EXPERIENCE & REASON

Coma With Diffuse White Matter Hemorrhages in

Juvenile Diabetic Ketoacidosis
Farid H. Mahmud, MDa, David A. Ramsay, MB, ChBb, Simon D. Levin, MDc, Ram N. Singh, MBBSd, Trevor Kotylak, MDe,
Douglas D. Fraser, MD, PhDd

aDivision of Pediatric Endocrinology, bDepartment of Pathology, Divisions of cPediatric Neurology and dPediatric Critical Care Medicine, and eDepartment of Radiology,

Children’s Hospital of Western Ontario, London, Ontario, Canada

The authors have indicated they have no financial relationships relevant to this article to disclose.

ABSTRACT
Cerebral edema is the most common neurologic complication of diabetic ketoacidosis in children. A minority of
young patients with intracerebral crises in diabetic ketoacidosis present with cerebrovascular accidents. We report 2
adolescent patients with diabetic ketoacidosis who presented with coma and diffuse white matter hemorrhages in the
absence of either cerebral edema or cerebrovascular accidents. These 2 cases illustrate a novel clinical and neuro-
pathologic description of diffuse white matter hemorrhages, possibly related to a cytotoxic process as the underlying
mechanism. These case descriptions emphasize that pediatric patients with diabetic ketoacidosis and coma can
present with pathology not related to either cerebral edema or cerebrovascular accidents.

C EREBRAL EDEMA (CE) is a major complication asso-

ciated with diabetic ketoacidosis (DKA) and occurs
in 0.46% to 1.0% of episodes of DKA in children.1–3
CASE REPORTS

PATIENT 1. The patient was a previously healthy 11-year-

Although rare, CE with DKA has a 21% to 24% mor-
tality rate and a 10% to 26% rate of neurologic disabil-
ity.1–3 Since the initial description that linked CE with
DKA,4 numerous published reports (coupled with ad-
vances in neuroimaging) have refined our understand-
ing that the neurologic complications of DKA should be
described by using the broader term “intracerebral com-
plications.”5 Other intracerebral complications that occur
with DKA include hemorrhage and arterial and venous
thrombus formation, which have been estimated on the
basis of clinical series as occurring in 10% of cases.5–14
Here we present 2 atypical cases of new-onset DKA
with coma and diffuse white matter hemorrhages in the
absence of radiologic or pathologic evidence of CE or
cerebrovascular accidents. Both patients were pro-
foundly acidotic and had greatly elevated serum ketone
levels. One patient died, and a postmortem examination
of the brain was performed; the other patient underwent
a diagnostic brain biopsy and experienced a protracted
recovery with lingering neuropsychological deficits.
old girl of aboriginal heritage who was living in a remote
northern community. Her previous medical history was
significant for obesity and normal test results of random
fasting blood sugar and hemoglobin A1c performed 3
years earlier because of a strong family history of type 2
diabetes.
She presented to a nursing station in northern On-
tario with labored, shallow breathing preceded by a
4-day history of emesis, lethargy, and influenza-like
symptoms in the absence of fever. On initial examina-
tion, her weight was 102 kg, height was 172 cm, BMI
was 34.5 kg/m2, respiratory rate was 22 breaths per
minute, pulse was 128 per minute, blood pressure was
94/59 mm Hg, temperature was 36.3°C, and Glasgow
Coma Scale (GCS) score was 13. Her blood glucose level
Key Words: diabetes, DKA, hemorrhage, white matter changes
Abbreviations: CE, cerebral edema; DKA, diabetic ketoacidosis; SIR, systemic
inflammatory response; GCS, Glasgow Coma Scale; CT, computed tomography; MRI,
magnetic resonance imaging
www.pediatrics.org/cgi/doi/10.1542/peds.2007-0366

These cases demonstrate acute neurologic dysfunction doi:10.1542/peds.2007-0366

with neuropathologic evidence of diffuse white matter
injury, which we propose is secondary to cytotoxic fac-
tors related to metabolic abnormalities and the systemic
inflammatory response (SIR).
Accepted for publication May 17, 2007
Address correspondence to Farid H. Mahmud, MD, Division of Pediatric Endocrinology, Children’s
Hospital of Western Ontario, 800 Commissioners Rd E, London, Ontario, Canada N6C 2V5. E-mail:
farid.mahmud@lhsc.on.ca
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2007 by the
American Academy of Pediatrics

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 TABLE 1 Comparison of Clinical, Initial Laboratory, and Diagnostic Data
Patient 1 Patient 2
Age, y 11 14
Blood glucose level (initial), mmol/L (mg/dL) 17 (306) 34.8 (685)
Sodium level (corrected), (reference range: 135–145 mmol/L) 141 140
Potassium level, (reference range: 3.0–5.5 mmol/L) 5.3 4.6
Chloride level, (reference range: 98–107 mmol/L) 110 104
Anion gap, mEq/L (reference range: 7–15 mEq/L) 29 23
Serum osmolarity (effective osmolarity), mOsm/L 359 (308) 344 (313)
Lactate, mmol/L (reference range: 0.9–2.5 mmol/L) 1.7 2.5
Arterial blood gas values
pH 6.96 6.74
PCO2 (mmHg) 31 32
PO2 (mmHg) 71 66
Bicarbonate (mmol/L) 7 4
Ketone level, mM (reference range: 0.058–0.170 mM)a 5.8 4.2
Creatine kinase level, (reference range: 26–140 U/L) 22 000 455
Myoglobin level (urine), ␮g/L (reference range: 0–12 ␮g/L) ⬎10 000 435
Amylase level, (reference range: 36–128 U/L) 755 800
Coagulation test results Normal Normal
Liver-function test results Normal Normal
Hemoglobin A1c, % (reference range: 4%–6%) 11.5 11.4
Initial fluids, mL/m2 per 24 h 3600 2700
Insulin therapy 0.1 U/kg bolus (transit) and 0.1 then 0.03 U/kg per h infusion
0.05 U/kg per h infusion
Cerebral imaging (CT and MRI/MRA) results Normal White matter changes
Toxicology results Negative Negative
Metabolic test results Negative Negative
Cerebrospinal fluid Normal Normal
Electroencephalography Burst suppression Diffuse slowing
Course in hospital Persistent acidosis; died at 72 h Coma for 8 d; slow recovery;
persistent neurologic deficits
The corrected sodium level was calculated as measured sodium ⫹ 0.016 ⫻ (serum glucose ⫺ 100), and effective serum osmolarity was calculated as 2(Na) ⫹ glucose (mmol/L) using values timed
with measured serum osmolarity. Arterial blood gases were measured within 2 hours after critical care admission and once stable ventilation was achieved. The insulin bolus was administered in
transit at the peripheral hospital. Coagulation studies included platelets, prothrombin time, partial thromboplastin time, fibrinogen, D-dimer, protein C, protein S, antithrombin III, and factor V Leiden
antibody. Metabolic tests included urine organic acids, serum amino acids, lactate, pyruvate, biotin, metachromatic leukodystrophy, and mitochondrial DNA point-mutation analysis. MRA indicates
magnetic resonance angiography.
a Blood ␤ -hydroxybutyrate.

was 17 mmol/L (306 mg/dL), and results of a urine
dipstick test were positive for ketones. A provisional
diagnosis of DKA was made, and the patient was given 2
L of normal saline delivered intravenously over 2 hours
and a single 10-U regular intravenous insulin push.
Maintenance fluids (normal saline with 20 mEq/L KCl)
were continued at 100 mL/hour. Because of the limited
medical resources in her community, the patient was
transferred to our tertiary care pediatric hospital by air
ambulance. Approximately 9 hours after her initial pre-
sentation, while in flight, there was a rapid deterioration
in her level of consciousness, and the plane was diverted
to the nearest medical center. There she was intubated,
ventilated, and given 100 g of intravenous mannitol
followed by 500 mL of 3% saline, which resulted in 1000
mL of urine output but no improvement in her level of
consciousness. In addition to intravenous saline boluses,
dopamine was administered to treat her hypotension
and poor perfusion.
On arrival at our hospital, the patient had a GCS score
of 3 in the absence of sedation. She received fluid and
further inotropic support to stabilize her blood pressure
and perfusion (heart rate: 130 beats per minute; blood
pressure: 80/30 mm Hg). Her examination was negative
for signs of trauma, her pupils were equal at 2 mm and
reactive to light; results of fundoscopy were normal, and
no abnormal brainstem signs were elicited. The remain-
der of her examination was normal except for a yellow
vaginal discharge. She did not have acanthosis nigricans.
Her laboratory data are summarized in Table 1.
Broad-spectrum antibiotic and antifungal coverage
was administered, and serum osmolality was corrected
slowly over 36 hours. Computed tomography (CT) and
MRI (Fig 1A and B) of the head were unremarkable.
Serial electroencephalograms demonstrated a burst-sup-
pression pattern consistent with profound encephalopa-
thy. Imaging of the chest (radiography and CT) revealed
interstitial pulmonary edema, and results of CT of her
abdomen and pelvis were normal. There was no evi-
dence for bacterial, fungal, or viral infection in cultures
and polymerase chain reaction testing of her blood,
urine, and cerebrospinal fluid (opening pressure: 25
mm H2O). Over the course of 3 days, the patient became
euglycemic on insulin infusion but remained on inotro-

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FIGURE 1
Normal imaging and postmortem neuropathology findings (patient 1). A and B, Head
MRI axial (fluid-attenuated inversion recovery) (A) and coronal view (T2) (B) images were
normal. C–F, Gross neuropathology. Small white matter hemorrhages are indicated (ar-
rows) in the anterior commissure (C), crura cerebri (D), a medullary pyramid (E), and the
cervical spinal posterior column (F). G, Microscopic review of the central nervous system
revealed numerous additional small microscopic vasculocentric lesions throughout the
white matter (hematoxylin, eosin, and Luxol fast blue were used; 2 lesions are present and
labeled 1 and 2). The gross and microscopic lesions had distinctive morphology. They
were centered on small blood vessels (arrow), and there were markedly eosinophilic,
sometimes asymmetric, inner rings formed by variable combinations of fibrin, necrotic
tissue, neutrophils, macrophages, axonal debris, and red blood cells (arrowhead) and
outer rings of pale white matter (asterisks) with scant inflammatory cells and no histo-
logical evidence of demyelination. H, Many of the neurones (white arrowheads indicate
examples of neurones) were characterized by indistinct (or “muddy”) cytoplasmic stain-
ing, vesicular (“watery”) nuclear chromatin, and prominent perineuronal spaces (with
homogeneous, faintly basophilic proteinaceous material, indicated by arrows). The peri-
neuronal spaces probably represent swollen astrocytic processes. Although it is difficult
to be sure of whether these changes were artifactual, they are otherwise nonspecific
postmortem findings in the brains from cases of various encephalopathies of toxic, sep-
tic, and metabolic origin.
pic support and was severely acidotic (pH ⬍ 7.1). Her
condition rapidly progressed to acute renal failure. As
dialysis was starting, a profound rise in her potassium
level, despite concerted measures to treat hyperkalemia,
resulted in ventricular tachycardia and asystole.
A postmortem examination was conducted the day
after her death and revealed congested, edematous lungs
with multifocal areas of necrosis; marked vascular con-
gestion with bilateral serous pleural effusions; hepato-
megaly with microvesicular fatty change; renal tubular
casts; and a normal heart. The pancreas did not show fat
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necrosis or fibrosis despite laboratory evidence of pan-
creatitis. There was no CE.
Multiple abnormalities were noted on neuropathol-
ogy including pin-point hemorrhages (Fig 1C–F) in the
hemispheric white matter and scattered throughout the
brainstem and spinal cord. These petechial hemorrhages
were characterized histologically by “ring-and-ball”
morphology (Fig 1G), namely a blood vessel surrounded
by an inner ring of red blood cells, fibrin, and inflam-
matory cells and an outer ring of pale myelin with no
evidence of demyelination. Many of the neurones (Fig
1H) also had an appearance consistent with postmortem
findings in the brains from patients with various enceph-
alopathies of toxic, septic, and metabolic origin.15 No
peripheral nerve abnormalities were seen, and the skel-
etal muscle was normal.
PATIENT 2. A 14-year-old previously well white girl pre-
sented to our pediatric emergency department with a
2-week history of polyuria, polydipsia, and a 2-kg
weight loss. The night before, she had felt lethargic and
went to bed early. Ten hours later, she was found un-
responsive and dyspneic. On examination, her weight
was 75 kg, height was 165.5 cm, BMI was 27.5 kg/m2,
temperature was 37.1°C, blood pressure was 60/40
mm Hg, heart rate was 103 beats per minute, respiratory
rate was 34 breaths per minute, and GCS score was 3.
She exhibited Kussmaul breathing, and her pupils were
4 mm bilaterally and weakly responsive to light. No
evidence of trauma or illicit drug use was reported. She
was intubated and ventilated. Fluids, inotropic support,
and broad-spectrum antibiotics were given. Her initial
blood glucose level was 34.8 mmol/L (685 mg/dL), and
she was profoundly acidotic and ketotic (Table 1). Man-
nitol (75 g) was administered to treat suspected CE,
although her CT brain scan was normal. A slow insulin
infusion (0.03 U/kg per hour) was started to avoid rapid
osmolar shifts.
Abnormal laboratory findings included low C-peptide
levels (190 pmol/L, in response to the elevated blood
glucose level of 20 mmol/L), elevated anti– glutamic acid
decarboxylase antibodies (0.23 nmol/L [reference:
⬍0.02 nmol/L]), and positive islet-cell antibody levels.
Results of the remainder of the metabolic, vasculitic, and
coagulation workups were negative, as were results from
all bacterial and fungal cultures and polymerase chain
reaction viral tests.
Her course in the hospital was complicated by acute
renal failure and transient elevations in her lipase and
pancreas-specific amylase level, which rose to twice the
reference values before normalizing over 3 days. She
remained comatose after correction of her metabolic
acidosis and hemodynamic instability. Although there
was no evidence of CE on imaging, an external ventric-
ular drain (opening pressure was 14 cm H2O with a
range of 12–18 cm [reference: ⬍20 cm]) was placed to
ensure normal intracranial pressure during correction of
her hyperosmolar state. MRI of the brain showed no CE.
There were, however, multiple well-defined hyperin-
tense T2 foci associated with petechial hemorrhages in-
volving the subcortical white matter U fibers bilaterally,
genu of corpus callosum, and the posterior limb of the
internal capsule bilaterally. There was a single focus of
enhancement associated with a lesion in the left frontal
lobe (Fig 2A and B). An angiogram showed numerous
small segmental foci of decreased vessel caliber in the
anterior and posterior circulations. On day 6 of admis-
sion, an MRI-guided left frontal craniotomy for brain
biopsy was performed on the lesion in the left frontal
lobe.
The brain biopsy showed no abnormalities of the
cortical neurons. There were extensive areas of petechial
hemorrhage (Fig 2C) surrounded by pale white matter,
with a ring-and-ball morphology (Fig 2D), with associ-
ated axonal injury but no evidence of demyelination (Fig
2E) or vasculitis (Fig 2F).
By day 10 of hospitalization, the patient demon-
strated a slow improvement in her neurologic condition
and no longer required ventilatory or inotropic support.
In the initial phase of her convalescence, she had severe
aphasia, very poor short-term memory, and motor
apraxia, which were suggestive of diffuse frontal and
temporal injury. She never exhibited focal motor or
FIGURE 2
sensory findings. She was transferred to a brain rehabil- Imaging and neurosurgical pathology findings (patient 2). A, Head MRI: single axial fluid-
itation unit and received intensive therapy over the next attenuated inversion recovery image demonstrating multiple well-defined foci of abnormal
2 months; she then was discharged from the hospital. increased T2 signal scattered throughout both cerebral hemispheres involving predomi-
nantly the subcortical white matter. B, Single coronal multiplanar gradient recalled acquisition
An MRI head scan was repeated 7 months after her image. The arrows demonstrate punctate foci of abnormal diminished T2 signal associated
initial presentation (data not shown). There was diffuse with these lesions compatible with petechial hemorrhage. C, This low-power view of a gyrus
subcortical white matter volume loss. The magnetic res- (stained with hematoxylin, eosin, and Luxol fast blue) illustrates multiple small and micro-
scopic hemorrhages (arrowheads) associated with “confluent” pallor (asterisks) of the myelin,
onance angiogram and venogram were normal. The pa- a thin layer of preserved subcortical myelin (arrows), and normal cortex. D–F, These photomi-
tient has been followed in our pediatric diabetes and crographs were taken from the same region; a vessel, labeled v, is identified for reference. In D,
neurology outpatient clinics. There is no neurologic def- stained with Luxol fast blue, hematoxylin, and eosin (which stains myelin blue), the central
hemorrhage was formed by perivascular necrosis (arrow), reminiscent of the lesions in patient
icit on formal examination, but she has moderate cog- 1, a concentric ring of red blood cells, and diffusely rarefied white matter that is speckled with
nitive deficits and short-term memory loss. She cur- eosinophilic astrocytes (arrowheads). Shown in E is a photomicrograph from a section treated
rently uses insulin glargine and aspart as part of a with neurofilament immunohistochemistry (which labels axons dusky brown). Note the
coarsening of axonal labeling in the center of the lesion, which indicates perivascular
multiple daily-injection regime and maintains her he- axonal injury (arrow), the loss (or separation) of axons in the red blood cell layer (asterisk),
moglobin A1c near 8.0%. She experiences occasional and the proportional labeling of axons compared with the myelin staining (illustrated in
episodes of moderate hypoglycemia and has not had D). Shown in F is a photomicrograph of a section treated with CD68 immunohistochem-
istry (which labels microglia [rod-shaped or spindled cells] and histiocytes [round cells]
subsequent admissions to the hospital for DKA. brown). Note that there is no predilection of the activated/proliferating microglia/histio-
cytes for the perivascular lesions. Marked accumulation of these cells only occurred ad-
DISCUSSION jacent to, and in, the layer of preserved subcortical myelin. The pathological findings in
case 2 are similar to those in case 1 with respect to the widely distributed small and
DKA is a common initial presentation of pediatric type 1 microscopic hemorrhages. The hemorrhagic lesions differ between the cases in that,
diabetes, with defined biochemical criteria including hy- compared with case 1, the lesions are more numerous, their mantle of red cells is more
perglycemia, acidosis, and ketosis and incidences among prominent, the perilesional myelin pallor is confluent, and the microgliosis and astrocy-
tosis is more prominent in case 2. The degree of gliosis in case 2 is likely to be a conse-
newly diagnosed patients ranging from 15% to 67% in quence of a longer interval between the onset of symptoms and pathological examina-
developed countries.16–18 Compared with adults, DKA in tion of the tissues. Note that in case 2 that the cortex, including the cortical neurones, was
children carries higher morbidity and mortality largely normal except for mild microgliosis.

because of intracerebral complications including CE and

cerebrovascular accidents.19
The most common central nervous system complica- reported acute neurologic complications in children.
tion of DKA in symptomatic children is CE, with major Large subarachnoid hemorrhages have been described in
cerebrovascular insults comprising the remainder of the 2 patients (aged 1 and 2 years), both of whom died6; in

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a radiographic series of 23 patients, 4 children showed
evidence of subarachnoid or intraventricular hemor-
rhages and 3 had hemorrhages and CE.7 Intracerebral
hematomas that occur with pediatric DKA have been
described in a 10-year-old girl with bitemporal posterior
intracerebral hematomas12 and in a 15-year-old girl with
focal neurologic signs and multiple cerebral hematomas
localized to the parietoocciptal region.10 Children with
DKA have also been described with stroke and brain
infarction.7,11,12 These major cerebrovascular events
likely relate to a hypercoagulable state, which occurs
with diabetes.20
In our report, neither patient had impaired coagula-
tion study results or neuroimaging or angiographic
changes to indicate major cerebrovascular disease. Both
patients presented in a coma that resolved in the surviv-
ing patient with no focal neurologic deficits. CE was not
present in either of our patients on neuroimaging, direct
intracranial pressure monitoring in patient 2, or on gross
or microscopic specimens taken. Medical therapy, in-
cluding mannitol, would not have completely reversed
any CE that may have been present.
Patients who present with severe DKA have been
shown to undergo significant metabolic, inflammatory,
and oxidative stresses consistent with a noninfectious
SIR. The SIR has been shown by elevated levels of proin-
flammatory cytokines including interleukins 6 and 1␤
and C-reactive protein,21–23 in addition to the generation
of reactive oxygen species and reduced levels of antioxi-
dants.24,25 Other markers of the inflammatory cascade
include complement activation, which has been demon-
strated on neurons, oligodendrocytes, and blood vessels
of adolescents who died as a result of CE in DKA.26,27 The
cerebral microvasculature in DKA is further modulated
by circulating ketones, ␤-hydroxybutyrate, and acetoac-
etate, which alter the permeability of endothelial cells in
vitro.28,29 Pediatric brains also take up and utilize ketones
at a four- to fivefold faster rate than adults, and ketones
accumulate in the brain of pediatric patients with
DKA.30,31 These features, coupled with larger brain vol-
umes, less developed osmoregulatory pathways, and
more porous blood-brain barriers, may also explain why
children who present with DKA are at increased risk of
intracerebral crises.32,33
Although MRI studies in children with diabetes have
not reported white matter changes similar to those de-
scribed in this report, hyperintense T2 white matter
lesions are well recognized in adults with cerebrovascu-
lar disease, hypertension, and/or diabetes and in older
healthy people as part of the aging process.34–37 Diffuse
white matter hemorrhages occur in response to localized
endothelial cell injury, usually secondary to localized
hypoxia and ischemia, with or without thrombocytope-
nia, in conditions such as disseminated intravascular
coagulopathy, thrombotic thrombocytopenic purpura,
and air and fat emboli.38 Acute lead poisoning in children
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and cerebral malaria are other causes.39,40 The petechial
hemorrhages detailed in this report occurred in the ab-
sence of coagulopathy or embolic disease and suggest
disruption of the small white matter vessels, presumably
related to a cytotoxic process. An analogous process has
been proposed to explain the pathogenesis of “septic
encephalopathy,” in which a systemic process, in this
case mediated by endotoxin, results in an SIR in combi-
nation with endothelial injury, ischemia, and break-
down of the blood-brain barrier.41–43 For the cases de-
scribed in this report, the presence of perivascular axonal
injury, rhabdomyolysis, and pulmonary edema favors
the operation of cytotoxic factors (separately or in com-
bination) that are peculiar to events associated with the
acute onset of DKA in children. These factors include
poor perfusion, acidosis, hyperglycemia, and ketonemia,
and their clinical and pathologic manifestations will vary
depending on the timing, extent, and particular combi-
nation of cytotoxic events. This phenomenon has been
described in pediatric DKA, with capillary disruption
producing facial and peripheral edema observed in the
absence of CE,44 CE without pulmonary edema,6,8 and,
like in our first patient, acute pulmonary edema without
evidence of cerebral findings.45,46 It remains unclear why,
faced with similar cytotoxic factors, some patients’ con-
ditions progress to CE and others do not.
Although we propose that these lesions resulted from
cytotoxic factors related to metabolic abnormalities and
the SIR, alternative etiologies require consideration.
These white matter lesions are unlikely to have been a
preexisting condition, because white matter abnormali-
ties are not commonly seen in normal children and
adolescents.34 An atypical form of disseminated intravas-
cular coagulopathy is a possibility, in which tests of
coagulation do not coincide with the hematologic insult;
however, there was no evidence of microthrombi, fibrin-
oid necrosis, or vasculitis seen on microscopy in either
case. Although we cannot exclude shock secondary to an
inflammatory state (ie, viral sepsis) leading indepen-
dently to endothelial dysfunction in cerebral vessels, this
seems unlikely, because pathology results for both pa-
tients was not consistent with hypoperfusion and infarc-
tion. Furthermore, we did not observe microscopic, isch-
emic changes in hippocampal neurons (red, pink
coloration), which present as part of the hypoxic-isch-
emic encephalopathy of septic shock. Both patients pre-
sented with hypotension, but distal perfusion was un-
likely to be significantly compromised because the
lactate levels on admission were within the reference
range, which indicates adequate oxygen delivery. Thus,
the specific brain pathologic findings and coma observed
in our patients is likely related directly to development
of DKA, perhaps combined with other unidentified risk
factors.
The cases described in this report contribute new
pathologic information to our understanding of DKA in
children. The pathologic findings in both cases were
similar with respect to the widely distributed small and
microscopic hemorrhages. The hemorrhagic lesions dif-
fered between the cases in that, compared with case 1,
the lesions were more numerous, the mantle of red cells
was more prominent, and the perilesional myelin pallor
was confluent in case 2. The extent of hemorrhages
between patients may have related also to the timing of
presentation, level of acidosis, ethnicity, and/or differ-
ences in BMI. Although both patients met criteria for
DKA, our first patient had multiple risk factors for type 2
diabetes, including aboriginal ancestry and elevated
BMI. Indeed, type 2 diabetes was demonstrated recently
to cause DKA in a significant number of presenting
adolescent cases.47 The first case presented here also
shares similarities with the previously reported case of a
black 16-year-old boy with a BMI of 33.8 kg/m2, hypo-
tension, and rhabdomyolysis who died as a result of
renal failure and was reported to present with hypergly-
cemic hyperosmolar coma.47 Our patient had profound
acidosis at presentation, a lower initial blood glucose
level, and significant ketonemia, which are more consis-
tent with DKA than hyperglycemic hyperosmolar coma,
although mixed presentations can occur.47,48 In the sec-
ond patient, we were careful to optimize fluids with
inotropic support and initiate insulin as a slow infusion.
In addition, the second patient had intracranial pressure
measurements to monitor the effects of the slow osmolar
correction.
CONCLUSIONS
We have described 2 cases of diffuse white matter focal
hemorrhages that may have been caused by a diabetic
small vessel injury, possibly caused by circulating cyto-
toxic factors. Physicians who care for children should be
aware that hyperglycemic coma in adolescents is not
only associated with CE. These cases provide further
clinical and neuropathologic insight into the cerebral
dysfunction present in children with severe DKA.
ACKNOWLEDGMENTS
Dr Fraser is supported by the Children’s Health Research
Institute and the Centre for Critical Illness Research and
is a strategic training fellow of the Canadian Institutes of
Health Research in the Canadian Child Health Clinician
Scientist Program.
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 Coma With Diffuse White Matter Hemorrhages in Juvenile Diabetic
Ketoacidosis
Farid H. Mahmud, David A. Ramsay, Simon D. Levin, Ram N. Singh, Trevor Kotylak
and Douglas D. Fraser
Pediatrics 2007;120;e1540; originally published online November 26, 2007;
DOI: 10.1542/peds.2007-0366
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright © 2007 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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 Coma With Diffuse White Matter Hemorrhages in Juvenile Diabetic
Ketoacidosis
Farid H. Mahmud, David A. Ramsay, Simon D. Levin, Ram N. Singh, Trevor Kotylak
and Douglas D. Fraser
Pediatrics 2007;120;e1540; originally published online November 26, 2007;
DOI: 10.1542/peds.2007-0366

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/120/6/e1540.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2007 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from pediatrics.aappublications.org at Leeszaal Wilhelmina on March 14, 2015