Comprehensive Review in Clinical Neurology: A Multiple Choice Question Book for the Wards and Boards

Chapter 17. Nutritional and Toxic Disorders of the Nervous System


 1. Which of the following drugs is not associated with withdrawal symptoms?

      a.  Cocaine

      b.  Lysergic acid diethylamide

      c.  Amphetamine

      d.  Alcohol

      e.  Opiates

Questions 2–6

 2. A 32-year-old man with a history of opiate abuse presents to the emergency department in suspected opiate overdose. Which of the following is not a typical finding in someone with opiate intoxication?

      a.  Hypotension

      b.  Decreased respirations

      c.  Bradycardia

      d.  Mydriasis

      e.  Decreased cough reflex

 3. What would be the most appropriate treatment for symptom reversal in this patient with suspected opiate overdose?

      a.  Intravenous naltrexone

      b.  Intravenous thiamine

      c.  Intravenous glucose

      d.  Intravenous flumazenil

      e.  Intravenous naloxone

 4. The following day when you are examining the patient on morning rounds, you suspect that he is having opiate withdrawal. Which of the following findings would not be expected in opiate withdrawal?

      a.  Nausea and vomiting

      b.  Diarrhea

      c.  Dry eyes

      d.  Myalgias

      e.  Diaphoresis

 5. What are the two main structures in the reward circuit that are thought to mediate drug addiction?

      a.  Amygdala and locus coeruleus

      b.  Ventral tegmental area and nucleus accumbens

      c.  Periaqueductal gray matter and arcuate nucleus

      d.  Nucleus accumbens and periaqueductal gray matter

      e.  Ventral tegmental area and periaqueductal gray matter

 6. Which opiate receptor class is involved with spinal analgesia?

      a.  Kappa (κ)

      b.  Beta (β)

      c.  Mu (μ)

      d.  Delta (δ)

      e.  Nociceptin (ORL1)

Questions 7–9

 7. A 41-year-old man presents with suspected amphetamine intoxication. What is the most complete answer regarding the mechanism of action of this substance?

      a.  Blocks reuptake of dopamine and norepinephrine

      b.  Causes direct release of dopamine and norepinephrine but does not block their reuptake

      c.  Causes direct release of dopamine

      d.  Causes direct release of dopamine and norepinephrine and blocks their reuptake

      e.  Causes direct release of norepinephrine

 8. Which of the following would be an unexpected finding in the patient depicted in question 7?

      a.  Tachycardia

      b.  Miosis

      c.  Hypertension

      d.  Cardiac arrhythmia

      e.  Dyskinesia

 9. Cocaine intoxication can present similarly to amphetamine intoxication. What is the primary mechanism of action of cocaine?

      a.  Causes direct release of dopamine and norepinephrine and inhibits their reuptake

      b.  Inhibits reuptake of dopamine and norepinephrine

      c.  Causes direct release of norepinephrine

      d.  Causes direct release of dopamine and norepinephrine but does not inhibit their reuptake

      e.  Causes direct release of dopamine

Questions 10–15

10. A 52-year-old man presents to the emergency department with altered mental status and somnolence. He smells strongly of alcohol and his blood alcohol level confirms your suspicion of intoxication. What would be the best next step in treatment of this patient?

      a.  Intravenous folate

      b.  Intravenous glucose

      c.  Intravenous thiamine

      d.  Intravenous flumazenil

      e.  Intravenous naloxone

11. On closer examination, you find that besides the confusion, he also has nystagmus, ophthalmoplegia, and ataxia. You suspect Wernicke’s encephalopathy. Which of the following structures would you not expect to find abnormalities in on an MRI of the brain?

      a.  Hypothalamus

      b.  Mammillary bodies

      c.  Caudate nucleus

      d.  Periaqueductal gray matter

      e.  Medial thalami

12. Two days after admitting the patient depicted in question 10, you begin to notice new-onset tremors, tachycardia, and hypertension. There is no history of epilepsy. What is the next most important medication to add for this patient, assuming initial standard therapy has been started?

      a.  Propranolol

      b.  Nimodipine

      c.  Lorazepam

      d.  Phenytoin

      e.  Zolpidem

13. The effect of alcohol on the CNS is mediated primarily by what mechanism of action?

      a.  GABA receptor stimulation

      b.  GABA receptor stimulation

      c.  GABA and GABA receptor stimulation

      d.  GABA receptor inhibition

      e.  GABA receptor inhibition

14. How long after the last drink does delirium tremens typically begin in an alcoholic patient?

      a.  6 to 12 hours

      b.  12 to 24 hours

      c.  24 to 36 hours

      d.  36 to 48 hours

      e.  48 to 96 hours

15. When seizures occur in an alcoholic patient, which of the following would be the least likely time frame for them to occur after the last drink?

      a.  6 to 12 hours

      b.  12 to 24 hours

      c.  24 to 36 hours

      d.  36 to 48 hours

      e.  72 to 96 hours

16. What is the primary mechanism of action of nicotine?

      a.  Nicotinic acetylcholine receptor inhibition

      b.  Acetylcholine reuptake inhibition

      c.  Norepinephrine receptor activation

      d.  Nicotinic acetylcholine receptor activation

      e.  Dopamine reuptake inhibition

17. What is the primary mechanism of action that explains the stimulant effects of caffeine?

      a.  Adenosine agonist

      b.  Nicotinic acetylcholine antagonist

      c.  Nicotinic acetylcholine agonist

      d.  Adenosine antagonist

      e.  Adenosine diphosphate antagonist

Questions 18–21

18. A 38-year-old man was brought to the emergency department in handcuffs. He had broken out of the first set of handcuffs. He was found running down the street naked and throwing concrete blocks through windows because he thought he was invisible and was fighting “clear, flat aliens.” On examination, after being wrestled in place by six police officers, he is found to be hypertensive, tachycardic, and hyperthermic and have rotatory nystagmus. What intoxicating substance do you suspect?

      a.  Lysergic acid diethylamide

      b.  3, 4-Methylenedioxymethamphetamine

      c.  Phencyclidine

      d.  Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine)

      e.  Mescaline (peyote)

19. What is the primary mechanism of action of the suspected substance ingested by the patient in question 18?

      a.  Serotonin receptor agonist

      b.  Dopamine receptor agonist

      c.  NMDA receptor agonist

      d.  Serotonin receptor antagonist

      e.  NMDA receptor antagonist

20. The hallucinogenic drugs, such as lysergic acid diethylamide, are all theorized to act predominantly at what neurotransmitter receptor system?

      a.  Dopamine

      b.  Serotonin

      c.  Norepinephrine

      d.  Acetylcholine

      e.  NMDA

21. Which of the following would be an uncommon finding with hallucinogen intoxication?

      a.  Tachycardia

      b.  Anxiety

      c.  Diaphoresis

      d.  Miosis

      e.  Synesthesias

Questions 22–23

22. A 29-year-old woman presents with a slowly progressive spastic paraparesis of her legs over 2 years. In addition to this finding on examination, you also see that she has absent vibratory sense and proprioception in her feet. She also mentions that she takes zinc supplementation twice daily for the last several years to prevent “colds.” Which of the following is the most likely etiology of these findings?

      a.  Vitamin E deficiency

      b.  Vitamin B12 deficiency

      c.  Copper excess

      d.  Zinc deficiency

      e.  Copper deficiency

23. Which of the following would be one of your primary treatment recommendations for the patient depicted in question 22?

      a.  Vitamin B12 replacement therapy

      b.  Chelation therapy

      c.  Copper supplementation

      d.  Increase zinc supplementation

      e.  Vitamin E supplementation

Questions 24–25

24. A 38-year-old woman with Crohn’s disease, chronic diarrhea, and steatorrhea is referred to your office for evaluation of gait instability and ataxia. On examination, you find that she has some dysmetria, mild dysarthria, and absent reflexes. What is the likely cause of these neurologic findings?

      a.  Vitamin A deficiency

      b.  Vitamin D deficiency

      c.  Vitamin B12 deficiency

      d.  Copper deficiency

      e.  Vitamin E deficiency

25. Which of the following would be one of your primary treatment recommendations for the patient depicted in question 24?

      a.  Vitamin E supplementation

      b.  Vitamin A supplementation

      c.  Copper replacement

      d.  Increased sunlight and vitamin D supplementation

      e.  Vitamin B12 replacement

26. Which of the following would be the least likely finding related to thiamine (vitamin B1) deficiency?

      a.  Neuropathy

      b.  Arrhythmia

      c.  Extensor plantar responses

      d.  Congestive heart failure

      e.  Wernicke-Korsakoff syndrome

27. A defect in production of which of the following underlies the pathophysiology of the neurologic findings in vitamin B12 deficiency?

      a.  Threonine

      b.  Serotonin

      c.  Homocysteine

      d.  Methionine

      e.  Serine

Questions 28–29

28. A 49-year-old woman and her very anxious husband present to your office with progressively worsening sensory loss and weakness, which began distally in her legs and moved proximally beginning approximately a week ago. You notice she has a diffuse macular rash that is pruritic and scaling on her palms and soles. Records indicate that she had presented to the emergency department 3 weeks prior with complaints of severe nausea, vomiting, and diarrhea, and the physician had noted that her breath smelled strongly of garlic. What do you suspect is the cause for these symptoms?

      a.  Guillain-Barré syndrome

      b.  Cyanide poisoning

      c.  Thallium poisoning

      d.  Arsenic poisoning

      e.  Mercury poisoning

29. For the patient depicted in question 28, what test finding would have confirmed your suspicion if it had been completed during her emergency department visit 3 weeks prior?

      a.  LP revealing albumino-cytologic dissociation

      b.  Elevated urinary arsenic level

      c.  Elevated urinary thallium level

      d.  Elevated urinary mercury level

      e.  Elevated urinary cyanide level

30. A 34-year-old man who works at an industrial electroplating plant presents to the emergency department with complaints of nausea, vomiting, headache, anxiety, eye and mucous membrane irritation, cough, and dyspnea. His skin is also flushed with a cherry-red color. He mentions that he just started this job and forgot to wear protective work gear. He mentions that he smelled a bitter, almond odor while working all day. What do you suspect as the cause of these symptoms?

      a.  Arsenic poisoning

      b.  Carbon monoxide poisoning

      c.  Thallium poisoning

      d.  Mercury poisoning

      e.  Cyanide poisoning

31. A 45-year-old mine worker is brought to your office by his wife. She says he has been exhibiting progressive personality changes and has become very anxious. On examination, you find a prominent intention tremor and notice that his gums appear very inflamed and tender to touch. What do you suspect may be the cause of these symptoms?

      a.  Lead toxicity

      b.  FTD

      c.  Mercury toxicity

      d.  Thallium toxicity

      e.  Manganese toxicity

32. A 19-year-old girl with a history of migraine presents to the emergency department with her parents during the first cold week in the fall months. She complains of a generalized headache, nausea, dizziness, and malaise. You notice her skin is quite flushed and, interestingly, her parents both exhibit similar symptoms. What should be the first-line treatment at this time?

      a.  Symptomatic management

      b.  An antibiotic for possible early bacterial infection

      c.  An antiviral for possible early influenza

      d.  High-flow oxygen

      e.  High-rate IV fluids

33. A 5-year-old boy is brought to your office with his parents. They had recently moved into a house built in the 1920s. They are concerned because their son has been having behavioral changes, psychomotor slowing, clumsiness, lethargy, frequent abdominal pain, and suffered an unprovoked seizure 4 days ago. In addition, you notice that he has more weakness with extension of his hands compared with flexion. What is the most likely explanation?

      a.  Carbon monoxide toxicity

      b.  Autistic spectrum disorder

      c.  Lead toxicity

      d.  Mercury toxicity

      e.  HSV encephalitis

34. While on hospital neurology consult service, you are asked to see a 46-year-old man with chronic liver disease on long-standing total parenteral nutrition who has become confused and uncoordinated with a new tremor, bradykinesia, and other parkinsonian features. What do you suspect to be the cause of these symptoms?

      a.  Parkinson disease

      b.  Manganese toxicity

      c.  Lead toxicity

      d.  Severe malnutrition

      e.  Copper deficiency

35. A 56-year-old man who is an alcoholic presents to the emergency department with headache, reduced visual acuity of new onset, and nausea. He tells you he has been drinking “anything he can get his hands on containing alcohol, even that stuff you put in a car.” What toxicity to you suspect?

      a.  Hexacarbon toxicity

      b.  Lead toxicity

      c.  Gasoline ingestion

      d.  Acrylamide toxicity

      e.  Methanol toxicity

36. A 49-year-old farmer presents to the emergency department after finishing spraying his crop for the year against insect damage. He thinks he accidentally sprayed some in his mouth approximately 20 minutes ago, and his wife reports he had a brief seizure before arriving. He is salivating and having difficulty breathing with excess secretions. On examination, you notice frequent fasciculations. On the basis of your suspicion, which of the following would not be a recommended treatment at this time?

      a.  Activated charcoal

      b.  Benzodiazepines

      c.  Pralidoxime

      d.  Gastric lavage

      e.  Atropine

37. A 67-year-old man who lives on a farm with his wife presents with complaints of blurred and double vision, difficulty swallowing, and neck and shoulder weakness. There is no diurnal variation. These symptoms have been progressively worsening over the last 2 days. He reports being very healthy otherwise and attributes his good health to growing his own food and storing all excess by canning. On examination, you find multiple cranial nerve abnormalities and fixed pupillary dilation, and he is unable to contract his deltoids against resistance. What diagnosis would you first suspect?

      a.  Myasthenia gravis

      b.  Lambert-Eaton myasthenic syndrome

      c.  Botulism

      d.  Guillain-Barré syndrome

      e.  Leptomeningeal carcinomatosis

Answer Key

1. b

2. d

3. e

4. c

5. b

6. a

7. d

8. b

9. b

10. c

11. c

12. c

13. b

14. e

15. e

16. d

17. d

18. c

19. e

20. b

21. d

22. e

23. c

24. e

25. a

26. c

27. d

28. d

29. b

30. e

31. c

32. d

33. c

34. b

35. e

36. d

37. c


1. b

Lysergic acid diethylamide does not produce a withdrawal syndrome. Lysergic acid is one of the ergot fungus’ diverse alkaloid components, and it is a potent mood-changing and hallucinogenic drug. It is discussed further in question 18. Cocaine, amphetamine, alcohol, and opiates all have well-defined withdrawal syndromes and are discussed in further questions.

A marijuana (Cannabis) withdrawal syndrome has been debated. The DSM-IV-TR criteria for cannabis dependence include physiologic tolerance but do not include a withdrawal syndrome. The World Health Organization’s International Classification of Diseases-10th Revision does recognize a cannabis withdrawal syndrome, which is not life threatening. The most common symptoms of a possible cannabis withdrawal syndrome include fatigue, discomfort, yawning, anxiety, depression, hypersomnia, anxiety, and psychomotor slowing. Marijuana is typically smoked, although it is also ingested orally when added to other foods or drinks. The active ingredient in cannabis is δ-9-tetrahydrocannabinol (THC). Common side effects include increased appetite (THC is sometimes used for anorexia and as an anti-emetic in cancer and AIDS patients), tachycardia, dry mouth, conjunctival injection, excessive laughter, memory impairment, poor attention span, sedation, paranoia, anxiety, delusions, impaired coordination, and poor insight and judgment. Chronic use frequently causes flat affect, apathy, and lack of motivation. THC is active in the ventral tegmental area, nucleus accumbens, hippocampus, caudate nucleus, and cerebellum. THC’s effects on the hippocampus may help explain the memory problems that can develop with the use of cannabis, and those on the cerebellum may help explain the loss of coordination and imbalance sometimes seen.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Hasin DS. Cannabis withdrawal in the United States: results from NESARC. J Clin Psychiatry. 2008; 69:1354–1363.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York, NY: McGraw-Hill; 2009.

 2. d, 3. e,  4. c,  5. b, 6. a

Opiate use and intoxication classically are associated with miosis, or pinpoint pupils, not mydriasis. Of note, this must be differentiated from pontine lesions, which can also cause pinpoint pupils. All of the other options can be seen with opiate intoxication, including decreased body temperature and coma. In addition to these findings, common side effects include euphoria, drowsiness, analgesia, and constipation (hence the use of opiates and opiate derivatives as anti-diarrheals). Opiate toxicity/overdose creates a “silent gut”, which can help in the diagnosis. Because of its cough suppressant effects, codeine is sometimes used in cough medicines.

Treatment of suspected opiate overdose includes the opioid antagonist naloxone at 0.4 to 2 mg intravenously every 2 to 3 minutes. The diagnosis should be questioned if there is no response even after administration of 10 mg. Naltrexone is also an opioid antagonist used in longer-term treatment opioid and alcohol dependence as opposed to naloxone, which is used in emergency settings. Thiamine is classically given before glucose in suspected Wernicke encephalopathy. Flumazenil is given for benzodiazepine overdose. The dose of flumazenil is 0.2 to 0.5 mg intravenously every minute to a maximum total dose of 5 mg.

Opiate withdrawal occurs within hours to several days of cessation. Withdrawal symptoms are often quite severe and cause significant functional impairment. They include dysphoria, myalgias, nausea, vomiting, rhinorrhea, lacrimation, piloerection, diaphoresis, diarrhea, mydriasis, fever, and insomnia. Difficulty often exists in differentiating opiate from sedative (e.g., alcohol, benzodiazepines) withdrawal. Hyperactive deep tendon reflexes (DTRs) can help in this differentiation because increased DTRs are typical in alcohol or sedative withdrawal but not opioid withdrawal. Therefore, if you see increased DTRs and give more opioids for suspected opioid withdrawal in the setting of actual sedative withdrawal, benzodiazepine or alcohol withdrawal seizures will be a likely complication.

Opiates are one of multiple euphoria-producing drugs. All euphoria-producing drugs cause release of dopamine from the midbrain to the forebrain in the reward circuit (ventral tegmental area and the nucleus accumbens). The caudate nucleus is included in this pathway. These areas contain especially high concentrations of dopaminergic synapses. The opiates also interact with other structures modulated by endorphins, including the amygdala, locus coeruleus, arcuate nucleus, thalamus, and the periaqueductal gray matter, which influence dopaminergic pathways indirectly. There are natural and synthetic forms of opiates. Opioid receptors are a group of G-protein coupled receptors, with opioids acting as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins, and ORL1. There are four major subtypes of opioid receptors. The first is δ, including subtypes δ1 and δ2. They are involved with analgesia, antidepressant effects, and physical dependence. The second is κ and includes κ1, κ2, and κ3. These are involved in spinal analgesia, sedation, miosis, and inhibition of antidiuretic hormone release. The third is μ and includes μ1, μ2, and μ3. The subtype μ1 is involved in supraspinal analgesia and physical dependence; μ2 is involved in respiratory depression, miosis, euphoria, reduced gastrointestinal motility, and physical dependence. The actions of μ3 are not clear. The fourth is ORL1/orphanin, which is involved in anxiety, depression, appetite, and development of tolerance to μ agonists.

 Bonci A, Bernardi G, Grillner P, et al. The dopamine-containing neuron: maestro or simple musician in the orchestra of addiction? Trends Pharmacol Sci. 2003; 24:172–177.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Corbett AD, Henderson G, McKnight AT, et al. 75 years of opioid research: the exciting but vain quest for the Holy Grail. Br J Pharmacol. 2006; 147(suppl 1):S153-S162.

 Gussow L. Myths of toxicology: thiamine before dextrose. Emerg Med News. 2007; 29(4):3–11.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York, NY: McGraw-Hill; 2009.

 7. d, 8. b,  9. b

Amphetamines work by causing direct release of dopamine and norepinephrine and inhibiting their reuptake. Cocaine works by primarily inhibiting presynaptic reuptake of dopamine (as well as serotonin and norepinephrine). Amphetamine and cocaine use present with similar findings, which include mydriasis (as opposed to opiates, which cause miosis), euphoria, tachycardia, cardiac arrhythmias, hypertension, nausea/vomiting, weight loss, diaphoresis, agitation, anxiety, respiratory depression, seizures, psychosis, formication (sensation of crawling bugs on skin), dyskinesias, and dystonia. Stroke and myocardial infarctions can occur.

Similar to all of the euphoria-producing drugs, the effects of amphetamines and cocaine are predominantly on the reward circuit (the ventral tegmental area and nucleus accumbens). Withdrawal symptoms are also similar with amphetamines and cocaine and include dysphoria, vivid/unpleasant dreams, increased appetite, insomnia or hypersomnia, agitation, or psychomotor retardation. The routes of amphetamine use are oral, nasal (snorting), inhalational (smoking), or intravenous. The routes of cocaine use are nasal (snorting), inhalational (smoking; crack cocaine), intravenous, or oral (chewing coca leaves).

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Derlet RW, Rice P, Horowitz BZ, et al. Amphetamine toxicity: experience with 127 cases. J Emerg Med. 1989; 7:157–161.

 Ritz MC, Lamb RJ, Goldberg SR, et al. Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science. 1987; 237:1219–1223.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York, NY: McGraw-Hill; 2009.

10. c, 11. c, 12. c, 13. b, 14. e, 15. e

This patient has suspected alcohol intoxication. Symptoms include confusion, somnolence, ataxia, dysarthria, hypotension (later hypertension), impaired judgment, and tachycardia. When this is suspected, intravenous thiamine has been classically recommended to precede intravenous glucose administration to avoid precipitation of Wernicke encephalopathy due to acute thiamine deficiency. However, more recent literature raises questions regarding the validity of this practice. Thiamine is converted to thiamine pyrophosphate, which acts as a cofactor in several metabolic pathways necessary in energy metabolism. When there is a high metabolic demand (such as after a glucose load) in the setting of thiamine deficiency, cellular damage occurs and Wernicke encephalopathy may result. Wernicke encephalopathy is characterized by confusion/mental status changes, ataxia, ophthalmoplegia, and nystagmus. The chronic phase of Wernicke encephalopathy is known as Korsakoff syndrome and is associated with anterograde amnesia, although there are components also of retrograde amnesia. MRI findings in Wernicke encephalopathy may include petechial hemorrhages classically in the mammillary bodies, but also in hypothalamus, medial thalami, and periaqueductal gray matter, sometimes even extending into the medulla, with atrophy in chronic stages. Acute thiamine deficiency does not typically lead to changes in the caudate nucleus.

Alcohol and other sedative-hypnotic drugs affect not only the basic structures of the reward circuit but also several other structures that use GABA as a neurotransmitter. GABA is one of the most widespread neurotransmitters in several parts of the brain, including the cortex, the cerebellum, hippocampus, amygdala, and superior and inferior colliculi. Alcohol exerts its effects by stimulation of the GABA receptor, similar to the mechanism of action of benzodiazepines. This is why benzodiazepines are used to prevent withdrawal symptoms. Alcohol also inhibits glutamate-induced excitation, which leads to additive CNS-depressant effects.

Chronic alcohol use has detrimental multi-systemic effects. Alcohol withdrawal can be quite severe and can even lead to death if not treated appropriately. Minor withdrawal symptoms begin within 6 to 36 hours from the last drink and include headache, tremors, diaphoresis, palpitations, insomnia, gastrointestinal upset, diarrhea, anorexia, agitation, and anxiety. Mentation is preserved during this period. Seizures can occur generally 6 to 48 hours after the last drink. Alcoholic hallucinosis begins at 12 to 48 hours and includes hallucinations (mostly visual but can also be auditory and tactile), intact orientation, and stable vital signs. Delirium tremens occurs at 48 to 96 hours if adequate prophylaxis is not initiated and is characterized by delirium, hallucinations, disorientation, agitation, encephalopathy, hypertension, tachycardia, arrhythmias, low-grade fever, and diaphoresis. In severe cases, delirium tremens can be fatal. β-Blockers and calcium channel blockers can be used for hypertension and tachycardia, although these will merely mask symptoms. Use of phenytoin or other anticonvulsants is appropriate in those with seizures and pre-existing epilepsy. This history is not present in the patient described, so it is not indicated here. Benzodiazepines such as lorazepam should be given as scheduled doses to prevent withdrawal symptoms (including seizures), and these are the most important medications to add in this setting. Alcohol withdrawal symptoms often occur in unrecognized alcoholic patients who are admitted for surgeries or other reasons. Zolpidem is a nonbenzodiazepine hypnotic used to treat insomnia, and not indicated in this setting.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York, NY: McGraw-Hill; 2009.

 Turner RC, Lichstein PR, Peden JG Jr, et al. Alcohol withdrawal syndromes: a review of pathophysiology, clinical presentation, and treatment. J Gen Intern Med. 1989; 4:432–444.

16. d

Nicotine is an agonist at nicotinic acetylcholine receptors. Nicotine leads to increased levels of several neurotransmitters, especially dopamine, in the reward circuits of the brain. This leads to euphoria, relaxation, and addiction. Nicotine in tobacco stimulates several areas in the reward circuit and its connections, such as the noradrenergic neurons of the locus coeruleus. Several other areas in the brain that secrete acetylcholine, such as the hippocampus and cortex, also appear to be affected by nicotine, and this may explain the increased attentiveness that smokers often describe after nicotine ingestion.

 Katzung, Bertram G. Basic and Clinical Pharmacology. New York, NY: McGraw-Hill; 2006.

17. d

Adenosine is a purine nucleotide that is released in the brain, primarily from astrocytes. Adenosine normally inhibits release of excitatory neurotransmitters, leading to reduced neuronal firing rate and decreased cortical excitability. Caffeine competitively antagonizes the adenosine A1 and A2A G-protein–coupled receptor subtypes. The resulting decreased activity of adenosine by caffeine leads to increased release of excitatory neurotransmitters, and thus the stimulating effects noted with caffeine.

 Shapiro RE. Caffeine and Headaches. Curr Pain Headache Rep. 2008; 12:311–315.

18. c, 19. e, 20. b, 21. d

This patient exhibits symptoms of intoxication with phenylcyclohexyl piperidine, more commonly known as phencyclidine (PCP). This was a drug developed initially as a dissociative anesthetic, primarily used in animals. It is structurally similar to ketamine, which is used for medical anesthesia. Hypertension, tachycardia, nystagmus (vertical, lateral, horizontal, or rotatory), decreased pain sensation (often causing superhuman appearance of strength), rage, muscle rigidity, seizures, bizarre behaviors, hallucinations, delusions, impaired judgment, confusion, dysarthria, ataxia, and myoclonic jerks are all characteristic findings in PCP intoxication. Its use can also lead to hyperthermia, autonomic instability, and multiorgan failure.

PCP is used by oral, intravenous, or intranasal routes. It acts as a noncompetitive antagonist at the glutamate NMDA receptor. PCP has been shown to affect biogenic amine (dopamine, norepinephrine, serotonin) release and reuptake. These actions probably account for the sympathomimetic effects of PCP.

PCP is structurally similar to ketamine, but it differs from ketamine in that it is longer acting, is more likely to cause seizures, and tends to cause more emergent confusion and delirium. Ketamine also acts as a noncompetitive antagonist of the NMDA receptor. It also has interactions with muscarinic, nicotinic, and cholinergic receptors and inhibits reuptake of norepinephrine, dopamine, and serotonin.

The other choices listed are of the psychedelic, or hallucinogenic, category. Although some symptoms can overlap with PCP intoxication, the symptoms described in this case are characteristic of PCP. Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) comes from specific types of mushrooms, and mescaline comes from the peyote cactus. Lysergic acid is one of the ergot fungus’ diverse alkaloid components, and lysergic acid diethylamide was popularized as a potent mood-changing and hallucinogenic drug. Use of the different hallucinogens leads to many similar symptoms including sensory distortions (such as synesthesias; “feeling” colors, “seeing” sound), illusions, hallucinations, euphoria, anxiety, tachycardia, palpitations, pupillary dilation (as opposed to opiates, which cause miosis), and diaphoresis. The hallucinogens primarily work at various serotonergic receptors. Different receptor subtypes are modulated by these various drugs, some of which may do so through agonism, whereas others through antagonism. The serotonin 5HT2 receptor is particularly thought to be involved in the action of these drugs. Some of these drugs may have some effects at dopamine and norepinephrine receptors. In addition, 3, 4-methylenedioxymethamphetamine (MDMA), or ecstasy, blocks reuptake of serotonin, and prolonged use of MDMA results in destruction of serotonergic neurons in the brain.

 Fantegrossi WE, Murnane KS, Reissig CJ. The behavioral pharmacology of hallucinogens. Biochem Pharmacol. 2008; 75(1):17–33.

 Romanelli F. Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate. Am J Health Syst Pharm. 2002; 59(11):1067–1076.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York, NY: McGraw-Hill; 2009.

 Smith KM, Larive LL, Fischer C, et al. Reorganization of ascending 5-HT axon projections in animals previously exposed to recreational drug 3,4-methelenedioxymetham-phetamine (MDMA, “Ecstasy”). J Neurosci. 1995; 15(8):5476–5485.

22. e, 23. c

This patient has copper deficiency related to excess zinc intake. This can be related to excess dietary intake (as in this case), overuse of denture cream, parenteral feeding deficiency, and gastrointestinal surgery. This syndrome occurs because zinc increases enterocyte metallothionein synthesis. These excess enterocyte metallothioneins easily bind copper. The resultant excessively bound copper within the enterocytes is then excreted when the enterocytes are sloughed off, resulting in impaired absorption. Copper deficiency myelopathy syndrome resembles the subacute combined degeneration seen with vitamin B12 deficiency. Copper deficiency causes a sensorimotor peripheral neuropathy with axonal loss features on electrodiagnostic studies combined with myelopathy in the form of spastic paraparesis and posterior column dysfunction. Pancytopenia is also frequently associated. Copper deficiency is discussed also in Chapter 11. The history of excess zinc makes this more likely than vitamin B12 deficiency in this particular patient. Vitamin E deficiency can mimic symptoms of spinocerebellar ataxia, which is not present in this patient.

 Goodman BP, Bosch EP, Ross MA, et al. Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy. J Neurol Neurosurg Psychiatry. 2009; 80:524–547.

 Kumar N, Gross JB Jr, Ahlskog JE. Copper deficiency myelopathy produces a clinical picture like subacute combined degeneration. Neurology. 2004; 63:33–39.

24. e, 25. a

This patient’s neurologic findings are likely the result of vitamin E deficiency related to chronic diarrhea and subsequent malabsorption of fat-soluble vitamins, that is, vitamins D, A, K, and E. These vitamins need to be supplemented, especially vitamin E as in this case. Symptoms resemble a spinocerebellar ataxia syndrome such as Friedrich ataxia and may include ataxia, dysarthria, areflexia, extensor plantar responses, and large fiber sensory loss. Presentation can occur at any age in the setting of chronic diarrhea and malabsorption diseases. Vitamin E deficiency is more likely to occur in childhood when a genetic etiology is present, such as α-tocopherol-transfer protein mutation or abetalipoproteinemia (Bassen-Kornzweig syndrome). Abetalipoproteinemia is caused by a mutation of a microsomal triglyceride transfer protein resulting in absence of apolipoprotein B–containing proteins. Laboratory findings show low vitamin E levels. Acanthocytosis may also be seen on peripheral smear. See discussion to question 22 for copper deficiency, and that to question 27 for vitamin B12 deficiency.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York, NY: McGraw-Hill; 2009.

 Satya-Murti S, Howard L, Krohel G, et al. The spectrum of neurologic disorder from vitamin E deficiency. Neurology. 1986; 36:917–921.

26. c

Extensor plantar responses would not be seen in thiamine (vitamin B1) deficiency. This deficiency would be more likely to cause peripheral neuropathy and flexor plantar responses. Thiamine deficiency in Wernicke-Korsakoff syndrome is discussed in question 10. Thiamine deficiency causes an axonal, sensorimotor peripheral neuropathy with weakness and distal sensory loss. This is termed “dry beriberi.” When it is associated with cardiac involvement in the form of cardiomegaly, cardiomyopathy, congestive heart failure, arrhythmia and tachycardia, and peripheral edema, it is called “wet beriberi.” Thiamine deficiency has also been reported to cause Leigh syndrome (Leigh subacute necrotizing encephalomyelopathy). Laboratory findings may include decreased serum thiamine, erythrocyte transketolase activity and urinary thiamine, with increased pyruvate and lactate levels, in addition to characteristic electrodiagnostic findings.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Pincus JH. Subacute necrotizing encephalomyelopathy (Leigh’s disease): a consideration of clinical features and etiology. Dev Med Child Neurol. 1972; 14:87–101.

 Tanphaichitr V. In: Shils M (Ed), Modern Nutrition in Health and Medicine, 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2000.

27. d

The neurologic deficits in vitamin B12 (cobalamin) deficiency are ultimately related to a defect in methionine production. Vitamin B12 is a cofactor for methionine synthase, which is involved in conversion of homocysteine to methionine and production of succinyl-CoA from methylmalonyl-CoA. Methionine is subsequently a precursor for S-adenosyl-l-methionine, which helps with methylation of myelin basic protein. Without this process, abnormal myelin structure results in neurologic deficit. The syndrome resulting from vitamin B12 deficiency is called subacute combined degeneration because of sensorimotor peripheral neuropathy combined with myelopathy, spastic paraparesis and posterior column dysfunction. Complete blood cell count may reveal a macrocytic anemia. Occasionally, vitamin B12 levels may be in the low normal or even normal range despite true deficiency. If clinical suspicion is present for deficiency, the levels of metabolic intermediaries homocysteine and methylmalonic acid should be checked, both of which would be elevated in vitamin B12 deficiency. Animal products (meat and dairy) provide the primary dietary source of vitamin B12 for humans. This puts older adults, alcoholics, patients with malnutrition, and strict vegans at high risk for development of deficiency.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Green R, Kinsella LJ. Current concepts in the diagnosis of cobalamin deficiency. Neurology. 1995; 45(8):1435–1440.

 Hemmer B, Glocker FX, Schumacher M, et al. Subacute combined degeneration: clinical, electrophysiological, and magnetic resonance imaging findings. J Neurol Neurosurg Psychiatry. 1998; 65:822–827.

 Lindenbaum J, Savage DG, Stabler SP, et al. Diagnosis of cobalamin deficiency, II: relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations. Am J Hematol. 1990; 34:99–107.

28. d, 29. b

This patient exhibits symptoms consistent with arsenic poisoning. Arsenic is a naturally occurring element most commonly incorporated into organic or inorganic compounds, both of which are very toxic. It can also occur in gas form. With acute exposure, symptoms may develop within minutes to hours and usually begin with gastrointestinal symptoms such as abdominal pain, nausea, vomiting, and diarrhea. A garlic odor on the breath is characteristic. These symptoms can be followed by hypotension, dehydration, and cardiac and respiratory instability. Delirium, encephalopathy, coma, and seizures may occur. Other acute manifestations include proteinuria, hematuria, and acute tubular necrosis. If patients survive, within 1 to 3 weeks, they can develop hepatitis, pancytopenia, and a symmetric sensorimotor peripheral neuropathy, which typically begins with distal paresthesias, followed rapidly by an ascending sensory loss and weakness, which mimics Guillain-Barré syndrome. The neuropathy can progress to intense burning pain, especially in the soles. In addition, dermatologic lesions can occur and may include alopecia, oral mucosal ulcerations, diffuse pruritic macular rash, and scaly rash on the palms and soles. A dry hacking cough and Mees lines (horizontal 1- to 2-mm white lines on the nails) may also occur. In chronic poisoning, the peripheral neuropathy and dermatologic symptoms are usually more prominent than the gastrointestinal symptoms. Cancers of the liver, bladder, kidney, skin, lung, nasal mucosa, and prostate have been reported with chronic exposure.

After a suspected acute ingestion of arsenic, abdominal radiographs may reveal gastrointestinal radiopaque material. Urine arsenic levels are preferable to blood arsenic levels, but both can be used. Fish or shellfish intake within the previous 48–72 hours can cause falsely elevated levels of arsenic. For chronic exposure, hair and nail samples can be analyzed for the presence of arsenic, and 24-hour urine arsenic or spot urine arsenic and creatinine levels can be checked. Additional evaluations should include renal and liver function tests, complete blood cell count, urinalysis, and electrodiagnostic testing if there are symptoms of peripheral neuropathy. A distal sensorimotor axonopathy is the typical finding.

Acute treatment includes fluid and electrolyte replacement, cardiac monitoring, activated charcoal, and chelation therapy. Chelation agents typically used include dimercaprol (British Anti-Lewisite) and meso-2,3-dimercaptosuccinic acid (succimer).

Although symptoms can mimic Guillain-Barré syndrome, the constellation of clinical symptoms and signs described and adequate evaluation should have ruled this out. Cyanide and mercury poisoning are discussed in questions 30 and 31 respectively. Thallium causes acute gastrointestinal symptoms, confusion, painful (mostly sensory) neuropathy with autonomic features, and alopecia, which classically occurs about 2 to 4 weeks after ingestion.

 Danan M, Dally S, Conso F. Arsenic-induced encephalopathy. Neurology. 1984; 34:1524.

 Flomenbaum N, Goldfrank L, Hoffman R, et al. Goldfrank’s Toxicologic Emergencies, 8th ed. New York, NY: McGraw-Hill; 2006.

 Windebank AJ. Arsenic. In: Spencer PS, Schaumburg HH (Eds), Experimental and Clinical Neurotoxicology. New York, NY: Oxford University Press; 2000.

 Yip L, Dart RC. Arsenic. In: Sullivan JB, Krieger GR (Eds), Clinical Environmental Health and Toxic Exposures. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

30. e

This patient exhibits symptoms of cyanide poisoning. In industrialized countries, the most common cause of cyanide poisoning are domestic fires due to combustion of products containing carbon and nitrogen, such as wool, silk, polyurethane (insulation/upholstery), and plastics. There are many industrial causes, such as electroplating in this case. There are also dietary causes, especially from ingestion of plant products from the family Rosaceae, including the seeds and pits of the plum, peach, pear, bitter almond, cherry laurel, apricot, and apple.

Cyanide is a rapidly lethal mitochondrial toxin that can cause death within minutes to hours of exposure. Cyanide competes with oxygen and binds to the ferric ion (Fe3+) of cytochrome oxidase a3, which inhibits this final enzyme in the mitochondrial cytochrome complex, resulting in cessation of oxidative phosphorylation. As a result, cells cannot use oxygen in their electron transport chain and must switch to anaerobic metabolism. Because of the decreased utilization of oxygen by tissues, venous oxyhemoglobin concentration will be high, making venous blood appear bright red and thus, the bright red coloration of skin, similar to the effects of carbon monoxide. Cyanide also causes toxic oxygen free radicals, release of glutamate, and inhibition of glutamic acid decarboxylase (the enzyme that helps form the inhibitory neurotransmitter GABA).

CNS symptoms include headache, anxiety, abnormal taste, encephalopathy, vertigo, and seizures. Cardiovascular symptoms include chest pain, initial tachycardia, and hypertension, then bradycardia and hypotension, atrioventricular block, and arrhythmias. Respiratory symptoms include initial tachypnea, then bradypnea and pulmonary edema. Gastrointestinal symptoms include nausea, vomiting, and abdominal pain. Skin symptoms include flushing, cherry-red color. Cyanosis may occur late. Renal and hepatic failure may also occur.

Laboratory evaluation reveals severe metabolic acidosis with increased anion gap, elevated lactate level, and elevated blood cyanide level. Levels of more than 3.0 mg/L correlate with death. Treatment must be initiated quickly, and includes removal of the cyanide source (such as from the skin) and activated charcoal. The Taylor Cyanide Antidote Package may be used. This includes amyl nitrite, sodium nitrite, and sodium thiosulfate. Hydroxocobalamin is also used to directly bind and neutralize cyanide and is often combined with sodium thiosulfate. See discussion to question 32 for carbon monoxide poisoning, question 31 for mercury poisoning, and question 28 and 29 for arsenic and thallium poisoning.

 Greenberg MI, Hamilton RJ, Phillips SD. Occupational, Industrial, and Environmental Toxicology. St Louis, MO: Mosby; 1997.

 Morocco AP. Cyanides. Crit Care Clin. 2005; 21:691–705.

 Sauer SW, Keim ME. Hydroxocobalamin: improved public health readiness for cyanide disasters. Ann Emerg Med. 2001; 37:635–641.

 Vogel S, Sultan T, Ten Eyck R. Cyanide poisoning. Clin Toxicol. 1981; 18:367–383.

31. c

This man exhibits symptoms consistent with mercury toxicity, likely from years of exposure in a mercury mine. The organic forms of mercury are the most toxic, such as dimethylmercury and methylmercury. Some fish and shellfish concentrate mercury in the form of methylmercury. However, inorganic forms of mercury, such as cinnabar, are also highly toxic by ingestion or inhalation of the dust. Besides mining, other occupational exposures to mercury include dentistry, chloralkali industries, and thermometer factories. It was called “mad hatter’s disease” in the past because hat makers frequently worked with mercury to set and shape hats. If inhaled, a fatal interstitial pneumonitis may occur. It can be absorbed through the skin and orally ingested. Other symptoms include severe intention tremor, cerebellar ataxia, paresthesias, tender and inflamed gums, excessive salivation, swollen salivary glands, change in personality, and psychiatric symptoms such as anxiety, irritability, fearfulness, memory loss, depression, and fatigue. Treatment includes chelation therapy with British Anti-Lewisite, penicillamine, 2,3 dimercaptopropane-1-sulfonate, and dimercaptosuccinic acid. See discussion to question 33 for lead poisoning, question 34 for manganese toxicity, Chapter 12 for FTD, and questions 28 and 29 for thallium toxicity.

 Berlin M. Mercury. In: Friberg L, Nordberg GF, Vouk VB (Eds), Handbook on the Toxicology of Metals, Vol. II. Amsterdam, The Netherlands: Elsevier; 1986.

 Schutte NP, Knight AL, Jahn O. Mercury and its compounds. In: Zenz C, Dickerson OB, Horovath EP (Eds), Occupational Medicine, 3rd ed. St Louis, MO: Mosby; 1994.

32. d

This woman has carbon monoxide (CO) poisoning. It commonly occurs at the change of seasons as winter months approach and people turn on their furnaces. Other family members in the same household may have similar symptoms, which gives a clue to diagnosis. CO is an odorless, tasteless, colorless gas. It binds to the iron moiety of heme in hemoglobin with much higher affinity than does oxygen, forming carboxyhemoglobin, which results in impaired oxygen transport and utilization. It competes with oxygen in binding hemoglobin. This binding leads to a structural change, which limits the ability of the other three oxygen binding sites to release oxygen to peripheral tissues and hence the cherry-red flushed coloration. It can also lead to CNS lipid peroxidation and delayed neurologic sequelae. Some sources include poorly functioning heating systems and improperly vented fuel-burning devices such as kerosene heaters, charcoal grills, camping stoves, gasoline-powered generators, and motor vehicles. Symptoms most commonly include headache, nausea, malaise, dizziness, and cherry-red skin coloration. Severe toxicity can cause seizures, encephalopathy, coma, and cardiovascular instability. Diagnosis is based on clinical history and elevated carboxyhemoglobin levels (which may be normally elevated to an extent in smokers). Treatment should include high-flow 100% oxygen via a nonrebreather mask. In severe cases, histopathology in chronic stages reveals necrosis in the globus pallidus and confluent areas of necrosis in subcortical white matter.

 Ernst A, Zibrak JD. Carbon monoxide poisoning. N Engl J Med. 1998; 339:1603–1608.

 Harper A, Croft-Baker J. Carbon monoxide poisoning: undetected by both patients and their doctors. Age Ageing. 2004; 33:105–109.

 Kao LW, Nanagas KA. Carbon monoxide poisoning. Emerg Med Clin North Am. 2004; 22(4):985–1018.

33. c

This boy most likely has lead intoxication, especially given the timing of symptoms in relation to moving into a very old house. Given this scenario, one must be concerned about the possibility of lead intoxication as lead-based paint in old houses has been a frequent etiology, especially in children. Many other occupational exposures are possible but would be seen more in adults. Lead inhibits the sulfhydryl-dependent enzymes such as γ-aminolevulinic acid dehydratase and ferrochelatase in heme synthesis, which causes disruption of hemoglobin synthesis and leads to the production of free erythrocyte protoporphyrins. Lead also competes with calcium in several biologic systems and processes, such as mitochondrial respiration and nerve functions, and has been implicated as contributing mechanisms in neurotoxicity. Common symptoms of lead toxicity include abdominal pain (lead colic), constipation, myalgias, arthralgias, seizures, psychomotor slowing, headache, and anorexia. Basophilic stippling of red blood cells and microcytic hypochromic anemia are often seen. In addition, a bluish pigmentation at the gum-tooth line is sometimes seen. A peripheral neuropathy classically with extensor weakness or “wrist/ankle drop” is associated with lead toxicity and is due to an axonal degeneration that primarily affects motor nerves. Generally, removal from the lead source is the only treatment needed, although chelation therapy with 2,3-dimercaptosuccinic acid succimer, and calcium disodium ethylenediaminetetraacetate are also available.

 Cullen MR, Robins JM, Eskenazi B. Adult inorganic lead intoxication: presentation of 31 new cases and a review of recent advances in the literature. Medicine (Baltimore). 1983; 62:221–247.

 Fischbein A, Hu H. Occupational and environmental exposure to lead. In: Environmental and Occupational Medicine, Rom WN, Markowitz SB (Eds), Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins; 2007.

 Thomson RM, Parry GJ. Neuropathies associated with excessive exposure to lead. Muscle Nerve. 2006; 33:732–741.

34. b

This patient most likely has manganese toxicity. It is most commonly seen in those with chronic liver disease (impaired biliary excretion), those receiving total parenteral nutrition containing manganese, and those in the welding and steel industries. Symptoms include parkinsonian features, tremors, incoordination, confusion, personality changes, hallucinations, agitation, psychosis (manganese madness), memory disturbances, headache, and aggression. Brain MRI may show high T1 signal predominantly in the globus pallidus. Chelation therapy with ethylenediaminetetraacetate has been used as treatment. Parkinson’s disease is discussed in Chapter 6, lead toxicity in question 33, and copper deficiency in question 22. Although this patient could certainly be malnourished, parkinsonian features do not result from malnutrition.

 Fell JM, Reynolds AP, Meadows N, et al. Manganese toxicity in children receiving long-term parenteral nutrition. Lancet. 1996; 347:1218–1221.

 McMillan DE. A brief history of the neurobehavioral toxicity of manganese: some unanswered questions. Neurotoxicology. 1999; 20:499–507.

 Wedler FC. Biochemical and nutritional role of manganese: an overview. In: Klimis-Tavantzis DJ (Ed), Manganese in Health and Disease. Boca Raton, FL: CRC Press; 1994.

35. e

This man likely has methanol poisoning from ingestion of a household product in an attempt to ingest alcohol. Methanol and ethylene glycol are found in automotive antifreeze, de-icing solutions, antifreeze, and windshield wiper fluid and solvents, among others. Symptoms include nausea, headache, visual complaints, blindness, dizziness and encephalopathy, inebriation, and sedation. Findings classically include necrosis of optic nerves and the putamen on neuroimaging. Toxicity occurs when methanol is oxidized by alcohol dehydrogenase and aldehyde dehydrogenase, forming the metabolite formate. Formate causes retinal injury and permanent blindness and injury to the basal ganglia (especially putamen). Fomepizole can also be used as treatment, which acts as an alcohol dehydrogenase inhibitor. Ethanol can also be used to competitively bind to alcohol dehydrogenase, preventing breakdown of methanol into its toxic metabolites. Treatment also consists of correction of systemic acidosis.

Acrylamide can cause seizures, encephalopathy, and peripheral neuropathy. Hexacarbon solvents are found in paints, glues (glue sniffing), and solvents, and they also cause peripheral neuropathy, euphoria, hallucinations, and headache. These symptoms do not fit with this patient’s clinical presentation, especially blindness.

 Kerns W, Tomaszewski C, McMartin K, et al. Formate kinetics in methanol poisoning. J Toxicol Clin Toxicol. 2002; 40:137–143.

 Liesivuori J, Savolainen H. Methanol and formic acid toxicity: biochemical mechanisms. Pharmacol Toxicol. 1991; 69:157–163.

 Sivilotti ML, Burns MJ, Aaron CK, et al. Reversal of severe methanol-induced visual impairment: no evidence of retinal toxicity due to fomepizole. J Toxicol Clin Toxicol. 2001; 39:627–631.

36. d

This patient likely has organophosphate/carbamate poisoning related to the use of insecticide/pesticide. The only listed item that is not recommended in this clinical situation is gastric lavage because of a substantial risk of aspiration, given the increased secretions and decreased mental status in many patients. Organophosphates and carbamates are potent cholinesterase inhibitors leading to severe cholinergic toxicity. Toxicity can result from ingestion, cutaneous exposure, or inhalation. Some organophosphates are also used as terrorist nerve agents and include tabun, sarin, and soman.

Two common mnemonics used to remember the cholinergic/muscarinic crisis signs are as follows:

 SLUDGE: Salivation, Lacrimation, Urination, Defecation, Gastric Emesis

 DUMBELS: Defecation, Urination, Miosis, Bronchorrhea/Bronchospasm/Bradycardia, Emesis, Lacrimation, Salivation

Often these patients will develop the “intermediate syndrome,” approximately 12 to 96 hours after exposure that consists of weakness, fasciculations, tachycardia, hypertension, decreased deep tendon reflexes, cranial nerve abnormalities, proximal muscle weakness, and respiratory insufficiency. In addition, some organophosphates can cause organophosphorus-induced delayed neuropathy, occurring 2 to 3 weeks after exposure. Symptoms include painful but transient “stocking-glove” paresthesias followed by a symmetrical motor polyneuropathy with flaccid weakness of the lower extremities, which ascends to the upper extremities. Neurobehavioral symptoms may also occur as chronic sequelae.

Atropine competes with acetylcholine at muscarinic receptors to help prevent cholinergic activation. Since atropine does not bind to nicotinic receptors, it is ineffective in treating neuromuscular dysfunction, so the cholinesterase-reactivating agent pralidoxime is typically given concurrently with atropine and is effective in treating manifestations resulting from activation of both muscarinic and nicotinic receptors. Benzodiazepines are used for organophosphate-related seizures and sometimes for seizure prophylaxis. Activated charcoal is recommended if presentation is within 1 hour of ingestion. Gastric lavage is not recommended as mentioned earlier.

 Eddleston M, Roberts D, Buckley N. Management of severe organophosphorus pesticide poisoning. Crit Care. 2001; 5(4):211–215.

 Moretto A, Lotti M. Poisoning by organophosphorus insecticides and sensory neuropathy. J Neurol Neurosurg Psychiatry. 1998; 64:463–468.

 Roberts DM, Aaron CK. Managing acute organophosphorus pesticide poisoning. Br Med J. 2007; 334:629–634.

 Rusyniak DE, Nañagas KA. Organophosphate poisoning. Semin Neurol. 2004; 24(2): 197–204.

 Sevim S, Aktekin M, Dogu O, et al. Late onset polyneuropathy due to organophosphate (DDVP) intoxication. Can J Neurol Sci. 2003; 30:75–78.

37. c

This patient describes symptoms most consistent with botulism, likely related to foodborne source from home canning. Botulism is a potentially life-threatening neuroparalytic syndrome resulting from exposure to botulinum toxin, produced by Clostridium botulinum. There are at least eight distinct types of botulinum toxin, although the most commonly involved is botulinum toxin A. There are multiple forms of botulism including foodborne botulism (ingestion of food contaminated by botulinum toxin), wound botulism (infection of a wound by C. botulinum, with subsequent production of neurotoxin), infantile botulism (ingestion of clostridial spores that then colonize the gastrointestinal tract and release toxin), adult enteric infectious botulism (toxin produced in the gastrointestinal tract), and inhalational botulism (aerosolized toxin related to acts of bioterrorism).

Botulinum toxin binds to the synaptotagmin II receptor on presynaptic cholinergic synapses and neuromuscular junctions. After the heavy chain of the toxin binds to the receptors, the light chain translocates into the nerve cell via endocytosis. Upon entering the cytoplasm, the toxin irreversibly inhibits acetylcholine release by cleaving various proteins involved in neuroexocytosis of acetylcholine. Botulinum toxin A and E cleave SNAP-25; botulinum toxin C cleaves SNAP-25 and syntaxin; and botulinum B, D, F, and G cleave synaptobrevin. Reversal of this inhibition requires sprouting of a new presynaptic terminal and formation of a new synapse. This generally takes 3 to 6 months. Although the toxin can be quite harmful, these effects are used for therapeutic purposes, such as for the treatment of dystonia, spasticity, and other neurologic disorders.

Symptoms related to foodborne botulism may begin within 12 to 36 hours after ingestion of the toxin but may be delayed for several days. Symptoms include acute onset of multiple cranial neuropathies, blurred vision (due to fixed pupillary dilation), symmetric descending weakness, urinary retention, and constipation. Gastrointestinal symptoms such as diarrhea, abdominal pain, nausea, and vomiting often precede neurologic symptoms in foodborne botulism.

Symptoms are not consistent with myasthenia gravis (there is no diurnal variation or other historical points to suggest fatigability; discussed in Chapter 10), Lambert-Eaton myasthenic syndrome (discussed in Chapter 10), or Guillain-Barré syndrome (which presents with ascending, not descending, weakness and without pupillary involvement; discussed in Chapter 9). He has no history of cancer and is otherwise healthy, making leptomeningeal carcinomatosis unlikely, especially with the abrupt onset of symptoms.

 Abrutyn E. Botulism. In: Fauci AS, Isselbacher KJ, Braunwald E, et al. (Eds), Principles of Internal Medicine, 14th ed. New York, NY: McGraw-Hill; 1998.

 Hughes JM, Blumenthal JR, Merson MH, et al. Clinical features of types A and B food-borne botulism. Ann Intern Med. 1981; 95:442–445.

 Jin R, Rummel A, Binz T, et al. Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity. Nature. 2006; 444(7122):1019–1020.