Download AANEM Case Report # 16 Botulism

AANEM Case Report # 16
Botulism
Ricardo A. Maselli, MD
Nandini Bakshi, MD
American Association of Neuromuscular &
Electrodiagnostic Medicine
AAEM CASE REPORT 16
ABSTRACT: Early diagnosis of botulism is essential for effective treatment. Electrophysiologic testing can be of major help to establish a prompt
diagnosis, but the classic electrodiagnostic features of botulism are often
elusive. Decrement or increment of compound muscle action potential
(CMAP) amplitudes to slow or fast rates of nerve stimulation are often unimpressive or totally absent. Reduction of CMAP amplitudes, denervation
activity, or myopathic-like motor unit potentials in affected muscles are found
more frequently but they are less specific. In general, the electrophysiologic
findings taken together suggest involvement of the motor nerve terminal,
which should raise the possibility of botulism. The case reported here illustrates a common clinical presentation of botulism. This study emphasizes
realistic expectations of the electrodiagnostic testing, the differential diagnosis, and the potential pitfalls often encountered in the interpretation of the
electrophysiologic data.
© 2000 American Association of Electrodiagnostic Medicine.
Muscle Nerve 23: 1137–1144, 2000
BOTULISM
RICARDO A. MASELLI, MD, and NANDINI BAKSHI, MD
Department of Neurology, University of California Davis, 1515 Newton Court,
Room 502, Davis, California 95616-4859, USA
Although there are a number of forms of botulism,
the food-borne, wound, and infant types of botulism
are the most clinically relevant.
This form of the disease results from the ingestion of food contaminated with
spores and organisms that have been maintained in
anaerobic conditions, resulting in germination and
toxin production. Botulinum neurotoxins are resistant to the proteolytic activity of stomach fluids because they are associated with accessory proteins that
protect them from proteolysis.38,39 In the alkaline
environment of the intestine, the toxins are dissociated from these accessory proteins, absorbed, and
transported via the circulation to the nerve terminals
of skeletal muscles and the peripheral autonomic
system. More than 12,000 cases of food-borne botulism have been recorded worldwide since 1951 with
Food-Borne Botulism.
Abbreviations: AChR, acetylcholine receptor; APB, abductor pollicis
brevis; AQM, acute quadriplegic myopathy; CK, creatine kinase; CMAP,
compound muscle action potential; EMG, electromyography; EPP, endplate potential; FCR, flexor carpi radialis; GBS, Guillain–Barré syndrome;
LES, Lambert–Eaton syndrome; MEPP, miniature endplate potential;
MCD, mean consecutive difference; MFS, Miller-Fisher Syndrome; MG,
myathenia gravis; MUP, motor unit potential; NCV, nerve conduction velocities; NMJ, neuromuscular junction; SNAP, sensory nerve action potential; SSFEMG, stimulated single-fiber electromyography
Key words: botulism, neuromuscular transmission, presynaptic, repetitive nerve stimulation, nerve terminal
Correspondence to: American Association of Electrodiagnostic Medicine, 421 First Avenue SW, Suite 300 East, Rochester, MN 55902; e-mail:
[email protected]
© 2000 American Association of Electrodiagnostic Medicine. Published
by John Wiley & Sons, Inc.
AAEM Case Report #16: Botulism
a case/fatality rate of 20%.17 About 34% of cases are
caused by type A, 52% type B, and 12% type E.18
Wound Botulism. This form of the disease results
from the contamination of wounds with bacteria and
bacterial spores that proliferate and produce the
toxin locally.9 The toxin is in turn transported to
peripheral synapses via the circulation. Only types A
and B have been encountered so far in wound botulism. Most cases have been reported in the United
States, with an overwhelming majority in the state of
California.42 Lately, most cases of wound botulism
have been reported in drug addicts in association
with subcutaneous tissue injection or “popping.”10
The infant variant of the disease
was first diagnosed in 1976 and is currently the most
common form of botulism in the United
States.1,11,31,34 This form results from the ingestion
of viable spores that germinate and colonize the intestinal tract. The neurotoxin produced in the intestine is transported via the circulation to peripheral
nerve terminals.26 Approximately half of the cases
reported in the United States have been identified in
the state of California.17
Infant Botulism.
At the nerve terminals, the toxin
binds via the carboxyterminal of the heavy chain to
an as yet unidentified receptor and is internalized
through a receptor-mediated endocytosis. Once inside the nerve terminal, the light chain cleaves one
Pathogenesis.
MUSCLE & NERVE
July 2000
1137
or two of the three key proteins involved in the process of neurotransmitter release. These proteins are:
VAMP or synaptobrevin of the synaptic vesicle membrane and SNAP-25 and syntaxin of the presynaptic
membrane.32 Botulinal toxins A and E hydrolyze
SNAP-25, whereas B, D, F, and G cleave VAMP. Botulinal toxin C cleaves both SNAP-25 and syntaxin2,26
(Fig. 1). This cleavage of synaptic proteins disrupts
the fusion but not the docking of synaptic vesicles to
the presynaptic membrane. Neuromuscular transmission fails as a result of reduction of synaptic
vesicle release and decrease of the endplate potential (EPP) quantal content.29
CASE REPORT
History. A 44-year–old man with a long-standing
history of intravenous drug use and “skin popping”
experienced rapidly progressing blurred vision, diplopia, dysphagia, and dysarthria. Two weeks prior to
the onset of these symptoms the patient developed
an abscess in his right arm at the site of previous
“popping.” This required antibiotic treatment with
cephalexin (Keflex) and ciprofloxacin. The patient
was initially admitted to a small community hospital
where he developed respiratory failure and required
mechanical ventilation. He was subsequently transferred to a university hospital.
On admission, 5 days after the onset
of symptoms, the patient was on ventilatory support
and fully alert. He communicated by squeezing the
Examination.
FIGURE 1. Targets of Clostridia neurotoxins in the fusion protein
complex. Schematic representation of some of the protein interactions involved in vesicle fusion and the sites of neurotoxin action. Botulinum toxins serotypes (BoNT/A to BoNT/F) and tetanus
toxin (TeTx) are indicated within boxes aimed at their targets
(modified from reference 2).
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AAEM Case Report #16: Botulism
examiner’s hand in response to questions. A relevant
finding in the general examination was the presence
of multiple scars and scrapes throughout the skin of
the abdomen and limbs. In addition, he had an abscess in his right shoulder. The neurologic examination showed very sluggish pupillary response to light,
limitation of horizontal gaze, and inability to move
the eyes vertically or to maintain the eyes opened.
There was moderate weakness of facial and tongue
movements. The tone and muscle strength were decreased in the upper and lower extremities but there
was no muscle atrophy or fasciculations. The weakest
muscles were the deltoid and iliopsoas muscles,
which barely provided strength to overcome gravity.
Deep tendon reflexes were mildly decreased in the
upper extremities but were normal in the lower extremities. Plantar responses were flexor. Sensory examination was normal and coordination could not
be properly assessed.
On admission, the patient had a
mildly elevated white blood cell count at 15,000/
mm3 and a low serum albumin level at 3 g/100 mL.
Cultures from the abscess discharge revealed the
presence of Staphylococcus aureus sensitive to ciprofloxacin and cephalexin (Keflex).
Laboratory Tests.
Electrodiagnostic Examination. The electrodiagnostic study was performed using a Nicolet Viking IV
electromyograph (Nicolet Biomedical Inc., Madison,
WI). Motor and sensory nerve conduction velocities
were measured using conventional techniques and
surface electrodes for stimulation and recording. Repetitive stimulation was performed in the right median nerve stimulating at wrist and recording from
the abductor pollicis brevis (APB) muscle. Needle
electromyography (EMG) was carried out using a
disposable monopolar needle electrode (Teca
Corp., Pleasantville, NY). Stimulated single-fiber
EMG (SSFEMG) was performed in the right deltoid
muscle using microstimulation of distal nerve
branches with a monopolar needle. Recording and
analysis of SSFEMG data were done as previously
described.25
Nerve conduction studies. Motor nerve conduction velocity in the right median nerve was normal at
62.5 m/s with a compound muscle action potential
(CMAP) amplitude of 5.2 mV peak-to-peak. The Fwave latency was also normal at 28.3 ms. The sensory
conduction velocity in the right median nerve was
normal at 61.5 m/s with a sensory nerve action potential (SNAP) amplitude of 14.1 mV. Stimulation of
MUSCLE & NERVE
July 2000
the right axillary nerve at Erb’s point with recording
from the deltoid muscle resulted in a CMAP of normal latency and decreased amplitude: 4 ms and 2.6
mV peak-to-peak, respectively.
Repetitive stimulation. There was no significant
decrement of CMAP amplitude during a train of
four stimuli delivered to the right median nerve at 2
HZ. Stimulation of the same nerve at 30 HZ with a
train of 12 stimuli resulted in a modest increment of
CMAP amplitudes of 20% (Fig. 2).
Needle EMG. The right first dorsal interosseous,
flexor carpi radialis (FCR), and deltoid muscles were
studied. There was no evidence of spontaneous activity in any of these muscles. In the FCR and deltoid
muscles there were polyphasic motor unit potentials
(MUPs). Furthermore, the MUPs were small in amplitude and very short in duration. The pattern of
recruitment in the distal muscles was normal. In the
deltoid muscle, the pattern of recruitment was reduced, probably as a result of complete blockade of
all the nerve terminals of some motor units. This
true reduction of MUPs coupled with the low amplitude of distant MUPs allowed the recognition of
MUPs located near the needle electrode even during
maximal effort. This “rapid firing” of short-duration
MUPs provided a seemingly combined myopathic
and neurogenic characteristic to the MUP recruitment pattern (Fig. 3).
Stimulated single-fiber EMG. A total of 23 measurements of jitter were performed during stimulation at 10 HZ, 20 HZ, and 40 HZ. The mean consecutive difference (MCD) was increased at these three
frequencies of stimulation. There was no improvement of jitter with high frequency of stimulation.
The MCD at 10 HZ was 41.7 ± 22.1 ms (n = 10), at 20
HZ was 40.2 ± 7.7 ms (n = 5), and at 40 HZ was 44.6
± 13.9 ms (n = 3) (Fig. 4).
Interpretation. The primary feature of the electrodiagnostic evaluation in this case was not pro-
FIGURE 2. Repetitive nerve stimulation test. (A) Stimulation of
the right median nerve at 2 HZ showed no significant decrement.
(B) Stimulation of the same nerve at 30 HZ resulted in a moderate
incremental response.
AAEM Case Report #16: Botulism
FIGURE 3. Needle electromyographic findings. (A) Myopathic
motor unit potentials (MUPs); (decreased amplitude, short duration) recorded from the right deltoid muscle. Because of the severe reduction of amplitudes of distant MUPs, one of the MUPs
can be distinguished from background activity even during activation at 25 HZ. (B) Recording from the same muscle of agematched control subjects.
vided by the repetitive stimulation but rather by the
needle EMG. It was shown that, even in severely affected muscles, the pattern of recruitment of MUPs
was normal or only moderately reduced. This suggests that the patient’s weakness was not due to an
abnormality of the central nervous system or a dysfunction of large-diameter motor nerve fibers. The
absence of involvement of large-diameter motor
nerve fibers was further supported by the normal
motor conduction velocities and normal F-wave latencies in affected muscles. On the other hand, the
marked reduction of MUP duration pointed to an
abnormality of the distal motor branch, the neuromuscular junction (NMJ), or the muscle fiber itself.
Acute diseases affecting distal motor nerve fibers
usually are associated with prolongation of motor
FIGURE 4. Stimulated single-fiber EMG. Example of marked increment of jitter in a single muscle fiber recorded from the right
deltoid muscle.
MUSCLE & NERVE
July 2000
1139
predominance type 1 fibers (about 80%). In addition, there were rare necrotic and degenerating fibers and macrophage infiltration. Electron microscopy showed no ultrastructural abnormalities of the
muscle fibers or motor endplates. However, several
endplates were found to be unopposed by nerve terminals indicating acute denervation. In vitro studies
with intracellular microelectrodes revealed severe reduction of the EPP quantal content (4.82 ± 3.84 in
the patient vs. 22.2 ± 2.8 in control subjects) (Fig. 5).
In addition, both the amplitudes and frequencies of
miniature endplate potentials (MEPPs) were reduced (MEPP amplitudes: 0.34 ± 0.1 mV in the patient and 0.81 ± 0.08 mV in control subjects; MEPP
frequencies: 2.3 ± 0.4/min in the patient and 4.0 ±
5.1 /min in control subjects) (Fig. 6). The reduction
of the EPP quantal content confirmed the presence
of presynaptic failure, whereas the additional reduction of amplitudes and frequencies of MEPPs were
consistent with underlying denervation Thus, the
findings of the in vitro physiology were in agreement
with the results of the structural studies and consistent with acute neurogenic atrophy. During the 12day hospitalization there was progressive improvement of cranial nerve function and pulmonary
function tests. However, the patient remained dependent on mechanical respiration and the proximal weakness in the limbs persisted. On day 9 of
admission the patient had a tracheostomy for continued ventilatory support. Three days later he was
discharged to a long-term facility.
distal latencies and that was not present in this case.
A dysfunction of the muscle fiber could result from
either an abnormality of the muscle fiber membrane, as in periodic paralysis, or muscle fiber destruction, as in an acute myopathy. Periodic paralysis
and other channelopathies are long-standing congenital diseases that cause episodic and transient
weakness. None of these clinical features were present in the patient. Acute myopathies are associated
with intense spontaneous activity (fibrillation and
positive sharp waves) and that was not observed in
this case. Diseases of the NMJ can be either presynaptic or postsynaptic. In both situations SSFEMG jitter is increased as it was in the patient. In acute
postsynaptic diseases, such as in myasthenia gravis
(MG) or during the effect of a paralyzing muscular
agent like vecuronium, the release of neurotransmitter is normal. When the release of neurotransmitter
is normal and the safety margin of the NMJ is diminished, repetitive stimulation at slow rates elicits
marked decrement.27 Because this was not observed
in the patient the repetitive stimulation at slow rates
suggested a presynaptic failure. Presynaptic failure
was further supported by the finding of CMAP increment at fast rates of stimulation. The two most common presynaptic disorders of neuromuscular transmission are Lambert–Eaton syndrome (LES) and
botulism. In both conditions CMAP amplitudes are
small. However, in LES, repetitive stimulation at fast
rates results in prominent CMAP increment, which is
usually more than 100%.24 On the other hand, in
botulism, the increment is ordinarily less than 100%,
as it was in the patient. In summary, the electrodiagnostic study was consistent with a presynaptic failure
of neuromuscular transmission and further suggested that the presynaptic failure was most likely
due to botulism.
Outcome. Two months later, the patient was discharged from the long-term facility in a wheelchair.
He started ambulating with a walker 4 months later.
Additional recovery occurred during the following 8
months, but he continued experiencing some de-
Clinical Course. The serum of the patient tested
negative for acetylcholine receptor (AChR) antibodies. However, the mouse bioassay performed by the
California State Department of Health Services using
serum of the patient revealed the presence of Botulinum toxin A. The patient was initially treated with
penicillin and trivalent botulism antitoxin (A, B, and
E). However, an immediate improvement was not
observed. Later, the patient developed bilateral lobe
consolidations and the antibiotic treatment was
changed to clindamycin and piperacillin to cover
Gram-negative organisms. On day 6 of admission the
patient had a muscle biopsy (left anconeus muscle)
to search for possible additional causes of weakness.
Light microscopy revealed the presence of a moderate number of angular atrophic fibers with a clear
FIGURE 5. Nerve evoked endplate potentials (EPPs). (A) Superimposed consecutive EPPs elicited in the biopsy of the patient by
microstimulation of the motor nerve terminal branch at 1 HZ. Note
the marked reduction and variability of EPP amplitudes. (B) Normal EPPs recorded from a muscle biopsy of a control subject.
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AAEM Case Report #16: Botulism
MUSCLE & NERVE
July 2000
FIGURE 6. Spontaneous miniature endplate potentials (MEPPs).
(A) Examples of reduced amplitude MEPPs. There is a homogeneous distribution of MEPP amplitudes. Note the absence of
large-amplitude MEPPs or “giant MEPPs.” (B) Amplitude distribution of MEPPs displayed in (A).
gree of shortness of breath up to 2 years after the
onset of symptoms.
DISCUSSION
This case exemplifies the apparent discrepancy between the severity of symptoms and the rather mild
electrodiagnostic abnormalities often encountered
in botulism. Patients with botulism are usually first
seen by the electrodiagnostic medicine consultant in
the intensive care unit while they are on mechanical
ventilatory support, and the electrophysiologic findings in these patients are often unimpressive. Motor
and sensory conduction velocities, including distal
motor and F-wave latencies are invariably normal.
This is an important point because it helps to distinguish botulism from an acute demyelinating neuropathy or Guillain–Barré syndrome (GBS). Clinically,
GBS is one of the most important differential diagnoses of botulism and the electrodiagnostic study
plays a fundamental role in the differentiation of
one from the other. The CMAP amplitudes in botulism are usually diminished, but the reduction of
CMAP amplitudes in this condition may be mild or
restricted to proximal muscles, which are as a rule
those most severely affected. This certainly may be
missed if the recording of CMAP amplitudes is limited to distal muscles, as is usually the case with conventional nerve conduction velocity studies. Reduction of CMAP amplitudes is also seen in axonal
AAEM Case Report #16: Botulism
neuropathy and this can lead to potential diagnostic
problems. However, in axonal neuropathy there is
often secondary demyelination that may result in additional abnormalities of the nerve conduction velocity study, including temporal dispersion and fragmentation of CMAPs and prolongation of F-wave
latencies.12 These findings are distinctively absent in
botulism. More importantly, because the pathogenic
mechanism of neuropathy is length dependent, the
abnormalities in this condition (i.e., reduction of
CMAP amplitudes) are more pronounced in distal
muscles, whereas in botulism the abnormalities are
more prominent in proximal muscles.29
Repetitive nerve stimulation is considered an important part of the electrodiagnostic study of human
botulism.16,36 In this case report, a modest CMAP
increment in response to high-frequency repetitive
nerve stimulation suggested presynaptic failure and
was consistent with the diagnosis of botulism. However, in the authors’ experience, which is based
mostly on intoxications due to Botulinum toxin type
A, incremental responses to fast-rate repetitive nerve
stimulation are often missing, even after studying
multiple nerves in serologically proven cases. This
observation is in sharp contrast to the report by
Cornblath and colleagues showing positive incremental responses to high-frequency repetitive stimulation in 92% of patients with infant botulism.7 It
should be noted that 96% of the cases reported by
these investigators were due to Botulinum type B.
Cherington reported that posttetanic facilitation is
seen more often in type B botulism (84% of patients) than in type A (62% of patients).6 It is tempting to speculate that the larger percentage of incremental responses in patients intoxicated with type B
in comparison with that of patients intoxicated with
type A may be due to the fact that neurotoxin types
A and B have different molecular targets at the nerve
terminal. Fakadej and Gutmann communicated that
long runs of repetitive stimulation at fast rates (40–
50 HZ for 10 s) often induce prominent incremental
responses in adult and infant forms of botulism.13
However, this observation was also made in cases
with patients intoxicated with neurotoxin type B;
therefore, the explanation just provided may also
apply to this situation.
Several cases of wound- and food-borne botulism
due to toxin type A have been investigated with intracellular microelectrode recordings.21,28 The most
constant findings were the reduction of EPP quantal
content and decrease of MEPP amplitudes and frequencies. These findings are very similar to those
encountered in human denervation,30 suggesting
that, in principle, Botulinum type A induces ultrater-
MUSCLE & NERVE
July 2000
1141
minal pharmacologic denervation. In contrast, in
type B intoxication there is less effect on MEPP amplitudes and frequencies but equal or even more
reduction of EPP quantal content than in type A.28
In addition, in type B there is marked desynchronization of EPP onsets or EPP jitter.15 All these findings suggest that toxin type B fundamentally interferes with the release of synaptic vesicles primed by
the impulse-evoked peak entry of Ca2+ into the nerve
terminal. Because tetanic stimulation increases the
entry of Ca2+ into the nerve terminal it is understandable that type B intoxication results more often
in incremental responses than type A.
Unfortunately, even when an incremental response to high-frequency repetitive stimulation is
unambiguously demonstrated, the diagnosis of botulism cannot be established with certainty because incremental responses to tetanic stimulation can be
seen in many conditions. Prominent incremental responses to tetanic stimulation (>100% increment
CMAP amplitude) are encountered, almost exclusively in LES. This feature can help to differentiate
LES from botulism, because in botulism large incremental responses are seldom observed. Nevertheless,
modest increments are occasionally detected in LES
as well, which can lead to potential diagnostic problems. In a recent study, Tim and associates reported
that only 37% of their LES patients had 100% CMAP
amplitude potentiation in the three muscles
tested.40 Furthermore, 78% of their patients had
100% CMAP facilitation in the abductor digiti quinti
muscle, whereas only 24% had a similar degree of
facilitation in the trapezius muscle. The higher frequency of facilitation in distal muscles of LES patients is important because the opposite pattern occurs in botulism where the larger frequency of
facilitation involves proximal muscles. Tim and colleagues also reported that 98% of their LES patients
showed a decremental response to slow-rate repetitive stimulation in muscles of the hand.40 This finding is also at variance with botulism where decrement in response to slow-rate repetitive nerve
stimulation is not consistent. The inconsistency of
decrement in botulism may result from the impairment of synaptic vesicle fusion induced by the neurotoxin. Because the decrement at slow rates of
stimulation results from transient depletion of synaptic vesicles at the active zones, an impairment of
vesicle fusion may prevent vesicle depletion and consequently the decrement.
A careful analysis of the configuration and pattern of recruitment of MUPs in clinically affected
muscles is one of the most useful parts of the electrodiagnostic assessment of botulism. Due to the
1142
AAEM Case Report #16: Botulism
complete blockade of neuromuscular transmission
in many muscle fibers the number of muscle fibers
contributing to the electrical field generated by the
whole motor unit decreases and the MUP duration
falls. In moderately affected muscles the number of
motor units is not diminished and therefore the pattern of MUP recruitment is normal. However, in severely affected muscles all the muscle fibers of a motor unit near the needle electrode may be blocked,
which may result in an apparent decrease in the recruitment of MUPs. Furthermore, polyphasic MUPs
are common because of the immediate change of
the motor unit architecture and subsequent reinnervation induced by the toxin. Thus the findings of the
needle examination are best described as comprising a combination of myopathic and neuropathic
abnormalities. Although these electrodiagnostic features are the most constant findings in botulism,
they are also the least specific. Therefore, it is advisable to include histologic assessment with muscle biopsy when the diagnosis of botulism is made only on
the basis of the electromyographic pattern. This
should appropriately exclude the possibility of an
underlying myopathic process.
Potential Pitfalls. The following situations can
pose special diagnostic problems (Table 1).
Miller–Fisher variant of GBS vs. botulism. Some of
the author’s patients were initially thought to have
Miller–Fisher syndrome (MFS). Both MFS and botulism classically present with hyporeflexia and generalized weakness with predilective involvement of cranial nerves. However, the nerve conduction velocity
studies in MFS show a characteristic absence of distal
sensory evoked responses that is not seen in botulism.14,37 Furthermore, the recruitment of MUPs in
affected muscles is diminished in MFS but is normal
in botulism. The presence of anti-GQ1b antibodies
in MFS or the positive mouse bioassay in botulism
can provide additional help for differentiating these
conditions.
Normal vs. abnormal electrodiagnostic study in botulism. Electrodiagnostic abnormalities in mild cases
of botulism may be quite subtle and difficult to detect with routine studies. However, a careful electrodiagnostic evaluation should uncover reduction of
CMAP amplitudes and short-duration MUPs in affected muscles.
Motor axonal neuropathy combined with myasthenia
vs. botulism. In principle, a combination of motor
neuropathy and myasthenia may reproduce all the
clinical symptoms encountered in botulism, including hyporeflexia and weakness of bulbar musculature. The electrodiagnosis in a hypothetical case of a
MUSCLE & NERVE
July 2000
Table 1. Electrodiagnosis of botulism and related disorders.
NCVs
↓NCV
↓CMAP amplitudes
↓SNAP amplitudes
EMG
Fibrillation and positive waves
Short duration MUPs
Myopathic recruitment
Repetitive nerve stimulation
Decrement (slow rate)
Increment (fast rate)
Botulism
MFS
LES
Axonal
neuropathy + MG
AQM
Myopathy
+ axonal neuropathy
−
+
−
+
+
++
−
++
−
+
++
+
−
++
−
+
++
+
+
++
+
+
−
−
−
+
+
++
+
+
++
++
+
++
++
+
+
+
−
−
++
+++
++
−
−
−
−
−
AQM, acute quadriplegic myopathy; CMAP, compound muscle action potential; EMG, electromyography; LES, Lambert–Eaton syndrome; MFS,
Miller–Fisher syndrome; MG, myasthenia gravis; MUP, motor unit potential; NCV, nerve conduction velocity; SNAP, sensory nerve action potential.
combined motor neuropathy and myasthenia may
show, as in botulism, reduction of CMAP amplitudes
and abnormalities of repetitive nerve stimulation.
However, in a motor neuropathy, due to frequent
secondary demyelination, additional abnormalities
of nerve conduction velocities occur. This includes
temporal dispersion and fragmentation of CMAPs
and prolongation of F-wave latencies, which are, as a
rule, absent in botulism. The presence of increment
to high-rate repetitive nerve stimulation may favor
botulism, but this finding may be present in other
conditions such as LES, myasthenia,20 and even in
motor neuron disease.33 Conversely, the absence of
increment or even the finding of decrement in response to fast repetitive stimulation does not rule out
the diagnosis of botulism. Unfortunately, other laboratory studies may not provide additional help. For
instance, as much as 15% of patients with generalized myasthenia do not have serum antibodies
against the AChR,41 and only 33% of patients with
wound botulism have seropositive mouse bioassay
for botulinum toxin.23 Ultimately, a motor point
muscle biopsy with microelectrode, immunohistochemistry, and ultrastructure of the NMJ and motor
nerves may be necessary to establish the diagnosis.
Acute quadriplegic myopathy in critically ill patients vs.
botulism. There have been numerous reports describing persistent quadriparesis in critically ill patients, usually following the administration of nondepolarizing neuromuscular blocking agents alone
or in combination with steroids.3,8 This condition is
poorly understood. The electrodiagnotic findings in
acute quadriplegic myopathy (AQM) are often strikingly similar to those seen in botulism. The similarities include reduction of CMAP amplitudes with normal sensory potentials and a myopathic EMG
pattern.4,19 In addition, both can show variable de-
AAEM Case Report #16: Botulism
grees of spontaneous EMG activity (fibrillation potentials and positive waves), absence of creatine kinase (CK) elevation, or unrevealing muscle biopsy.
In the authors’ experience, the spontaneous activity
is more intense in AQM and repetitive nerve stimulation at fast rates is more likely to induce incremental responses in botulism. Furthermore, direct
muscle stimulation often reveals electrical inexcitability in AQM but not in botulism.35
Proximal myopathy combined with neuropathy vs. botulism. The combination of myopathy and neuropathy, although infrequent, does happen occasionally,
particularly if both conditions represent the neurologic manifestation of a paraneoplastic syndrome or
a connective tissue disease.5,22 Electrodiagnosis usually demonstrates, as in botulism, reduced CMAP
amplitudes and normal recruitment of shortduration MUPs. Histologic examination with conventional muscle biopsy may be sufficient to differentiate these two clinical situations.
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