tion, resulting in severe hyperinflation and ultimate
pneumothorax. Our case emphasizes that late- or
sudden-onset presentation of wheezing, especially if
unresponsive to usual asthma treatment or if requiring hospitalization, should raise suspicion that the
cause may not be asthma, and the differential diagnosis should include airway masses.1
Suzette T. Gjonaj, MD
Diana B. Lowenthal, MD
Allen J. Dozor, MD
Division of Pediatric Pulmonology
Department of Pediatrics
New York Medical College
Valhalla, NY 10595
Gustavo Stringel, MD
Division of Pediatric Surgery
Department of Surgery
New York Medical College
Valhalla, NY 10595
Fig 3. Chest radiograph immediately after extubation shows resolution of massive hyperinflation.

thoracotomy).6,10 Intrathoracic masses are difficult to
identify on posteroanterior views of chest radiographs as overlying soft tissue partially obscures the
trachea, and lateral views show the distal trachea,
but the thoracic inlet obscures the upper trachea.3,4,8,9 –11 Other diagnostic methods include a variety of radiographic techniques such as magnetic
resonance imaging, computed tomography, magnified airway films, and fluoroscopy.8 Clinically the
patient may have a normal alveolar-arterial gradient,
suggesting that the respiratory distress is from extrathoracic airway obstruction rather than pulmonary disease. Monophonic wheezing, which sounds
the same in all lung fields, may be present at the
physical examination in a patient with obstruction of
a single central airway. Pulmonary function tests
would reveal a fixed intrathoracic airway obstruction
with no response to bronchodilators.3–5,8,10
Neurogenic tumors are the rarest of the various
types of endotracheal tumors, with only 29 reported
cases in the world literature.1,3 The two types of neurogenic tracheal tumors are neurilemomas and neurofibromas, and the latter are less common.9 Only 12 cases
of neurofibromas have been reported, with 3 in the
pediatric age group.3,5,6,10,12,13 The majority of the neurofibromas occur in the lower third of the trachea,
followed by the upper third and the middle third.2 The
ages of the patients range from 6 to 71 years with no
gender difference. In the pediatric age group, benign
tracheal lesions are more common compared with malignant lesions in adults.8 Neurofibromas can be associated with von Recklinghausen’s disease, although
they occur more frequently in the absence of this disease.3– 6,8,11,13 Recurrence and malignancy of neurofibromas have been reported.5,13 Neurofibromas can successfully be removed by rigid bronchoscopy.12
In the English-language literature, this patient
seems to be the first to present with respiratory arrest
caused by an endotracheal neurofibroma. The tracheal lumen was severely obstructed by the large
intratracheal tumor and possible mucus accumula-

REFERENCES
1. Goode JG, Wetmore RF, Keon TP. Anesthetic management of a child
with an intratracheal tumor. Anesth Analg. 1986;65:1227–1230
2. Weber AL, Grillo HC. Tracheal tumors: a radiological, clinical and
pathological evaluation of 84 cases. Radiol Clin North Am. 1978;2:227–246
3. Davies MJ, Hall DR, Ross BA. Rare tracheal tumors: two case reports of
primary neurogenic tumors occurring in the trachea. Respir Med. 1993;
86:145–146
4. Rutledge J, Harolds JA. Intratracheal neurofibroma. South Med J. 1983;
76:1063–1065
5. Ma CK, Raju U, Fine G, Lewis JW. Primary tracheal neurilemoma. Arch
Pathol Lab Med. 1981;105:187–189
6. Horowitz AG, Khalil KG, Verani RR, Guthrie AM, Cowan DF. Primary
intratracheal neurilemoma. J Thorac Cardiovasc Surg. 1983;85:313–320
7. Sidman J, Wood RE, Poole M, Postma DS. Management of plexiform
neurofibroma of the larynx. Ann Otol Rhinol Laryngol. 1987;96:53–55
8. Lossos IS, Breuer R, Lafair JS. Endotracheal neurofibroma in a patient
with von Recklinghausen’s disease. Eur Respir J. 1988;1:464 – 465
9. Le-Tian X, Zhen-Fu S, Ze-Jian L, Lian Hun W, Zhong WZ. Tracheobronchial tumors: an eighteen-year series from Capital Hospital, Peking,
China. Ann Thorac Surg. 1983;35:590 –596
10. Meredith HC, Valicenti JF. Solitary neurofibroma of the airway. Br J
Radiol. 1978;51:218 –219
11. Thijs-Van Nies A, Van de Brekel B, Buytendijk HJ. Neurofibroma of the
trachea: a case report. Thorax. 1978;33:121–123
12. Karlan MS, Livingston PA, Baker DC. Diagnosis of tracheal tumors. Ann
Otol Rhinol Laryngol. 1973;82:790 –799
13. Khan SU, Lenox R, Mehta AC. Endotracheal neurofibromas. J Bronchol.
1995;2:143–144

Basal Ganglia Infarction in a Child
With Disulfiram Poisoning
ABBREVIATIONS. CT, computed tomography; SPECT, singlephoton emission computed tomography; MRI, magnetic resonance imaging.

Disulfiram is used worldwide to treat alcoholism.
The presence of this drug in the home makes it a
potential agent encountered in accidental poisoning.
Received for publication Jul 8, 1996; accepted Oct 11, 1996.
Reprint requests to (M.W.L.-L.) Critical Care Medicine, Children’s Hospital
of Michigan, 3901 Beaubien Blvd, Detroit, MI 48201–5629.
PEDIATRICS (ISSN 0031 4005). Copyright © 1997 by the American Academy of Pediatrics.

EXPERIENCE AND REASON

605

Fig 1. Right and left sagittal singlephoton emission computed tomographic images of the brain show areas
of decreased perfusion in the frontal
and parietal cortex and basal ganglia
bilaterally.

We report a child who ingested disulfiram and subsequently had unusual and prolonged neurologic
manifestations of dystonia, complete loss of developmental milestones, and spastic tetraparesis.
CASE REPORT
A 5-year-old girl was seen at the referring hospital for upper
respiratory tract infection for 7 days and vomiting for 2 days. She
was incoherent and unresponsive, with significant dehydration
and cold clammy extremities on the day of admission. A bedside
glucose test indicated low blood sugar. Two doses of 25% dextrose
(2 mL/kg) and 0.1 mg/kg naloxone were administered. Laboratory data obtained before the above intervention included serum
sodium, 141 mEq/L; potassium, 6.0 mEq/L; chlorides, 106
mEq/L; carbon dioxide content, 5 mEq/L; blood urea nitrogen, 90
mg/dL; creatinine, 1.4 mg/dL; glucose, 359 mg/dL; lactic acid, 1.3
mmol/L; and osmolality, 340 mOsm/kg. Capillary blood gas measurement showed a pH of 7.12, Pco2 of 18 mm Hg, Po2 of 98
mm Hg, and serum bicarbonate of 5.5 mEq/L. A complete blood
count and spinal fluid showed no abnormalities. Subsequently, a
diagnosis of diabetic ketoacidosis was made. Intravascular volume expansion was carried out using 300 mL of lactated Ringer’s
solution. She was transferred to the Children’s Hospital of Michigan. At arrival to the intensive care unit, the physical examination
revealed the following: temperature, 36.6°C (rectal); heart rate, 132
beats/min; Kussmaul breathing at a rate of 36 breaths/min; and
blood pressure, 122/76 mm Hg. She had cold, clammy extremities.
She remained comatose, with occasional spontaneous, nonpurposeful movements. No focal neurologic deficits were noted. Serum glucose was 551 mg/dL. A comprehensive toxicologic screen
including an alcohol panel did not reveal the presence of any
drugs or toxins in the urine or serum. Continuous infusions of
insulin and bicarbonate were started. Soon after admission, hypotension developed despite aggressive intravascular volume expansion and inotropic support with dobutamine and dopamine.
The patient had generalized tonic-clonic seizures, which resolved
with the administration of lorazepam (0.1 mg/kg) and diphenylhydantoin (15 mg/kg). Activated charcoal with sorbitol was administered for suspicion of ingestion of a toxic substance. A history subsequently obtained from the patient’s father revealed that
he was currently taking disulfiram for alcoholism. He could not
account for 19 tablets (250 mg per tablet) of disulfiram. The container had teeth marks on the lid, and a part of a tooth, which
matched the patient’s broken-off lateral incisor, was found in the
bottle.

606

EXPERIENCE AND REASON

Insulin and bicarbonate infusions were discontinued. There
were no further seizures. Her hemodynamic status stabilized, and
inotropic agents were discontinued. She was observed to have
multiple lucid intervals during which she seemed to recognize her
parents and to respond to verbal stimuli. However, she again
became unresponsive on the fifth hospital day. Additionally, she
had dystonic activity, with eye deviation, turning her head to one
side, with tonic flexion of the upper extremities and fist clenching.
Computed tomography (CT) of the brain 5 days after the disulfiram ingestion showed areas of low attenuation in the basal
ganglia bilaterally, involving the globus pallidus and caudate
nuclei, consistent with infarction. The dystonic activity persisted
and worsened. She was treated with increasing doses of levodopa
and clonazepam. On the 10th hospital day, single-photon emission
computed tomography (SPECT) of the brain with technetium 99m
exametazime (Ceretec) showed multiple areas of decreased perfusion in the frontal and parietal cortex bilaterally and markedly
diminished perfusion of the basal ganglia, which persisted after
intravenous administration of acetazolamide (Fig 1). These findings were consistent with multiple cortical and basal ganglia
infarcts bilaterally. Magnetic resonance imaging (MRI) revealed
increased signal intensity in the caudate nuclei, putamen, and, to
a lesser extent, the globus pallidus bilaterally on proton density–
and T2-weighted images (Fig 2). Despite maximum doses of levodopa and clonazepam, the patient continued to have worsening
dystonia and remained comatose.
She underwent extensive rehabilitation and was discharged 4
months after admission with persistence of dystonic movements.
She also had spastic quadriparesis, bowel and bladder incontinence, and loss of all developmental milestones.
Two years after ingestion, at the age of 7 years, the patient
continues to have intermittent dystonic activity. She can now
speak three or four words, follow simple commands, and answer
some questions. She has generalized rigidity, which is worse on
the right side. The SPECT of the brain performed 2 years after
disulfiram ingestion shows persistence of infarcted areas in both
basal ganglia, with left-side predominance and hypoperfusion of
frontal, parietal, and temporal cortex bilaterally, associated with
areas of infarcts in the cingulate gyrus on each side.

DISCUSSION

The major metabolic pathway involving the oxidation of alcohol is through alcohol dehydrogenase,
using nicotinamide adenine dinucleotide as the hydrogen acceptor. Disulfiram interferes with the oxi-

Fig 2. T2-weighted magnetic resonance image showing increased
signal intensity in the basal ganglia bilaterally.

dative metabolism of ethanol by competing with
nicotinamide adenine dinucleotide for aldehyde dehydrogenase, leading to the accumulation of acetaldehyde. In the presence of disulfiram, the ingestion
of ethanol leads to the accumulation of acetaldehyde,
which produces the unpleasant symptoms associated
with this drug. Disulfiram intoxication in the absence
of ethanol has been well described in adults.1 Neuropsychiatric symptoms such as headache, peripheral neuropathies, catatonia, depression, and acute
psychosis are common. Very rarely, hepatotoxicity
and Parkinson-like symptoms have been reported.
There are only a few case reports of acute intoxication with disulfiram in children, none of which describes dystonia as a persistent neurologic deficit.2–5
The diagnosis of disulfiram poisoning can be difficult. Symptoms may occasionally resemble diabetic
ketoacidosis with acidosis disproportionate to the
degree of dehydration and hyperglycemia as a common accompanying symptom. Furthermore, disulfiram is not detected by standard toxicologic screens.
Its metabolites can be measured only by highly specialized laboratory techniques, which are not readily
available. It is rapidly cleared from the circulation,
and frequently neither the drug nor its metabolites
can be detected despite the use of sophisticated tests.
Our patient presented with hyperglycemia, hyperosmolar coma, and ketosis, with a negative toxicologic
screen, and was thought to have diabetic ketoacidosis.
After oral administration, 80% of disulfiram is absorbed rapidly from the gastrointestinal tract and
reduced in the blood to diethyldithiocarbamate by
the glutathione reductase system in erythrocytes. Diethyldithiocarbamate is metabolized in the liver by
conjugation with glucuronic acid as the primary detoxifying mechanism. A small amount of diethyldi-

thiocarbamate is broken down by nonenzymatic degradation to form carbon disulfide and diethylamine,
which are rapidly excreted by the kidneys. The exact
mechanism of disulfiram-mediated encephalopathy
is not known. However, diethydithiocarbamate and
carbon disulfide have been implicated and have been
shown to inhibit the activity of the enzyme dopamine-b-hydroxylase, leading to the accumulation of
dopamine, producing a relative deficiency of adrenaline and noradrenaline in the area of the basal ganglia. Dopamine-mediated cellular injury may be related to its ability to induce excitatoxic effects of
glutamate- and calcium-mediated cell death, as well
as to impair the cellular ability to eliminate free
oxygen radicals.6,7 Lesions of the basal ganglia observed with CT and MRI have been described in
adult patients with clinical manifestations of movement disorders such as Parkinsonism, catatonic akinesia, and dystonias.8,9 The persistent infarcts observed in the basal ganglia and cortical regions in our
patient are consistent with these reports. Lesions
noted on anatomic and functional imaging studies
correlate with the extrapyramidal symptoms noted
in this patient. The inhibition of dopamine b-hydroxylase activity also accounts for the altered sympathetic tone, hypotension, and arrhythmias noted in
disulfiram poisoning.10
The possibility of disulfiram poisoning should be
entertained in a patient with acute onset of hyperglycemia, ketosis, hypotension, and extrapyramidal
symptoms. The diagnosis depends mainly on the
history, clinical findings, and circumstantial evidence. Both CT and MRI studies are valuable in
demonstrating central nervous system involvement.
In addition, functional brain imaging with SPECT at
baseline and after intravenous administration of acetazolamide is a sensitive means of localizing and
evaluating the full extent of brain infarction and
ischemia. In our patient, infarcts in the frontal cortex
were best demonstrated on brain SPECT. Acetazolamide increases cerebral blood flow by 30% compared with baseline levels without changing regional
flow distribution.11 The vessels in the areas of brain
infarction do not dilate after acetazolamide administration, whereas the vessels in the normal areas of the
brain and regions of cerebral ischemia dilate, enhancing the radioactivity ratio between regions of high
flow and areas with no flow or low flow. This permits differentiation of areas of ischemia and infarction.
There is no specific therapy for disulfiram toxicity.
The treatment involves the support of cardiorespiratory and metabolic function in the acute phase and
the treatment of seizures and extrapyramidal manifestations with appropriate drugs and rehabilitation.
In summary, this case report illustrates the severity of neurologic damage in a child after acute intoxication with disulfiram. It underscores the need to
entertain the diagnosis of disulfiram poisoning in
any child who presents with hyperglycemia and ketoacidosis with cardiovascular instability and signs
of central nervous system involvement disproportionate to those observed in hyperosmolar or diabetic
coma.
EXPERIENCE AND REASON

607

Prashant Mahajan, MD
Mary W. Lieh-Lai, MD, FCCP
Ashok Sarnaik, MD, FCCM
Department of Pediatrics
Children’s Hospital of Michigan
Wayne State University School of Medicine
Detroit, MI 48201
Sam R. Kottamasu, MD
Department of Radiology
Children’s Hospital of Michigan
Wayne State University School of Medicine
Detroit, MI 48201

the nongenital rash. Herpes zoster (HZ), although
uncommon in healthy children, must also be included in the differential diagnosis of painful genital
or anal vesicular rash. Reactivation of the varicella
zoster virus (VZV) along sacral dermatomes can result in highly suggestive painful vesicles. Although
viral culture is the standard of reference for viral
identification, rapid direct immunofluorescence assay (DFA) of vesicular contents is a clinically useful
way to determine the infectious cause of a suspicious
rash.

REFERENCES

CASE REPORT

1. Liddon SC, Satran R. Disulfiram (Antabuse) psychosis. Am J Psychiatry.
1967;123:1284 –1289
2. Wokitel E. Vergiftung mit Antabus bei einem 10 jahrigen madchen. Arch
Kinderheilk. 1960;161:145–149
3. Buksowicz C. Sezpol mozgowy u dziecka w nastepstevie ostrego zatrucia antabusen. Neurol Neurochir I Psychiatria Pol. 1962;12:293–295
4. Benitz EW, Jatro DS. Disulfiram intoxication in a child. J Pediatr. 1984;
105:487– 489
5. Reichederfer TE. Acute disulfiram poisoning in a child. Q J Stud Alcohol.
1969;30:724 –728
6. Hekkila RE, Cabbat FS, Conhen A. In vivo inhibition of superoxide
dismutase in mice by diethyldithiocarbamate. J Biol Chem. 1976;251:2182
7. Rothmann S, Olney J. Glutamate and the pathophysiology of hypoxicischemia damage. Ann Neurol. 1986;19:105–111
8. Krauss JK, Mohadju M, Wakhloo AK, Mudinger F. Dystonia and akinesia due to pallidoputaminal lesions after disulfiram intoxication.
Movement Disorders. 1991;6:166 –170
9. Harawa S, Matsuchita M. An autopsy case of disulfiram induced psychosis with Parkisonian syndrome. Seishin Shinkeigaku Zasshi. 1982;86:
503–512
10. Goldstein M, Anagnoste B, Lauber E, McKeregahan MR. Inhibition of
dopamine b-hydroxylase by disulfiram. Life Sci. 1964;3:763–767
11. Bonte FJ, Denous MD, Reisch JS. The effect of acetazolamide on regional
cerebral blood flow in normal human subjects as measured by singleproton emission computed tomography. Invest Radiol. 1988;23:564 –568

A previously healthy 91⁄2-year-old girl presented to her primary
care physician with a complaint of a painful perianal rash with
dyschezia for 4 days. She was afebrile and denied abdominal pain,
vomiting, diarrhea, dysuria, pruritis, or a generalized skin rash.
Perianal vesicles were identified and considered to be highly
suspicious for HSV. The possibility of sexual abuse was discussed
with the family. The child’s parents had no concern about sexual
abuse, and the child denied any prior sexual assault. Because of
the presumptive diagnosis of HSV, a report of suspected child
sexual abuse was made to the local child welfare agency. The child
was referred to the emergency department at Children’s Hospital
of Philadelphia for further evaluation and care.
In the emergency department, vaginal swabs were sent for
Gram stain and routine vaginal culture. Vaginal and rectal cultures for gonorrhea and chlamydia were obtained. The vesicles
were unroofed, and vesicular contents were sent for culture and
DFA testing for both HSV and VZV. Laboratory methods used for
both viral culture and DFA are described by Coffin and Hodinka.3
Oral acyclovir was prescribed, and follow-up in the hospital’s
child abuse clinic was arranged.
The patient was examined the following day in the clinic. Her
general physical examination results were normal for age. She was
prepubertal with Tanner stage I breasts and pubic hair. Her genital examination revealed a scant, thin vaginal discharge without
odor. The hymen showed early estrogenization with an annular
configuration and smooth, symmetric contours. There were no
hymenal injuries, and no vulvar vesicles were seen. The anal
examination revealed multiple vesicles in different stages of healing, predominantly in the right perianal region (Figure).
Vaginal Gram stain showed no white blood cells or bacteria.
The DFA test was negative for HSV and positive for VZV. After
further inquiry, we learned that the patient had primary varicella
infection at 2 years of age. A few scarred pox marks were identified on the child’s forehead. The diagnosis of HZ in the S-5
dermatome was made. Stool softeners were prescribed. The primary care physician was notified of the diagnosis, and follow-up
was arranged. Child welfare officials were also notified of the
diagnosis, and the investigation of possible sexual abuse was
terminated. Vaginal and rectal cultures for gonorrhea and chlamydia were ultimately negative. A routine vaginal culture grew
normal flora. Twenty-six days after the collection of specimens,
VZV was isolated by viral culture and confirmed by immunofluorescence.

Perianal Herpes Zoster Presenting
as Suspected Child Abuse
ABBREVIATIONS. HSV, herpes simplex virus; HZ, herpes zoster;
VZV, varicella zoster virus; DFA, direct immunofluorescence assay.

The appearance of a vesicular rash in the anogenital area of a child should alert the practitioner to the
possibility of herpes simplex virus (HSV) infection
and potential sexual abuse. However, careful attention to other sources of infection must be made to
avoid unfounded suspicion of abuse. The rash of
primary varicella zoster has been demonstrated to
mimic HSV infection.1,2 In two published case studies, varicella vesicles began in the anogenital region
before progressing to a more typical diffuse distribution of lesions. In these cases the diagnosis of suspected child abuse was made before the eruption of
Received for publication Aug 5, 1996; accepted Oct 10, 1996.
Reprint requests to (C.W.C.) Division of General Pediatrics, Children’s
Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Room
2416, Philadelphia, PA 19104.
PEDIATRICS (ISSN 0031 4005). Copyright © 1997 by the American Academy of Pediatrics.

608

EXPERIENCE AND REASON

DISCUSSION

The proper recognition of physical and infectious
indicators of child sexual abuse can help identify
victimized children. However, careful exclusion of
other possible diagnoses is necessary to avoid the
trauma of an unjustified investigation.4 Both HSV1
and HSV2 have been reported in sexually abused
children,5,6 and a thorough evaluation of possible
sexual abuse is indicated for children with genital
HSV infection. HSV and VZV infections may be clinically indistinguishable, especially when vesicles are
isolated to a single dermatome.7,8 Primary HSV infection is generally associated with systemic symptoms, including fever, headache, malaise, and myal-