28 Coma Exam

GOAL = to distinguish glasgow coma scale
toxic = metabolic cause
structural cause eye opening
spontaneous =4
to speech =3
to pain =2
no response =1

hypervwntilation

and... hypoxemia or metabolic vertbral response
abc respiratory patterns orientated =5
acidosis
confused =4
inappropriate words =3
incomprehensible sounds =2
no response =1
vitals NIH stroke scale

consiousness motor response
neurologic exam pulse alert =0
coma =3 obeys =6
blood pressure localizes =5
rectal temperature withdraw to pain =4
mental status orientation
month =1 aqbnormal flexion =3
eye exam abnormal extension =2
occulocephalic age =1
no response =1
exam
occulovesticular neck commands
exam open eyes =1
menigismus close eyes =1
motor exam thyromegaly make fist =1
at rest = release fist =1 interpretation
movements
posturing total = 13 - 15
visual field minor head injury = 13 - 15
purposeful movement head ingury normal =0 moderate = 9 - 12
= intact brainstem and hemianopia =1 severe + coma = <=8
cortex hemotympanum bilateral loss =2 = significant mortality risk
cephalematoma
CSF leakage nose, ear canal
response to pain faciaL Palcy
posturing show teeth =1
abduction = cardiopulmonary raise eyebrows =1
decerebrate squeeze eyes shut =1 acute motor weakness causes
wheezes, rales movement disorders
or adduction= murmurs
decorticate irregular rythms
no drift =0 Syndromes which feature DYSKINESIAS as a
chest scars
triple flexion cannot resist gravity =2 cardinal manifestation of the disease process.
response no movement =4 Included in this category are :
amputation =9 degenerative,
asymmetric response abdomen
hereditary,
4 limbs passively move = strenght post-infectious,
flaccid paralysis bowel sounds left arm 90 degrees
ascites medication-induced,
right arm 90 degrees post-inflammatory, and
hepatomegaly = ~ encephalopathy left leg 90 degrees
abdominal aortic aneyrysm post-traumatic conditions
right leg 90 degrees

limb ataxia infectious [ diptheria - poliomyelitis ]
nose finger
skin hell knee metabolic [ thyrotoxicosis - hypophosphatemia -
jauntice hypermagnesemia - porphyria ]
absent = o
petechie both limbs = 2
hydration toxins [ botulism - buckthorn - seafood [ paralytic
skin temperature sensory loss shellfish toxin, tetrodoxin ]]
needle tracks pin prick and compare both sides
face, arm, trunk, legs
compound exposures [ arsenic - thalium - lead ]
autisms = involuntary protective acts normal = 0
severe loss = 2 medications [ dapsone ]
yawn, hiccup, sneezing, swallowing
language
normal = 0 tick paralysis
aphasia = mute = 3
occulovesticular exam autoimmune causes [ myasthenia gravis -
speech clarity polymyositis - demyelinating disease [ guillain barre,
both eyes slow towards cold, fast to middline = normal, no coma normal articulation = 0 chrionic inflammatory demyelinating
unintelligible = 2
polyneuropathy]]
both eyes deviate from cold = coma with intact brainstem intubated = 9

no eye movement = brainstem injury extinction, inatention
none = 0
complete = 2
investigation :
1 eye movement at the side of stimulus = braqinstem structural
lesion, internuclear opthalmoplegia myopathy
hemiparesis

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Comparison of the contents of various Effects of Sea Buckthorn Oil on Dry
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Journal of agricultural and food Cream ; Base cream ; SBA24 Sea
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Tetrodotoxin
From Wikipedia, the free encyclopedia

Tetrodotoxin (also known as "tetrodox" and frequently abbreviated as Tetrodotoxin
TTX) is a potent neurotoxin with no known antidote. There have been
succesful tests of a possible antidote in mice, but further tests must be
carried out to determine efficacy in humans.[1] Tetrodotoxin blocks action
potentials in nerves by binding to the pores of the voltage-gated, fast sodium
channels in nerve cell membranes.[2] The binding site of this toxin is located
at the pore opening of the voltage-gated Na+ channel. Its name derives from
Tetraodontiformes, the name of the order that includes the pufferfish,
porcupinefish, ocean sunfish or mola, and triggerfish, several species of
which carry the toxin. Although tetrodotoxin was discovered in these fish
and found in several other animals (e.g., Blue-ringed Octopus, Rough-
skinned newt,[3] and Naticidae[4]) it is actually the product of certain
bacteria such as Pseudoalteromonas tetraodonis, certain species of
Pseudomonas and Vibrio, as well as some others.

Its mechanism of action, selective block of the Na channel, was showed
definitively in 1964 by Toshio Narahashi and John Moore at Duke
University, using Moore's sucrose gap voltage clamp technique.[5]
IUPAC
name Octahydro-12-(hydroxymethyl)-2-imino-
Contents 5,9:7,10a-dimethano-10aH-[1,3]dioxocino
[6,5-d]pyrimidine-4,7,10,11,12-pentol
 1 Sources in nature Other anhydrotetrodotoxin, 4-epitetrodotoxin,
 2 Biochemistry names tetrodonic acid, TTX
 2.1 Physiology Identifiers
 2.2 Medical uses CAS 4368-28-9
 2.3 Total synthesis number
PubChem 20382
 3 Poisoning
SMILES
 3.1 Toxicity
C([C@@]1([C@@H]2[C@@H]3[C@H](N=C(N
 3.2 History [C@@]
 3.3 Symptoms and treatment
34C([C@@H]1O[C@@]([C@H]4O)(O2)O)O)N)O)
O)O
 3.4 Geographic frequency of toxicity
Properties
 3.5 Food analysis
Molecular C11H17N3O8
 4 Regulation formula
 5 See also Molar mass 319.27 g mol−1
 6 References Except where noted otherwise, data are given for
 7 External links materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Sources in nature
Tetrodotoxin has been isolated from widely differing animal species, including western newts of the genus Taricha (where it
was termed "tarichatoxin"), pufferfish, toads of the genus Atelopus, several species of blue-ringed octopodes of the genus
Hapalochlaena (where it was called "maculotoxin"), several sea stars, an angelfish, a polyclad flatworm, several species of
Chaetognatha (arrow worms), several nemerteans (ribbonworms) and several species of xanthid crabs. The toxin is variously
used as a defensive biotoxin to ward off predation, or as both a defensive and predatory venom (the octopodes, chaetognaths
and ribbonworms). Tarichatoxin and maculotoxin were shown to be identical to tetrodotoxin in 1964 and 1978, respectively.
Recent evidence has shown the toxin to be produced by bacteria within blue-ringed octopuses.[6] The most common source of
bacteria associated with TTX production is Vibrio bacteria, with Vibrio alginolyticus being the most common species.
Pufferfish,[7] chaetognaths,[8] and nemerteans[9] have been shown to contain Vibrio alginolyticus and TTX.

Biochemistry

Tetrodotoxin binds to what is known as site 1 of the fast voltage-gated sodium channel. Site 1 is located at the extracellular
pore opening of the ion channel. The binding of any molecules to this site will temporarily disable the function of the ion
channel. Saxitoxin and several of the conotoxins also bind the same site.

The use of this toxin as a biochemical probe has elucidated two distinct types of voltage-gated sodium channels present in
humans: the tetrodotoxin-sensitive voltage-gated sodium channel (TTX-s Na+ channel) and the tetrodotoxin-resistant voltage-
gated sodium channel (TTX-r Na+ channel). Tetrodotoxin binds to TTX-s Na+ channels with a binding affinity of 5-15
nanomolar, while the TTX-r Na+ channels bind TTX with low micromolar affinity. Nerve cells containing TTX-r Na+
channels are located primarily in cardiac tissue, while nerve cells containing TTX-s Na+ channels dominate the rest of the
body. The prevalence of TTX-s Na+ channels in the central nervous system makes tetrodotoxin a valuable agent for the
silencing of neural activity within a cell culture.

Physiology

The toxin blocks the fast Na+ current in human myocytes (the contractile cells of the muscles), thereby inhibiting their
contraction. By contrast, the sodium channels in pacemaker cells of the heart are of the slow variety, so action potentials in the
cardiac nodes are not inhibited by the compound. The poisoned individual therefore dies not because the electrical activity of
the heart is compromised, but because the muscles are effectively paralyzed.

Medical uses

Blocking of fast Na+ channels has potential medical use in treating some cardiac arrhythmias. Tetrodotoxin has proved useful
in the treatment of pain (originally used in Japan in the 1930s) from such diverse problems as terminal cancer,[10] migraines,
and heroin withdrawal.[11] Some people even put pufferfish on their face for beauty reasons.

Total synthesis

Y. Kishi et al. Nagoya University, Nagoya, Japan, (now at Harvard University) reported the first total synthesis of D,L-
tetrodotoxin in 1972.[12][13] M. Isobe et al. at Nagoya University, Japan[14][15][16] and J. Du Bois et al. at Stanford University,
USA, reported the asymmetric total synthesis of tetrodotoxin in 2003.[17] The two 2003 syntheses used very different
strategies, with Isobe's route based on a Diels-Alder approach and Du Bois's work using C-H bond activation.

Poisoning
Tetrodotoxin is 100 times more poisonous than potassium cyanide.[18] Fish poisoning by consumption of members of the order
Tetraodontiformes is extremely serious. The skin and organs (e.g. liver) of the pufferfish can contain levels of tetrodotoxin
sufficient to produce paralysis of the diaphragm and death due to respiratory failure.[19] Toxicity varies between species and at
different seasons and geographic localities, and the flesh of many pufferfish may not usually be dangerously toxic. It is not
always entirely fatal, however; at near-lethal doses, it can leave a person in a state of near-death for several days, while the
person continues to be conscious. It is for this reason that tetrodotoxin has been alleged to be an ingredient in Haitian
voodooism and the closest actual manifestation to zombieism in the physical world, an idea that was popularized by Harvard-
trained ethnobotanist Wade Davis in a 1983 paper, and in his 1985 book, The Serpent and the Rainbow. However, this idea
was dismissed by the scientific community in the 1980s, as the descriptions of voodoo zombies do not match the symptoms
displayed by victims of tetrodotoxin poisoning, and the alleged incidents of zombies created in this manner could not be
substantiated.[20]

Toxicity

The Material Safety Data Sheet for tetrodotoxin lists the oral median lethal dose (LD50) for mice as 334 μg per kg.[21]
Assuming that the lethal dose for humans is similar, 25 milligrams (0.000881 oz) of tetrodotoxin would be expected to kill a
75 kg (170 lb) person. The amount needed to reach a lethal dose by injection is much smaller, 8 μg per kg,[22] or a little over
one-half milligram (0.00002 oz) per person.

History

The first recorded cases of tetrodotoxin poisoning were from the logs of Captain James Cook from 7 September 1774.[19] He
recorded his crew eating some local tropic fish (pufferfish), then feeding the remains to the pigs kept on board. The crew
experienced numbness and shortness of breath, while the pigs were all found dead the next morning. In hindsight, it is clear
that the crew received a mild dose of tetrodotoxin, while the pigs ate the pufferfish body parts that contain most of the toxin,
thus killing them.

The toxin was first isolated and named in 1909 by Japanese scientist Dr. Yoshizumi Tahara.[19]

Symptoms and treatment

The diagnosis of pufferfish poisoning is based on the observed symptomology and recent dietary history.

Symptoms typically develop within 30 minutes of ingestion but may be delayed by up to four hours; however, death once
occurred within 17 minutes of ingestion.[19] Paresthesias of the lips and tongue are followed by sialorrhea, sweating, headache,
weakness, lethargy, ataxia, incoordination, tremor, paralysis, cyanosis, aphonia, dysphagia, seizures, dyspnea, bronchorrhea,
bronchospasm, respiratory failure, coma, and hypotension. Gastroenteric symptoms are often severe and include nausea,
vomiting, diarrhea, and abdominal pain. Cardiac arrhythmias may precede complete respiratory failure and cardiovascular
collapse.

The first symptom of intoxication is a slight numbness of the lips and tongue, appearing between 20 minutes to three hours
after eating poisonous pufferfish.[19] The next symptom is increasing paresthesia in the face and extremities, which may be
followed by sensations of lightness or floating. Headache, epigastric pain, nausea, diarrhea, and/or vomiting may occur.
Occasionally, some reeling or difficulty in walking may occur. The second stage of the intoxication is increasing paralysis.
Many victims are unable to move; even sitting may be difficult. There is increasing respiratory distress. Speech is affected, and
the victim usually exhibits dyspnea, cyanosis, and hypotension. Paralysis increases and convulsions, mental impairment, and
cardiac arrhythmia may occur. The victim, although completely paralyzed, may be conscious and in some cases completely
lucid until shortly before death. Death usually occurs within 4 to 6 hours, with a known range of about 20 minutes to 8 hours.

If the patient survives 24 hours, then recovery without any residual effects will usually occur over several days.[23]

Therapy is supportive and based on symptoms, with aggressive early airway management.[19] If ingested, treatment can consist
of emptying the stomach, feeding the victim activated charcoal to bind the toxin, and taking standard life-support measures to
keep the victim alive until the effect of the poison has worn off.[19] Alpha adrenergic agonists are recommended in addition to
intravenous fluids to combat hypotension. Anticholinesterase agents have been used with mixed success. No antidote has been
developed.

Geographic frequency of toxicity

Poisonings from tetrodotoxin have been almost exclusively associated with the consumption of pufferfish from waters of the
Indo-Pacific ocean regions. Several reported cases of poisonings, including fatalities, involved pufferfish from the Atlantic
Ocean, Gulf of Mexico, and Gulf of California. There have been no confirmed cases of tetrodotoxicity from the Atlantic
pufferfish, Sphoeroides maculatus. However, in three studies, extracts from fish of this species were highly toxic in mice.
Several recent intoxications from these fishes in Florida were due to saxitoxin, which causes paralytic shellfish poisoning with
very similar symptoms and signs. The trumpet shell Charonia sauliae has been implicated in food poisonings, and evidence
suggests that it contains a tetrodotoxin derivative. There have been several reported poisonings from mislabelled pufferfish and
at least one report of a fatal episode in Oregon when an individual swallowed a Rough-skinned Newt Taricha granulosa.

In 2009, a major scare in the Auckland Region of New Zealand was sparked after several dogs died eating sea slugs on
beaches. Children and pet owners were asked to avoid beaches, and recreational fishing was also interrupted for a time. After
exhaustive analysis, it was found that the sea slugs must have ingested tetrodotoxin which is also found in puffer fish.[24]

Statistical factors

From 1974 through 1983 there were 646 reported cases of pufferfish poisoning in Japan, with 179 fatalities. Statistics from the
Tokyo Bureau of Social Welfare and Public Health indicate 20–44 incidents of fugu poisoning per year between 1996 and

2006 in the entire country, leading to 34–64 hospitalizations and 0–6 deaths per year, for an average fatality rate of 6.8%.[25]
Of the 23 incidents recorded within Tokyo between 1993 and 2006, only one took place in a restaurant, while the others all
involved fishermen eating their catch.[25]

Only a few cases have been reported in the United States, and outbreaks in countries outside the Indo-Pacific area are rare,
except in Haiti, where tetrodotoxin is thought by some believers in voodoo mythology[20] to play a key role in the creation of
so-called zombie poisons.[26]

Genetic background is not a factor in susceptibility to tetrodotoxin poisoning. This toxicosis may be avoided by not consuming
animal species known to contain tetrodotoxin, principally pufferfish; other tetrodotoxic species are not usually consumed by
humans. Poisoning from tetrodotoxin is of particular public health concern in Japan, where pufferfish, "fugu", is a traditional
delicacy. It is prepared and sold in special restaurants where trained and licensed chefs carefully remove the viscera to reduce
the danger of poisoning. There is potential for misidentification and mislabelling, particularly of prepared, frozen fish products.

Food analysis

The mouse bioassay developed for paralytic shellfish poisoning (PSP) can be used to monitor tetrodotoxin in pufferfish and is
the current method of choice. An HPLC method with post-column reaction with alkali and fluorescence has been developed to
determine tetrodotoxin and its associated toxins. The alkali degradation products can be confirmed as their trimethylsilyl
derivatives by gas chromatography/mass spectrometry. These chromatographic methods have not yet been validated.

Regulation
In the USA, tetrodotoxin appears on the select agents list of the Department of Health and Human Services,[27] and scientists
must register with HHS in order to use tetrodotoxin in their research. However, investigators possessing less than 100 mg are
exempt from regulation.[28]

See also
 Conotoxin
 Neurotoxin
 Saxitoxin
 Tectin
 Clairvius Narcisse, a Haitian alleged to have been buried alive under the effect of the drug

References
1. ^ Rivera VR, Poli MA, Bignami GS. Prophylaxis and treatment with a monoclonal antibody of tetrodotoxin poisoning in mice.
Toxicon. Sep 1995;33(9):1231-7. [Medline].
2. ^ Hwang DF, Noguchi T (2007). "Tetrodotoxin poisoning". Adv. Food Nutr. Res 52: 141–236. doi:10.1016/S1043-4526(06)52004-2.
PMID 17425946.
3. ^ Hogan CM (2008-12-02). "Rough-Skinned Newt Taricha granulosa". GlobalTwitcher.com.
http://www.globaltwitcher.com/artspec_information.asp?thingid=43182. Retrieved 2009-04-06.
4. ^ Hwang DF, Tai KP, Chueh CH, Lin LC, Jeng SS (1991). "Tetrodotoxin and derivatives in several species of the gastropod
Naticidae". Toxicon 29 (8): 1019–24. doi:10.1016/0041-0101(91)90084-5. PMID 1949060.
5. ^ Voltage clamp at Scholarpedia
6. ^ Hwang DF, Arakawa O, Saito T, Noguchi T, Simidu U, Tsukamoto K, Shida Y, Hashimoto K (1988). "Tetrodotoxin-producing
bacteria from the blue-ringed octopus Octopus maculosus". Marine Biology 100 (3): 327–332. doi:10.1007/BF00391147.
7. ^ Noguchi, T.; Hwang, D.F.; Arakawa, O.; Sugita, H.; Deguchi, Y.; Shida, Y.; Hashimoto, K. (1987), "Alginolyticus, a tetrodotoxin-
producing bacterium, in the intestines of the fish Fugu vermicularis", Marine Biology 94 (4): 625–630, doi:10.1007/BF00431409,
http://www.springerlink.com/index/U26218G3808816N8.pdf, retrieved 2009-04-06
8. ^ Thuesen EV Kogure K (1989), "Kogure 1989. Bacterial production of tetrodotoxin in four species of Chaetognatha", Biological
Bulletin, Marine Biological Laboratory, Woods Hole 176: 191–194, doi:10.2307/1541587
9. ^ Carroll, S.; McEvoy, E.G.; Gibson, R. (2003), "The production of tetrodotoxin-like substances by nemertean worms in conjunction
with bacteria", Journal of experimental marine biology and ecology 288 (1): 51–63, doi:10.1016/S0022-0981(02)00595-6,
http://linkinghub.elsevier.com/retrieve/pii/S0022098102005956
10. ^ Hagen NA, du Souich P, Lapointe B, Ong-Lam M, Dubuc B, Walde D, Love R, Ngoc AH; on behalf of the Canadian Tetrodotoxin
Study Group (2008). "Tetrodotoxin for Moderate to Severe Cancer Pain: A Randomized, Double Blind, Parallel Design Multicenter

Study". J Pain Symptom Manage 35: 420. doi:10.1016/j.jpainsymman.2007.05.011. PMID 18243639.
11. ^ Stimmel, Barry (2002). "12: Heroin Addiction". Alcoholism, drug addiction, and the road to recovery: life on the edge. New York:
Haworth Medical Press. ISBN 0-7890-0553-0. ""Tetrodotoxin blocks the sodium currents and is believed to have potential as a
potent analgesic and as an effective agent in detoxoification from heroin addiction without withdrawal symptoms and without
producing physical dependence""
12. ^ Kishi Y, Aratani M, Fukuyama T, Nakatsubo F, Goto T, Inoue S, Tanino H, Sugiura S, Kakoi H (December 1972). "Synthetic
studies on tetrodotoxin and related compounds. 3. A stereospecific synthesis of an equivalent of acetylated tetrodamine". J. Am.
Chem. Soc 94 (26): 9217–9. doi:10.1021/ja00781a038. PMID 4642370.
13. ^ Kishi Y, Fukuyama T, Aratani M, Nakatsubo F, Goto T, Inoue S, Tanino H, Sugiura S, Kakoi H (1972). "Synthetic studies on
tetrodotoxin and related compounds. IV. Stereospecific total syntheses of DL-tetrodotoxin". J. Am. Chem. Soc 94 (26): 9219–9221.
doi:10.1021/ja00781a039. PMID 4642371.
14. ^ Ohyabu N, Nishikawa T, Isobe M (2003). "First Asymmetric Total Synthesis of Tetrodotoxin". J. Am. Chem. Soc 125 (29): 8798–
8805. doi:10.1021/ja0342998. PMID 12862474.
15. ^ Nishikawa T, Urabe D, Isobe M (2004). "An Efficient Total Synthesis of Optically Active Tetrodotoxin". Angewandte Chemie
International Edition 43 (36): 4782–4785. doi:10.1002/anie.200460293. PMID 15366086.
16. ^ Douglass Taber (2005-05-02). "Synthesis of (-)-Tetrodotoxin". Organic Chemistry Portal. organic-chemistry.org.
http://www.organic-chemistry.org/Highlights/2005/02May.shtm. Retrieved 2008-05-29.
17. ^ Hinman A, Du Bois J (2003). "A Stereoselective Synthesis of (-)-Tetrodotoxin". J. Am. Chem. Soc 125 (38): 11510–11511.
doi:10.1021/ja0368305. PMID 13129349.
18. ^ Reference to 100 times more poisonous.
19. ^ a b c d e f g Clark RF, Williams SR, Nordt SP, Manoguerra AS (1999). "A review of selected seafood poisonings". Undersea Hyperb
Med 26 (3): 175–84. PMID 10485519. http://archive.rubicon-foundation.org/2314. Retrieved 2008-08-12.
20. ^ a b Hines, Terence; "Zombies and Tetrodotoxin"; Skeptical Inquirer; May/June 2008; Volume 32, Issue 3; pp. 60–62.
21. ^ Material Safety Data Sheet Tetrodotoxin ACC# 01139 https://fscimage.fishersci.com/msds/01139.htm
22. ^ Material Safety Data Sheet Tetrodotoxin. Sigma-Aldrich Version 1.6 updated 10 March 2007.
23. ^ Toxicity, Tetrodotoxin -Theodore I Benzer, MD, PhD
24. ^ Puffer fish toxin blamed for deaths of two dogs - The New Zealand Herald, Saturday 15 August 2009
25. ^ a b 危険がいっぱいふぐの素人料理東京都福祉保健局
26. ^ Anderson WH (1988). "Tetrodotoxin and the zombie phenomenon". Journal of Ethnopharmacology 23 (1): 121–6.
doi:10.1016/0378-8741(88)90122-5. PMID 3419200.
27. ^ HHS and USDA Select Agents and Toxins 7 CFR Part 331, 9 CFR Part 121, and 42 CFR Part 73.
http://www.cdc.gov/od/sap/docs/salist.pdf
28. ^ Federal Register. Vol. 70, No. 52. Friday, March 18, 2005. http://www.cdc.gov/od/sap/42_cfr_73_final_rule.pdf

External links
 MeSH Tetrodotoxin
 Tetrodotoxin: essential data (1999)
 Tetrodotoxin from the Bad Bug Book at the U.S. Food and Drug Administration website
Retrieved from "http://en.wikipedia.org/wiki/Tetrodotoxin"
Categories: Neurotoxins | Ion channel toxins | Guanidines | Biological toxin weapons

 This page was last modified on 20 December 2009 at 21:20.
 Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. See Terms
of Use for details.
Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization.
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Tick paralysis

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Half Life: 28 hours (range 10-50 hours)


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Disorders A - Z What is Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)?
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Research literature What is Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)?
Clinical Trials Chronic inflammatory demyelinating polyneuropathy (CIDP) is a neurological disorder characterized by progressive
At NIH weakness and impaired sensory function in the legs and arms. The disorder, which is sometimes called chronic
Worldwide relapsing polyneuropathy, is caused by damage to the myelin sheath (the fatty covering that wraps around and
protects nerve fibers) of the peripheral nerves. Although it can occur at any age and in both genders, CIDP is more
Partner Organizations common in young adults, and in men more so than women. It often presents with symptoms that include tingling or
numbness (beginning in the toes and fingers), weakness of the arms and legs, loss of deep tendon reflexes
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The course of CIDP varies widely among individuals. Some may have a bout of CIDP followed by spontaneous
Find People recovery, while others may have many bouts with partial recovery in between relapses. The disease is a treatable
cause of acquired neuropathy and initiation of early treatment to prevent loss of nerve axons is recommended.
About NINDS However, some individuals are left with some residual numbness or weakness.

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The Holly Building 104 1/2 Forrest Ave. 60 East 42nd Street
Narberth, PA 19072 Suite 942
info@gbs-cidp.com New York, NY 10165-0999
http://www.gbs-cidp.org info@neuropathy.org
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Articles | Departments | Patient Information

An Algorithm for the Evaluation of Peripheral
Neuropathy
ANN NOELLE PONCELET, M.D.,
University of California, San Francisco, San Francisco, California

The diagnosis of peripheral neuropathies can be frustrating, time consuming
and costly. Careful clinical and electrodiagnostic assessment, with attention
to the pattern of involvement and the types of nerve fibers most affected,
narrows the differential diagnosis and helps to focus the laboratory
evaluation. An algorithmic approach to the evaluation and differential
diagnosis of a patient with peripheral neuropathy is presented, based on
important elements of the clinical history and physical examination, the use of
electromyography and nerve conduction studies, autonomic testing,
cerebrospinal fluid analysis and nerve biopsy findings. The underlying cause
of axonal neuropathies can frequently be treated; demyelinating neuropathies
are generally managed with the assistance of a neurologist.

The incidence of peripheral neuropathy is not known, but it is a common feature of many
systemic diseases. Diabetes and alcoholism are the most common etiologies of peripheral
neuropathy in adults living in developed countries. The primary worldwide cause of
treatable neuropathy is leprosy.1 Neuropathies associated with human immunodeficiency
virus (HIV) infection account for an increasing number of cases. Peripheral neuropathy has
numerous other causes, including hereditary, toxic, metabolic, infectious, inflammatory,
ischemic and paraneoplastic disorders. The number of peripheral neuropathies for which an
etiology cannot be found despite extensive evaluation ranges from 13 to 22 percent.2,3 Many
undiagnosed patients (up to 42 percent) are found, after a careful family history and
examination of kin, to have a familial neuropathy.2

The evaluation of a peripheral neuropathy can be time-consuming and costly. A systematic
approach based on a careful clinical and electrodiagnostic assessment can help narrow the
possibilities and tailor the laboratory evaluation to a specific differential diagnosis.

Anatomy
The peripheral nerves include the cranial nerves (with Diabetes and alcoholism are the
most common causes of
the exception of the second), the spinal nerve roots, peripheral neuropathy in the
the dorsal root ganglia, the peripheral nerve trunks and United States.

their terminal branches, and the peripheral autonomic
nervous system. By convention, the motor neurons
and their diseases are considered separately.

Nerves are composed of different types of axons.
Large, myelinated axons include motor axons and the
sensory axons responsible for vibration sense, The most common presentation
of peripheral neuropathy is distal
proprioception and light touch. Small myelinated symmetric sensorimotor
axons are composed of autonomic fibers and sensory dysfunction.
axons and are responsible for light touch, pain and
temperature. Small, unmyelinated axons are also
sensory and subserve pain and temperature. Neuropathies involving primarily the latter two
fiber types are called small-fiber neuropathies.

FIGURE 1.
Algorithm for evaluation of a patient with a peripheral neuropathy. (ECG=electrocardiogram;
EMG/NCS=electron microscopy/nerve conduction studies; AIDS=acquired immunodeficiency
syndrome; FVC=forced vital capacity)

Clinically, large-fiber neuropathies can be distinguished from small-fiber neuropathies
during neurologic testing: large fibers carry sensation for vibration and proprioception,
while small fibers carry sensation for pain and temperature. Sensation for light touch is
carried by both large and small nerve fibers.

Pathophysiology
Although peripheral neuropathy has multiple etiologies, the nerve has a limited number of
ways to respond to injury.4,5 The damage can occur at the level of the axon (i.e.,
axonopathy). A disruption of the axons (e.g., trauma) results in degeneration of the axon
and the myelin sheath distal to the site of the injury (i.e., Wallerian degeneration). In most
toxic and metabolic injuries, the most distal portion of the axons degenerates, with
concomitant breakdown of the myelin sheath (known as "dying-back," or length-

dependent, neuropathy).

Neuronopathies occur at the level of the motor neuron or dorsal root ganglion, with
subsequent degeneration of their peripheral and central processes. Because the injury is at
the level of the cell body, recovery is often incomplete.

Myelinopathies occur at the level of the myelin sheath and can be inflammatory or
hereditary. In acquired demyelinating neuropathies, the injury is often patchy or segmental.
Because the axons are relatively spared, recovery is often rapid (weeks to months) and
complete. Hereditary abnormalities of myelin are usually diffuse, with a slowly progressive
course.

Diagnostic Approach
The differential diagnosis of peripheral neuropathy is significantly narrowed by a focused
clinical assessment that addresses several key issues (Figure 1). The first issue is, does the
patient actually have a neuropathy? Causes of generalized weakness include motor neuron
disease, disorders of the neuromuscular junction and myopathy. Peripheral neuropathy can
also be mimicked by myelopathy, syringomyelia or dorsal column disorders, such as tabes
dorsalis. Hysterical symptoms can sometimes mimic a neuropathy.

TABLE 1
Neuropathies by Pattern of Involvement

Focal Multifocal
Entrapment Diabetes mellitus
Common sites of Vasculitis
compression Polyarteritis nodosa
Myxedema Systemic lupus
Rheumatoid arthritis erythematosus
Amyloidosis Sjögren's syndrome
Acromegaly Sarcoidosis
Compressive Leprosy
neuropathies HIV/AIDS
Trauma Multifocal variant of CIDP
Ischemic lesions Hereditary predisposition to
Diabetes mellitus pressure palsies
Vasculitis
Leprosy
Sarcoidosis
Neoplastic infiltration or
compression

HIV=human immunodeficiency virus; AIDS=acquired
immunodeficiency syndrome; CIDP=chronic inflammatory
demyelinating polyradiculoneuropathy.
Information from Thomas PK, Ochoa J. Symptomatology
and differential diagnosis of peripheral neuropathy. In:
Dyck PJ, Thomas PK, eds. Peripheral neuropathy.
Philadelphia: Saunders, 1993:749-74.

It is useful to determine the pattern of involvement. Is the neuropathy focal, multifocal or
symmetric? Focal neuropathies include common compressive neuropathies such as carpal
tunnel syndrome, ulnar neuropathy at the elbow or peroneal neuropathy at the fibular
head6,7 (Table 1).8 A multifocal neuropathy suggests a mononeuritis multiplex that may be
caused, for example, by vasculitis or diabetes (Table 1).8

If the neuropathy is symmetric, is it proximal or distal? Most toxic and metabolic
neuropathies present as a distal symmetric or dying-back process (Table 2).9 Proximal
sensory neuropathies are rare and include porphyria.6 Predominantly motor neuropathies
are often proximal and include acquired inflammatory neuropathies such as Guillain-Barré
syndrome8,9 (Table 3).8 An exception is lead neuropathy, which initially affects motor fibers
in radial and peroneal distributions.

TABLE 2
Distal Symmetric Sensorimotor Polyneuropathies

Endocrine diseases Carcinomatous axonal
Diabetes mellitus sensorimotor polyneuropathy

Hypothyroidism Lymphomatous axonal
Acromegaly sensorimotor polyneuropathy

Nutritional diseases Infectious diseases
Alcoholism Acquired immunodeficiency
Vitamin B12 syndrome
deficiency Lyme disease
Folate deficiency
Whipple's disease Sarcoidosis
Postgastrectomy
syndrome
Gastric restriction Toxic neuropathy
surgery for Acrylamide
obesity Carbon disulfide
Thiamine deficiency Dichlorophenoxyacetic acid
Ethylene oxide
Hexacarbons
Hypophosphatemia Carbon monoxide
Organophosphorus esters
Critical illness Glue sniffing
polyneuropathy
Metal neuropathy
Connective tissue Chronic arsenic intoxication
diseases Mercury
Rheumatoid arthritis Gold
Polyarteritis nodosa Thallium
Systemic lupus
erythematosus Medications (see Table 8)
Churg-Strauss
vasculitis
Cryoglobulinemia

Amyloidosis

Gouty neuropathy

Adapted with permission from Donofrio PD, Albers JW.
AAEM minimonograph #34. Polyneuropathy: classification
by nerve conduction studies and electromyography.
Muscle Nerve 1990;13:889-903.

A limited number of neuropathies involve the cranial nerves (Table 4).8 Guillain-Barré
syndrome frequently involves the facial nerves. Another uncommon pattern is greater
involvement of the arms than the legs (Table 4).8 Leprosy tends to involve cutaneous
nerves in cooler areas of the body, such as the tip of the nose, the pinna of the ear and the
volar surfaces of the arms.

TABLE 3 TABLE 4
Proximal Symmetric Motor Neuropathies with Less Common
Polyneuropathies Patterns of Involvement

Guillain-Barré syndrome
Neuropathies with cranial
Chronic inflammatory demyelinating
polyradiculoneuropathy nerve involvement
Diabetes mellitus Diabetes mellitus
Porphyria Guillain-Barré syndrome
Osteosclerotic myeloma
Waldenstrom's macroglobulinemia HIV/AIDS
Monoclonal gammopathy of Lyme disease
undetermined significance Sarcoidosis Neoplastic invasion
Acute arsenic polyneuropathy of skull base or meninges
Lymphoma
Diphtheria Diphtheria
HIV/AIDS Neuropathies predominant in
Lyme disease
Hypothyroidism upper limbs
Vincristine (Oncovin, Vincosar PFS) Guillain-Barré syndrome
toxicity Diabetes mellitus
Porphyria
Hereditary motor sensory
HIV=human immunodeficiency virus;
neuropathy
AIDS=acquired immunodeficiency
Vitamin B12 deficiency
syndrome.
Hereditary amyloid neuropathy
Information from Thomas PK, Ochoa type II*
J. Symptomatology and differential Lead neuropathy

diagnosis of peripheral neuropathy. In:
Dyck PJ, Thomas PK, eds. Peripheral HIV=human immunodeficiency
neuropathy. Philadelphia: Saunders, virus; AIDS=acquired
1993:749-74. immunodeficiency syndrome.
*--Carpal tunnel syndrome
resulting from amyloid deposits in
the flexor retinaculum.
Information from Thomas PK,
Ochoa J. Symptomatology and
differential diagnosis of
peripheral neuropathy. In: Dyck
PJ, Thomas PK, eds. Peripheral
neuropathy. Philadelphia:
Saunders, 1993:749-74.

Neuropathies can be categorized according to the fiber type that is primarily involved.
Most toxic and metabolic neuropathies are initially sensory and later may involve the
motor fibers (Table 2).9 Pure sensory neuropathies or neuronopathies can result from drug
toxicity (e.g., thalidomide, cisplatin [Platinol]), paraneoplastic syndromes or nutritional
deficiencies (Table 5).8,9 Primarily motor neuropathies include Guillain-Barré syndrome8,9
(Table 38). Alcoholism and diabetes can both cause small-fiber, painful neuropathies (Table
5).8,9 Autonomic involvement occurs in many small-fiber neuropathies but can also occur in
Guillain-Barré syndrome and is sometimes life-threatening (Table 5).8,9 It is important to
distinguish whether the neuropathy is axonal, demyelinating, or both. This differentiation is
best achieved using nerve conduction studies (NCS) and electromyography (EMG).

TABLE 5
Comparative Patterns of Neuropathies and Neuronopathies by Fiber Type

Pure sensory neuropathies and Small-fiber neuropathies
neuronopathies Leprosy
Paraneoplastic Diabetes mellitus
Medications (see Table 8) Alcoholic neuropathy
Carcinomatous sensory neuronopathy Amyloidosis
AIDS
Hereditary
Neuropathies with autonomic
involvement
Diabetic neuropathy
Lymphomatous sensory neuronopathy Amyloidosis
Porphyria
Paraneoplastic neuropathy
Lymphoma
Thallium, arsenic, mercury toxicity
Thiamine deficiency
Sjögren's syndrome Vincristine (Oncovin, Vincosar PFS)
Paraproteinemias toxicity
Nonsystemic vasculitic neuropathy Guillain-Barré syndrome
Idiopathic sensory neuronopathy Alcoholic neuropathy
Styrene-induced peripheral Acute pandysautonomia
neuropathy HIV/AIDS
Primary biliary cirrhosis
Crohn's disease
Chronic gluten enteropathy
Vitamin E deficiency
Hereditary sensory neuropathy types I
and IV
Friedreich's ataxia

AIDS=acquired immunodeficiency syndrome; HIV=human immunodeficiency
virus.
Information from Donofrio PD, Albers JW. AAEM minimonograph #34.

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