Hypernatremic
Hemorrhagic
Encephalopathy
Richard S. K. Young, MD, MPH,
and Bradley T. Truax, M D
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A 12-year-old juvenile diabetic was inadvertently
given 5 0 0 ml of hypertonic saline intravenously. He
developed hypernatremia, hyperosmolality, metabolic
acidosis, and hyperglycemia. Seizures and stupor ensued, followed by coma and death. Computerized cranial tomography revealed numerous small subcortical
hemorrhages that were verified postmortem.
Young RSK, Truax BT: Hypernatremic
hemorrhagic encephalopathy .
Ann Neurol 5:588-591, 1979

Hypernatremia resulting from excessive solute administration is not uncommon in pediatric practice
and may be due to parenteral administration of
hypertonic saline or from improper preparation of
infant formulas [4]. Neurological complications
range from irritability and convulsions to stupor and
coma. The present case was remarkable because of
numerous subcortical hemorrhages documented
antemortem by computerized cranial tomography.

Generalized seizures again developed and he was treated
with phenobarbital.
O n transfer to the Massachusetts General Hospital at 24
hours the blood pressure was 94/48. He was acidotic ( p H
7.06), ketotic (acetone 1: I 6 dilutions), hypernatremic
(sodium 173), hyperglycemic (glucose 635), and hyperosmolar (398 mOsm per liter). Despite aggressive management with constant insulin infusion (up to 28 units per
hour), antibiotics, and fluid therapy with 0.9"; saline and
albumin, he continued to deteriorate.
Neurological examination at 36 hours revealed that he
was flaccid with no spontaneous movements except for
shallow respirations. An electroencephalogram showed
generalized delta slowing. Sixty hours after initial presentation severe hypotension developed. Large volumes of
dilute urine were formed (300 ml per hour), and he was
treated for diabetes insipidus. At 72 hours he had no
spontaneous respirations.
A CT scan (Fig 1 ) showed numerous small hemorrhages
scattered throughout the subcortical white matter. An inrracranial monitoring device showed normal intracranial
pressure (8 mm Hg). At 96 hours no neurological activity
was demonstrable by examination or EEG.

Neu ropathological Findings
The fresh brain weighed 1,600 gm and was diffusely
edematous. Bilateral uncal herniations were visible. The
dural sinuses were patent, and the epidural and subdural
spaces were free of blood. The most prominent finding was

F i g I . Cranial tomographic scan Jhozcfing numeroiis jiihcortira/ heniorrhages.

A 12-year-old juvenile diabetic developed an abscess at an
injection site. O n admission to an outlying hospital, he was
lethargic and febrile (38.2"C). Serum electrolytes were:
sodium, 1 3 5 ; potassium, 3.1; chloride, 105; and carbon
dioxide, 1 5 mEq per liter, and the blood glucose was 321
mgldl.
He was first treated with 20 units of regular insulin and
500 ml of 0.9% saline. He then inadvertently received 500
ml of 5% saline. He became combative, complained of
headache, and vomited. Generalized seizures ensued, followed by coma. Serum electrolytes were: sodium, 172;
potassium, 2.4; and chloride, 145 mEq per liter. Lasix,
Decadron, phenytoin, and 5c;. dextrose in 0.45Tf saline
were given.
Twelve hours after admission, examination revealed no
reaction to painful stimuli and absent deep tendon reflexes.
The pupils were sluggish, but corneal reflexes were present. Arterial blood analysis showed p H of 6.87, Po, of
196, and P C O of
~ 30.1. He was intubated and hyperventilated, and began making feeble spontaneous movements.
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From the Pediatric Neurology Unit, Massachusetts General Hospital, and the Department of Neurology, Harvard Medical School,
Boston, MA.
Accepted for publication Nov 20, 1978.
Address reprint requests to Dr Young, Pediatric Neurology Unit,
Massachusetts General Hospital, Boston, MA 02 114.

588

0364-5134/79/060588-04$01.25 @ 1978 by Richard S. K. Young

FiR 2. Coronul section oJthe brctin demonstruling diffuse
prtechirrf and jubcortrrai hemorrhagej.

numerous subcortical hemorrhages, usually located at the
junction of the cortex and its underlying white matter (Fig
2). T h e y were as large as 1.5 x 1 .O cm and were distributed
equally throughout the hemispheres.
Microscopic examination revealed diffuse cerebral
edema with widened extracellular spaces. The blood vessels were markedly congested with columns o f intact erythrocytes. No platelet or fibrin aggregates were seen. The
arrerics showed necrosis of the vessel wall with extravasation of red blood cells and proteinaceous material. Capillary ring hemorrhages were also present (Figs 3, 4). The
pituitary gland had several areas of microscopic infarction.
Discussion
This patient presented with moderate hyperglycemia
and minimal metabolic imbalance d u e t o his diabetes.
Following an acute sodium load, h e developed a
number of metabolic aberrations typical of the
hypernatremic state: hyperosmolality, acidosis, and
severe hyperglycemia. Metabolic acidosis accompanies a rise in serum osmolality and is thought to be
the result of changes in cellular permeability [6]. It
may be aggravated by diabetic or starvation ketosis
and by decreased excretion of hydrogen ion. Hyperglycemia may also accompany hypernatremia and exacerbate hyperosmolality, as it did in this case.
Considerable attention has been directed toward
understanding how these varied metabolic changes

result in the neuropathological lesions o f hypernatremia. Changes in osmolality are pathologically
significant when they are rapid and accompanied by
sudden fluid shifts 171.Since the sodium ion has relatively limited access to the intracellular space, in t h e
presence of sudden hypernatremia water moves from
the brain cells to dilute the extracellular compartment. T h e resultant brain shrinkage places stress o n
the falx and the venous sinuses, leading to tearing of
the bridging veins and subdural hemorrhage [ 5 ] .
Sludging may occlude small vessels or a major dural
sinus. Intraparenchymal hemorrhages, occasionally
found in the subcortical white matter of both cerebrum and cerebellum, may be d u e to tearing of intracerebral veins, possibly as a result of distention followed by rupture [2, 81.
Treatment of the hypernatremic state that develops as a result of pure solute gain (as opposed to
hypernatremic dehydration) consists of infusion of
free water 133. T h e rate of infusion is governed by the
rate of solute diuresis attainable with saluretics (e.g.,
furosemide). Just as sudden hypertonicity does not
allow the brain to protect itself by production of
idiogenic osmoles, sudden reduction of serum
sodium does not allow the brain time to rid itself of
t h e idiogenic osmoles. Thus, extremely rapid reduction o f serum sodium may lead to isotonic water intoxication with subsequent development of cerebral
edema [71.
T h e reported mortality rate associated with hypernatremia varies from 7 to 20% El]. Morbidity in-

Casc Report: Young and Truax: Hypernatremic Hemorrhagic Encephalopathy

589

Fig 3 . Capi l l ary ring hemorrhage. I H 6 E ; ~ 4 4 before
0
25%
redrrrt ion. i

Fig 4. Arteriole w i t h nerroJis of i'essel ufalla n d extrariasation
of proteinareous material. (LFBIHGE: x560 before 2Sr4
redurt ion. )

5 9 0 Annals of Neurology

Vol 5

No 6 June 1979

cludes recurrent seizures, hemiplegia, and mental
retardation, which is seen in up to 159% of survivors
[9, 101. CT scanning is a useful tool for documenting
cerebral hemorrhage or infarction and may shed light
on the pathogenesis of the neurological deficits in
survivors.
We are grateful for the comments of Drs Robert DeLong and E. P.
Richardson.

References
1 . Arieff AI, Guisado R: Effects o n the C N S of hypernatremic

and hypanatremic states. Kidney Int 10:104-116, 1976
2. Elton NW, Elton WJ, Nazareno JP: Pathology of acute salt
poisoning in infants. Am J Clin Pathol 39:252-264, 1963

3. Feig PU, McCurdy DK: The hypertonic state. N Engl J Med
297: 1444- 1454, 1977
4. Finberg L, Kiley J. Luttrell CN: Mass accidental salt poisoning
in infancy. JAMA 184:187-190, 1963
5. Finberg L, Luttrell C N , Redd H: Pathogenesis of lesions in
the nervous system in hypernatrernic states. Pediatrics
23146-53, 1959
6. Hogan GR: Hypernatremia-problems
in management.
Pediatr Clin North Am 23r569-574, 1976
7 . Loeb J N : The hyperosmolar state. N Engl J Med 290:1184,
1974
8. Luttrell C N , Finberg L: Hemorrhagic encephalopathy induced
by hypernatremia. A M A Arch Neurol Psychiatry 8 1:424432, 1959
9. Macaulay D, Watson M: Hypernatremia in infants as a cause
of brain damage. Arch Dis Child 42:485, 1967
10. Morris Jones PH, Houston 1B: Prognosis of the neurological
complications of acute hypernatremia. Lancet 2: 1385-1 389,
1967

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