Download Hypophosphatemia Masquerading as Meningitis

Hypophosphatemia Masquerading
as Meningitis
L W E S L E Y A L D R E D , M D ; M E L A N I E M C C A U L E Y, M D ;
J A S O N P I C K E T T; C O N N E L L K N I G H T;
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, butalbitalASA-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


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
References
 Maalouf NM, Heller HJ, Odvina CV, Kim PJ, Sakhaee K. Bisphosphonate-
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induced hypocalcemia: report of 3 cases and review of literature. Endocr
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Rosen CJ, Brown S. Severe hypocalcemia after intravenous
bisphosphonate therapy in occult vitamin D deficiency. N Engl J Med.
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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): 215-22.
Subramanian R, Khardori R. Severe hypophosphatemia. Pathophysiologic
implications, clinical presentations, and treatment. Medicine (Baltimore).
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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