical for that of PRES, and significant improvement of symptoms can be expected.

Identification of a Novel Natriuretic Protein in Patients With Cerebral-Renal Salt Wasting-Implications for Enhanced Diagnosis.

BACKGROUND: The most vexing problem in hyponatremic conditions is to differentiate the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from cerebral/renal salt wasting (C-RSW). Both have identical clinical parameters but diametrically opposite therapeutic goals of water- restricting water-logged patients with SIADH or administering salt and water to dehydrated patients with C-RSW. While C-RSW is considered a rare condition, the report of a high prevalence of C-RSW in the general hospital wards creates an urgency to differentiate one syndrome from the other on first encounter. We decided to identify the natriuretic factor (NF) we previously demonstrated in plasma of neurosurgical and Alzheimer diseases (AD) who had findings consistent with C-RSW. METHODS: We performed the same rat renal clearance studies to determine natriuretic activity (NA) in serum from a patient with a subarachnoid hemorrhage (SAH) and another with AD and demonstrated NA in their sera. The sera were subjected to proteomic and SWATH (Sequential Windowed Acquisition of All) analyses which identified increased levels of haptoglobin related protein (Hpr) without signal peptide (Hpr-WSP). RESULTS: Recombinant Hpr with His tag at the N terminus had no NA. Hpr-WSP had a robust NA in a dose-dependent manner when injected into rats. Serum after recovery from C-RSW in the SAH patient had no NA. CONCLUSIONS: Hpr-WSP may be the NF in C-RSW which should be developed as a biomarker to differentiate C-RSW from SIADH on first encounter, introduces a new syndrome of C-RSW in AD and can serve as a proximal diuretic to treat congestive heart failure.

External ventricular drains: Management and complications.

BACKGROUND: Insertion of an External Ventricular Drain (EVD) is arguably one of the most common and important lifesaving procedures in neurologic intensive care unit. Various forms of acute brain injury benefit from the continuous intracranial pressure (ICP) monitoring and cerebrospinal fluid (CSF) diversion provided by an EVD. After insertion, EVD monitoring, maintenance and troubleshooting essentially become a nursing responsibility. METHODS: Articles pertaining to EVD placement, management, and complications were identified from PubMed electronic database. RESULTS: Typically placed at the bedside by a neurosurgeon or neurointensivist using surface landmarks under emergent conditions, this procedure has the ability to drain blood and CSF to mitigate intracranial hypertension, continuously monitor intracranial pressure, and instill medications. Nursing should ensure proper zeroing, placement, sterility, and integrity of the EVD collecting system. ICP waveform analysis and close monitoring of CSF drainage are extremely important and can affect clinical outcomes of patients. In some institutions, nursing may also be responsible for CSF sampling and catheter irrigation. CONCLUSION: Maintenance, troubleshooting, and monitoring for EVD associated complications has essentially become a nursing responsibility. Accurate and accountable nursing care may have the ability to portend better outcomes in patients requiring CSF drainage.

Posterior reversible encephalopathy syndrome is not associated with mutations in aquaporin-4.

Posterior reversible encephalopathy syndrome (PRES) is characterized by acute reversible subcortical vasogenic edema that is typically bilateral and self-limiting. It preferentially affects posterior regions of the brain. Clinical manifestations include encephalopathy, seizures, headache, and cortical blindness. PRES may be precipitated by hypertensive crises such as eclampsia and by immunosuppressive agents. The pathophysiology of PRES is incompletely understood. Disordered cerebral autoregulation leading to protein and fluid extravasation is thought to be important.(1) Other theories implicate endothelial dysfunction or vasospasm.(2).

Worldwide reported use of IV tissue plasminogen activator for acute ischemic stroke.

BACKGROUND AND PURPOSE: Intravenous tissue plasminogen activator is the most effective treatment for acute ischemic stroke, and its use may therefore serve as an indicator of the available level of acute stroke care. The greatest burden of stroke is in low- and middle-income countries, but the extent to which intravenous tissue plasminogen activator is used in these countries is unreported. SUMMARY OF REVIEW: A systematic review was performed searching each country name AND 'stroke' OR 'tissue plasminogen activator' OR 'thrombolysis' using PubMed, Embase, Global Health, African Index Medicus, and abstracts published in the International Journal of Stroke (Jan. 1, 1996-Oct. 1, 2012). The reported use of intravenous tissue plasminogen activator was then analyzed according to country-level income status, total expenditure on health per capita, and mortality and disability-adjusted life years due to stroke. There were 118,780 citations reviewed. Of 214 countries and independent territories, 64 (30%) reported use of intravenous tissue plasminogen activator for acute ischemic stroke in the medical literature: 3% (1/36) low-income, 19% (10/54) lower-middle-income, 33% (18/54) upper-middle-income, and 50% (35/70) high-income-countries (test for trend, P < 0.001). When considering country-level determinants of reported intravenous tissue plasminogen activator use for acute ischemic stroke, total healthcare expenditure per capita (odds ratio 3.3 per 1000 international dollar increase, 95% confidence interval 1.4-9.9, P = 0.02) and reported mortality rate from cerebrovascular disease (odds ratio 1.02, 95% confidence interval 0.99-1.06, P = 0.02) were significant, but reported disability-adjusted life years from cerebrovascular diseases and gross national income per capita were not (P > 0.05). Of the 10 countries with the highest disability-adjusted life years due to stroke, only one reported intravenous tissue plasminogen activator use. CONCLUSIONS: By reported use, intravenous tissue plasminogen activator for acute ischemic stroke is available to some patients in approximately one-third of countries. Access to advanced acute stroke care is most limited where the greatest burden of cerebrovascular disease is reported.

Prognostic value of clinical and radiological signs in the postoperative outcome of spinal dural arteriovenous fistula.

STUDY DESIGN: Retrospective consecutive case series. OBJECTIVE: To determine predictors of outcome in patients undergoing surgical treatment of spinal dural arteriovenous fistula (SDAVF). SUMMARY OF BACKGROUND DATA: Most previous studies assessing postoperative outcome in patients with SDAVF have been limited due to small population size, lack of sufficient information on presurgical variables, or short time of postoperative follow-up. Consequently, the most reliable predictors of functional outcome after treatment of SDAVF are not yet well established. METHODS: Retrospective analysis of consecutive patients with SDAVF treated surgically between June 1985 and March 2008 in our institution. The Aminoff-Logue gait (G) and micturition (M) scores were used to stratify the degree of disability and the G + M score was used as the primary outcome measure. Demographics, clinical presentation, time to diagnosis, fistula level, presurgical motor and sphincter impairment, and magnetic resonance imaging findings were assessed as prognosticators for postoperative outcomes. RESULTS: One hundred fifty-three patients were analyzed. Mean follow-up was 31 ± 36.2 months. Most patients were improved (44%) or stable (34%) upon the last follow-up. Among preoperative variables, worsening weakness with exertion was associated with a better G + M score at the last follow-up (P < 0.001) and presence of pinprick level was associated with a worse G + M score at the last follow-up (P = 0.020). On multivariable analysis, worsening weakness with exertion was associated with better outcome at the last follow-up, and higher G score at presentation and higher G + M score at discharge were associated with worse outcome at the last follow-up. Magnetic resonance images obtained postoperatively for 104 patients (mean, 19.1 ± 22.5 mo) showed complete resolution or improvement of the presurgical T2 signal abnormalities in 83.6% of cases. Changes in postoperative magnetic resonance image and fistula level did not correlate with functional outcomes. CONCLUSION: The degree of preoperative disability from SDAFV does not determine who will benefit most from surgery and even patients with severe deficits can improve after treatment. Patients with preoperative exertional claudication and without pinprick level on examination have greater chances of postsurgical improvement. LEVEL OF EVIDENCE: 4.

Cervicomedullary injury after pneumococcal meningitis with brain edema.

OBJECTIVES: To demonstrate a rare but potential mechanism of quadriplegia in a patient with fulminant pneumococcal meningitis complicated by severe intracranial hypertension. DESIGN: Case report. SETTING: Intensive care unit. PATIENT: A 21-year-old man who presented with 3 days of headache, combativeness, and fever. INTERVENTION: Antibiotics and steroids were initiated after lumbar puncture yielded purulent cerebrospinal fluid and streptococcus pneumoniae. RESULTS: The patient's course was complicated by severe cerebral edema necessitating intracranial pressure monitoring and intracranial pressure-targeted therapy. Within 5 days he developed quadriplegia and areflexia. Brain and cervical spine magnetic resonance imaging revealed patchy areas of T2 signal hyperintensity with associated gadolinium enhancement in the superior cervical spinal cord, cerebellar tonsils, and medulla. CONCLUSIONS: Quadriplegia secondary to tonsillar herniation in fulminant meningitis is rare but should be considered in patients with acute quadriparesis after treatment of increased intracranial pressure. Magnetic resonance imaging signal changes and gadolinium enhancement may be demonstrated. Significant improvement of cord symptoms can be expected.

The clinical and radiological presentation of spinal dural arteriovenous fistula.

STUDY DESIGN: Retrospective consecutive case series. OBJECTIVE: To assess the symptoms, neurologic signs, and radiologic findings in a large series of patients with myelopathy due to spinal dural arteriovenous fistula (SDAVF). SUMMARY OF BACKGROUND: The clinical diagnosis of SDAVF is difficult because presenting symptoms and signs can be similar to those seen with spinal canal stenosis or peripheral nerve or root disorders. METHODS: We reviewed 153 consecutive patients with SDAVF treated surgically at our institution between 1985 and 2008. Before surgery, all patients had detailed neurologic examination, 147 patients had spinal magnetic resonance imaging (MRI) and all but one, had spinal angiography. We evaluated associations between symptoms, physical signs, spinal cord T2 signal abnormality on MRI, and fistula level on angiogram. RESULTS: Mean age was 63.5 years and 119 (77.8%) were men. Weakness and sensory changes are usually symmetric and ascend from the lower extremities. Presenting symptoms included leg weakness (74 patients, 48.4%), leg sensory disturbances (41 patients, 26.8%), pain involving back or legs (31 patients, 20.3%), and sphincter disturbances (6 patients, 3.9%). Worsening weakness with exertion was present in 66 (43.1%) patients and correlated with thoracic fistula location (P=0.04). Pinprick level was identified in 57 (37.3%) patients; L1 level (22.8%) was the most common, followed by T10 (19.3%). Fistula level (±2 levels) corresponded to pinprick level in only 40% of these patients. T2 signal abnormality involved the conus in 95% of our patients. Highest cord level of T2 signal hyperintensity (±2 levels) corresponded to pinprick level in 25% of cases. CONCLUSION: Leg weakness exacerbated by exercise, likely due to worsening hypertension in the arterialized draining vein, is a common manifestation of thoracic SDAVF. Although a sensory level is often found, it cannot reliably guide the level of imaging. Thus, the entire spine should be examined with MRI when an SDAVF is suspected.

Neurological injury in adults treated with extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) may be urgently used as a last resort form of life support when all other treatment options for potentially reversible cardiopulmonary injury have failed. OBJECTIVE: To examine the range and frequency of neurological injury in ECMO-treated adults. DESIGN: Retrospective clinicopathological cohort study. SETTING: Mayo Clinic, Rochester, Minnesota. PATIENTS: A prospectively collected registry of all patients 15 years or older treated with ECMO for 12 or more hours from January 2002 to April 2010. INTERVENTION: Patients were analyzed for potential risk factors for neurological events and death using logistic regression and Cox proportional hazards models. MAIN OUTCOME MEASURES: Neurological diagnosis and/or death. RESULTS: A total of 87 adults were treated (35 female [40%]; median age, 54 years [interquartile range, 31]; mean duration of ECMO, 91 hours [interquartile range, 100]; overall survival >7 days after ECMO, 52%). Neurological events occurred in 42 patients who received ECMO (50%; 95% confidence interval [CI], 39%-61%). Diagnoses included subarachnoid hemorrhage, ischemic watershed infarctions, hypoxic-ischemic encephalopathy, unexplained coma, and brain death. Death in patients who received ECMO who did not require antecedent cardiopulmonary resuscitation was associated with increased age (odds ratio, 1.24 per decade; 95% CI, 1.03-1.50; P = .02) and lower minimum arterial oxygen pressure (odds ratio, 0.79; 95% CI, 0.68-0.92; P = .03). Although stroke was rarely diagnosed clinically, 9 of 10 brains studied at autopsy demonstrated hypoxic-ischemic and hemorrhagic lesions of vascular origin. CONCLUSION: Severe neurological sequelae occur frequently in adult ECMO-treated patients with otherwise reversible cardiopulmonary injury (conservative estimate, 50%) and include a range of potentially fatal neurological diagnoses that may be due to the precipitating event and/or ECMO treatment.