Diabetic Ketoacidosis

Neurologic Collapse During Treatment

Follo wed by Se vere De velopmental Morbidity

Brian Rogers, MD, Irene Sills, MD, Michael Cohen, MD, F. Glen Seidel, MD

Diabetic Ketoacidosis (DKA) remains the leading cause of death in children with type I diabetes
mellitus. Complications occurring during DKA treatment include cerebral edema and neurologic
collapse. Developmental outcomes following neurologic deterioration during DKA have varied from
no sequelae to severe developmental disabilities.
A total of three children developed neurologic deterioration during treatment of DKA at Buffalo
Children’s Hospital between 1984 and 1987. The authors treated aggressively for cerebral edema.
Characteristic findings on the computed tomography (CT) scans and magnetic resonance imaging
(MRI) of the brain included hemorrhagic infarctions of the thalami, basal ganglia and lentiform nuclei.
The authors conducted developmental follow-up examinations between 1-1/2 - 3 years following
recovery from DKA coma. Although they noted significant recoveries over time, developmental
disabilities persisted.
The clinical courses and neuroradiographic findings of these patients are compatible with sequelae
of central brain stem herniation and cytotoxic brain injury. Continued efforts are needed in the
prevention and early detection of clinically significant cerebral edema during treatment of DKA.

From the Divisions of Developmental Pediatrics and Developmental

Disabilities and of General Pediatrics, and from the Departments of
Neurology and Radiology, Robert Warner Rehabilitation Center,
Children’s Hospital of Buffalo, State University of New York at Buffalo,
School of Medicine and Biomedical Science, Buffalo, New York.
Correspondence to: Brian Rogers, MD, Robert Warner Rehabilita-
tion Center, 936 Delaware Avenue, Buffalo, NY 14209.
Received for publication May 1989, revised September 1989, and
accepted February 1990.

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 DIABETIC
common cause
KETOACIDOSIS (DKA) is the most
of death in children with type I diabetes
mellitus.’I Most of the deaths associated with DKA are
secondary to central nervous system (CNS) pathology,
primarily cerebral edema.’ Neurologic deterioration dur-
ing treatment of DKA is often associated with severe
cerebral edema and signs of brain stem herniation.2.3 The
development of brain stem herniation has been linked with
high mortality and morbidity.’-’
We report the short- and long-term neurodevelopmental
morbidity and neuroradiographic abnormalities in three
children who developed neurologic collapse during treat-
ment of DKA at Buffalo Children’s Hospital (CHOB)
between 1984 and 1987. Potential etiologies of these
unfortunate complications will be reviewed.
Case Reports
Patient 1
Patient 1 was a nine-year-old girl who was diagnosed as
having diabetes mellitus at 20 months of age and treated
with daily subcutaneous insulin. She was attending regu-
lar third grade, achieving A and B grades and by no report
had a right-sided tonic seizure and was started on intrave-
nous phenobarbital. She required a tracheostomy 10 days
after admission. Computed tomography (CT) performed
12 days after admission, demonstrated what appeared to
be a hemorrhage into the right basal ganglia. A follow-up
CT scan taken 21 days after admission confirmed a hem-
orrhagic infarction of the right caudate nucleus and the
anterior limb of the internal capsule. Nonhemorrhagic and
edema of the thalami were also present (Fig. 1). Approxi-
mately five weeks after admission, she had a severe
communication disorder and asymmetric spastic
quadraparesis. She was dependent on nasogastric feedings
and was subsequently transferred to a community hospital
for chronic care.
Three years later, she was referred for an evaluation of
her behavior. She had frequent stereotypical behaviors,
pica, wild mood swings and an attention deficit disorder
with hyperactivity. A left hemiparesis was noted. She
ambulated independently, but was clumsy. The WISC-R
Intelligence Test revealed a full-scale IQ score of 53, a
verbal score of 60, and a performance score of 54. Addi-
tional diagnoses included mild mental retardation and an
uneven cognitive profile. She required a personal aide in
a special education classroom.

had behavioral problems.

She was referred from a local community hospital to
CHOB with a diagnosis of DKA. She was lethargic but
could follow simple commands; she also had an ataxic
gait. Her heart rate was 110/minute, respiratory rate (RR)
32/minute, and blood pressure (BP) 110/80. Kussmaul
respirations were present, and she appeared dehydrated.
The rest of the general physical and neurologic examina-
tions were normal. Serum tested strongly positive for
ketones. See Tables 1-2 for treatments and initial chem-
istry values. Within one hour of admission, she was given
50 ml of 25% albumin and 30 mEq NaHCO.3
Approximately 6 1/2 hours after she arrived to CHOB,
labored grunting respirations were noted. Her heart rate
was 170/minute and BP 115/60 and her respirations were
described as erratic. She responded to pain, but made no
posturing movements. Her pupils were of normal size, but
unreactive. Funduscopic exam revealed no papilledema
or hemorrhages. There were no spontaneous movements.
She quickly became apneic, but was immediately resusci-
tated, maintaining a normal heart rate and blood pressure.
She was intubated and given 32 grams of mannitol intra-
venously. See Table 2 for blood chemistry values.
Patient 1 required intermittent mandatory ventilation FIG. 1A. Patient 1 (10 mm CT without contrast). There is an area of
increased attenuation in the right caudate nucleus and anterior limb of the
for 12 hours. On day two, she was noted to have decorti- internal capsule (arrowheads) as well as areas of edema/infarction in the
cate posturing to pain and intact brain stem function. She thalami bilaterally, right more than left (arrows).

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 Patient 2

Patient 2 was a nine-year-old white girl diagnosed as

having diabetes mellitus at 2-1/2 years of age and treated
with subcutaneous insulin. She attended a regular fourth
grade class and was an above average student.
She was taken to a local community hospital because of
persistent vomiting. She was alert and orientated. Her
heart rate was 124/minute, RR 44/minute, and BP 115/76.
Kussmaul respiration were present and she was diagnosed
as having DKA. Four hours after treatment was started

(Table 1) she responded only to deep pain. Blood chem-

FIG. 1 B. Patient 1 (10 mm CT after intravenous contrast). The right sided
abnormalities all show contrast enhancement. These findings are consis-
tent with hemorrhagic infarction.
istry values were obtained (Table 2) and she was immedi-
ately given 50 ml of 25 % albumin, 12.5 grams of mannitol
and 4 mg of dexamethasone intravenously. She was
stabilized and transferred to Children’s Hospital of Buf-
falo.
On arrival to CHOB, Patient 2 was in coma. Large
ketonuria was noted. She responded only to deep pain.
Kussmaul respirations were present. A left exotropia and
unequal, unreactive pupils were noted. Papilledema was
present. Three days after presentation, DKA had been
resolved. Cranial nerve functions were normal, but marked
encephalopathy persisted. Six days following admission,
brain MRI demonstrated diffuse signal abnormalities con

TABLE 1. Fluid, Electrolyte, and Insulin Therapy Before Onset of Coma

*Duration of treatment prior to coma.

TABLE 2. Serum Chemistry Values on Admission and at Coma Onset

*
Duration of diagnosis
t Calcula~ion of corrected Na+: 1.6 mEq of Na+ to be added for every 100 mg/100 ml of glucose over 100 mg/100 ml.

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sistent with edema and hemorrhagic infarctions of the
basal ganglia, upper brain stem, and the surrounding
portions of the frontal, temporal, and occipital lobes (Fig.
2). An electroencephalogram (EEG) revealed generalized
slowing and poor background development.
FIG. 2A., B. (Patient 2) Axial MRI (Contiguous 5 mm T2 weighted images
(TR 3000, TE 40). There are multiple areas of high signal involving the
cerebral peduncles. medial temporal lobes, and frontal lobes (A) and the
lentiform nuclei bilaterally (B). T1 weighted images (not shown) showed tiny
areas of high signal suggesting microhemorrhage in these areas of abnor-
mality. These findings are consistent with hemorrhagic infarction
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Seventeen months following onset of DKA coma, blood
glucose levels showed wide variation, and there were
episodes of hypoglycemia that required treatment. She
required gastrostomy feedings and her posture was that of
quadriplegia in flexion with extension of the left leg. Her
hands were clenched and there were multiple joint
contractures. She had a right gaze preference.
Oculocephalic reflexes were absent. A central right facial
paresis, profound mental retardation and asymmetric mixed
quadriplegia were documented.
Patient 3
Patient 3 was diagnosed as having diabetes mellitus at
10 years of age. She received daily insulin and attended a
regular eighth grade class and was an honor student prior
to admission.
At 14 years of age, she presented with a two-day history
of weakness, glucosuria and ketonuria. On presentation,
she was alert and cooperative. Her heart rate was 125/
minute, RR 20/minute and BP 120/87. There was right
upper quadrant abdominal tenderness. Her neurologic
examination was normal. Large ketonuria was present.
Initial blood chemistry values are listed in Table 2.
She was admitted to a general pediatric ward. About
eight hours after admission, she complained of a headache
and was described as &dquo;sleepy.&dquo; Her heart rate was 100/
minute and BP 100/70. Approximately 10-1/2 hours after
admission, she was found responsive only to deep pain.
Her blood pressure was 115/80 and RR 24/minute. Pupils
were midposition, dilated and unresponsive. Funduscopic
examination revealed no papilledema. Otherwise, cranial
nerves were intact. Plantar responses were upgoing bilat-
erally. See Table 2 for blood chemistry values. She was
given 80 ml of 25% albumin and 25 g of mannitol
intravenously within one hour of neurologic deterioration.
She remained in a coma for about 36 hours. A CT scan
four days after admission demonstrated a definite area of
low attenuation involving the left lentiform nucleus as
well as subtle areas within the thalami and peduncles
bilaterally (Fig. 3). These abnormalities were confirmed
on follow-up scans and were felt to represent areas of
edema and infarction. Two months after admission, she
had a mild left hemiparesis and was discharged.
Patient 3 was given a psychological assessment 14
months after discharge. The Stanford Binet Intelligence
Test full-scale IQ was 70. She was reevaluated, approxi-
mately three years after her coma, while she was in good
health. She required special education classes designed
for head-injured adolescents. She was classified as learn-
ing disabled by her school system and she underwent
speech, physical and occupational therapies. She was also
described as emotionally labile, requiring adult supervi-
sion. General physical examination was normal, cranial
nerves were intact and no visual field deficits were noted.
She engaged in conversation and her speech was clear. A
mild left hemiparesis was noted.
FIG. 3. Patient 3 (10 mm CT without contrast) four days after admission
demonstrates a well-defined area of low attenuation involving the left
lentiform nucleus (arrow) as well as subtle areas within the thalami and
peduncles bilaterally (arrowheads).
Discussion .
All children admitted to CHOB between 1984 and 1987
who had neurologic deterioration while being treated for
DKA were the subjects of this case series. Our patients
were initially alert and responsive on admission, only to
experience a severe neurologic collapse 4 -10-1/2 hours
into treatment. Encephalopathy and signs of brain stem
dysfunction were uniformly present. Neuroimaging re-
vealed hemorrhagic infarctions of the basal ganglia, inter-
nal capsules, thalami and lentiform nuclei (Fig. 1-3).
Following prolonged recovery periods of up to three
years, persistent deficits in corticospinal and higher cog-
nitive function were present in all cases.
Survivors of neurologic collapse during treatment for
DKA have had variable outcomes. Rubin et al.’reported
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aseries of six children with hyperosmolar diabetic coma.
All had significant metabolic acidosis and four out of six
had ketonuria. They all experienced significant neuro-
logic deteriorations, and two survived. One survivor
remained in a coma for five days and made a complete
recovery. The other survivor remained comatose for two
months and developed optic atrophy and blindness. Other
investigators have reported normal outcomes following
varying periods of follow-up.’,’
In recent years, investigators have coupled clinical
observations with various neuroimaging techniques.
Lufkin and colleagues6 reported a 15-year-old survivor of
DKA coma who, on follow-up, developed
panhypopituitarism, optic atrophy and learning problems
in school. Approximately 1-1/2 weeks following admis-
sion, an EMI scan was normal. In a case series of three
children experiencing neurologic collapse during treat-
ment for DKA, Jos et al.1 reported two survivors. A 5 1//
2-year-old boy experienced neurologic collapse after re-
ceiving eight hours of treatment for DKA. A CT scan
perforrried three weeks after the episode revealed diffuse
cortical atrophy and necrosis of the basal ganglia. On
follow-up, the boy was described as bedridden, requiring
rehabilitation hospital. The other survivor was a seven-
year-old girl who, on follow-up, had a residual right
hommonous hemianopsia. A CT scan revealed a hypodense
area in the left occipital lobe. Another case report de-
scribed a 13-year-old male survivor who developed tran-
sient third-nerve paresis and amnesia for the first three
days of hospitalization. Follow-up confirmed a full clinical
recovery and a normal cranial CT scan.’° More recently,
one survivor developed isolated growth hormone defi-
ciency, hemiplegia and aphasia.55 A CT scan revealed
cerebral atrophy and infarction of the thalamus and hypo-
thalamus. Kanter et al.&dquo; reported two survivors who had
CT scan showing brain infarctions involving areas supplied
by the posterior cerebral artery. Both patients were
reported to be recovering.
The high mortality and morbidity associated with neu-
rologic collapse during treatment for DKA have been
linked with the development of severe cerebral edema and
brain stem herniation .2’ The clinical courses of most
patients share many common features. Increasing leth-
argy or agitation often develops during the first few hours
of treatment .2-6,8-1 ’ This is followed by a rather abrupt
neurologic deterioration, usually 4-12 hours of presenta-
tion. Patients often develop poor or unreactive pupillary
responses to light, as well as other signs of brain stem
dysfunction, including absence of oculocephalic reflexes
and apnea. In most patients, these signs develop quite
455
rapidly, often within one hour. These findings are most
compatible with central brain stem herniation,12 but the
typical rostral-caudal progression of signs in central brain
stem herniation have been present only inconsistently.2-lo
In recent reports and in our own case series, common
neuroradiographic findings aredescribed.5, 11 During the
course of central or uncal brain stem herniation, there are
a number of vascular compromises that may occur at the
tentorial notch.’2 The posterior cerebral artery can be
compressed during brain stem herniation. This artery has
important branches, including the interpeduncular,
thalamoperforate, thalamogeniculate and the cortical
branches. Compression and limited flow through these
branches can produce infarctions of the cerebral peduncles,
oculomotor and trochlear nuclei, thalamus, geniculate
body and the inferiormedial parts of the temporal lobe and
medial occipital lobes.
Kanter et al.&dquo; reported a four-year-old girl who lapsed
into a coma and had signs of brain stem herniation. Two
days following admission, hypodense areas were demon-
strated bilaterally in the thalamus and right occipital and
posterior parietal lobes on CT scan. Similar CT scan
findings were reported in an eight-year-old boy with
traumatic subdural hematoma, producing transtentorial
brain stem herniation.’3 Infarctions of the posterior limb
of the internal capsule, globus pallidus and hippocampus
are also possible, causing compression of the anterior
choroidal artery between the dentate gyrus and the lateral
margin of the tentorium during herniation. 12
Central herniation with compression of the posterior
cerebral and anterior choroidal arteries could account for
most of the neuroradiographic findings in our patients
(Fig. 1-3). Significant traction can be exerted on the
hypothalamus and pituitary during hemiation.’2 This
process could explain the previous case reports of tha-
lamic and hypothalamic infarctions associated with pan-
hypopituitarism and isolated growth hormone deficiency
in survivors of DKA coma and clinical significant cerebral
edema.5,66
The use of coma scales has been proven quite useful in
the evaluation and treatment of other types of encepha-
lopathies.14-17 Both mortality and morbidity have been
associated with the depth and duration of coma in head-
injured children. 14- 11 The prevention of clinically signifi-
cant cerebral edema during DKA should continue to be a
focus of our efforts.’ Detailed, objective mental status and
neurologic examinations throughout treatment for DKA
may prove useful in identifying signs of impending central
or uncal herniation, thus enabling early aggressive treat-
ment.
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There has been a wide spectrum of clinical outcomes in
survivors of neurologic collapse during treatment for
DKA.5-ll Neurologic recovery can be significant, but can
be followed by persistently abnormal neurologic exami-
nations and functional handicaps in academic achieve-
ment and social skills. These areas of performance should
be assessed in all survivors of neurologic collapse during
treatment for DKA.
Acknowledgments
Special thanks to Michael Msall, MD, for his thoughtful
review of the manuscript, and to Maureen Codd for her
secretarial assistance.
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