Escolar Documentos
Profissional Documentos
Cultura Documentos
n e w e ng l a n d j o u r na l
of
m e dic i n e
1156
Dr. Sarah M. Barnett (Neurology): An 8-day-old boy was admitted to the neonatal intensive care unit of this hospital because of weakness and lethargy.
The patient was born after a full-term gestation to a 26-year-old primigravida at
a birthing center. The mother had received prenatal care with normal screening laboratory tests, including a positive test result for antibody to rubella and negative test
results for group B streptococcus, rapid plasma reagin, hepatitis C, and human
immunodeficiency virus. The prenatal course was uncomplicated; the mother had
no fever or other symptoms of infection, and there was no change in fetal movement in the days before delivery. The birth weight was 3 kg, the length 49.5 cm,
and the head circumference 33 cm. The Apgar scores were 6 at 1 minute and 7 at
5 minutes.
Immediately after birth, there were signs of respiratory distress, including grunting and flaring, and the infant was admitted to another hospital. On examination,
the temperature was 36.8C, the pulse 128 beats per minute, the respiratory rate
44 breaths per minute with grunting, and the oxygen saturation 97% while the
patient was breathing ambient air. A systolic ejection murmur (grade 2 out of 6) was
heard; hypospadias and a hydrocele in the right scrotum were noted, and ecchymosis was present on the left thumb. The remainder of the examination was normal.
Newborn screening for metabolic abnormalities was normal; other laboratory-test
results are shown in Table 1. An electrocardiogram revealed a normal sinus rhythm.
The respiratory distress resolved. Brain-stem auditory evoked responses were abnormal bilaterally. An appointment was made for additional audiology testing, and
the patient was discharged home on the fourth hospital day with follow-up later
that day with his pediatrician. During the next 5 days, he breast-fed well and was
appropriately interactive. Two days before admission, additional outpatient auditory
testing confirmed the presence of bilateral congenital sensorineural deafness.
On the day before admission, the patient was seen by his pediatrician at noon
and appeared well. In the midafternoon, he became disinterested in breast-feeding
Downloaded from www.nejm.org on May 10, 2009 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
1 Day before
Admission,
at Other Hospital
On
Admission
Hematocrit (%)
42.066.0
49.5
37.4
40.1
Hemoglobin (g/dl)
13.521.5
11.9
12.3
Variable
2nd Hospital
Day
500021,000
9600
10,200
9700
Neutrophils (%)
3048
55
50
47
Lymphocytes (%)
4081
30
34
32
15
21
Monocytes (%)
411
010
150,000450,000
173,000
81,000
1
0.52.5
2.2
3,900,0006,300,000
4,490,000
88126
Glucose (mg/dl)
60100
93
5.97.5
5.2
Albumin (g/dl)
3.44.8
3.2
8.510.5
10.0
Calcium (mg/dl)
Ionic calcium (mmol/liter)
83
99
111
9.4
1.141.30
1.29
15350
163
47150
32
1055
18
Lactate (mmol/liter)
0.52.2
1.1
Pyruvate (mmol/liter)
0.080.16
0.09
* To convert the values for glucose to millimoles per liter, multiply by 0.05551. To convert the values for calcium to millimoles per liter, multiply by 0.250.
Reference values are affected by many variables, including the patient population and the laboratory methods used. The
ranges used at Massachusetts General Hospital for newborns and infants are estimates derived from a combination of
published normal ranges and internal data for these age groups.
The reference range was obtained from the first hospital where the patient was admitted.
Downloaded from www.nejm.org on May 10, 2009 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
1157
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
Differ en t i a l Di agnosis
Dr. Kevin J. Staley: An acute encephalopathy developed in this patient at 8 days of age. This is a
difficult clinical situation because of the urgency
with which treatable disorders must be identified
from a broad list of potential causes. The initial
Downloaded from www.nejm.org on May 10, 2009 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
On Admission
Colorless
Amber
Pink
Clear
Slight
Moderate
None
Yes
Yes
None
9920
16,278
030
18
23
Neutrophils (%)
Lymphocytes (%)
50
83
Monocytes (%)
44
Macrophages (%)
Variable
Color
Turbidity
Xanthochromia
Red cells (per
mm3)
Comments
Yellow crystals
present
Protein (mg/dl)
555
503
350
Glucose (mg/dl)
5075
35
34
Negative
Negative
Negative
0.52.2
2.9
0.501.70
Gram stain
1.23
No organisms seen
Acid-fast stain
No organisms seen
Negative
Culture
Sterile
Sterile
* To convert the values for glucose to millimoles per liter, multiply by 0.05551. PCR denotes polymerase chain reaction.
Reference values are affected by many variables, including the patient population and the laboratory methods used. The
ranges used at Massachusetts General Hospital for newborns and infants are estimates derived from a combination of
published normal ranges and internal data for these age groups.
Unclassified cells included a cluster of large, immature cells with indistinct borders, suggestive of germinal matrix cells.
Trauma is an important consideration in an afebrile infant presenting with acute changes in mental status, particularly in light of the history of an
unwitnessed fall. The increase in head circumference from 33 to 35.5 cm in the 8 days before admission and the tense anterior fontanelle could
be the consequence of traumatic intracranial bleeding. Retinal hemorrhage is strongly associated with
traumatic brain injury and at this age is unlikely
to be related to delivery.1 The cerebrospinal fluid
was bloody and did not clear, and the xanthochromia indicates bleeding at least several hours
before the lumbar puncture.2 Although basilar
skull fractures can cause hearing loss, trauma is
not a likely cause of this infants bilateral sensory
deafness.3
Radiologic examinations are the best means
to evaluate closed head injuries associated with
reduced levels of consciousness. May we review
the imaging studies?
Dr. P. Ellen Grant: The initial CT demonstrated
intraventricular hemorrhage with ventriculomegaly and multifocal, symmetrical hemorrhage and
edema of the deep gray nuclei, cerebral white
matter, cerebellar white matter, and pons, with
sparing of the subcortical white matter (Fig. 1).
The cerebral sulci were effaced, and the sutures
were widened, consistent with severe cerebral
Downloaded from www.nejm.org on May 10, 2009 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
1159
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
ARTIST: mst
Line
H/T
Combo
4-C
H/T
SIZE
33p9
whelming
swelling. MRI 15 hours after admission confirmed
AUTHOR, PLEASE
NOTE: infections in infancy. However, hypoFigurewith
has been
redrawnthermia
and type has
been
due
toreset.
infection is usually associated with
the presence of recent hemorrhage,
more
Please check carefully.
extensive petechial hemorrhage in the deep gray shock,5 and there were few such signs in this
nuclei, pons, and dentate nucleiJOB:
and involvement
infant.ISSUE:
Other9-11-08
vital signs were normal, no sugges35911
of the inferior vermis (Fig. 2). The findings on tive findings were reported from the initial physMRA were normal. The features of the blood prod- ical examination, and the initial laboratory evalucts (dark on T2-weighted images and isointense uations did not reveal evidence of multisystem
to slightly bright on T1-weighted images) sug- involvement.
gested that the hemorrhage was approximately
Bacterial meningitis in this age group is most
2 to 4 days old. MRI on the third day revealed frequently due to group B streptococci, Escherichia
no new hemorrhage. The severe, diffuse swelling coli, or Listeria monocytogenes.6 Although there was
was resolving, and the ventricles had decreased no nuchal rigidity on the initial physical examinain size. However, apart from the cortex and sub- tion, its absence does not exclude meningeal ircortical white matter, the brain remained abnor- ritation in very young infants. The cell counts in
mally bright on T2-weighted images in areas not the blood and cerebrospinal fluid are not suggesinvolved by hemorrhage.
tive of bacterial infection, particularly an advanced
In summary, the images show a devastating infection causing this degree of encephalopathy.
brain injury with diffuse edema and hemorrhage. The MRI findings of symmetric injury to deep
The most striking aspect of the pattern of involve- nuclei and brain-stem structures are not suggesment is its symmetry.
tive of meningitis, in which the cerebral cortex is
Dr. Staley: The imaging studies demonstrate in- most frequently compromised, presumably due to
tracranial hemorrhage, but there are no skull frac- its greater proximity to the inflamed meninges.7
tures; there is no evidence of subdural or subarach- Although perforating arteries supplying deep brain
noid bleeding; there are no signal changes on MRI structures are occasionally compromised in mensuggestive of shear injury,4 and the symmetry and ingitis, the extent and symmetry of the lesions in
location of the hemorrhages would be very un- this patient do not suggest such a cause.
usual for trauma.
Congenital infections present in the perinatal
period, and two of these, rubella and cytomegalic
Infection
virus, are associated with congenital sensorineural
Infections are important treatable causes of acute deafness. This infant did not have microcephaly,
encephalopathy in infancy. Although this infant systemic involvement, intracranial calcifications,
was afebrile, hypothermia is frequent in over- or retinopathy, making congenital infection un1160
Downloaded from www.nejm.org on May 10, 2009 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
Figure 2. Axial T2-Weighted Fast SpinEcho Images from Initial MRI, Showing Marked Ventriculomegaly
and Intraventricular Hemorrhage, with Severe Cerebral Edema.
At the level of the midcerebellum (Panel A), hemorrhage is present in the posterior pons and dentate nuclei (outRETAKE
1st
AUTHOR Staley
lined by arrows) on a background ofICM
markedly
edematous pons and cerebellum (high T2 signal). At the level of the
2nd
REG F FIGURE
2a-c
deep gray nuclei (Panel B), hemorrhage is seen to involve all deep gray-matter structures
(outlined by arrows) on a
3rd
CASE
TITLE
background of marked edema (high T2 signal). At the level of the lateral ventricular
Revised bodies (Panel C), multiple reEMail
Line
4-C
gions of hemorrhage are present (arrows).
SIZE
Enon
ARTIST: mst
FILL
H/T
Combo
H/T
33p9
Downloaded from www.nejm.org on May 10, 2009 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
1161
The
n e w e ng l a n d j o u r na l
1162
of
m e dic i n e
Downloaded from www.nejm.org on May 10, 2009 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
tal day. Our immediate clinical diagnosis was lifethreatening intracranial hypertension due to hemorrhage, a neurosurgical emergency. Within a few
minutes, the child was intubated and a ventricular tap was performed. The vital signs rectified,
the decerebrate state relaxed, and the fontanelles
relaxed. That afternoon, MRI showed the remarkable pattern described above, which essentially
excluded virtually all diagnoses but a mitochondrial disorder.
Cl inic a l Di agnosis
Mitochondrial encephalopathy with intracranial
hemorrhage.
Dr . K e v in J. S ta l e y s Di agnosis
Leigh-like syndrome of mitochondrial encephalopathy.
Downloaded from www.nejm.org on May 10, 2009 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
1163
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
1164
Downloaded from www.nejm.org on May 10, 2009 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
Downloaded from www.nejm.org on May 10, 2009 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
1165
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
Dr. Staley reports holding a patent for the treatment of neonatal seizures with bumetanide, which is not licensed and is not
associated with revenue; and Dr. Hedley-Whyte, having an equity
interest in Becton Dickinson. No other potential conflict of interest relevant to this article was reported.
References
1. Kaur B, Taylor D. Fundus hemor-
1166
Downloaded from www.nejm.org on May 10, 2009 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh syndrome. Mol Genet Metab 2007;90:10-4.
Copyright 2008 Massachusetts Medical Society.
Lantern Slides Updated: Complete PowerPoint Slide Sets from the Clinicopathological Conferences
Any reader of the Journal who uses the Case Records of the Massachusetts General Hospital as a teaching exercise or reference
material is now eligible to receive a complete set of PowerPoint slides, including digital images, with identifying legends,
shown at the live Clinicopathological Conference (CPC) that is the basis of the Case Record. This slide set contains all of the
images from the CPC, not only those published in the Journal. Radiographic, neurologic, and cardiac studies, gross specimens,
and photomicrographs, as well as unpublished text slides, tables, and diagrams, are included. Every year 40 sets are produced,
averaging 50-60 slides per set. Each set is supplied on a compact disc and is mailed to coincide with the publication of the
Case Record.
The cost of an annual subscription is $600, or individual sets may be purchased for $50 each. Application forms for the current
subscription year, which began in January, may be obtained from the Lantern Slides Service, Department of Pathology,
Massachusetts General Hospital, Boston, MA 02114 (telephone 617-726-2974) or e-mail Pathphotoslides@partners.org.
Downloaded from www.nejm.org on May 10, 2009 . Copyright 2008 Massachusetts Medical Society. All rights reserved.
1167