Functional

Question 1

Which of the following findings is most likely in a patient who has intrathecal baclofen withdrawal
syndrome during malfunction of a baclofen pump?
Answers:
A. Pruritis
B. Bradycardia
C. Respiratory depression
D. Hypotonia
E. Hypothermia

Answer 1

Pruritis

Discussion:
Signs of baclofen withdrawal can be remembered by the acronym ITB: itchy, twitchy and bitchy.
Patients in baclofen withdrawal can develop itchiness, increased spasticity and mood disturbances
that can progress into delirium or psychosis. Baclofen withdrawal can be life threatening. Late
symptoms of baclofen withdrawal include the previously mentioned symptoms plus fever and
tachycardia. Neuropsychiatric symptoms can progress to hallucinations, delusions or paranoia.
Life threatening manifestations include seizure, rhabdomyolysis, disseminated intravascular
coagulopathy, and malignant hyperthermia. Oral baclofen and IT baclofen can be administered for
withdrawal, however oral doses ( > 120 mg/day divided into 6 to 8 doses) may not reach sufficient
CNS concentrations. Adjuvant therapy for baclofen withdrawal includes administration of
benzodiazepines.
References:
Raslan, Ahmed M., and Kim Burchiel. “Chapter 29-IDDS for Spasticity, Dystonia and Rigidity.”
Functional Neurosurgery and Neuromodulation, Elsevier, St. Louis, MO, 2019.
Ross, James C., et al. “Acute intrathecal baclofen withdrawal: a brief review of treatment
options.” Neurocritical Care1 (2011): 103-108.

Question 2

A 54-year-old man is scheduled for stereotactic radiosurgery for typical trigeminal neuralgia. Which
of the following is the most appropriate prescription to the 100% isodose line?
Answers:
A. 20Gy
B. 40Gy
C. 80Gy
D. 130Gy
E. 100Gy

Answer 2

80Gy

Discussion:
Trigeminal neuralgia is typically treated between 70-90Gy to the 100% isodose line. 40Gy is a
common distractor because that is the common dose to the 50% isodose line. 130Gy would a be
a dose typical for thalamotomy at the 100% isodose line, and 20Gy would be a typical dose for
metastatic tumors. The main principle of radiosurgery for trigeminal neuralgia, regardless of the
technique, is to target the trigeminal nerve with high precision in a single session, based on highresolution MRI and CT studies. Several large Gamma Knife surgery (GKS) series demonstrate
safety and efficacy of this technique with long-term and very-long-term results. A small number of
studies have reported safety and efficacy outcomes for linear accelerator (LINAC) and CyberKnife
RS (CKR) for trigeminal neuralgia but with a limited number of patients and follow-up periods.
References:
Regis J, Metellus P, Hayashi M, Roussel P, Donnet A, Bille-Turc F. Prospective controlled trial of
gamma knife surgery for essential trigeminal neuralgia. 2006 Jun; 104(6):913-24.
Ganz, Jeremy. Gamma Knife Neurosurgery. Austria, Springer Vienna, 2010

Question 3

A 34-year-old man has drug-resistant complex partial and secondarily generalized seizures.
Comprehensive presurgical epilepsy evaluation suggests right-sided temporal lobe epilepsy. MR
imaging of the brain shows right mesial temporal lobe sclerosis. Which of the following
neurosurgical procedures is associated with the greatest likelihood of seizure freedom in this
case?
Answers:
A. Vagal nerve stimulation (VNS)
B. Responsive neurostimulation (RNS) to the right hippocampus
C. Corpus Callosotomy
D. Temporal lobectomy with amygdalohippocampectomy
E. Laser interstitial thermal therapy (LITT) amygdalohippocampectomy

Answer 3

Temporal lobectomy with amygdalohippocampectomy

Discussion:
Assuming left brain dominance, the described patient would be a prime candidate for temporal
lobectomy with amygdalohippocampectomy. The original randomized controlled trial demonstrated
that nearly 60% of patients were seizure free at 1-year post-operatively. Larger meta-analyses
have shown the likelihood of an Engel-Class I (free of debilitating seizures) outcome of close to
70%. Newer, less invasive options like LITT amygdalohippocampectomy (which just target the
mesial structures and spare the lateral cortex, unlike traditional temporal lobectomy) have a slightly
lower rate of Engel-Class I outcome but do seem to have fewer side effects than temporal
lobectomy, especially neuro-cognitive deficits. VNS would not be expected to lead to seizure
freedom but rather an approximate 50% decrease in seizure frequency. Results with RNS seem to
indicate an improvement in seizure reduction over time, with initial 1-year seizure reduction of
~45%, 2-year seizure reduction of ~50-55%, and 9-year seizure reduction of up to 75%. Corpus
callosotomy destroys the major commissural connection between the right and left hemisphere
preventing contralateral spread of focal seizure activity. As a result, the ictal loss of consciousness
associated with patients who have drop attacks is avoided. This is not the correct answer here, as
the patient does not have drop attacks but rather complex partial and secondarily generalized
seizures and evaluation which demonstrates temporal lobe epilepsy.
References:
Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal-lobe
epilepsy. N Engl J Med. 2001 Aug 2;345(5):311-8.2.
Englot DJ, Birk H, Chang EF. Seizure outcomes in nonresective epilepsy surgery: an update.
Neurosurg Rev. 2017 Apr;40(2):181-94.

Question 4

Which of the following is the most appropriate first step in the treatment of a patient who is
diagnosed with Tourette syndrome?
Answers:
A. Botox injection
B. Deep Brain Stimulation
C. Anticonvulsant
D. Physical therapy
E. Behavioral Therapy

Answer 4

Behavioral Therapy

Discussion:
Tourette syndrome (TS) is a chronic neurodevelopmental disorder characterized by motor and
phonic tics that occur with a childhood onset. The syndrome is commonly associated with other
neuropsychiatric comorbidities (attention deficit hyperactivity disorder [ADHD], obsessive
compulsive disorder [OCD], and other behavioral manifestations). Diagnosis requires multiple
motor tics and at least one vocal tic to be present for more than a year. Tics are sudden, repetitive,
nonrhythmic movements that involve discrete muscle groups, while vocal (phonic) tics
involve laryngeal, pharyngeal, oral, nasal or respiratory muscles to produce sounds.
Genetic studies have shown that Tourette’s is highly heritable, but no single gene has been
identified. Behavioral therapies using habit reversal training (HRT), exposure and response
prevention (ERP) and Comprehensive Behavioral Intervention for Tics (CBIT) are first line therapy.
Neuroleptic medications have historically been and continue to be the medications with the most
proven efficacy in controlling tics. These medications work by blocking dopamine receptors, and
are associated with a high side effect profile. The traditional antipsychotic drugs are associated
with tardive dyskinesia when used long-term, and parkinsonism, dystonia, dyskinesia, and akathisia when used short-term. Benzodiazepines and alpha-adrenergic blockers are also
employed. For severely affected patients, deep brain stimulation (DBS) has the potential to
improve refractory and disabling symptoms, and targets that have been studied include the
anterior limb of internal capsule, globus pallidus internus and thalamic nuclei.
References:
Schrock LE, Mink JW, Woods DW, Porta M, Servello D, Visser-Vandewalle V, Silburn PA, Foltynie
T, Walker HC, Shahed-Jimenez J, Savica R, Klassen BT, Machado AG, Foote KD, Zhang JG, Hu
W, Ackermans L, Temel Y, Mari Z, Changizi BK, Lozano A, Auyeung M, Kaido T, Agid Y, Welter
ML, Khandhar SM, Mogilner AY, Pourfar MH, Walter BL, Juncos JL, Gross RE, Kuhn J, Leckman
JF, Neimat JA, Okun MS; Tourette Syndrome Association International Deep Brain Stimulation
(DBS) Database and Registry Study Group. Tourette syndrome deep brain stimulation: a review
and updated recommendations. Mov Disord. 2015 Apr;30(4):448-71. doi: 10.1002/mds.26094.
Epub 2014 Dec 5. PMID: 25476818.
Wilhelm S, Peterson AL, Piacentini J, et al. Randomized trial of behavior therapy for adults with
Tourette syndrome. Arch Gen Psychiatry 2012; 69: 795– 803.

Question 5

A 54-year-old woman with Parkinson disease is evaluated because of worsening symptoms
despite treatment with a high dosage of carbidopa-levodopa. Her symptoms include bradykinesia,
tremor, freezing of gait, depression, urinary incontinence, and REM sleep disorder. Which of the
following symptoms is most likely to improve with deep brain stimulation?
Answers:
A. bradykinesia
B. urinary incontinence
C. REM sleep disorder
D. freezing of gait
E. depression

Answer 5

bradykinesia

Discussion:
Deep Brain Stimulation (DBS) for Parkinson’s Disease (PD) primarily improves the cardinal motor
symptoms, i.e. bradykinesia, rigidity, and tremor. Both GPi and STN DBS are shown to significantly
improve these symptoms along with decrease the amount of “off-time.” Studies have shown that
both GPi and STN are equally efficacious in treating motor symptoms. Vim DBS would be
expected to improve tremor but not address other cardinal motor symptoms of PD, and is as such
typically reserved for the diagnosis of tremor dominant Parkinson disease (TD-PD). Regarding
gait, specifically freezing of gait, such symptoms may be less responsive to DBS. In general, a
good guide to help predict the responsiveness of axial symptoms to DBS is to gauge whether they
respond to dopaminergic medications; if there is response to dopaminergic medications, there will
likely also be improvement with DBS. Non-motor symptoms such as sleep disturbance and urinary
incontinence have been reported to improve in small STN DBS studies; however, these symptoms
would not typically be expected to improve following DBS. The VA cooperative study revealed that
depression scores improved slightly in response to GPi DBS, however worsened in response to
STN DBS.
References:
Follett, KA, Weaver FM, Stern M, et al. Pallidal versus subthalamic deep-brain stimulation for
Parkinson’s disease. N Engl J Med. 2010 Jun;362(22):2077-91
Ramirez-Zamora A, Ostrem JL. Globus Pallidus Interna or Subthalamic Nucleus Deep Brain
Stimulation for Parkinson Disease : A Review. JAMA Neurol. 2018 Mar;75(3):367-72

Question 6

A 35-year-old woman with epilepsy undergoes invasive epileptic monitoring with subdural grids. A
postoperative CT scan of the head shows a 6-mm subdural collection underneath the craniotomy
with 3 mm of midline shift. The patient is asymptomatic. Which of the following is the most
appropriate next step in management?
Answers:
A. Schedule for middle meningeal artery embolization
B. Return to operating room for evacuation of subdural hematoma and removal of subdural
grids
C. Close neurological monitoring in intensive care unit only without follow up imaging
D. Return to operating room for evacuation of subdural hematoma
E. Close neurological monitoring in intensive care unit and follow up imaging

Answer 6

Close neurological monitoring in intensive care unit and follow up imaging

Discussion:
Asymptomatic, radiographic intracranial hemorrhage is a common complication noted following
implantation of electrodes for invasive monitoring in epilepsy. This risk is increased with the
implantation of subdural grids. In this case, as the patient is asymptomatic, it is reasonable to
monitor the patient’s neurological function closely in the intensive care unit and arrange for follow
up imaging to confirm hematoma stability.
References:
Schmit, RF, Wu, C, Lang, MJ, Soni, P, Williams Jr, KA, Boorman, DW, Evans, JJ, Sperling, MR,
and Sharan AD. Complications of subdural and depth electrodes in 269 patients undergoing 317
procedures for invasive monitoring in epilepsy. Epilepsia. 2016. 57(10):1697-1708.
Starr, P. A., Larson, P. S., Barbaro, N. M. (2009) Neurosurgical Operative Atlas: Functional
neurosurgery. Germany: Georg Thieme Verlag.

Question 7

Focal midbrain atrophy is most commonly seen on MR imaging of the brain in a patient with which of the
following neurological disorders?
Answers:
A. Multisystem atrophy
B. Huntington’s Disease
C. Corticobasal degeneration
D. Progressive supranuclear palsy
E. Parkinson’s Disease

Answer 7

Progressive supranuclear palsy

Discussion:
Atypical parkinsonism syndromes comprise the following: dementia with Lewy bodies (DLB),
multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal
degeneration (CBD). These syndromes are characterized by the abnormal deposition of the
proteins a-synuclein and tau. The site of deposition is correlated with the clinical features of each
syndrome. Hallmark clinical feature of PSP include supranuclear vertical gaze palsy and early
postural instability with falls. Radiographic MRI features include midbrain atrophy with an axial AP
diameter less than 15 mm. Symptomatic mild improvement is seen in patients with levodopa,
amantadine and botox, but no long-term therapy is available.
References:
Levin J, Kurz A, Arzberger T, Giese A, Höglinger GU. The Differential Diagnosis and Treatment of
Atypical Parkinsonism. Dtsch Arztebl Int. 2016;113(5):61-69. doi:10.3238/arztebl.2016.0061
Stamelou M, Knake S, Oertel WH, Höglinger GU. Magnetic resonance imaging in progressive
supranuclear palsy. J Neurol. 2011 Apr;258(4):549-58. doi: 10.1007/s00415-010-5865-0. Epub
2010 Dec 22. PMID: 21181185

Question 8

The emotion of fear originates in which of the following structures in the brain?
Answers:
A. Anterior nucleus of the thalamus
B. Subthalamic nucleus
C. Substantia Nigra
D. Periaqueductal Gray
E. Amygdala

Answer 8

Amygdala

Discussion:
Studies across species demonstrate that the amygdala, which is primarily modulated by
serotonergic inputs, is a crucial structure involved in the fear response, including its acquisition,
storage, and expression of conditioned fear. Several other brain structures also play a role,
including the hippocampus (providing context) and the brainstem and hypothalamus (expressing
physiological responses). The lateral nucleus of the amygdala is thought to encode the association
between a conditioned stimulus and unconditioned stimulus in the fear response.
The other structures listed (Periaqueductal Gray, Subthalamic Nucleus, and Anterior nucleus of the
thalamus) are generally not directly implicated as the origin of the fear response.
References:
Bocchio M, McHugh SB, Bannerman DM, et al. “Serotonin, Amygdala and Fear: Assembling the
Puzzle,” Front Neural Circuits. 2016 Apr 5;10:24.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/27092057/
Hartley, C and Phelps, E. “Changing fear: the neurocircuitry of emotion regulation”
Neuropsychopharmacology. 2010 Jan; 35(1):136-146.
Pubmed Web link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055445/#bib40

Question 9

During radiosurgery, which of the following is a generally accepted upper limit of radiation
exposure to the optic chiasm?
Answers:
A. 13Gy
B. 10Gy
C. 20Gy
D. 40Gy
E. 8Gy

Answer 9

10Gy

Discussion:
This is an area of intense study and some controversy. For stereotactic radiosurgery, doses below
10Gy have a <1% risk of radiation-induced optic neuropathy. One large and often cited study
showed that 12Gy had a similar risk, but this has not been replicated, and 10 Gy is the more
common cut-off. There is wide agreement that >12Gy is largely unsafe, and 10 or less is largely
safe. Controversy only exists in the 10-12Gy range. Recommended dose tolerances for standard
fraction radiation, the optic chiasm and optic nerve tolerances are below 55Gy.
References:
Charles Mayo 1, Mary K Martel, Lawrence B Marks, John Flickinger, Jiho Nam, John Kirkpatrick,
Radiation dose-volume effects of optic nerves and chiasm, Int J Radiat Oncol Biol Phys 2010 Mar
1;76(3 Suppl):S28-35. doi: 10.1016/j.ijrobp.2009.07.1753.
Sellar and Parasellar Tumors: Diagnosis, Treatments, and Outcomes. Germany, Thieme, 2011.
Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J
Radiat Oncol Biol Phys 1991;21(1):109–122

Question 10

Which of the following is the most likely sign of an overdose of intrathecal baclofen?
Answers:
A. Rhabdomyolysis
B. Seizures
C. Fever
D. Pruritus
E. Malignant hyperthermia

Answer 10

Seizures

Discussion:
The correct answer is seizures. Baclofen is a GABA-B agonist, and GABA-B is an inhibitory
G-protein coupled receptor found on pre-synaptic and post-synaptic terminals. It is used to treat
spasticity, and it can be administered orally or intrathecally. Overdose of baclofen can cause
sedation, confusion, muscle weakness, hypoventilation, and seizures. Baclofen withdrawal can
cause rebound spasticity, fever, hyperthermia, pruritus, hallucinations and malignant hyperthermia.
Baclofen use and overdose has been associated with epileptic seizures in patients with MS and
structural brain lesions.
References:
Albright, A. Leland. “Topical review: baclofen in the treatment of cerebral palsy.” Journal of Child
Neurology 11.2 (1996): 77-83.
Watve, S. V., et al. “Management of acute overdose or withdrawal state in intrathecal baclofen
therapy.” Spinal Cord 50.2 (2012): 107-111.
Shirley, Kelly W., et al. “Intrathecal baclofen overdose and withdrawal.” Pediatric emergency
care 22.4 (2006): 258-261.
Kofler, M., et al. “Epileptic seizures associated with intrathecal baclofen
application.” Neurology 44.1 (1994): 25-25.
Schuele, S. U., et al. “Incidence of seizures in patients with multiple sclerosis treated with
intrathecal baclofen.” Neurology 64.6 (2005): 1086-1087.

Question 11

Which of the following techniques best distinguishes radiation necrosis from tumor recurrence?
Answers:
A. Contrast enhanced T1 MRI
B. MR Perfusion cerebral blood volume imaging
C. MR Perfusion cerebral blood flow imaging
D. T2-FLAIR MRI
E. CT Perfusion Cerebral blood flow

Answer 11

MR Perfusion cerebral blood volume imaging

Discussion:
Separating radiation necrosis from tumor progression represents a common clinical challenge.
There is a role for both MR Spectroscopy as well as MR perfusion imaging.
Using MR perfusion, cerebral blood volume (rather than blood flow) is the key indicator. Tumor
recurrence is associated with the formation of complex networks of abnormal blood vessels with
increased permeability around the tumor site that appear as regions of hyperperfusion with higher
blood volume. Treatment necrosis, on the other hand, is associated with regions of reduced
perfusion because of treatment-induced vascular endothelial damage and coagulative necrosis.
Abnormal and highly permeable blood vessels growing around the site of a recurrent tumor result
in higher relative cerebral blood volume values than in normal brain tissue. In contrast, treatment
necrosis hinders blood flow and is associated with lower relative cerebral blood volume values.
CT Perfusion may also be helpful in determining radiation necrosis from tumor progression, but
may not be as accurate as MR perfusion. Contrasted T1 and FLAIR images are usually not able
to separate these entities. Biopsy is the most reliable method for differentiating treatment necrosis
from tumor recurrence; however, brain tumor biopsies carry the risks associated with surgery.
References:
Ming-Tsung Chuang 1, Yi-Sheng Liu 1, Yi-Shan Tsai 1, Ying-Chen Chen 1, Chien-Kuo Wang 1,
Differentiating Radiation-Induced Necrosis from Recurrent Brain Tumor Using MR Perfusion and
Spectroscopy: A Meta-Analysis, PLoS One. 2016 Jan 7;11(1):e0141438. doi:
10.1371/journal.pone.0141438. eCollection 2016.
Rahmathulla, Gazanfar, Nicholas F. Marko, and Robert J. Weil. “Cerebral radiation necrosis: a
review of the pathobiology, diagnosis and management considerations.” Journal of Clinical
Neuroscience 20.4 (2013): 485-502

Question 12

The glial membrane is primarily permeable to which of the following ions?
Answers:
A. Calcium
B. Chloride
C. Potassium
D. Sodium
E. Magnesium

Answer 12

Potassium

Discussion:
In normal conditions, potassium levels in the extracellular central nervous system space is tightly
regulated by glial cells. This is performed both actively via Na, K-ATPase pumps, and passively
via Na-K-Cl cotransporters and K inwardly rectifying channels. This high permeability to potassium
allows glial cells to buffer and maintain a fairly steady state concentration of potassium in the CNS
extracellular space.
References:
Kofuji, P and Newman, EA. Potassium Homeostasis in Glia. Encyclopedia of Neuroscience. 2009.
Vol 7, pp 867-872.
Albright, A. Leland, et al. Principles and Practice of Pediatric Neurosurgery.
Germany, Thieme, 2007.

Question 13

Within the first 5 to 20 minutes after an adult with convulsive status epilepticus experiences a
seizure, which of the following medications is a Level I recommendation for treatment?
Answers:
A. mannitol
B. lorazepam
C. levetiracetam
D. 10% dextrose
E. fosphenytoin

Answer 13

lorazepam

Discussion:
Lorazepam is the correct answer. Status epilepticus (SE) is defined as 2 or more consecutive
seizures without return to baseline, or more than 30 minutes of continuous seizure activity. SE
constitutes a medical emergency and is managed by ABC evaluation. Benzodiazepines are the
mainstay of medical management. Lorazepam 4-8mg IV bolus is often first-line therapy. SE
refractory to IV bolus of benzodiazepine should be treated with fosphenytoin 15-20mg/kg IV load.
Reversible causes of SE should be sought and rapidly treated, including hypoglycemia,
hyponatremia, toxic substance screen, etc.
References:
Arif H, Hirsch LJ. Treatment of status epilepticus. Semin Neuroli. 2008 Jul;28(3):342-354. Epub
2008 Jul 24.
Pang T, Hirsch LJ. Treatment of Convulsive and Nonconvulsive Status Epilepticus. Curr Treat
Options Neurol. 2005 Jul;7(4):247-259.
Appleton R, Macleod S, Martland T. Drug management for acute tonic-clonic convulsions including
convulsive status epilepticus in children. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD001905.
Glauser T, Shinnar S, Gloss D, et al: Evidence-Based Guideline: Treatment of Convulsive Status
Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy
Society. Epilepsy Currents. Jan/Feb;16(1):48-61.

Question 14

During development, neuroblasts migrate along which of the following types of cells?
Answers:
A. Schwann Cells
B. Microglia
C. Astrocytes
D. Radial Glia
E. Oligodendrogliomas

Answer 14

Radial Glia

Discussion:
Radial glial cells derive from neuroepithelial cell stem cells that divide, producing another radial
glial cell and neuroblast. Radial glia also provide the scaffolding for neuroblast migration during
embryonic development. They project from the ventricular zone outward. A neuroblast is a
primitive nerve cell that is in a post-mitotic state which will not further divide and will develop into a
neuron after migration along the radial glia. Focal cortical dysplasia may be attributed to errors in
neuroblast migration.
Microglia are macrophage-like immune defense cells that reside in the central nervous system.
Dysfunction of microglia have been implicated in neurodegenerative diseases, including
Alzheimer’s disease and Parkinson’s disease.
Schwann Cells produce myelin in the peripheral nervous system (1 Schwann cell to 1 axon) while
Oligodendrocytes produce myelin in the central nervous system (1 Oligodendrocyte will myelinate
multiple axons). Diseases involving Schwann cells include Guillain-Barre syndrome, chronic
inflammatory demyelinating polyneuropathy, and Charcot-Marie-Tooth Disease. The most
common disease involving Oligodendrocytes is multiple sclerosis.
Astrocytes are glial cells of the central nervous system with an abundance of roles. They provide
foot processes that make up an important part of the blood brain barrier. They provide guidance
for axons, support of synapses, and maintenance of the extracellular environment. Astrocytes are
implicated in Alzheimer’s disease, Huntington disease, amyotrophic lateral sclerosis, and other
neurodegenerative diseases.
References:
Parnavelas, JG and Bagirathy, N. Radial Glial Cells. Neuron. 2001. Sep;31(6):881-884.
Albright, A. Leland, et al. Principles and Practice of Pediatric
Neurosurgery. Germany, Thieme, 2007.
Bachiller, S, Jimenez-Ferrer, I, Paulus, A, et al. Microglia in Neurological Diseases: A Road Map to
Brain-Disease Dependent-Inflammatory Response. Frontiers in Cellular Neuroscience. Epub 18
Dec 2018.
Ness, JK and Goldberg, MP. Neuroglia. 2009. Oxford Scholarship Online. DOI: 10.1093/acprof:oso
/9780195152227.001.0001

Question 15

The synthesis of which of the following factors is inhibited by warfarin?
Answers:
A. Factor XI
B. Factor XIII
C. Factor V
D. Factor XII
E. Factor II

Answer 15

Factor II

Discussion:
Warfarin competitively inhibits the vitamin K epoxide reductase complex 1 (VKORC1), an essential
enzyme for activating the vitamin K available in the body. Through this mechanism, warfarin can
deplete functional vitamin K reserves and thereby reduce the synthesis of active clotting factors.
The hepatic synthesis of coagulation factors II, VII, IX, and X, as well as coagulation regulatory
factors protein C and protein S, require the presence of vitamin K. Vitamin K is an essential
cofactor for the synthesis of all these vitamin K-dependent clotting factors. The half-life of warfarin
is generally 20 to 60 hours (mean: 40 hours). However, this can be highly variable among
individuals.
References:
Hamilton, Mark G. “Chapter 5- Drugs Affecting Coagulation and Platelet Function.” Handbook of
Bleeding and Coagulation for Neurosurgery, Thieme, New York, 2015.
DeWald, Tracy A., Jeffrey B. Washam, and Richard C. Becker. “Anticoagulants: pharmacokinetics,
mechanisms of action, and indications.” Neurosurgery Clinics4 (2018): 503-515.
Patel S, Singh R, Preuss CV, et al. Warfarin. [Updated 2022 Jan 19]. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK470313/

Question 16

A 75-year-old man undergoes transcranial resection of a large olfactory groove meningioma. On
emergence from anesthesia, he has three generalized seizures within 30 minutes without
regaining consciousness. Each seizure is stopped quickly by intravenous administration of
midazolam. A CT scan of the head rules out hematoma. Which of the following is the most
appropriate next step in management?
Answers:
A. fosphenytoin
B. isoflurane
C. fourth dose of benzodiazepine
D. keppra
E. sodium valproate

Answer 16

fosphenytoin

Discussion:
Fosphenytoin is the correct answer. Status epilepticus (SE) is defined as 2 or more consecutive
seizures without return to baseline, or more than 30 minutes of continuous seizure activity. SE
constitutes a medical emergency and is managed by ABC evaluation. Benzodiazepines are the
mainstay of medical management. Lorazepam 4-8mg IV bolus is often first-line therapy. SE
refractory to IV bolus of benzodiazepine, such as midazolam, should be treated with fosphenytoin
15-20mg/kg IV load. Reversible causes of SE should be sought and rapidly treated, including
hypoglycemia, hyponatremia, toxic substance screen, etc.
References:
Glauser T, Shinnar S, Gloss D, et al. Evidence-Based Guideline: Treatment of Convulsive Status
Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy
Society. Epilepsy Curr. 2016 Jan-Feb;16(1):48-61.
Usery JB, Michael LM 2nd, Sills AK, et al. A prospective evaluation and literature review of
levetiracetam use in patients with brain tumors and seizures. J Neurooncol. 2010
Sep;99(2):251-60.
Mazurkiewicz-Beldzinska M, Szmuda M, Zawadzka M, et al. Current treatment of convulsive status
epilepticus - a therapeutic protocol and review. Anaesthesiol Intensive Ther. 2014 SepOct;46(4):293-300

Question 17

When treating dystonia with deep brain stimulation, which of the following globus pallidus nuclei is
targeted?
Answers:
A. Interna
B. Externa
C. Lateral
D. Inferior
E. Medial

Answer 17

Interna

Discussion:
Deep brain stimulation (DBS) is FDA-approved for dystonia targeting the globus pallidus interna
(GPi). While the GPi is medially oriented, it is not named using this convention. Lateral to it is the
globus pallidus externa (GPe), but stimulation of this area does not result in comparable clinical
efficacy. Inferior to the GPi is the optic tract. Stimulation of this area causes phosphenes. Deep
brain stimulation (DBS) appears to be most effective in those with primary or hereditary dystonic
conditions such as torticollis or cervical dystonia and dystonia musculorum deformans (DYT1
dystonia). Secondary dystonias, such as those due to cerebral palsy, do not respond as well to GPi
DBS as primary dystonias. GPi DBS can also help tardive dyskinesia, which is a movement
disorder caused by certain medications. Published data is limited on the ideal dystonia target
location within the posterolateroventral GPi, as well as how clinical outcome or dystonia type may
correlate with target location.
References:
Israel Z, Burchiel KJ, eds. Microelectrode Recording in Movement Disorder Surgery. 1st ed. New
York, NY: Thieme; 2004.
Bakay R, ed. Movement disorder surgery: The Essentials. 1st ed. New York, NY: Thieme; 2009.
Tolleson C, Pallavaram S, Li C, Fang J, Phibbs F, Konrad P, Hedera P, D’Haese PF, Dawant BM,
Davis TL. The optimal pallidal target in deep brain stimulation for dystonia: a study using a
functional atlas based on nonlinear image registration. Stereotact Funct Neurosurg.
2015;93(1):17-24. doi: 10.1159/000368441. Epub 2014 Dec 9. PMID: 25502118; PMCID:
PMC4348210

Question 18

A 32-year-old man with partial complex epilepsy undergoes dominant anterior temporal lobectomy
(3 cm) and amygdalohippocampectomy. This patient is most likely to exhibit which of the following
postoperative language deficits?
Answers:
A. A decline in verbal fluency
B. A decline in attention
C. A decline in attention
D. A decline in naming
E. A decline in verbal IQ

Answer 18

A decline in naming

Discussion:
Dominant temporal lobectomy is associated with declines in verbal naming, as exhibited by word
finding difficulty and worsened performance on the Boston Naming Test. Earlier age of onset of
epilepsy appears to be protective against this.
Pooled estimates indicated a risk to verbal memory with left-sided temporal surgery occurring in
44% of patients, twice as high as the rate for right-sided surgery (20%). Naming was reduced in
34% of left-sided temporal patients, with almost no patients with gains (4%). On average, there
was a low rate of IQ and executive functioning changes after surgery regardless of side of
resection. Weighted averages indicate an increased likelihood of improvement in verbal fluency
with left-sided temporal surgery that is nearly three times greater than the rate of losses (27% vs.
10%).
Self-reported cognitive declines after epilepsy surgery are uncommon, with an average of 9% of
patients reporting losses, and an average of twice as many reporting gains (18%), and gains were
most often reported in the very domains where losses were found on objective tests (i.e., verbal
memory and language).
IQ, executive function, and attention are generally unaffected by dominant temporal lobectomy.
Verbal fluency has been shown to improve following dominant temporal lobectomy in a systemic
review.
References:
Busch R et al. “Estimating risk of word-finding difficulty of word-finding problems in adults
undergoing epilepsy surgery,” Neurology. 2016 Nov 29;87(22):2363-2369.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/27815406/
Sherman E et al. “Neuropsychological outcomes aft er epilepsy surgery: systemic review and
pooled estimates” Epilepsia. 2011 May; 52(5):857-69
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/21426331/

Question 19

Preganglionic sympathetic nerve fibers release which of the following neurotransmitters at their
synapses?
Answers:
A. Serotonin
B. Dopamine
C. Acetylcholine
D. Substance P
E. Norepinephrine

Answer 19

Acetylcholine

Discussion:
Preganglionic sympathetic nerve fibers release acetylcholine. Postganglionic sympathetic nerve
fibers release norepinephrine, except for the sweat glands which have cholinergic innervation.
Substance P is a neurotransmitter associated with painful stimuli and inflammation. Serotonin is a
monoamine neurotransmitter and in the central nervous system is primarily released by neurons of
the raphe nuclei of the reticular formation. Dopamine is the major catecholamine of the CNS and is
used as a paracrine messenger outside of the CNS.
References:
Edward J. Johns, Chapter 17 - Autonomic regulation of kidney function, Editor(s): Ruud M. Buijs,
Dick F. Swaab, Handbook of Clinical Neurology, Elsevier, Volume 117, 2013, Pages 203-214
Kandel, E. R. (2012). Principles of Neural Science, Fifth Edition. United Kingdom: McGraw-Hill
Education.

Question 20

When vincristine chemotherapy is used to treat malignant brain tumors, which of the following is
the most common adverse effect?
Answers:
A. subacute combined degeneration of the cord
B. Peripheral neuropathy
C. Progressive multifocal leukoencephalopathy
D. Pancytopenia
E. Hearing loss

Answer 20

Peripheral neuropathy

Discussion:
Peripheral neuropathy is the correct answer. Vincristine belongs to a group of drugs known as the
vinca alkaloids. Vincristine acts by binding to tubulin and inhibiting the formation of microtubules.
This inhibition causes mitosis to arrest at metaphase, through the disruption of mitotic spindle
formation. The FDA-approved indications of vincristine are acute lymphocytic leukemia, lymphoid
blast crisis of chronic myeloid leukemia, and Hodgkin and non-Hodgkin lymphoma. Vincristine also
has off-label uses including central nervous system (CNS) tumors, Ewing sarcoma, gestational
trophoblastic tumors, multiple myeloma, ovarian cancer, primary CNS lymphoma, small cell lung
cancer, and adult thymoma. Vincristine induces an axonal sensorimotor peripheral neuropathy
characterized by distal to proximal sensory, motor and autonomic disruption, manifesting as
numbness, paresthesia, neuropathic pain, weakness, constipation, urinary retention and
orthostatic hypotension. Vincristine induced peripheral neuropathy can continue despite reductions
in dosing (“coasting effect”) and persist for years after cessation of treatment.
References:
Vincristine-induced peripheral neuropathy in pediatric cancer patients. Mora et al. Am J Cancer
Res. 2016; 6(11): 2416–2430.
Vincristine-induced peripheral neuropathy is driven by canonical NLRP3 activation and IL-1β
release. Starobova et al. J Exp Med (2021) 218 (5): e20201452

Question 21

For intrathecal administration of baclofen in patients with spastic quadriparesis, particularly in the arms, it is
most appropriate to place the catheter tip at which of the following spinal levels?
Answers:
A. T10-T12
B. C1-C4
C. T8-T9
D. C5-T2
E. T5-T7

Answer 21

C5-T2

Discussion:
For patients with spastic quadriparesis requiring ITB (intrathecal baclofen), the optimal catheter tip
should be positioned between C5-T2. Spinal levels of T10-T12 are advocated for spastic diplegia;
spinal levels of C1-4 are recommended for generalized dystonia. Baclofen is a muscle relaxant
and anti-spasticity drug that is a structural analogue of the inhibitory neurotransmitter gammaaminobutyric acid (GABA). Baclofen binds to presynaptic GABA-B receptors within the brain stem,
dorsal horn of the spinal cord and other CNS sites. In most cases, intrathecal catheters inserted to
treat spastic tetraparesis or generalized dystonia should be positioned more superiorly than those
typically described.
When Penn et al 1989 developed ITB therapy to treat lower-extremity spasticity in patients with
spinal cord injury and multiple sclerosis, they placed the catheter tip at the lumbar enlargement,
T10–12. Kroin et al 1993 demonstrated that if baclofen is infused in the lumbar region, the
resulting concentration is fourfold higher than that at the cervicomedullary junction. If a patient
suffers upper-and lower-extremity spasticity, placement of the catheter more cephalad along the
spine will result in a greater baclofen concentration at the cervical enlargement.
References:
Albright AL, Turner M, Pattisapu JV. Best-practice surgical techniques for intrathecal baclofen
therapy. J Neurosurg. 2006 Apr;104(4 Suppl):233-9.
McCall, Todd D., and Joel D. MacDonald. “Cervical catheter tip placement for intrathecal baclofen
administration.” Neurosurgery3 (2006): 634-640.
Kroin JS, Ali A, York M, & Penn RD: The distribution of medication along the spinal canal after
chronic intrathecal administration. Neurosurgery 33:226–230, 1993
Penn RD, Savoy SM, Corcos D, , Latash M, , Gottlieb G, & Parke B, et al.: Intrathecal baclofen for
severe spinal spasticity. N Engl J Med 320:1517–1521, 1989.

Question 22

Three years ago, a patient who had undergone surgery for treatment of a suprasellar
craniopharyngioma received radiotherapy consisting of 6000 rads delivered through two opposed
temporal ports. A contrast-enhanced CT scan now shows a mass in the medial temporal lobe.
Which of the following is the most likely diagnosis?
Answers:
A. Glioma
B. Hemangiopericytoma
C. Craniopharyngioma
D. Lymphoma
E. Choroid plexus papilloma

Answer 22

Glioma

Discussion:
The most common brain tumors that are related to radiation exposure are meningiomas and
gliomas. Since the stem asks for a tumor in the temporal lobe and meningioma is not a choice,
glioma is the only reasonable selection left. Increased risk of brain tumors are consistently
observed in relation to ionizing radiation exposure, and generally ionizing radiation is more strongly
associated with risk for meningioma compared with glioma. The positive association between
ionizing radiation exposure and risk for glioma is stronger for younger vs. older ages at exposure.
There has not been a consistently identified effect modification on the risk for meningioma by sex,
age at exposure, time since exposure, or attained age.
References:
Joseph P Neglia 1, Leslie L Robison, Marilyn Stovall, Yan Liu, Roger J Packer, Sue Hammond,
Yutaka Yasui, Catherine E Kasper, Ann C Mertens, Sarah S Donaldson, Anna T Meadows, Peter D
Inskip. New primary neoplasms of the central nervous system in survivors of childhood cancer: a
report from the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2006 Nov 1;98(21):1528-37.
doi: 10.1093/jnci/djj411.
Radiation-induced Meningiomas. In: Cappabianca P, Solari D, ed. Meningiomas of the Skull Base:
Treatment Nuances in Contemporary Neurosurgery. 1st Edition. Stuttgart: Thieme; 2018.
Braganza MZ, Kitahara CM, Berrington de González A, Inskip PD, Johnson KJ, Rajaraman P.
Ionizing radiation and the risk of brain and central nervous system tumors: a systematic review.
Neuro Oncol. 2012;14(11):1316-1324. doi:10.1093/neuonc/nos208

Question 23

A 50-year-old woman undergoes placement of a deep brain stimulator lead into the subthalamic
nucleus for Parkinson disease. The lead is turned on intraoperatively to check for side effects. At
2.0 volts, the patient experiences significant dysarthria and contralateral facial pulling. The lead
should be repositioned in which of the following directions?
Answers:
A. Lateral
B. Anterior
C. Inferior
D. Medial
E. Superior

Answer 23

Medial

Discussion:
An effectively placed deep brain stimulator (DBS) lead in the subthalamic nucleus targets the
central motor territory in the dorsolateral part of the nucleus. An electrode too anterior or lateral will
cause motor side effects including facial contractions (pulling) or dysarthria due to internal capsule
stimulation. If too medial, the lead may stimulate the red nucleus, causing sweating and anxiety, or
oculomotor nerve roots, causing diplopia. If too posterior, the lead may induce uncomfortable
paresthesias due to stimulation of the medial lemniscus. If too inferior, the lead may stimulate the
substantia nigra, which may cause akinesia.
References:
Starr PA. Placement of deep brain stimulators into the subthalamic nucleus or Globus pallidus
internus: technical approach. Stereotact Funct Neurosurg. 2002;79(3-4):118-45. doi:
10.1159/000070828. PMID: 12890973.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/12890973/
Starr PA, Christine CW, Theodosopoulos PV, Lindsey N, Byrd D, Mosley A, Marks WJ Jr.
Implantation of deep brain stimulators into the subthalamic nucleus: technical approach and
magnetic resonance imaging-verified lead locations. J Neurosurg. 2002 Aug;97(2):370-87. doi:
10.3171/jns.2002.97.2.0370. PMID: 12186466.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/12186466/

Question 24

A 60-year-old man undergoes bilateral subthalamic nucleus deep brain stimulation (DBS) for
Parkinson disease (PD). Postoperatively, prior to turning on the stimulator, there is a notable
decrease in his bradykinesia and rigidity. Which of the following is the most likely cause for the
observed improvement in this patient’s symptoms?
Answers:
A. resumption of patient’s home PD medication(s)
B. placebo effect
C. bilateral intracerebral hemorrhage at DBS electrode site
D. Prolonged effect of sedatives (e.g. propofol) given during beginning stages of DBS
procedure
E. microlesioning effect

Answer 24

microlesioning effect

Discussion:
The clinical scenario depicted here describes the well-known microlesioning effect frequently seen
with STN DBS (along with GPi and Vim DBS). Here, the mere act of placing an electrode induces
local trauma (edema) which can provide for clinical benefit. It is for this reason that practitioners
may wait up to a month to begin DBS programming following electrode placement to allow for
abatement of microlesion induced edema and its clinical benefit. Beyond this, animal studies have
demonstrated the mere placement of electrodes can result in local changes in adenosine and
glutamate. As such, the microlesioning effect may be due to local “damage” of brain tissue as well
as a biochemical response. While bilateral DBS electrode hematomas could additionally present
with microlesion type picture, depending on the size of the hematoma there may be additional
clinical signs and symptoms seen, such as hemiparesis, neurologic deficit, decrease in
consciousness, etc.
The placebo effect has been well documented in the PD literature, as the expectation of
improvement leads to increases in dopamine in the ventral striatum and nucleus accumbens.
Some groups have reported that the placebo effect in PD may account for up to 40% of the clinical
improvement following DBS. However, most neurosurgeons/movement disorder neurologists
advise patients that clinical benefit does not occur until active stimulation/programming. As such,
patients (even those informed of the microlesion effect) would not necessarily expect clinical
benefit until following Internal Pulse Generator (IPG) placement and commencement of
stimulation.
References:
Tykocki T, Nauman P, Koziara H, et al. Microlesion effect as a predictor of the effectiveness of
subthalamic deep brain stimulation for Parkinson’s disease. Stereotact Funct Neurosurg.
2013;91(1):12-7.
Singh A, Kammermeier S, Mehrkens JH, et al. Movement kinematic after deep brain stimulation
associated microlesions. J Neurol Neurosurg Psychiatry. 2012 Oct;83(10):1022-6

Question 25

A 28-year-old man with complex partial seizures is initially treated with levetiracetam. The seizures
persist despite maximal dosage. Carbamazepine and phenytoin are added, but both are stopped
due to intolerable side effects. He continues to have one to two seizures with secondary
generalization per month causing significant debilitation. Which of the following is the most
appropriate next step in management?
Answers:
A. Change levetiracetam to extended release and gradually add back phenytoin at low doses
B. Surgical workup for epilepsy surgery
C. Start ketogenic diet
D. Start physical therapy
E. Addition of clobazam

Answer 25

Surgical workup for epilepsy surgery

Discussion:
The described patient has trialed anti-epileptic drugs (AEDs) yet continues to have debilitating
seizures meeting the International League Against Epilepsy’s definition of medically intractable
epilepsy (failure of two or more AEDs). Studies have shown that once medication refractory
epilepsy has been established, further adjustments/additions of other AEDs are unlikely to control
seizures. As this patient has now been deemed medically intractable, he should undergo surgical
workup to determine candidacy for epilepsy surgery which has been proven to be very effective in
treating medication refractory epilepsy. Surgical workup would start with video EEG and
neuroimaging studies to characterize/localize the seizures and identify any potential structural
abnormalities with the brain. Further non-invasive localization can be performed as necessary with
nuclear imaging in efforts to identify seizure foci. Should localizing efforts still be unclear or
discordant, further workup can be performed with intracranial EEG (with either subdural grids/strips
or stereo EEG) to identify the seizure focus. Pending the results of localization studies, more
definitive surgeries can be offered such as resective surgery (if able) or neuromodulatory
procedures such as responsive neurostimulation (RNS), deep brain stimulation (DBS), or vagal
nerve stimulation (VNS).
The ketogenic diet (high fat, normal/adequate protein, extremely low carbohydrate intake) has
been a long-established strategy in treating seizures. The exact mechanism is somewhat
unknown, but the diet is felt to alter the ‘excitability’ of the brain. In general, this diet (for epilepsy)
is more favored in children than in adults, as the somewhat limited diet/food choices make this a
difficult to maintain diet. Thus, although the ketogenic diet is an option, surgical workup for epilepsy
surgery is a better choice here. Physical therapy has not been shown to decrease seizure
frequency.
References:
Wiebe S, Blume WT, Girvin JP, Eliasziw M, Effectiveness and Efficiency of Surgery for Temporal
Lobe Epilepsy Study Group. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N
Engl J Med. 2001 Aug 2;345(5):311-318.
Wiebe S, Jette N. Pharmacoresistance and the role of surgery in difficult to treat epilepsy. Nat Rev
Neurol. 2012 Dec;8(12):669-677. Epub 2012 Sep 11

Question 26

A 27-year-old man undergoes brain mapping and electrocorticography for removal of a seizure
focus. Which of the following is the most appropriate anesthetic agent to administer to this patient?
Answers:
A. Inhaled volatile anesthetic agent
B. Alprazolam
C. Lidocaine
D. Midazolam
E. A combination of Propofol, Dexmedetomidine, and Fentanyl/Remifentanyl titrated to the desired anesthetic level.

Answer 26

A combination of Propofol, Dexmedetomidine, and Fentanyl/Remifentanyl titrated to the desired anesthetic level

Discussion:
Current recommendations for anesthetic utilized during awake craniotomy is not standardized, with
many institutions following similar versions of anesthetic plan. It is important, however, to avoid
utilizing benzodiazepines when utilizing electrocorticography, as this can blunt EEG for days postadministration. Dexmedetomidine, an alpha-2 adrenoceptor agonist, provides sedation, anxiolytic
effects, and analgesia, and is commonly chosen due to its short recovery time after
discontinuation. Local anesthetics like lidocaine are used for scalp blocks for awake craniotomy.
Propofol also has dose-dependent effects through GABA A agonist activity and limits reliable
electrocorticography when used in general anesthesia doses. However, electrocorticography can
be reliably obtained 20-30 minutes after propofol discontinuation. Short-acting opioids allow other
anesthetic agents to be used at lower doses. Inhaled agents are only used under general
anesthesia with a secured airway and hinder brain-mapping techniques by globally depressing
brain and spinal cord activity. Motor mapping is the most common type of brain mapping that is
performed on a sleeping patient, but in this context inhaled agents are also avoided.
References:
Prontera A, Baroni S, Marudi A, et al. Awake craniotomy anesthetic management using
dexmedetomidine, propofol, and remifentanil. Drug Des Devel Ther. 2017;11:593-598. Published
2017 Mar 3. doi:10.2147/DDDT.S124736
Stevanovic, Ana, et al. “Anaesthesia management for awake craniotomy: systematic review and
meta-analysis.” PLoS One5 (2016): e0156448.
Baltuch, Gordon H., and Cukiert, Arthur. Operative Techniques in Epilepsy
Surgery. Germany, Thieme, 2019.
Mahato, D., Chaichana, K. L., Quinones-Hinojosa, A. (2019). Brain Mapping: Indications and
Techniques. Brazil: Thieme

Question 27

A 24-year-old primigravid woman is evaluated at 32 weeks’ gestation for seizures, hypertension,
proteinuria, hemolysis, elevated liver enzymes, and thrombocytopenia. Which of the following is
the most definitive treatment for this patient?
Answers:
A. steroid treatment and conservative management until term
B. Antihypertensive medications
C. Immediate delivery
D. Magnesium sulfate infusion
E. Steroid treatment followed by delivery within 48 hours

Answer 27

Steroid treatment followed by delivery within 48 hours

Discussion:
Steroid treatment followed by delivery within 48 hours is the correct answer. The patient has
HELLP syndrome, Hemolysis, Elevated Liver enzymes and Low Platelets (thrombocytopenia). This
serious and potentially fatal condition when untreated occurs in 0.5-0.9% of pregnancies, and in
10-20% of patients that suffer from pre-eclampsia, seizures occur commonly. Before 34 weeks of
pregnancy, the favored approach is steroid treatment to promote fetal lung maturation followed by
delivery within 48 hrs. After 34 weeks, immediately delivery is recommended. Below 24 weeks,
termination of pregnancy should be considered. While magnesium and antihypertensives should
be administered, these are not definitive treatments for HELLP.
References:
Haram K, Svendsen E, Abildgaard U. The HELLP syndrome: Clinical issues and management.
Review. BMC Pregnancy Childbirth. 2009 Feb 26;9:8.
Sibai BM, ed. Hypertension. In: Gabbe SG, Niebyl JR, Simpson JL, et al, eds. Obstetrics: Normal
and problem pregnancies. 6th ed.. Philadelphia, PA: Saunders, 2012. HELLP syndrome,
neurocritical care.

Question 28

Autonomic dysfunction, particularly postural hypotension, is a common secondary symptom in
patients with which of the following conditions?
Answers:
A. Cerebellar ischemic stroke
B. Essential Tremor
C. Tourette’s Syndrome
D. Parkinson Disease
E. Localization related Epilepsy

Answer 28

Parkinson Disease

Discussion:
Autonomic dysfunction is an important non-motor feature of Parkinson’s disease (PD). This
includes gastrointestinal malfunction, cardiovascular dysregulation, urinary disturbance, sexual
dysfunction, thermoregulatory, and pupillo-motor and lacrimation abnormalities. The two core
findings of autonomic pathology in PD are autonomic neuronal destruction and α-synuclein
accumulation. In the peripheral autonomic nervous system, the vagus nerve, sympathetic nerve
fibers, and enteric neural plexus exhibit these findings. SNCA gene duplication and triplication are
associated with cardiac sympathetic denervation in PD. Gradual position changes and briefly
sitting before standing are recommended. Fludrocortisone can increase intravascular volume and
Midodrine and droxidopa can increase peripheral vascular resistance and have been successfully
used for the treatment of postural hypotension in PD. Pyridostigmine is a cholinesterase
inhibitor that can enhance cholinergic neurotransmission in both sympathetic and parasympathetic
terminals and can be considered as well.
References:
A. Palma, H. Kaufmann. Treatment of autonomic dysfunction in Parkinson disease and other
synucleinopathies. Mov. Disord., 33 (2018), pp. 372-390
L. Schoffer, R.D. Henderson, K. O’Maley, J.D. O’Sullivan. Nonpharmacological treatment,
fludrocortisone, and domperidone for orthostatic hypotension in Parkinson’s disease. Mov.
Disord., 22 (2007), pp. 1543-1549

Question 29

Which of the following constitutes the customary radiation therapy regimen for glioblastoma?
Answers:
A. 60 Gy in 2 Gy fractions 5 days/week
B. 60 Gy in 5 Gy fractions 3 days/week
C. 60 Gy delivered as a radiosurgical fraction
D. 60 Gy in 2 Gy fractions 1 day/week
E. 30 Gy in 2 Gy fractions 5 days/week

Answer 29

60 Gy in 2 Gy fractions 5 days/week

Discussion:
Multiple clinical trials have shown that a total of 60Gy delivered in fractions is the optimal radiation
treatment for glioblastoma (GBM). The Stupp protocol is considered the standard of care
treatment for glioblastoma for which after resection, fractionated radiation therapy is delivered
concurrent with daily temozolomide therapy. Once or thrice weekly is too few fractions that would
delay the delivery of the radiation therapy. 60 Gy delivered as a radiosurgical fraction is incorrect
because it doesn’t fractionate the therapy. Long-term risks of fractionated radiation therapy include
radiation necrosis, neurocognitive decline, and neuroendocrine dysfunction.
References:
Brem, Steven, and Abdullah, Kalil G.. Glioblastoma E-Book. United States, Elsevier Health
Sciences, 2016.
Stupp, Roger et al. “Radiotherapy plus concomitant and adjuvant temozolomide for
glioblastoma.” The New England journal of medicine 352,10 (2005): 987-96.
doi:10.1056/NEJMoa043330

Question 30

A 70-year-old man undergoes globus pallidus internus deep brain stimulation (DBS) for Parkinson
disease with awake intraoperative testing. Stimulation through all contacts of the DBS lead at a
frequency of 135 Hz and pulse width of 60 ms results in improvement in tremor and rigidity at 1.8 V
to 2.0 V. Contractions of the contralateral mouth and arm are elicited when the stimulation is turned
up to 1.9 V to 2.4 V. Which of the following is the most appropriate next step in the procedure?
Answers:
A. Withdraw electrode 1 mm
B. Reposition electrode 1 mm medially
C. Reposition electrode 1 mm laterally
D. Leave electrode in present location
E. Reposition electrode 1 mm posterolaterally

Answer 30

Reposition electrode 1 mm posterolaterally

Discussion:
This intra-operative testing scenario demonstrates improvement in Parkinson’s disease (PD)
cardinal symptoms indicating that the electrode is likely within the GPi. However, at similar
amplitudes there is also contractions of contralateral mouth/arm, signifying stimulation of the
neighboring internal capsule. At this level, the internal capsule is postero-medial to the GPi.
Withdrawing the electrode 1 mm would have no effect on internal capsule stimulation. This
movement would be recommended if there was activation of the optic tract (i.e. phosphenes),
which is located ventral to the GPi. A 1 mm medial movement would result in a movement toward
the internal capsule and thus still result in internal capsule stimulation, likely at even lower
amplitudes. Repositioning the lead laterally or postero-laterally would both move the lead away
from the internal capsule. As the therapeutic target for DBS is the posteroventral region of the GPi,
a postero-lateral repositioning would allow for the lead to be moved away from the internal capsule
and still remain within the therapeutic region of the GPi.
References:
Rezai AR, Kopell BH, Gross RE, et al. Deep brain stimulation for Parkinson’s disease: Surgical
issues. Mov. Disord. 2006;21:S197-S218.
Deep-Brain Stimulation for Parkinson’s Disease Study Group, Obeso JA, Olanow CW, et al. Deepbrain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in
Parkinson’s disease. N Engl J Med. 2001 Sep 27;345(13):956-63.

Question 31

A 30-year-old woman is evaluated because of a five-year history of primary generalized dystonia.
She has maximized medical therapy. Which of the following is the most appropriate surgical
intervention?
Answers:
A. Sternocleidomastoid muscle myotomy and spinal accessory nerve resection
B. Intrathecal baclofen pump
C. bilateral GPi DBS
D. bilateral thalamic Deep Brain Stimulation (DBS)
E. bilateral GPi Radiofrequency (RF) lesioning

Answer 31

bilateral GPi DBS

Discussion:
Randomized controlled trials for GPi DBS for generalized and segmental dystonia have shown
significant improvements in the motor subscore of the Burke-Fahn-Marsden Dystonia Rating
Scale. Long term results up to 5 years demonstrate durability of improvement, establishing GPi
DBS as first line surgical therapy for medication refractory generalized (and segmental) dystonia.
Bilateral RF lesioning is no longer routinely performed due to unacceptably high rates of
complication (speech/swallowing difficulties). Bilateral thalamic DBS, intrathecal baclofen, and
myotomy have all been performed for dystonia, however are not first line therapies.
References:
Volkmann J, Wolters A, Kupsch A, et al. Pallidal deep brain stimulation in patients with primary
generalised or segmental dystonia: 5-year follow-up of a randomised trial. Lancet Neurol. 2012
Dec;11(12):1029-38.
Kupsch A, Benecke R, Müller J, et al. Pallidal deep-brain stimulation in primary generalized or
segmental dystonia. N Engl J Med. 2006 Nov 9;355(19):1978-90

Question 32

A woman who was found unconscious on the street is brought to the emergency department. She
is febrile and has muscle rigidity. She has a subcutaneous, subcostal infusion pump. An x-ray film
of the lumbosacral spine is shown. Administration of which of the following is most appropriate?
Answers:
A. Narcan
B. Morphine
C. Vancomycin and piperacillin-tazobactam
D. Amitriptyline
E. Baclofen

Answer 32

Baclofen

Discussion:
The patient is most likely in baclofen withdrawal given the infusion pump and her symptoms
(muscle rigidity and fever) in the setting of a disconnected catheter. Baclofen withdrawal can be
life-threatening, and she needs immediate baclofen. Oral baclofen and IT baclofen can be
administered for withdrawal, however oral doses ( > 120 mg/day divided into 6 to 8 doses) may not
reach sufficient CNS concentrations. Adjuvant therapy for baclofen withdrawal includes
administration of benzodiazepines. Baclofen withdrawal may mimic other diseases including
sepsis, meningitis, autonomic dysreflexia, malignant hyperthermia, or neuroleptic malignant
syndrome.
References:
Raslan, Ahmed M., and Kim Burchiel. “IDDS for Spasticity, Dystonia and Rigidity.” Functional
Neurosurgery and Neuromodulation, Elsevier, St. Louis, MO, 2019.
Miracle, A C et al. “Imaging evaluation of intrathecal baclofen pump-catheter systems.” American
journal of neuroradiologyvol. 32,7 (2011): 1158-64. doi:10.3174/ajnr.A2211
Hsieh JC, Penn RD. Intrathecal baclofen in the treatment of adult spasticity. Neurosurgery Focus
2006; 21(2):E5.
Zuckerbraun NS, Ferson SS, Albright AL, Vogeley, E. Intrathecal baclofen withdrawal: emergent
recognition and management. Pediatric Emergency Care 2004; 20(11):759-64

Question 33

Question:
Inferior extension of a therapeutic lesion placed in the posteroventral globus pallidus pars internus
may induce which of the following adverse outcomes?
Answers:
A. Hemianopia
B. Dysarthria
C. Paresthesias
D. Hemiparesis
E. Aphasia

Answer 33

Hemianopia

Discussion:
The globus pallidus pars interna is a target for pallidotomy for relief of motor symptoms of
Parkinson’s disease. A lesion that is too inferior will disrupt the optic tract, leading to possible
hemianopia. If too medial or posterior, the lesion will cause disruption in fibers of the internal
capsule, possibly resulting in hemiparesis or other motor deficits. A lesion too lateral or anterior will
be in the globus pallidus pars externa, which will not improve symptoms. Parkinsonian tremor,
rigidity, and hypokinesia can be effectively abolished by posteroventral pallidotomy. The positive
effect of posteroventral pallidotomy is believed to be based on the interruption of some striopallidal
or subthalamopallidal pathways, which results in disinhibition of medial pallidal activity necessary
for movement control.
References:
Laitinen LV, Bergenheim AT, Hariz MI. Leksell’s posteroventral pallidotomy in the treatment of
Parkinson’s disease. J Neurosurg. 1992 Jan;76(1):53-61.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/1727169/
Hariz MI, Bergenheim AT. A 10-year follow-up review of patients who underwent Leksell’s
posteroventral pallidotomy for Parkinson disease. J Neurosurg. 2001 Apr;94(4):552-558.Hariz MI,
De Salles AA. The side-effects and complications of posteroventral pallidotomy. Acta Neurochir
Suppl. 1997;68:42-48.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/11302652

Question 34

A 9-year-old girl with Lennox-Gestaut syndrome is evaluated for epilepsy surgery. She is on
multiple antiepileptic medications and has multiple seizure types, including atonic seizures (drop
attacks). Which of the following surgical interventions is most appropriate for this seizure
semiology?
Answers:
A. deep brain stimulation of the thalamus
B. corpus callosotomy
C. vagal nerve stimulation
D. hemispherotomy
E. stereoelectroencephalography

Answer 34

vagal nerve stimulation

Discussion:
Vagal nerve stimulation (VNS) is the correct answer. Atonic seizures are now classified by the
International League Against Epilepsy (ILAE) in 2017 as generalized motor seizures with the
subtype atonic. These seizures are a form of generalized epilepsy characterized by rapid loss of
muscular tone causing falls to the ground due to rapid seizure generalization, i.e. drop attacks. The
rapid nature of the falls can cause severe injuries. Atonic seizures, aka drop attacks, are treated
with vagal nerve stimulation as first-line and corpus callosotomy for patients that do not respond to
VNS. For atonic seizures specifically, VNS typically results in 57.6% of patients having at least
50% reduction in seizures, and corpus callosotomy 85.6%. Side-effects for VNS are typically mild
with voice changes (22%); side-effects for corpus callosotomy include disconnection syndrome
(13.2%).
References:
Rolston et al. Corpus callosotomy versus vagus nerve stimulation for atonic seizures and drop
attacks: A systematic review. Epilepsy Behav. 2015 Oct; 51: 13–17.
Smyth MD, Kassabah HS, eds. Palliative surgical procedures for epilepsy. In: Cohen AR, ed.
Pediatric Neurosurgery: Tricks of the Trade. 1st ed. New York, NY: Thieme; 2015:712-22.
Graham D, Tisdall MM, Gill D. Corpus callosotomy outcomes in pediatric patients: A systematic
review. Epilepsia. 2016 Jul;57(7):1053-68

Question 35

A 17-year-old boy who is right-hand dominant undergoes a left anterior temporal lobectomy for
treatment of epilepsy that is secondary to mesial temporal sclerosis and refractory to medical
therapy. Which of the following postoperative deficits is most likely in this patient?
Answers:
A. Contralateral homonymous superior quadrantanopia
B. Oculomotor nerve palsy
C. Trochlear nerve palsy
D. Contralateral Hemiplegia
E. Contralateral homonymous hemianopia

Answer 35

Contralateral homonymous superior quadrantanopia

Discussion:
The most common postoperative deficit noted following an anterior temporal lobectomy is a
contralateral homonymous superior quadrantanopia (pie in the sky defect) due to injury of Meyer’s
loop. One of the most catastrophic, although rare, complications is inadvertent injury to the
anterior choroidal artery, which can result in a contralateral hemiparesis or hemiplegia and
contralateral homonymous hemianopia. Injury to the cranial nerves is also rare, with the most
commonly injured cranial nerve being the oculomotor nerve.
References:
Mathon, et al. Complications after surgery for mesial temporal lobe epilepsy associated with
hippocampal sclerosis. World Neurosurgery. 2017. Jun;102:639-650.
Mengesha, T et al. “Visual field defects after selective amygdalohippocampectomy and standard
temporal lobectomy.” Journal of neuro-ophthalmology : the official journal of the North American
Neuro-Ophthalmology Society 29,3 (2009): 208-13

Question 36

A 75-year-old woman with osteoporosis is evaluated because of a six-month history of thoracic
back pain. Examination shows no radicular pain or neurological deficits. X-ray studies show
multiple compression fractures. Which of the following is the most appropriate pharmacotherapy
to increase bone formation in this patient?
Answers:
A. Alendronate
B. Denosumab
C. Teriparatide
D. Abaloparatide
E. Calcitonin-salmon

Answer 36

Alendronate

Discussion:
Bisphosphonates remain the first line therapy for the treatment of osteoporosis. They function to
inhibit osteoclastic bone reabsorption and may stimulate osteoblasts, inducing bone mineralization.
Teriparatide is a 34 amino acid sequence of human parathyroid hormone that leads to the
formation of new bone. Denosumab is a human monoclonal antibody that is an inhibitor of RANKL
(receptor activator of nuclear factor kappa-B ligand). It prevents the development of osteoclasts.
Abaloparatide is also a parathyroid hormone-related protein, like teriparatide, but shown to lead to
greater bone mineral density increases with less hypercalcemia. Calcitonin inhibits osteoclast
activity and renal tubular reabsorption of calcium. In the PROOF study, intranasal salmon
calcitonin given in conjunction with calcium and vitamin D led to reduced risk of new vertebral
fractures in postmenopausal women with osteoporosis. Non-pharmacologic treatment includes fall
prevention, smoking cessation, diet modification, and exercise.
References:
Tu, Kristie N et al. “Osteoporosis: A Review of Treatment Options.” P & T : a peer-reviewed journal
for formulary management vol. 43,2 (2018): 92-104.
Benzel, Edward C.. Biomechanics of Spine Stabilization. Germany, Thieme, 2014.
Chesnut, C H 3rd et al. “A randomized trial of nasal spray salmon calcitonin in postmenopausal
women with established osteoporosis: the prevent recurrence of osteoporotic fractures study.
PROOF Study Group.” The American journal of medicine 109,4 (2000): 267-76.
doi:10.1016/s0002-9343(00)00490-3

Question 37

A woman who is receiving 450 mcg/day of intrathecal baclofen via an implanted infusion pump is
evaluated because of the sudden onset of sweating, pruritus, and muscle spasms, after refilling
her prescription two weeks ago. Which of the following is the most likely explanation for these
symptoms?
Answers:
A. Pump site infection
B. Baclofen withdrawal
C. Meningitis
D. Baclofen overdose
E. Spinal fluid leak

Answer 37

Baclofen withdrawal

Signs of baclofen withdrawal may include itchiness, twitching, and irritability. Patients in baclofen
withdrawal can develop itchiness, increased spasticity and mood disturbances that can progress
into delirium or psychosis. Baclofen withdrawal can be life threatening. Late symptoms of baclofen
withdrawal include the previously mentioned symptoms plus fever and tachycardia.
Neuropsychiatric symptoms can progress to hallucinations, delusions, or paranoia. Life threatening
manifestations include rhabdomyolysis, disseminated intravascular coagulopathy, and malignant
hyperthermia. Oral baclofen and IT baclofen can be administered for withdrawal, however oral
doses ( > 120 mg/day divided into 6 to 8 doses) may not reach sufficient CNS concentrations.
Adjuvant therapy for baclofen withdrawal includes administration of benzodiazepines.
References:
Raslan, Ahmed M., and Kim Burchiel. “IDDS for Spasticity, Dystonia and Rigidity.” Functional
Neurosurgery and Neuromodulation, Elsevier, St. Louis, MO, 2019.
Ross, James C., et al. “Acute intrathecal baclofen withdrawal: a brief review of treatment
options.” Neurocritical Care1 (2011): 103-108

Question 38

A 67-year-old man underwent placement of subthalamic deep brain stimulator leads for Parkinson
disease two weeks ago. CT scans of the head with and without contrast show a nonenhancing
3 × 3 × 4-cm hypodensity centered around the right lead. Which of the following is the most
appropriate next step in management?
Answers:
A. Anti-epileptic medication
B. Antibiotics
C. Short course of low-dose steroids
D. Biopsy
E. Removal of the DBS system

Answer 38

Short course of low-dose steroids

Discussion:
An infrequent but likely under-recognized postoperative complication of DBS surgery is peri-lead
edema, characterized by a non-enhancing hypodensity surrounding the DBS lead. Patients may
present with seizure, headache, confusion, or focal deficit. Symptoms typically resolve along with
the edema over a period of days to a few weeks. Infection should be ruled out with a contrasted
scan (CT or MRI) and infectious markers should be obtained (CRP, ESR), but if negative, peri-lead
edema is the most likely diagnosis. It can be managed conservatively, and a short course of
steroids is typically recommended. Removal of the system is not necessary, and biopsy is not
indicated as peri-lead edema typically resolves spontaneously. If patients do not present with
seizures, anti-epileptic medications are not necessary. If infection is ruled out, antibiotics are not
necessary.
References:
Deogaonkar M, Nazzaro JM, Machado A, Rezai A. Transient, symptomatic, post-operative, noninfectious hypodensity around the deep brain stimulation (DBS) electrode. J Clin Neurosci. 2011
Jul;18(7):910-5. doi: 10.1016/j.jocn.2010.11.020. Epub 2011 May 14. PMID: 21571534.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/21571534/
Saitoh T, Enatsu R, Mikami T, Suzuki Y, Kanno A, Kitagawa M, Mikuni N. Peri-electrode edema
after deep brain stimulation. J Clin Neurosci. 2019 Jan;59:29-31. doi: 10.1016/j.jocn.2018.11.026.
Epub 2018 Nov 22. PMID: 30472347.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/30472347/

Question 39

Which of the following is the first-line treatment for craniocervical dystonia?
Answers:
A. benzodiazepine
B. Botulinum toxin
C. GPI deep brain stimulation
D. baclofen
E. peripheral denervation

Answer 39

Botulinum toxin

Discussion:
Botulinum toxin is the correct answer. Craniocervical dystonias are hyperkinetic movement
disorders manifested by abnormal involuntary movements of the cranial muscles, characterized by
intermittent or sustained muscle contractions. The most common are blepharospasm and
oromandibular dystonia. Meige syndrome is a variant that describes co-existent blepharospasm
and oromandibular dystonia. First line treatment is with botulinum toxin. Medications such as
benzodiazepines, levodopa and anticholinergic medications are less efficacious. Selective
peripheral denervation can be considered in cervical dystonia. GPI Deep Brain Stimulation (DBS)
can be considered in medically refractory cases.
References:
Panov F, Gologorsky Y, Connors G, et al. Deep Brain Stimulation in DYT1 Dystonia: A 10-year
Experience. Neurosurgery. 2013 Jul;73(1):86-93; discussion 93.
Albanese A, Barnes MP, Bhatia KP, et al. A systematic review on the diagnosis and treatment of
primary (idiopathic) dystonia and dystonia plus syndromes: report of an EFNS/MDS-ES Task
Force. Eur J Neurol. 2006 May;13(5):433-44.
Ozelius L, Kramer PL, Moskowitz CB, et al. Human gene for torsion dystonia located on
chromosome 9q32-q34. Neuron. 1989;2:1427-34.
Treatment of Blepharospasm and Oromandibular Dystonia with Botulinum Toxins. Travis J.W.
Hassell * and David Charles Toxins 2020, 12, 0269; doi:10.3390/toxins12040269
Reese, R.; Gruber, D.; Schoenecker, T.; Bäzner, H.; Blahak, C.; Capelle, H.H.; Falk, D.; Herzog, J.;
Pinsker, M.O.; Schneider, G.H.; et al. Long-term clinical outcome in meige syndrome treated with
internal pallidum deep brain stimulation. Mov. Disord. 2011, 26, 691–698

Question 40

Which of the following processes activates ion channels in hair cells?
Answers:
A. Magnesium efflux
B. Ligand binding
C. Calcium influx
D. Sodium efflux
E. Mechanical deflection

Answer 40

Mechanical deflection

Discussion:
The auditory hair cells are located within the spiral organ of Corti on the thin basilar membrane in
the cochlea. Cochlear hair cells are of two types, known as outer and inner hair cells. The outer
hair cells mechanically amplify low-level sound that enters the cochlea. The inner hair cells
transform the sound vibrations in the cochlea into electrical signals that are then relayed via
the auditory nerve to the brainstem and auditory cortex. Hair cells of the inner ear are specialized
mechanosensory cells which convert mechanical stimuli produced by sound waves via the
cochlea, or head movement via the vestibular system, into electrical signals. Hair cells are highly
polarized cells with specialization for sensing mechanical stimuli. The deflection of the haircell stereocilia opens mechanically gated ion channels that allow positively charged ions, mainly
potassium and calcium, to enter the cell. The hair cell itself does not generate an action potential.
Instead, the influx of positive ions from the endolymph in the scala media depolarizes the cell,
resulting in a receptor potential. This receptor potential opens voltage-gated calcium channels and
triggers the release of neurotransmitters at the basal end of the cell. The neurotransmitters diffuse
across the narrow space between the hair cell and a nerve terminal, where they then bind
to receptors in the synapse and trigger action potentials.
References:
Qiu X, Müller U. Mechanically Gated Ion Channels in Mammalian Hair Cells. Front Cell Neurosci.
2018;12:100. Published 2018 Apr 11. doi:10.3389/fncel.2018.00100
LeMasurier M, Gillespie PG. Hair-cell mechanotransduction and cochlear amplification. Neuron.
2005 Nov 3;48(3):403-15. doi: 10.1016/j.neuron.2005.10.017. PMID: 16269359.

Question 41

Which of the following best describes the structural characteristics of nociceptive nerve fibers
found in the dorsal roots?
Answers:
A. Alpha Motor Neurons
B. Group B Nerve Fibers
C. Myelinated Fibers
D. Group A Nerve Fibers
E. Group C Nerve Fibers

Answer 41

Group C Nerve Fibers

Discussion:
The structural characteristics of nociceptive nerve fibers found in the dorsal roots are composed of
Group C Nerve Fibers and terminate in laminae I and II in the dorsal horn. These are unmyelinated
nerve fibers and relate to the slow aspect of pain stimuli. Group A fibers have four subdivisions
based on myelination and axonal diameter, both relating to the nerve conduction velocity. Larger
diameter and increased myelination lead to increased conduction velocity. Lightly myelinated Aδ
nociceptive neurons are expectedly associated with fast pain response and terminate in laminae II
and V. Group B fibers are myelinated with small diameter and primarily relay autonomic
information. Somatic muscle fibers are innervated by an alpha motor neuron which has a cell body
in either the spinal cord or brain stem.
References:
Pinto V, Szucs P, Lima D, Safronov BV. Multisegmental A{delta}- and C-fiber input to neurons in
lamina I and the lateral spinal nucleus. J Neurosci. 2010 Feb 10;30(6):2384-95. doi:
10.1523/JNEUROSCI.3445-09.2010. PMID: 20147564; PMCID: PMC6634039.
Kandel, E. R. (2012). Principles of Neural Science, Fifth Edition. United Kingdom: McGraw-Hill
Education.
Surgical Management of Pain. Burchiel K, ed. 2nd Edition. New York: Thieme; 2015

Question 42

The efficacy of intrathecal baclofen in decreasing spasticity is due to its effect at which of the
following receptors?
Answers:
A. GABA-B receptors
B. Ryanodine receptors
C. alpha-2 adrenergic receptors
D. Muscarinic cholineragic receptors
E. Nicotinic cholinergic receptors

Answer 42

GABA-B receptors

Discussion:
GABA-B receptors is correct. Baclofen is a GABA-B agonist, and GABA-B is an inhibitory
G-protein coupled receptor found on pre-synaptic and post-synaptic terminals. It is used to treat
spasticity, and it can be administered orally or intrathecally. Overdose of baclofen can cause
sedation, confusion, muscle weakness, hypoventilation, and seizures. Baclofen withdrawal can
cause rebound spasticity, fever, hyperthermia, pruritus, hallucinations and malignant hyperthermia.
Baclofen use and overdose has been associated with epileptic seizures in patients with Multiple
Sclerosis and structural brain lesions.
References:
Albright, A. Leland. “Topical review: baclofen in the treatment of cerebral palsy.” Journal of Child
Neurology 11.2 (1996): 77-83.
Watve, S. V., et al. “Management of acute overdose or withdrawal state in intrathecal baclofen
therapy.” Spinal Cord 50.2 (2012): 107-111.
Shirley, Kelly W., et al. “Intrathecal baclofen overdose and withdrawal.” Pediatric emergency
care 22.4 (2006): 258-261.
Kofler, M., et al. “Epileptic seizures associated with intrathecal baclofen
application.” Neurology 44.1 (1994): 25-25.
Schuele, S. U., et al. “Incidence of seizures in patients with multiple sclerosis treated with
intrathecal baclofen.” Neurology 64.6 (2005): 1086-1087.

Question 43

In a 60-year-old man, when is an essential tremor likely to be most pronounced?
Answers:
A. When Sitting relaxed
B. When Drinking alcohol
C. When Sleeping
D. When Fatigued
E. When Taking a Beta-blocker for hypertension

Answer 43

When Fatigued

Discussion:
Essential (ET) tremor is a monosymptomatic, predominant postural or kinetic tremor which usually
slowly progresses over the years. ET involves hand tremor in 94%, head tremor in 33%, voice
tremor in 16% and leg tremor in 12% of the patients. ET may be hereditary and about 50–70% of
the patients improve with intake of alcohol. ET-related tremors do not occur during sleep but
worsen with stress, fatigue, intense activity, cold, heat, caffeine, or social performance scenarios.
The typical candidate for DBS has medication refractory symptoms affecting quality of life and the
ability to work. In these patients, treatment with propranolol and primidone at maximum tolerated
doses does not result in sufficient symptom alleviation. However, not every patient may be eligible
for this procedure. Various other functional neurosurgical procedures are available, including
radiofrequency thalamotomy, focused ultrasound and radiosurgery. Targets other than VIM, such
as the posterior subthalamic area (PSA) or the dentato-rubro-thalamic tract (DRT), may be
considered as well.
References:
Kremer NI, Pauwels RWJ, Pozzi NG, Lange F, Roothans J, Volkmann J, Reich MM. Deep Brain
Stimulation for Tremor: Update on Long-Term Outcomes, Target Considerations and Future
Directions. J Clin Med. 2021 Aug 5;10(16):3468. doi: 10.3390/jcm10163468. PMID: 34441763;
PMCID: PMC8397098.
Zesiewicz TA, Chari A, Jahan I, Miller AM, Sullivan KL (September 2010). “Overview of essential
tremor”. Neuropsychiatric Disease and Treatment. 6: 401–8.

Question 44

During the creation of a burr hole for a deep brain stimulator, an awake, sedated patient has
sudden onset of coughing, hypotension, and hypoxia. The clinical presentation suggests which of
the following potential complications?
Answers:
A. Cardiac arrythmia
B. Thromboembolus
C. Air embolus
D. Vagal response
E. Raised intracranial pressurev

Answer 44

Air embolus

Discussion:
The nature of deep brain stimulation raises the risk of venous air embolus. Patients are positioned
semi-reclined, decreasing venous pressure in the skull emissary veins, which can entrain air.
Additionally, breathing patterns in awake patients may further increase negative pressure, resulting
in entrained air that can obstruct the pulmonary circulation. Symptoms of air embolism include
coughing, hypoxia, and hypotension. Treatment includes flooding the field with saline, lowering the
head, cardiopulmonary support, and possible aspiration of the air via a central venous catheter.
References:
Suarez S, Ornaque I, Fábregas N, et al. Venous air embolism during Parkinson surgery in patients
with spontaneous ventilation. Anesth Analg. 1999 Apr;88(4):793-794.Hooper AK, Okun
MS, Foote KD, et al. Venous air embolism in deep brain stimulation. Stereotact Funct Neurosurg.
2009;87(1):25-30. Epub 2008 Nov 27.

Question 45

Bilateral lesions of which of the following structures are associated with profound impairment of
memory for recent events, but leave remote memory intact?
Answers:
A. Lateral geniculate nucleus
B. Hippocampus
C. Amygdala
D. Ventral intermediate nucleus
E. Anterior cingulate cortex

Answer 45

Hippocampus

Discussion:
William Scoville and Brenda Milner’s classic 1957 report of patient H.M. and others who underwent
bilateral mesial temporal resections demonstrated that bilateral hippocampal resection resulted in
memory impairment which created both “anterograde and some retrograde amnesia but left early
memories and technical skills intact.”1 Patients with only bilateral resections of the amygdala did
not demonstrate memory impairment.1
Bilateral lesions of the ventral intermediate nucleus are expected to put patients at risk for speech
and balance difficulty, but not memory problems.2
Bilateral lesions of the anterior cingulate cortex are used as a treatment for intractable pain;
memory deficits are not a reported complication.3
Bilateral lesions of the lateral geniculate nucleus would be expected to cause visual impairment.
References:
Scoville WB, Milner, B “Loss of recent memory after bilateral hippocampal lesions,” J Neurology
Neurosurgery and Psychiatry. 1957 Feb; 20(1):11-21.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/13406589/
Alshaikh J, Fishman P “Revisiting bilateral thalamotomy for tremor” Clinical Neurology and
Neurosurgery. 2017 Jul;158:103-107.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/28505539/
Sharim J, Pouratian N, “Anterior Cingulotomy for the Treatment of Chronic Intractable Pain: A
Systemic Review,” Pain Physician. Nov-Dec 2016; 19(8): 537-550.
Pubmed Web link https://pubmed.ncbi.nlm.nih.gov/27906933/

Question 46

Absence or attenuation of wave V of the brain-stem auditory evoked response (BAER) indicates a
central conduction abnormality at which brain-stem level?
Answers:
A. Cochlear Nerve
B. Inferior colliculus
C. Lateral Lemniscus of midbrain
D. Superior Olivary Complex
E. Cochlear Nucleus

Answer 46

Inferior colliculus

Discussion:
Brainstem auditory evoked responses (BAERs) are electrical signals produced by the nervous
system related to the transmission of acoustic input. They are highly reproducible and contain
multiple waves that indicate a level of acoustic signal transmission: (I) Cochlear Nerve), (II)
Cochlear Nucleus, (III) Superior Olivary Complex (Pons), (IV) Lateral Lemniscus in Midbrain, (V)
Inferior Colliculus.
BAERS can be a useful adjunct for surgeries that may put a patient’s hearing at risk, as they are
minimally affected by anesthesia. Most commonly, BAERs are used in surgeries in the posterior
fossa, including tumor surgeries such as vestibular schwannoma resection and microvascular
decompression for trigeminal neuralgia.
References:
D. Legatt. Encyclopedia of the Neurological Sciences (Second Edition), 2014.
Habib SH and Habib SS. Auditory brainstem response: An overview of neurophysiological
implications and clinical applications -A Narrative Review. J Pak Med Assoc. 2021.
Sep;71(9):2230-2236. doi: 10.47391/JPMA.03-432.PMID: 34580520
Chen TC, Rabb C, and Apuzzo ML. Complex technical methologies and their applications in the
surgery of intracranial meningiomas. Neurosurg Clin N Am. Apr;5(2):231-81.

Question 47

A 17-year-old girl with a ten-year history of complex partial seizures is referred for vagal nerve
stimulation. The source of the epilepsy is not well localized. Numerous medications have failed to
control the seizures. Which of the following is the most likely outcome of vagal nerve stimulation in
this patient?
Answers:
A. Reduction in seizures without reduction in seizure medications
B. No clinically significant change in seizures
C. Reduction in seizures with reduction in seizure medications
D. Atrial arrhythmia
E. Sudden unexplained death in epilepsy (SUDEP)

Answer 47

Reduction in seizures without reduction in seizure medications

Discussion:
Vagal nerve stimulation (VNS) has long been established as an effective therapy for multiple types
of epilepsy including focal, multifocal, and diffuse/generalized epilepsies. While effective, VNS is
seldom viewed as a “curative” therapy that can abolish seizures. Large clinical series demonstrate
seizure reduction between 50-60% without significant changes/reductions in the amount of AEDs
taken. Neither SUDEP nor atrial arrhythmia are common complications of VNS.
References:
Elliott RE, Rodgers SD, Bassani L, et al. Vagus nerve stimulation for children with treatmentresistant epilepsy: a consecutive series of 141 cases. J Neurosurgical Pediatrics. 2011 May;
7(5):491-500.
Pediatric Epilepsy Surgery: Preoperative Assessment and Surgical
Treatment. Germany, Thieme, 2019.

Question 48

Operative management of palmar hyperhidrosis typically involves ablation of which of the following
sympathetic ganglia?
Answers:
A. C8 root
B. Kuntz nerves
C. grey rami communicantes
D. Thoracic sympathetic chain
E. Stellate ganglion

Answer 48

Thoracic sympathetic chain

Discussion:
Thoracic sympathetic chain is the correct answer. Palmar hyperhidrosis is characterized by
excessive sweating of the hands. There are numerous treatments which vary in efficacy, including
anticholinergic medications, local botox injection, iontophoresis of the hands and aluminum-based
antiperspirants. Thoracoscopic or posterior paraspinal approaches to the thoracic sympathetic
chain (typically T2 and T3) can be used to interrupt the sympathetic outflow to the hands. Kuntz
nerves are peripheral branches from the sympathetic chain that can be a source of recurrence if
not ablated. Disruption of the stellate ganglion causes Horner’s syndrome and should be avoided.
Selective blockage of the stellate ganglion has been utilized for craniofacial hyperhidrosis.
References:
Thoracic sympathectomy for hyperhidrosis: from surgical indications to clinical results. Vannucci, Araújo. J Thorac Dis. 2017 Apr; 9(Suppl 3): S178–S192.
Effect of botulinum toxin in stellate ganglion for craniofacial hyperhidrosis: a case report. Park, et
al. J Int Med Res. 2021 Mar; 49(3): 03000605211004213
Palmar hyperhidrosis—which is the best level of denervation using video-assisted thoracoscopic
sympathectomy: T2 or T3 ganglion? Yazbek et al. Journal of Vascular Surgery. 2005;42(2):
281-285

Question 49

A right-handed 28-year-old man with intractable epilepsy undergoes an intracranial electrode
investigation that localizes his seizures to the left medial superior frontal gyrus and cingulate gyrus,
approximately 2 to 3 cm anterior to the motor strip. Which of the following typically temporary
deficits is most likely to result from resection of this region?
Answers:
A. Contralateral hemisensory deficit
B. Decline in short-term memory
C. Visual field disturbance
D. Anosmia
E. Contralateral paralysis and mutism

Answer 49

Contralateral paralysis and mutism

Discussion:
The described symptoms are characteristic of supplementary motor area (SMA) syndrome. The
area of seizure localization (left medial superior frontal gyrus and cingulate gyrus, approximately
2-3 cm anterior to the motor strip) refers to the supplementary motor area (SMA). The SMA is
thought to be a critical component of higher coordination for voluntary movement. There is a strong
functional connection between the bilateral SMAs. Accordingly, when one side loses function (as in
this question, due to resection), connectivity to the contralateral SMA temporarily decreases in the
acute phase; however, connectivity eventually recovers leading to only a temporary deficit. Deficits
can resolve within the first post-operative week, but can take up to 2-9 weeks. The clinical findings
of paralysis in SMA syndrome differ from that of paralysis seen secondary to damage to the
pyramidal tract. In SMA syndrome, tone is often preserved or even normal, while with damage to
the pyramidal tract initial tone is flaccid with eventual increased tone developing during recovery.
Visual field disturbances (classically contralateral superior quadrantanopsia) can be seen with
temporal lobectomies or laser amygdalohippocampectomies with damage to the optic radiations
(Meyer’s loop). Declines in short-term memory are also possible with temporal lobectomies,
especially on the dominant lobe. Contralateral hemisensory deficit would be expected with
surgery/damage to the primary somatosensory cortex located posterior to the motor cortex.
References:
Luders HO, ed. Textbook of Epilepsy Surgery. 1st ed. England: Informa UK Ltd; 2008.
Nakajima R, Kinoshita M, Yahata T, et al. Recovery time from supplementary motor area
syndrome: relationship to postoperative day 7 paralysis and damage of the cingulum. J Neurosurg
132:865-874, 2020.

Question 50

A 20-year-old man has had tremors of the head and upper extremities for the past two years.
Ocular examination shows Kayser-Fleischer rings. Which of the following findings is most likely to
confirm the diagnosis?
Answers:
A. Iron accumulation on liver biopsy
B. High serum copper
C. High serum ceruloplasmin
D. Low serum ceruloplasmin
E. Low urine copper

Answer 50

Low serum ceruloplasmin

Discussion:
Wilson’s disease is an autosomal recessive genetic disorder in which excess copper builds up in
the body affecting the liver and brain. Liver-related symptoms include vomiting, ascites, pruritis
and, ultimately, liver failure. Brain-related symptoms include tremors, rigidity, dysarthria, personality
changes, anxiety, and psychosis.
[1]
The disease is caused by a mutation in the Wilson disease protein (ATP7B) gene on chromosome
13. This protein transports excess copper into bile, where it is excreted in waste products. MRI
brain may also demonstrate the characteristic “face of the giant panda” pattern described as
preservation of normal signal intensity in the red nuclei and lateral portion of the pars reticulata of
the substantia nigra, high signal in the tegmentum, and hypointensity of the superior colliculus. The
combination of neurological symptoms, Kayser–Fleischer rings and a low ceruloplasmin level is
considered sufficient for the diagnosis of Wilson’s disease. Serum copper is low, which may seem
paradoxical given that Wilson’s disease is a disease of copper excess. However, 95% of plasma
copper is carried by ceruloplasmin which is low in Wilson’s disease. Urine copper is elevated. Liver
biopsy shows high level of copper accumulation. Wilson’s disease is typically treated with dietary
changes and medication. Dietary changes involve eating a low-copper diet and not using copper
cookware. Medications used include chelating agents such as d-penicillamine and zinc
supplements. References:
Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML (2007). “Wilson’s
disease”. Lancet. 369 (9559):
397–408. doi:1016/S0140-6736(07)60196-2. PMID17276780. S2CID 24663871. Robertson WM (February 2000). “Wilson’s disease”. Arch. Neurol. 57 (2):
276–77. doi:1001/archneur.57.2.276. PMID10681092

Question 51

A 27-year-old man is evaluated for mild developmental delay and medically refractory epilepsy.
Seizure semiology and EEG suggest multifocal epilepsy. He has frequent drop attacks that have
resulted in several orthopedic injuries and emergency department visits every one to two months.
Which of the following is the most appropriate procedure for reducing this patient’s drop attacks?
Answers:
A. Temporal Lobectomy
B. Corpus callosotomy
C. Multiple subpial transections (MST)
D. Responsive neurostimulation (RNS)
E. Deep brain stimulation to the anterior nucleus of the thalamus

Answer 51

Corpus callosotomy

Discussion:
The described patient has frequent drop attacks with several resultant orthopedic injuries as a
result. Continual drop attacks can prove extremely dangerous with resultant traumatic brain injury
(TBI) or cervical spine fracture/injury possibly occurring. Corpus callosotomy destroys the major
commissural connection between the right and left hemisphere, preventing contralateral spread of
focal seizure activity. As a result, the ictal loss of consciousness is avoided. Responsive
neurostimulation (RNS) may be less suited for multifocal epilepsy, as the current RNS systems can
only target 2 distinct areas and, as such, may have less utility in epilepsy with more than 2 foci.
Recently, small case series have shown promise with responsive neurostimulation to thalamic
targets such as the anterior nucleus of the thalamus and the centromedian nucleus. As such,
moving forward RNS may have more utility in multifocal epilepsy. DBS to the anterior nucleus of
the thalamus was validated in the SANTE trial showing 2-year seizure reduction rates of about
50%. The majority of the patients in the SANTE trial exhibited temporal lobe epilepsy, and the
mechanism through which deep brain stimulation to the anterior nucleus of the thalamus works is
through modulating the limbic network. MST more recently has shown more modest results than
when originally described, and is traditionally utilized in focal epilepsy in eloquent brain in which
resective surgery would typically be not indicated. Temporal lobectomy is most useful when
seizures can be attributed to the temporal lobe, which is not the history given here.
References:
Englot DJ, Birk H, Chang EF. Seizure outcomes in nonresective epilepsy surgery: an update.
Neurosurg Rev. 2016 May 21.
Maehara, Taketoshi, and Hiroyuki Shimizu. “Surgical outcome of corpus callosotomy in patients
with drop attacks.” Epilepsia 42.1 (2001): 67-71.

Question 52

A 56-year-old man has a resting tremor in his left arm that persists with maintained posture but
diminishes with movement. Neurological examination shows no other abnormalities. Which of the
following is the most likely diagnosis?
Answers:
A. Essential Tremor
B. Dystonic Tremor
C. Chorea
D. Physiological tremor
E. Parkinson’s Disease

Answer 52

Parkinson’s Disease

Discussion:
Parkinson’s disease (PD) is a progressive, idiopathic, degenerative disorder of the basal ganglia
due to loss of dopaminergic neurons in the substantia nigra. The symptoms usually emerge slowly,
and as the disease worsens, non-motor symptoms become more common. Motor symptoms
include resting tremor, rigidity, bradykinesia, and freezing of gait. Dementia, depression, anxiety, and apathy may occur as well as insomnia and dysautonomia. The basal ganglia are subcortical
nuclei controlling voluntary actions and have been implicated in PD. The prevailing model of basal
ganglia function states that two circuits, the direct and indirect pathways, originate from distinct
populations of striatal medium spiny neurons (MSNs) and project to different output structures.
These circuits are believed to have opposite effects on movement. Specifically, the activity of direct
pathway MSNs is postulated to promote movement, whereas the activation of indirect pathway
MSNs is hypothesized to inhibit it. Their activity is modulated by D1 and D2 dopamine receptors
contained in the substantia nigra, pars compacta. Initial treatment is typically with physical therapy
and medications, including levodopa (L-DOPA), MAO-B inhibitors, or dopamine agonists. As the
disease progresses, these medications become less effective, while at the same time producing
side effects marked by involuntary muscle movements known as dyskinesias. For medically
refractory PD, DBS or lesioning is considered. Targets include the VIM thalamus, globus pallidus
internus, or subthalamic nucleus, depending on predominant symptoms and neuropsychiatric
profile.
References:
Armstrong MJ, Okun MS (February 2020). “Diagnosis and Treatment of Parkinson Disease: A
Review”. JAMA. 323(6):548-560. doi:1001/jama.2019.22360. PMID 32044947. Jankovic J (April 2008). “Parkinson’s disease: clinical features and diagnosis”. Journal of
Neurology, Neurosurgery, and Psychiatry. 79 (4):
368–76. doi:10.1136/jnnp.2007.131045. PMID 18344392

Question 53

A patient with essential tremor is evaluated for continued debilitating tremor despite maximal
medical therapy. The option of deep brain stimulation is discussed with the patient. Which of the
following brain regions is most likely to be recommended for targeting?
Answers:
A. Globus Pallidus Interna
B. Subthalamic Nucleus
C. Ventral intermediate nucleus of the thalamus
D. Globus Pallidus Externa
E. Anterior thalamus

Answer 53

Ventral intermediate nucleus of the thalamus

Discussion:
Deep brain stimulation of the ventral intermediate (VIM) nucleus of the thalamus is most effective
for essential tremor. Tremor is characterized by involuntary rhythmic muscle contractions that can
occur in one or more body parts. Essential tremor (ET) prominently affects the upper-limbs during
voluntary movements, but can also affect the lower-limbs, head, and chin. Patients with tremordominant Parkinson’s disease and patients with cerebellar tremors may also respond to chronic
VIM stimulation but to a lesser extent. The subthalamic nucleus and globus pallidus interna (GPi)
are targets for Parkinson’s disease. The ANT thalamus is a target for epilepsy and the globus
pallidus externa (GPe) is not a Deep Brain Stimulator (DBS) target.
References:
Chen T, Mirzadeh Z, Chapple K, et al. “Asleep” deep brain stimulation for essential tremor. J
Neurosurg. 2016;124(6):1842-9.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/26613177/
Zhang K, Bhatia S, Oh MY, Cohen D, Angle C, Whiting D. Long-term results of thalamic deep brain
stimulation for essential tremor. J Neurosurg. 2010 Jun;112(6):1271-6. doi:
10.3171/2009.10.JNS09371. PMID: 19911883.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/19911883/

Question 54

In a patient with increased intracranial pressure and significant systemic hypertension, the
treatment most likely to decrease cerebral perfusion pressure is administration of which of the
following?
Answers:
A. 500 cc of 3% saline IV
B. Sodium nitroprusside IV
C. 5 mg IV Labetalol
D. 1 g/ kg Mannitol
E. 30 cc of 23.4% saline IV

Answer 54

Sodium nitroprusside IV

Discussion:
Cerebral blood flow (CBF) is thought to be maintained by autoregulation when mean arterial
pressure (MAP) ranges from approximately 60 to 150 mmHg following modulation of pial and large
cerebral artery tone. CBF may be affected by changes in MAP within these limits, particularly by
reduction in MAP. Sodium nitroprusside will reduce systemic vascular resistance more than
cerebral vascular resistance, causing a preferential blood flow to the low resistance systemic
vascular bed rather than the cerebral vascular bed, and thus will lower cerebral perfusion pressure
(CPP) and increase intracranial pressure. Hypertonic saline boluses can lower ICP and thereby
increase CPP.
References:
Immink RV, van den Born BJ, van Montfrans GA, Kim YS, Hollmann MW, van Lieshout JJ.
Cerebral hemodynamics during treatment with sodium nitroprusside versus labetalol in malignant
hypertension. Hypertension. 2008 Aug;52(2):236-40. doi:
10.1161/HYPERTENSIONAHA.108.110395. Epub 2008 Jul 7. PMID: 18606905.
Rosner, Michael J., Sheila D. Rosner, and Alice H. Johnson. “Cerebral perfusion pressure:
management protocol and clinical results.” Journal of neurosurgery6 (1995): 949-962
Mendelow, A D et al. “Effect of mannitol on cerebral blood flow and cerebral perfusion pressure in
human head injury.” Journal of neurosurgery 63,1 (1985): 43-8. doi:10.3171/jns.1985.63.1.0043

Question 55

A 62-year-old man has had involuntary movements of the right side of the body (hemiballismus) for
the past two weeks. He sustained a lacunar infarction in the region of the left subthalamic nucleus
two weeks ago. Which of the following is the most appropriate treatment?
Answers:
A. Intrathecal baclofen
B. STN Deep Brain Stimulation
C. Botulinum toxin
D. Anti-dopaminergic medications
E. Anti-psychotic medications

Answer 55

Anti-dopaminergic medications

Discussion:
The development of hemiballism after an injury to the subthalamic nucleus (STN), such as a
hypertensive hemorrhage or stroke, is rare but has been reported. Abnormal movements following
a stroke can occur immediately or can be delayed and progressive. Hemichorea-hemiballism
arising after stroke may improve with medical therapy, but in certain circumstances neurosurgical
intervention may be appropriate, particularly for refractory symptoms. Antidopaminergic
medications are first line therapy, followed by anticonvulsants and antipsychotic medications.
Some success has been reported with botox injection and intrathecal baclofen therapy in select
cases. Although definitive evidence is lacking, the relative safety and reversibility of GPi DBS
makes it a valuable proposition for those suffering from the disease.
References:
Pabaney A, Ali R, Lewitt PA, Sidiropoulos C, Schwalb JM. Successful Management of
Hemorrhage-Associated Hemiballism After Subthalamic Nucleus Deep Brain Stimulation with
Pallidal Stimulation: a Case Report. World Neurosurg. 2015 Oct;84(4):1176.e1-3. doi:
10.1016/j.wneu.2015.06.070. Epub 2015 Jul 9. PMID: 26164193.
Ramirez-Zamora A, Eisinger RS, Haider SA, Youn Y, Shin D, Molho ES, Pilitsis JG. Pallidal deep
brain stimulation and intraoperative neurophysiology for treatment of poststroke hemiballism. Ann
Clin Transl Neurol. 2018 May 21;5(7):865-869. doi: 10.1002/acn3.573. PMID: 30009204; PMCID:
PMC6043765.

Question 56

Which of the following Parkinsonian symptoms fails to improve with deep brain stimulation of the
subthalamic nucleus?
Answers:
A. Falling
B. Speech impairment
C. Freezing
D. All of the other answers
E. Gait disturbance

Answer 56

All of the other answers

Discussion:
Deep brain stimulation for Parkinson’s disease is indicated for medically refractory resting tremor,
rigidity, bradykinesia, and dyskinesia, targeting either the subthalamic nucleus (STN) or globus
pallidus interna (GPi). Symptoms that do not typically or consistently respond to DBS include
freezing, falls, gait disturbance, and speech impairment.
Stimulation of the STN is the most common and improves core motor symptoms better than
medication in patients with advanced PD. The majority of nonmotor symptoms, such as mood,
impulse control disorders, sleep, and some autonomic dysfunctions may also improve. Quality of
life (QoL) is improved significantly. Internal globus pallidus (GPi) stimulation seems to have similar
short-term efficacy. Although short-term QoL improvement seems to be similar to that for
subthalamic nucleus (STN) DBS - gait and speech may be better improved - long-term data are
rare for GPi DBS. Thalamic stimulation in the ventral intermediate nucleus (VIM) is applied only in
tremor-dominant elderly patients.
References:
Deuschl G, Paschen S, Witt K. Clinical outcome of deep brain stimulation for Parkinson’s disease.
Handb Clin Neurol. 2013;116:107-28.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/24112889/
St George RJ, Carlson-Kuhta P, Nutt JG, et al. The effect of deep brain stimulation randomized by
site on balance in Parkinson’s disease. Mov Disord. 2014
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/24532106/

Question 57

The most effective treatment of hyperhidrosis of the hand is resection of which of the following
structures?
Answers:
A. Kuntz nerves
B. Thoracic sympathetic chain
C. C8 root
D. Stellate ganglion
E. grey rami communicantes

Answer 57

Thoracic sympathetic chain

Discussion:
Thoracic sympathetic chain is correct. Palmar hyperhidrosis is characterized by excessive
sweating of the hands. There are numerous treatments which vary in efficacy, including
anticholinergic medications, local botox injection, iontophoresis of the hands and aluminum-based
antiperspirants. Thoracoscopic or posterior paraspinal approaches to the thoracic sympathetic
chain (typically T2 and T3) can be used to interrupt the sympathetic outflow to the hands. Kuntz
nerves are peripheral branches from the sympathetic chain that can be a source of recurrence if
not ablated. Disruption of the stellate ganglion causes Horner’s syndrome and should be avoided.
Selective blockage of the stellate ganglion has been utilized for craniofacial hyperhidrosis.
References:
Thoracic sympathectomy for hyperhidrosis: from surgical indications to clinical results. Vannucci, Araújo. J Thorac Dis. 2017 Apr; 9(Suppl 3): S178–S192.
Effect of botulinum toxin in stellate ganglion for craniofacial hyperhidrosis: a case report. Park, et
al. J Int Med Res. 2021 Mar; 49(3): 03000605211004213
Palmar hyperhidrosis—which is the best level of denervation using video-assisted thoracoscopic
sympathectomy: T2 or T3 ganglion? Yazbek et al. Journal of Vascular Surgery.2005;42(2):
281-285

Question 58

Hemiballismus is most likely caused by a lesion at which of the following sites?
Answers:
A. Field of Forel
B. Substantia Nigra
C. Globus pallidus Internus
D. Caudate Nucleus
E. Subthalamic Nucleus

Answer 58

Subthalamic Nucleus

Discussion:
Hemiballismus is a hyperkinetic involuntary movement disorder characterized by intermittent,
sudden, violent, involuntary, flinging, or ballistic high amplitude movements involving the arm and
leg. The development of hemiballism after an injury to the subthalamic nucleus (STN) can occur.
Etiologies include stroke, hemorrhage, toxo-metabolic exposure, tumors, infections such as
toxoplasmosis or tuberculomas and paraneoplastic syndrome. Abnormal movements can occur
immediately or can be delayed and progressive. Hemichorea-hemiballism arising after an insult
may improve with medical therapy with anti-dopaminergic medications, but in certain
circumstances neurosurgical intervention may be appropriate particularly for refractory symptoms.
Although definitive evidence is lacking, the relative safety and reversibility of GPi DBS makes it a
valuable proposition for those suffering from the disease.
References:
Pabaney A, Ali R, Lewitt PA, Sidiropoulos C, Schwalb JM. Successful Management of
Hemorrhage-Associated Hemiballism After Subthalamic Nucleus Deep Brain Stimulation with
Pallidal Stimulation: a Case Report. World Neurosurg. 2015 Oct;84(4):1176.e1-3. doi:
10.1016/j.wneu.2015.06.070. Epub 2015 Jul 9. PMID: 26164193.
Evidente VG, Gwinn-Hardy K, Caviness JN, Alder CH. Risperidone is effective in severe
hemichorea/hemiballismus. Mov Disord. 1999 Mar;14(2):377-9. doi:
10.1002/1531-8257(199903)14:2PMID: 10091643.

Question 59

Dopaminergic projections to the nucleus accumbens primarily come from which of the following
structures?
Answers:
A. Caudate
B. Putamen
C. Ventral tegmental area
D. Substantia nigra
E. Arcuate Nucleus

Answer 59

Ventral tegmental area

Discussion:
Dopaminergic neurons in the ventral tegmental area project to the nucleus accumbens, mediating
reward as a part of the dopaminergic-behavioral system. The mesolimbic dopaminergic system is
an important ascending and activating component of the medial forebrain bundle involved in
learning, as well as in the motivational effects of electric brain stimulation. Increasing dopamine
levels into the nucleus accumbens with psychostimulants enhances the rewarding properties of
self-stimulation itself. The mesolimbic dopaminergic system is considered a key circuitry involved
in appetite, attention to rewards, behavioral persistence, and the avoidance of punishment.
Dopaminergic neurons in the substantia nigra project to the striatum (caudate and putamen) as a
part of the dopaminergic-motor system.
Dopaminergic neurons in the arcuate nucleus of the hypothalamus play a role in the dopaminergicendocrine system regulating prolactin release.
References:
Castillo Diaz F, Caffino L, Fumagalli F, “Bidirectional role of dopamine in learning and memoryactive forgetting,” Neuroscience Behavioral Review. 2021 Dec; 131:953-963.
Pubmed Web link: https://pubmed.ncbi.nlm.nih.gov/34655655/
Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia A-S, Mooney R, Platt L, White LE.
Neuroscience. 6th ed. New York, NY: Oxford University Press: Sinauer Associates, Inc.; 2018.
Alcaro A, Huber R, Panksepp J. Behavioral functions of the mesolimbic dopaminergic system: an
affective neuroethological perspective. Brain Res Rev. 2007;56(2):283-321.
doi:10.1016/j.brainresrev.2007.07.014
Pubmed Web link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2238694/

Question 60

Sympathetic preganglionic neurons in the splanchnic nerves primarily innervate which of the
following structures?
Answers:
A. Superior Cervical Ganglion
B. Coccygeal Ganglion
C. Inferior Mesenteric Ganglion
D. End-organs
E. Celiac Ganglion

Answer 60

Celiac Ganglion

Discussion:
Preganglionic sympathetic nerve fibers within the splanchnic nervous system innervate the celiac
ganglion via the greater and lesser splanchnic nerves. The celiac plexus provides sympathetic
tone to most of the abdominal viscera. Celiac plexus neurolysis is a pain management option for
patients with unresectable pancreatic cancer. Autonomic hyperreflexia occurs in approximately
30% of quadriplegic patients from spinal cord injury due to lesions at or above T6, above the
splanchnic outflow track.
References:
McCausland C, Sajjad H. Anatomy, Back, Splanchnic Nerve. [Updated 2021 Aug 11]. In:
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK549856/
Kandel, E. R. (2012). Principles of Neural Science, Fifth Edition. United Kingdom: McGraw-Hill
Education.
Surgical Management of Pain. Burchiel K, ed. 2nd Edition. New York: Thieme; 2015

Question 61

Which of the following is the most effective deep brain stimulation target for primary generalized
dystonia?
Answers:
A. Globus Pallidus Internus
B. Caudate Nucleus
C. VIM thalamus
D. Cingulate gyrus
E. Subthalamic Nucleus

Answer 61

Globus Pallidus Internus

Discussion:
Primary generalized dystonia is a syndrome characterized by sustained muscle contractions
causing twisting and repetitive movements or abnormal postures with resultant physical and social
incapacity in patients with normal cognitive function. Generally, the most common oral medical
therapy includes anticholinergics, GABAergics, and muscle relaxants. Pharmacologic treatments
have limited efficacy, and injections of botulinum toxin are useful only in restricted areas (e.g., the
face and neck). Deep brain stimulation (DBS) at the internal globus pallidus (GPi) has emerged as
the best therapeutic option for patients with disabling primary dystonia that is poorly responsive to
pharmacologic treatment. Sustained motor and quality-of-life improvements after pallidal DBS has
been well documented up to 3 years. Stimulation at 60 Hz and shorter pulse width seem to
achieve sustained clinical outcomes.
References:
Lubarr N, Bressman S. Treatment of generalized dystonia. Curr Treat Options Neurol. 2011
Jun;13(3):274-89. doi: 10.1007/s11940-011-0122-0. PMID: 21455718.
Rodrigues FB, Duarte GS, Prescott D, Ferreira J, Costa J. Deep brain stimulation for dystonia.
Cochrane Database Syst Rev. 2019 Jan 10;1(1):CD012405. doi:
10.1002/14651858.CD012405.pub2. PMID: 30629283; PMCID: PMC6353249