1. Hypophosphatemia Masquerading as Meningitis
L Wesley Aldred, MD; Melanie Mccauley, MD;
Jason Pickett; Connell Knight;
Mohammad Ullah, MD
University of Mississippi Medical Center

2. 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

3. 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

4. Physical Exam VS: T 99.6, RR 22, BP 140/90, HR 105 C-collar in place
Photophobia

5. Initial Differential Diagnosis
Meningitis
Drug overdose
Intracranial lesion
Electrolyte abnormalities

6. 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

7. Investigations

8. Investigations
Lumbar puncture attempted by two physicians but unsuccessful

9. 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

10. 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

11. Hospital Course Full electrolyte panel ordered given new nystagmus
K+ 2.5 mmol/L, Ca mg/dL, Mg 1.6 mg/dL, Ph 0.6 mg/dL
Follow-up PTH found to be pg/mL
Replaced electrolytes  hospital day 4: nystagmus and confusion resolved

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

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

14. 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

15. 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

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

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

18. When All Else Fails…
Blame the bisphosphonate

19. References
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Rosen CJ, Brown S. Severe hypocalcemia after intravenous bisphosphonate therapy in occult vitamin D deficiency. N Engl J Med. 2003; 348 (15):
Silvis SE, DiBartolomeo AG, Aaker HM. Hypophophatemia and neurological changes secondary to oral caloric intake: a variant of hyperalimentation syndrome. AM J Gastroenterol. 1980; 73 (3):
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 bisphosphonates: implications for osteoporosis management. Mayo Clinic Proc. Jul 2009; 85 (7):
Liamis G, Milionis HJ, Elisaf M. Medication-induced hypophosphatemia: a review. QJM. 2010; 103 (7):