The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne

Case Records of the Massachusetts General Hospital

TABLE 1. HEMATOLOGIC LABORATORY VALUES.

VARIABLE

Weekly Clinicopathological Exercises

FOUNDED

BY

RICHARD

C.

CABOT

R O B E R T E . S C U L L Y , M. D. , Editor
E U G E N E J. M A R K , M. D. , Associate Editor
W I L L I A M F. M C N E E L Y , M. D. , Associate Editor
J O - A N N E O. S H E P A R D , M. D. , Associate Editor
S A L L Y H . E B E L I N G , Assistant Editor
S T A C E Y M. E L L E N D E R , Assistant Editor
C H R I S T I N E C . P E T E R S , Editorial Staff

ON DAY OF
ADMISSION

Hematocrit (%)
White-cell count (per mm3)
Differential count (%)
Neutrophils
Band forms
Lymphocytes
Monocytes
Platelet count (per mm3)
Prothrombin time
Partial-thromboplastin time

ON SECOND
HOSPITAL DAY

45
7,000

50
20,600

66
0
27
7
389,000
Normal
Normal

82
3
6
9
477,000

Case 12-2001

PRESENTATION OF CASE

A 16-year-old boy was admitted to the hospital because of an altered mental and emotional status.
At an uncertain interval before admission, the patient began to have diarrhea. One week before admission, a sore throat and productive cough developed,
with a vague sensation of fever, and he took an antihistamine. Although usually quiet, he became confused on noon of the day before admission and began
to talk nonsense. He was seen at another hospital,
where he mentioned something that suggested an injection of illicit drugs. He spat at the nursing staff and
used profane language. After haloperidol had been
injected, he became more calm. Four-point restraints
were applied. He then began to hyperventilate and became rigid. He was rushed to this hospital.
The patient had been born in Cambodia, but had
lived in this country since infancy. His high-school
grades were average or below average. He had no history of previous medical illness. He had smoked both
tobacco and marijuana. The patients mother had given him herbal tea because of the diarrhea, but he
took no prescription medications. He reportedly had
taken two pills of an over-the-counter influenza remedy the day before admission and one on the day of
admission. His four siblings were well; his mother had
a history of depression.
The temperature was 37.7C, the pulse was 100,
and the respirations were 19. The blood pressure was
140/60 mm Hg.
On examination, the patient was briefly awake and
calm but grimacing. There was no evidence of repeated venipunctures. He resisted examination of the oropharynx. The general physical examination showed no
abnormalities. The patient knew that he was in a hos-

TABLE 2. BLOOD CHEMICAL

VARIABLE

AND

ENZYME VALUES.*

ON DAY OF
ADMISSION

Urea nitrogen (mg/dl)

Creatinine (mg/dl)
Uric acid (mg/dl)
Albumin and globulin
Calcium
Phosphorus (mg/dl)
Glucose (mg/dl)
Total and conjugated bilirubin
Sodium (mmol/liter)
Potassium (mmol/liter)
Chloride (mmol/liter)
Carbon dioxide (mmol/liter)
Lactic acid (mmol/liter)
Creatine kinase (U/liter)
Pyruvate (mmol/liter)

Normal
Normal
2
Normal
Normal
2.5
154
Normal
138
3.0
107
27.5

ON SECOND
HOSPITAL DAY

9
1.5
Normal
Normal
Normal
173
143
3.1
109
7.3
4
620
0.32

*To convert the value for urea nitrogen to millimoles per

liter, multiply by 0.357. To convert the value for creatinine
to micromoles per liter, multiply by 88.4. To convert the value for uric acid to micromoles per liter, multiply by 59.48.
To convert the value for phosphorus to millimoles per liter,
multiply by 0.3229. To convert the values for glucose to millimoles per liter, multiply by 0.05551.
The normal range is 0.008 to 0.16 mmol per liter.

pital but could not name the day or month and responded minimally to most questions.
Laboratory tests were performed (Tables 1 and 2).
An electrocardiogram revealed a sinus tachycardia at
a rate of 111, with nonspecific T-wave flattening. Radiographs of the soft tissues of the neck and single
images of the chest and abdomen showed no abnor-

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CASE RECORDS OF TH E MAS SACH USET TS GENERA L H OS PITA L

malities. A throat swab was obtained for culture. Ceftriaxone and acyclovir were administered intravenously. The patient again used profane language and spat
at the nursing staff; on two occasions he pulled out
an intravenous catheter. Throughout his hospital stay,
his temperature did not exceed 37.7C.
Early on the second hospital day, a computed tomographic scan of the head (Fig. 1), obtained without
the intravenous administration of contrast material,
showed no abnormalities. The findings on a radiograph of the chest were normal. A lumbar puncture
was performed (Table 3). The temperature was 37.5C.
On neurologic examination, the patient knew his
name, that of the hospital, and the date. At times he
babbled, exhibited motor agitation, and then appeared
to go to sleep but was awakened promptly by noxious
stimuli. The optic disks were not seen. No obvious
cranial-nerve defect was detected. He moved his arms
and legs with apparently equal strength while resisting
the four-point restraints. The deep-tendon reflexes
were +++ and symmetric, except that the ankle jerks
were ++++, with clonus; the plantar responses were
flexor. Episodes of migrating rippling movements of
arm and leg muscles, which sometimes progressed to
twitching of the affected limbs, were observed. Dur-

TABLE 3. FINDINGS

ON

LUMBAR PUNCTURE.*

VARIABLE

FINDING

Appearance of fluid
Clear, colorless
Cells
Absent
Microorganisms
Absent
Glucose (mg/dl)
91
Total protein (mg/dl)
15
PCR tests for human herpesviruses 1 and 2
Negative
*To convert the value for glucose to millimoles per liter,
multiply by 0.05551. PCR denotes polymerase chain reaction.

ing these episodes, each of which lasted several seconds, the patient was able to speak. An electroencephalographic study showed abundant muscle artifact
without evidence of seizure activity.
In the early afternoon of the second day, the patient became extremely rigid and unresponsive, with
his jaws tightly clenched; the pulse was 180 and regular, the respirations were 60 or higher, and the peak
blood pressure was 160/90 mm Hg. No clonic activity was witnessed. Ten minutes after the patient had
become rigid and unresponsive, lorazepam (2 mg) was
injected intravenously, and within one minute, the
rigidity and tachypnea had subsided. Blood and urine
specimens were obtained immediately after this episode. The urine was markedly positive for occult
blood; the sediment contained 0 to 2 white cells and
3 to 5 red cells per high-power field. Laboratory tests
were performed (Tables 1 and 2). Venous-blood gas
levels were measured, and one hour later, arterialblood gas levels were measured (Table 4). Tests of
blood and urine specimens for toxic substances (Table 5) were all negative.
A diagnostic procedure was performed.

TABLE 4. BLOOD GAS VALUES

ON SECOND HOSPITAL DAY.

VARIABLE

Partial pressure of oxygen (mm Hg)

Partial pressure of carbon dioxide
(mm Hg)
Bicarbonate (mmol/liter)
pH

Figure 1. Axial Computed Tomographic Scan of the Brain, Obtained at the Level of the Frontal Horns, Showing a Normal Appearance of the Lenticular Nuclei (Straight Arrow) and Thalamus
(Curved Arrow).

AFTER THE
ONE
ADMINISTRATION HOUR
OF LORAZEPAM* LATER

74
32
8
7.03

143
35
19
7.3

*Values are for venous blood.

Values are for arterial blood. At the time of the measurements, the patient was breathing an enriched oxygen mixture.

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TABLE 5. TESTS

FOR

TOXIC SUBSTANCES.*

Antihistamines other than diphenhydramine

Ethanol
Methanol
Ethylene glycol
Salicylate
Ibuprofen
Theophylline
Barbiturates
Benzodiazepines
Cyclic antidepressants
Some phenothiazines
Cocaine
Cannabinoids
Phencyclidine
Heroin
Amphetamines, including methamphetamine
and 3,4-methylenedioxymethamphetamine
(ecstasy), with special tests for ketamine,
lysergic acid diethylamide, mescaline
(peyote), psilocybin, and hippuric acid (a
toluene metabolite), among other agents.
*None of the substances were detected.

DIFFERENTIAL DIAGNOSIS

DR. MARK H. LIBENSON*: This boy presented in

a state of confusion, with subsequent episodes of pronounced muscle rigidity, during which he remained
conscious. The final episode of muscle stiffening was
severe enough to cause lactic acidosis, an increase in
the creatine kinase level, and renal involvement manifested by a rise in the creatinine level. A markedly
positive test for occult blood in the urine, with only
a few red cells in the sediment, suggests the presence
of either hemoglobinuria or myoglobinuria; in view
of the episodes of muscle rigidity and the stable hematocrit, this finding indicates the presence of myoglobinuria as a complication of rhabdomyolysis. The final explanation for this boys disorder will have to
account for both the altered mental status and the
intense convulsions involving the whole body, with
preserved consciousness.
May we review the radiographs?
DR. MICHAEL H. LEV: The lateral plain films of
the neck, the anteroposterior film of the chest, and the
nonenhanced CT scan of the head (Fig. 1) all showed
normal findings.
Causes of an Acute Confusional State

DR. LIBENSON: The differential diagnosis of an acute

confusional state in a teenager is extensive. Primary
*Director, Epilepsy Center for Children, Floating Hospital for Children
at New England Medical Center; assistant professor of pediatrics and neurology, Tufts University School of Medicine both in Boston.

disorders of the central nervous system must be considered, such as infection, inflammation, vascular disorders, trauma, epilepsy, psychiatric disorders, tumor,
hydrocephalus, other disorders of intracranial pressure,
and migraine. The central nervous system may also
be secondarily affected by systemic disorders or diseases of specific organ systems, which may alter the
structure or function of the nervous system through
a variety of metabolic or temperature derangements,
exposure to toxins, circulatory factors, or anatomical
changes. In this case, the episodes of muscle rigidity,
which represent a much more distinctive symptom
than the boys state of confusion, will help narrow the
differential diagnosis considerably.
Causes of Confusion with Episodic Muscle Rigidity
Drugs

This boys history of marijuana use suggests that

he may possibly have abused other drugs as well. The
list of drugs of abuse that cause changes in mental status is long. Among them, however, phencyclidine deserves special consideration in the light of this patients
motor symptoms. Phencyclidine intoxication can have
many manifestations, but agitation and confusion are
typical. Horizontal, vertical, or rotatory nystagmus and
hypertension are seen in over half the cases, and the
deep-tendon reflexes may be increased.1,2 Muscle rigidity throughout the body, sometimes accompanied
by jerky limb movements or muscle twitching, is seen
in only 5 percent of patients but is a distinctive finding. Focal dystonias, including trismus (lockjaw), oculogyric crises, and torticollis, may also occur.1 The
muscle rigidity may be so severe that it precipitates
rhabdomyolysis and myoglobinuria, resulting in renal
failure.3 The absence of both nystagmus and marked
hypertension and the negative results of toxicologic
screening make the diagnosis of phencyclidine intoxication unlikely in this case.
Since this boy had his first episode of muscle rigidity soon after receiving an injection of haloperidol,
the possibility that the drug caused the muscle stiffening must be considered. The neuroleptic malignant
syndrome is an uncommon complication of neuroleptic use, occurring in about 0.2 percent of treated
patients.4 The cardinal signs are muscle rigidity and
fever. Autonomic instability is also seen, with increased
cardiac and respiratory rates and unstable blood pressure. The muscle rigidity is usually of the lead-pipe
variety (diffuse rigidity like that of a thin-walled lead
pipe), with or without cogwheeling, and may progress
to rhabdomyolysis and myoglobinuria. The syndrome
may cause agitation or a state of depressed consciousness ranging from drowsiness to coma. The symptoms
usually develop over a period of several hours or days,
however, rather than abruptly, as in this patient,4 and
in most severe cases, the rigidity is continuous rather
than episodic.5 In 98 percent of patients, the temper-

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CASE RECORDS OF TH E MASSACH USET TS GENERA L H OS PITA L

ature exceeds 38C, whereas this patients temperature was lower.4 Furthermore, the alteration in his
mental status preceded the administration of haloperidol, so if the drug caused the muscle rigidity, a
separate diagnosis would have to be established to account for the preexisting confusion.
Viral Encephalitis

In a patient who has an altered mental status soon

after the onset of an illness that may be an infection,
the diagnosis of viral encephalitis should be considered. Patients with viral encephalitis typically present
with some combination of headache, fever, altered
consciousness, behavioral and speech disturbances, seizures, and focal neurologic signs6,7; the specific combination of symptoms depends on the causative agent
and the severity of the infection. There is usually a
moderately elevated protein level in the cerebrospinal
fluid and pleocytosis, both of which were absent in
this patient. Herpes simplex virus is the most frequently identifiable cause of viral encephalitis. In a study of
110 patients with biopsy-confirmed herpes simplex
virus encephalitis, white cells were absent in the cerebrospinal fluid in only 3 patients and the white-cell
count exceeded 50 cells per cubic millimeter in nearly
80 percent of the patients; 92 percent had fever on
presentation.8 This patient did not have fever or a
high white-cell count in the cerebrospinal fluid, nor
did he have asymmetric or multifocal neurologic signs.
In patients with herpes simplex virus encephalitis, the
electroencephalogram often shows periodic, lateralized epileptiform discharges (i.e., distinctive, often
sharp complexes appearing every two to four seconds
over the temporal lobe or more broadly over an entire hemisphere).9 Since fever, pleocytosis, and periodic, lateralized epileptiform discharges were absent
in this patient and since the results of cerebrospinal
fluid culture and polymerase-chain-reaction tests were
negative, the diagnosis of viral encephalitis such as that
caused by herpes simplex virus is unlikely.
Rabies may be associated with confusion and episodes of muscle stiffening. In the northeastern United States, where this patient was treated, raccoons are
the largest reservoir of the rabies virus, which usually
enters the body through the bite of an infected animal, traveling by retrograde axoplasmic flow toward
the spinal cord at a rate of 8 to 20 mm per day. After
an incubation period of 30 to 90 days, a nonspecific
prodrome consisting of low-grade fever, malaise, nausea or vomiting, cough, and headache develops and
typically lasts 1 to 4 days.10 In many patients, pain
and paresthesias develop near the bite wound.7,11 Two
clinical forms of infection have been described. The
dumb, or paralytic, form, which occurs in less than
20 percent of cases, resembles the GuillainBarr
syndrome, with ascending paralysis and loss of the
deep-tendon reflexes. A characteristic symptom of the
furious form of rabies infection, which is more com-

mon, is hydrophobia, with inspiratory spasms involving the pharynx and larynx when the patient attempts
to swallow liquid. These 5-to-15-second spasms may
be associated with facial grimacing and extension of
the neck and back, which may evolve to opisthotonos.
Some patients become agitated and disoriented and
have hallucinations; others remain calm and oriented.12
Examination reveals a waxing-and-waning pattern of
muscle contractions, with facial grimacing, hyperreflexia, muscle twitching, and other involuntary movements. Brain-stem involvement, with multiple cranialnerve abnormalities, is a hallmark of rabies infection.
Although there is no history of an animal bite in this
case, in up to a quarter of cases, the patient and family
members do not recall an exposure. The viral strain
varies according to the animal species, and in patients
who report no history of an animal bite, the strains
carried by bats are implicated most often.10 The rarity of rabies infection in the region in which this patient resides, the absence of cranial-nerve findings, and
the temporal course of his illness all argue against rabies as an explanation for the clinical findings.
Epilepsy

Both confusion and episodes of body stiffening can

be caused by epileptic seizures and related phenomena. A state of confusion often follows an epileptic seizure but is typically brief in young, otherwise healthy
persons and improves continuously after the seizure.
Less frequently, continuous seizure activity (nonconvulsive status epilepticus) causes prolonged confusion.
The two major types of nonconvulsive status epilepticus are complex partial status epilepticus and absence
status epilepticus; each type is associated with a characteristic electroencephalographic pattern. The electroencephalographic findings in this case, however,
were normal. Epileptic seizures may also cause stiffening of a single limb, which spreads to involve one side
and subsequently both sides of the body. The nature
and progression of the stiffening and twitching in this
patient, with the migration of symptoms from one
limb to another, are not characteristic of an epileptic
seizure. When seizure activity engulfs the whole body
in a convulsion, consciousness with responsiveness is
almost never preserved, as it was in this patient. This
patients ability to speak during episodes of generalized
rigidity and the absence of generalized rapid spikes on
the electroencephalogram rule out epilepsy as a cause
of the episodes.
Tetanus

The opisthotonos-like rigidity in this patient brings

to mind the diagnosis of tetanus, which is caused by
tetanospasmin, the exotoxin elaborated by Clostridium
tetani, an anaerobic, spore-forming rod usually detected in infected wounds. The spores are commonly
found in samples of soil but have also been isolated
from other sources such as house dust and cultured

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surfaces in operating rooms. The interval between the

wound and the onset of symptoms of tetanus is typically 4 to 20 days, but much longer intervals have
been reported. In most cases, the patient is either unimmunized or incompletely immunized.13,14 Generalized tetanus begins with restlessness and irritability.
Lockjaw is the initial sign in more than half the cases; in other cases, patients first report neck stiffness or
dysphagia. Overactivity of the facial muscles gives rise
to the classic appearance of risus sardonicus (sardonic
smile). As the disease progresses, sudden tonic contractions of the muscles cause dramatic, painful episodes of opisthotonos, flexion of the elbows, clenching of the fists, and hyperextension of the legs, during
which the patient remains fully conscious findings
similar to those in this patient. Accompanying glottal
and laryngeal spasms can lead to cyanosis, asphyxia,
and death. The spasms may result in fractures of the
spine or long bones. Autonomic dysfunction is also
common, often manifested by tachycardia and labile
hypertension. Hospitalized patients may die unexpectedly from cardiac causes; complications of management in the intensive care unit may also result in
death.14-17
In generalized tetanus, tetanus toxin enters the
bloodstream and acts on presynaptic nerve terminals
of the brain-stem and spinal inhibitory interneurons,
blocking the release of the inhibitory neurotransmitters glycine and g-aminobutyric acid. Thus, tetanus
toxin blocks the inhibition of antagonist muscle
groups that occurs during the activation of agonist
muscles, resulting in exaggerated motor responses.18
This interneuron-mediated inhibition can be demonstrated by electromyography. After a stretch reflex,
there is a brief pause in electromyographic activity, reflecting the inhibition mediated by these interneurons.
Agents that block this inhibition, such as tetanus toxin and strychnine, shorten or abolish the normal brief
pause in electromyographic activity, a phenomenon
best observed in the masseter muscle. There are no
other distinctive laboratory findings in tetanus, although the level of creatine kinase may be elevated as
a result of rhabdomyolysis.
Despite the availability of a safe and effective vaccine against tetanus, 124 cases were reported to the
Centers for Disease Control and Prevention between
1995 and 1997; only 13 percent of the patients had
received a primary series of tetanus toxoid before the
onset of the disease.19 Younger male immigrants with
incomplete immunization are at high risk for the disease.13 This patient was an immigrant, but we are not
given information about his history of immunization.
Although the patient did not have a history of a suspicious wound, the absence of such a history does not
necessarily rule out tetanus. In one study, 25 of 100
patients with tetanus had no obvious source of infection; another 30 patients had wounds that they did
not consider serious enough to warrant medical atten-

tion.14 Although episodes of stiffening with preserved

consciousness suggest the diagnosis of tetanus, the
absence of an identified source of infection, the patients prominent confusion, and the rapid onset of
his symptoms argue against this diagnosis.
Strychnine Poisoning

Strychnine was introduced in Germany as a poison

for rats and other animals in the 16th century. Like tetanus toxin, strychnine blocks the action of spinal and
brain-stem inhibitory interneurons, causing a clinical
syndrome that includes episodes of marked muscle
rigidity, but strychnine poisoning causes more prominent alterations in mental status. Strychnine, unlike
tetanus toxin, acts as a selective, competitive antagonist of glycine at its postsynaptic receptors in the spinal cord and brain stem.20 The effects of strychnine at
higher levels of the nervous system are also believed
to be mediated by postsynaptic blockade of the action
of glycine.21
Early in the 20th century, strychnine poisoning
was considered the most common cause of accidental
death in children under five years of age.22 During the
years of prohibition of alcohol in the United States,
strychnine mixed with corn whiskey was implicated in
a number of deaths. As late as 1965, strychnine was
found in various tonics and cathartic agents in the
American pharmacopeia.23 It has no known therapeutic use, and its disappearance from American pharmacies is thought to account for the marked decrease
in the frequency of accidental strychnine poisoning.
Strychnine is currently used in various rodenticides
and pesticides, and some homeopathic and traditional
remedies contain trace amounts.24 Since the 1960s,
most cases of strychnine poisoning have been the result of suicide attempts or the use of strychnine to
adulterate street drugs, such as heroin and especially
cocaine.25
Strychnine is rapidly absorbed from the gastrointestinal tract, with symptoms developing as soon as
10 to 20 minutes after ingestion. The poison is eliminated mainly by hepatic metabolism, with first-order
kinetics and a serum half-life of 10 to 16 hours, although up to 20 percent of the amount ingested may
be excreted in urine.20,26 The initial symptoms of poisoning include nervousness, a hyperalert state, and
confusion.27 Stiffness is first noted in the face and neck.
Contraction of the facial muscles may cause risus sardonicus. The initial symptoms are soon followed by
episodes of overwhelming muscle rigidity throughout
the body in response to even minimal stimuli. Opisthotonic posturing may be so severe that only the
head and the heels touch the bed, with all voluntary
muscles in full contraction. The patient is fully conscious during the episodes, confirming the noncortical origin of the convulsions. In between the spasms,
which last from 30 seconds to 2 minutes, the muscles
become completely relaxed. During severe convul-

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CASE RECORDS OF TH E MAS SACH USET TS GENERA L H OS PITA L

CLINICAL DIAGNOSIS

Acute psychosis
? Tetanus.
? Strychnine poisoning.
DR. MARK H. LIBENSONS DIAGNOSIS

Strychnine poisoning.
PATHOLOGICAL DISCUSSION

DR. JANE M. YANG: On the morning of the second hospital day, the toxicology service was consulted.
The patients urine was analyzed by high-performance
liquid chromatography in combination with photodiode-array detection (Fig. 2). A compound that was
eluted in 4.5 minutes had a characteristic ultraviolet

0.005

Absorbance Units

sions, there is respiratory arrest, and the combination of sustained muscle contraction and hypoventilation may result in rhabdomyolysis, myoglobinuria,
and severe lactic acidosis. A number of cases with pH
of 6.6 or less and subsequent recovery have been reported.25 Without treatment, the patient usually dies
from asphyxia and cardiac arrest after two to five such
episodes.21,25 The spasms are usually treated effectively
with benzodiazepines, phenobarbital, or pentobarbital. These drugs probably ameliorate the convulsions
through their agonist effects on g-aminobutyric acid,
increasing the amount of neuronal inhibition in the
spinal cord. Occasionally, it is necessary to induce paralysis with an agent such as pancuronium. Prophylactic endotracheal intubation and mechanical ventilation should be considered in cases of severe poisoning.
Aggressive treatment with intravenous fluids may diminish the deleterious effects of myoglobinuria on the
kidneys and improve the lactic acidosis.25
In this case, the clinical syndrome of a state of confusion and episodes of muscle rigidity resulting in
rhabdomyolysis is most consistent with strychnine poisoning. The duration of this patients illness is somewhat longer than that usually reported. Most patients
are treated with gastric lavage and instillation of charcoal at the first sign of poisoning.
How was this boy exposed to strychnine? A variety
of traditional remedies are known to be used by Cambodian immigrants, including coin rubbing, moxibustion, and the use of traditional herbs, aromatic oils,
and teas.27-29 Strychnine, in the form of the nut of the
Strychnos nux-vomica plant, is a traditional Cambodian remedy.
Although electromyography would have been a
valuable diagnostic procedure in this case, it would
not have distinguished between generalized tetanus
and strychnine poisoning. The diagnostic procedure
was probably a test of the urine, gastric contents, or
blood for strychnine. The herbal tea prepared by
the patients mother may have been made from the
strychnos nut and may thus have been the source of
the strychnine.

0.001
0

Retention Time (min)

Figure 2. Chromatogram of a Urine Specimen from the Patient.
A liquid chromatograph (QA-1, Waters Chromatography, Milford, Mass.) and photodiode detector (990 PDA, Waters Chromatography) were used with a liquid-chromatographycyanopropylsilyl column (Supelco, Bellefonte, Pa.) (mobile phase: 60
percent acetonitrile, 15 percent methanol, and 25 percent phosphate buffer [pH, 6.9]).
The peak at 4.5 minutes (arrow) represents strychnine.

spectrum corresponding to that for strychnine. In addition, a sample of strychnine had the same elution
time and spectrum (Fig. 3). Analysis by gas chromatographymass spectrometry, which is considered the
gold standard for toxicologic identification, confirmed
the presence of strychnine in the urine.
The source of the strychnine was not identified, despite extensive toxicologic analysis for drugs of abuse.
The patient did not have a history of exposure to
pesticides or rodenticides. The only other suspected
source of strychnine was the over-the-counter herbal
preparation that the patient took. A report of strychnine poisoning from the strychnos nut, a traditional
Cambodian remedy,27 suggests that the remedy this
patient took also contained strychnine. The pills (Fig.
4), known in Cambodian as of tha tup (of the heavens) were cylindrical, very hard, nonuniform, and difficult to dissolve, despite the use of aqueous solutions
with various levels of pH and different organic solvents. Those that we were able to dissolve were positive for diphenhydramine and chlorpheniramine. The
package insert states that the medication is an energy
booster and that it can be used to treat a wide variety of ailments, ingested as a tea or swallowed whole
in pill form. This patient reportedly took two pills for
his influenza-like symptoms on the day before admission and one more on the day of admission.
This patients unusually prolonged clinical course,
with the first sustained episode of generalized rigid-

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Absorbance Units

0.03

0.02

0.01

0.00
220

240

260

280

300

320

Wavelength (nm)
Figure 3. Ultraviolet Absorption Spectra of Compound from the Urine Specimen (Solid Line) and a
Sample of Strychnine (Broken Line).

ity occurring 18 hours after he had taken the last pill,

could have been caused by delayed absorption of the
strychnine. Delayed and prolonged toxicity is a welldocumented result of sustained release of substances
from enteric-coated medications. Certain agents, such
as iron, are also known to form concretions in the gut
that slow absorption. In addition, the diphenhydramine and chlorpheniramine that were found in both
the herbal product and blood and urine specimens
from the patient are antihistamines that exert anticholinergic effects, including delayed gastrointestinal motility and absorption. The absorption of strychnine
may therefore have peaked close to the time of sustained rigidity.
During the evening of the second hospital day, the
patient had another episode of sustained rigidity of
unknown duration, which improved after the administration of another dose of lorazepam. Hyperreflexia
and fasciculations diminished and finally ceased on the
following day. Previous medical records confirmed
that the patient had received a tetanus booster 18
months before admission. Despite the neuromuscular
improvement, the patient continued to be intermittently agitated, delusional, fearful, and disoriented for
several days. The administration of risperidone resulted in partial improvement of his mental status. After
an 11-day hospitalization, he was discharged with a
concurrent diagnosis of psychosis. He is currently
being seen by a psychiatrist. His medications are ris-

Figure 4. Cambodian Herbal Pills.

peridone, lorazepam, valproic acid, and benztropine.

His psychosis appears to be in remission, and he is
functioning fairly well at home and in school.
DR. EUGENE J. MARK: Has strychnine poisoning
been reported to unmask psychosis?
DR. LIBENSON: I am not aware of any such report.
ANATOMICAL DIAGNOSES

Strychnine poisoning.
Bipolar disease.

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CASE RECORDS OF TH E MAS SACH USET TS GENERA L H OS PITA L

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Copyright 2001 Massachusetts Medical Society. All rights reserved.