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Erythropoietin-Associated Posterior Reversible Encephalopathy Syndrome

White, Jessica Daley; Anne, Madhurima; Muralidharan, Rajanandini
INTRODUCTION/BACKGROUND:This case demonstrates an underrecognized cause of posterior reversible encephalopathy syndrome (PRES). CASE REPORT/METHODS: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/CONCLUSIONS: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.
PMID: 33942791
ISSN: 2331-2637
CID: 4866202

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

Maesaka, John K; Imbriano, Louis J; Pinkhasov, Aaron; Muralidharan, Rajanandini; Song, Xiaomin; Russo, Leileata M; Comper, Wayne D
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.
PMID: 33526214
ISSN: 1538-2990
CID: 4776002

Efficacy of modafinil, methylphenidate, amantadine, and zolpidem in consciousness recovery in intensive care unit patients with traumatic brain injury

Oommen, Jomi K.; Wang, Shan; Axelrad, Alexander; Hanna, Adel; Muralidharan, Rajanandini; Osias, Jules; Fazzari, Melissa; Ali, Fahd
OBJECTIVE: Traumatic brain injury (TBI) is the most common cause of death and disability in persons between 15 and 30 years of age. Although various pharmacological agents have been reported to enhance consciousness recovery, few trials have studied these medications in patients with acute TBI. The objective of this study was to determine the effect of modafinil, methylphenidate, amantadine, and zolpidem in improving wakefulness in patients with TBI in an intensive care unit (ICU) setting and to identify any adverse drug reactions. METHODS: Retrospective chart review identified all patients prescribed modafinil, methylphenidate, amantadine, or zolpidem; only patients older than 18 years with TBI in an ICU setting were further analyzed. The electronic medical record was used to retrieve clinical data including patient demographics, mechanism of TBI, drug dosage, treatment duration, Glasgow Coma Scale (GCS) score, length of time to improve GCS score, hospital length of stay, reported adverse drug reactions associated with above medications, and mortality. The primary outcome was the rate of positive response in the clinical neurological exam. Secondary outcomes included change in baseline and final GCS score, time to response, duration of treatment, change in GCS score over time, length of hospital stay, and in-hospital mortality. Descriptive statistics were used to analyze the data. RESULTS: The final analysis included a total of 53 patients. Median ages ranged from 44.0 to 61.5 years; 85% of patients were male. Baseline median GCS score was 8.0 in the amantadine group; 6.5, modafinil; 7.5, methylphenidate; and 7.0, zolpidem. The highest positive response rate was 90% in the amantadine group, followed by modafinil, 77%; methylphenidate, 50%; and zolpidem, 36%. The change in baseline GCS score and median final GCS score for amantadine, modafinil, methylphenidate, and zolpidem was 2.5, 3.0, 1.0, and 0, respectively (P = 0.20). The median time to response in days was 1.5, 1.0, 0.5, and 1.0, respectively. Change in GCS score over time for amantadine, modafinil, methylphenidate, and zolpidem was 0.16, 0.38, 0.12, and 0, respectively. Though rare, the most common adverse events were agitation, hypertension, and posturing. CONCLUSION: It remains to be determined if these medications have a role in reducing ICU and hospital length of stay, length of mechanical ventilation, tracheostomies, and overall medical costs in managing TBI patients. In our study amantadine was associated with the highest overall positive response rate when used as an awakening agent in TBI. Modafinil was associated with the largest change in GCS score over time.
ISSN: 1052-1372
CID: 4332642

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

Marcelino, Gretchen P; Collantes, Cyril Manuel C; Oommen, Jomi K; Wang, Shan; Baldassari, Heather; Muralidharan, Rajanandini; Hanna, Adel
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.
PMID: 31258313
ISSN: 1052-1372
CID: 4090242


Oommen, Jomi; Wang, Shan; Axelrad, Alexander; Hanna, Adel; Muralidharan, RajaNandini; Osias, Jules; Fazzari, Melissa; Ali, Fahd
ISSN: 0090-3493
CID: 4227782


Lien-Khuong Tran; Muralidharan, RajaNandini; Singhal, Ravish; Salama, Salama
ISSN: 0090-3493
CID: 3535312

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

Matiello, Marcelo; Muralidharan, Rajanandini; Sun, David; Rabinstein, Alejandro A; Weinshenker, Brian G
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).
PMID: 27066556
ISSN: 2376-7839
CID: 3535132

External ventricular drains: Management and complications

Muralidharan, Rajanandini
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/CONCLUSIONS: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.
PMID: 26069848
ISSN: 2229-5097
CID: 3535122

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

Berkowitz, Aaron L; Mittal, Manoj K; McLane, Hannah C; Shen, Gordon C; Muralidharan, Rajanandini; Lyons, Jennifer L; Shinohara, Russell T; Shuaib, Ashfaq; Mateen, Farrah J
BACKGROUND AND PURPOSE/OBJECTIVE: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/RESULTS: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.
PMID: 24207029
ISSN: 1747-4949
CID: 3535112

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

Muralidharan, Rajanandini; Mandrekar, Jay; Lanzino, Giuseppe; Atkinson, John L; Rabinstein, Alejandro A
STUDY DESIGN/METHODS: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/BACKGROUND: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/CONCLUSIONS: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/METHODS:4.
PMID: 23392413
ISSN: 1528-1159
CID: 3535102