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 bisphosphonates 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/mL, salicylate <1 mg/dL, alcohol <10 mg/dL 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/dL, Mg 1.6 mg/dL, Ph 0.6 mg/dL Follow-up PTH found to be 278.3 pg/mL 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 Drug overdose 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° hyperPTH  dec reabsorption of PO4 in proximal tubule Decreased osteoclastic activity leads to decreased release of PO4 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 bisphosphonate

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