Hypophosphatemia Masquerading as Meningitis L WESLEY ALDRED MD

Hypophosphatemia Masquerading as Meningitis L WESLEY ALDRED, MD; MELANIE MCCAULEY, MD; JASON PICKETT; CONNELL KNIGHT; MOHAMMAD ULLAH, MD UNIVERSITY OF MISSISSIPPI MEDICAL CENTER

Objectives �Review the causes of altered mental status �Illustrate the importance of revisiting your differential diagnosis in the face of treatment failure �Discuss how bisphonates contributed to this case �Examine the signs and symptoms of hypophosphatemia

History � 68 yo WF with RA and osteoporosis found unresponsive �Found with fentanyl patch in place �Some response to naloxone �Complained of HA and stated that “pirates attacked [her] ship” �Home medicines: fentanyl patch, alprazolam, butalbital. ASA-caffeine-codeine

Physical Exam �VS: T 99. 6, RR 22, BP 140/90, HR 105 �C-collar in place �Photophobia

Initial Differential Diagnosis �Meningitis �Drug overdose �Intracranial lesion �Electrolyte abnormalities

Investigations �WBC 21. 4 �UDS: +benzodiazepines, +opiates, +barbiturates �Acetaminophen <15 mcg/m. L, salicylate <1 mg/d. L, alcohol <10 mg/d. L �Na+ 130, K+ 2. 9, Ca++ 9. 3 �Urinalysis negative for UTI

Investigations

Investigations �Lumbar puncture attempted by two physicians but unsuccessful

Initial Differential Diagnosis �Meningitis SIRS+, CXR negative, UA normal �Drug overdose Acute drug overdose vs chronic polypharmacy �Intracranial lesion No large masses, no acute hemorrhage No focal deficits to suggest ischemic event �Electrolyte abnormalities Mild hyponatremia, hypokalemia Take note, no Mg or Ph at admission

Hospital Course �Admitted for sepsis secondary to meningitis �Started on ceftriaxone, vancomycin, and ampicillin �Hospital day 2: witnessed seizure activity, resolved with lorazepam �Hospital day 3: developed vertical nystagmus and remained confused

Hospital Course �Full electrolyte panel ordered given new nystagmus �K+ 2. 5 mmol/L, Ca++ 7. 7 mg/d. L, Mg 1. 6 mg/d. L, Ph 0. 6 mg/d. L �Follow-up PTH found to be 278. 3 pg/m. L �Replaced electrolytes hospital day 4: nystagmus and confusion resolved

Hospital Course �Blood cultures negative �Patient afebrile �WBC trending down �Hospital day 4: d/c antibiotics with continued improvement

Chart Review �IV infusion of zoledronic acid 3 days prior to admission

Discussion �Causes of altered mental status Meningitis � SIRS+, photophobia, CSF unable to be obtained Drug overdose � Fentanyl patch, benzodiazepines, barbiturates � Responded to naloxone CNS lesion � s/p fall; CT head negative for bleed � No focal deficits to suggest ischemic event Electrolyte abnormalities � Not investigated thoroughly enough at admission

Discussion �Pathogenesis of hypophosphatemia after zoledronic acid infusion Zoledronic acid dec Ca++ 2° hyper. PTH dec reabsorption of PO 4 in proximal tubule Decreased osteoclastic activity leads to decreased release of PO 4 from bone compartment into serum

Discussion �SIRS and hypophosphatemia Hypophosphatemia associated with cardiac arrhythmias Hypophosphatemia shown to decrease diaphragmatic strength Hypophosphatemia associated with leukocyte abnormalities

Discussion �Neurologic manifestations of hypophosphatemia Metabolic encephalopathy resulting from ATP depletion Mild irritability Paresthesia Generalized seizures Coma

When All Else Fails… �Blame the bisphonate

References � Maalouf NM, Heller HJ, Odvina CV, Kim PJ, Sakhaee K. Bisphonate- induced hypocalcemia: report of 3 cases and review of literature. Endocr Pract. 2006; 12 (1): 48 -53. � Rosen CJ, Brown S. Severe hypocalcemia after intravenous bisphonate therapy in occult vitamin D deficiency. N Engl J Med. 2003; 348 (15): 1503 -4. � Silvis SE, Di. Bartolomeo AG, Aaker HM. Hypophophatemia and neurological changes secondary to oral caloric intake: a variant of hyperalimentation syndrome. AM J Gastroenterol. 1980; 73 (3): 215 -22. � Subramanian R, Khardori R. Severe hypophosphatemia. Pathophysiologic implications, clinical presentations, and treatment. Medicine (Baltimore). 2000; 79 (1): 1 -8. � Kennel K, Drake M. Adverse effects of bisphonates: implications for osteoporosis management. Mayo Clinic Proc. Jul 2009; 85 (7): 632 -638. � Liamis G, Milionis HJ, Elisaf M. Medication-induced hypophosphatemia: a review. QJM. 2010; 103 (7): 449 -59