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A 9-month-old baby with subdural hematomas, retinal
hemorrhages, and developmental delay
JANE F. KNAPP, MD, Section Editor; Authors: SARAH E. SODEN, MD; MAJED J. DASOUKI,
MD; IRENE R. WALSH, MD
From the Section of Behavioral and Developmental Pediatrics (S.E. Soden), the
Section of Medical Genetics and Molecular Medicine (M.J. Dasouki), and the
Division of Emergency Medicine (I.R. Walsh), The Childrenīs Mercy Hospital,
Kansas City, Missouri.
PEDIATRIC EMERGENCY CARE 2002;18:44-47
Key Words: Glutaric aciduria; retinal hemorrhages; subdural hematomas;
developmental delay; child abuse
CASE
A 9-month-old male presented to an emergency department (ED) after collapsing in
his home. His parents reported that he fell backward while kneeling on a
carpeted floor at home. He struck his head on the floor, stiffened briefly, and
then became limp for 5 to 10 minutes. Perioral cyanosis developed during the
episode, but it resolved with 2 rescue breaths. He was transported by ambulance
to the local hospital. Upon arrival in the ED, he was awake and alert. Physical
examination was documented as normal. A computed tomography (CT) scan of the
head was done, interpreted in the ED as normal, and the patient was discharged.
The following day, he developed vomiting and returned to the ED. A diagnosis of
otitis media was made, and he was discharged. Two days later, he was admitted to
the community hospital for recurrent vomiting and dehydration. A repeat CT was
done, which showed a right isoattenuating (subacute) parietal subdural hematoma
(Fig. 1). The next day he was noted to have less irritability and good oral
intake, and was discharged. No additional studies were obtained.
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 FIG. 1. A CT scan taken at the time of the
patientīs first admission to the community hospital. It shows an iso-attenuating
(subacute) subdural hemorrhage adjacent to the right parietal lobe.
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Six weeks later, while cruising along furniture, he fell again. He stiffened,
developed rhythmic jerking of all extremities, and then lost consciousness for
approximately 5 minutes. In the local ED, he was noted to have extreme
irritability and vomiting. A head CT scan was repeated (Fig. 2). It showed
bilateral hypoattenuating extraaxial fluid collections and an acute subdural
hemorrhage on the right. The CT scan was also interpreted as showing concentric
effacement of the ventricular system and sulci, suggestive of increased
intercranial pressure. He underwent urgent craniotomy for decompression and
placement of a subdural drain. Intraoperatively, bleeding vessels were
cauterized, and a subdural membrane was identified.
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 FIG. 2. A repeat CT scan 6 weeks later.
Chronic subdural hematomas/hygromas are now apparent as hypo-attenuating
bilateral extraaxial fluid collections. A hyper-attenuating (acute) subdural
hemorrhage is also seen layering on the right.
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The patient was transferred to the Childrenīs Mercy Hospital (CMH) for further
management. On detailed past medical history, his parents reported that his
trunk control seemed to lag behind that of other children. He had recently begun
to crawl and pull to a stand, but could not yet sit independently. There was no
history of easy bruising or bleeding, and no family history of bleeding
disorders. On physical examination he was sleepy but woke to painful stimuli.
Pertinent findings included a prominent forehead and relative macrocephaly. Head
circumference was 47.5 cm (90%) while weight and height were between the 10 and
25%. He was also noted to have truncal hypotonia. The liver edge was palpated 4
cm below the subcostal margin; the liver span was not recorded. A retinal
examination revealed multiple intraretinal and 1 subhyaloid hemorrhage. Mild
papilledema was also present. Hemoglobin was 10.1 g/dL. The prothrombin time
(PT) was elevated at 16.3 seconds (normal 10.8-13.9 sec); however, the partial
thromboplastin time (PTT), fibrinogen, and D-dimers were all within normal
limits. His blood chemistry showed a CO2 of 14 mmol/L with an anion gap of 15
mmol/L. A skeletal survey demonstrated no fractures.
DIFFERENTIAL DIAGNOSIS
At the time of presentation to CMH, this patient had evidence of both chronic
and acute subdural bleeding, as well as retinal hemorrhages. One or more falls
from standing or kneeling in an otherwise healthy child would not result in such
findings (1,2). Identification of a subdural hemorrhage necessitates further
evaluation. A thorough examination for possible child abuse is indicated, as is
a careful consideration of underlying medical conditions that increase a childīs
susceptibility to intracranial bleeding.
Malignancies, infections, and coagulation disorders are among the medical
conditions to consider. Our patient did have a mildly elevated prothrombin time
when he arrived at CMH, but it had previously been normal, and he had no other
findings consistent with a bleeding diathesis. It is important to remember that
release of cerebral thromboplastin can cause a secondary coagulopathy in some
patients with cerebral injury. Additional laboratory work, including the
measurement of individual clotting factors, may be necessary if the diagnosis is
uncertain.
Duhaime described another group of patients with increased vulnerability to
subdural hemorrhages in 1992. Patients with enlarged extraaxial spaces, such as
those with shunted hydrocephalus or cortical atrophy, may have stretching of
their bridging veins across these spaces, making the patients susceptible to
profuse bleeding caused by relatively small acceleration forces (3).
A high index of suspicion for inborn errors of metabolism is necessary when
evaluating infants with unusual or unexplained deterioration. Glutaric aciduria
type 1 is an autosomal recessive condition, which typically presents in the 1st
or 2nd year of life. Subdural hematomas and retinal hemorrhages have been
reported in some cases (4). The risk of subdural hematomas and effusions in
affected patients is estimated at 20 to 30% (5). Ocular findings, including
hemorrhages and cataracts, were discovered in more than 40% of patients in a
recent series (6). Increased intracranial pressure and alterations in protein
synthesis or structure of the lens membrane were proposed as possible
etiologies.
The leading cause of serious head injury in infants is child abuse (1).
Evaluation for abuse must not be delayed during investigation for other
underlying medical conditions. Thorough histories should be taken while the
events are still fresh in the minds of the childīs caretakers. A skeletal
survey, ophthalmology examination, and careful inspection of the integument are
essential components of the early management of young children presenting with
subdural hematomas of uncertain etiology. In most cases, hospitalization and
referral to child protection services for further investigation is warranted.
Differentiation of retinal hemorrhages caused by shaking/impact syndrome from
those caused by other mechanisms can be challenging. Numerous hemorrhages
involving all layers of the retina and extending to the periphery are
characteristic of intentional trauma (7). The presence of retinal folds and
retinoschisis is also strongly suggestive (Fig. 3). Retinal photography is
valuable for documentation and review.
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FIG. 3. A retinal photograph of a victim of shaking/impact syndrome showing
diffuse, multilayered retinal hemorrhages and a retinal fold.
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HOSPITAL COURSE
The patient was admitted to the pediatric intensive care unit, and the Child
Protection Team was consulted. Their recommendations included screening for
glutaric aciduria type 1 (GA1). Metabolic serum and urine studies were obtained.
The patient was fully awake, and stable for transfer to the pediatric ward by
the following day. Two liters of bloody fluid drained from the subdural catheter
during the first week. His metabolic studies returned during the second week of
hospitalization. Urine organic acid testing showed elevated excretion of
3-hydroxyglutaric acid and glutaric acid (4583 mmol/mol creatanine, normal <10
mmol/mol). These findings, along with reduced serum free and acyl carnitine, are
characteristic of GA1.
Appropriate dietary management was initiated, including carnitine and riboflavin
supplements, and a diet with restricted lysine and tryptophan. His hospital
course was complicated by an infection of the subdural drain. The drain was
removed, but subdural effusions reaccumulated, and the patient developed
increased intracranial pressure. He ultimately required placement of a subdural-peritoneal
shunt. The family received extensive education on the management of patients
with GA1. Importantly, prior to their childīs discharge, they were given a
written plan for acute management of subsequent illnesses or metabolic crises
that could be provided to health care workers unfamiliar with GA1.
His illness was complicated by poor oral intake, making gastrostomy tube
placement necessary. Challenging episodes of irritability, seizures, and severe
dystonia developed. Dystonia did not respond to treatment with
carbidopa-levodopa (Sinemet; DuPont Merck Pharmaceutical, Wilmington, DE) or
baclofen. Direct intramuscular injections of botulinum toxin resulted in partial
relief of the painful dystonic posturing. Ultimately, he underwent a
neurosurgical procedure, bilateral pallidotomy, to control his dystonia.
DISCUSSION
Glutaric aciduria type 1, an autosomal recessive inborn error of metabolism, was
first described by Goodman, et al. in 1975 (8). Affected individuals have
abnormal metabolism of lysine, tryptophan, and hydroxylysine due to a deficiency
of the mitochondrial enzyme glutaryl-CoA dehydrogenase. Glutaryl-CoA accumulates
proximal to the enzymatic block, and is hydrolyzed to glutaric acid. The enzyme
has been mapped to chromosome 19p13.2 (9) and the incidence has been estimated
at 1 in 30,000 (10). Affected individuals typically have normal or near normal
development in early infancy. Subtle early findings, such as truncal hypotonia
and relative macrocephaly as seen in this patient, are often present but easily
overlooked. Patients frequently suffer an episode of metabolic decompensation
during their first or second year of life. The mild hypovolemia, hypoglycemia,
and fever tolerated by most infants and toddlers during routine childhood
illnesses can be devastating to these patients. They develop a catabolic state
with accumulation of metabolic byproducts resulting in neurotoxicity. Some
children present with a clinical picture common to other organic acidemias with
hypoglycemia, acidosis, and hyperammonemia. However, many will not have acidosis
(4). Affected individuals may present with unexplained altered mental status,
atypical movements, seizures, or irritability. Classically, patients develop
dystonia and athetosis with relative sparing of intellect (11). A subset of
individuals has a more insidious onset and some remain asymptomatic into
adulthood (14,20). Historically, misdiagnoses have included infectious
encephalopathy, athetoid cerebral palsy, Reye syndrome, and shaking/impact
syndrome (19,21,22).
Elevated glutaric acid can be detected in the blood, urine, cerebrospinal fluid
(CSF), and tissues (12). Patients have a secondary carnitine deficiency, which
is detectable with serum testing. Glutaric acid has been shown to have a direct
toxic effect on striatal cells in vitro (13). Concentrations of -aminobutyric
acid are low in the basal ganglia of these patients, and the metabolism of -aminobutyric
acid is affected by glutaric acid (14). Quinolinic acid, an intermediary of
tryptophan metabolism, is another possible source of neurotoxicity (15). The
caudate and putamen shrink markedly in response to metabolic insult.
Histologically, neuronal loss and gliosis are seen (16). Fatty changes of the
liver, heart, and kidneys have been described on postmortem examination and may
be secondary to mitochondrial toxicity (17).
A number of radiologic findings are characteristic of GA1. Changes on CT scan
can be present even prior to the 1st metabolic crisis, and are an important
early diagnostic clue (18). Frontotemporal atrophy, subdural fluid collections,
widened CSF spaces, particularly wide sylvian fissures, and dilated insular
cisterns are frequently described on CT scan or MRI (18,19). Progressive
cortical atrophy, white matter attenuation, and basal ganglia changes appear
with disease progression. On MRI, basal ganglia changes typically begin with
increased T2 signal and progress to loss of volume, particularly of the caudate
and putamen (14).
There is compelling evidence that dietary management and prevention of a
catabolic state during illness reduce morbidity and mortality (12,19). Ideally,
a low lysine and tryptophan diet with carnitine and riboflavin supplements
should be started in infancy. Irritability, anorexia, vomiting, lethargy, and
worsening hypotonia are signs of metabolic decompensation in these patients and
should be considered a metabolic emergency. The child may appear toxic or
encephalopathic. Anion gap acidosis may be present. Glucose should be
administered at twice the patientīs basal metabolic rate. Administration of
insulin may also be necessary during the glucose infusion to maintain blood
glucose between 100 and 150 mg/dL. Recovery may depend on the renal clearance of
non-volatile dicarboxylic acids. This requires intravascular volume expansion to
establish vigorous urine output. A urine pH greater than 7.5 has been
recommended, as well as close attention to maintenance of a normal serum sodium
and potassium. In cases in which profound acidosis persists despite volume
expansion and glucose infusion, treatment with sodium bicarbonate can be
considered.
Differentiation between GA1 and intentional trauma may be extremely difficult.
In our case, hypotonia, an atypical developmental history, and accelerated head
growth were important clues. The early hospital course at CMH was also atypical
for that of a shaken baby. For example, this patient had extremely large
subdural fluid collections, yet he was awake and alert by the second hospital
day. In anatomically normal brains, large subdural hemorrhages are often the
result of angular acceleration of the brain. This results in severe shearing of
bridging vessels and shearing forces on the brain parenchyma. This type of
parenchymal damage is known as diffuse axonal injury and causes profound
neurologic sequelae and can be fatal (3,23).
Premorbid signs of GA1 may be subtle or nonexistent, and some authors have
argued that all infants being evaluated for the shaking/impact syndrome should
be screened for GA1. While there is an increasing awareness of GA1 among child
protection experts, there is no consensus regarding screening at this time.
CONCLUSIONS
Infants who present with unexplained subdural and retinal hemorrhages most often
are victims of child abuse. However, an autosomal recessive metabolic disorder,
glutaric aciduria type 1, is a known cause of these findings in children. Urine
organic acid testing will show a characteristic large peak of glutaric acid and
3hydroxy glutaric acid. The diagnosis can be confirmed through testing of enzyme
activity in cultured fibroblasts and leukocytes or through a genetic mutation
analysis. Early recognition and treatment of this disorder has the potential for
reducing the morbidity and mortality associated with GA1.
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Address for reprints: Sarah Soden, MD, Section of Behavioral and Developmental
Pediatrics, The Childrenīs Mercy Hospital, 2401 Gillham Road, Kansas City, MO
64108; e-mail: ssoden@cmh.edu
The authors would like to acknowledge Drs. M. Stass-Isern and T. Hug for the
retinal photograph, Drs. R. Gravis and L. Lowe for their assistance with the
radiology, and Dr. M. Tuchman for performing the initial urine organic analysis
on this patient.
Pediatr Emerg Care 2002 February;18(1):44-47
Copyright Đ 2002 Lippincott Williams & Wilkins
All rights reserved
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