Other General

Question 1

Baclofen belongs to which of the following drug classes?
Answers:
A. Dopaminergic agents
B. GABA Receptor agonists
C. NMDA-receptor antagonists
D. Selective serotonin reuptake inhibitors
E. Anticholinergic agents

Answer 1

GABA Receptor agonists

Discussion:
Baclofen is a GABA B receptor agonist that acts as an inhibitory neurotransmitter that blocks
monosynaptic and polysynaptic reflexes. Anticholinergic agents block acetylcholine from binding to
muscarinic receptors; examples include oxybutynin, which relaxes bladder smooth muscle cells.
NMDA-receptor antagonists include medications such as memantine as well as opioids such as
methadone. Dopaminergic agents include dopamine precursors, such as L-DOPA, reuptake
inhibitors and receptor agonists. Selective serotonin reuptake inhibitors (SSRIs) include widely
used antidepressants such as escitalopram and sertraline.
References:
McIntyre A, Mays R, Mehta S, et al. Examining the effectiveness of intrathecal baclofen on
spasticity in individuals with chronic spinal cord injury: a systematic review. J Spinal Cord Med.
2014 Jan;37(1):11-8. Khurana SR, Garg DS. Spasticity and the use of intrathecal baclofen in
patients with spinal cord injury. Phys Med Rehabil Clin N Am. 2014 Aug;25(3):655-69, ix. doi:
10.1016/j.pmr.2014.04.008. PMID: 25064793. Bolzoni F, Esposti R, Jankowska E, Hammar I.
Interactions Between Baclofen and DC-induced Plasticity of Afferent Fibers within the Spinal Cord.
Neuroscience. 2019 Apr 15;404:119-129. doi: 10.1016/j.neuroscience.2019.01.047. Epub 2019
Jan 31. PMID: 30710669. National Center for Biotechnology Information (2021). PubChem
Compound Summary for CID 2284, Baclofen. Retrieved May 23, 2021 from
https://pubchem.ncbi.nlm.nih.gov/compound/Baclofen.

Question 2

Exposure to organophosphate insecticides produces neurologic symptoms because these
substances have which of the following effects?
Answers:
A. Reversible inhibition of acetylcholinesterase
B. Competitive antagonism of muscarinic acetylcholine receptors
C. Irreversible inhibition of acetylcholinesterase
D. Competitive antagonism of nicotinic acetylcholine receptors
E. Agonism of nicotinic acetylcholine receptors

Answer 2

Irreversible inhibition of acetylcholinesterase

Discussion:
Organophosphates irreversibly bind to and inhibit acetylcholinesterase at nicotinic and muscarinic
receptors leading to accumulation of ACh in the synaptic cleft resulting in over-stimulation of
nicotinic and muscarinic ACh receptors and impeded neurotransmission. The typical symptoms of
a cholinergic toxidrome are agitation, muscle weakness, muscle fasciculations, miosis,
hypersalivation, sweating, and diarrhea. Severe poisoning may cause respiratory failure, altered
consciousness, confusion, seizures, and/or death. An example of a reversible AChE inhibitor is
donepezil, a treatment for Alzeimer’s disease. Organophosphates do not exert their effects on the
receptors themselves. Antagonism of muscarinic ACh receptors is the mechanism of action of
atropine. Overdose of atropine can resut in an anti-cholinergic toxidrome (mydriasis, decreased
sweating, elevated temperature,tachycardia, changes in mental status). Antagonism of nicotinic
ACh receptors is the mechanism of action of many neuromuscular blocking drugs as antagonism
of the nicotinic receptors does not allow for depolarization thus effectively blocking muscle
contraction.
References:
Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM. Acetylcholinesterase inhibitors:
pharmacology and toxicology. Curr Neuropharmacol. 2013;11(3):315-335.
doi:10.2174/1570159X11311030006. Naughton SX, Terry AV Jr. Neurotoxicity in acute and
repeated organophosphate exposure. Toxicology. 2018 Sep 1;408:101-112. doi:
10.1016/j.tox.2018.08.011. Epub 2018 Aug 23. PMID: 30144465; PMCID: PMC6839762.

Question 3

A 62-year-old man with a long-standing history of alcohol abuse is brought to the emergency
department because of disorientation and ataxia. Oral temperature is 33.9°C (93.0°F).
Examination shows horizontal gaze nystagmus. Immediate administration of which of the following
is most appropriate?
Answers:
A. glucose
B. flumazenil
C. thiamine
D. tPA
E. naloxone

Answer 3

thiamine

Discussion:
This patient appears to be experiencing Wernicke encephalopathy, an acute, reversible condition
caused by severe thiamine (vitamin B1) deficiency, often due to chronic heavy alcohol use.
Wernicke encephalopathy is an emergency and requires immediate high-dose IV thiamine therapy.
The classical triad of confusion, oculomotor dysfunction, and gait ataxia is seen in about a third of
patients. Chronic thiamine deficiency can progress to Korsakoff syndrome which is characterized
by irreversible personality changes, anterograde and retrograde amnesia, and confabulation.
Glucose administration should never occur before thiamine adnimistration as glucose increases
demand for thiamine thus worsening the patient’s encephalopathy.
References:
Latt N, Dore G. Thiamine in the treatment of Wernicke encephalopathy in patients with alcohol use
disorders. Intern Med J. 2014 Sep;44(9):911-5. doi: 10.1111/imj.12522. PMID: 25201422. Goetz C.
Textbook of Clinical Neurology. 2007.

Question 4

The effects of abnormal lead absorption are most likely to be reflected by changes in the
Answers:
A. frontal lobes
B. peripheral nerves
C. spinal cord
D. hippocampus
E. cerebellum

Answer 4

peripheral nerves

Discussion:
The peripheral nerves are most commonly affected in adult lead poisoning. Although the CNS is
most commonly affected in children, adults with lead exposure typically present with a peripheral
polyneuritis most commonly affecting the extensor muscles suppled by the radial and peroneal
nerves. Foot drop and wrist drop are common clinical manifestations. Pathological changes
include segmental demyelination and axonal degeneration with concomitant endoneural edema of
Schwann cells. CNS injury can occur in adults with lead poisoning but the threshold is significantly
higher than for children.
References:
National Research Council. 1993. Measuring Lead Exposure in Infants, Children, and Other
Sensitive Populations. Washington, DC: The National Academies Press. https://doi.org/10.17226
/2232. Bressler J, Kim KA, Chakraborti T, Goldstein G. Molecular mechanisms of lead
neurotoxicity. Neurochem Res. 1999;24:595–600.

Question 5

Which of the following neuropathic pain medications works by binding to voltage-gated calcium
channels in neurons?
Answers:
A. Diazepam
B. Gabapentin
C. Ketamine
D. Ketorolac
E. Methocarbamol

Answer 5

Gabapentin

Discussion:
Gabapentin demonstrates significant efficacy and success in the treatment of neuropathic pain.
The drug demonstrates high affinity for binding to voltage-gated calcium channels, particularly
alpha-2-delta-1, which thereby inhibits the release of excitatory neurotransmitters in the
presynaptic terminal. Ketorolac is a first-generation non-steroidal anti-inflammatory drug (NSAID)
which inhibits prostaglandin synthesis by competitively blocking the enzyme cyclooxygenase
(COX). The exact mechanism of action of methocarbamol is not established, however, it is
postulated to inhibit synaptic acetylcholinesterase. Diazepam is a benzodiazepime which
potentiates the inhibitory efect of γ-aminobutyric acid on neuronal transmission. Ketamine
functions as an NMDA receptor antagonist, however, its exact meechanism of action remains
unknown.
References:
1. Wiffen PJ, Derry S, Moore RA, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia -
an overview of Cochrane reviews. Cochrane Database Syst Rev. 2013;11:CD010567.2. Chen L,
Mao J. Update on neuropathic pain treatment: ion channel blockers and gabapentinoids. Curr Pain
Headache Rep. 2013;17(9):359. Zamponi GW, Striessnig J, Koschak A, Dolphin AC. The
Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future
Therapeutic Potential. Pharmacol Rev. 2015 Oct;67(4):821-70. doi: 10.1124/pr.114.009654. PMID:
26362469; PMCID: PMC4630564.

Question 6

Baclofen, a drug that is used both orally and intrathecally in the treatment of spasticity, exerts its
action through which of the following means?
Answers:
A. GABA agonist
B. D2 Dopamine receptor agonist
C. 5-HT2B Agonism
D. GABA antagonist
E. NMDA-receptor antagonism

Answer 6

GABA agonist

Discussion:
Baclofen is a GABA agonist, acting by reducing the release of excitatory neurotransmitters and
substance P by binding to the GABA-B receptor. GABA antagonists include drugs that produce
stimulant or convulsant effects and are largely used to counteract overdoses of sedatives, such as
the GABA-A receptor antagonist flumazenil. D2 Dopamine receptor agonists include dopaminergic
drugs such as pramipexole which are utilized to treat symptoms of Parkinson’s Disease. NMDAreceptor antagonists include drugs such as ketamine, memantine and amantadine. Selective
serotonin reuptake inhibitors such as fluoxetine act as 5-HT2B agonists.
References:
Furr-Stimming E, Boyle AM, Schiess MC. Spasticity and intrathecal baclofen. Semin Neurol. 2014
Nov;34(5):591-6. doi: 10.1055/s-0034-1396012. Epub 2014 Dec 17. PMID: 25520030. Dvorak EM,
Ketchum NC, McGuire JR. The underutilization of intrathecal baclofen in poststroke spasticity. Top
Stroke Rehabil. 2011 May-Jun;18(3):195-202. doi: 10.1310/tsr1803-195. PMID: 21642057.
Chapter 64. In: Albright AL, Pollack IF, Adelson PD, eds. Principles and Practice of Pediatric
Neurosurgery. Thieme Medical Publishers:1160

Question 7

The clinical triad of coma, pinpoint pupils, and depressed respiration is most consistent with
Answers:
A. Meningoencephalitis
B. Hyponatremia
C. Narcotic overdose
D. Seizure
E. Epidural hematoma

Answer 7

Narcotic overdose

Discussion:
The triad of coma, pinpoint pupils, and depressed respirations are most consistent with narcotic
overdose. All of the above answer choices are possible causes of coma but are not as likely as
narcotic overdose. A patient with a trauma causing an epidural hematoma will usually have
lateralizing signs. Additionally, although seizures, hypoglycemia, and infection may cause a
comatose or minimally reactive state, the triad of pinpoint pupils, decreased respirations, and
coma are not common in these situations.
References:
Boyer EW. Management of opioid analgesic overdose. N Engl J Med. 2012;367(2):146-155.
doi:10.1056/NEJMra1202561. Lalley PM. Opioidergic and dopaminergic modulation of respiration.
Respir Physiol Neurobiol. 2008 Dec 10;164(1-2):160-7. doi: 10.1016/j.resp.2008.02.004. PMID:
18394974; PMCID: PMC2642894. Stein C. The control of pain in peripheral tissue by opioids. N
Engl J Med 1995;332:1685-1690

Question 8

Which of the following medications is most likely to include reversible cerebral vasoconstrictive
syndrome as a side effect?
Answers:
A. Aspirin
B. Rosuvastatin
C. Nimodipine
D. Metoprolol
E. Sertraline

Answer 8

Sertraline

Discussion:
Reversible cerebral vasoconstrictive syndrome (RCVS) is a clinical syndrome characterized by
acute thunderclap headache, emesis and nausea. RCVS is supposedly due to a transient
disturbance in the control of cerebrovascular tone. The syndrome demonstrates segmental
vasoconstriction on angiography and reversibility of the lesion. The syndrome is often triggered by
vasoactive substances, including selective serotonin reuptake inhibitors such as sertraline, or illicit
substances such as cocaine. More than half the cases occur post partum or after exposure to
adrenergic or serotonergic drugs. Manifestations have a uniphasic course, and vary from pure
cephalalgic forms to rare catastrophic forms associated with hemorrhagic and ischemic strokes,
brain edema, and death. The calcium channel blocker nimodipine seems to reduce thunderclap
headaches within 48 hr of administration, but has no proven effect on hemorrhagic and ischemic
complications.
References:
Ducros A, Boukobza M, Porcher R, et al. The clinical and radiological spectrum of reversible
cerebral vasoconstriction syndrome. A prospective series of 67 patients. Brain. 2007 Dec;130(Pt
12):3091-101. Ducros A. Reversible cerebral vasoconstriction syndrome. Lancet Neurol. 2012
Oct;11(10):906-17. doi: 10.1016/S1474-4422(12)70135-7. PMID: 22995694.

Question 9

A 23-year-old woman with T2 quadriplegia is brought to the emergency department with increased
spasticity, dysphoria, pruritus, and a temperature of 40.6°C (105.0°F). Her spasticity has been
controlled with a baclofen pump implant for the past three years. She subsequently has a seizure
in the emergency department. Which of the following is the most likely diagnosis?
Answers:
A. Neuroleptic-Malignant Syndrome
B. Baclofen overdose
C. Malignant Hyperthermia
D. Autonomic Dysreflexia
E. Baclofen withdrawal

Answer 9

Baclofen withdrawal

Discussion:
Symptoms of intrathecal baclofen (ITB) withdrawal begin as a return of spasticity, rigidity and
pruritis. Abrupt withdraw, however, can prompt generalized seizures, hallucinations, muscle rigidity,
fevers, labile blood pressures and lethargy. If not treated promptly with supportive measures and
high-dose benzodiazeppine infusion prior to resumption of intrathecal baclofen therapy, the
syndrome can progress to include rhabdomyolysis (with markedly elevated plasma creatine kinase
levelsm, elevated transaminase levels, hepatic and renal failure, disseminated intravascular
coagulation, and rarely death.
ITB withdrawal is mediated by an abrupt decrease in central nervous synstem GABA transmission.
Autonomic dysreflexia is caused by disconnection of major splanchnic sympathetic outflow from
supraspinal control due to ongoing nociceptive stimulus below the level of a spinal cord lesion in a
T6 or higher spinal cord injury patient. Hallmarks include paradoxical bradycardia with
hypertension, the absence of fever, as well as piloerection and pallor below the level of injury with
flushing, vasodilation and profuse sweating above the SCI level. Malignant hyperthermia is
mediated by a ryanodine receptor mutation that causes calcium leakage from the sarcoplasmic
reticulum. It typically occurs in the setting of initiating anesthesias, particularly with halothane
agents, and presents as tetanic muscle contractions that are unresponsive to centrally acting
muscles relaxants. Although neuroleptic malignant syndrome also presents with profound
generalized rigidity, it is caused by an acute loss of hypothalamic dopaminergic transmission,
typically in the setting of initiating dopamine-blocking neuroleptic agents or after abrupt cessation
of a dopamine agonist. Clinical features also include hyperactive autonomic function, leukocytosis
at onset, tachycardia and hypertension. Overdosage of ITB is characterized by rostral progression
of hypotonia, respiratory depression, coma, and seizures in the absence of fevers and rigidity.
References:
Coffey R, Edgar T, Francisco G, Graziani V, Meythaler J, Ridgely P, Sadiq S, Turner M. Abrupt
withdrawal from intrathecal baclofen: recognition and management of potentially life-threatening
syndrome. Arch Phys Medical Rehabilitation 2002: 83:735-41.
Steinbok P. Neurosurgical Management of Hypertonia in Children. Neurosurgery Quarterly. 2002:
63-78

Question 10

A 21-year-old art student is evaluated because of bilateral arm weakness. On examination, he
demonstrates 4/5 weakness in dorsiflexion of both wrists. His sensation is normal. He notes that
his latest project is creating painted ceramic coffee cups that he also uses for drinking. An EMG
shows evidence of a peripheral motor neuropathy causing the wrist drop. Administration of which
of the following is most likely to be the most appropriate treatment?
Answers:
A. iron
B. folate
C. observation alone
D. prednisone
E. penicillamine

Answer 10

penicillamine

Discussion:
This patient is most likely experiencing wrist drop secondary to peripheral neuropathy caused by
lead poisoning. The student may be unintentially ingesting lead by drinking from cups made with
lead-based paint. Lead poisoning typically causes a peripheral polyneuropathy that most
commonly affects the radial and peroneal nerves thus causing wrist or foot drop. Other common
symptoms of lead poisoning include cognitive impairment, anemia, abdominal pain, and
constipation. In addition to removing exposure to the offending lead-based paint, this patient may
be treated with a chelating agent such as penicillamine if their blood lead levels are elevated.
References:
Kim HC, Jang TW, Chae HJ, et al. Evaluation and management of lead exposure. Ann Occup
Environ Med. 2015;27:30. Published 2015 Dec 15. doi:10.1186/s40557-015-0085-9. Bressler J,
Kim KA, Chakraborti T, Goldstein G. Molecular mechanisms of lead neurotoxicity. Neurochem Res.
1999;24:595–600. Vij A. Hemopoietic, hemostatic and mutagenic effects of lead and possible
prevention by zinc and vitamin C. Al Ameen J Med Sci. 2009;2:27–36.

Question 11

Which of the following pharmacologic agents acts as an extracerebral decarboxylase inhibitor?
Answers:
A. Carbidopa
B. Phenylalanine
C. Levodopa
D. Pyridoxine
E. Tyrosine

Answer 11

Carbidopa

Discussion:
Extracerebral decarboxylase inhibitors such as carbidopa inhibit peripheral metabolism of
levodopa. This allows a greater proportion of peripheral levodopa to cross the blood–brain barrier
and be utilized in the brain rather than metabolized peripherally. Levodopa is used to increase
dopamine concentrations in the brain for the treatment of Parkinson’s disease and dopamineresponsive dystonia. Coadministration of pyridoxine without an extracerebral decarboyxlase
inhibitor accelerates the peripheral decarboxylation of Levodopa to such an extent that it negates
the effects of levodopa administration. Levodopa is produced from the amino acid l-tyrosine by the
enzyme tyrosine hydroxylase.
References:
Calne, D. B.; Reid, J. L.; Vakil, S. D.; Rao, S.; Petrie, A.; Pallis, C. A.; Gawler, J.; Thomas, P. K.;
Hilson, A. (1971). “Idiopathic Parkinsonism treated with an extracerebral decarboxylase inhibitor in
combination with levodopa.” British Medical Journal. 3 (5777):
729–732. doi:10.1136/bmj.3.5777.729. PMC 1798919. PMID 4938431. Gershanik OS. Improving
L-dopa therapy: the development of enzyme inhibitors. Movement Disorders : Official Journal of
the Movement Disorder Society. 2015 Jan;30(1):103-113. DOI: 10.1002/mds.26050.

Question 12

The most common manifestation of alcohol withdrawal syndrome is
Answers:
A. peripheral neuropathy
B. ataxia
C. hallucinations
D. seizures
E. autonomic hyperactivity

Answer 12

autonomic hyperactivity

Discussion:
The most common symptoms of alcohol withdrawal syndrome of the choices are autonomic
changes. Alcohol withdrawal syndrome will manifest with tachycarcardia, fever, and other signs of
autonomic hyperactivity. These symptoms can begin as early as 6 hours after the patient has last
consumed alcohol. Seizures and hallucinations can also occur, but these findings are less
common and typically occur later in the course of alcohol withdrawal. Peripheral neuropathy and
ataxia are not typically associacted with alcohol withdrawal but rather chronic alcohol misuse.
Peripheral neuropathy can occur with a megaloblastic anemia secondary to cobalamin deficiency
and ataxia may result from Korsakoff syndrome and chronic thiamine deficiency.
References:
Mirijello A, D’Angelo C, Ferrulli A, Vassallo G, Antonelli M, Caputo F, Leggio L, Gasbarrini A,
Addolorato G. Identification and management of alcohol withdrawal syndrome. Drugs. 2015
Mar;75(4):353-65. doi: 10.1007/s40265-015-0358-1. PMID: 25666543; PMCID: PMC4978420.
McKeon A, Frye MA, Delanty N. The alcohol withdrawal syndrome. J Neurol Neurosurg Psychiatry.
2008 Aug;79(8):854-62. doi: 10.1136/jnnp.2007.128322. Epub 2007 Nov 6. PMID: 17986499.
Sachdeva A, Choudhary M, Chandra M. Alcohol Withdrawal Syndrome: Benzodiazepines and
Beyond. J Clin Diagn Res. 2015 Sep;9(9):VE01-VE07. doi: 10.7860/JCDR/2015/13407.6538.
Epub 2015 Sep 1. PMID: 26500991; PMCID: PMC4606320.

Question 13

In 2009, the United States Food and Drug Administration mandated updated labeling for all
anticonvulsant medications to indicate an increased risk of which of the following?
Answers:
A. Weight Gain
B. Dystonia
C. Stevens-Johnson Syndrome
D. Suicidal Ideation
E. Aplastic Anemia

Answer 13

Suicidal Ideation

Discussion:
In 2008, the FDA conducted a meta-analysis of 199 placebo-controlled trials of 11 antiepileptic
agents, including gabapentin, divalproex, felbamate, lamotrigine, levetiracetam, oxcarbazepine,
pregabalin, tiagabine, topiramate, zonisamide, and carbamazepine. Of the 43,892 patients
captured, the risk of suicidality was twice as likely in patients receiving these medications relative
to placebo controls (0.43% versus 0.22%). Risks were found to increase soon after initiation of the
agent and persisted through at least six months of use. The FDA subsequently issued a safety
mandate warning of suicidal ideation and risk associated with antiepileptic medications.
Depression is not uncommon among patients with chronic epilepsy, however, suicidality has not be
shown to correlate with the severity of illness. Recognition of this risk should be considered and
patients starting anticonvsulvie medication for any indication should be counseled appropriately.
References:
Arana A, Wentworth CE, Ayuso-Mateos JL, et al. Suicide-related events in patients treated with
antiepileptic drugs. N Engl J Med. 2010 Aug 5;363(6):542-551.
Mula M, Kanner AM, Schmitz B, Schachter S. Antiepileptic drugs and suicidality: an expert
consensus statement from the Task Force on Therapeutic Strategies of the ILAE Commission on
Neuropsychobiology. Epilepsia 2013;54:199-203.
Hesdorffer DC, Kanner AM. The FDA alert on suicidality and antiepileptic drugs: fire or false
alarm? Epilepsia 2009;50:978-986.

Question 14

A patient who takes vitamin supplements reports headaches, diplopia, and diffuse myalgias.
Examination shows papilledema and dry, scaly skin. The patient is most likely consuming an
excess of which of the following vitamins?
Answers:
A. Niacin
B. Vitamin A
C. Pyridoxine
D. Vitamin E
E. Vitamin C

Answer 14

Vitamin A

Discussion:
The clinical scenario best describes a patient with chronic vitamin A toxicity. Vitamin C toxicity can
lead to GI symptoms, fatigue, and nephrolithiasis due to increased calcium oxalate formation.
Vitamin E toxicity is rare but can cause increased risk of bleeding and coagulopathy as high doses
may alter Vitamin K metabolism. Niacin and Pyridoxine are B vitamins which can be associated
with facial flushing and sensory peripheral neuropathy when taken in excess, respectively.
References:
Penniston KL, Tanumihardjo SA. The acute and chronic toxic effects of vitamin A. Am J Clin Nutr.
2006 Feb;83(2):191-201. doi: 10.1093/ajcn/83.2.191. PMID: 16469975. Leo MA, Lieber CS.
Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and
carcinogenicity. Am J Clin Nutr. 1999 Jun;69(6):1071-85. doi: 10.1093/ajcn/69.6.1071. PMID:
10357725. Olson JM, Ameer MA, Goyal A. Vitamin A Toxicity. 2021 Feb 11. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 30422511

Question 15

A 65-year-old man has a 10-year history of complex partial seizures that are uncontrolled with
carbamazepine at standard therapeutic levels. He also is being treated for chronic atrial fibrillation
with warfarin. Which of the following medications is the most appropriate substitution for the
carbamazepine?
Answers:
A. Phenobarbital
B. Valproic Acid
C. Leviteracetam
D. Phenytoin
E. Primidone

Answer 15

Leviteracetam

Discussion:
Carbamazepine, phenytoin, phenobarbital and primidone (henceforth referred to collectively as
enzyme-inducing AEDs) stimulate the activity of a variety of cytochrome P450 (CYP) enzymes,
including CYP1A2, CYP2C9, CYP2C19 and CYP3A4, as well as glucuronyl transferases (GT) and
epoxide hydrolase. Because these enzymes are involved in the biotransformation of the majority of
therapeutic agents, patients taking enzyme inducing AEDs metabolize at a faster rate a wide range
of concomitantly administered medications, whose dosage requirements may be consequently
increased. Valproic acid differs from other older generation AEDs in being an inhibitor rather than
an inducer of drug metabolizing enzymes, including those involved in the oxidation of
phenobarbital, the glucuronidation of lamotrigine and the conversion of carbamazepine-10,11-
epoxide to the corresponding diol, epoxide hydrolase. Levetiracetam, gabapentin and pregabalin
have not been reported to cause or be a target for clinically relevant pharmacokinetic drug
interactions.
References:
Juurlink DN. Drug interactions with warfarin: what clinicians need to know. CMAJ
2007;177:369-71. Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin
Pharmacol 2005; 61:246-55. The Treatment of Epilepsy, ed Shorrons et al. 2004. p. 443-450.

Question 16

A patient with glioblastoma who is treated with temozolomide is most likely to have which of the
following complications?
Answers:
A. myelosuppression
B. hearing loss
C. peripheral neuropathy
D. cardiomyopathy
E. pulmonary fibrosis

Answer 16

myelosuppression

Discussion:
An uncommon but predictable complication of temozolamide at higher doses is myelosuppression.
Temozolamide has a relatively benign side effect profile with most patients only experiencing mild
GI symptoms and a smaller number of patients experiencing alopecia or a rash. Myelosuppresion
caused by temozolamide appears to be reversible and typically resolves quickly after lowering the
dose. Of the common chemotherapeutics, bleomycin and busulfan are known to cause pulmonary
fibrosis, doxorubicin and trastuzumab is associated with cardiomyopathy, vincristine is often
associated with peripheral neuropathy, and cisplatin and carboplatin are associated with nephroand ototoxicity.
References:
Schwenka J, Ignoffo RJ. Temozolomide. A new option for high-grade astrocytomas. Cancer Pract.
2000 Nov-Dec;8(6):311-3. doi: 10.1046/j.1523-5394.2000.86004.x. PMID: 11898150. Ening G,
Osterheld F, Capper D, Schmieder K, Brenke C. Risk factors for glioblastoma therapy associated
complications. Clin Neurol Neurosurg. 2015 Jul;134:55-9. doi: 10.1016/j.clineuro.2015.01.006.
Epub 2015 Jan 9. PMID: 25942630. Arulananda S, Lynam J, Sem Liew M, Wada M, Cher L, Gan
HK. Clinical correlates of severe thrombocytopenia from temozolomide in glioblastoma patients.
Intern Med J. 2018 Oct;48(10):1206-1214. doi: 10.1111/imj.14000. PMID: 29923272.

Question 17

A patient with posterior interosseous nerve syndrome is able to extend the wrist because of
sparing of innervation to which of the following muscles?
Answers:
A. Pronator
B. Extensor carpi radialis longus
C. Extensor carpi ulnaris
D. Extensor carpi radialis brevis
E. Brachioradialis

Answer 17

Extensor carpi radialis longus

Discussion:
The posterior interosseous nerve is a distal branch of the radial nerve that provides motor
innervation to the supinator, extensor carpi radialis brevis, extensor digitorum communis, extensor
digiti minimi, extensor carpi ulnaris, abductor pollicis, extensor pollicis brevis, extensor pollicis
longus, and extensor indicis. The classic finding is preserved wrist extension as the extensor carpi
radialis longus branches proximal to the leading edge of the supinator the most common
entrapment point of the posterior interosseous nerve. The pronator is a motor branch of the
median nerve that provides distal forearm innervation of the pronator muscle. The brachioradialis
is innervated by the radial nerve and provides elbow flexion, innervation occurs prior to the leading
edge of the supinator and is spared in PIN syndrome.
References:
Posterior Interosseous Nerve Syndrome Rachel Wheeler, Alexei DeCastro 1 In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. 2020 Oct 27. PMID: 31082090
Strohl AB, Zelouf DS. Ulnar Tunnel Syndrome, Radial Tunnel Syndrome, Anterior Interosseous
Nerve Syndrome, and Pronator Syndrome. J Am Acad Orthop Surg. 2017 Jan;25(1):e1-e10. doi:
10.5435/JAAOS-D-16-00010. PMID: 27902538.
Dang AC, Rodner CM. Unusual compression neuropathies of the forearm, part I: radial nerve. J
Hand Surg Am. 2009 Dec;34(10):1906-14. doi: 10.1016/j.jhsa.2009.10.016. PMID: 19969199.

Question 18

The precursor of levodopa is
Answers:
A. Glutamate
B. Glycine
C. Tyrosine
D. Asparagine
E. Arginine

Answer 18

Tyrosine

Discussion:
During dopamine synthesis, tyrosine hydroxylase catalyzes the hydroxylation of tyrosine to
levodopa. Tyrosine hydroxylase functions as the rate-limiting enzyme during dopamine and
catecholamine synthesis. Arginine is the precursor for nitric oxide
References:
Meiser, J., Weindl, D. & Hiller, K. Complexity of dopamine metabolism. Cell Commun Signal 11, 34
(2013). Godwin-Austen RB, Tomlinson EB, Frears CC, Kok HW. Effects of L-dopa in Parkinson’s
disease. Lancet. 1969 Jul 26;2(7613):165-8. doi: 10.1016/s0140-6736(69)91417-2. PMID:
4183130

Question 19

Central pontine myelinolysis is associated with which of the following?
Answers:
A. Rapid correction of acute hyponatremia
B. Rapid correction of acute hypernatremia
C. Rapid correction of chronic hypernatremia
D. Rapid correction of chronic hyponatremia
E. Rapid correction of hypokalemia

Answer 19

Rapid correction of chronic hyponatremia

Discussion:
Central pontine myelinolysis (CPM) is associated with the rapid correction of chronic (great than 48
hours) hyponatremia. Rapid correction of severe symptomatic acute hyponatremia can typically be
achieved without sequelae. However, patients who are chronically hyponatremic may be at risk for
developing central pontine myelinolysis. The most recent recommendations are not to exceed 8-10
mmol/l/day of correction to avoid this complication although CPM can still occur with smaller rises
in smaller sodium. Rapid correction of hypernatremia can result in cerebral edema, not CPM, as
shifts in tonicity cause an influx of fluid into cells. CPM typically presents several days after a rapid
correction of chronic hyponatremia. The initial signs of CPM include dysarthria, dysphagia (from
corticobulbar tract involvement), quadriparesis (from corticospinal tract involvement), and possible
oculomotor and pupillary abnormalities. This can present as “locked-in syndrome” in severe cases.
References:
Martin RJ. Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes.
Journal of Neurology, Neurosurgery & Psychiatry 2004;75:iii22-iii28. http://dx.doi.org/10.1136
/jnnp.2004.045906. Giuliani C, Peri A. Effects of Hyponatremia on the Brain. J Clin Med. 2014 Oct
28;3(4):1163-77. doi: 10.3390/jcm3041163. PMID: 26237597; PMCID: PMC4470176

Question 20

Benzodiazepines that are used to treat alcohol withdrawal syndrome are most likely to target which
of the following neurotransmitter receptors?
Answers:
A. µ-opioid receptor
B. 5-HT1A serotonergic receptor
C. dopamine D2 receptors
D. type A γ-aminobutyric acid receptor
E. H1 histaminergic receptor

Answer 20

type A γ-aminobutyric acid receptor

Discussion:
Alcohol withdrawal syndrome is mediated by reduced neurotransmission in type A γ-aminobutyric
acid receptors and enhanced neurotransmission in glutamate (N-methyl-D-aspartate) pathways.
Benzodiazepines demonstrate cross-tolerance with ethanol at type A γ-aminobutyric acid
receptors, making them effective in the treatment of alcohol withdrawal related seizures. Opioid
drugs are agonists at µ-opioid receptors, where they inhibit cAMP. Repeated cocaine and
amphetamine administration has been found to facilitate decreased expression of postsynaptic
dopamine D2 receptors, leading to pilot studies investigating dopamine agonist pharmacotherapies
for stimulant withdrawal. To date, no agents have demonstrated reliable efficacy. Antihistamines
act at H1 histaminergic receptors and activation of 5-HT1A serotonergic receptor is involved in the
mechanism of anction of many antidepressant, antipsychotic and anxiolytic medications.
References:
Kosten TR, OConnor PG. Management of drug and alcohol withdrawal. N England J Med.
2003;348:1786-1795.
Maldonado JR. Novel Algorithms for the Prophylaxis and Management of Alcohol Withdrawal
Syndromes-Beyond Benzodiazepines. Crit Care Clin. 2017 Jul;33(3):559-599. doi:
10.1016/j.ccc.2017.03.012. PMID: 28601135.
Dixit D, Endicott J, Burry L, Ramos L, Yeung SY, Devabhakthuni S, Chan C, Tobia A, Bulloch MN.
Management of Acute Alcohol Withdrawal Syndrome in Critically Ill Patients. Pharmacotherapy.
2016 Jul;36(7):797-822. doi: 10.1002/phar.1770. Epub 2016 Jun 30. PMID: 27196747

Question 21

After several years of successful treatment of Parkinson disease with levodopa, a 65-year-old man
has sudden onset of episodes of profound bradykinesia and rigidity that occur and then resolve.
Which of the following is the most likely cause of these episodes?
Answers:
A. Dietary protein restriction
B. Use of multiple antiparkinson medications
C. Concomitant use of other psychoactive medications
D. “On - Off” Phenomenon of sustained levodopa treatment
E. Autonomic dysfunction

Answer 21

“On - Off” Phenomenon of sustained levodopa treatment

Discussion:
The “on-off” phenomenon of oscillating clinical response to levodopa is an invariable consequence
of sustained therapy, reflecting fluctations in absorption and transport of the drug. Strategies to
address this phenomenon seek to smooth out fluctuations in antiparkinsonian medications by
utilizing longer-acting agents, such as dopamine agonists or COMT inhibitors, as well as restricting
dietary protein that competes with levodopa absorption in the small intetine.
References:
Nutt JG, Woodward WR, Hammerstad JP, et al. The On–Off Phenomenon in Parkinson’s Disease -
Relation to Levodopa Absorption and Transport. N Engl J Med. 1984 Feb 23;310(8):483-8. Stocchi
F, Antonini A, Barone P, Tinazzi M, Zappia M, Onofrj M, Ruggieri S, Morgante L, Bonuccelli U,
Lopiano L, Pramstaller P, Albanese A, Attar M, Posocco V, Colombo D, Abbruzzese G; DEEP
study group. Early DEtection of wEaring off in Parkinson disease: the DEEP study. Parkinsonism
Relat Disord. 2014 Feb;20(2):204-11. doi: 10.1016/j.parkreldis.2013.10.027. Epub 2013 Nov 5.
Erratum in: Parkinsonism Relat Disord. 2015 Jul;21(7):827. PMID: 24275586. Nutt JG. On-off
phenomenon: relation to levodopa pharmacokinetics and pharmacodynamics. Ann Neurol. 1987
Oct;22(4):535-40. doi: 10.1002/ana.410220415. PMID: 3324948.

Question 22

Fifteen minutes after receiving 10 mg of prochlorperazine intravenously, a patient develops sudden
deviation of the eyes upward and to the right and extension of the neck, back, and arms with slight
torsion of the neck. The most appropriate treatment is administration of which of the following?
Answers:
A. lorazepam
B. cyproheptadine
C. dantrolene
D. baclofen
E. benztropine

Answer 22

benztropine

Discussion:
This patient appears to be experiencing an acute dystonic reaction to prochlorperazine which
should be treated promptly with benztropine. Dantrolene is used to treat neuroleptic malignant
syndrome which is also a possible adverse reaction to prochlorperazine but typically occurs hours
to days after initiation of treatment. Although muscle rigidity occurs in neuroleptic malignant
syndrome, it should also be associated with an elevated temperature. Lorazepam is a first line
therapy aborting seizures. Baclofen is also an effective treatment for dystonia but benztropine is a
better choice in this clinical scenario because the causal agent is prochlorperazine. Cyproheptidine
can be used in the treatment of mild cases of serotonin syndrome which classically presents in a
patient who is being treated with multiple serotonergic drugs who develop altered mental status,
muscle rigidity, and autonomic instability.
References:
Campbell D. The management of acute dystonic reactions. Aust Prescr 2001;24:19-20. Bateman
DN, Darling WM, Boys R, Rawlins MD. Extrapyramidal reactions to metoclopramide and
prochlorperazine. QJM 1989;71:307-11. Oyewole A, Adelufosi A, Abayomi O. Acute dystonic
reaction as medical emergency: a report of two cases. Ann Med Health Sci Res. 2013
Jul;3(3):453-5. doi: 10.4103/2141-9248.117932. PMID: 24116333; PMCID: PMC3793459.

Question 23

A patient undergoes excision of the cervical lymph nodes in the posterior cervical triangle. Which
of the following structures is most likely to be damaged?
Answers:
A. Dorsal Scapular Nerve
B. Suprascapular nerve
C. Long thoracic Nerve
D. Spinal Accessory Nerve
E. Phrenic Nerve

Answer 23

Spinal Accessory Nerve

Discussion:
Injury to the spinal accessory nerve (CN XI) most commonly occurs with lymph node bioposy or
radial neck dissection. Injury can cause abnormal or weakness in shoulder function and potentially
winging of the scapula. Injury to the long throcic nerve is more common with axillary dissection and
causes classic winging of the scapula. The phrenic nerve can be injured resulting in diaphragm
weakness or paralysis (hemidiaphragm). The dorsal scapular nerve arises from the C5 nerve root
and provides function to the rhomboids. Although isolated injury is rare, Injury to the dorsal
scapular nerve can result in scapular winging. The suprascapular nerve innervates the supra- and
infraspinatus muscles. Injury commonly occurs with upper trunk brachial plexus injuries resulting in
weakness in shoulder abduction and external rotation.
References:
Extra and Intramuscular Distribution of the Thoracodorsal Nerve with Regard to Nerve
Reconstruction Surgeries. Malalasekera A, Beneragama T, Kanesu S, Sahathevan V, Jayasekara
R.J Reconstr Microsurg. 2016 Jun;32(5):358-60. doi: 10.1055/s-0036-1579541. Epub 2016 Feb
18.
PMIUD:26890860
https://pubmed.ncbi.nlm.nih.gov/33090551/

Question 24

Meralgia paresthetica most likely results from entrapment of which of the following nerves?
Answers:
A. Femoral nerve
B. Saphenous nerve
C. Lateral femoral cutaneous nerve
D. Ilioinguinal nerve
E. Obturator nerve

Answer 24

Lateral femoral cutaneous nerve

Discussion:
Compression of the lateral femoral cutaneous nerve causes pain and numbness in the outer thigh.
Compression typically occurs as the nerve traverses between the iliac crest and inguinal ligament.
The femoral neve originates from the L2, L3, and L4 nerve roots. Injury causes weakness of knee
extension (vastus medialis, vastus lateralis, and vastus intermedius). The ilioinguinal nerve
originates from the rostral lumbar plexus (L1). It provides sensory innervation to the genitals and
more innervation to the transverse obdominus and obliques. The saphenous nerve a cutaneous
branch that also provides just sensory innervation but in contrast to the lateral femoral cutaneous
nerve, innervation is on the medial lower extremity. The obturator nerve also originates from L2,
L3, and L4 nerve roots providing motor innervation to the external obturator, adductor longus,
adductor brevis, adductor magnus, and gracilis.
References:
Meralgia Paresthetica. Coffey R, Gupta V.2021 Feb 6. In: StatPearls [Internet]. Treasure Island
(FL): StatPearls Publishing; 2021 Jan–. PMID: 32491667
Grossman MG, Ducey SA, Nadler SS, Levy AS. Meralgia paresthetica: diagnosis and treatment. J
Am Acad Orthop Surg. 2001 Sep-Oct;9(5):336-44. doi: 10.5435/00124635-200109000-00007.
PMID: 11575913.
Lee SH, Shin KJ, Gil YC, Ha TJ, Koh KS, Song WC. Anatomy of the lateral femoral cutaneous
nerve relevant to clinical findings in meralgia paresthetica. Muscle Nerve. 2017
May;55(5):646-650. doi: 10.1002/mus.25382. Epub 2017 Jan 3. PMID: 27543938.

Question 25

A patient has a peripheral neuropathy that primarily affects motor fibers and is relatively sensory
sparing. The patient also has hypochromic, microcytic anemia. The most likely cause is
Answers:
A. folate deficiency
B. copper deficiency
C. lead exposure
D. alcohol use disorder
E. iron deficiency

Answer 25

lead exposure

Discussion:
Of the answers listed, this patient’s relatively sensory sparing peripheral neuropathy and
hypochromic, microcytic anemia can best be explained by lead poisoning. Although iron deficiency
can also cause a microcytic anemia, an associated peripheral neuropathy makes this unlikely.
Folate deficiency, alcohol use disorder, and copper deficiency can also cause anemia. However,
these typically result in a macrocytic anemia.
References:
Kim HC, Jang TW, Chae HJ, et al. Evaluation and management of lead exposure. Ann Occup
Environ Med. 2015;27:30. Published 2015 Dec 15. doi:10.1186/s40557-015-0085-9. Bressler J,
Kim KA, Chakraborti T, Goldstein G. Molecular mechanisms of lead neurotoxicity. Neurochem Res.
1999;24:595–600. Vij A. Hemopoietic, hemostatic and mutagenic effects of lead and possible
prevention by zinc and vitamin C. Al Ameen J Med Sci. 2009;2:27–36.

Question 26

A 55-year-old woman with trigeminal neuralgia is scheduled to undergo microvascular
decompression. Laboratory studies on admission show a sodium level of 123 mEq/L. Which of the
following medications most likely caused this patient’s hyponatremia?
Answers:
A. Topiramate
B. Oxcarbazepine
C. Zonisamide
D. Baclofen
E. Gabapentin

Answer 26

Oxcarbazepine

Discussion:
Both carbamazepine and oxcarbazepine are effective agents in the treatment of trigeminal
neuralgia, however, they are associated with hyponatremia. Gabapentin, which is more commonly
associated with weight gain, peripheral edema and behavioral changes, can be used as a second
line agent in trigeminal neuralgia patients who present with hyponatremia after initiation of
carbamazepine or oxcarbamazepine therapy.
References:
Kofke WA. Antiepileptic and antipsychotic drugs. In: Evers AS, Maze M, Kharasch ED, eds.
Anesthetic Pharmacology. 2nd ed. Cambridge, England: Cambridge University Press; 2011:595.
Zhou M, Chen N, He L, Yang M, Zhu C, Wu F. Oxcarbazepine for neuropathic pain. Cochrane
Database Syst Rev. 2017 Dec 2;12(12):CD007963. doi: 10.1002/14651858.CD007963.pub3.
PMID: 29199767; PMCID: PMC6486101.

Question 27

Drugs of which of the following classes are contraindicated in patients with Lewy body dementia?
Answers:
A. NMDA-receptor antagonists
B. Nicotinic and muscarinic agonists
C. Antiepileptic agents
D. Cholinesterase inhibitors
E. First-generation antipsychotics (typical neuroleptics)

Answer 27

First-generation antipsychotics (typical neuroleptics)

Discussion:
Dementia with Lewy bodies (DLB) is a progressive dementia syndrome characterised by
fluctuating cognition, parkinsonism and visual hallucinations. Nearly half of patients with DLB
exposed to neuroleptics such as haloperidol demonstrate severe reactions that include worsening
spontaneous parkinsonism, cognitive decline, drowsiness, and features of neuroleptic malignant
syndrome (NMS). Together, these sensitivity reactions carry a three-fold increase in mortality.
Conversely, cholinesterase inhibitors as well as nicotinic and muscarinic agonists are drug
therapeutics aimed to target cholinergic deficiency in Alzheimer’s and Lewy Body Dementia.
Similarly, NMDA-receptor antagonists are a class of drugs with treatment efficacy in Alzheimer’s
disease.
References:
Ballard C, Grace J, McKeith I, et al. Neuroleptic sensitivity in dementia with Lewy bodies and
Alzheimer’s disease. Lancet. 1998 Apr 4;351(9108):1032-3. Hershey LA, Coleman-Jackson R.
Pharmacological Management of Dementia with Lewy Bodies. Drugs Aging. 2019
Apr;36(4):309-319. doi: 10.1007/s40266-018-00636-7. PMID: 30680679; PMCID: PMC6435621.
Henriksen AL, St Dennis C, Setter SM, Tran JT. Dementia with lewy bodies: therapeutic
opportunities and pitfalls. Consult Pharm. 2006 Jul;21(7):563-75. doi: 10.4140/tcp.n.2006.563.
PMID: 16934009.

Question 28

A patient with a diagnosis of Parkinson disease comes to the clinic exhibiting dyskinetic
movements of the head and upper extremities while at rest in a chair. He reports that the
movements have steadily become more prominent over the past two years. Medications include
multivitamins and carbidopa-levodopa, which he has been taking for approximately six years.
Which of the following is the most likely cause of this patient’s dyskinetic movements?
Answers:
A. Levodopa
B. Progression of Parkinson’s Disease
C. Apomorphine
D. Aspirin
E. Multivitamin

Answer 28

Levodopa

Discussion:
Although levodopa is one of the most effective drugs in the treatment of Parkinson’s disease, longterm use is often complicated by significant disabling dyskinesias. Although the exact
pathogenesis of levodopa-induced dyskinesias (LID) is incompletely understood, animal models
suggest that pulsatile stimulation of postsynaptic receptors due to intermittent levodopa
administration leasd to a downstream cascade of protein and gene alterations in striatal output that
promotes dyskinesias.
References:
Zesiewicz TA, Sullivan KL, Hauser RA. Levodopa-induced dyskinesia in Parkinson’s disease:
epidemiology, etiology, and treatment. Curr Neurol Neurosci Rep. 2007 Jul;7(4):302-10. doi:
10.1007/s11910-007-0046-y. PMID: 17618536. Thanvi B, Lo N, Robinson T. Levodopa-induced
dyskinesia in Parkinson’s disease: clinical features, pathogenesis, prevention and treatment.
Postgrad Med J. 2007 Jun; 83(980):384-8. Vijayakumar D, Jankovic J. Drug-Induced Dyskinesia,
Part 1: Treatment of Levodopa-Induced Dyskinesia. Drugs. 2016 May;76(7):759-77. doi:
10.1007/s40265-016-0566-3. PMID: 27091215.

Question 29

A 25-year-old man is found unconscious in his family’s garage with a car’s engine still running. He
is hypotensive and tachycardic but responds to resuscitation maneuvers. Three days later, he is
poorly responsive and undergoes an MR image of the brain. Which of the following brain regions is
most likely to show localized injury on the MR image?
Answers:
A. thalamus
B. cerebellum
C. occipital lobe
D. pons
E. globus pallidus

Answer 29

globus pallidus

Discussion:
A typical characteristic of carbon monoxide poisoning is DWI restriction in the bilateral globus
pallidus on MRI of the brain. Although the exact correlation is unknown, it is hypothesized that the
GP is preferentially affected because it is an area that is easily affected due to poor anastomotic
blood supply or that CO may binds directly to heme iron in the GP, which happens to be a brain
region with high iron content. Additional areas in the basal ganglia can also be affected but the
most common finding is necrosis of the GP. Other radiological characteristics of CO poisoning
include demylination in the cortical white matter, including the corpus callosum, and atrophy of the
hippocampus.
References:
Hopkins RO, Fearing MA, Weaver LK, Foley JF. Basal ganglia lesions following carbon monoxide
poisoning. Brain Inj. 2006 Mar;20(3):273-81. doi: 10.1080/02699050500488181. PMID: 16537269.
Rose JJ, Wang L, Xu Q, McTiernan CF, Shiva S, Tejero J, Gladwin MT. Carbon Monoxide
Poisoning: Pathogenesis, Management, and Future Directions of Therapy. Am J Respir Crit Care
Med. 2017 Mar 1;195(5):596-606. doi: 10.1164/rccm.201606-1275CI. Erratum in: Am J Respir Crit
Care Med. 2017 Aug 1;196 (3):398-399. PMID: 27753502; PMCID: PMC5363978. Chapter 64:
Neurologic complications of carbon monoxide intoxication. In: Vodušek DB, Boller F, eds.
Handbook of Clinical Neurology. Vol. 120. Elsevier B.V.; 2014:971-977. Prockop LD, Chichkova RI.
Carbon monoxide intoxication: an updated review. J Neurol Sci. 2007 Nov 15;262(1-2):122-30. doi:
10.1016/j.jns.2007.06.037. Epub 2007 Aug 27. PMID: 17720201.

Question 30

Long-term use of proton pump inhibitors to decrease gastric acid production is associated with
which of the following serum deficiencies?
Answers:
A. Vitamin B6
B. Vitamin B12
C. Vitamin D
D. Vitamin B1
E. Vitamin A

Answer 30

Vitamin B12

Discussion:
Vitamin B12 deficiency is relativeVitamin B12 deficiency is relatively common in the elderly and
can lead to neurologic damage, anemia, dementia, and other complications. During digestion,
gastric acid is required for proteolytic cleavage of vitamin B12 from ingested dietary proteins.
Proton pump inhibitors and histamine 2 recepter antagonists suppress the production of gastric
acid and can lead to malabsorption of vitamine B12. Cyanocobalamin (B12) deficiency can cause
subacute combined degeneration of the spinal cord, which presents as peripheral neuropathy,
ataxia and spastic paraparesis.
Vitamin A is also absorbed in the intestinal lumen and deficiency can lead to vision problems.
Thiamine (Vitamin B1) is absorbed in the small intestine by passive diffusion and active transport;
deficiency causes Wernicke encephalopathy (lateral rectus palsy, ataxia, confusion) and Beriberi
(peripheral neuropathies, autonomic dysfunction and axonal degeneration).
Vitamin D is a fat-soluble vitamin absorbed in the small intestine and produced endogenously with
ultraviolet exposure to the skin.
Pyridoxine (B6) is absorbed in the jejunum by passive diffusion. B6 deficiency can be seen in
malabsorption syndromes such as ulcerative colitis, other genetic disorders such as
homocystinuria, and with medication usage (i.e. isoniazid).ly common in the elderly and can lead
to neurologic damage, anemia, dementia, and other complications. During digestion, gastric acid is
required for proteolytic cleavage of vitamin B12 from ingested dietary proteins. Proton pump
inhibitors and histamine 2 recepter antagonists suppress the production of gastric acid and can
lead to malabsorption of vitamine B12. Cyanocobalamin (B12) deficiency can cause subacute
combined degeneration of the spinal cord, which presents as peripheral neuropathy, ataxia and
spastic paraparesis.Vitamin A is also absorbed in the intestinal lumen and deficiency can lead to
visual deficiency. Thiamine (Vitamin B1) is absorbed in the small intestine by passive diffusion and
active transport; deficiency causes Wernicke encephalopathy (lateral rectus palsy, ataxia,
confusion) and Beriberi (peripheral neuropathies, autonomic dysfunction and axonal
degeneration). Vitamin D is a fat soluble vitamin absorbed in the small intestine and produced
endogenously with ultraviolet exposure to the skin. Pyridoxine (B6) is absorbed in the jejunum by
passive diffusion. B6 deficiency can be seen in malabsorption syndromes such as ulcerative colitis,
other genetic disorders such as homocystinuria, and with medication usage (i.e. isoniazid).
References:
Lam JR, Schneider JL, Zhao W, et al. Proton pump inhibitor and histamine 2 receptor antagonist
use and vitamin B12 deficiency. JAMA. 2013 Dec 11;310(22):2435-42. Miller JW. Proton Pump
Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications.
Adv Nutr. 2018 Jul 1;9(4):511S-518S. doi: 10.1093/advances/nmy023. PMID: 30032223; PMCID:
PMC6054240.

Question 31

A 23-year-old man with a history of depression and drug abuse is evaluated for agitation and a
confused state. Examination shows tachycardia, mydriasis, anhidrosis, and urinary retention. This
suggests intoxication with a drug with which of the following actions?
Answers:
A. Beta-adrenergic receptor blockade
B. Muscarinic receptor antagonist
C. GABA receptor agonist
D. Calcium-channel blockade
E. Opioid receptor antagonism

Answer 31

Muscarinic receptor antagonist

Discussion:
The anticholinergic toxidrome is characterized by dilated pupils (mydriasis), tachycardia, mentalstatus changes, anhidrosis, urinary retention, dry mouth, flushed skin, absent bowel sounds and
temperature elevations. The patient presents with concern for anticholinergic toxicity, indicating
overdose of a drug with muscarinic acetylcholine receptor antagonism. Pure anticholinergic toxicity
is often seen in antidepressant overdose, particularly with tricyclic antidepressants and
phenothiazines.
References:
Holstege CP, Borek HA. Toxidromes. Crit Care Clin. 2012 Oct;28(4):479-98. doi:
10.1016/j.ccc.2012.07.008. Epub 2012 Aug 27. PMID: 22998986. Benarroch EE. Basic
Neurosciences with Clinical Applications. Philadelphia: Butterworth Heinemann/Elsevier; 2006

Question 32

Which of the following findings is most likely in a patient with arsenic poisoning?
Answers:
A. choreiform movements
B. garlic odor breath
C. thin dark line around the gum margins
D. cherry red skin
E. deep horizontal ridges in the fingernails

Answer 32

garlic odor breath

Discussion:
Garlic odor breath is the most likely symptoms of arsenic poisoning among these answer choices.
Arsenic in gas form gives off this distinctive garlic odor which can often be smelled on the breath of
a patient with acute arsenic poisoning. Arsenic poisoning occurs most often through ingestion of
contaminated drinking water. Patients may also present with altered mental status, peripheral
neuropathy, QT-prolongation, and long-term exposure increases risk of several cancers including
lung cancer, squamous cell carcinoma, and hepatic angiosarcoma. Cherry red skin is classically
described in cyanide or CO poisoning. Burton’s lines present as darkening around the outline of
the gum and can be found in patients with lead poisoning. Nervous system involvment in arsenic
poisoning typically presents as a primarily sensory peripheral neuropathy, not choreiform
movements. Although arsenic can affect the fingernails, the description of deep horizontal ridges in
the fingernails is classic for Beau’s lines which can occur in a variety of illnesses. Mees lines,
which present as a white horizontal line across the nailbed without a palpable ridge, can be caused
by arsenic toxicity.
References:
Mochizuki H. Arsenic Neurotoxicity in Humans. Int J Mol Sci. 2019;20(14):3418. Published 2019
Jul 11. doi:10.3390/ijms20143418. Baker BA, Cassano VA, Murray C; ACOEM Task Force on
Arsenic Exposure. Arsenic Exposure, Assessment, Toxicity, Diagnosis, and Management:
Guidance for Occupational and Environmental Physicians. J Occup Environ Med. 2018
Dec;60(12):e634-e639. doi: 10.1097/JOM.0000000000001485. PMID: 30358658.

Question 33

The medication most commonly used for management of Ménière disease is an antagonist of
which of the following receptor types?
Answers:
A. serotonin receptors
B. histamine receptors
C. GABA receptors
D. NMDA receptors
E. acetylcholine receptors

Answer 33

histamine receptors

Discussion:
One of the most common drugs used to treat Menieres disease is betahistine which is an
antagonist of histamine H3 receptors. Its exact mechanism of action is unclear but a 2016
Cochrane review found that for patients with Meniere’s disease, the effect of betahistine was
stronger than placebo, with Menieres disease patients reporting a 56% reduction in vertigo when
taking betahistine as compared with placebo. The other main class of drugs used to treat Menieres
disease are diuretics. The most common diuretics used to treat Menieres disease are thiazides
with or without potassium-sparing diuretics such as hydrochlorothiazide/triamterene or
spironolactone as well as the carbonic anhydrase inhibitor acetazolamide as a second-line therapy.
References:
Basura GJ, Adams ME, Monfared A, Schwartz SR, Antonelli PJ, Burkard R, Bush ML, Bykowski J,
Colandrea M, Derebery J, Kelly EA, Kerber KA, Koopman CF, Kuch AA, Marcolini E, McKinnon BJ,
Ruckenstein MJ, Valenzuela CV, Vosooney A, Walsh SA, Nnacheta LC, Dhepyasuwan N,
Buchanan EM. Clinical Practice Guideline: Ménière’s Disease. Otolaryngol Head Neck Surg. 2020
Apr;162(2_suppl):S1-S55. doi: 10.1177/0194599820909438. PMID: 32267799. Scholtz AW, Hahn
A, Stefflova B, Medzhidieva D, Ryazantsev SV, Paschinin A, Kunelskaya N, Schumacher K,
Weisshaar G. Efficacy and Safety of a Fixed Combination of Cinnarizine 20 mg and
Dimenhydrinate 40 mg vs Betahistine Dihydrochloride 16 mg in Patients with Peripheral Vestibular
Vertigo: A Prospective, Multinational, Multicenter, Double-Blind, Randomized, Non-inferiority
Clinical Trial. Clin Drug Investig. 2019 Nov;39(11):1045-1056. doi: 10.1007/s40261-019-00858-6.
PMID: 31571128; PMCID: PMC6800407.

Question 34

Which of the following neuropathic pain medications works by inhibiting monoamine uptake?
Answers:
A. Gabapentin
B. Methocarbamol
C. Tizanidine
D. Pregabalin
E. Amitriptyline

Answer 34

Amitriptyline

Discussion:
Amitryptyline is a tricyclic antidepressant (TCA) which acts by blocking monoamine reuptake of
serotonin and norepinephrine. It remains a mainstay in pharmacological treatment of neuropathic
pain and demonstrates efficacy at lower doses in this setting than required in the treatment of
depression. Both gabapentin and pregabalin are utilized in the treatment of neuropathic pain but
act on the voltage-gated calcium channels in neurons. The exact mechanism of action of
methocarbamol is not established, however, it is postulated to inhibit synaptic acetylcholinesterase.
Tizanidine acts as a central alpha-2-adrenergic receptor agonist, thereby increasing presynaptic
inhibition of motor neurons.
References:
Mika J, Zychowska M, Makuch W, et al. Neuronal and immunological basis of action of
antidepressants in chronic pain - clinical and experimental studies. Pharmacol Rep.
2013;65(6):1611-21. Moore RA, Derry S, Aldington D, et al. Amitriptyline for neuropathic pain and
fibromyalgia in adults. Cochrane Database Syst Rev. 2012;12:CD008242

Question 35

In patients with antibiotic-associated encephalopathy, which of the following agents is most likely to
cause cerebellar dysfunction and focally abnormal MR imaging?
Answers:
A. Vancomycin
B. Bacitracin
C. Metronidazole
D. Gentamicin
E. Cefuroxime

Answer 35

Metronidazole

Discussion:
Metronidazole, utilized to treate a variety of protozoal and bacterial infections, can lead to central
nervous system toxicity in exceedingly rare cases. Toxicity presents as cerebellar dysfunction,
altered mental status or seizures and radiographic findings include bilateral T2-hypreintense signal
in the dentate nuclei, vestibular nuclei and tegmentum of the superior olivary nucleus. Antibioticassociated encephalopathy can be divided into 3 unique clinical phenotypes: encephalopathy
commonly accompanied by seizures or myoclonus arising within days after antibiotic
administration (caused by cephalosporins and penicillin); encephalopathy characterized by
psychosis arising within days of antibiotic administration (caused by quinolones, macrolides, and
procaine penicillin); and encephalopathy accompanied by cerebellar signs and MRI abnormalities
emerging weeks after initiation of antibiotics (caused by metronidazole).
References:
Bhattacharyya S, Darby RR, Raibagkar P, et al. Antibiotic-associated encephalopathy. Neurology.
2016 Mar 8;86(10):963-71. Bottenberg MM, Hegge KA, Eastman DK, Kumar R. Metronidazoleinduced encephalopathy: a case report and review of the literature. J Clin Pharmacol. 2011
Jan;51(1):112-6. doi: 10.1177/0091270010362905. Epub 2010 Mar 10. PMID: 20220041. Rizvi I,
Garg RK, Kumar N, Pandey S, Malhotra HS. Metronidazole-associated encephalopathy: a
reversible condition. Intern Emerg Med. 2018 Dec;13(8):1323-1325. doi:
10.1007/s11739-018-1904-0. Epub 2018 Jun 29. PMID: 29959650

Question 36

A 79-year-old man with hypertension, hepatitis C, and chronic liver dysfunction experiences three
focal seizures; two of the seizures were of the secondary generalized type. The seizures are
thought to be related to a previous hemispheric stroke. Which of the following is the most
appropriate antiepileptic medication to use in this patient?
Answers:
A. Phenytoin
B. Valproic Acid
C. Levetiracetam
D. Felbamate
E. Phenobarbital

Answer 36

Levetiracetam

Discussion:
Newer antiepileptic drugs without, or with minimal, hepatic metabolism, such as levetiracetam,
lacosamide, topiramate, gabapentin, and pregabalin should be used as first-line therapy.
Medications undergoing extensive hepatic metabolism, such as valproic acid, phenytoin, and
felbamate should be used as drugs of last resort. Other antiepileptic drugs, including
phenobarbital, benzodiazepines, and ethosuximide, have only rarely been linked to hepatotoxicity.
References:
Asconapé JJ. Use of antiepileptic drugs in hepatic and renal disease. Handb Clin Neurol.
2014;119:417-32. doi: 10.1016/B978-0-7020-4086-3.00027-8. PMID: 24365310. Carlson C,
Anderson CT. Special Issues in Epilepsy: The Elderly, the Immunocompromised, and Bone Health.
Continuum (Minneap Minn). 2016 Feb;22(1 Epilepsy):246-61. Vidaurre J, Gedela S, Yarosz S.
Antiepileptic Drugs and Liver Disease. Pediatr Neurol. 2017 Dec;77:23-36. doi:
10.1016/j.pediatrneurol.2017.09.013. Epub 2017 Sep 22. PMID: 29097018.

Question 37

Which of the following medications is most likely to cause idiopathic intracranial hypertension?
Answers:
A. Baclofen
B. Nimodipine
C. Minocycline
D. Carbidopa
E. Levetiracetem

Answer 37

Minocycline

Discussion:
Minocycline and other tetracyclines have been implicated in the development of intracranial
pressure that meets diagnostic criteria for idiopathic intracranial hypertension (IIH). The postulated
pathophysiology is that it elevates intracranial pressure by acting to reduce cerebrospinal fluid
absorption at the arachnoid villi.
References:
Orme DR, Vegunta S, Miller MA, Warner JEA, Bair C, McFadden M, Crum AV, Digre KB, Katz BJ.
A Comparison Between the Clinical Features of Pseudotumor Cerebri Secondary to Tetracyclines
and Idiopathic Intracranial Hypertension. Am J Ophthalmol. 2020 Dec;220:177-182. doi:
10.1016/j.ajo.2020.07.037. Epub 2020 Jul 30. PMID: 32738227.
Copy. Friedman DI. Pseudotumor cerebri. Neurosurg Clin N Am. 1999 Oct;10(4):609-21, viii. Jay
WM, Jay S. Benign intracranial hypertension with tetracycline therapy. J Pediatr. 1978
Nov;93(5):901-2. doi: 10.1016/s0022-3476(78)81136-6. PMID: 712516.

Question 38

Botulinum toxin exerts its effects at the
Answers:
A. Post-synaptic membrane of the neuromuscular junction
B. Synaptic cleft of the neuromuscular junction
C. Post-synaptic membrane of spinal inhibitory interneurons
D. Pre-synaptic membrane of the neuromuscular junction
E. Pre-synaptic membrane of spinal inhibitory interneurons

Answer 38

Pre-synaptic membrane of the neuromuscular junction

Discussion:
Botulinum toxin exerts effects at the presynaptic membrane of the neuromuscular junction through
binding and cleaving SNARE proteins thus preventing the release of acetylcholine at the NMJ,
causing a flaccid paralysis. Tetanus toxin is also endocytosed by the presynaptic motor neuron but
is transported retrograde to exert its effects at the presynaptic membrane of spinal inhibitory
interneurons which prevents inhibition of excitatory potentials thus resulting in a spastic paralysis.
References:
Goonetilleke A, Harris JB. Clostridial neurotoxins. J Neurol Neurosurg Psychiatry. 2004;75 Suppl
3(Suppl 3):iii35-iii39. doi:10.1136/jnnp.2004.046102. Montecucco C, Schiavo G. Structure and
function of tetanus and botulinum neurotoxins. Q Rev Biophys. 1995 Nov;28(4):423-72. doi:
10.1017/s0033583500003292. PMID: 8771234. Rossetto O, Seveso M, Caccin P, Schiavo G,
Montecucco C. Tetanus and botulinum neurotoxins: turning bad guys into good by research.
Toxicon. 2001 Jan;39(1):27-41. doi: 10.1016/s0041-0101(00)00163-x. PMID: 10936621