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Life Long Learning in Neurology - part 8 pdf

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PET scans have utility, again, in establishing a diagnosis but at this point have not proven practical in following disease progression; genetic status has utility for predicting disease

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E Subjects with depression are easily screened out of trials

Correct Answer: The correct answer is A Bearing in mind the caveats above as well as cultural, linguistic, and

other factors that may have influenced large clinical trials in aMCI, the author concludes that the high rate of

conversion of study subjects from aMCI to AD (minimally double or triple the conversion rate in the general

population) points to a valuable group of subjects for future clinical trials The author notes that MCI, while a

difficult concept for some hysicians, has been well received in the modern literature and has proven a useful group

of patients to enter into clinical trials APOE4 carriers do skew conversion rates from aMCI to AD; screening

subjects with depression out of clinical trials is felt to have influenced, for example, the rivastigmine trial's lower

conversion rate to AD Donepezil did show a treatment benefit for 12 months in all subjects and up to 24 months in

APOE+ subjects

23 Which of the following studies has been used with accuracy to follow progression of Alzheimer's disease?

A FDG-PET scans for increasing areas of decreased parietal metabolism

B Genotyping for APOE4 status

C Serial lumbar punctures for A beta 1-42 protein levels

D Serial lumbar punctures for CSF tau levels

E Structural MRI for hippocampal and brain volume

Correct Answer: The correct answer is E Although many techniques and biomarkers are currently under study, of

the above studies, only choice E, with demonstration of continuing loss of hippocampal and whole brain volume,

has been demonstrated to correlate well with clinical progression of Alzheimer's disease A beta 1-42 and tau levels

in CSF have some correlation when a diagnosis is being established, but they are felt to have some overlap with

normal aging and have not been used to study disease progression PET scans have utility, again, in establishing a

diagnosis but at this point have not proven practical in following disease progression; genetic status has utility for

predicting disease probability of developing Alzheimer's disease at a particular age but is of no utility in tracking

disease progression

24 A 65-year-old man is sent to the physician for gait problems of 1-year's duration He notes difficulty keeping up

with his wife on their morning walks, although he is not short of breath and his legs and back don't hurt He feels as

though his legs are heavy Further history reveals some urinary urgency without a problem initiating his stream He

is treated for hyperlipidemia and mild hypertension In his 30s, he was involved in a severe motor vehicle accident

for which he was hospitalized; he was unconscious for several days after his head struck the windshield at that

time On examination, he is fully alert and oriented but somewhat slow to respond; facial expression is normal, and

no tremor is seen Head circumference is 58 cm His gait is slow with normal caliber steps but with a tendency to

"stick to the ground." MRI scan of the brain done prior to his appointment reveals ventriculomegaly with mild

diffuse atrophy A diagnosis of normal pressure hydrocephalus (NPH) is entertained Which of the following

statements is true regarding prognosis after surgery in this patient if NPH is diagnosed?

A It is good because of a possible secondary cause for NPH

B It is poor because he has brain atrophy on imaging studies

C It is poor because of the normal head circumference

D It is worse because of the presence of prior hypertension

E It is worse due to prior head injury

Correct Answer: The correct answer is A Patients who have a prior history of either a head injury or some other

possible cause of a previous meningeal process (including subarachnoid hemorrhage or meningitis) may have

secondary hydrocephalus; thus, per the author of chapter 6, Normal Pressure Hydrocephalus, they are more likely

to improve with surgery It is incorrect that prognosis is worse due to previous head injury The patient's brain

atrophy is described as minor Normal head circumference does not infer a poor prognosis Although the

relationship between NPH and systemic hypertension is an area of active research, choice D would seem to be

incorrect in this patient because it is a mild finding

25 A 67-year-old woman has had gradually progressive memory problems for the past 3 years She was diagnosed

with Alzheimer's disease and started on donepezil about 2 years ago, but she and her family did not think it made

any difference, so she stopped taking it after about 4 months A few months later, she began to see people in the

corner of her bedroom at night, and she became convinced that they were trying to steal her clothes This gradually

evolved into an ongoing conviction that there was a conspiracy to steal her clothes, and she began to hoard them,

shouting and making threatening gestures whenever her husband collected her laundry On a few occasions, she

actually hit her husband About a year ago, she started walking more slowly, and over the past 6 months she has

had four falls without a clear reason Her examination is notable for moderate parkinsonism and mild dementia,

with a Mini-Mental State Examination (MMSE) score of 23/30 Which of the following medications would be most

likely to result in clinical deterioration?

A Clonazepam

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B Haloperidol

C Memantine

D Rivastigmine

E Trazodone

Correct Answer: The correct answer is B This patient meets criteria for probable dementia with Lewy bodies (DLB), with the central feature (dementia) and two core features (spontaneous parkinsonism and recurrent visual hallucinations) Her systematized delusions are a supportive feature Patients with DLB can have severe neuroleptic sensitivity, so medications such as haloperidol should be avoided

26 Which of the following behavioral symptoms is (are) most common in patients with Alzheimer's disease?

A Apathy

B Delusions

C Disinhibition

D Euphoria

E Hallucinations

Correct Answer: The correct answer is A Apathy and dysphoria are the two most pervasive neuropsychiatric symptoms at all stages of Alzheimer's disease (AD) Delusions and hallucinations are fairly common in more advanced AD but still not as common as apathy and dysphoria Disinhibition is also less common than apathy and dysphoria, and euphoria is uncommon at all stages of AD

27 A 70-year-old man is referred to a physician for further evaluation of cognitive problems His wife states that

he has been forgetful for about 2 years and that he "sleeps all day and doesn't do anything." Previously, he would work in the garden or read Approximately 4 months ago, he began to have problems walking such that it is very difficult for him to initiate his gait He has fallen on at least five occasions On physical examination, he is noted to

be abulic but attempts to follow all commands; grasp and snout reflexes are present He is able to recall a recent item in the news No aphasia is present He needs assistance to get to a standing position and then appears stuck to the ground He finally starts walking by taking very small propulsive steps An outside MRI scan shows ventriculomegaly and frontal atrophy In considering evaluation for a shunt, what advice can the clinician give to the patient and his wife?

A Cognitive performance is unlikely to improve

B The MRI suggests Parkinson's disease

C The patient is probably depressed

D The patient's age precludes shunting

E The patient's gait is very likely to improve

Correct Answer: The correct answer is A The author of chapter 6, Normal Pressure Hydrocephalus, notes that patients whose dementia preceded their gait abnormality are less likely to respond to surgery, particularly in terms

of cognitive improvement The patient's gait may improve, even if the patient has more than one type of pathology; however, evidence for "very likely" improvement is scant It is not true that the patient's age precludes shunting; the patient's presentation does not suggest idiopathic Parkinson's, nor can that be determined by MRI It might be difficult to determine whether the patient is depressed, but this is not suggested by the patient's attempt to cooperate with the examiner

28 A 65-year-old woman is brought to the physician for evaluation by her husband for difficulty with cognition Her husband reports a 1-year history of increasing problems with "getting her words out." The patient feels she is blocking on her words She is college-educated and worked in real estate Initial evaluation shows normal orientation and memory; on a standard naming test she scores in the moderately impaired range She otherwise drives, keeps a checkbook, and runs the household Her general medical history is significant for hypertension Neurologic and neuropsychological evaluation does not reveal depression, although she is frustrated about her inability to express herself MRI scan of the brain reveals moderate deep white matter disease Which of the following is the most likely diagnosis at this time?

A Alzheimer's disease

B Executive dysfunction

C Frontotemporal dementia

D Mild cognitive impairment, single domain

E Multi-infarct dementia

Correct Answer: The correct answer is D This patient currently displays a deficit in language manifested by nonfluency with otherwise retained memory Her nonlanguage functions are described as normal and her activities

of daily living are well maintained Executive dysfunction is not apparent, and her deficit in only one cognitive domain does not suggest Alzheimer's disease at this point nor frontotemporal dementia Although the patient has

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white matter disease on her scan, there is no suggestion of multiple strokes, and this could be considered a common

finding in the setting of hypertension Single domain mild cognitive impairment best describes her current deficit

29 Which of the following behavioral symptoms is (are) most likely to improve in response to cholinesterase

inhibitors?

A Aberrant motor behavior

B Delusions

C Disinhibition

D Dysphoria

E Hallucinations

Correct Answer: The correct answer is D The greatest impact of cholinesterase inhibitors in most trials has been on

apathy and mood symptoms

30 Which of the following pairs of conditions can be differentiated most reliably using currently available

structural imaging modalities?:

A Alzheimer's disease (AD) from dementia with Lewy bodies

B Alzheimer's disease (AD) from frontotemporal dementia (FTD)

C Alzheimer's disease (AD) from mild cognitive impairment (MCI)

D Dementia with Lewy bodies from mild cognitive impairment

E Mild cognitive impairment (MCI) from normal aging

Correct Answer: The correct answer is B Structural imaging techniques are important in distinguishing the

structural patterns of atrophy in FTD and AD and in identifying the contribution of cerebrovascular disease to

dementia The pattern of atrophy in dementia with Lewy bodies has not yet been well established Structural MRI

scans of subjects with mild cognitive impairment show patterns of atrophy similar to those seen in patients with

AD, but the severity is intermediate between that of normal controls and patients with AD; the overlap is too large

to have prognostic value in individual patients

31 An 80-year-old man who has not been previously seen by a physician for cognitive problems is brought in for

an expedited appointment because of abrupt worsening of his mentation following prostate surgery His wife

reports that she had noted some decline in his short-term memory and driving skills in the 6 months preceding his

surgery; however, she attributed this to "old age" and did not bring him to the doctor Following his surgery, he was

prescribed hydrocodone briefly and was also given a sleeping medicine to take home Now, 2 weeks after surgery,

he has been sleeping a great deal and has failed to recognize family members on a few occasions He is concerned

that someone has been sneaking into the house at night On testing, the patient is cooperative, but does not know

the date or any recent news He cannot spell the word world in reverse and does not recall who operated on him He

asks if George is in the next room The rest of his examination is nonfocal What is the most immediate step for the

physician to take at this time?

A Prescribe a cholinesterase inhibitor

B Reassure the family that the patient will improve

C Refer for neuropsychological evaluation

D Send the patient for an EEG

E Stop the patient's new medications

Correct Answer: The correct answer is E In approximately 5% of patients, according to the author of chapter 2,

Alzheimer's Disease, a reversible cause of dementia may be found, although the vast majority are found to have

neurodegenerative or ischemic disease However, even among those with irreversible underlying disease, 25% to

40% may be found to have either a correctable metabolic problem or to be taking a drug that has worsened the

situation Withdrawing the offending drug or correcting the metabolic abnormality may give transient functional

improvement and should be done In the case above, the patient may need to be referred for neuropsychological

evaluation or prescribed a cholinesterase inhibitor at some point; epilepsy mimicking a dementia is uncommon, and

reassuring the family is insufficient as an immediate step

32 Progranulin mutations have been associated with which of the following diseases?

A Alzheimer's disease

B Corticobasal degeneration

C Dementia with Lewy bodies

D Frontotemporal dementia

E Progressive supranuclear palsy

Correct Answer: The correct answer is D Although some cases of frontotemporal dementia are associated with

mutations in the gene for tau protein or at least with neuronal inclusions that contain tau protein, many are not

Progranulin mutations have been identified as the cause of frontotemporal dementia in some of these tau-negative

cases

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33 Over several decades, different criteria have been proposed to clinically diagnose vascular dementia, with some criteria more conservative than others In a large series of 480 cases of incident dementia in the Cardiovascular Health Study, application of NINDS-AIREN criteria was least likely to lead to a diagnosis of probable vascular dementia Which of the following neurologic abnormalities is required by these criteria to make the diagnosis?

A Aphasia or hemispatial neglect

B Frontal release signs

C Hemiparesis

D Memory impairment

E Mild brain atrophy

Correct Answer: The correct answer is D The NINDS-AIREN criteria for probable vascular dementia (VaD) are considered the most conservative of current measures, requiring fulfillment of criteria in several domains Among those are cognitive impairment in memory and two other domains as well, making memory impairment the correct answer Aphasia or hemispatial neglect may be true but is not sufficient Frontal release signs may be found in the absence of vascular pathology, and mild brain atrophy is not discussed While hemiparesis fulfills the criterion for focal neurologic signs, it would be insufficient without the presence of memory impairment

34 Compared with PET scans of patients with Alzheimer's disease, PET scans of patients who have dementia with Lewy bodies show more pronounced hypometabolism in which of the following locations?

A Frontal lobe

B Medial temporal lobe

C Occipital lobe

D Posterior cingulate gyrus

E Precuneus

Correct Answer: The correct answer is C The patterns of hypometabolism and hypoperfusion are very similar in Alzheimer's disease and dementia with Lewy bodies, but patients with dementia with Lewy bodies appear to have more reduction of activity in the occipital lobes, which are relatively spared in patients with Alzheimer's disease

35 A 72-year-old man is diagnosed with amnestic mild cognitive impairment (aMCI) by a clinician after presenting with a 2-year history of short-term memory loss His wife is concerned that he is developing Alzheimer's disease because she cared for her own elderly parent with dementia Which of the following is a reasonable estimate of the yearly conversion to Alzheimer's disease in patients diagnosed with aMCI?

A 0.5%

B 1%

C 10%

D 20%

E 25%

Correct Answer: The correct answer is C Although there has been some variability in studies concerning conversion rates from aMCI to Alzheimer's disease, 10% per year is cited as a reasonable figure, with the percentage somewhat higher in a neurology referral-based population and somewhat lower in the general population

36 In a patient who developed dementia and spontaneous parkinsonism concurrently, the presence of which of the following features would meet the criteria for the diagnosis of probable dementia with Lewy bodies?

A Autonomic dysfunction

B Depression

C Prominent slow-wave activity on EEG, with temporal lobe transient sharp waves

D REM sleep behavior disorder

E Systematized delusions

Correct Answer: The correct answer is D In a patient with the central feature (dementia) and one core feature (in this case, spontaneous parkinsonism), the presence of any other core feature or suggestive feature will meet criteria for the diagnosis of probable dementia with Lewy bodies (DLB) REM sleep behavior disorder is one of the three suggestive features included in the current diagnostic criteria for DLB; all of the other features listed are supportive features, which do not contribute to the determination of whether a patient meets criteria for probable DLB

37 Which of the following ratios of signals on MRI spectroscopy (MRS) provides the most consistent and reliable differentiation between patients with Alzheimer's disease and control subjects?

A Choline to creatine plus phosphocreatine (Cho/Cr)

B Choline to myoinositol (Cho/MI)

C Myoinositol to creatine plus phosphocreatine (MI/Cr)

D N-acetylaspartate to creatine plus phosphocreatine (NAA/Cr)

E N-acetylaspartate to myoinositol (NAA/MI)

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Correct Answer: The correct answer is E To control across subjects and study centers, Cr is typically used for a

reference signal; it is thought to be unaffected in patients with dementia Patients with Alzheimer's disease have

reduced levels of NAA (a marker of neuronal density) and increased levels of MI (a marker of glial cell activity)

Consequently, the NAA/Cr ratio is reduced and the MI/Cr ratio is increased, but these measures have less

specificity than the NAA/MI ratio, which is robust in discriminating patients with AD from healthy controls While

some studies have identified elevated Cho and Cho/Cr ratios in Alzheimer's disease, others have reported normal

levels

38 An 86-year-old Hispanic man is brought to the physician for follow-up He was diagnosed 1 year previously

with Alzheimer's disease after exhibiting progressive loss of short-term memory and decreased function in

activities of daily living He has a sister, aged 83, who has mild problems with short-term memory; his parents died

in their 60s and apparently had well-preserved cognition He worked as a tool-and-dye maker in a machine shop

He is otherwise quite healthy and is treated only for mild hypertension Which of the following risk factors is most

closely associated with Alzheimer's disease in this patient?

A Age

B Education level

C Family history

D Gender

E Race

Correct Answer: The correct answer is A The author of chapter 2, Alzheimer's Disease, notes that "the major risk

factor for Alzheimer's disease is aging." Persons in the age category of 85 have an estimated 35% to 50%

prevalence of the disease Race as a risk factor is not discussed In terms of gender, there is actually a slightly

higher risk for the disease in women; family history is significant, with about a 20% chance of having an affected

sibling or parent in patients with Alzheimer's disease Education level has been raised as an issue with suggestion

of a positive association between higher education and reduced risk or later onset of disease, but this is not

definitive

39 A 75-year-old woman with a long history of hyperlipidemia and hypertension is brought to the physician by her

husband because of problems with her memory Her husband reports that he has noticed a gradual worsening in

function over the past year such that he has had to take over the family finances and has had to help out more with

household chores At times, his wife seems somewhat slow to answer, and he wonders if she hasn't had a "bunch of

mini strokes." On examination, she is alert and oriented to the month and day of the week Both generative and

confrontational naming are impaired, but comprehension is intact She is able to bisect a line and performs a

calculation Recall is one out of three items at 5 minutes There are no focal motor or sensory findings Gait is

normal An MRI scan of the brain shows moderate deep white matter disease, an old right basal ganglia lacunar

infarct, and bilateral hippocampal atrophy Based on the above findings, what is the most likely diagnosis in this

patient?

A Alzheimer's disease

B Binswanger syndrome

C Mild cognitive impairment

D Vascular cognitive impairment

E Vascular dementia

Correct Answer: The correct answer is A The patient described above presents with a progressive, not truly

stepwise decline primarily in short-term memory and language skills with impairment of function but without other

focal neurologic signs Even by liberal criteria, the patient does not have a vascular dementia, nor does she meet the

definition of cognitive impairment caused by cerebrovascular disease Her impairment in activities of daily living

makes mild cognitive impairment incorrect Binswanger syndrome is also incorrect because the patient does not

exhibit a slow progressive decline in gait and cognition Therefore, Alzheimer's disease is the most likely diagnosis

40 Dysphoria is most prevalent among patients in which of the following categories?

A Cognitively normal elderly

B Mild Alzheimer's disease

C Mild cognitive impairment

D Moderate Alzheimer's disease

E Late Alzheimer's disease

Correct Answer: The correct answer is E Dysphoria, like most behavioral symptoms, increases in prevalence with

increasing severity of Alzheimer's disease

Sleep Disorder June 2007

1 A 15-year-old boy has had episodes of arousals during sleep occurring once or twice a week since the age of 5

He typically will get out of bed and walk around his room with a blank stare On a few occasions, he has appeared

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to look for something in a dresser drawer or manipulate objects on his desk He does not usually speak or respond during these episodes His parents usually lead him back to his bed, where he then remains asleep, for the remainder of the night In the morning, he will have no memory of these events Which of the following clinical or epidemiologic features is most consistent with this patient's disorder?

A Epileptiform abnormalities on EEG

B Occurrence during REM sleep

C Occurrence more common in the later half of the nightly sleep cycle

D Provocation of episodes by obstructive sleep apnea

E Worsening with age

Correct Answer: The correct answer is D This patient most likely suffers from sleepwalking, a disorder of arousal occurring during non-REM sleep It is not associated with epileptiform abnormalities on EEG but may be associated with increased amounts of slow-wave sleep on polysomnography Sleepwalking typically occurs during the first third of the sleep period Approximately 30% of children and 1% to 3% adults have episodes of sleepwalking Among children, the disorder will usually lessen and disappear with maturity First-degree relatives are at increased risk of developing this disorder Obstructive sleep apnea has been noted to be a provocative factor for sleepwalking in adults and children

2 A 68-year-old man undergoes polysomnography because his wife reports the development of a somewhat alarming high-pitched sound, as if he is straining for air, in addition to his usual snoring Stridor is suspected and confirmed by laryngoscopic examination, showing restriction of vocal cord abduction Nocturnal inspiratory stridor

is most commonly found in which of the following neurodegenerative illnesses?

A Alzheimer's disease

B Dementia with Lewy bodies

C Huntington's disease

D Multiple system atrophy

E Parkinson's disease

Correct Answer: The correct answer is D The most characteristic respiratory sleep disorder in multiple system atrophy is nocturnal stridor, which may be due to a neuronopathy of the recurrent laryngeal nerve and/or overactivity of the posterior cricoarytenoid muscles

3 A technician is scoring the polysomnographic recording of a 42-year-old man who is being evaluated for sleep apnea He is currently examining a page of 30-second epochs that each contains approximately 30% to 40% of high-amplitude 03-Hz to 2.0-Hz activity According to the American Academy of Sleep Medicine sleep scoring manual, he should score these epochs as which of the following sleep-wake states?

A Non-REM (NREM) 1

B NREM 2

C NREM 3

D NREM 4

E REM

Correct Answer: The correct answer is C The new American Academy of Sleep Medicine (AASM) scoring criteria use wakefulness, REM sleep, and only three stages of NREM sleep, not four as in the old Rechtschaffen and Kales criteria Under AASM criteria, NREM 3 (N3) is present when 20% or more of a 30-second epoch contains slow-wave activity

4 A 60-year-old woman reports a 20-year history of leg discomfort that is most prominent and bothersome in the evening It often interferes with falling asleep She can obtain complete temporary relief by moving her feet or walking around Her medical history is remarkable for hypertension, hyperlipidemia, renal calculi, and gastroesophageal reflux, for which she is on several medications The neurologic examination is normal Of the patient's medications, which of the following is most likely to exacerbate her leg discomfort?

A Allopurinol

B Atorvastatin

C Hydrochlorothiazide

D Metoclopramide

E Metoprolol

Correct Answer: The correct answer is D This patient has restless legs syndrome (RLS), a condition associated with dopaminergic dysfunction in the CNS Medications with dopaminergic blocking activity, including antipsychotics and antiemetics, may worsen the symptoms of RLS

5 A 56-year-old man presents to his physician for evaluation of loud snoring and excessive daytime sleepiness He notes frequent nocturnal awakenings with sweating and sometimes vivid dreams of "drowning." His body mass

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index is 32 kg/m2 In addition to his obesity, which of the following physical characteristics or components of the

medical history are likely to lead to his sleep-related breathing problems?

A Caffeine consumption

B Marfan's syndrome

C Prior tonsillectomy

D Short uvula

E Wide hard palate

Correct Answer: The correct answer is B In addition to obesity, the physical characteristics that increase the risk of

obstructive sleep apnea (OSA) include a narrow high-arched palate, macroglossia, dental overbite, elongated

swollen uvula, neck circumference greater than 17 inches, enlarged inferior nasal turbinates, septal deviation, and

enlarged tonsils and adenoids Alcohol consumption prior to sleep may also increase the risk of OSA Caffeine

consumption is not associated with increased risk for OSA Patients with Marfan's syndrome are at increased risk

of developing OSA, presumably because of their tendency to have narrowed facial features and, possibly, increased

joint laxity of the temporomandibular joint

6 Skeletal atonia during REM sleep is now known to be regulated by a specific group of neurons Destruction of

this group of neurons or its connections can cause REM sleep without atonia in rats or REM sleep behavior

disorder in humans Which of the following is the group of neurons that is required to generate REM

sleep-associated skeletal atonia?

A Basal forebrain nuclei

B Dorsal raphe nucleus

C Solitary tract nucleus

D Sublaterodorsal nucleus

E Suprachiasmatic nucleus

Correct Answer: The correct answer is D The sublaterodorsal nucleus of the pontine reticular formation in humans

is equivalent to the subcoeruleus or peri-locus coeruleus alpha region in cats Damage to the sublaterodorsal

nucleus or its connections can cause REM sleep without atonia in rats and REM sleep behavior disorder in humans

Degeneration of the basal forebrain neurons, as in Alzheimer's dementia, is associated with insomnia The

suprachiasmatic nucleus is the primary internal circadian clock in mammals Both the raphe nuclei and the nucleus

of the solitary tract have been shown to be involved in regulation of various aspects of sleep, but specific lesions do

not cause loss of REM sleep skeletal atonia

7 A 14-year-old boy presents with prolonged episodes of hypersomnolence lasting days He has had three

episodes, each lasting 3 to 10 days, in the past 2 years that have been disruptive to his schoolwork During these

episodes he spends most of the day and night asleep in bed and arises only briefly to eat large amounts of food in a

compulsive fashion Blood work and MRI performed during an episode are normal A polysomnogram done during

the episode shows reduced sleep efficiency, and an EEG shows diffuse cortical slowing Between episodes he is

neurologically normal with normal behavior at school and at home He takes no medications and uses no

recreational drugs Which of the following treatments or medications would be most likely to be helpful in this

disorder?

A Electroconvulsive therapy

B Gabapentin

C Haloperidol

D Lithium

E Psychotherapy

Correct Answer: The correct answer is D This patient most likely has Kleine-Levin syndrome (KLS) KLS is an

idiopathic disorder usually affecting boys in the second decade of life The disorder is characterized by prolonged

episodes of hypersomnolence typically lasting days In association with the hypersomnolence, some patients

exhibit hypersexuality or other compulsive behaviors The polysomnogram often shows reduced sleep efficiency

and diffuse EEG slowing during the episode but is normal in between episodes Blood work and neuroimaging are

normal No large treatment trials have been conducted for this rare disorder; lithium may be the most effective

medication, although some patients respond to stimulants The other treatments listed have not been shown to be

consistently effective

8 A 40-year-old woman reports a 6-month history of severe insomnia She states, "I don't sleep at all I'm sure that

I don't sleep for more than 1 or 2 hours each night." She has been able to work full time as a receptionist but

reports, "I'm not as sharp as I should be." She has had no episodes of excessive daytime sleepiness, and she usually

does not take a daytime nap Her husband reports that she is generally asleep on the occasions that he awakens to

go to the bathroom at night She generally tries to go to bed at a specified time each night and avoids caffeine and

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alcohol in the evening She denies depressed mood and reports no stressors other than her lack of sleep Which of the following types of insomnia best characterizes this patient's disorder?

A Adjustment sleep disorder

B Idiopathic insomnia

C Inadequate sleep hygiene

D Paradoxical insomnia

E Psychophysiologic insomnia

Correct Answer: The correct answer is D This patient has paradoxical insomnia It is characterized by reportedly severe insomnia without evidence of an objective sleep disturbance and without significant daytime impairment as would be expected with the reported sleep disturbance Psychophysiological insomnia is associated with a heightened level of arousal with negative conditioning for sleep Adjustment sleep disorder is insomnia associated with a specific stressor Inadequate sleep hygiene is a disorder characterized by irregular scheduling of sleep times, stimulant and alcohol use prior to sleep, and engaging in alerting activities prior to sleep Idiopathic insomnia is a long-standing, often lifelong, form of insomnia without associated etiologic factors or stressors

9 A 45-year-old woman develops an uncomfortable crawling sensation in her calves each night as she tries to fall asleep She can obtain relief only with leg movement Her neurologic examination is normal, and her serum ferritin level is greater than 50 µg/L Pramipexole, ropinirole, levodopa, and opioids alleviate the symptoms, but each has produced intolerable side effects Which of the following medications would be most helpful in treating this patient's symptoms?

A Bromocriptine

B Ferrous sulfate

C Gabapentin

D Nortriptyline

E Zolpidem

Correct Answer: The correct answer is C Dopamine agonists are considered the best first-line therapy for restless legs syndrome (RLS) However, the patient has already experienced side effects from three other dopaminergic drugs, and the ergot-based dopaminergic agonists such as pergolide and bromocriptine are less used currently because of the risk of cardiac valvular fibrosis Opioids are a good second-line therapy, but the patient has already experienced side effects from opioids Iron therapy is only helpful if the serum ferritin is in the bottom third of the normal range (less than 50 µg/L), and it may take a few months to work since iron crosses the blood-brain barrier poorly Gabapentin and clonazepam may be helpful in some patients Zolpidem has no known effect in the treatment of RLS Antidepressants such as nortriptyline may sometimes worsen the symptoms of RLS

10 A 10-year-old boy has episodes occurring during sleep in which he awakens and has rhythmic jerking of his right face, speech arrest, and drooling The episodes occur in the early part of the sleep period He has had no daytime episodes Which of the following EEG findings is most likely to be associated with this patient's disorder?

A Atypical spike-and-wave

B Centrotemporal spikes

C 3 Hz spike-and-wave

D Normal EEG

E Wicket waves

Correct Answer: The correct answer is B This patient most likely has benign focal epilepsy with centrotemporal spikes (benign rolandic epilepsy), which occurs in children between the ages of 5 and 12 years It is characterized

by nocturnal focal motor seizures affecting the face and hemibody, often with expressive language difficulties and drooling These episodes usually occur in the first 2 hours of sleep The episodes usually resolve as the child reaches puberty Anticonvulsants often are not required The EEG shows centrotemporal spikes Wicket waves are

a normal variant seen in an awake EEG Atypical spike-and-wave and 3 Hz spike-and-wave would be associated with other types of seizure disorders

11 A 42-year-old man has a known diagnosis of narcolepsy with cataplexy His disease has been reasonably well controlled for many years with lifestyle changes and a medication regimen He travels across country on a business-related trip and forgets to bring his medication with him He sleeps poorly the first night there and the next day experiences four episodes of cataplexy Withdrawal of which of the following medications is most likely to cause rebound cataplexy?

A Clomipramine

B Dextroamphetamine

C Modafinil

D Pemoline

E Sodium oxybate

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Correct Answer: The correct answer is A Abrupt discontinuation of tricyclic antidepressants and, to a lesser

degree, selective serotonin reuptake inhibitor agents may cause rebound cataplexy including status cataplecticus

Rebound cataplexy is not seen with sodium oxybate or the other agents

12 In order to make a diagnosis of obstructive sleep apnea in an adult patient, what is the minimal respiratory

disturbance index required on an overnight polysomnogram?

A 5

B 10

C 15

D 20

E 25

Correct Answer: The correct answer is A The respiratory disturbance index (RDI) refers to the combined total

number of apneas, hypopneas, or respiratory effort-related arousals (RERAs) that occur per hour of sleep In order

to make a diagnosis of obstructive sleep apnea (OSA), an RDI of 5 or greater is required An RDI of 5 to 15 is

associated with mild OSA An index of 15 to 30 is associated with moderate OSA, and an RDI greater than 30 is

consistent with severe OSA

13 Where are the hypocretin-containing neurons located?

A Lateral hypothalamus

B Locus coeruleus

C Midbrain raphe nucleus

D Oral pontine reticular nucleus

E Ventrolateral preoptic nucleus

Correct Answer: The correct answer is A The hypocretin-containing neurons are located in the perifornical and

lateral hypothalamus, from which they project widely to numerous brain nuclei, including those involved in control

of sleep and wakefulness The hypocretin-containing neurons are believed to activate a motor facilitatory system in

the locus coeruleus and the raphe nuclei The oral pontine reticular nucleus is believed to be involved in the

modulation of REM sleep The ventrolateral preoptic nucleus is a sleep-promoting nucleus

14 A 72-year-old man with moderate dementia with clinical features most consistent with Alzheimer's disease has

been experiencing sleep disturbances with frequent nocturnal awakenings Which of the following features are

most likely to be found in this man compared with normal age-matched controls?

A Decrease in daytime sleep

B Decrease in suprachiasmatic nuclei cell number

C Increased CSF melatonin levels

D Neuritic plaque deposition in pineal gland

E Neurofibrillary tangles in the retinal ganglion cell layer

Correct Answer: The correct answer is B Patients with Alzheimer's disease have been demonstrated to have an

approximately 60% decrease in the total suprachiasmatic nuclei cell number (with associated neurofibrillary tangle

formation) compared with age-matched controls, suggesting that this region is integrally involved in the

degenerative processes of Alzheimer's disease (AD) Daytime sleep is generally increased in patients with AD CSF

melatonin levels are decreased in patients with AD Neuritic plaques have not been demonstrated in the pineal

gland Cell loss is seen in the retinal ganglion cell layer without the presence of neurofibrillary tangles

15 A 46-year-old woman is working many hours in an effort to become a partner in her law firm She also has

three teenaged children and tries her best to attend as many of their activities as possible She estimates that she

feels best when she sleeps 7 hours per night but actually manages to sleep approximately 5.5 hours per night She

describes herself as chronically fatigued She does not have time to exercise and has gained 20 lbs in the last year

Which of the following metabolic changes is most likely to result from her sleep deprivation?

A Decreased blood glucose levels

B Decreased carbohydrate intake

C Increased ghrelin levels

D Increased glucose clearance rate

E Increased leptin levels

Correct Answer: The correct answer is C Sleep deprivation has been shown to have multiple effects on appetite,

diet, and metabolism In a sleep deprivation state, blood levels of ghrelin, a hormone secreted by the stomach that

stimulates appetite, are increased The blood levels of leptin, an endogenous hormone released by fat cells that

signals satiety, are decreased Hunger, appetite, and carbohydrate consumption increase with sleep deprivation

Sleep deprivation is also associated with decreased brain glucose utilization, lower insulin responses to glucose,

slower glucose clearance rates, and increased blood glucose levels Partial sleep deprivation can cause reversible

features of a prediabetic state

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16 A 6-year-old boy has had episodes of enuresis 4 to 5 nights per week He has never been continent at night since birth His development otherwise has been normal There are no symptoms to suggest sleep-disordered breathing His physical examination is normal In addition to limiting fluid intake prior to sleep and waking strategies to empty the bladder, which of the following medications would be most helpful in treating this problem?

A Benztropine

B Clonazepam

C Desmopressin

D Fluoxetine

E Ropinirole

Correct Answer: The correct answer is C This patient has primary enuresis, which will most likely spontaneously remit before adolescence Interventions such as limiting nighttime fluid intake and various waking strategies before wetting occurs are appropriate treatments Bedtime desmopressin (DDAVP), which concentrates urine and therefore reduces urine volume, is helpful, although most children will relapse once the drug is stopped Tricyclics are also effective medications for enuresis, although side effects may limit their use

17 A 25-year-old medical student presents reporting insomnia He and his girlfriend report he has had difficulty falling asleep and/or staying asleep for 3 months He is an MD-PhD candidate in the PhD phase of his studies and

is trying to complete his thesis by June so that he may enter the last 2 clinical years of medical school in time to join his girlfriend's class Since he does not have regular classes, he stays up late some nights to work and not others He has no routine time to get up in the morning In his push to finish, he no longer takes a daily run for exercise as he once did He does not like to work in absolute quiet, so he generally has the television on in the background while he works and leaves it on when he tries to go to sleep He estimates that he drinks four cans of soda in the evening Which of the following best describes the type of his insomnia?

A Idiopathic

B Inadequate sleep hygiene

C Paradoxical

D Psychophysiologic

E Sleep-onset association type

Correct Answer: The correct answer is B Inadequate sleep hygiene is one cause of secondary or comorbid insomnia It is due to daily habits and practices that are not conducive to obtaining adequate sleep, such as variable sleep and wake times, inappropriate use of caffeine, and keeping the television on at night Psychophysiologic insomnia is a form of chronic insomnia often persisting after resolution of an acute stressor, clearly not the case here The fact that the insomnia is of recent onset makes an idiopathic insomnia unlikely He is not experiencing paradoxical insomnia or sleep state misperception as his girlfriend can attest to his poor sleep Sleep-onset association type is a form of childhood insomnia related to excessive reliance on certain environmental stimuli to fall asleep

18 For the past 6 months, a 75-year-old man has had arousals during sleep in which he exhibits violent behaviors, including kicking and slapping his wife He appears to be asleep or confused during these episodes, and on awakening he has no memory of them However, he does report having vivid and sometimes violent dreams during the nights he has these episodes Which of the following disorders is most likely to develop in this patient?

A Amyotrophic lateral sclerosis

B Cataplexy

C Obstructive sleep apnea

D Parkinson's disease

E Schizophrenia

Correct Answer: The correct answer is D This patient has REM sleep behavior disorder (RBD), which is characterized by abnormal motor behaviors occurring during REM sleep, often associated with action-filled dreams RBD often heralds the development of a neurodegenerative disorder, such as Parkinson's disease or diffuse Lewy body disease The other disorders listed are not usually associated with RBD

19 A 24-year-old third-year medical student who is rotating through his core clerkships is sent for evaluation for excessive sleepiness During the preclinical years, he noted increasing difficulties with staying awake throughout the many hours of classes He thought that this was due to the long hours sitting, the fact that not all of the material fascinated him to the same degree, and the long hours that he studied at night He also felt that his memory and concentration were impaired by this excessive sleepiness However, despite the fact that he really does enjoy the ward experience, he finds himself often nodding off to sleep during ward rounds Last month his cardiology service attending called him in to talk about this behavior He reports that his nighttime sleep has been fitful at times, especially during rotations with heavy call schedules He has also had two embarrassing spells during this year in which he suddenly fell to the ground without loss of consciousness and was unable to move for several seconds in

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