Neurobiology Flashcards
Histaminergic neurons are located in which of the following anatomic locations of the brain?
Answers:
A. Cerebellum
B. Supraoptic nucleus
C. Tuberomammilary nucleus of the posterior hypothalamus
D. Ventral posteriolateral nucleus
E. Lateral pulvinar nucleus
Tuberomammilary nucleus of the posterior hypothalamus
Discussion:
Histamine plays a role as a neuromodulator in several complex functions, including wakefulness,
feeding behavior, motivation and goal-directed behaviors. Despite broad projections throughout
the CNS, histaminergic neurons are located solely in the tuberomammillary nucleus of the
posterior hypothalamus. The thalamus is made predominantly of relay cells and interneurons.
The supraoptic nucleus is made of magnocellular neurosecretory cells that produce vasopressin.
There are five types of neurons in the cerebellum including Purkinje, basket, stellate and golgi cells
(inhibitory) and granule cells (excitatory).
References:
Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008
Jul;88(3):1183-241.
Hu W, Chen Z. The roles of histamine and its receptor ligands in central nervous system disorders:
An update. Pharmacol Ther. 2017 Jul;175:116-132. doi: 10.1016/j.pharmthera.2017.02.039. Epub
2017 Feb 20. PMID: 28223162
Myelin increases action potential velocity by increasing which of the following?
Answers:
A. Insulation
B. Sodium channel conductance
C. Resting potential
D. Capacitance
E. Passive current flow
Insulation
Discussion:
Increasing internal, cytoplasmic axon diameter is correlated with decreased internal resistance to
passive flow of current. Myelin decreases membrane capacitance by decreasing the charge stored
on both sides of the membrane. Sodium channels are present at the nodes of Ranvier allowing for
saltatory conduction, and the properties of the channel are not directly impacted by myelination.
The resting membrane potential of the neuron is ~-70mV and is not dependent on myelination.
Myelination increases insulation, or electrical resistance, preventing loss of ions across the axon
membrane, which is one of the contributors (along with decreased membrane capacitance) that
increase conduction velocity of myelinated neurons.
References:
Arundine M, Tymianski M. Molecular mechanisms of glutamate-dependent neurodegeneration in
ischemia and traumatic brain injury. Cell Mol Life Sci. 2004 Mar;61(6):657-68.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/15052409/
Schmidt H, Knosche TR. Action potential propagation and syncronisation in myelinated axons.
PLOS Comp Biol. 2019 Oct 17;15(10):e1007004.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/31622338/
Which of the following brain-stem regions has a high concentration of norepinephrine-containing
neurons, projects diffusely to the cortex, and is involved with the physiologic responses to stress
and panic?
Answers:
A. Dorsal motor nucleus of the vagus
B. Paraventricular nucleus
C. Locus coeruleus
D. Nucleus ambiguus
E. Edinger-Westphal nucleus
Locus coeruleus
Discussion:
The locus coeruleus, located near the pontomesencephalic junction, is the major noradrenergic
nucleus of the brain and plays a central role in the regulation of arousal and autonomic activity.
Activation of the locus coeruleus produces an increase in sympathetic activity and a decrease in
parasympathetic activity via numerous excitatory projections to the majority of the cerebral cortex
as well as the basal forebrain, thalamus, dorsal raphe, and spinal cord.
The dorsal motor nucleus of the vagus nerve receives afferent input from the GI tract, heart, and
bronchi of the lungs and receives indirect projections from the locus coeruleus. The locus
coeruleus also projects to other nuclei that influence the autonomic nervous system, including the
nucleus ambiguus, which is involved in the regulation of cardiovascular activity, and the EdingerWestphal nucleus, involved in pupillary constriction. The paraventricular nucleus of the
hypothalamus also receives projections from the locus coeruleus and contains oxytocin and
vasopressin neurosecretory cells that project to the posterior pituitary gland.
References:
Samuels ER, Szabadi E. Functional neuroanatomy of the noradrenergic locus coeruleus: its roles
in the regulation of arousal and autonomic function part I: principles of functional organisation. Curr
Neuropharmacol. 2008;6(3):235-253. doi:10.2174/157015908785777229.
Pubmed Web link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687936/
Benarroch EE. Locus coeruleus. Cell Tissue Res. 2018 Jul;373(1):221-232. doi:
10.1007/s00441-017-2649-1. Epub 2017 Jul 7. PMID: 28687925.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/28687925/
Suárez-Pereira I, Llorca-Torralba M, Bravo L, Camarena-Delgado C, Soriano-Mas C, Berrocoso E.
The Role of the Locus Coeruleus in Pain and Associated Stress-Related Disorders. Biol
Psychiatry. 2021 Dec 16:S0006-3223(21)01838-2. doi: 10.1016/j.biopsych.2021.11.023. Epub
ahead of print. PMID: 35164940.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/35164940/
Decerebrate rigidity in the primate results from transection of the brainstem
Answers:
A. Dorsal to the red nucleus
B. Ventral to the red nucleus
C. Lateral to the red nucleus
D. Caudal to the red nucleus
E. Rostral to the red nucleus
Caudal to the red nucleus
Discussion:
Decorticate and decerebrate rigidity are pathological posturing responses. Decorticate rigidity is
caused by a lesion rostral to the red nucleus at the intercollicular level, whereas decerebrate
rigidity is caused by a lesion caudal to the red nucleus. The mechanism for decorticate posturing is
not well elucidated. In primates, the rubrospinal tract influences primitive grasp reflexes. The
rubrospinal tract carries signals from the red nucleus to the spinal motor neurons and causes a
flexion, grasping type reflex of the upper extremities. The cerebral cortex inhibits that reflex
normally. Thus, transection of the brainstem rostral to the red nucleus causes disinhibition of that
reflex producing flexion of the upper limbs and extension of the lower limbs. Decerebrate posturing
has been shown in primates by transecting the brainstem at the intercollicular level (at or below the
level of the red nucleus). The vestibulospinal tract plays a major role in decerebrate posturing. The
vestibulospinal pathways have an excitatory effect on extensor motor neurons in the spine and an
inhibitory effect on flexor motor neurons. The vestibular nucleus, through the vestibulospinal tract,
produces activation of extensor motor neurons in the spinal cord and inhibition of flexor motor
neurons. However, in normal physiological conditions, the cerebral cortex and cerebellum inhibit
the vestibular nucleus and prevents this reflex. Decerebrate posturing results from a disconnection
between those higher modulatory centers and the vestibular nuclei, and results in unsuppressed
extensor posturing.
References:
Knight J, Decker LC. Decerebrate And Decorticate Posturing. [Updated 2021 Nov 30]. In:
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK559135/
Pubmed Web link: https://www.ncbi.nlm.nih.gov/books/NBK559135/
Whitney E, Alastra AJ. Neuroanatomy, Decerebrate Rigidity. 2021 Jul 31. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 31613467.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/31613467/
A 55-year-old woman is evaluated because of a three-week history of headache and complete left
abducens nerve palsy after undergoing a gross total resection of a single right frontal brain
metastasis nine months ago. A contrast-enhanced MR image shows stable postoperative changes
in the right frontal lobe. Which of the following is the most likely diagnosis?
Answers:
A. aseptic meningitis
B. Carcinomatous meningitis
C. intracranial hypertension
D. radiation necrosis
E. new brain metastases
Carcinomatous meningitis
Discussion:
Leptomeningeal carcinomatosis (LC) is defined as infiltration of the leptomeninges by metastatic
carcinoma, a relatively uncommon but devastating complication of many malignancies. Although
only 5% of patients with breast cancer develop leptomeningeal involvement, it remains the most
common etiology of LC. It can occur as a late-stage complication of systemic progression or
present as the first sign of metastatic disease, with or without parenchymal brain metastases.
Lobular carcinomas have a higher propensity to metastasize into the meninges when compared to
ductal carcinoma, especially the triple-negative subtype, which usually is associated with a shorter
interval between metastatic breast cancer diagnosis and the development of LC. Prognosis
remains poor, with median survival of 4 months for patients receiving state-of-the-art treatment.
Cranial nerve findings without evidence of mass lesions are commonly seen. New brain
metastases and radiation necrosis would usually demonstrate mass lesions on MRI in the tumor
bed or elsewhere.
References:
Franzoi MA, Hortobagyi GN. Leptomeningeal carcinomatosis in patients with breast cancer. Crit
Rev Oncol Hematol. 2019 Mar;135:85-94. doi: 10.1016/j.critrevonc.2019.01.020. Epub 2019 Feb
1. PMID: 30819451.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/30819451/
Van Horn A, Chamberlain MC. Neoplastic meningitis. J Support Oncol. 2012 Mar-Apr;10(2):45-53.
doi: 10.1016/j.suponc.2011.06.002. Epub 2011 Sep 23. PMID: 22005214.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/22005214/
Chamberlain MC. Neoplastic meningitis. Oncologist. 2008 Sep;13(9):967-77. doi:
10.1634/theoncologist.2008-0138. Epub 2008 Sep 5. PMID: 18776058.
PubMed Web Link: https://pubmed.ncbi.nlm.nih.gov/18776058/
Fast antegrade axonal transport is dependent upon adenosine triphosphate and which of the
following proteins?
Answers:
A. Protein C
B. microtubules
C. Kinesin
D. neurofilaments
E. dynein
Kinesin
Discussion:
Anterograde and retrograde transport of cellular cargo depend on molecular motors, such as
kinesin and dynein, that move along microtubules. Anterograde axonal transport uses kinesin as a
protein motor. They can move cargo such as vesicles synthesized in the endoplasmic reticulum.
Retrograde axonal transport uses dynein as a protein motor. Retrograde transport means moving
cargo towards the minus end of the microtubule.
Neurofilaments are present in the cytoplasm of neurons as part of the cytoskeleton.
Neurofilaments play a key structural role in axons. Protein C is involved in the coagulation
cascade.
References:
Kandel ER, Schwartz JH. Principles of Neural Science. 4th ed. McGraw-Hill Medical, 2000:
99-103.
Maday S, Twelvetrees AE, Moughamian AJ, Holzbaur EL. Axonal transport: cargo-specific
mechanisms of motility and regulation. Neuron. 2014;84(2):292-309.
doi:10.1016/j.neuron.2014.10.019
NMDA receptor depolarization by glutamate involves displacement of which of the following ions
from the receptor?
Answers:
A. Na+
B. Ca2+
C. K+
D. Cl-
E. Mg2+
Mg2+
Discussion:
NMDA receptors, a glutamate receptor, responds to glutamate binding by allowing flow of Na+, K+,
and Ca2+. This requires first a significant depolarization that releases the Mg2+ ion from the pore
of the channel. However, with excessive glutamate binding, excitotoxicity occurs leading to an
increased influx of Ca2+ and neuronal damage. Memantine, a glutamatergic NMDA receptor
antagonist, acts in a manner that mimics the action of Mg2+. Cl- can act as a modifier in NMDA
receptor activity.
References:
NMDA receptor complex. Scatton, B. Fundam Clin Pharmacol . 1993;7(8):389-400.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/8294079/
Long-term synaptic potentiation. Brown TH, Chapman PF, Kairliss EW, Keenan CL. Science. 1988
Nov 4;242(4879):724-8.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/2903551/
Biology of the NMDA Receptor. Chapter 13. Van Dongen AM, Ed. Boca Raton (FL): CRC
Press/Taylor & Francis; 2009
Which of the following is the major inhibitory neurotransmitter of the brain?
Answers:
A. Norepinephrine
B. Epinephrine
C. Acetylcholine
D. GABA
E. Glutamate
GABA
Discussion:
GABA is the major inhibitory neurotransmitter in the brain. It functions to reduce neuronal
excitability in the following manner. GABA works through both ionotropic receptors (GABAA and
GABAC receptors) which are pentameric transmitter gated Cl- channels. GABAB receptors are
metabotropic inhibitory receptors. Binding of a GABA molecule stimulates a second messenger
system via phospholipase C and adenylyl cyclase that lead to slow opening of K channels or
inhibition of Ca2+ channels.
Glutamate is the principal excitatory neurotransmitter in the central nervous system (CNS) and
works on NMDA, AMPA, kainite, and G protein-linked receptors. Acetylcholine has several roles in
the brain and other organs. It is present in junctions between neurons and other types of cells
such as myocytes and cells in glandular tissue. Norepinephrine and epinephrine are
neurotransmitters used in the autonomic nervous system.
References:
Mordecai P. Blaustein MD , Joseph P.Y. Kao PhD and Donald R. Matteson PhD. Synaptic
physiology II. Cellular Physiology and Neurophysiology, 13, 160-184
M. Neal Waxham. Neurotransmitter Receptors. Fundamental Neuroscience, Chapter 8, 163-187.
Allen MJ, Sabir S, Sharma S. GABA Receptor. [Updated 2022 Feb 17]. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
Pubmed Link: https://www.ncbi.nlm.nih.gov/books/NBK526124/
The end product of dopamine metabolism is:
Answers:
A. Tyrosine
B. Norepinephrine
C. Vanillomandelic acid (VMA)
D. Homovanillic acid
E. Epinephrine
Homovanillic acid
Discussion:
Tyrosine is a precursor to dopamine through the action of tyrosine hydroxylase, which generates
L-DOPA. Vanillomandelic acid (VMA) is the major metabolite of norepinephrine metabolism.
Dopamine is a precursor to epinephrine and norepinephrine. Methylation of DOPAC, a degradation
product of dopamine by MAO, yields HVA, the primary end product of dopamine metabolism.
References:
Meiser J, Weindl D, Hiller K. Complexity of dopamine metabolism. Cell Commun Scignal. 2013
May 17;11(1):34.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/23683503/
Jenner WN, Rose FA. Dopamine 3-O-supphate, an end product of L-dopa metabolism in
Parkinson patients. Nature. 1974 Nov 15;252(5480):237-8.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/4422149/
Which of the following is the predominant form of neuronal cell death in chronic neurodegenerative
diseases?
Answers:
A. Autophagy
B. Pyroptosis
C. Non-programmed necrosis
D. Oncosis
E. Apoptosis
Apoptosis
Discussion:
In neurodegenerative diseases, apoptosis is believed to be the major death pathway for neurons.
Apoptosis is a type of programmed cell death. The cytomorphological features of an apoptotic cell
include shrinkage, chromosome condensation and DNA fragmentation. During this process,
apoptotic bodies eventually form in many cases and cellular contents generally do not leak out,
which is believed to minimize the eliciting of immunological responses. Pyroptosis is the highly
inflammatory process of lytic, programmed cell death. Oncosis is a non-apoptotic (nonprogrammed) form of cell death. It occurs in response to cell membrane damage and results from
sharp rise in intracellular Ca2+ followed by water and ions, swelling, and eventual rupture.
Autophagy is the process a cell takes to remove dysfunctional components through its lysosome.
References:
Chi H, Chang HY, Sang TK. Neuronal cell death mechanisms in major neurodegenerative
diseases. Int J Mol Sci. 2018;19(10):E3082.
Pubmed Link: https://pubmed.ncbi.nlm.nih.gov/30304824/
Wang Y, Qin ZH. Molecular and cellular mechanisms of excitotoxic neuronal death. Apoptosis.
2010;15(11):1382-1402.
Conduction velocity along an axon is accelerated by…
Answers:
A. Voltage-gated ion channels
B. Decrease axon diameter
C. Increase axon diameter
D. Demyelination
E. Decrease number of Nodes of Ranvier
Increase axon diameter
Discussion:
Strategies for increasing conduction velocity of nerve fibers include increasing the diameter of the
axon core and myelination of the axon. Nerve conduction in myelinated axons is referred to as
saltatory conduction due to the manner in which the action potential jumps from one node to the
next. Nodes of Ranvier increase speed of conduction in this manner. Together, increased
diameter, myelination, and Nodes of Ranvier results in faster conduction of the action potential.
References:
LaMantia, Anthony-Samuel, et al. Neuroscience. United Kingdom, Oxford University Press,
Incorporated, 2012
A 42-year-old man is brought to the emergency department because of the sudden onset of
syncope. On arrival, he is hoarse, with palatal deviation to the right and a decreased gag
response. The involved anatomic structures are most likely localized to which of the following
regions of the brain?
Answers:
A. Internal Capsule
B. Foramen of Monro
C. Midbrain
D. Thalamus
E. Medulla
Medulla
Discussion:
The nuclei of cranial nerves IX and X are located in the medulla. The caudal portion of the nucleus
tractus solitarius (NTS) has a role in cardiovascular, respiratory, and gastrointestinal system control
through baroreceptors and chemoreceptors in the carotid body (cranial nerve IX), as well as the
aortic arch (cranial nerve X), and an insult to the NTS could result in the sudden onset syncope the
patient experienced if there was an acute drop in blood pressure. An injury to the vagus nerve
distal to the takeoff of the pharyngeal branches or a lesion of the recurrent laryngeal nerve will
present with hoarseness due to ipsilateral vocal fold paralysis. A more proximal vagal nerve lesion
that damages the pharyngeal branch of the vagus nerve will cause deviation of the uvula to the
contralateral side. The nucleus ambiguus in the upper medulla is a motor nucleus that supplies the
striated muscles of the pharynx, larynx, and upper esophagus via cranial nerves IX, X, and XI and
helps to coordinate swallowing, gagging, and coughing. The other anatomic structures listed would
not be expected to explain the constellation of symptoms this patient is experiencing.
References:
Basinger H, Hogg JP. Neuroanatomy, Brainstem. 2021 May 8. In: StatPearls [Internet]. Treasure
Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 31335017.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/31335017/
Iordanova R, Reddivari AKR. Neuroanatomy, Medulla Oblongata. 2021 Jul 31. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 31869070.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/31869070/
Angeles Fernández-Gil M, Palacios-Bote R, Leo-Barahona M, Mora-Encinas JP. Anatomy of the
brainstem: a gaze into the stem of life. Semin Ultrasound CT MR. 2010 Jun;31(3):196-219. doi:
10.1053/j.sult.2010.03.006. PMID: 20483389.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/20483389/
An 8-year-old boy is evaluated because of the inability to walk. At 4 years of age, he had
progressive difficulty with walking and climbing stairs and a waddling gait. Current examination
shows weakness in all limbs, proximally more than distally. Sensory examination shows no
abnormalities. Which of the following is the most likely diagnosis?
Answers:
A. McArdle’s disease
B. Myotonic dystrophy
C. Becker’s muscular dystrophy
D. Duchenne muscular dystrophy
E. Fasciculohumeral dystrophy
Duchenne muscular dystrophy
Discussion:
Duchenne’s muscular dystrophy (DMD) is the most common type of muscular dystrophy. While it is
mostly a male-predominant and X-linked recessive disease, 30% of cases occur as a result of
spontaneous mutations in the DMD gene which lead to absent dystrophin. The peak age of onset
is between 2–5 years, after which there is rapid disease progression including to atrophy of the
shoulder and pelvic girdles as well as pseudohypertrophy of the calves due to fatty and fibrous
replacement. As a result of the severe atrophy, patients often are seen using the Gower maneuver
to stand and develop a waddling gait. In addition to these physical limitations, patients have
chronic respiratory insufficiency and may develop cardiomyopathy. Serum creatine kinase (CK)
levels are significantly elevated. Muscle biopsy demonstrates muscle fiber necrosis and
regeneration. Life expectancy is about 28 years.
Becker’s MD is a clinically less severe form of dystrophy compared to Duchenne’s MD. It is also a
male-predominant X-linked recessive disease, however there is abnormal dystrophin as opposed
to absent. Clinically, patients also have muscle pseudohypertrophy, however they do not have
muscle fiber necrosis or regeneration. Serum CK is elevated, but not as significant as those with
DMD. Similar to DMD, patients are non-ambulatory at a young age, however their life expectancy
is nearly twice as long.
Facioscapulohumeral dystrophy is characterized by involvement of the face, shoulder, and upper
arms. It is milder than DMD or Becker’s MD and may have preservation of the forearm
musculature, resulting in a classic “Popeye” appearance. There are no associated symptoms such
as pseudohypertrophy, cognitive delay, or CHF, though patients may exhibit sensorineural hearing
loss. There is no fiber necrosis or regeneration, and the serum CK is normal.
Myotonic dystrophy is the most common muscular dystrophy caused by a trinucleotide repeat on
chromosome 19. It is inherited in an autosomal dominant fashion and patients often present with
facial then distal extremity weakness or myotonia. Patients may also exhibit cardiac dysrhythmias,
cognitive delay, cataracts (90%), endocrine dysfunction, temporalis and masseter atrophy, and
frontal balding.
Metabolic myopathies typically involve the proximal lower limbs, and unlike facioscapulohumeral or
myotonic dystrophy, rarely involve the face and eyes. McArdle’s disease has an autosomal
recessive inheritance pattern with myophosphorylase deficiency. Patients are only symptomatic
during increased activity, which often manifests as cramp-like pains with myalgias, increased CK,
and myoglobinuria.
References:
Citow Comprehensive Neurosurgery Board Review 3rd Ed. 2019, p340-341
Yiu EM, Kornberg AJ. Duchenne muscular dystrophy. J Paediatr Child Health. 2015
Aug;51(8):759-64. doi: 10.1111/jpc.12868. Epub 2015 Mar 9. PMID: 25752877.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/25752877
Broomfield J, Hill M, Guglieri M, Crowther M, Abrams K. Life Expectancy in Duchenne Muscular
Dystrophy: Reproduced Individual Patient Data Meta-analysis. Neurology. 2021 Dec
7;97(23):e2304-e2314. doi: 10.1212/WNL.0000000000012910. Epub 2021 Oct 13. PMID:
34645707; PMCID: PMC8665435.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/34645707
Which of the following medications has demonstrated effectiveness in extending life expectancy in
patients with amyotrophic lateral sclerosis?
Answers:
A. Edaravone
B. Riluzole
C. Bevacizumab
D. Idarucizumab
E. IVIg
Riluzole
Discussion:
Amyotrophic lateral sclerosis (ALS) is progressive motor neuron disease with a median survival of
2-3 years following initial symptom onset. Characterization of the disease is variable due to a
number of different genotypes and phenotypes. Typically, there is sporadic inheritance, however
there are also genetic variants such as an autosomal dominant inherited form of superoxide
dismutase 1 (SOD1) mutation that is linked to a rapidly progressive phenotype in the USA. ALS
often manifests with insidious asymmetric weakness in a single limb. Neuronal denervation is
manifested as atrophy and fasciculations in the hands, and can often be seen in the bulbar
muscles leading to impairment in facial and tongue movements as well as swallowing and
chewing. Definitive diagnosis includes EMG/NCS which demonstrate both fasciculations and
fibrillations. Due to notable corticospinal involvement, there is significant spasticity as well as
hyperreflexia. Eventually, there is development of the hallmark feature of the loss of both upper
and lower motor neuron function. It should be noted that sensory changes are absent, as
degeneration is limited to the lateral corticospinal tract, preserving the dorsal columns and
spinothalamic tract. Histological examination demonstrates this degeneration of the lateral
corticospinal tracts and the anterior horn of the spinal cord, as well as Bunina bodies.
Riluzole (Rilutek) is a glutamatergic neurotransmission inhibitor and is the only drug approved by
the USA Food and Drug Administration for ALS treatment with modest benefits on survival.
Riluzole may increase median survival by about 2-3 months in patients with ALS.
Edaravone (Radacava) is a neuroprotective antioxidant that reduces motor neuron death in ALS
patients. Studies have shown it may delay physical deterioration in ALS patients by 33% compared
to placebo.
Bevacizumab (Avastin) is an anti-angiogenesis agent that binds to vascular endothelial growth
factor A (VEGF-A) to prevent interaction with endothelial cell surface receptors, hence reducing
vascular growth of tumors. Bevacizumab has been shown to inhibit the growth of human tumor cell
lines, including GBM in mice.
Idarucizumab (Praxbind) is a reversal agent for dabigatran (Pradaxa). It is a monoclonal antibody
fragment that binds Pradaxa with an affinity significantly higher than that of dabigatran-thrombin.
IVIg therapy may be used in the treatment of ALS, however there are no controlled studies which
demonstrate a reduction in disease progression or increase in life expectancy.
References:
Al-Chalabi, A., Hardiman, O. The epidemiology of ALS: a conspiracy of genes, environment and
time. Nat Rev Neurol 9, 617–628 (2013). https://doi.org/10.1038/nrneurol.2013.203
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/24126629
Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron
disease (MND). Cochrane Database Syst Rev. 2012 Mar 14;2012(3):CD001447. doi:
10.1002/14651858.CD001447.pub3. PMID: 22419278; PMCID: PMC7055506.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/22419278/
Bhandari R, Kuhad A, Kuhad A. Edaravone: a new hope for deadly amyotrophic lateral sclerosis.
Drugs Today (Barc). 2018 Jun;54(6):349-360. doi: 10.1358/dot.2018.54.6.2828189. PMID:
29998226.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/29998226/
Which of the following ocular findings is most associated with tuberous sclerosis?
Answers:
A. Kayser-Fleischer ring
B. Optic glioma
C. Retinal hamartoma
D. Peripheral vision loss
E. Acute unilateral vision loss
Retinal hamartoma
Discussion:
Tuberous Sclerosis Complex (TSC) is a phakomatosis which is typically transmitted in an
autosomal dominant fashion due to a sporadic mutation on chromosome 9 (TSC1, hamartin) or 16
(TSC2, tuberin). A definitive diagnosis includes either a pathogenic mutation for TSC, or fulfillment
of the clinical diagnostic criteria. Clinical diagnosis of TSC includes either two major features or
one major feature with at least 2 minor features. Major features include: hypomelanotic macules
(≥3, at least 5-mm diameter), angiofibromas (≥3) or fibrous cephalic plaque, ungual fibromas (≥2),
shagreen patch, multiple retinal hamartomas, cortical dysplasias, subependymal nodules,
subependymal giant cell astrocytoma, cardiac rhabdomyoma, lymphangioleiomyomatosis, and
angiomyolipomas (≥2). Minor features include: “confetti” skin lesions, dental enamel pits (>3),
intraoral fibromas (≥2), retinal achromic patch, multiple renal cysts, and nonrenal hamartomas.
Kayser-Fleisher rings are copper deposits in the cornea associated with Wilson’s disease.
Optic gliomas are low grade gliomas that may be associated with neurofibromatosis-1 (NF1),
particularly when bilateral. The peak age for onset is 3–5 years with a female predominance.
Peripheral vision loss typically occurs with lesions of the optic chiasm. Retinal hamartomas rarely
affect vision.
Acute unilateral vision loss is often due to central retinal artery occlusion. Risk factors include
hypertension, diabetes, and age. This is not typically associated with tuberous sclerosis.
References:
Citow Comprehensive Neurosurgery Board Review 3rd Ed. 2019, p268
Hodgson N, Kinori M, Goldbaum MH, Robbins SL. Ophthalmic manifestations of tuberous
sclerosis: a review. Clin Exp Ophthalmol. 2017 Jan;45(1):81-86. doi: 10.1111/ceo.12806. Epub
2016 Sep 15. PMID: 27447981.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/27447981/
Northrup H, Krueger DA; International Tuberous Sclerosis Complex Consensus Group. Tuberous
sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous
Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013 Oct;49(4):243-54. doi:
10.1016/j.pediatrneurol.2013.08.001. PMID: 24053982; PMCID: PMC4080684.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/24053982
A 25-year-old woman is evaluated because of complaints of horizontal diplopia. On
ophthalmic examination, she is found to have normal straight and leftward gaze. With right gaze,
she has impaired left eye adduction and horizontal nystagmus of the right eye. These findings are
most likely caused by which of the following?
Answers:
A. One and a half syndrome
B. Internuclear ophthalmoplegia
C. Optic neuritis
D. Horner’s Syndrome
E. Cranial nerve VI palsy
Internuclear ophthalmoplegia
Discussion:
Internuclear ophthalmoplegia (INO) is caused by a lesion of the medial longitudinal fasciculus, a
paired white matter tract that passes through the brainstem in the midline ventral to the cerebral
aqueduct and the 4th ventricle. This syndrome is characterized by impaired adduction of the
ipsilateral eye with nystagmus of the abducting eye. The MLF forms a connection between all of
the ocular motor nuclei and plays a crucial role in saccadic eye movements. Saccades are initiated
by the frontal eye fields, pass through the contralateral paramedian pontine reticular formation
(PPRF) and then through the MLF. The impaired adduction on the same side as the MLF lesion
that is a hallmark of an INO is due to the fact that excitatory neurons from the abducens nucleus
fail to reach the medial rectus muscle. Causes of an INO include trauma, infection, neoplasm,
vasculitis, infarction, and brainstem hemorrhage.
A lesion involving both the PPRF and the MLF causes a “one and a half syndrome”, whereby all
horizontal eye movements are lost except abduction in the contralateral eye. A cranial nerve VI
palsy causes an ipsilateral lateral rectus palsy characterized by unilateral impaired abduction, and
can be caused by neoplasm, vascular disease, or trauma with elevated intracranial pressures.
Horner’s syndrome is characterized by ptosis, miosis, and anhidrosis on the affected side and
results from disruption of the sympathetic nerve supply to the eye. This can be caused by a carotid
artery dissection, a tumor of the neck or chest cavity, or a lesion in the midbrain or orbit. Optic
neuritis is inflammation of the optic nerves secondary to autoimmune, demyelinating, infectious, or
paraneoplastic causes. Optic neuritis typically presents as acute, unilateral, painful vision loss.
References:
Wilhelm H. Disorders of the pupil. Handb Clin Neurol. 2011;102:427-66. doi:
10.1016/B978-0-444-52903-9.00022-4. PMID: 21601076.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/21601076/
Kochar PS, Kumar Y, Sharma P, Kumar V, Gupta N, Goyal P. Isolated medial longitudinal
fasciculus syndrome: Review of imaging, anatomy, pathophysiology and differential diagnosis.
Neuroradiol J. 2018 Feb;31(1):95-99. doi: 10.1177/1971400917700671. Epub 2017 May 25. PMID:
28541157; PMCID: PMC5789990.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/28541157/
Frohman TC, Galetta S, Fox R, Solomon D, Straumann D, Filippi M, Zee D, Frohman EM. Pearls &
Oy-sters: The medial longitudinal fasciculus in ocular motor physiology. Neurology. 2008 Apr
22;70(17):e57-67. doi: 10.1212/01.wnl.0000310640.37810.b3. PMID: 18427066.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/18427066/
Which of the following is the only afferent tract in the superior cerebellar peduncle?
Answers:
A. Corticopontine tract
B. Ventral (anterior) spino-cerebellar tract
C. Olivo-cerebellar tract
D. Cuneo-cerebellar tract
E. Dorsal (posterior) spinocerebellar tract
Ventral (anterior) spino-cerebellar tract
Discussion:
The superior cerebellar peduncle contains one afferent tract, the ventral (anterior) spino-cerebellar
tract, which conveys proprioceptive information from the ipsilateral lower limb. These fibers
decussate in the spinal cord, ascend, enter the cerebellum via the superior cerebellar peduncle,
and cross again, thus terminating on the ipsilateral side from which the fibers originated. The
dorsal (posterior) spinocerebellar tract, cuneo-cerebellar tract, and olivo-cerebellar tract all carry
information to the cerebellum via the inferior cerebellar peduncle. The dorsal (posterior)
spinocerebellar tract carries proprioceptive information from muscle spindles and relay in the
dorsal nucleus of Clarke in the spinal cord. The fibers ascend ipsilaterally along the lateral aspect
of the cord and do not decussate. The cuneo-cerebellar tract is the homologous tract for the upper
limb and relays in the accessory (external) cuneate nucleus in the lower medulla. The olivocerebellar tract originates in the inferior olivary nucleus, decussates in the medulla, and terminates
in the contralateral cerebellum. Those axons are comprised of climbing fibers to the main dendritic
branches of the Purkinje neurons. The cortico-pontine tract is a large group of fibers that descend
via the internal capsule, enter the brainstem by way of the cerebral peduncle, decussate at the
level of the pons and pass through the middle cerebellar peduncle to enter the cerebellum in order
to provide cortical information relevant to motor commands and planned motor activities.
References:
Brogna C, Lavrador JP, Kandeel HS, Beyh A, Ribas EC, Vergani F, Tolias CM. Medial-tonsillar
telovelar approach for resection of a superior medullary velum cerebral cavernous malformation:
anatomical and tractography study of the surgical approach and functional implications. Acta
Neurochir (Wien). 2021 Mar;163(3):625-633. doi: 10.1007/s00701-020-04418-2. Epub 2020 Jun
10. PMID: 32524247.
Pubmed Web link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886669/
Rahimi-Balaei M, Afsharinezhad P, Bailey K, Buchok M, Yeganeh B, Marzban H. Embryonic stages
in cerebellar afferent development. Cerebellum Ataxias. 2015 Jun 11;2:7. doi:
10.1186/s40673-015-0026-y. PMID: 26331050; PMCID: PMC4552263.
Pubmed Web link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552263/
Keser Z, Hasan KM, Mwangi BI, Kamali A, Ucisik-Keser FE, Riascos RF, Yozbatiran N, Francisco
GE, Narayana PA. Diffusion tensor imaging of the human cerebellar pathways and their interplay
with cerebral macrostructure. Front Neuroanat. 2015 Apr 8;9:41. doi: 10.3389/fnana.2015.00041.
PMID: 25904851; PMCID: PMC4389543.
Pubmed Web link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389543/
In the intraoperative view of the fourth ventricle shown, which of the following structures is
indicated by the arrow?
Answers:
A. Obex
B. Foramina of Luschka
C. Area postrema
D. Stria Medullaris
E. Facial colliculus
Stria Medullaris
Discussion:
The stria medullaris white matter fibers are derived from axons from the arcuate nucleus. The stria
medullaris emerge from the median sulcus and run in a transverse direction across the floor of the
4
th ventricle to enter into the inferior cerebellar peduncles. The stria medullaris forms a portion of
the cochlear division of the vestibulocochlear nerve.
The facial colliculus is found lateral to the median sulcus in the 4th ventricle and contains branchial
motor nerve fibers of cranial nerve VII. The area postrema is one of the chemoreceptor trigger
zones and lies in the caudal 4th ventricular floor just rostral to the obex, the inferior point of the
floor of the 4th ventricle. The foramina of Luschka are located at the superolateral portion of the 4th
ventricle bilaterally and aid in CSF drainage.
References:
Roesch ZK, Tadi P. Neuroanatomy, Fourth Ventricle. [Updated 2021 Aug 11]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
Pubmed Web link: https://www.ncbi.nlm.nih.gov/books/NBK546577/
Mercier P, Bernard F, Delion M. Microsurgical anatomy of the fourth ventricle. Neurochirurgie. 2021
Feb;67(1):14-22. doi: 10.1016/j.neuchi.2018.04.010. Epub 2018 Jun 3. PMID: 29875069.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/29875069/
Longatti P, Fiorindi A, Feletti A, D’Avella D, Martinuzzi A. Endoscopic anatomy of the fourth
ventricle. J Neurosurg. 2008 Sep;109(3):530-5. doi: 10.3171/JNS/2008/109/9/0530. PMID:
18759587.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/18759587/
The dentatothalamic tract decussates in which of the following locations?
Answers:
A. Red nucleus
B. Midbrain
C. Superior cerebellar peduncle
D. Dentate nucleus
E. Ventral lateral nucleus of the thalamus
Midbrain
Discussion:
The dentatothalamic tract is the major efferent pathway arising from the dentate nucleus in the
cerebellum. Utilizing the dentatothalamic tract, the dentate nucleus sends output signals via the
ipsilateral superior cerebellar peduncle prior to decussating in the midbrain tegmentum and
synapsing in the contralateral red nucleus and ventral lateral nucleus of the thalamus. Efferent
fibers from the dentate nucleus are involved in the modulation of motor neurons as well as neurons
involved in conscious thought and visuospatial function. An injury to the dentatothalamic tract,
such as that caused by a cerebellar infarct, can result in severe ataxia.
References:
Petersen KJ, Reid JA, Chakravorti S, Juttukonda MR, Franco G, Trujillo P, Stark AJ, Dawant BM,
Donahue MJ, Claassen DO. Structural and functional connectivity of the nondecussating dentatorubro-thalamic tract. Neuroimage. 2018 Aug 1;176:364-371. doi:
10.1016/j.neuroimage.2018.04.074. Epub 2018 May 4. PMID: 29733955; PMCID: PMC6002752.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/29733955/
Meola A, Comert A, Yeh FC, Sivakanthan S, Fernandez-Miranda JC. The nondecussating pathway
of the dentatorubrothalamic tract in humans: human connectome-based tractographic study and
microdissection validation. J Neurosurg. 2016 May;124(5):1406-12. doi:
10.3171/2015.4.JNS142741. Epub 2015 Oct 9. PMID: 26452117.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/26452117/
de Leon AS, M Das J. Neuroanatomy, Dentate Nucleus. [Updated 2021 Jul 31]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
Pubmed Web link: https://www.ncbi.nlm.nih.gov/books/NBK554381
Geniculate ganglia project to which of the following nuclei?
Answers:
A. Gustatory Nucleus
B. Vestibular nuclei
C. Abducens nucleus
D. Inferior salivary nucleus
E. Dorsal motor nucleus
Gustatory Nucleus
Discussion:
The geniculate ganglion is a sensory ganglion of cranial nerve VII, and contains the cell bodies of
fibers responsible for conducting taste sensation from the anterior 2/3 of the tongue. The
geniculate ganglion also contributes to sensory innervation of the palate, pinna, and ear canal.
Nerve fibers running from the tongue through the chorda tympani merge with the facial nerve and
pass through the geniculate ganglion before entering the nervus intermedius and synapsing within
the gustatory nucleus in the pontine tegmentum.
The abducens nucleus is a motor nucleus located just ventral to the floor of the 4th ventricle. It
provides innervation to the lateral rectus muscle of the eye, which is responsible for abduction. The
vestibular nuclei are located along the lateral portion of the 4th ventricle in the pons and are
responsible for balance. The dorsal motor nucleus of the vagus nerve receives afferent input from
the GI tract, heart, and bronchi of the lungs. The inferior salivary nucleus contains postganglionic
parasympathetic fibers of cranial nerve IX that serve to innervate the parotid gland.
References:
Dulak D, Naqvi IA. Neuroanatomy, Cranial Nerve 7 (Facial). 2021 Jul 31. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 30252375.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/30252375/
Basinger H, Hogg JP. Neuroanatomy, Brainstem. [Updated 2021 May 8]. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
Pubmed Web link: https://www.ncbi.nlm.nih.gov/books/NBK544297/
Myckatyn TM, Mackinnon SE. A review of facial nerve anatomy. Semin Plast Surg. 2004
Feb;18(1):5-12. doi: 10.1055/s-2004-823118. PMID: 20574465; PMCID: PMC2884691.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/20574465/
A 32-year-old woman presents to the clinic for evaluation of leg weakness. She says she has
noticed recent intermittent blurriness of vision with mild slurred speech in the late afternoon.
Ophthalmic examination shows normal pupillary responses to light and accommodation. Which of
the following subsequent tests is most likely to yield the correct diagnosis?
Answers:
A. Lumbar Puncture
B. Electromyography
C. CT chest
D. brain biopsy
E. brain MRI
Electromyography
Discussion:
Based on question stem history, the patient appears to have myasthenia gravis. Single-fiber
electromyography has the highest sensitivity (90%). It has proved to be the most sensitive
technique in detecting a neuromuscular transmission defect in comparison with the tensilon test,
repetitive stimulation, and acetylcholine receptor antibody estimation. Tests for serum antibodies
are highly specific but lack sensitivity when there is pure ocular involvement. A lumbar puncture,
brain MRI, and brain biopsy are unlikely to reveal a diagnosis of myasthenia gravis. Computed
tomography of the chest is usually ordered to rule out thymoma once a diagnosis of myasthenia
gravis has been confirmed.
References:
Bourque PR, Breiner A. Myasthenia gravis. CMAJ. 2018 Sep 24;190(38):E1141. doi:
10.1503/cmaj.180656. PMID: 30249760; PMCID: PMC6157498.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/30249760/
Morrison BM. Neuromuscular Diseases. Semin Neurol. 2016 Oct;36(5):409-418. doi: 10.1055/s0036-1586263. Epub 2016 Sep 23. PMID: 27704495.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/27704495/
Sieb JP. Myasthenia gravis: an update for the clinician. Clin Exp Immunol. 2014
Mar;175(3):408-18. doi: 10.1111/cei.12217. PMID: 24117026; PMCID: PMC3927901.
Pubmed Web link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927901/
Which of the following substances is the primary neurotransmitter secreted by postganglionic
sympathetic neurons?
Answers:
A. Norepinephrine
B. Serotonin
C. Acetylcholine
D. Histamine
E. Glutamate
Norepinephrine
Discussion:
Norepinephrine is the primary neurotransmitter released by postganglionic sympathetic cells. It
binds to receptors on target tissues to cause effects associated with the sympathetic response.
Some postganglionic sympathetic cells—including those involved with sweat glands or in the
kidney—release acetylcholine or dopamine instead. The preganglionic sympathetic cells release
acetylcholine to activate the receptors on postganglionic cells. Serotonin, glutamate, and histamine
are important neurotransmitters involved in other receptors. Serotonin’s main receptor is 5-HT.
Serotonin acts both centrally and peripherally in the nervous system. Glutamate’s main receptors
are NMDA receptors, kainite receptors, AMPA receptors, and metabotropic glutamate receptors
(mGLuR). Glutamate acts in the central and peripheral nervous system. Histamine is a central
nervous system neurotransmitter. It acts via H1, H2, and H3 receptors and is involved in
wakefulness pathways.
References:
Development of neurotransmitter phenotypes in sympathetic neurons. Apostolova G, Dechant G.
Auton Neurosci. 2009 Nov 17;151(1):30-8.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/19734109/
Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System.
Wehrwein EA, Orer HS, Barman SM. Compr Physiol. 2016 Jun 13;6(3):1239-78.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/27347892/
To which of the following transmitters does the postsynaptic quisqualate receptor respond?
Answers:
A. Glutamate
B. Acetylcholine
C. Serotonin
D. GABA
E. Dopamine
Glutamate
Discussion:
The quisqualate receptor is also known as AMPA receptor and responds to the neurotransmitter
glutamate. Acetylcholine, GABA, serotonin, and dopamine are all important neurotransmitters that
act on other receptors but does not lead to a response within the quisqualate receptor. For
example, GABA’s main receptors are GABAA and GABAB. Serotonin’s main receptor are 5-HT
receptors. Dopamine acts on D1-like and D2-like receptors. Acetylcholine’s main receptors are
nAchR and mAchR (nicotinic and muscarinic).
References:
Neuroscience, 4th Edition. Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Sunderland (MA):
Sinauer Associates; 2008. Pp 129-131
Activation and Desensitization Mechanism of AMPA Receptor-TARP Complex by Cryo-EM. Chen
S, Zhao Y, Wang Y, Shekhar M, Tajkhorshid E, Gouaux E. Cell. 2017 Sep
7;170(6):1234-1246.e14.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/28823560/
Diversity in AMPA receptor complexes in the brain. Jacobi E, von Engelhardt J.
Curr Opin Neurobiol. 2017 Aug;45:32-38.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/28376410/
Patients with which of the following types of carcinoma are most likely to develop paraneoplastic
limbic encephalitis?
Answers:
A. nonsmall cell lung cancer
B. lymphoma
C. glioblastoma multiforme
D. leptomeningeal disease
E. small cell lung cancer
small cell lung cancer
Discussion:
Limbic encephalitis (LE) is a paraneoplastic syndrome that is one specific entity of a more
generalized disease process called paraneoplastic encephalomyelitis. There is a strong
association between paraneoplastic encephalomyelitis and small cell lung cancer (SCLC). In
patients with paraneoplastic encephalomyelitis, there is a 75% chance that the underlying
malignancy is SCLC. It is estimated that 40–50% of patients with LE have SCLC and 20–30% of
patients have a testicular malignancy.
Limbic encephalitis typically presents with subacute development of memory impairment,
confusion, and alteration of consciousness, often accompanied by seizures and temporal lobe
signal change on MRI. Limbic encephalitis is often a syndrome of subacute onset that usually
develops over days or weeks, at most a few months.
References:
Soomro Z, Youssef M, Yust-Katz S, Jalali A, Patel AJ, Mandel J. Paraneoplastic syndromes in
small cell lung cancer. J Thorac Dis. 2020 Oct;12(10):6253-6263. doi: 10.21037/jtd.2020.03.88.
PMID: 33209464; PMCID: PMC7656388.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/33209464/
Pelosof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis and treatment.
Mayo Clin Proc. 2010 Sep;85(9):838-54. doi: 10.4065/mcp.2010.0099. Erratum in: Mayo Clin Proc.
2011 Apr;86(4):364. Dosage error in article text. PMID: 20810794; PMCID: PMC2931619.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/20810794/
Graus F, Dalmau J. Paraneoplastic neurological syndromes. Curr Opin Neurol. 2012
Dec;25(6):795-801. doi: 10.1097/WCO.0b013e328359da15. PMID: 23041955; PMCID:
PMC3705179.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/23041955/
The pupillary light reflex is located in the ipsilateral
Answers:
A. Edinger-Westphal Nucleus
B. Medial Geniculate Nucleus
C. Optic Tract
D. Calcarine Cortex
E. Optic Canal
Edinger-Westphal Nucleus
Discussion:
The Edinger-Westphal nucleus is responsible for ipsilateral pupillary constriction. These nuclei of
CN III receive projections from the pretectal nucleus in the brainstem. The axons of these
preganglionic parasympathetic neurons send signals along the oculomotor nerve to the postganglionic nerve fibers of the ciliary ganglion, resulting in stimulation of the pupillary sphincter
muscle and pupillary constriction.
The optic nerves bilaterally leave the orbit through the optic canal, and meet at the optic chiasm in
front of the pituitary gland. The optic tract contains ipsilateral temporal fibers and contralateral
nasal fibers. The calcarine cortex is the primary visual cortex in the occipital lobe. The medial
geniculate nucleus is not involved in the visual pathway.
References:
Yoo H, Mihaila DM. Neuroanatomy, Pupillary Light Reflexes and Pathway. [Updated 2021 Aug 11].
In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan
Pubmed Web link: https://www.ncbi.nlm.nih.gov/books/NBK553169/
Kardon R. Pupillary light reflex. Curr Opin Ophthalmol. 1995 Dec;6(6):20-6. doi:
10.1097/00055735-199512000-00004. PMID: 10160414.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/10160414/
Cranial Nerves: Anatomy and Clinical Comments. Linda Wilson-Pauwels, Elizabeth Akesson, and
Patricia A. Stewart. B.C. Decker Inc, 1988
Which of the following types of receptor is associated with motor end-plates of skeletal muscles?
Answers:
A. Glutamate receptor
B. Beta adrenergic receptor
C. Acetylcholine receptor
D. Alpha adrenergic receptor
E. GABA receptor
Acetylcholine receptor
Discussion:
The acetylcholine receptor is associated with the post-synaptic membrane potential of the
neuromuscular junction. The alpha adrenergic receptor is the target of norepinephrine in smooth
muscle sphincter contraction. The beta adrenergic receptor is the target of norepinephrine in
detrusor relaxation. The GABA receptor is a primary receptor for inhibitory signals in the CNS.
The glutamate receptor receives predominantly excitatory neurotransmitters in the CNS.
References:
Fundamentals of Neuroscience. 3rd edition. Squire, Berg, B.,oom, Du Lac, Ghosh, Spitzer.
Chapter 29. Pgs 681-685, and Chapter 18, 416-419.
Rudolf R, Khan MM, Witzemann V. Motor Endplate-Anatomical, Functional, and Molecular
Concepts in the Historical Perspective. Cells. 2019 Apr 27;8(5):387. doi: 10.3390/cells8050387.
PMID: 31035624; PMCID: PMC6562597
The miniature end-plate potential (MEPP) is a result of
Answers:
A. Inhibition of binding of vessels containing Acetylcholine on post-synaptic membrane
B. Inhibition of release of vesicles containing Acetylcholine from pre-synaptic membrane
C. Increased acetylcholinesterase activity within the synaptic cleft
D. Spontaneous release of vesicles containing Acetylcholine across synaptic cleft
E. Stimulation by presynaptic motor neuron causing depolarization at pre-synaptic
membrane
Spontaneous release of vesicles containing Acetylcholine across synaptic cleft
Discussion:
Miniature end plate potentials (MEPP) are spontaneous occurring depolarizations that occur with
release of vesicles containing Acetylcholine (ACh) into the synaptic cleft in absence of stimulation
of the presynaptic neuron. These MEPP are not large enough to cause a postsynaptic action
potential due to low quanta of release of ACh. The summation of ACh release seen with
stimulation of the pre-synaptic neuron causes depolarization and EPPs that lead to action
potentials at the post-synaptic membrane. Inhibition of the ACh vesicle binding on postsynaptic
membrane causes paralysis as seen in certain toxins. The same is seen in inhibition or release of
these vesicles from the presynaptic membrane. Increased acetylcholinesterase activity can
increase the response at the postsynaptic membrane but is not related to isolated MEPP.
References:
On the factors which determine the amplitude of the miniature end-plate potential.
Katz B, Thesleff S.J Physiol. 1957 Jul 11;137(2):267-78.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/13449877/
Neuroscience, 4th Edition. Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Sunderland (MA):
Sinauer Associates; 2008
At the second cervical segment, the spinal trigeminal tract merges with the
Answers:
A. fibers from vestibular ganglion (CN VIII)
B. fibers from geniculate ganglion (CN V)
C. fibers from nodose/superior ganglion (CNX)
D. fibers from petrosal ganglion (CN IX)
E. fibers from ciliary ganglion (CN III)
fibers from nodose/superior ganglion (CNX)
Discussion:
The spinal trigeminal tract is primarily located in the pons, rostral and caudal medulla and is part of
the ventral trigeminothalamic tract which carries pain, temperature and poorly-localized touch
information from the head and neck regions to the VPM of the thalamus and eventually the
somatosensory cortex. Fibers from CN V (trigeminal/semilunar ganglion), CN VII (geniculate
ganglion), CN IX (petrosal ganglion), and CN X (nodose/superior ganglion) merge together to form
the spinal trigeminal tract. Fibers from the nodose ganglion of CN X merge with the trigeminal tract
at the upper cervical region and synapse at the spinal trigeminal nucleus (STN). Fibers from the
secondary neurons then decussate and form part of the medial lemniscus which ascends and
synapses with the tertiary neurons in the VPM of the thalamus.
References:
Patel NM, M Das J. Neuroanatomy, Spinal Trigeminal Nucleus. 2021 Oct 14. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 30969551.
Adam Fisch. Chapter 15 - Clinical Examination of the Cranial Nerves. Editor(s): R. Shane Tubbs,
Elias Rizk, Mohammadali M. Shoja, Marios Loukas, Nicholas Barbaro, Robert J. Spinner, Nerves
and Nerve Injuries, Academic Press, 2015, Pages 195-225, ISBN 9780124103900. Pubmed Web
link: https://doi.org/10.1016/B978-0-12-410390-0.00016-0
Which of the following fibers have a slow conduction velocity and a slow rate of firing?
Answers:
A. A-delta fibers
B. A-alpha fibers
C. B fibers
D. C fibers
E. A-beta fibers
C fibers
Discussion:
There are two main classes of nerve fibers involved in transmitting pain signals. C fibers are
unmyelinated small-diameter fibers that convey thermal pain. These fibers therefore have the
slowest conduction velocity. A fibers are myelinated and fast conductors. The conduction speed
of a C fiber is 0.5-2 m/s whereas A-delta fibers are 5-40 m/s. A-delta fibers respond to mechanical
stimuli and produce the sensation of localized and sharp pain. A-alpha fibers carry proprioceptive
information. A-beta fibers carry touch sensations.
References:
McGlone F, Wessberg J, Olausson H. Discriminative and affective touch: sensing and feeling.
Neuron. 2014;82(4):737-755
Pubmed Link: https://pubmed.ncbi.nlm.nih.gov/24853935/
Lawson SN. Phenotype and function of somatic primary afferent nociceptive neurones with C-,
Adelta- or Aalpha/beta-fibres. Exp Physiol. 2002;87(2):239-244
Pubmed Link: https://pubmed.ncbi.nlm.nih.gov/11856969
The superior olivary nuclei are most closely related to which of the following cranial nerves?
Answers:
A. Glossopharyngeal nerve
B. Cochlear nerve
C. Olfactory nerve
D. Vagus nerve
E. Vestibular nerve
Cochlear nerve
Discussion:
The superior olivary nuclei are most closely related to the cochlear nerve. This complex of nuclei
contains binaural neurons that receive input from both ears. Ipsilateral afferents are excitatory,
while contralateral inputs are inhibitory. The inhibitory effect is mediated by interneurons located in
the nucleus of the trapezoid body. The superior olivary complex responds to intensity and temporal
differences that exists between the ipsilateral and contralateral ears. Sound entering the ipsilateral
ear stimulates the cochlear nucleus more intensely and earlier than sound entering the
contralateral ear. That small difference is emphasized through crossed inhibition and provides
spatial information about where that sound stimulus is coming from.
References:
Christov F, Nelson EG, Gluth MB. Human Superior Olivary Nucleus Neuron Populations in
Subjects With Normal Hearing and Presbycusis. Ann Otol Rhinol Laryngol. 2018
Aug;127(8):527-535. doi: 10.1177/0003489418779405. Epub 2018 Jun 4. PMID: 29862839.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/29862839/
Sanes DH, Friauf E. Development and influence of inhibition in the lateral superior olivary nucleus.
Hear Res. 2000 Sep;147(1-2):46-58. doi: 10.1016/s0378-5955(00)00119-2. PMID: 10962172.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/10962172/
Cant NB, Casseday JH. Projections from the anteroventral cochlear nucleus to the lateral and
medial superior olivary nuclei. J Comp Neurol. 1986 May 22;247(4):457-76. doi:
10.1002/cne.902470406. PMID: 3722446.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/3722446/
Which of the following neurotransmitters is produced by Purkinje cells of the cerebellum?
Answers:
A. Serotonin
B. GABA
C. Acetylcholine
D. Glutamate
E. Dopamine
GABA
Discussion:
Purkinje cells form a single layer at the interface of the granular and molecular layers in the
cerebellum and give rise to an elaborate dendritic tree that radiates into the molecular layer.
Purkinje cell axons project either to the cerebellar nuclei (cells arising from all areas of the
cerebellar cortex), or to the vestibular nuclei (cells arising from the vermis and flocculonodular
lobe) and exhibit an inhibitory effect via use of GABA. The synthesis of acetylcholine occurs in the
terminal ends of axons. Serotonin is a monoamine neurotransmitter that is synthesized and stored
in presynaptic neurons and located in cell bodies in the pons and midbrain. Dopamine is
synthesized in neurons and cells in the adrenal glands from phenylalanine through tyrosine,
DOPA, and then to dopamine.
References:
D.E. Haines and G.A. Mihailoff. The Cerebellum. Fundamental Neuroscience for Basic and
Clinical Applications, Chapter 27, 394-412.e1
Zorrilla de San Martin J, Trigo FF, Kawaguchi SY. Axonal GABAA receptors depolarize presynaptic
terminals and facilitate transmitter release in cerebellar Purkinje cells. J Physiol. 2017 Dec
15;595(24):7477-7493. doi: 10.1113/JP275369. Epub 2017 Nov 21. PMID: 29072780; PMCID:
PMC5730858
Which of the following proteins compose gap junctions and form electrical synapses between
neurons?
Answers:
A. mCX12 protein
B. mCX4
C. Orexin
D. GFAP
E. Connexin Protein
Connexin Protein
Discussion:
Gap junctions are channel-like structures that allow for electrical and metabolic communication
between cells. Multiple proteins make up gap junctions. These include connexin proteins,
mCX36, mCX45, and MCX57. mCX12 and mCX4 are not involved in gap junctions.
Glial Fibrillary Acidic Protein (GFAP) is a member of the intermediate filament family of proteins. It
is expressed in astrocytes and ependymal cells. Orexin (hypocretin) is a hypothalamic
neuropeptide involved in arousal, wakefulness, and appetite.
References:
Sohl G, Maxeiner S, Willecke K. Expression and functions of neuronal gap junctions. Nat Rev
Neurosci. 2005 Mar;6(3): 191-200.
Pubmed Link: https://pubmed.ncbi.nlm.nih.gov/15738956/
Maday S, Twelvetrees AE, Moughamian AJ, Holzbaur EL. Axonal transport: cargo-specific
mechanisms of motility and regulation. Neuron. 2014 Oct 22;84(2):292-309. doi:
10.1016/j.neuron.2014.10.019. Epub 2014 Oct 22. PMID: 25374356; PMCID: PMC4269290.
Pubmed Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269290/
Which of the following is best described as the stimulation of multipotential stem cells to
differentiate into functioning osteogenic cells?
Answers:
A. Differentiation
B. Osteoinduction
C. Osteoconduction
D. Osseointegration
E. Osteogenesis
Osteoinduction
Discussion:
Osteoinduction is the process of inducing osteogenesis and occurs during bone healing. It involves
the recruitment of immature cells and the stimulation of these cells to develop into pre-osteoblasts.
An example of an osteoinductive material is bone morphogenic protein (BMP).
Osteoconduction is the process of bony growth on a surface and is affected by the threedimensional properties of a material.
Osseointegration is the process of direct fusion of the implant and bone without intervening
tissues.
Differentiation is the process of multipotent stem cells developing into specialized cell types.
Osteogenesis is the process of providing cells for bone formation which may be achieved by stem
cells, osteoblasts, and/or osteocytes.
References:
Albrektsson T, Johansson C. Osteoinduction, osteoconduction and osseointegration. Eur Spine J.
2001 Oct;10 Suppl 2(Suppl 2):S96-101. doi: 10.1007/s005860100282. PMID: 11716023; PMCID:
PMC3611551.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/11716023/
Maji, K., & Pramanik, K. (2021). Electrospun scaffold for bone regeneration. International Journal
of Polymeric Materials and Polymeric Biomaterials, 1–16.
Pubmed Web link: https://doi.org/10.1080/00914037.2021.1915784
Maslak, J.P., Casper D.S., Pelle, D. (2022) Spine Fusion: Biology and Biomechanics. In
Steinmetz, M.P., Berven, S.H., Benzel, E. (Ed), Benzel’s Spine Surgery, Techniques,
Complications Avoidance, and Management (5th ed., pp 122-129). Elsevier, Inc
Which of the following is the major noradrenergic nucleus of the brain?
Answers:
A. Edinger-Westphal nucleus
B. Nucleus ambiguus
C. Locus coeruleus
D. Paraventricular nucleus
E. Dorsal motor nucleus of the vagus
Locus coeruleus
Discussion:
The locus coeruleus, located near the pontomesencephalic junction, is the major noradrenergic
nucleus of the brain, and plays a central role in the regulation of arousal and autonomic activity.
Activation of the locus coeruleus produces an increase in sympathetic activity and a decrease in
parasympathetic activity via numerous excitatory projections to the majority of the cerebral cortex
as well as the basal forebrain, thalamus, dorsal raphe, and spinal cord.
The dorsal motor nucleus of the vagus nerve receives afferent input from the GI tract, heart, and
bronchi of the lungs and receives indirect projections from the locus coeruleus. The locus
coeruleus also projects to other nuclei that influence the autonomic nervous system, including the
nucleus ambiguus, which is involved in the regulation of cardiovascular activity, and the EdingerWestphal nucleus, involved in pupillary constriction. The paraventricular nucleus of the
hypothalamus also receives projections from the locus coeruleus and contains oxytocin and
vasopressin neurosecretory cells that project to the posterior pituitary gland.
References:
Samuels ER, Szabadi E. Functional neuroanatomy of the noradrenergic locus coeruleus: its roles
in the regulation of arousal and autonomic function part I: principles of functional organisation. Curr
Neuropharmacol. 2008;6(3):235-253. doi:10.2174/157015908785777229.
Pubmed Web link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687936/
Berridge CW, Waterhouse BD. The locus coeruleus-noradrenergic system: modulation of
behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev. 2003
Apr;42(1):33-84. doi: 10.1016/s0165-0173(03)00143-7. PMID: 12668290.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/12668290/
Berridge CW. Noradrenergic modulation of arousal. Brain Res Rev. 2008 Jun;58(1):1-17. doi:
10.1016/j.brainresrev.2007.10.013. Epub 2007 Dec 4. PMID: 18199483; PMCID: PMC2517224.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/18199483/
The majority of primary proprioceptive neurons of the muscles of mastication are located in the
Answers:
A. Supratrigeminal nucleus
B. Pontine nucleus
C. Mesencephalic nucleus
D. Pars oralis and pars interpolaris
E. Pars caudalis
Supratrigeminal nucleus
Discussion:
Mastication involves a complex series of events. The majority of primary proprioceptive neurons of
the muscles of mastication are located in the supratrigeminal nucleus. Proprioceptive information
comes from the spindle-rich muscles of mastication (temporalis, masseter, medial pterygoid) and
periodontal ligaments. This nucleus controls mastication directly through excitatory and inhibitory
inputs to the trigeminal nucleus. Tactile and nociceptive information from food in the mouth is
provided to the pontine and spinal nuclei, respectively. The mesencephalic nucleus contains cell
bodies of primary unipolar sensory neurons, which receive information from neuromuscular
spindles in the masticatory muscles and Ruffini endings in the suspensory periodontal ligaments of
the teeth via the mandibular division and the maxillary/mandibular divisions of the trigeminal nerve,
respectively. Most of the mesencephalic fibers descend in the small tract of Probst and terminate in
the supratrigeminal nucleus. The pontine nucleus processes discriminative tactile information from
the face and oronasal cavity. The spinal nucleus is divided into two minor nuclei (pars oralis and
pars interpolaris) and one main nucleus (pars caudalis), which receive nociceptive and thermal
information from the face.
References:
Yoshida A, Inoue M, Sato F, Morita Y, Tsutsumi Y, Furuta T, Uchino K, Akhter F, Bae YC, Tachibana
Y, Inoue T. Efferent and afferent connections of supratrigeminal neurons conveying orofacial
muscle proprioception in rats. Brain Struct Funct. 2022 Jan;227(1):111-129. doi:
10.1007/s00429-021-02391-9. Epub 2021 Oct 5. PMID: 34611777.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/34611777/
Luo P, Moritani M, Dessem D. Jaw-muscle spindle afferent pathways to the trigeminal motor
nucleus in the rat. J Comp Neurol. 2001 Jul 2;435(3):341-53. doi: 10.1002/cne.1034. PMID:
11406816.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/11406816/
Price S, Daly DT. Neuroanatomy, Trigeminal Nucleus. 2021 May 8. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 30969645.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/30969645/
The transmembrane potential of a neuron at rest occurs directly as a result of the gradient for
which of the following?
Answers:
A. potassium
B. calcium
C. ATP
D. chlorine
E. sodium
potassium
Discussion:
The resting membrane potential of a neuron results from several ion species crossing the plasma
membrane through a variety of ion channels and transporters. As the ions move across the
membrane, so do their charges. The resting membrane potential is defined as the difference in
charge across the cell membrane when it is in a non-excited state. It is calculated using the
Nernst Equation. Sodium and potassium ions play a key role in resting membrane potential.
Potassium ion concentration is higher inside of the neuron compared to the extracellular space.
Because potassium ions will diffuse out of the cell when at rest, this creates a negative resting
potential.
References:
Fundamentals of Neuroscience. 3rd edition. Squire, Berg, B.,oom, Du Lac, Ghosh, Spitzer.
Chapter 6. Pgs 120-127.
Chrysafides SM, Bordes S, Sharma S. Physiology, Resting Potential. [Updated 2021 Apr 21]. In:
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK538338/
Baroreceptor afferent fibers from the carotid sinus synapse in which of the following locations?
Answers:
A. Dorsal lower medulla
B. Ventral upper medulla
C. Dorsal upper midbrain
D. Dorsal upper medulla
E. Ventral lower medulla
Dorsal upper medulla
Discussion:
Baroreceptor afferent fibers from the carotid sinus synapse onto medially placed cells of the
solitary nucleus (the baroreceptor center, which is located within the upper medulla oblongata) via
the glossopharyngeal nerve. Baroreceptor neurons of the solitary nucleus respond by stimulating
cardioinhibitory neurons in the dorsal (motor) nucleus of the vagus nerve. Preganglionic,
cholinergic parasympathetic vagal fibers synapse on mural ganglion cells on the posterior wall of
the heart. Postganglionic, cholinergic parasympathetic fibers reduce sinoatrial node pacemaker
firing, thus decreasing the heart rate.
References:
Iskander AJ, Naftalovich R, Yang X. The carotid sinus acts as a mechanotransducer of shear
oscillation rather than a baroreceptor. Med Hypotheses. 2020 Jan;134:109441. doi:
10.1016/j.mehy.2019.109441. Epub 2019 Oct 18. PMID: 31726427.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/31726427/
Porzionato A, Macchi V, Stecco C, De Caro R. The Carotid Sinus Nerve-Structure, Function, and
Clinical Implications. Anat Rec (Hoboken). 2019 Apr;302(4):575-587. doi: 10.1002/ar.23829. Epub
2018 May 2. PMID: 29663677.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/29663677/
Shoukas AA. Overall systems analysis of the carotid sinus baroreceptor reflex control of the
circulation. Anesthesiology. 1993 Dec;79(6):1402-12. doi: 10.1097/00000542-199312000-00032.
PMID: 8267213
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/8267213/
When released from the cell membrane, which of the following substances causes the generation
of prostaglandins?
Answers:
A. Arachidonic acid
B. Nitric Oxide
C. Acetylcholine
D. Glutamate
E. Substance P
Arachidonic acid
Discussion:
Prostaglandins are lipid mediators that act upon platelets, endothelium, uterine and mast cells.
Prostaglandins play a key role in inflammation. Additionally, they regulate platelet aggregation as
well as blood vessel constriction/dilation. Prostaglandins are synthesized from arachidonic acid,
which is created from diacylglycerol via phospholipase-A2. Then, arachidonic acid is converted to
different prostaglandins via the cyclooxegenase pathway.
Substance P, a neurotransmitter in the pain pathway, is a neuropeptide made of 11 amino acids.
Glutamate is an excitatory neurotransmitter in the CNS and is a nonessential amino acid. Nitric
oxide, which can be used as a medication, exists in a gaseous state composed of 2 atoms.
Acetylcholine, which serves as a neurotransmitter at the neuromuscular junction, is derived from
choline and an acetyl group derived from coenzyme acetyl-CoA.
References:
Thomas D. Pollard MD, William C. Earnshaw PhD, FRS, Jennifer Lippincott-Schwartz PhD and
Graham T. JohnsonMA, PhD, CMI. Second Messengers. Cell Biology, Chapter 26, 443-462.
Nathanson, J. A., & Greengard, P. (1977). “Second Messengers” in the Brain. Scientific American, 237(2), 108–119. http://www.jstor.org/stable/24954007
The principal ion involved in glutamate excitotoxicity is
Answers:
A. K+
B. Zn2+
C. Na+
D. Ca2+
E. Mg2+
Ca2+
Discussion:
Glutamate receptors are classified as ionotropic or metabotropic. Ionotropic receptors respond to
glutamate binding by allowing for flow of Na+, K+, and Ca2+. However, with excessive glutamate
binding, excitotoxicity occurs leading to an increased influx of Ca2+ and neuronal damage. Zn2+
and Mg2+ can lead to modulation of electric potentials in particular receptors such as NMDA but
do not play a role in excitotoxicity.
References:
Neuroscience, 2nd Edition. Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Sunderland (MA):
Sinauer Associates; 2001.
Glutamate receptor ion channels: structure, regulation, and function. Traynelis SF, Wollmuth LP,
McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R.
Pharmacol Rev. 2010 Sep;62(3):405-96.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/20716669/
Wang Y, Qin ZH. Molecular and cellular mechanisms of excitotoxic neuronal death. Apoptosis.
2010 Nov;15(11):1382-402.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/20213199
Cyclic adenosine monophosphate activates which of the following?
Answers:
A. Caspase 3
B. Protein kinase C
C. Protein kinase A
D. Protein kinase B
E. Caspase 8
Protein kinase A
Discussion:
Protein kinase A mediates most cyclic adenosine monophosphate (cAMP) activities in cells. It is
also known as cAMP dependent protein kinase. cAMP transforms protein kinase A from its inactive
form to active form, allowing for it to perform numerous cellular functions throughout the body.
Protein kinase B (Akt) and Protein kinase C are activated by hormones, phospholipids, or other
ligands as component of cell signaling but is not directly activated by cAMP. Caspases 3 and 8 are
involved in the apoptosis pathway and not associated with cAMP.
References:
Cyclic AMP, protein kinase A, and phosphodiesterases: proceedings of an international workshop.
Stratakis CA. Horm Metab Res. 2012 Sep;44(10):713-5
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/22951901/
Neuroscience, 2nd Edition. Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Sunderland (MA):
Sinauer Associates; 2001
A 57-year-old man experienced an ischemic insult to the brainstem one year ago. He now has
extensive rigidity of his limbs. Which of the following pathways is most likely responsible for this
rigidity?
Answers:
A. Demyelination of peripheral nerves resulting in decreased somatic impulse conductivity
B. Loss of the spinal reflex arc
C. Loss of proprioception input from the dorsal column-medial lemniscus tract resulting in joint immobility
D. loss of cerebral regulatory signals and hyperexcitability of the reticulospinal and vestibulospinal tracts
E. Unopposed activation of gamma motor neurons
loss of cerebral regulatory signals and hyperexcitability of the reticulospinal and vestibulospinal tracts
Discussion:
The reticulospinal tract is part of the extrapyramidal system and is primarily responsible for
locomotion and postural control via the medial pontine and lateral medullary tracts. Additionally, the
vestibulospinal tract is composed of lateral and medial tracts, each responsible for increasing antigravity muscle tone in response to the head being tilted to one side. These fibers are directly
associated with the cerebellum allowing an indirect cerebellar influence on the spinal cord. Fibers
descend ipsilaterally through the anterior funiculus of the same side of the spinal cord, synapsing
on the extensor anti-gravity motor neurons. They function by inciting excitation of the extensor
motor neurons controlling muscle tone and anti-gravity posture.
Therefore, an injury to the brainstem and subsequent loss of the cerebral (corticospinal) regulatory
signals and hyperexcitability of the reticulospinal and vestibulospinal tracts results in severe rigidity
and extensor motor neuron activity.
References:
Zaaimi B, Edgley SA & Baker SN. Reticulospinal and ipsilateral corticospinal tract contributions to
functional recovery after unilateral corticospinal lesion. 2009 Abstract Viewer/Itinerary Planner,
Programme No. 568.529. Society for Neuroscience, Washington, DC.
Fitzgerald MJT, Gruener G, Mtui E. Clinical Neuroanatomy and Neuroscience. Fifth Edition.
Philadelphia: Elsevier Saunders, 2007
Crossman AR, Neary D. Neuroanatomy. An illustrated colour text. Third Edition. Philadelphia:
Elsevier, 2005
Auditory pathways travel in the brain stem via which of the following?
Answers:
A. Superior Colliculus
B. Trigeminal Ganglion
C. Facial Colliculus
D. Superior Olivary Nucleus
E. Greater Petrosal Nerve
Superior Olivary Nucleus
Discussion:
The ascending auditory pathway begins with the cochlear nucleus on the dorsolateral side of the
brainstem. From there, neurons travel through the superior olivary nucleus in the pons before
passing through the lateral lemniscus of the pons and midbrain to the inferior colliculus. The
trigeminal ganglion is not involved in this process. The greater petrosal nerve provides innervation
to the lacrimal gland. The facial colliculus is located in the floor of the fourth ventricle and contains
axons from cranial nerve VII.
References:
B Biacabe, JM Chevallier, P Avan, P Bonfils. Functional Anatomy of auditory brainstem nuclei:
application to the anatomical basis of brainstem auditory evoked potentials. Auris Nasus Larynx.
2001 Jan;28(1): 85-94. doi: 10.1016/s0385-8146(00)00080-8. PMID: 11137368
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/11137368/
CM Hackney. Anatomical Features of the auditory pathway from cochlea to cortex. Br Med Bull.
1987 Oct;43(4):780-801. doi: 10.1093/oxfordjournals.bmb.a072218. PMID: 3329925
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/3329925/
Cranial Nerves: Anatomy and Clinical Comments. Linda Wilson-Pauwels, Elizabeth Akesson, and
Patricia A. Stewart. B.C. Decker Inc, 1988
A 22-year-old woman has a three-week history of blurred vision, particularly on left gaze. On
examination, conjugate gaze to the right is full and normal. On left gaze, the left eye demonstrates
left-beating nystagmus while the right eye is slow to adduct. The causative lesion is most likely
located in which of the following areas?
Answers:
A. LEFT medial longitudinal fasciculus
B. RIGHT medial longitudinal fasciculus
C. RIGHT paramedial pontine reticular formation
D. RIGHT abducens nucleus
E. LEFT abducens nucleus
RIGHT medial longitudinal fasciculus
Discussion:
The medial longitudinal fasciculus is a myelinated fiber bundle that connects the ipsilateral
oculomotor nucleus to the contralateral abducens nucleus. The ipsilateral oculomotor nucleus
innervates the medial rectus, while the abducens nucleus controls the lateral rectus. Injury to the
MLF causes internuclear ophthalmoplegia, which is impairment of contralateral gaze due to
inability to adduct the ipsilateral eye and nystagmus during abduction of the contralateral eye.
The paramedian pontine reticular formation (PPRF) controls horizontal saccadic eye movements
and receives input from the contralateral frontal eye fields. The PPRF projects to the abducens
nucleus and contralateral oculomotor nucleus. Unilateral injury to the PPRF impairs ipsilateral
horizontal gaze.
The abducens nucleus projects to both the ipsilateral lateral rectus and contralateral oculomotor
nucleus. Injury to the abducens nucleus induces an impairment of ipsilateral horizontal gaze,
similar to that of PPRF injury.
References:
Fiester P, Baig SA, Patel J, Rao D. An Anatomic, Imaging, and Clinical Review of the Medial
Longitudinal Fasciculus. J Clin Imaging Sci. 2020 Dec 18;10:83. doi: 10.25259/JCIS_49_2020.
PMID: 33408958; PMCID: PMC7771398.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/33408958/
Kochar PS, Kumar Y, Sharma P, Kumar V, Gupta N, Goyal P. Isolated medial longitudinal
fasciculus syndrome: Review of imaging, anatomy, pathophysiology and differential diagnosis. The
Neuroradiology Journal. 2018;31(1):95-99. doi:10.1177/1971400917700671
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/28541157
The structure indicated by the arrow in the figure shown is primarily involved in which of the
following functions?
Answers:
A. Coordination of eye movements during horizontal gaze
B. Auditory processing
C. Proprioception
D. Fine motor movements
E. Swallowing
Coordination of eye movements during horizontal gaze
Discussion:
The medial longitudinal fasciculus (MLF) are a group of fiber tracts located near the midline of the
pons and midbrain. The MLF carries both excitatory and inhibitory neurons from the frontal eye
fields, paramedian pontine reticular formation (PPRF), and cranial nerves III, IV, and VI. The MLF
is the final common pathway for conjugate eye movements including saccades, smooth pursuit,
and vestibulocochlear reflexes. The MLF plays a vital role in coordinating horizontal eye
movements by interconnecting the oculomotor and abducens nuclei in the brainstem. The MLF
does not play a role in the other functions listed above.
References:
Kochar PS, Kumar Y, Sharma P, Kumar V, Gupta N, Goyal P. Isolated medial longitudinal
fasciculus syndrome: Review of imaging, anatomy, pathophysiology and differential
diagnosis. Neuroradiol J. 2018;31(1):95-99. doi:10.1177/1971400917700671
Pubmed Web link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789990/
Fiester P, Rao D, Soule E, Andreou S, Haymes D. The Medial Longitudinal Fasciculus and
Internuclear Opthalmoparesis: There’s More Than Meets the Eye. Cureus. 2020;12(8):e9959.
Published 2020 Aug 23. doi:10.7759/cureus.9959
Pubmed Web link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510542/
Lee SH, Kim JM, Kim JS. Update on the medial longitudinal fasciculus syndrome. Neurol Sci. 2022
Mar 8. doi: 10.1007/s10072-022-05967-3. Epub ahead of print. PMID: 35258687.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/35258687/
On the illustration shown, which of the following sites (A-E) of a brainstem lesion corresponds with
facial palsy?
Answers:
A. A
B. B
C. D
D. E
E. C
A. A
Discussion:
A. Facial colliculus
B. Stria medullaris
C. Hypoglossal triangulare
D. Vagaries triangle
E. Area postrema
Facial palsy is due to interruption of the ipsilateral facial nerve fibers as they loop behind (dorsal
to) the abducens (CN VI) nucleus at the facial colliculus of the dorsal pons within the floor of the
4th ventricle.
Tumors arising from the floor of the fourth ventricle can additionally disrupt the activity of the
abducens nucleus, damaging both motor and internuclear neurons, resulting in paralysis of the
lateral rectus muscle ipsilateral to the lesion and failure of the contralateral medial rectus.
References:
Yoo, Hannah; Mihaila, Dana M. (2022), “Neuroanatomy, Facial Colliculus”, StatPearls, Treasure
Island (FL): StatPearls Publishing, PMID 32310367, retrieved 2022-03-26
Pubmed Web link: https://doi.org/10.1016/C2014-0-03718-5
Which of the following is the primary function of the structure indicated by the arrow in the figure
shown?
Answers:
A. Eye abduction
B. Expressive speech
C. Coordination of fine motor movements
D. Receptive speech
E. Sound localization
Coordination of fine motor movements
Discussion:
The inferior olivary nuclei are located in the superior medulla. The inferior olivary nuclei provide the
main source of cerebellar climbing fibers, which project through the contralateral inferior cerebellar
peduncle to terminate on Purkinje cells in the cerebellar cortex as well as on the deep cerebellar
nuclei. The inferior olivary nuclei receive information from both the spinal cord and the motor
cortex and serves as a relay station between the spine and cerebellum. The superior olivary nuclei
integrate motor and sensory information to provide feedback to cerebellar neurons.
The superior olivary nucleus participates in sound localization and analysis. The inferior olivary
nucleus is not known to have a role in expressive or receptive speech. Eye abduction is carried out
via abducens nerve (CN VI) innervation of the lateral rectus muscle.
References:
Paul MS, M Das J. Neuroanatomy, Superior and Inferior Olivary Nucleus (Superior and Inferior
Olivary Complex) [Updated 2021 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls
Publishing; 2022 Jan-.
Pubmed Web link: https://www.ncbi.nlm.nih.gov/books/NBK542242/
Ruigrok TJ. Cerebellar nuclei: the olivary connection. Prog Brain Res. 1997;114:167-92. doi:
10.1016/s0079-6123(08)63364-6. PMID: 9193144.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/9193144/
Bengtsson F, Hesslow G. Cerebellar control of the inferior olive. Cerebellum. 2006;5(1):7-14. doi:
10.1080/14734220500462757. PMID: 16527758.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/16527758/
An otherwise healthy 27-year-old man is brought to the emergency department because of the
sudden onset of a headache when he lifted a heavy object at work. Neurological examination, CT
scan of the head, and examination of CSF show no abnormalities. One week later, he returns to
the emergency department because of persistent headaches and left abducens nerve palsy. No
other abnormalities are noted. An MR image with gadolinium is shown. Which of the following is
the most likely diagnosis?
Answers:
A. subarachnoid hemorrhage
B. leptomeningeal disease
C. Chiari malformation
D. venous sinus thrombosis
E. intracranial hypotension
intracranial hypotension
Discussion:
The patient’s symptoms, as well as the MR findings, are most consistent with intracranial
hypotension. Brain imaging findings of spontaneous intracranial hypotension include:
A. Dural (pachymeningeal) enhancement
B. Brain sagging
C. Venous distension sign
D. Subdural collections
E. Pituitary engorgement
Subarachnoid hemorrhage would demonstrate acute blood in the sulci on MRI, and a venous sinus
thrombosis would demonstrate venous hemorrhage on MRI or an abnormal flow void.
References:
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Pathogenesis, Diagnosis, and Treatment. Neuroimaging Clin N Am. 2019 Nov;29(4):581-594. doi:
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