Differential Diagnosis of Acute Flaccid Paralysis and Its Role in Poliomyelitis Surveillance

Epidemiologic Reviews
Copyright 2000 by The Johns Hopkins University School ot Hygiene and Public Health
All rights reserved
Vol. 22, No. 2

Pnnted in U.S.A.
Differential Diagnosis of Acute Flaccid Paralysis and Its Role in Poliomyelitis

Surveillance
Arthur Marx,1 Jonathan D. Glass,2 and Roland W. Sutter1
Acute flaccid paralysis (AFP) is a clinical syndrome characterized by rapid onset of weakness, including (less frequently) weakness of the muscles of respiration and swallowing, progressing to maximum severity within several
days to weeks. The term "flaccid" indicates the absence of
spasticity or other signs of disordered central nervous system motor tracts such as hyperreflexia, clonus, or extensor
plantar responses (1). When applied to voluntary muscles,
"paralysis" means loss of contraction due to interruption of
motor pathways from the cortex to the muscle fiber. It is
preferable to use the term "paresis" for slight loss of motor
strength and "paralysis" or "plegia" for severe loss of motor
strength (1). The differential diagnosis of AFP varies considerably with age. No single operational clinical case definition of AFP or paralytic poliomyelitis that combines both
high sensitivity and high specificity has emerged (2-4). The
currently used case definition increases sensitivity in detecting the existence of AFP but tends to decrease specificity in
detecting paralytic poliomyelitis.
INTRODUCTION
AFP is a complex clinical syndrome with a broad array of

potential etiologies. Accurate diagnosis of the cause of AFP
has profound implications for therapy and prognosis. If
untreated, AFP may not only persist but also lead to death
due to failure of respiratory muscles. AFP, a syndrome that
Received for publication October 11,1999, and accepted for publication June 9, 2000.
Abbreviations: AFP, acute flaccid paralysis; AIDP, acute inflammatory demyelinating polyradiculoneuropathy; AIDS, acquired
immunodeficiency syndrome; AMAN, acute motor axonal neuropathy; GM,, glycolipid ganglioside-monosialic acid; CIDP, chronic
inflammatory demyelinating polyradiculoneuropathy; HIV, human
immunodeficiency virus; SIDP, subacute inflammatory demyelinating
polyradiculoneuropathy.
1
Centers for Disease Control and Prevention, National
Immunization Program, Vaccine-Preventable Disease Eradication
Division, Atlanta, GA.
2
Emory University School of Medicine, Atlanta, GA.
Correspondence to Dr. Roland W. Sutter, Centers for Disease
Control and Prevention, 1600 Clifton Road NE (Mailstop E-05),
Atlanta, GA 30333 (e-mail: rws4@cdc.gov).
Reprint requests to the Centers for Disease Control and
Prevention, National Immunization Program, Publication Requests,
1600 Clifton Road NE (Mailstop E-52), Atlanta, GA 30333.
298
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encompasses all cases of paralytic poliomyelitis, also is of

great public health importance because of its use in surveillance for poliomyelitis in the context of the global polio
eradication initiative.
In 1988, the World Health Assembly adopted a resolution
calling for global eradication of poliomyelitis by the year
2000 (5). At the end of 1999, 30 countries worldwide
remained polio-endemic, and intense activity is currently
being directed towards interrupting virus transmission in 10
remaining high priority countries facing particular challenges (6). Despite these challenges, the goal of polio eradication appears to be within reach. AFP surveillance is a key
strategy for monitoring the progress of polio eradication and
is a sensitive instrument for detecting potential poliomyelitis
cases and poliovirus infection. Current levels of surveillance
have made it possible to document a substantial reduction in
morbidity due to poliomyelitis. To ensure the success of the
poliomyelitis eradication initiative, it has become critical
that surveillance be intensified so that the absence of wild
poliovirus circulation can be verified with confidence in
countries not reporting confirmed cases of poliomyelitis.
The objectives of this review are to describe 1) the clinical characteristics, epidemiology, and differential diagnosis
of potential causes of AFP, including distribution by age,
gender, time, ethnicity, and geographic region; 2) the
anatomic, morphologic, and pathophysiologic mechanisms
associated with causes of AFP; 3) the region- or countryspecific significance of these etiologies; 4) the potential of
these etiologies to cause epidemics of AFP; and 5) an algorithm for determining the correct diagnosis and etiology of
AFP for use in clinical examinations and laboratory studies.
This review is intended to provide greater assurance to
clinicians concerning the accuracy of the diagnosis of AFP,
including the rational use of limited resources when it may
not be practical to conduct a detailed clinical assessment,
and to raise awareness among health workers and surveillance coordinators about the importance of accurately diagnosing and differentiating AFP. The presentation of our findings and the subsequent discussion provide an overview of
possible causes of AFP and focus on diagnostically helpful
characteristics of AFP, as well as regional or countryspecific experience.
For better understanding of the clinical characteristics and
differential diagnosis of AFP, we focus in this review on
grouping causes of AFP by pathophysiologic mechanisms
and anatomic sites of action, an aspect incompletely
DEFINITION OF ACUTE FLACCID PARALYSIS
Differential Diagnosis of Acute Flaccid Paralysis
explored in previous review articles. We discuss etiologies

that have emerged or become more significant recentlyfor
instance, neurologic complications in patients with acquired
immunodeficiency syndrome (AIDS). We also provide an
overview of causes of paralytic illness in developing countries that are commonly misdiagnosed as AFP.
METHODS
CLINICAL APPROACH TO PATIENTS WITH AFP
Each case of AFP is a clinical emergency and requires

immediate examination. The clinical investigation of AFP is
often limited by the existing health infrastructure and available resources. For all cases, a detailed clinical description
of the symptoms should be obtained, including fever, myalgia, distribution, timing, and progression of paralysis. The
symptoms of paralysis may include gait disturbance, weakness, or troubled coordination in one or several extremities.
Careful assessment of the patient's personal history (recent
illness, exanthem (erythema migrans in Lyme borreliosis),
timing, food and water consumption, exposure to chemicals
(organic solvents), insect (tick) or snake bites, family history, vaccinations, and psychogenic problems, including
dementia) is crucial in order to narrow the differential diagnosis. Trauma or spinal cord compression should be kept in
mind as an obvious cause of AFP. Depending on the geo-
graphic region, the skin and scalp should be carefully

inspected for ticks, stings from insects, spiders, or scorpions, and snake bites.
Figure 1 shows an algorithm for the clinical evaluation of
limb or respiratory weakness. The signs of AFP should be
evaluated clinically by performing a comprehensive neurologic examination, including assessment of muscle strength
and tonus, deep tendon reflexes, cranial nerve function, and
sensation (tactile sensation, vibration, and kinesthetic perception). Particular attention should be paid to the presence
of meningismus, signs of disordered central nervous system
function (ataxia), or autonomic nervous system abnormalities (bowel and bladder dysfunction, sphincter tonus, neurogenic reflex bladder) (7). Fasciculation is often cited as a
sign of anterior horn cell damage, but it may also be present
in demyelinating neuropathies (8). Electrophysiologic studies are very important for determining the diagnosis and
prognosis of lower motor neuron disease; nerve conduction
velocity and electromyographic studies, for instance, are
used to differentiate demyelinating neuropathies from
axonal neuropathies (7).
In currently or recently polio-endemic countries, every
case of AFP should be reported, regardless of its presumed
etiology. Two stool specimens should be collected within 14
days after onset of paralysis, and virus isolation should be
performed by a qualified laboratory (if this is not feasible,
stool specimens should still be collected up to 2 months
from the onset of paralysis) (9). If indicated, serologic testing, isolation, and immunologic assays should be carried out
for enteroviruses, human immunodeficiency virus (HIV),
Herpesviridae (cytomegalovirus, Epstein-Barr virus, herpes
simplex virus types 1 and 2, varicella-zoster virus),
Mycoplasma pneumoniae, Campylobacter jejuni, and
Borrelia species, as well as a VDRL (Venereal Disease
Research Laboratory) test. Testing for antinuclear and antiGMj (glycolipid ganglioside-monosialic acid) glycoconjugate antibodies may be needed to confirm diagnoses of
immunologic or autoimmune disorders.
If the necessary infrastructure and resources are available,
further laboratory tests may be indicated for differentiating
res
1
Muscle biopsy
Myasthtnia
BotuKcm.
Tttanus, Drugs
Polymyoitte,
Toodc mycpathy,
ICU mycpathy
FIGURE 1. Algorithm for the evaluation of patients with limb or respiratory weakness. NMJ, neuromuscular junction; CK, creatine kinase;
AMAN, acute motor axonal neuropathy; AIDP, acute inflammatory demyelinating polyneuropathy; ICU, intensive care unit.
Epidemiol Rev Vol. 22, No. 2, 2000
All available electronic databases, including Medline

(1966 to date), Biosis (1969 to date), and CAB Health (1973
to date), were systematically reviewed for reports on AFP in
any language available. Records in CAB Health are
extracted from the Public Health and Tropical Medicine
Database. Textbooks, monographs, conference proceedings,
and other sources were reviewed and searched for crossreferences. In addition, experts in the field, including health
officials in World Health Organization regional offices and
individual countries, were consulted. Our observations from
clinical and epidemiologic field experience were included in
this review.
299
1. Differential diagnosis of acute flaccid paralysis: clinical and epidemiologic characteristics
condition,
r, or agent
or horn cells of
spinal cord
omyelitis
Pain
Pleocytosis
in
cerebrospinal
fluid
Nerve
conduction
study
Paralysis in 1% of the
infected; nonspecific
prodrome (abortive
poliomyelitis)
Incubation period
7-14 days
(4-35 days)
24-48 hours to onset

of full paralysis;
proximal > distal,
asymmetrical
Yes
No
Yes
Rare
+/-
Yes
Yes
Aseptic meningitis Reduced

(moderate
CMAPt
polymorphoamplitude
nuclear
leukocytes at
2-3 days)
Hand-foot-and-mouth
disease, aseptic
meningitis, AHCt
As in poliomyelitis
As in poliomyelitis
Yes
No
Yes
None
+/-
Yes
Yes
As in poliomyelitis
Reduced
CMAP
amplitude
As in poliomyelitis
As in poliomyelitis
Yes
No
Yes
None
+/-
Yes
Yes
As in poliomyelitis
Reduced
CMAP
amplitude
Months to years
Acute, symmetrical,
ascending
No
Yes
Yes
Yes
+/-
Yes
No
Incubation period
10-21 days
Acute, symmetrical,
ascending
Yes
Yes
Yes
No
+/-
+/-
+/-
Yes
Incubation period
5-15 days
Acute, proximal,
asymmetrical
Yes
+/-
+/-
No
Yes
+/-
+/-
Yes
Abno
Reduced
CMAP amp.
Preceding infection,
bilateral facial
weakness
Hours to 10 days
Acute, symmetrical,
ascending
(days to 4 weeks)
No
Yes
+/-
No
No
Yes
+/-
No
Reduced
CMAP
amplitude,
demyelination
Fulminant, widespread
paralysis, bilateral
facial weakness,
tongue involvement
Hours to 10 days
1-6 days
No
No
Yes
No
Yes
Yes
No
Dene
Reduced
p
CMAP
ti
amplitude,
axonal degeneration
Subacute ascending
hypotonic
+/-
Yes
Yes
Yes
Yes
Yes
Mixed axon- Dene

al degena
eration and
demyelination
F30SSil
Yes
Yes
No
Yes
No
Axonal
degeneration
Exanthematous vesicular eruptions
anese encephlitis virus
te motor
xonal neuopathy
'"
and rt
...ma_.
symptoms
Reduced
or
ReMenin- absent sidual
bladder
gismus
deep
paralydystendon
sis
function
reflexes
Progression
of paralysis
neurotropic
viruses
bies virus
n-Barrd
syndrome
te inflammaory polyradicloneuropathy
Onset of
paralysis
Clinical
findings
cine-associated
aralytic poliomyelitis
cella-zoster
irus
omegalovirus
olyradiculomyelopathy
traumatic
sciatic neuritis
amuscular
Acute, asymmetrical
luteal injection
Hours to 4 days
Complete, affected
limb
No
Ele
myo
Dene
npolio enteroirus
Fever
at
onset
Dene
Dene
Sciat
d
v
nsverse myelitis
transverse
Preceding Mycoplasma
pneumoniae,
litis
Schistosoma, other
parasitic or viral
infection
al abscess
Headache, back pain,

local spinal tenderness, meningismus
In severe cases,
palatal paralysis,
blurred vision
Incubation period
1-8 weeks
(paralysis
8-12 weeks
after onset
of illness)
Abdominal pain,
diplopia, loss of
accommodation,
mydriasis
Incubation period
18-36 hours
nskia
mboldtiana,
alderoni
Hours to days
Yes
Normal
Norm
Yes
Yes
Yes
Yes
Yes
Yes
+/-
Moderate
Normal
Norm
No
Yes
Severe
Yes
Yes
Yes
+/-
Moderate
Normal
Norm
Yes
Yes
No
No
No
Yes
+/-
Demyelination
No
No
No
No
No
Facilitation
with repetitive
stimuli
No
No
Yes
Yes
No
Reduced
CMAP
amp.
No
No
No
No
Yes
+/-
+/-
+/-
Weeks to months
after tick
exposure
Subacute, multifocal
Yes
Yes, increased
protein
Late
d
v
Norm
d
v
Dene
Decrement Norm
on rep.
stimulus
Multifocal
No
No
No
No
No
No
No
No
Sudden,
complete
Hours to days:
prolonged
blockade
No
No
No
Yes
No
Yes
No
No
Subacute, proximal > distal
Weeks to months
No
No
Yes
No
No
Yes
No
Normal or
Myop
reduced
CMAP
Hours to days
Yes
No
Yes
No
No
No
No
Normal or
Myop
reduced
CMAP
Yes
No
Yes
No
No
No
No
Normal or
Myop
reduced
CMAP
Weakness, fatigability,
diplopia, ptosis,
dysarthria
Preceding gastroenteritis
Yes
No
Erythema migrans,
bilateral facial
paralysis, cardiac
abnormalities
nosis
Yes,
early
Yes
borreliosis
apsing fever)
myositis
No
No
Acute, symmetrical
ascending
Neoplasma, autoimmune disease
Yes
Acute, symmetrical
ascending
Latency period
5-10 days
rs of muscle
myositis
Yes
No
Ocular symptoms
epolarizing
gs
Yes
Rapid, descending,
symmetrical
te paralysis
s of the
euromuscular
unction
henia gravis
Yes
of Clostridbotulinum
Hours to days
Complete
Complete
cord
pression;
ma
thies
xin of
ynebacum
htheriae
Acute, lower
limbs symmetrical,
hypotonia/
lower limbs
Subacute myalgia Days

and weakness
Table cont
302
Marx et al.
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DIFFERENTIAL DIAGNOSIS OF AFP
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The list of underlying causes of AFP is broad (table 1) and

may vary by age and geographic region. The etiologies of
AFP are often associated with specific pathophysiologic
mechanisms or anatomic-morphologic changes, which may
help in establishing the correct clinical diagnosis (figure 2).
The causes and differential diagnoses of AFP have been
reviewed previously (8, 12-16), including reviews on paralytic illness in infants (17) and children (18-21) and in tropical regions (12, 13,22-24).
CO
other viral or bacterial infections. A lumbar puncture and

examination of the cerebrospinal fluid may be indicated to
exclude bacterial infection of the nervous system. Bacterial
infections frequently demonstrate large numbers of polymorphonuclear leukocytes, with low glucose and high protein
levels. Of course, culture will frequently identify the specific
organism involved. Cultures for bacteria are negative, identifying the illness as "aseptic" meningitis. However, clinicians
should keep in mind that intramuscular injections may
aggravate the risk of paralysis in poliovirus-infected individuals (10, 11). Imaging of the spine (radiography, computed
tomography, or magnetic resonance imaging (if available))
may be indicated to rule out spinal cord compression,
trauma, myelopathy, spondylotic polyradiculopathy, or neoplasm. Laboratory test methods, if feasible, should include
red blood cell and white blood cell differentials (e.g., nucleated and stippled red blood cells with karyorrhexis in arsenic
poisoning, basophilic stippling of white blood cells in lead
poisoning); determination of red blood cell sedimentation
rate; and measurement of serum and urinary levels of sodium,
potassium, calcium, magnesium, chloride, carbonate, creatinine, uric acid, porphyrins (porphobilinogen, 8-aminolevulinic acid), and thyroxin. Measurement of enzyme activity
(e.g., serum creatine kinase, acetylcholinesterase activity in
red blood cells or plasma in case of organophosphate intoxication) may be indicated. An electrocardiogram may be indicated to establish the diagnosis of electrolyte metabolism disorders, such as hypokalemic periodic paralysis.
Manifestations outside of the nervous system may include
skin ("raindrop" pigmentation) and nail (Mee's lines)
changes in arsenic poisoning, or abdominal colic and blue
lines in the gums in lead poisoning. More extensive screening for chemical compounds in serum, urine, fingernails
(arsenic), or hair (thallium) may be needed at a later time;
therefore, clinical specimens should be collected and stored.
LESION OF THE ANTERIOR HORN CELLS OF THE

SPINAL CORD
CO O
Viruses targeting motor neurons
S E
I?
O CD
5 O )
IS
2g
co .2
fe 53 5
O O C
1*
'--
If
52
IU
Polioviruses. Poliomyelitis. Poliomyelitis is caused by

three serotypes of poliovirus, a neurotropic RNA virus of the
family Picornaviridae, genus Enterovirus (25). Poliovirus
type 1 has the highest ratio of paralytic infection to subclinical infection and is the most frequent cause of epidemics of
paralytic disease. Poliovirus types 2 and 3 are less neurovirulent. Type 2 wild poliovirus was the first serotype to be
Acute Transverse Myelitis
303
Dorsal Root Ganglia:

Herpes, CMV, Rabies
Anterior Horn Cell:
Poliomyelitis, Enterovirus
Polyradiculomyelopathy:
CMV, Carcinomatous
Meningitis
Spinal Cord Compression:

Space Occuping Lesions
Anterior Spinal Artery

Syndrome
Myasthenia, Botulism,
Tetanus, Neuromuscular
Blocking Agents,
Plant and Snake Toxins
Myelin:
AIDP, Diphtheria
Muscle:
Polymyositis,
Toxic Myopathy,
ICU Myopathy
FIGURE 2. Pathophysiologic mechanisms and anatomic sites of etiologic factors for acute flaccid paralysis. CMV, cytomegalovirus; AMAN,
acute motor axonal neuropathy; AMSAN, acute motor-sensory axonal neuropathy; AIDP, acute inflammatory demyelinating polyneuropathy;
ICU, intensive care unit. (Adapted with permission from Ho et al. (99)).
eradicated in the Americas; as of 1999, the only remaining

foci of type 2 wild poliovirus transmission were detected in
northern India (26). Type 3 wild poliovirus caused a major
outbreak of paralytic disease in Angola in 1999 (27).
Poliomyelitis is transmitted by person-to-person spread
through fecal-oral and oral-oral routes, or occasionally by a
common vehicle (e.g., water, milk). The incubation period is
typically 7-14 days (range, 3-35 days). When nonimmune
persons are exposed to wild poliovirus, inapparent infection
is the most frequent outcome (72 percent) (25). "Abortive
poliomyelitis," also referred to as "minor illness," is the
most frequent form (24 percent) of the disease. Nonparalytic
poliomyelitis (including aseptic meningitis) occurs in 4 percent of patients. Only 1/1,000 to 1/100 infected individuals
develop paralytic disease (28-30). Reports of greater ratios
of paralytic infection to subclinical infection in
poliomyelitis are not based on consistent case ascertainment, or are not representative of the range in the majority
of literature reports (30, 31). Initial clinical symptoms may
include fever, fatigue, headache, vomiting, constipation (or
less commonly diarrhea), stiffness in the neck, and pain in
the limbs. A diphasic course featuring these relatively nonspecific symptoms with acute onset of paralysis during the
second phase is seen mostly in young children, and is uncommon in individuals over 15 years of age. A monophasic
course, with more gradual onset of symptoms and someEpidemiol Rev Vol. 22, No. 2, 2000
times excruciating myalgia, is seen in adults (29).

Distinguishing characteristics of paralytic poliomyelitis are
1) fever at onset, 2) rapid progression of paralysis within
24-48 hours, 3) asymmetrical distribution of limb paralysis,
affecting proximal limb muscles more than distal limb muscles, 4) preservation of sensory nerve function with (often
severe) myalgia, and 5) residual paralysis after 60 days (16,
25). Paralytic poliomyelitis may show an early cerebrospinal fluid infiltrate of polymorphonuclear leukocytes;
however, these are replaced after 2-3 days by moderate
numbers of lymphocytes and monocytes (32). The protein
content of the cerebrospinal fluid is elevated only slightly,
but it rises gradually in paralytic cases until the third week,
generally returning to normal by the sixth week. Glucose
levels are usually within the normal range.
Research by Sabin (28), Bodian (33), and Horstmann and
Paul (34) laid the foundation for understanding of the pathophysiologic and immunologic mechanisms leading to paralytic poliomyelitis. Mendelsohn et al. (35) developed the
concept that motor neuron cells expressing a specific receptor for poliovirus are susceptible to virus adherence and
multiplication, leading to the subsequent destruction of
motor neurons responsible for activating muscles. Anterior
horn cell disease, including the appearance of inflammatory
cells and motor neuron loss in the spinal cord, normally
occurs within the first 2 weeks. Affected nerve cells do not
Neuromuscular Junction:
304
Marx et al.
sion and eradication of wild poliovirus. Since a live attenuated strain of the virus is used in oral poliovirus vaccine,
the Sabin-derived virus may occasionally revert to a
neurovirulent strain, potentially causing paralytic illness
that is clinically identical to poliomyelitis resulting from
wild-type virus. The overall risk of vaccine-associated
paralytic poliomyelitis in the United States and Latin
America is one case per 2.5 million oral poliovirus vaccine
doses; the risk in Romania is one case per 183,000 oral
poliovirus vaccine dosesa 14-fold increased risk (49,
50). Three distinct groups are at risk of vaccine-associated
disease: recipients of oral poliovirus vaccine (mostly
infants receiving their first dose), persons in contact with
oral poliovirus vaccine recipients (mostly unvaccinated or
inadequately vaccinated adults), and immunocompromised
individuals (51). However, neither HIV infection nor AIDS
has been associated with an increased risk of paralytic disease due to wild-type or Sabin-derived poliovirus (52).
There is no long-term carrier state in infected immunocompetent persons, regardless of the clinical course.
However, prolonged shedding of Sabin-derived poliovirus
has been shown to occur in immunocompromised patients
with B-cell deficiencies (53).
Nonpolio enteroviruses. Nonpolio enteroviruses have
been associated with polio-like paralytic disease, frequently
accompanied by other clinical syndromes, such as aseptic
meningitis, hand-foot-and-mouth disease, and acute hemorrhagic conjunctivitis. Coxsackieviruses A and B, echovirus
(54), enterovirus 70 (24, 55), and enterovirus 71 (56-65)
have been implicated in polio-like paralytic disease.
Outbreaks of acute hemorrhagic conjunctivitis with radiculomyelitis and paralytic illness in India, Taiwan, Thailand,
and Panama were etiologically linked to enterovirus 70 (24,
55). Muscle weakness and wasting associated with
enterovirus 70 is usually severe and permanent (24).
Among all known nonpolio enteroviruses, enterovirus 71
has been most strongly implicated in outbreaks of central
nervous system disease and AFP, first described in
California during 1969- 1973 (60). Global attention focused
on enterovirus 71 when severe epidemics of central nervous
system disease occurred in Japan in 1973 (56) and in
Bulgaria in 1975 (57). Of 705 patients infected with
enterovirus 71 in Bulgaria, 149 (21 percent) developed
paralysis, and 44 (29 percent) of those persons died. Young
children under 5 years of age were most frequently affected.
Further outbreaks were reported in Hungary in 1978 (63)
and in Philadelphia, Pennsylvania, in 1987 (59). Household
clusters of acute neurologic disease associated with
enterovirus 71 were reported among children in Brazil in
1988-1990 (62). The most recent outbreaks were reported in
Malaysia in 1997 (66) and in Taiwan in 1998 (64, 65).
Antecedent illness (7-14 days before onset of AFP) was
generally characterized by fever, vomiting, diarrhea,
lethargy, nuchal rigidity, irritability, and anorexia; at 60-day
follow-up, these patients suffered from residual paralysis
with weakness and muscle wasting (67). Although signs of
polio-like illness were found less frequently in AFP patients
with isolation of nonpolio enterovirus than in polioviruspositive patients, nonpolio enterovirus infection may be
regenerate, which results in the inability of affected muscles

to function; however, axonal sprouting may result in some
recovery of function (7, 25). Poliomyelitis may lead to
severe asymmetrical atrophy and skeletal deformities.
Paralytic poliomyelitis may be associated with significant
mortalitydie case fatality rate, which is generally 5-10
percent among polio patients, was as high as 20-30 percent
during outbreaks in the early 20th century (36, 37), and it
increases with age (38, 39). The case fatality rate was 12
percent in a polio outbreak among young adults in Albania
in 1996 (38). Most of these patients died from complications
of bulbar paralysis, i.e., respiratory failure. Although children under 5 years of age are most frequently affected, outbreaks of poliomyelitis with high attack rates among adults
have been described (25, 36-38, 40). The greater severity
among older patients is consistent with that observed in outbreaks among susceptible adults (38, 40, 41).
Besides age, being unvaccinated or inadequately vaccinated (42), and lower socioeconomic status (16, 43), several
factors have been shown to increase the risk of acquiring
paralytic manifestations, including intramuscular injections,
infection, stress, strenuous exercise, surgery (e.g., tonsillectomy), trauma, and pregnancy. The term "provocation
poliomyelitis" describes the enhanced risk of paralytic manifestations that follows intramuscular injection, and it occurs
when inflammation in muscle coincides with poliovirus
infection; entry of poliovirus to nerve endings in die muscle
is facilitated, and paralysis occurs 430 days later (44).
Aggravation occurs when signals from a particular muscle
(from physical activity or inflammation) cause increased
blood flow in the relevant segments of the spinal cord which
have already been invaded by poliovirus; increased severity
of paralysis occurs 24-48 hours later (44).
Poliomyelitis changed from a comparatively rare disease
into an epidemic disease during the late 19th century and
early 20th century. Epidemics in Sweden in 1887-1911 and
in Vermont in 1894 preceded the great New York epidemic
of 1916, in which 27,000 children and adults were affected
and 6,000 (22 percent) died (36, 37). Large epidemics continued to occur around the world through the 1950s, until the
poliovirus vaccine was introduced. Endemic spread and outbreaks of poliomyelitis continue to occur among incompletely vaccinated populations in Eastern Europe, the
Middle East, Asia, and Africa, particularly in countries
affected by conflict (6).
Vaccine-associated paralytic poliomyelitis. Inactivated,
injectable poliovirus vaccine, which was developed by
Salk (45) following the discovery by Enders et al. (46) that
large quantities of poliovirus could be grown in tissue culture, was licensed in the United States in 1955. Several
weeks after the introduction of inactivated poliovirus vaccine in the spring of 1955, cases of vaccine-associated
paralytic poliomyelitis (known as "the Cutter incident")
were reported in association with the use of incompletely
inactivated vaccine (47). Oral poliovirus vaccine, developed by Sabin (48), was licensed in the United States in
1961. Oral poliovirus vaccine has been effectively used to
control poliomyelitis and is the vaccine recommended by
the World Health Organization for interrupting transmis-
suggest that Japanese encephalitis virus myelitis is caused

by anterior horn cell damage, and the clinical presentation
mimics poliomyelitis in many respects, including weakness
and wasting beyond 60 days after onset of paralysis.
POLYRADICULONEUROPATHIES
Landry-Guillain-Barre-Strohl syndrome
Landry-Guillain-Barre-Strohl syndrome, hereafter called

Guillain-Barre syndrome, is a disorder of peripheral nerves,
characterized by subacute (days to weeks) progression of
motor-sensory dysfunction not associated with meningismus or fever. The syndrome was first described by Landry
in 1859 and by Guillain, Barre, and Strohl in 1916. The
diagnostic criteria developed by Asbury and Cornblath (74),
based on the pathophysiologic and morphologic understanding of Guillain-Barre syndrome, correspond to those of
acute inflammatory demyelinating polyradiculoneuropathy
(AIDP). There is increasing evidence that what is diagnosed
as Guiltem-Barre" syndrome may include conditions originating from a variety of underlying pathogenic mechanisms
(75). In the absence of wild virus-induced poliomyelitis,
Guillain-Barre syndrome is the most common cause of AFP
in many parts of the world, and it accounts for over 50 percent of AFP cases in both industrialized and developing
countries (76, 77). The annual incidence globally is 1-2 per
100,000 population (78); however, there are differences by
region and ethnicity. Guillain-Barre syndrome is an important cause of AFP among children (21), but the incidence
increases with age, and it is most common in the elderly
(77). Rarely, cases in infants have been reported (21).
Guillain-Barre syndrome occurs in 50-70 percent of its
patients within 2-28 days after a gastrointestinal or respiratory infection (21). It is characterized by 1) afebrile onset,
2) ascending symmetrical paralysis progressing within days
to weeks (in >90 percent of patients, the nadir occurs by 4
weeks), and 3) disturbances of sensory function (74). If respiratory muscles become involved, the patient may die of
respiratory failure. Patients surviving the acute phase frequently (>80 percent) recover functionally (74). In severe
cases, persistent residual paresis occurs; however, the
majority of patients in this group ultimately have a good
functional recovery (74). The presence of bilateral facial
weakness, a normal cell count and elevated protein level in
the cerebrospinal fluid, and electrophysiologic evidence of
abnormal conduction support the diagnosis of GuillainBarre syndrome.
Preceding infection with C. jejuni has been identified as
the most common etiologic factor of Guillain-Barre syndrome (79). Infection with M. pneumoniae, Herpesviridae
(cytomegalovirus, Epstein-Barr virus, varicella-zoster
virus), HIV, measles virus, mumps virus, rubella virus, viral
hepatitis, influenza A and B viruses, vaccinia virus, and
nonpolio enteroviruses (Coxsackievirus, echovirus) have
been demonstrated in epidemiologic studies to precede
Guillain-Barre syndrome. Malignant lymphoma, alcoholism, liver cirrhosis, and thyroid disorders (hyperthyroidism, Hashimoto thyroiditis) have been linked to
Guillain-Barre syndrome (80). Preceding vaccination
clinically indistinguishable from paralytic poliomyelitis

without laboratory studies (55, 67).
Other neurotropic viruses. Rabies and rabies vaccines.
Rabies manifests after an incubation period of 1-2 months
(or, infrequently, years). Typical rabies includes an "excitement" phase characterized by behavioral and autonomic
nervous system abnormalities. A minority of cases will
progress directly to a paralytic phase ("dumb" rabies) (68).
Following nonspecific prodromal symptoms with paresthesia of the bitten area, paralytic rabies manifests as ascending
AFP with sphincter involvement and sensory disturbances.
Death from respiratory and bulbar paralysis occurs after a
longer illness than is seen in furious rabies. Differential
diagnoses of paralytic rabies include postvaccinal
encephalomyelitis, poliomyelitis, Guillain-Barre syndrome,
and other causes of Landry-type ascending paralysis (68).
Neuroparalytic post-rabies vaccine encephalomyelitis,
Guillain-Barre syndrome, and allergic neuritis were
described after the administration of earlier rabies vaccines,
namely the Semple and Hempt types (see sections on
Guillain-Barre syndrome and peripheral neuropathies
below), and varied in severity from neuritic and dorsolumbar myelitic paraplegic forms to the ascending Landry-type
paralytic form (69). Nerve tissue cell rabies vaccines produce a rate of one neuroparalytic adverse event per 200 vaccine recipients, whereas the complication rate is much lower
in vaccines derived from cell culture (69, 70).
Herpesviridae. Herpesviridae (cytomegalovirus, EpsteinBarr virus, varicella-zoster virus) are a group of neurotropic
DNA viruses that may cause AFP associated with GuillainBarre syndrome, opportunistic infections of the nervous system in individuals with AIDS, and acute transverse myelitis
(see sections on Guillain-Barre syndrome, acute transverse
myelitis, and neurologic disorders associated with HIV,
AIDS, or opportunistic infections below). Herpes simplex
virus encephalitis is the most common form of nonepidemic
viral encephalitis in the world, with an annual incidence of
1-3 cases per million population; all age groups may be
affected, including newborns infected at birth (usually with
herpes genitalis, herpes simplex virus type 2) (71). Both
cytomegalovirus and herpes simplex virus type 2 may cause
polyradiculoneuropathies (see section below).
Viral meningoencephalitis. Viral meningoencephalitis
may be caused by neurotropic viruses (paramyxovirus (parainfluenzavirus, mumps virus), togovirus, arbovirus, Herpesviridae), parasites (Trichinella spiralis; see section below), or
stroke of the spinal cord (71, 72). Meningoencephalitis generally manifests with central nervous system signs such as
disorientation, convulsion, or coma, and transient flaccidity
may only precede the classic spasticity of upper motor neuron
lesions (71). In the case of Herpesviridae or rabies virus,
meningoencephalitis is due to direct invasion of brain cells,
but it may be a secondary immunologic response to infection
or immunization (parainfectious or postinfectious encephalitis) (71, 72).
Japanese encephalitis virus. Japanese encephalitis virus, a
flavivirus, is endemic in Southeast Asia, parts of China, and
the Indian Subcontinent; in specific areas, it may be an
important cause of AFP (73). Electrophysiologic studies
305
306
Marx et al.
Subacute and chronic inflammatory demyelinating

polyradiculoneuropathy
Subacute inflammatory demyelinating polyradiculoneuropathy (SIDP) and chronic inflammatory demyelinating

polyradiculoneuropathy (CIDP) may be considered variants
of AIDP (90). CIDP is defined as an acquired demyelinating
neuropathy with insidious onset and progression over at
least 8 weeks (as opposed to AIDP, which progresses over a
period of up to 4 weeks, and SIDP, which progresses over
48 weeks) (90). All of the clinical features reported for
AIDP have been seen in CIDP, including ascending, sym-
metrical AFP, disturbances of sensory function, cranial

nerve involvement, respiratory failure, autonomic disturbances, and albuminocytologic dissociation and dysimmunoglobulinemia in the cerebrospinal fluid (90).
Electrophysiologic studies allow one to distinguish CIDP
from inherited demyelinating or axonal neuropathy (91).
Acute motor axonal neuropathy
Acute motor axonal neuropathy (AMAN), also referred to

as "Chinese paralytic syndrome," is a distinct disease entity
that appears different from AIDP and poliomyelitis because
of its primarily axonal involvement (88, 89, 92). Recent
research documented excessive axonal degeneration without
preceding demyelination and suggested that the target antigen may lie on the axon (92). AMAN has been described,
particularly during the summer months, among children and
young adults in northern China (88) and has also been
reported in Mexico (93), Spain (94), India (recently
described as "Asian paralysis syndrome") (95, 96), Pakistan
(97), and South Korea (80). Characteristic features of
AMAN include fulminant and widespread paralysis with
slow and usually incomplete recovery, bilateral facial weakness, frequent involvement of the tongue, normal sensory
perception, and normal cerebrospinal fluid cell count (88,
98). Early symptoms of this disease include leg weakness
and resistance to neck flexion. The weakness ascends
rapidly, affects symmetrically the arms and respiratory muscles, and progresses to the maximum extent of weakness
within 6 days, on average. Electromyographic studies indicate denervation potentials in weak muscles and suggest that
this entity may be a reversible distal motor nerve terminal or
anterior horn lesion. Serum antibodies to C. jejuni are frequently elevated (88, 99). Acute motor-sensory axonal neuropathy (89) is seen throughout the world, is rarer than
AIDP and AMAN, and probably does not have a seasonal
variation.
Neurologic disorders associated with HIV infection,
AIDS, or opportunistic infections
Neurologic disorders, including AFP, may complicate HIV

infection and AIDS (100). Such disorders may be caused by
1) HIV infection or AIDS; 2) opportunistic infections (e.g.,
Herpesviridae (cytomegalovirus, Epstein-Barr virus, herpes
simplex virus, varicella-zoster virus), Giardia lamblia,
Toxoplasma gondii, Mycobacterium tuberculosis, or
Treponema pallidum (syphilis)); or 3) vitamin B 12 deficiency
and other deficiencies of AIDS cachexia contributing to the
neuropathic process in terminal AIDS. Nucleoside antiretroviral agents and prophylactic and therapeutic drugs used to
treat HTV-associated complications may cause motor-sensory
neuropathies and myopathies but are generally not associated
with AFP. In the early stages of AIDS, AIDP, CIDP, isolated
cranial or other mononeuropathies, and brachial plexopathy
can occur. In later stages, opportunistic infection of peripheral
nerves by cytomegalovirus can cause syndromes of subacute
progressive polyradiculomyelopathy (cytomegaloviruspolyradiculomyelopathy) (101).
against rabies (especially with the Semple-type vaccine

(69); see section on rabies vaccines above), influenza,
typhoid fever, rubella, or cholera and administration of vaccines containing tetanus toxoid (Td, DT), anti-tetanus toxin
serum, or plasma-derived hepatitis B virus have been associated with Guillain-Barre syndrome. A causal association
between use of oral poliovirus vaccine and Guillain-Barre
syndrome has been suggested but has been ruled out by
more recent studies (81, 82).
Outbreaks of Guillain-Barre syndrome were reported in
Colombia in 1968 and in Jordan in 1976 (83). In the United
States, during 1976-1977, 516 individuals aged 18 years or
older who had received the influenza A/New Jersey vaccine
and 432 unvaccinated individuals developed Guillain-Barre
syndrome; the swine influenza component was not added to
the vaccine after 1977, and there were no further cases of
Guillain-Barre syndrome (84, 85).
Understanding of the immunopathogenesis of GuillainBarre syndrome, including the primarily demyelinating and
axonal forms, is based mainly on the following: 1) preceding infection with specific organisms, most notably C. jejuni
and M. pneumoniae; 2) the contribution of antibody- and
complement-mediated mechanisms of immune injury;
3) glycoconjugate antigens' being likely targets of immune
attack, and expression of anti-GM! glycoconjugate antibodies' possibly being associated with C. jejuni infection (86);
4) heterogeneity of immunologic targets on nerve fibers;
5) the presence of Ranvier nodes as immunologic targets;
and 6) "molecular mimicry," a host-generated immune
response to infectious organisms or tumor cells that share
antigenic determinants with the host's tissue. C. jejuni may
contain GM^like epitopes inducing the expression of antiGM| antibodies, which cross-react with antigenic determinants on nerve fibers. High titers of immunoglobulin G and
immunoglobulin M anti-GM! antibodies have been found in
5-85 percent of patients with Guillain-Barre syndrome, as
well as acute motor axonal neuropathy and autoimmune disease, including myasthenia gravis and polymyositis (86).
AIDP with acute lymphocytic infiltration and
macrophage-mediated demyelination reproduces the clinical
and pathologic features of Guillain-Barre syndrome most
often reported in North America, Europe, and Australia (87).
In other parts of the world, it has recently become clear that
some cases of Guillain-Barre syndrome have extensive
axonal degeneration with only minimal evidence of demyelination (88, 89).
ACUTE MYELOPATHIES
Acute transverse myelitis
As a cause of AFP, acute transverse myelitis is less frequent than Guillain-Barre syndrome or paralytic nonpolio
enterovirus infection; the reported annual incidence is less
than one case per 2 million population (104). The common presentation includes, in the initial phase of spinal
shock, weakness of the lower extremities, AFP, urinary
distention (neurogenic bladder), constipation, hyporeflexia, sensory impairment (sensory level), severe pain,
and paresthesia. After 2-3 weeks, hyperreflexia and spasticity appear. Among patients with acute transverse
myelitis, approximately one third fully recover, one third
partially recover, and the rest remain disabled or die
(105).
Acute transverse myelitis has been associated with M.
pneumoniae, Herpesviridae (cytomegalovirus, Epstein-Barr
virus, varicella-zoster virus), rabies virus, hepatitis A virus,
and enteric fever. Parasitic infection may involve the spinal
cord or brain stem, including Schistosoma mansoni and
Schistosoma haematobium, Cysticercus cellulosae, Taenia
solium and Taenia multiceps, Echinococcus granulosus
(cystic hydatid disease) and Echinococcus multilocularis,
and paragonimiasis (104). Cases of acute transverse myelitis
have been documented following administration of oral
poliovirus vaccine, tetanus toxoid (DT, Td), and cholera,
typhoid fever, and plasma-derived hepatitis B virus vaccine,
but the evidence has been considered inadequate to confirm
a causal relation (106). The illness may be suggestive of

encephalomyelopathy or a tumor rather than poliomyelitislike paralysis. Diagnostic testing (eosinophilia, positive
parasite-specific complement fixation tests) or empirical
treatment (antiparasitic agents) may provide clinical leads as
to the etiology.
Acute myelopathy due to spinal cord compression
(space-occupying lesions, spinal block, epidural
abscess) or anterior spinal artery syndrome
Acute myelopathy may occur because of the presence of

space-occupying lesions or spinal blocke.g., paraspinal
or epidural abscess, tumor or hematoma, or anterior spinal
artery syndrome (107). The common presentations include
weakness of the lower extremities, AFP, urinary distention,
constipation, hyporeflexia, sensory impairment, and paresthesia. A slightly elevated protein level in cerebrospinal
fluid may be found. There have been reports of acute transverse myelitis with sensory disturbances and AFP of both
lower limbs following intragluteal penicillin injection
(108). These accidents were probably due to mistaken
intraarterial injection of the drug, with retrograde progression through branches of the internal iliac artery up to the
spinal cord.
TRAUMA
Acute traumatic sciatic neuritis associated with
intramuscular gluteal injection
Administration of intramuscular injections in the gluteal

region is still common practice, despite the potential risk of
direct trauma or postinjection neuritis. The World Health
Organization recommends that diphtheria-tetanus-pertussis
vaccines and other intramuscular injections be given at the
anterolateral aspect of the upper thigh (109). A history of
recent injections in paralyzed limbsfor the treatment of
febrile infections, for instanceprovides a characteristic
lead for diagnosing traumatic neuritis. Traumatic neuritis
needs to be differentiated from aggravation poliomyelitis
(see section on poliomyelitis above).
Spinal cord injury
Trauma should always be considered clinically as a cause

of AFP. However, paralysis that is clearly associated with
trauma should not be included in the AFP reporting system.
Cardiovascular disorders, surgical complications
Postoperative spinal cord damage due to ischemia may

occur because of the interruption of critical radicular arteries at the lower thoracic or high lumbar vertebral levels, and
may result in total paraplegia orparaparesis (107). High aortic clamping and hypotension increase the probability of this
occurrence. The clinical examination in such cases reveals
AFP, areflexia, sensory loss, patulous sphincter, and reflex
neurogenic bladder (107).
Cytomegalovirus causes meningoencephalitis, myelitis,

and cytomegalovirus-polyradiculomyelopathy (101) (see
section on neurotropic viruses above). Cytomegaloviruspolyradiculomyelopathy is a rare but distinctive clinical
syndrome causing subacute ascending hypotonic lower
extremity weakness, often preceded or accompanied by
pain and paresthesia in the legs and perineum, with areflexia, urinary retention, and loss of sphincter control
(101). Tactile, vibratory, and kinesthetic impairments and
sensory levels are noted in certain patients. The cerebrospinal fluid typically shows prominent representation
of polymorphonuclear leukocytes, elevated protein levels,
and low glucose levels. Electrophysiologic studies typically demonstrate features of axonal neuropathy associated with varying degrees of demyelination. The differential diagnosis of cytomegalovirus-polyradiculomyelopathy
includes the following opportunistic conditions affecting
the lumbosacral nerve roots and spinal cord: herpes simplex virus type 2, varicella-zoster virus, T. gondii, T. pallidum, and other bacterial infections (101).
Varicella-zoster virus infection may cause symmetrical
ascending AFP, mimicking or potentially causing GuillainBarre syndrome (102). Frequently in zoster patients, pain
and paresthesia precede the belt-like vesicular eruption following sensory dermatomes. Rarely, a somewhat similar
clinical picture may be seen in patients suffering from
Herpesvirus simiae infection of the central nervous system
following a monkey bite (19). Varicella also has been associated with AMAN (103).
307
308
Marx et al.
PERIPHERAL NEUROPATHIES
Toxic neuropathies
Diphtheria neuropathy is an infrequent complication (-10

percent) among patients infected with Corynebacterium
diphtheriae. Patients with more severe manifestations of
diphtheria (toxic forms) are at greater risk of developing
cranial and peripheral neuropathy, which makes its appearance during the initial acute phase of illness or 8-12 weeks
later. The neuropathy is mostly distal and mixed motorsensory disease (111), characterized by palatal palsy, early
sensory signs and symptoms, fever, and reduced or absent
deep tendon reflexes. Studies of nerve conduction velocity
demonstrate prominent demyelination with signs of denervation upon electromyography.
Tick bite paralysis manifests 5-10 days after a tick
attaches itself. The onset of the illness is rapid, with prodromal symptoms including irritability, anorexia, pain and
paresthesia in the extremities, and ataxia and being followed
by symmetrical, ascending AFT within 12-36 hours. If the
tick is not removed, the illness will eventually involve bulbar musculature and will lead to a fatal outcome in up to 12
percent of patients. Paralysis usually (but not always)
resolves rapidly after tick removal (13). Ocular symptoms,
if present, may provide clues with which to differentiate tick
paralysis from Guillain-Barr6 syndrome, myasthenia gravis,
or botulism (112). Various Dermacentor and Ixodes species,
mainly in North America and Australia but also in tropical
areas, are known to produce paralysis in humans and in
domestic and wild animals (13). While tick toxin was
thought to block neuromuscular transmission, recent reports
indicate that ticks elaborate a toxin directed at the largediameter motor or sensory nerves, particularly the motor
nerve terminals (112).
Neuropathy associated with Lyme borreliosis (113) may
manifest as cranial neuropathy, most commonly facial palsy,
Louse- or tickborne relapsing fever caused by several

Borrelia species occurs worldwide and may cause AFP
(114). Borreliae in tick-borne relapsing fever more frequently cause neuroparalytic complications, while louseborne borreliae cause more severe systemic illness and
greater mortality.
The ingestion of the ripe fruit of Karwinskia humboldtiana (tullidora, coyotillo, buckthorn, wild cherry), which
grows in northern Mexico, Central America, and the US
states of Texas and New Mexico, produces a progressive
ascendent symmetrical AFP resembling Guillain-Barr6 syndrome that in severe cases may cause bulbar paralysis and
death (115, 116). K. humboldtiana has caused outbreaks of
AFP in Nicaragua (117). Wild berries of Karwinskia
calderoni in El Salvador may contribute to the elevated rate
of AFP (erroneously attributed to Guillain-Barre syndrome)
seen among children in the Americas.
Gloriosa superba (climbing lily, glory lily), found in
Africa and Asia, contains colchicine, which impairs rapid
axonal transport in peripheral nerves, resulting in axonal
neuropathy; it also causes myopathy (22). Other poisonous
plants implicated in paralytic illness include Aconitum
napellus (monkshood); Callilepsis species (daisy);
Gelsemium (jasmineblossoms); Heliotropum (bush tea
shrub); Melochia species (stems); and Oenanthe species
(parsnip) (19).
A variety of chemicals, metals, and drugs have been associated with motor-sensory neuropathies. Exposure (often
agricultural or industrial) to chemicals such as lead, arsenic
(118), and thallium, as well as glue-sniffing (119), may
cause peripheral motor neuropathy. Historically, epidemic
neuropathies in Jamaica and England could be linked to
chronic arsenic intoxication rather than nutritional deficiency. Arsenic-containing compounds such as melarsoprol
are still being used in developing countries for the treatment
Anatomically, two broad categories of peripheral neuropathy can be distinguished in terms of the pattern of involvement of the peripheral nervous system: 1) polyradiculoneuropathies involve the spinal roots and peripheral nerve trunks,
and 2) poly neuropathies, which result in bilaterally symmetrical disturbance of function, tend to be associated with agents
that act diffusely on the peripheral nervous system, such as
toxic substances, deficiency states, systemic metabolic disorders, and certain types of autoimmune reactions.
Toxic neuropathies are an important group of disorders in
neurologic practice in the tropics. Distal axonal degeneration ("dying back phenomenon") is the neuronal dysfunction in most toxic neuropathies (13). Neuropathies may
occur in the course of infectious diseases, such as diphtheria, borreliosis, and rabies. Acute peripheral neuropathy
with features similar to those of Guillain-Barre syndrome
can occur in acute beriberi, acute intermittent porphyria,
AIDS, paralytic rabies, cytomegalovirus infection, EpsteinBarr virus infection (110), and hepatitis B virus infection,
and following the administration of Semple-type rabies vaccine (69) (see section on rabies vaccines above).
radiculoneuropathy, or symmetrical distal neuropathy. Lyme

disease, caused by the spirochete bacterium Borrelia
burgdorferi, is characterized by erythema migrans, high
acute-phase serum titers of immunoglobulin M and
immunoglobulin G Borrelia antibodies, and lymphocytosis
and increased total protein levels in the cerebrospinal fluid
(113). Ixodes ticks, the vector of Lyme disease, are prevalent
mainly in North America, Europe, Eastern Europe, and
northeastern China. The incubation period between tick
exposure and erythema migrans is 3-32 days; within weeks
or months after the appearance of erythema migrans, a variety of neurologic abnormalities may occur. Lyme meningitis affects nerve roots as the spirochete bacteria pass through
the subarachnoid space. AFP due to Lyme polyradiculoneuropathy may develop 68 weeks after the tick bite and is
painful and asymmetrical. Weakness that may affect both
the lower and upper limbs develops within 4 weeks after
onset, much more slowly than in poliomyelitis. Deep tendon
reflexes are usually depressed, and sensory loss is dermatomal (72). Lyme borreliosis also may cause facial paralysis, which is bilateral in 50 percent of cases; in the absence
of other clinical systemic features, it may be indistinguishable from idiopathic facial paralysis (Bell's palsy; see section below).
of African trypanosomiasis (sleeping sickness) and may

cause Guillain-Barre syndrome-like AFP (120).
Many antimicrobial or chemotherapeutic agents may
cause peripheral neuropathy. Symptoms are mainly sensory,
but distal weakness can occur. Antirheumatic drugs (gold,
colchicine) have been associated with peripheral neuropathy
(22). The number of cases involved is relatively small, and
cessation of treatment with these compounds results in
regression of the neurologic symptoms. This observation
also applies to chemotherapeutic agents (Vmca alkaloids
and platinum-containing compounds).
DISEASES OF THE NEUROMUSCULAR JUNCTION
bas of Africa, Vipiridae (including rattlesnakes), and the

coral snakes of America, produce neurotoxins; however,
only cobra and krait bites have been associated with neuroparalytic syndromes in the absence of any other symptom
except local pain. An interesting early morning syndrome of
acute oculobulbar palsy with flaccid paralysis, resembling
the clinical picture seen with elapid snake bite but without
evidence of snake bite, has been reported in India (12, 125).
The features of acute onset of ptosis, external ophthalmoplegia, and bulbar paralysis with mild to moderate weakness, in the absence of a history of snake bite, could be confounded with myasthenia gravis, acute infective
polyneuritis, or poisoning because of numerous agents' acting at the neuromuscular junction, but they should be distinctive enough to differentiate this syndrome from paralytic
poliomyelitis.
Tetrodotoxin poisoning from consumption of puffer fish
(fugu, Sphaeroides maculatus) results in a fatality rate of up
to 60 percent (126). Within several hours after consumption,
individuals develop circumoral paresthesia spreading to the
limbs and trunk, with AFP and difficulty in breathing (126).
Tetrodotoxin may act at the motor end plate as well as on
axon and muscle membranes, and patients clinically
respond to treatment with anticholinesterase drugs (126).
The known plant toxins most commonly implicated in
paralytic illness due to neuromuscular blockade are curare,
camethonium, and hemlock extract (127).
Organophosphorus esters are used mainly as insecticides,
petroleum additives, and modifiers of plastics (128). Most
inhibit acetylcholinesterase activity; some, used as pesticides, helminthicides, or war gases, are extremely potent.
The main symptoms include acute weakness of the hands,
calf pain preceding paresthesia and weakness of the limbs,
absent ankle jerks, foot-drop, and claw-hand (13). The muscle paralysis caused by delayed neuropathy (2-3 weeks after
organophosphorus exposure) should be differentiated from
the intermediate syndrome (3-4 days postexposure), which
affects the neuromuscular junction and carries the risk of
respiratory paralysis and death (13, 22, 129).
Outbreaks of neuropathy resulting from exposure to triorthocresyl phosphate, a potent organophosphate, have
occurred in Morocco, Jamaica, the United States, South
Africa ("Durban mystery disease"; see "Other Clinical
Syndromes Causing AFP" below) (19), India (13), and Sri
Lanka (13). The consumption of accidentally contaminated
or adulterated food products (Jamaican ginger tonic,
Romanian liquor, or contaminated cooking oil, mustard oil,
or flour) may lead to paralytic disease (130). Outbreaks in
Sri Lanka were linked to sesame-derived gingili oil given to
teenage girls at menarche and to adult women after childbirth; these women exhibited the characteristic wrist-drop
and claw-hand (13). Triorthocresyl phosphate intoxication
typically begins with aching pain in the calves, followed by
paresthesia, numbness, and weakness distally in the lower
extremities, along with a high incidence of pyramidal signs
(13). Upon examination, ankle jerks are diminished or
absent; knee jerks, however, are usually exaggerated, suggesting upper motor neuron involvement (destruction of
corticospinal tracts and the spinal cord, including anterior
The skeletal neuromuscular junction, the most exposed

and most vulnerable synapse known, is the site of primary
pathology in disorders such as myasthenia gravis and
Lambert-Eaton myasthenic syndrome (121). Both syndromes are rare, characterized by weakness and fatigability
of skeletal muscles. High titers of anti-GM, glycoconjugate
antibodies in patients with myasthenia suggest an autoimmune disorder (86). Endogenous chemicals such as calcium
and magnesium, when in excess or deficit, will affect the
neuromuscular junction (122). Exogenous chemicals such
as organophosphates inhibit acetylcholinesterase activity,
leading to neuromuscular blockage and muscle paralysis. A
large number of drugs also alter neuromuscular transmission, acting either directly in nondepolarizing neuromuscular blocking agents or through adverse effects (e.g., aminoglycosides, phenytoin) (23).
A variety of naturally occurring toxins of animal, plant,
and bacterial origin are capable of causing disorders of neuromuscular transmission.
Botulism is caused by the exotoxin of Clostridium botulinum. Botulism toxin can cause descending paralysis
characterized by symmetrical impairment of cranial nerves,
followed by a descending pattern of weakness or paralysis
of the extremities and trunk (123).
Tetanus exotoxin from the spores of Clostridium tetani is
a major cause of perinatal mortality, and it may also cause
AFP of the muscles innervated by the affected cranial nerves
(i.e., cephalic tetanus) (124). The latent period for the neurologic syndrome is 14 days in neonates and 6-10 days in
adults (range, 3-21 days). Tetanus toxin is carried intraaxonally within membrane-bound vesicles to spinal motor
neurons, where it causes presynaptic inhibition of spinal
glycinergic neurons (22). Subclinical axonopathy has also
been described in patients recovering from tetanus.
Animal toxins leading to neuroparalytic syndromes
include those derived from the venom of various snakes,
arthropods, and marine creatures and those derived from the
skin excretions of "dart-poison" frogs, poisonous fish, shellfish, and crabs (producing the active agents ciguatoxin,
tetrodotoxin, saxitoxin, and domoic acid). Neurotoxins produced by elapid snakes, particularly the African and Asian
cobra (Naja) and the krait of southern Asia (Bungaris), may
cause acute neuroparalytic syndromes in 30-50 percent of
victims, including AFP, ophthalmoplegia, and bulbar and
respiratory palsy. Many elapid snakes, including the mam-
309
310
Marxetal.
horn cell damage) rather than peripheral axonal neuropathy

or neuromuscular blockade (1, 13).
WEAKNESS ASSOCIATED WITH CRITICAL ILLNESS
Idiopathic inflammatory myopathy (polymyositis) rarely

may cause Guillain-Barre' syndrome-like AFP (137). The
onset more frequently is subacute and insidiously progressive over weeks, months, or even years. Proximal limb muscles are mostly affected, but respiratory weakness, cardiac
problems, or dysphagia may occur. The diagnosis is based
on electromyographic abnormalities, elevated serum creatine kinase levels, and muscle biopsy. As in other autoimmune disorders, high titers of anti-GM, glycoconjugate antibodies are found in polymyositis patients as well (86).
Polymyositis is primarily found among females aged 20-40
years. Associated conditions often include lung cancer and
autoimmune disease (systemic lupus erythematosus and
mixed connective tissue disorder). Inflammatory
polymyositis may also be associated with viral (HIV, human
T-lymphotropic virus type 1, nonpolio enterovirus), parasitic {Toxoplasma), or bacterial (Lyme disease) infections
(137).
Hereditary motor and sensory neuropathies, historically
called spinal muscular atrophies or muscular dystrophies,
may affect the anterior horn cells of the spinal cord.
Werdnig-Hoffmann disease is a rapidly progressing, often
fatal disorder with onset during the first year of life;
Wohlfart-Kugelberg-Welander disease is a more benign disorder with onset in late childhood or early adolescence
(138). The etiology and pathogenesis of hereditary motor
and sensory neuropathies are still incompletely understood
(139).
Trichinosis is characterized by painful myopathic weakness potentially mimicking poliomyelitis, periorbital
swelling, splinter hemorrhages, and fever, and it also may
manifest as meningoencephalitis, mononeuropathies,
polyneuropathies, and radiculitis (140). Signs of spinal cord
damage have included paraparesis, hyperalgesia and
decreased deep tendon reflexes of the lower extremities, urinary retention, and bladder anesthesia. The diagnosis is
based on eosinophilia, serologic testing, history of preceding gastrointestinal illness, consumption of contaminated
pork or walrus meat, and the presence of larvae of the nematode helminth Trichinella spiralis upon muscle biopsy
(141). Although it is prevalent in tropical and temperate
areas, trichinosis is also a serious medical problem among
Native populations in Arctic regions.
NEUROPATHIES OCCURRING IN SYSTEMIC OR
METABOLIC DISORDERS
Acute hypokalemic periodic paralysis is a rare cause of

AFP (142). Two thirds of cases are due to hypokalemic
familial periodic paralysis, a disease that exhibits autosomal-dominant inheritance and mostly affects Caucasian
male children and adolescents (142). Familial periodic
paralyses have been divided into three main forms according to precipitating factors and the patient's potassium level
at the time of an attack: 1) Hypokalemic familial periodic
paralysis is usually precipitated by a meal rich in carbohydrates, and it has the tendency to manifest in the morning
Acute weakness syndromes in critically ill patients can be

categorized into three major groups with different etiologies: 1) critical illness polyneuropathy; 2) neuromuscular
junction abnormalities, subdivided into myasthenia-like
syndromes and prolonged neuromuscular blockade; and
3) myopathy, including acute disuse (cachectic), necrotizing,
and thick filament (myosin) loss myopathy (131). Recent
data also suggest that physiologic muscular inexcitability
due to sodium channel dysfunction, rather than morphologic
changes of the muscle, may contribute to weakness in critically ill patients (132).
Nondepolarizing neuromuscular blocking agents, used
with increasing frequency in critically ill patients, have been
associated with prolonged muscle weakness (133).
Individuals with status asthmaticus treated with bronchodilators, antibiotics, and high dose corticosteroids and
paralyzed with vecuronium to facilitate mechanical ventilation have developed flaccid quadriplegia with areflexia.
Brief weakness lasting for several hours to several days is
probably the result of prolonged neuromuscular blockade,
while more prolonged weakness lasting for several weeks to
months is probably caused by myopathy. Clinically, patients
develop AFP with intact sensation and cognition.
Neuromuscular dysfunction in patients with sepsis is
increasingly being reported (131, 134). The common underlying pathogenic process in these syndromes appears to be
systemic inflammatory response syndrome, induced by
infection or trauma and accentuated by the administration of
steroids or neuromuscular blocking agents (131). Flaccid
quadriplegia with the inability to wean from ventilatory support despite full cardiopulmonary recovery is the typical
presentation. Electrophysiologic studies often demonstrate
the presence of axonal polyneuropathies, abnormalities of
neuromuscular transmission, or acute myopathies. Recovery
in strength usually occurs over a period of weeks to months.
Variants of critical illness polyneuropathy may affect endstage uremic or diabetic patients developing axonal, predominantly motor polyneuropathy.
First described by Hopkins and Shield in 1974 (135), acute
postasthmatic amyotrophy (Hopkins syndrome) is characterized by sudden onset of AFP of an arm or a leg with completely preserved sensibility approximately 1 week after an
asthma attack. All children in the initial case description were
under 10 years of age, and most were male. To date, fewer
than 30 cases have been described in the literature. The AFP
is probably due to a lesion of the anterior horn cells of the
spinal cord, but evidence indicates a more widespread pathologic process. The etiology is unknown, but infectious or
immunologic mechanisms are likely. It has been suggested
that a combination of immune suppression with the stress of
an acute asthma attack, concurrent infection, or corticosteroid
therapy renders patients susceptible to viral invasion of anterior horn cells. Infections with M. pneumoniae and other
agents have been associated with Hopkins syndrome (136).
DISORDERS OF THE MUSCLE
OTHER CLINICAL SYNDROMES CAUSING AFP
Other entities that have been misdiagnosed as

poliomyelitis include osteoarticular trauma, acute cerebellitis, retroperitoneal tumors, infection of an intervertebral
disc, scurvy, Caffey's disease (infantile cortical hyperostosis), postictal hemiparesis (Todd's paralysis), and "floppy
infant" syndrome (18, 20).
An important psychological element was observed in a
condition known as epidemic neuromyasthenia, also
referred to as "the summer grippe," "Iceland disease," or
"Durban mystery disease," which has been reported in various parts of the United States, Iceland, South Africa, and
England (19). Reports from South Africa suggest an association with the organic compound triorthocresyl phosphate
(19) (see "Diseases of the Neuromuscular Junction"), while
recent reports suggest that neuromyasthenia may be caused
by a low-virulence but neuropathic type 2 poliovirus (148).
Although it is not included in the surveillance case definition of AFP, facial paralysis may be associated with
poliovirus infection, Guillain-Barr6 syndrome, or AMAN
(149). The most common form of facial paralysis, idiopathic
Bell's palsy (150), is characterized by complete flaccid
facial paralysis. Eighty percent of affected individuals
recover within a few months. A rather typical clinical course
of Bell's palsy allows one to focus differential diagnostic
investigation predominantly on the rapid identification of
treatable infections such as those caused by varicella-zoster
virus or borreliae (149). Other causes of facial paralysis
include enterovirus infection, HIV infection, Ramsay-Hunt
syndrome (presumably due to varicella-zoster virus infection of the geniculate ganglion), Guillain-Barre syndrome
(mainly affecting cranial nerves VII and IX-XII), AMAN,
and sarcoidosis (uveoparotid fever or sarcoidosis, Heerfordt
syndrome).
PARALYTIC SYNDROMES COMMONLY MISDIAGNOSED
AS AFP
Conditions commonly misdiagnosed as AFP can be

grouped into two broad etiologic categories: paralytic illness
associated with nutritional toxins (151) and chronic central
nervous system disease, frequently with dementia. The links
between these two etiologic categories are influenced by
postinfective tropical malabsorption and micronutrient and
mineral deficiency from food and water. Cobalamin (vitamin B )2 ) deficiency causes pernicious anemia and can also
result in severe polyneuropathy with symmetrical paralysis
and atrophy (152). Chronic cycad poisoning (evergreens,
seeds), in conjunction with deficiency syndromes, has been
implicated in the etiology of these clusters of paralytic illness.
Clusters of amyotrophic lateral sclerosis, Parkinson
dementia, and a subacute paralytic condition reminiscent of
Guillain-Barre' syndrome, referred to as "poliomyeloradiculitis" because of the asymmetrical distribution of paralysis
(152), must be differentiated from poliomyelitis, other nonpolio enterovirus infections, and micronutrient deficiency
syndromes.
hours after rest. 2) Potassium-sensitive familial periodic

paralysis usually has its onset before the age of 10 years; the
attacks are less severe than those of the hypokalemic form
and tend to occur during the daytime. 3) In familial adynamia episodica hereditaria, first described by Gamstorp
(143), glucose prevents potassium-induced attacks of AFP.
Familial periodic paralysis and other muscle disorders leading to attacks of weakness that occur intermittently in otherwise normal people have been linked to disturbed function
of skeletal muscle ion channels ("channelopathies") (144).
Depending on the type of familial periodic paralysis, the
diagnosis is established by the demonstration of changes in
serum potassium levels during the attack, the presence of
electromyographic and electrocardiographic abnormalities,
and the use of muscle biopsy and potassium-, glucose-, or
insulin-loading tests.
Thyrotoxic periodic paralysis is a syndrome defined by
characteristic clinical, electromyographic, biochemical, and
microscopic features. Asian, Hispanic, and Native American
males aged 30-60 years are most commonly affected.
Clinical manifestations include acute-onset progressive
symmetrical weakness leading to AFP of the extremities and
other muscle groups (acute episodes of flaccid paraplegia or
tetraplegia) which is induced by excess levels of exogenous
or endogenous (Graves' disease) thyroid hormones and after
high carbohydrate ingestion or heavy exertion. This syndrome is distinct from thyrotoxic myopathy and familial
periodic paralysis. Because of its association with use of
diuretics, the syndrome is found in older individuals and
needs to be differentiated clinically from Guillain-Barre'
syndrome.
Acute intermittent porphyria may cause a rapidly progressing peripheral neuropathy with motor-sensory signs
and symptoms and consequent AFP (145). Acute intermittent porphyria may include abdominal pain and psychological and neurologic signs (disturbances of consciousness and
mentation, convulsions), but not all attacks progress to the
neurologic stage. The initial episode often occurs in early
adolescence. The classic ruby-red coloration or measurement of porphyrins (porphobilinogen, 8-aminolevulinic
acid) in the urine helps confirm the diagnosis.
Sporadic cases of hypokalemic paralysis are associated
with various underlying disorders, such as renal tubular
acidosis, primary hyperaldosteronism (Conn's disease)
(146), and secondary hyperaldosteronism due to licorice
(Glycyrrhiza glabra) ingestion (22). Barium salts contaminating table salt or flour have been associated with
Chinese outbreaks of hypokalemic paralytic disease
known as "Pa Ping" or "Kiating" paralysis (147) (Pa Ping
and Kiating are areas in China's Szechwan Province).
Gossypol, a phenolic compound present in the seeds and
root barks of cotton plants (Gossypium, family Malvaceae)
and used in cottonseed oil for domestic cooking, is probably also responsible for epidemics of hypokalemic paralysis in China (22). Paralysis develops within 24 hours,
along with dysarthria, areflexia, and dysphagia. Disorders
of muscle energy metabolism causing AFP (Leigh's and
McArdle's disease) may be confounded with GuillainBarre' syndrome.
311
312
Marxetal.
GEOGRAPHIC DISTRIBUTION OF PARALYTIC

ILLNESSES
Host or environmental factors may considerably influence the occurrence and frequency of AFP. For instance, the
ability to metabolize certain drugs or compounds may vary
between certain populations (isoniazid toxicity in Japan;
thyrotoxic periodic paralysis mostly among Asian, Latin,
and Native American men). The spread of C. jejuni infections, in conjunction with host, dietary, and sanitary factors,
may account for summertime epidemics of AMAN without
geographic clustering in northern China. The spread of
potential vectors determines the occurrence of tickborne
paralysis or borreliosis (Lyme disease, relapsing fever)
causing GuiUain-Barre syndrome-like AFP. The geographic
distribution of genetically determined neuromuscular diseases may be influenced by genetic factors, while environmental factors may be associated with nonhereditary
immunologic myopathies and neuropathies. Exposure to
manmade or naturally occurring toxins, such as those found
in toxic plants (e.g., K. humboldtiana, K. calderoni), venomous animals (e.g., snakes, scorpions, frogs), contami-
nated water or food, or infectious agents, combined with

deficiency syndromes, may lead to a wide array of toxic
neuropathies, mostly in tropical areas (13).
CONCLUSIONS
AFP is a complex clinical syndrome that requires immediate and careful evaluation of the differential diagnoses.
Each case of AFP is an emergency, from both a clinical perspective and a public health perspective, and precise knowledge of the etiology, underlying pathophysiologic mechanisms, and anatomic-morphologic changes involved has
profound implications for prognosis and treatment. The
underlying pathology, precise cellular basis, or pathophysiologic mechanisms for certain causes of AFP are not yet
understood. The examples of Guillain-Barre' syndrome, neurologic complications in AIDS, acute transverse myelitis,
and Hopkins syndrome illustrate the complex and multifactorial interaction between different pathogenic factors,
including preceding or concurrent infection with neurotropic agents, along with inadequate immune or autoimmune responses of the nervous system. Infections with neurotropic viruses and other infectious agents may set in
motion a pathologic immune process that inappropriately
targets central or peripheral myelin or peripheral axons (8,
99). The association between infection with C. jejuni, M.
pneumoniae, S. mansoni, or 5. haematobium and a variety of
causes of AFP, such as AIDP, AMAN, Hopkins syndrome,
and acute transverse myelitis, is intriguing and has drawn
considerable research interest. The role of infectious agents
and immune processes as significant causes of AFP may be
complemented by a variety of naturally occurring or manmade toxins.
The list of underlying causes of AFP is broad, and there is
substantial variation by age, ethnicity, and geographic area.
In the absence of wild virus-induced poliomyelitis, the acute
demyelinating form of Guillain-Barr6 syndrome (AIDP)
accounts for at least 50 percent of AFP cases globally (16,
77), followed in frequency by paralytic nonpolio enterovirus
infection, the motor axonal form of Guillain-Barre syndrome (AMAN), traumatic neuritis, and acute transverse
myelitis.
The campaign to eradicate poliomyelitis is at a critical
stage. The smallpox eradication program demonstrated the
need for accurate surveillance, while a factor contributing to
the failure of earlier eradication programs was the absence
of the capacity to establish surveillance meeting these high
standards. Without accurate disease surveillance, it is
impossible to conduct an effective disease control or eradication program or to measure the disease burden and the
effect of intervention measures.
Because poliomyelitis is on the verge of eradication,
accurate surveillance for AFP must be intensified. The
global incidence rate of nonpolio AFP would be expected to
be 1 per 100,000 among children under 15 years of age
under conditions of optimal surveillance with complete case
ascertainment (78). Achieving and maintaining this detection rate is considered the most sensitive performance criterion for any AFP surveillance system. Epidemiologic and
Tropical myeloneuropathies, a serious health problem in

tropical regions, include tropical spastic paraparesis and
tropical ataxic neuropathy. Although tropical myeloneuropathies are multifactorial, specific etiologic agentse.g.,
cyanogenic glycosides from cassava (129), lathyrism (153),
postinfective tropical malabsorption, and human T-cell lymphotropic virus (154)have been implicated. Toxicity from
cyanide or cyanoglycosides in cassava can be exacerbated
by relative deficiencies of B vitamins (thiamine (vitamin
Bj), riboflavin (vitamin B2), and cobalamin (vitamin B12))
and sulfur-containing amino acids, which are necessary for
the detoxification of these compounds. Nutritional
myelopathies have been documented in Sub-Saharan Africa.
Isolated nonprogressive spastic paraparesis of acute onset
has been reported as "konzo" in the Democratic Republic of
the Congo and the Central African Republic and as "mantakassa" in Mozambique and Tanzania (22, 155). Seasonal
outbreaks have been linked epidemiologically to consumption of bitter cassava (Manihot esculenta, Manihot utilissima) (13). Cassava roots contain naturally occurring
cyanogens, and the plant's toxicity is enhanced with
decreased intake of foods with sulfur-containing amino
acids, which promote cyanide detoxification. Acute hydrocyanide poisoning may result from consuming toxic winged
beans, and chronic cyanide acid poisoning may result from
consuming poorly washed manioc.
Lathyrism is the classic cause of epidemic outbreaks of
tropical spastic paraparesis associated with excessive ingestion of certain flowering peas in times of famine (Lathyrus
sativus (chickling pea), Lathyrus clymenwn (Spanish vetch),
Lathyrus cicera (flat-podded pea)), Phascolus, and several
grasses (156). Lathyrism is still endemic in regions of India,
Bangladesh, and Ethiopia and continues to be a public
health problem. Lathyrism has been associated with outbreaks of paralytic illness in Myanmar (World Health
Organization, unpublished data).
Differential Diagnosis of Acute Flaccid Paralysis 313
ACKNOWLEDGMENTS
The authors thank Dr. Peter Strebel, Dr. Muireann
Brennan, Dr. Bernard Moriniere, and Dr. Gina Tambini for
technical advice; Jeff Colby and Patricia Smith for graphic
assistance; and Jessie Aukes, Onnalee Henneberry, Pam
Martin, Matthew Nwosu, and Katherine Tucker for assistance in searching the literature.
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Epidemiologic Reviews

Vol. 22, No. 2

Differential Diagnosis of Acute Flaccid Paralysis and Its Role in Poliomyelitis

Arthur Marx,1 Jonathan D. Glass,2 and Roland W. Sutter1

AFP is a complex clinical syndrome with a broad array of

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encompasses all cases of paralytic poliomyelitis, also is of

DEFINITION OF ACUTE FLACCID PARALYSIS

Differential Diagnosis of Acute Flaccid Paralysis

explored in previous review articles. We discuss etiologies

CLINICAL APPROACH TO PATIENTS WITH AFP

Each case of AFP is a clinical emergency and requires

graphic region, the skin and scalp should be carefully

Epidemiol Rev Vol. 22, No. 2, 2000

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All available electronic databases, including Medline

1. Differential diagnosis of acute flaccid paralysis: clinical and epidemiologic characteristics

24-48 hours to onset

Aseptic meningitis Reduced

Mixed axon- Dene

Exanthematous vesicular eruptions

anese encephlitis virus

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Headache, back pain,

Subacute, proximal > distal

Neoplasma, autoimmune disease

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Subacute myalgia Days

DIFFERENTIAL DIAGNOSIS OF AFP

The list of underlying causes of AFP is broad (table 1) and

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other viral or bacterial infections. A lumbar puncture and

LESION OF THE ANTERIOR HORN CELLS OF THE

Viruses targeting motor neurons

Polioviruses. Poliomyelitis. Poliomyelitis is caused by

Differential Diagnosis of Acute Flaccid Paralysis

Acute Transverse Myelitis

Dorsal Root Ganglia:

Spinal Cord Compression:

Anterior Spinal Artery

eradicated in the Americas; as of 1999, the only remaining

times excruciating myalgia, is seen in adults (29).

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regenerate, which results in the inability of affected muscles

Differential Diagnosis of Acute Flaccid Paralysis

Epidemiol Rev Vol. 22, No. 2, 2000

suggest that Japanese encephalitis virus myelitis is caused

Landry-Guillain-Barre-Strohl syndrome, hereafter called

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clinically indistinguishable from paralytic poliomyelitis

Subacute and chronic inflammatory demyelinating

Subacute inflammatory demyelinating polyradiculoneuropathy (SIDP) and chronic inflammatory demyelinating

metrical AFP, disturbances of sensory function, cranial

Acute motor axonal neuropathy (AMAN), also referred to

Neurologic disorders, including AFP, may complicate HIV

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against rabies (especially with the Semple-type vaccine

Differential Diagnosis of Acute Flaccid Paralysis

a causal relation (106). The illness may be suggestive of

Acute myelopathy may occur because of the presence of

Administration of intramuscular injections in the gluteal

Trauma should always be considered clinically as a cause