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Cranial nerve deficit: A clue to the diagnosis of ethylene glycol poisoning
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CASE REPORTS
Cranial Nerve Deficit: A Clue to the Diagnosis of Ethylene Glycol Poisoning BIFF F. PALMER, M.D., EDWIN H. EIGENBRODT, M.D., WILLIAM L. HENRICH, M.D. Da//as,
T
he hallmarks of ethylene glycol toxicity include acute renal failure, an anion gap acidosis, and calcium oxalate crystalluria [l]. This following report describes two patients who lacked several of these hallmarks; in each case, the diagnoseswere delayed until unusual cranial nerve abnormalities occurred.
CASEREPORTS Patient 1 A 57-year-old white man wastransferred to the Dallas Veterans Administration with a four-day history of mild abdominal pain and anuria. Past medical history was significant for a femoral-femoral bypass. On examination the patient was alert, oriented, lucid, and appeared well. Vital signs were normal. Mild diffuse abdominal tenderness without rebound was noted. The following values were obtained during laboratory evaluation (mEq/L): sodium 138, potassium 4.2, chloride 100, and bicarbonate 22; the blood urea nitrogen level was 67 mg/dL, and the creatinine level was 12.5 mg/dL. Urinalysis revealed 300 mg/dL protein by dipstick, greater than 50 red blood cells per high-power field, occasional granular casts, and no crystals (X3). The hematocrit was 34.7%, and the white blood cell count was 9,800/mm3. Renal sonographic results were normal. Given persistent anuria, the history of peripheral vascular disease, and abdominal pain, a diagnosis of renal artery occlusion was entertained. Results of a renal arteriogram were completely normal. Hemodialysis was begun 10 days after the patient’s initial admission. On Day 11 of hospitalization, the patient was noted to be dysarthric and to have evidence of cranial nerve V, VII, and VIII abnormalities. Physical examination demonstrated drooping of the right side of the face and an inability to completely close the right eye. Decreasedsensation to pinprick was present on the right side of the face, and the patient was deaf bilaterally. Results of computerized tomographic examination of the brain were normal. Examination of the cerebrospinal fluid showed 51 to 70 white blood cells/mm3 (90% polymorphonuclear leukocytes), protein 198 mg/dL, and glucose 52 mg/dL. VDRL, cryptococcal antigen, and all microbial culture specimenswere negative. On the twelfth, day of hospitalization, the patient developed bilateral facial diplegia and sensory loss.The left cornea1 reflex was absent and a gag reflex could no longer be elicited. Nerve conduction studies confirmed the presence of bilateral peripheral VII nerve palsies. On Day 13, the patient’s sensorium decreased;by Day 14, frank coma was present, and the patient required From the University of Texas Southwestern Medical Center at Da?as. and Dallas Veterans Administration Medical Center, Dallas, Texas. Requests for reprints should be addressed to William L. Henrich, M.D., Dallas Veterans Administration Medical Center (11161). 4500 South Lancaster Road, Dallas, Texas 75216. Manuscript submitted February 3, 1989. and accepted in revised form March 22, 1989.
Texas
intubation. The patient died of a cardiac arrest on Day 22. At the onset of neurologic abnormalities (Day ll), a urinary ethylene glycol level had been obtained; this value was 196.3 mg/L (high-performance liquid chromatographic methodology). At the postmortem examination, diffuse calcium oxalate crystal deposition was noted within kidney parenchyma. Patient 2 A 53-year-old alcoholic white man was admitted to the Dallas Veterans Administration with four days of decreased urine output. He denied other complaints and specifically denied ingestion of any nephrotoxic agents. The patient was alert and oriented, and had no prior medical history other than alcohol consumption. On physical examination, he was a well-appearing man with normal vital signs. Results of the physical examination were entirely normal. Electrolyte levels were as follows (mEq/L): sodium 139, chloride 101, potassium 4.7, and bicarbonate 24; the blood urea nitrogen level was58 mg/dL, and the creatinine level was 4.7 mg/dL. Urinalysis showed no crystals, two to five white blood cells per high-power field, five to 10 red blood cells per high-power field, and 100 mg/dL protein; plasma methanol and ethylene glycol levels were negative. No osmolar gap was present. The results of sonographic testing were normal, and renal scintigraphy (diethylenetriamine per&acetic acid) showeddecreased but symmetric flow bilaterally. On the sixth day of hospitalization, hemodialysis was initiated. On Day 8, the patient developed complete deafnessbilaterally; vestibular function remained intact. On Day 12, ethylene glycol was detectable but not quantified in urine. The patient underwent hemodialysis for one year and then died of a cardiac arrest. The postmortem examination revealed a marked deposition of calcium oxalate crystals in the kidney (Figure 1). COMMENTS The differential diagnosis of anuric acute renal failure includes complete urinary obstruction, bilateral cortical necrosis, severe glomerulonephritis, and vascular occlusion of the renal arteries or veins [2]. Ethylene glycol poisoning presenting as anuric renal failure has been noted previously [3,4]. However, usually the diagnosis of ethylene glycol poisoning is suspected by the history or by findings of an anion gap acidosisand calcium oxalate crystals in the urinary sediment [l]. In the casespresented, the patients repeatedly denied ingestion of ethylene glycol and had normal anion gaps,while calcium oxalate crystals were absent in the urine. The clue to the diagnosisof ethylene glycol poisoning in these patients was the appearance of cranial nerve abnormalities days after presentation. Classically, ethylene glycol poisoning has been divided into three phases[3]: (1) intoxication occurs, ranging from stupor to frank coma (three to 12 hours after ingesJuly 1989 The American Journal of Medicine
Volume 87
91
ETHYLENE
GLVCOL
POISONING
/ PALMER
ET AL.
Figure 1. Renal cortex partially polarized to show numerous doubly refractile calcium oxalate crystals in renal tubules and interstitium (hematoxylin and eosin stain; original magnification X100, re~ duced by 25%).
tion); (2) cardiopulmonary failure may occur (within 72 hours); and (3) renal failure occurs, ranging from mild azotemia to frank anuria. There is considerable overlap in these phases. Isolated cranial nerve deficits are very unusual, with only three previous cases reporting facial paralysis occurring six to 15 days after ingestion [5-71. The diagnosis in Patient 1 was made by the demonstration of ethylene glycol in urine examined 11 days after the initial presentation. Detectable levels of ethylene glycol in urine are present for as long as 17 days after ingestion, whereas serum levels are generally undetectable by Day 5 [l]. This fact was illustrated in Patient 2, in whom a plasma sample for ethylene glycol was negative on Day 4 but a urine specimen was positive on Day 9. These cases serve to emphasize the variable presentations possible with ethylene glycol poisoning. Obviously, the lack of a history and absence of characteris-
92
July 1989
The American
Journal
of Medicine
Volume
87
tic clinical findings do not exclude the diagnosis. The development of neurologic abnormalities later in the clinical course is not generally appreciated. Finally, evaluation of the urine for ethylene glycol is useful for several weeks after ingestion.
REFERENCES 1. Parry MF. Wallach R: Ethylene glycol poisoning. Am J Med 1974; 57: 143-150. 2. Rudnick MR. Basti CP. Elfinbein IB. Narins RG: The differential diagnosis of acute renal failure. In: Brenner EM. Lazarus MJ, eds. Acute renal failure. Philadelphia: WE Saunders Co, 1983; 176-222. 3. Friedman EA. Greenberg JR Merrill JP. Dammin GJ: Consequences of ethylene glycol poisoning. Am J Med 1962; 32: 891-900. 4. Collins JM, Hennes DM, Holzgang CR, Gourley RT, Porter GA: Recovery after prolonged oliguria due to ethylene glycol intoxication. Arch Intern Med 1970; 25: 1059-1062. 5. Eierger JR, Ayyar DR: Neurological complicationsof ethylene glycol intoxication. Arch Neural 1981: 38: 724-726. 6. Fellman DM: Facial diplegia following ethylene glycol ingestion. Arch Neurol 1982: 39: 729-740 7. Mallya KB. Mendis T. Guberman A: Bilateral facial paralysis following ethylene glycol ingestion. Can J Neural Sci 1986; 13: 340-341.
CASE REPORTS
Cranial Nerve Deficit: A Clue to the Diagnosis of Ethylene Glycol Poisoning BIFF F. PALMER, M.D., EDWIN H. EIGENBRODT, M.D., WILLIAM L. HENRICH, M.D. Da//as,
T
he hallmarks of ethylene glycol toxicity include acute renal failure, an anion gap acidosis, and calcium oxalate crystalluria [l]. This following report describes two patients who lacked several of these hallmarks; in each case, the diagnoseswere delayed until unusual cranial nerve abnormalities occurred.
CASEREPORTS Patient 1 A 57-year-old white man wastransferred to the Dallas Veterans Administration with a four-day history of mild abdominal pain and anuria. Past medical history was significant for a femoral-femoral bypass. On examination the patient was alert, oriented, lucid, and appeared well. Vital signs were normal. Mild diffuse abdominal tenderness without rebound was noted. The following values were obtained during laboratory evaluation (mEq/L): sodium 138, potassium 4.2, chloride 100, and bicarbonate 22; the blood urea nitrogen level was 67 mg/dL, and the creatinine level was 12.5 mg/dL. Urinalysis revealed 300 mg/dL protein by dipstick, greater than 50 red blood cells per high-power field, occasional granular casts, and no crystals (X3). The hematocrit was 34.7%, and the white blood cell count was 9,800/mm3. Renal sonographic results were normal. Given persistent anuria, the history of peripheral vascular disease, and abdominal pain, a diagnosis of renal artery occlusion was entertained. Results of a renal arteriogram were completely normal. Hemodialysis was begun 10 days after the patient’s initial admission. On Day 11 of hospitalization, the patient was noted to be dysarthric and to have evidence of cranial nerve V, VII, and VIII abnormalities. Physical examination demonstrated drooping of the right side of the face and an inability to completely close the right eye. Decreasedsensation to pinprick was present on the right side of the face, and the patient was deaf bilaterally. Results of computerized tomographic examination of the brain were normal. Examination of the cerebrospinal fluid showed 51 to 70 white blood cells/mm3 (90% polymorphonuclear leukocytes), protein 198 mg/dL, and glucose 52 mg/dL. VDRL, cryptococcal antigen, and all microbial culture specimenswere negative. On the twelfth, day of hospitalization, the patient developed bilateral facial diplegia and sensory loss.The left cornea1 reflex was absent and a gag reflex could no longer be elicited. Nerve conduction studies confirmed the presence of bilateral peripheral VII nerve palsies. On Day 13, the patient’s sensorium decreased;by Day 14, frank coma was present, and the patient required From the University of Texas Southwestern Medical Center at Da?as. and Dallas Veterans Administration Medical Center, Dallas, Texas. Requests for reprints should be addressed to William L. Henrich, M.D., Dallas Veterans Administration Medical Center (11161). 4500 South Lancaster Road, Dallas, Texas 75216. Manuscript submitted February 3, 1989. and accepted in revised form March 22, 1989.
Texas
intubation. The patient died of a cardiac arrest on Day 22. At the onset of neurologic abnormalities (Day ll), a urinary ethylene glycol level had been obtained; this value was 196.3 mg/L (high-performance liquid chromatographic methodology). At the postmortem examination, diffuse calcium oxalate crystal deposition was noted within kidney parenchyma. Patient 2 A 53-year-old alcoholic white man was admitted to the Dallas Veterans Administration with four days of decreased urine output. He denied other complaints and specifically denied ingestion of any nephrotoxic agents. The patient was alert and oriented, and had no prior medical history other than alcohol consumption. On physical examination, he was a well-appearing man with normal vital signs. Results of the physical examination were entirely normal. Electrolyte levels were as follows (mEq/L): sodium 139, chloride 101, potassium 4.7, and bicarbonate 24; the blood urea nitrogen level was58 mg/dL, and the creatinine level was 4.7 mg/dL. Urinalysis showed no crystals, two to five white blood cells per high-power field, five to 10 red blood cells per high-power field, and 100 mg/dL protein; plasma methanol and ethylene glycol levels were negative. No osmolar gap was present. The results of sonographic testing were normal, and renal scintigraphy (diethylenetriamine per&acetic acid) showeddecreased but symmetric flow bilaterally. On the sixth day of hospitalization, hemodialysis was initiated. On Day 8, the patient developed complete deafnessbilaterally; vestibular function remained intact. On Day 12, ethylene glycol was detectable but not quantified in urine. The patient underwent hemodialysis for one year and then died of a cardiac arrest. The postmortem examination revealed a marked deposition of calcium oxalate crystals in the kidney (Figure 1). COMMENTS The differential diagnosis of anuric acute renal failure includes complete urinary obstruction, bilateral cortical necrosis, severe glomerulonephritis, and vascular occlusion of the renal arteries or veins [2]. Ethylene glycol poisoning presenting as anuric renal failure has been noted previously [3,4]. However, usually the diagnosis of ethylene glycol poisoning is suspected by the history or by findings of an anion gap acidosisand calcium oxalate crystals in the urinary sediment [l]. In the casespresented, the patients repeatedly denied ingestion of ethylene glycol and had normal anion gaps,while calcium oxalate crystals were absent in the urine. The clue to the diagnosisof ethylene glycol poisoning in these patients was the appearance of cranial nerve abnormalities days after presentation. Classically, ethylene glycol poisoning has been divided into three phases[3]: (1) intoxication occurs, ranging from stupor to frank coma (three to 12 hours after ingesJuly 1989 The American Journal of Medicine
Volume 87
91
ETHYLENE
GLVCOL
POISONING
/ PALMER
ET AL.
Figure 1. Renal cortex partially polarized to show numerous doubly refractile calcium oxalate crystals in renal tubules and interstitium (hematoxylin and eosin stain; original magnification X100, re~ duced by 25%).
tion); (2) cardiopulmonary failure may occur (within 72 hours); and (3) renal failure occurs, ranging from mild azotemia to frank anuria. There is considerable overlap in these phases. Isolated cranial nerve deficits are very unusual, with only three previous cases reporting facial paralysis occurring six to 15 days after ingestion [5-71. The diagnosis in Patient 1 was made by the demonstration of ethylene glycol in urine examined 11 days after the initial presentation. Detectable levels of ethylene glycol in urine are present for as long as 17 days after ingestion, whereas serum levels are generally undetectable by Day 5 [l]. This fact was illustrated in Patient 2, in whom a plasma sample for ethylene glycol was negative on Day 4 but a urine specimen was positive on Day 9. These cases serve to emphasize the variable presentations possible with ethylene glycol poisoning. Obviously, the lack of a history and absence of characteris-
92
July 1989
The American
Journal
of Medicine
Volume
87
tic clinical findings do not exclude the diagnosis. The development of neurologic abnormalities later in the clinical course is not generally appreciated. Finally, evaluation of the urine for ethylene glycol is useful for several weeks after ingestion.
REFERENCES 1. Parry MF. Wallach R: Ethylene glycol poisoning. Am J Med 1974; 57: 143-150. 2. Rudnick MR. Basti CP. Elfinbein IB. Narins RG: The differential diagnosis of acute renal failure. In: Brenner EM. Lazarus MJ, eds. Acute renal failure. Philadelphia: WE Saunders Co, 1983; 176-222. 3. Friedman EA. Greenberg JR Merrill JP. Dammin GJ: Consequences of ethylene glycol poisoning. Am J Med 1962; 32: 891-900. 4. Collins JM, Hennes DM, Holzgang CR, Gourley RT, Porter GA: Recovery after prolonged oliguria due to ethylene glycol intoxication. Arch Intern Med 1970; 25: 1059-1062. 5. Eierger JR, Ayyar DR: Neurological complicationsof ethylene glycol intoxication. Arch Neural 1981: 38: 724-726. 6. Fellman DM: Facial diplegia following ethylene glycol ingestion. Arch Neurol 1982: 39: 729-740 7. Mallya KB. Mendis T. Guberman A: Bilateral facial paralysis following ethylene glycol ingestion. Can J Neural Sci 1986; 13: 340-341.