Chapter 18: Neurology

A 75-year-old right-handed man presents to the emergency department (ED) with dizziness that started 5 hours ago. His dizziness consists of a spinning sensation and he feels off balance as he walks. He reports coughing when trying to drink water earlier, but otherwise notes no other symptoms. He has an unremarkable past medical history and is taking no medications. On examination, he is found to have left-sided ptosis and left facial numbness to pinprick. Gag reflex is absent. Motor examination is otherwise unremarkable. Sensory examination revealed decreased pinprick sensation of the right arm and leg. He is unsteady while walking, tending to lean leftward.

Question 18.1.1 What is the most likely diagnosis in this patient?

A) Acute vestibulitis/labyrinthitis

B) Benign paroxysmal positional vertigo (BPPV)

C) Cerebellar stroke

D) Brain stem stroke

E) Ménière attack

Answer 18.1.1 The correct answer is "D." Although dizziness can be associated with all of the above disorders, a brain stem stroke is the most likely answer. The associated symptoms of ptosis (suggestive of Horner syndrome), absent gag reflex with patient report of possible dysphagia, and crossed sensory findings (left side face, right side body) are most consistent with brain stem localization. In peripheral etiologies of vertigo ("A," "B," and "E"), one would not expect sensory phenomena, ptosis, or swallowing difficulties. In BPPV, one would expect brief attacks, lasting seconds to minutes, and not a prolonged attack. In Ménière's, there is often some history of tinnitus and/or hearing loss (low frequency initially). A pure cerebellar stroke would not be expected to have sensory findings.

In conferring with your colleague, she asks if you are going to give tissue plasminogen activator (tPA).

Question 18.1.2 Which one of the following is NOT a contraindication to intravenous (IV) tPA?

A) Age >75

B) INR >1.7

C) Platelets <100,000

D) Stroke within last 3 months

E) Glucose <50

F) Hemorrhage seen on head CT

Answer 18.1.2 The correct answer is "A." Acute stroke treatment with thrombolytics may be of benefit if administered to carefully selected patients within 3 hours of symptom onset or 4.5 hours of symptom onset if certain criteria are met (see Table 18-1). When administered properly, the number needed to treat for improvement at 3 months is 6. However, there is no survival benefit. The risk of hemorrhage is 6% (1 in 16). Of those with symptomatic hemorrhagic transformation, 60% are fatal. There is no upper age cutoff for administration of tPA. Strong contraindications include minor or rapidly improving symptoms as well as those listed in Table 18-1. In selected patients, there is a role for neurointerventional procedures including intra-arterial tPA and thrombectomy. Unlike IV tPA, there are not clearly defined criteria for inclusion/exclusion. In general, patients should be within 6 hours of onset of symptoms and have well-localized symptoms.

The patient is outside of the 4.5-hour window for thrombolysis and has a blood pressure of 200/100 mm Hg.

Question 18.1.3 The best next step in treatment at this point is to:

A) Administer IV labetalol with a blood pressure goal of 140/90 mm Hg

B) Administer IV labetalol with a blood pressure goal of 130/85 mm Hg

C) Administer IV nitroglycerin with a blood pressure goal of 150/90 mm Hg

D) Administer sublingual nifedipine with a blood pressure goal of 160/95 mm Hg

E) Monitor the patient's blood pressure and avoid anti-hypertensives

Answer 18.1.3 The correct answer is "E." Do not treat this patient's blood pressure unless the blood pressure is >220 mm Hg systolic or >120 mm Hg diastolic; and even then the goal would be to reduce blood pressure by 15% over 24 hours. Treating blood pressure during the acute phase of ischemic stroke reduces central nervous system (CNS) perfusion and puts ischemic brain at risk. Obviously, this does not apply if the patient has a hypertensive urgency or hypertensive crisis (e.g., heart failure or other end-organ dysfunction). Note that this is for ischemic stroke and not hemorrhagic stroke. Lowering the blood pressure to a systolic of around or below 160 mm Hg is indicated in hemorrhagic stroke. In this scenario, if you use an anti-hypertensive, labetalol or nicardipine is preferred. Why labetalol or nicardipine and not nitrates? Nitrates cause intracranial vasodilatation increasing CNS pressure.

Question 18.1.4 After admission to a monitored bed, which of the following diagnostic evaluations is LEAST likely to be of further benefit in this patient?

A) Fasting lipid profile

B) Magnetic resonance angiography (MRA) of the head and neck

C) Fasting glucose

D) Hypercoagulable testing

E) Transesophageal echocardiogram

Answer 18.1.4 The correct answer is "D." Hypercoagulable states are an uncommon cause of stroke. If you are unable to determine the origin of a clot in a thromboembolic stroke and the patient is otherwise low-risk (let's say a healthy 25-year-old male who runs marathons), then you can consider a workup for a hypercoagulable state. Such an evaluation is not useful in most stroke patients—like your typical 80-year-old hypertensive female, even if her carotid Dopplers and echocardiogram are negative. In addition to monitoring the patient for signs of neurologic decline or complications, evaluation of potential risk factors for recurrent stroke is an integral part of stroke care. Hypertension, hyperlipidemia, cardiac arrhythmia or structural defects, illicit drug use (IV drugs and stimulants), smoking, and diabetes mellitus are risk factors for recurrent stroke and should be evaluated. MRA allows noninvasive evaluation of intracranial and cervical blood vessels in both the anterior and posterior circulation. Echocardiography is also an important part in the evaluation of stroke, and transesophageal echocardiography is more sensitive for identifying thrombotic sources for stroke when compared with transthoracic echo.

The patient is found to have a lateral medullary stoke on MRI and has heavy atherosclerotic burden in his vertebral arteries. Echocardiogram and telemetry are normal.

Question 18.1.5 What would be the optimal antithrombotic medication in this patient for prevention of recurrent stroke?

A) Coumadin (warfarin)

B) Aspirin

C) Plavix (clopidogrel)

D) Aggrenox (aspirin/dipyridamole)

E) Pletal (cilostazol)

Answer 18.1.5 The correct answer is "B." In patients with a noncardiogenic source for their stroke, there is no data to support the use of anticoagulation (warfarin) for stroke prevention. Similarly, there is no prospective data to support a role for cilostazol or pentoxifylline in the prevention of stroke.

With regard to antiplatelet agents, aspirin is the first-line choice. There is no benefit to dual therapy (i.e., clopidogrel [Plavix] and aspirin). There is also no benefit in increasing the dose of aspirin to more than 81 mg every day. If a patient fails aspirin (recurrent stroke of same mechanism), either change to clopidogrel or Aggrenox (combination aspirin/dipyridamole); both are equally effective in stroke prevention. Because of cost, most authors recommend aspirin as a primary preventive agent in those who have had a transient ischemic attack (TIA).

It seems that there is a 2-for-1 special on neurologic symptoms in your ED this evening (well, at least isn't a three-fer with 3 kids in the same family all of whom have colds… and the parent is sure they have pneumonia). Your next patient is a 59-year-old male who appears to have had a simple TIA with left-sided focal weakness. The TIA lasted <10 minutes and the patient has a normal blood pressure and is nondiabetic.

Question 18.1.6 His risk of having a stroke in the 48 hours after a simple TIA is:

A) 1%

B) 5%

C) 10%

D) 20%

E) 30%

Answer 18.1.6 The correct answer is "A." The overall risk of stroke ranges from 4% to 20% in the 90 days after a TIA. This is a pretty wide range. To narrow down the range a bit, the ABCD² (Table 18-2) has been developed and takes into account age, duration of symptoms, blood pressure, and diabetes. This can be used to predict the 48-hour risk of stroke.

Rapid evaluation of the at-risk patient is warranted, although it is unclear if earlier interventions make a difference (beyond starting antiplatelet agents, etc.).

Objectives: Did you learn to…

• Identify signs/symptoms suggestive of acute ischemic stroke (cerebral infarction)?

• Initiate a diagnostic evaluation for a patient with a possible stroke?

• Describe the role of intravenous and/or intra-arterial tPA in the treatment of acute ischemic stroke?

• Evaluate options for secondary prevention of stroke?

• Assess stroke risk after TIA?

Which of the following referrals for carotid endarterectomy is most likely to result in a benefit to the patient?

A) A symptomatic woman with 70% or greater stenosis to a surgeon who has a 5% complication rate

B) An asymptomatic man with 60% stenosis to a surgeon who has a 7% complication rate

C) A symptomatic woman with a 50% to 69% stenosis and a life expectancy of >5 years to a surgeon who has a 5% complication rate

D) None of the above

E) All of the above

The correct answer is "A." All sources agree that a symptomatic patient who has 70% stenosis of the carotid will benefit from surgery provided that the surgeon's complication rate is sufficiently low. Men, but not women, seem to have a benefit with symptomatic stenosis of 50% to 69% if the life expectancy is >5 years and the surgeon's complication rate is <6% (NNT 22). In asymptomatic patients, those with >60% stenosis will benefit from carotid endarterectomy, but NNT is 33 and the benefit is less than those with symptomatic disease. Stenting is another option. It seems as though long-term outcomes with stenting and endarterectomy are about the same although more data is needed (N Engl J Med. 2016 Feb 1). Stenting seems to be worse than endarterectomy in patients over 70, however (Lancet. 2016 Feb 12).

A 35-year-old female presents for worsening right-sided posterior neck pain that radiates to her right occiput. The pain has been dull and intermittent for about a week and associated with some right posterior scalp tenderness. She became alarmed today because she felt dizzy after her workout. She describes several minutes of vertigo that resolved a few hours ago. Now, sitting in your examination room, she denies vision changes, muscle weakness, numbness, paresthesia, swallowing problems, and speech deficits. Since she's training for a "Viking's Valor Race," she has intensified her workouts in the past few weeks, lifting heavier weights. She is relatively healthy but does take lisinopril for hypertension due to fibromuscular dysplasia. Her vitals are normal. Her neurological examination is normal.

The most appropriate next step in the care of this patient is:

A) Reassurance, rest from exercise, ibuprofen

B) Referral to a neurologist

C) Initiation of aspirin 81 mg daily

D) Urgent head CT

E) Urgent MRI/MRA of the head and neck

The correct answer is "E." This patient is presenting with symptoms concerning for vertebral artery dissection. Extracranial arterial dissections of the head and neck are relatively more common causes of stroke in young adults compared with older adults. Fortunately, many patients experience symptoms of dissection (typically head and/or neck pain, although a Horner syndrome can develop in patients with carotid artery dissection) prior to having a stroke and can be identified early if the physician is attentive and orders the appropriate test. In this case, "D" is not the right test. Head CT would be unlikely to show anything since she does not currently have neurologic signs or symptoms. Even with a CT angiogram of the brain, the extracranial neck arteries (where the problem exists) would not be visualized. Thus, the imaging must include the head and neck and must provide views of the arteries. If "E" is not available, CTA of the head and neck is a reasonable alternative. Classically, an angiogram was used to make the diagnosis, but it is more common now to use MRA or CTA. Of note, patients with fibromuscular dysplasia are more likely to have vertebral and carotid artery dissections, but the vast majority of patients with vertebral or carotid dissection do not have any known connective tissue disorder. Case series of dissections often describe a minor trauma (e.g., weight lifting, amusement park rides, various sports, "fender bender" accidents, chiropractic neck manipulation, etc.) prior to the onset of symptoms.

A 24-year-old right-handed woman presents to you in the ED after her second episode of loss of consciousness. The first spell occurred 6 months ago and was associated with a 60-second loss of consciousness and jerking movements of her arms and legs. Following the spell, she was confused for about 15 minutes. At that time, her initial ED evaluation was unremarkable. She presents today following a spell that occurred about 45 minutes ago. Her friends observed her to fall to the ground and shake her arms and legs for about 2 minutes. They could not get her to respond during this time. Afterward, she was confused and they brought her to the ED. Upon arrival in the ED, she is mildly drowsy but otherwise oriented. She has no memory of the earlier events. Her general medical examination and neurological examination are unremarkable.

Question 18.2.1 Which of these tests would be LEAST helpful in determining the etiology of this spell?

A) Urine toxicology screen

B) Electrolytes

C) Neuroimaging (head CT or MRI)

D) Electrocardiogram (ECG)

E) Electroencephalogram (EEG)

Answer 18.2.1 The correct answer is "D." In this case, ECG would be the lowest yield, as this spell is most suggestive of seizure. Syncopal episodes, which are often of primary cardiac etiology, are generally of shorter duration without postictal confusion. Although a few tonic–clonic movements can be seen with syncope (convulsive syncope), it would be atypical for those movements to continue throughout the entire period of loss of consciousness.

All of the other tests would be useful. Evaluation of a first-time seizure should include assessment for alcohol or other drug withdrawal (especially benzodiazepines and barbiturates) as well as drug intoxication (cocaine, methamphetamine, and other sympathomimetics). Infection, including meningitis and encephalitis, can provoke a seizure. Hyponatremia, hypernatremia, hypocalcemia, hypoglycemia, hyperglycemia, hypomagnesemia, hypophosphatemia, and uremia are all associated with seizures. To rule out structural lesions (e.g., tumor and AV malformation) and hemorrhage, neuroimaging should be performed. Although MRI has greater sensitivity, it is often not available in a timely manner, and thus, CT is the modality of choice. EEG would be able to assess for any seizure activity waveforms.

Evaluation in the ED, including electrolytes, CBC, brain CT scan, and urine toxicology, is unremarkable. An electroencephalogram (EEG) is obtained in the ED and read as normal. The patient is feeling well and does not wish to remain in the hospital. Her friends assure you that they will be with her over the next 24 hours. She returns to your clinic in 2 days.

Question 18.2.2 After reviewing her test results with her, what do you recommend for further management?

A) Continued follow-up with no further workup or treatment

B) Video/EEG monitoring

C) Initiate treatment with antiepileptic drug(s)

D) Tilt table testing

E) Whirligig testing

Answer 18.2.2 The correct answer is "C." This is this patient's second seizure. In adults with a first seizure, only 30% to 60% will go on to have a second seizure. In patients who have a second seizure, the likelihood of going on to have a third is 80% to 90%; therefore, after a second unprovoked seizure, treatment is recommended. Video/EEG monitoring ("B") is appropriate for classifying spells of unclear etiology. In order for video/EEG to be an effective tool, the patient should have spells frequently enough to capture them during a reasonable inpatient stay (3 days average). Tilt table testing ("D") would not be of value, as syncope is unlikely to be the cause of these spells, and whirligig testing ("E") is not a real thing (but it may be in a Dr. Seuss book!).

You discuss her case with the neurologist, Dr. Lotta Branes, who recommends that she start an antiepileptic drug (AED) since this is her second unprovoked seizure. "Huh? What?" you say. "Start her on an antiepileptic drug? Didn't she have a negative EEG?"

Question 18.2.3 What is the sensitivity of a single interictal EEG for seizure focus?

A) 20%

B) 30%

C) 50%

D) 60%

E) 90%

Answer 18.2.3 The correct answer is "D." A single interictal EEG has only a 60% sensitivity for picking up a seizure focus. The sensitivity goes up to 90% after three interictal EEGs. However, this still means that an EEG will be negative in 10% of those with seizures even after three EEGs.

She has multiple questions about AEDs … and so do you!

Question 18.2.4 Which of the following AEDs is NOT typically associated with weight gain?

A) Depakote (valproic acid)

B) Lamictal (lamotrigine)

C) Tegretol (carbamazepine)

D) Neurontin (gabapentin)

Answer 18.2.4 The correct answer is "B." Depakote, Tegretol, and Neurontin are all associated with weight gain. Gabitril (tiagabine) is also associated with weight gain. Lamictal is typically weight neutral. Felbatol (felbamate) and Topamax (topiramate) are associated with weight loss.

Question 18.2.5 Which of the following adverse effects is NOT typically associated with phenytoin (Dilantin)?

A) Cerebellar atrophy

B) Gingival hyperplasia

C) Stevens–Johnson syndrome

D) Hypertension

E) Bone demineralization

Answer 18.2.5 The correct answer is "D." Phenytoin (Dilantin) is associated with a number of idiosyncratic effects including cerebellar atrophy, hirsutism, Stevens–Johnson syndrome, and gingival hyperplasia. Diplopia and nystagmus can be prominent side effects, particularly with supratherapeutic doses. Dizziness, drowsiness, fatigue, headache, nausea, vomiting, weight loss, and urine discoloration (pink, red, or reddish-brown) are among some of the side effects seen with phenytoin. Many AEDs cause increased metabolism of vitamin D via the liver. Long-term use of AEDs may lead to osteoporosis, so vitamin D supplementation with calcium is routine. Phenytoin is associated with hypotension and cardiac dysrhythmia (particularly with IV administration) and can cause "purple glove syndrome" if the peripheral IV infiltrates. This is due to the solution/carrier for the drug. Fosphenytoin (Cerebyx) does not have risk of "purple glove syndrome" and has much lower incidences of hypotension and arrhythmias, so is the formulation of choice when giving phenytoin IV.

Question 18.2.6 Which of the following AEDs is NOT Class D for pregnancy?

A) Valproic acid (Depakote)

B) Phenytoin (Dilantin)

C) Lamictal (lamotrigine)

D) Phenobarbital

E) Primidone

Answer 18.2.6 The correct answer is "C." The newer AEDs including Neurontin (gabapentin), Lamictal (lamotrigine), Keppra (levetiracetam), Trileptal (oxcarbazepine), Gabitril (tiagabine), and Zonegran (zonisamide) are currently Class C in pregnancy. Valproic acid, phenytoin, phenobarbital, primidone, and carbamazepine are all Class D drugs in pregnancy. Topiramate has been associated with birth defects and should be avoided. In particular, valproic acid has a known association with neural tube defects. As a result, it is recommended that all women of childbearing age be on folate and a prenatal vitamin while on AEDs. It is not recommended that women discontinue AEDs when pregnant, but simplifying to monotherapy is recommended if possible.

Question 18.2.7 Which of the following drugs does NOT have potential interactions with oral contraceptives?

A) Depakote (valproic acid)

B) Tegretol (carbamazepine)

C) Trileptal (oxcarbazepine)

D) Dilantin (phenytoin)

E) Topamax (topiramate)

Answer 18.2.7 The correct answer is "A." Interactions with oral contraceptives, decreasing the efficacy of the OCP not the anticonvulsant, have been reported with oxcarbazepine, phenobarbital, phenytoin, lamotrigine, and topiramate.

Zonisamide, (zongran), valproic acid (Depakote), tiagabine (Gabitril), levetiracetam (Keppra), gabapentin (Neurontin), and felbamate (Felbatol) do not interfere with oral contraceptives. A barrier method of contraception, in addition to oral contraceptives, is recommended in women on AEDs, particularly those with known interactions with oral contraceptives.

Question 18.2.8 Which of the following is NOT part of routine counseling with epilepsy and initiation of therapy with an antiepileptic drug?

A) Work safety

B) Calcium and vitamin D supplementation

C) Driving

D) Alcohol consumption

E) Epilepsy surgery

Answer 18.2.8 The correct answer is "E." Epilepsy surgery is reserved for patients who are intractable to medical management and have failed at least two AEDs. Exceptions would include patients with focal pathology (e.g., malignancy or vascular malformation). "B," calcium and vitamin D supplementation, should be initiated in patients on AEDs due to increased risk of osteoporosis. "A" and "C," work and driving safety issues, should be discussed. Most states have specific laws regarding driving and seizures and the time before resumption of driving privileges varies greatly; check the laws in your state(s) of practice. Epileptic patients should be warned of potentially dangerous activities at work and home (e.g., working on ladders, with heavy equipment, bathing, and swimming). "D," alcohol use, should be discussed with patients. Patients should also be warned of potential factors that could lower their seizure threshold, including alcohol consumption, herbal ephedra supplements, sleep deprivation, infection, and medication noncompliance.

Objectives: Did you learn to…

• Evaluate a patient with a potential new diagnosis of epilepsy?

• Identify some areas of specific concern regarding women's issues in epilepsy?

• Recognize commonly encountered or serious side effects with antiepileptic drugs?

• Counsel of patients with epilepsy for daily activities and regarding medication management?

All of the following are indicated in the treatment of petit mal seizures (aka absence seizures, aka generalized nonconvulsive epilepsy) EXCEPT:

A) Ethosuximide

B) Acetazolamide

C) Valproic acid

D) Clonazepam

E) Phenytoin

The correct answer is "E." Phenytoin is not indicated in the treatment of petit mal seizures. The other options are indicated. Other drugs known to be useful in petit mal seizures include lamotrigine, phenobarbital, and topiramate.

A 60-year-old left-handed man comes in with a complaint of numbness and tingling in his lower extremities for about 10 months. He notes no weakness. He has had type 2 diabetes mellitus for 6 years and has a 30 pack-year smoking history. Examination reveals decreased sensation to light touch, pin-prick, and vibratory sensation in the feet extending to 7 cm below the knees symmetrically. You also notice lack of hair on his leg to the same level. Chest, abdomen, and upper extremities have normal sensation. His reflexes are 1+ in the upper extremities and quadriceps with absent Achilles bilaterally. The remainder of his neurological and general medical examination is unremarkable. He says his diet is good but always brings you a dozen doughnuts when he visits … with one or two missing.

Question 18.3.1 This history is most consistent with:

A) Stroke

B) Early mononeuritis multiplex

C) Guillain–Barré syndrome (GBS)

D) Brown–Sequard syndrome

E) Peripheral neuropathy

Answer 18.3.1 The correct answer is "E." This is the quintessential presentation of a patient with diabetic peripheral neuropathy. "A" is incorrect because of the distribution. Bilateral distal lower extremity sensory changes are not likely from a stroke. "B," mononeuritis multiplex, is—at least initially—not in a stocking-glove distribution. Patients with mononeuritis multiplex will notice a stepwise loss of sensation and motor ability in discrete peripheral nerve distributions. Eventually, these may become confluent and resemble a stocking-glove neuropathy. However, this is found late in the disease. Additionally, there is usually motor involvement. "C" is unlikely because GBS has a relatively rapid onset and is associated with motor findings. "D," Brown–Sequard syndrome, is the result of a lesion in one side of the spinal cord. Patients have diminished proprioception, vibration sense and strength on the side of the lesion, decreased sharp sensation, and loss of temperature sense on the other side. Since our patient's findings are symmetrical in both distribution and manifestation, it is not Brown–Sequard syndrome.

Question 18.3.2 Which of the following laboratory tests would NOT be useful in helping to determine a particular cause of this patient's neuropathy?

A) Serum immunofluorescence electrophoresis

B) TSH/free T4

C) Hemoglobin A_1C

D) Electrolytes (Na, K, Cl, CO₂)

E) Vitamin B₁₂

Answer 18.3.2 The correct answer is "D." Electrolytes are not likely to give us a diagnosis in this patient. The initial evaluation of a patient with "stocking-glove" sensory loss should focus on finding potentially treatable causes of neuropathy. These would include hypothyroidism ("B") and vitamin B₁₂ deficiency ("E"). In addition, serum immunofluorescence electrophoresis ("A") can help to identify monoclonal gammopathy, which is associated with neuropathy. Hemoglobin A_1C ("C") is a marker of glycemic control in diabetes and would be associated with diabetic polyneuropathy. Serum heavy metal levels may also be of use.

Your patient is on a number of medications.

Question 18.3.3 Which of the following medications is known to cause a peripheral neuropathy?

A) Metronidazole

B) HMG-CoA reductase inhibitors

C) Amiodarone

D) Disulfiram

E) All of the above

Answer 18.3.3 The correct answer is "E." All of the above can cause a peripheral neuropathy. Some of the other drugs that can cause neuropathy include phenytoin, isoniazid, several chemotherapeutic agents, nitrofurantoin, ddC, and D4T. See Table 18-3 for more causes of peripheral neuropathy.

Question 18.3.4 Electrophysiological testing (electromyography and nerve conduction studies or EMG/NCV) can be helpful for all of the following EXCEPT:

A) Confirming the presence of sensory deficits

B) Identifying subclinical motor deficits

C) Identifying a specific etiology of the neuropathy (e.g., diabetic vs. B₁₂ deficiency vs syphilis)

D) Determining axonal damage versus demyelination as the primary pathologic process

E) Differentiating between primarily myopathic and neuropathic processes

Answer 18.3.4 The correct answer is "C." EMG and NCV are not capable of yielding results specific to the etiology of neuropathy (e.g., identifying diabetic neuropathy vs. B₁₂ vs. syphilis); however, they can yield a pattern suggestive of a particular etiology. For example, increasing motor reaction to repeated stimulation is classic Eaton–Lambert syndrome (a paraneoplastic syndrome), while a decreasing motor response with repeated stimulation is suggestive of myasthenia gravis. EMG and NCV can be helpful in confirming the presence of a radiculopathy in the proper clinical setting. They can also determine if the process is primarily axonal (damage directly to the axons/reduction in the number of axons) versus demyelinating (damage to the myelin sheath). NCV can confirm the presence of sensory deficits (although NCV is looking at large fibers and may not identify small fiber, painful neuropathies) as well as identifying subclinical motor involvement. EMG and NCV can be used to differentiate between myopathic and neuropathic processes.

After being followed in clinic for several years, the patient begins to complain of a painful, burning sensation developing in his feet and ankles. This pain developed gradually over the last few years in the areas that previously were numb. He has a friend who was started on gabapentin (Neurontin) for a similar problem and is wondering if this would be a good drug for him.

Question 18.3.5 Which of the following is NOT an adverse reaction or contraindication to gabapentin?

A) Dizziness

B) Peripheral edema

C) Fatigue and drowsiness

D) Hepatic disease

E) Paresthesias

Answer 18.3.5 The correct answer is "D." Gabapentin (Neurontin) is renally—rather than hepatically—cleared. Also, it is not metabolized by the liver. In the setting of renal dysfunction, reduced dosing is necessary. Although gabapentin is generally well-tolerated, numerous side effects have been reported. Among the most prominent complaints are those of dizziness, vertigo, and ataxia. Fatigue and drowsiness are also relatively common adverse effects; paresthesias, myalgias, and weakness have also been reported. Peripheral edema (particularly lower extremities) and facial edema are also seen as a result of therapy with gabapentin. Titrating slowly to the target dose over several weeks can improve tolerance.

Your patient is concerned about swelling in his legs, as he has had problems with this in the past and does not want to try gabapentin at this time.

Question 18.3.6 All of the following medications would be a reasonable FIRST choice for treatment of painful neuropathy EXCEPT:

A) Amitriptyline

B) Topical lidocaine ointment

C) Oxycodone

D) Topical capsaicin cream

E) Valproic acid

Answer 18.3.6 The correct answer is "C." Narcotics are not the treatment of choice for peripheral neuropathy and tend not to be as effective in this setting as in other types of pain. Tricyclic antidepressants (TCAs) are commonly used in the setting of neuropathic pain and remain the first-line therapy. The evidence for TCAs suggests they are superior to other classes of drugs. If pain is confined to a small area, a topical treatment such as capsaicin cream or topical lidocaine may be effective. Lidoderm patches prescribed outside the setting of post-herpetic neuralgia represent an off-label use.

Question 18.3.7 What is the most common infectious cause of peripheral neuropathy in the world (not just in the United States)?

A) HIV

B) Lyme

C) Leprosy

D) Hepatitis C

E) Tuberculosis

Answer 18.3.7 The correct answer is "C." The most common infectious cause of peripheral neuropathy in the world is leprosy. Leprosy (Hansen disease) is caused by Mycobacterium leprae, an acid-fast bacillus. It usually presents with a hypopigmented anesthetic patch. The sensory deficits start with loss of temperature sensation followed by loss of pain and then tactile sensations. Modalities carried by the posterior columns (proprioception and vibration) are spared. Sensation in the palms, soles, mid-chest, and mid-back is preserved until late in the disease.

HIV can cause peripheral neuropathy, most commonly being a symmetric, distal polyneuropathy. Autonomic dysfunction and mild weakness accompany distal paresthesias and burning sensations with sensory loss. Keep in mind that many of the medications used in HIV therapy are also associated with peripheral neuropathies.

Early neurologic manifestations of Lyme disease include lymphocytic meningitis, cranial neuropathy (a Bell palsy-like picture), or painful radiculoneuritis. Guillain–Barré syndrome (GBS), and mononeuritis multiplex can be seen early in the course of Lyme disease. Advanced (late) neurologic complications of Lyme disease include peripheral neuropathy and encephalomyelitis.

Hepatitis B and C can cause peripheral nerve manifestations. Hepatitis B has been associated with GBS (demyelinating) and mononeuritis multiplex. Hepatitis C is also associated with multiple mononeuropathies.

Tuberculosis has rarely been associated with neuropathy, but isoniazid is well-known to cause peripheral neuropathy (that's why we prescribe pyridoxine with it).

Objectives: Did you learn to…

• Recognize common etiologies of peripheral neuropathy?

• Identify appropriate uses of electrophysiological testing?

• Identify types of neuropathy that are potentially treatable?

• Prescribe medical therapy for painful peripheral neuropathy?

Which of the following is most likely to cause an isolated wrist drop?

A) C-3 disk lesion

B) Ulnar nerve compression

C) Radial nerve compression

D) C-4 disk lesion

E) Median nerve compression

The correct answer is "C." Compression of the radial nerve (such as sleeping with someone's head on your arm) can cause an isolated wrist drop, the so-called "Saturday Night Palsy." Suspect alcohol or other drug abuse in patients with this lesion. It is pretty hard to get this type of compressive lesion if you are not passed out or very sedated. "B," ulnar nerve compression (cubital tunnel syndrome), presents with pain and numbness in the elbow and fourth and fifth fingers and weakness of the intraosseous muscles (weakness with spreading fingers). "E," median nerve compression (including carpal tunnel syndrome), leads to numbness on the palmar surface of the thumb and fingers two, three, and the radial half of four. There is weakness and perhaps atrophy of the thenar muscles (unable to maintain opposition of thumb to fifth finger against resistance).

A 25-year-old woman presents to your clinic complaining of a bifrontal headache that started this morning. She describes the pain as throbbing and 8/10 in severity. She is complaining of photophobia and nausea. She has had similar headaches in the past, lasting a few hours to all day. She is unable to work during these headaches and prefers a dark, quiet room (as do we all). The physical examination, including neurological examination, is unremarkable.

Question 18.4.1 Which of the following statements is most accurate?

A) She likely does not have migraine headaches because her headache is bilateral

B) She likely does not have migraine headaches because they most commonly present in the fourth to fifth decade of life

C) She likely does not have migraine headaches because they rarely occur in the morning

D) She likely has migraine headaches

Answer 18.4.1 The correct answer is "D." She likely has migraine headaches. Migraine headaches may vary considerably in severity, time of day, and characteristics. The International Headache Society (IHS) has a useful classification system with criteria for the diagnosis of migraine headaches (Table 18-4). "B" is incorrect because migraine headaches typically present in the first three decades of life. Attacks typically last less than 1 day although they may occasionally last longer. Migraine headaches are typically moderate to severe in intensity, may occur at any time during the day, and occur with or without aura. Most migraine headaches are unilateral, preceded by aura, and accompanied by nausea and vomiting. They are more prevalent among women, with a 1-year prevalence rate of approximately 18% in women, 6% in men, and 4% in children. Family history is important as 80% of patients with migraine headache have a first-degree relative with migraines.

Migraine headaches were formerly classified as classic type (migraine with aura) and common type (migraine without aura). Typical auras develop over several minutes and last for less than 60 minutes. Auras may involve visual, language, sensory, or motor deficits. The visual auras are by far the most common and may appear as photopsias (flashes of light), scotomas (blind spots), or complex shapes that build or move across the visual field. The IHS criteria for migraine with aura are listed in Table 18–5.

You have decided to treat this woman's migraine headache.

Question 18.4.2 Which medication would be LEAST appropriate for acute management of her headache?

A) Oral ibuprofen

B) Intranasal sumatriptan

C) IV meperidine (Demerol)

D) Intranasal DHE

Answer 18.4.2 The correct answer is "C." The least appropriate treatment from the above list would be Demerol (meperidine). The long-term use of opiates for rescue therapy has not been found to improve the quality of life in patients with migraines. Oral NSAIDs ("A"), including aspirin and combination analgesics containing caffeine, are a first-line choice for mild-to-moderate migraine attacks or severe attacks that have been NSAID responsive in the past. "B," the "migraine-specific" treatments, commonly called the "triptans" (e.g., sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan—wow, talk about "me too" drugs …), are effective and relatively safe for the acute treatment of migraine headaches. Triptans are an appropriate initial treatment choice in patients with moderate-to-severe migraines who have no contraindications to their use (see below). Alternative vasoconstrictive agents, including DHE nasal spray (dihydroergotamine, "D"), can provide a safe and effective treatment of acute migraine attacks. DHE can be administered IV as well. Vasoconstrictive side effects, including the risk of coronary artery spasm, should specifically be discussed with patients prior to initiation of therapy.

Question 18.4.3 Which of the following statements is correct?

A) If a patient does not respond to sumatriptan, there is no point in trying another triptan because the patient will not respond

B) DHE and sumatriptan may be safely used within the same 24-hour time period

C) Sumatriptan use is contraindicated in patients with known coronary artery disease, regardless of age

D) Flushing, sweating, and paresthesias after a dose of sumatriptan is an indication of a severe reaction and continued use of this medication is contraindicated

Answer 18.4.3 The correct answer is "C." The triptans should not be used in patients with known coronary disease. Patients who do not respond to one triptan may respond to other triptans, and a trial of other triptans is appropriate. Also, a patient may respond initially to a triptan but not respond on other occasions. Each triptan has a maximum recommended dose, and a good rule of thumb is that the initial dose may be repeated once in a 24-hour period of time. However, avoid the use of DHE within 24 hours after a triptan has been given due to increased vasoconstriction and the possibility of vasospasm.

Question 18.4.4 Contraindications to the use of "triptans" include all of the following EXCEPT:

A) Lung cancer

B) Uncontrolled hypertension

C) Use of an MAO inhibitor within the last 2 weeks

D) Use of an ergot preparation within the last 24 hours

Answer 18.4.4 The correct answer is "A." Lung cancer is not a contraindication to the use of triptans. In addition to "B" to "D," caution should be used in patients with history of stroke, known cardiac risk factors, and impaired liver function.

Your patient has decided to take ibuprofen for her headaches. This medication seemed to be effective at first, but she notes for the last several weeks that she is taking two to three doses of ibuprofen per day without significant headache relief. She has had a dull bilateral headache that is moderate in severity for the last 2 weeks. The medication dulls the headache but it comes right back. She has no personal or family history of coronary artery disease.

Question 18.4.5 Which of the following statements is correct?

A) She likely has a tension headache and should increase her frequency of ibuprofen and continue to take it on a daily basis

B) She likely has a medication-overuse headache in addition to chronic migraine headache (status migrainous) and should taper and then discontinue ibuprofen

C) A medication such as sumatriptan used on a daily basis does not increase the risk of rebound headache

D) She likely does not have medication-overuse headache because opiates are the only medications that increase the risk of these headaches

Answer 18.4.5 The correct answer is "B." See below for a detailed explanation.

Question 18.4.6 Which of the following medications taken on a frequent basis is LEAST likely to cause medication-overuse or rebound headache?

A) Sumatriptan

B) Morphine

C) Ibuprofen

D) Amitriptyline

E) All of the above are equally likely to cause rebound headache

Answer 18.4.6 The correct answer is "D." Frequent use of opiates, acetaminophen, NSAIDs, ergotamine, triptans, and any other analgesics may put a patient at risk for medication-overuse or rebound headache. Although analgesic rebound headache characteristics can vary significantly, the patient typically reports a pattern of headache that decreases modestly in severity with the use of their analgesic of choice, and then in 2 to 4 hours (depending on the medication), the headache returns to its previous severity or worsens further. Failure to repeat analgesic use results in a withdrawal headache (similar to the caffeine withdrawal headaches physicians often experience when they miss their morning coffee). In the case of triptans, the headache may not worsen for many hours or even until the next day, but a cycle of regular use of the medication is still established. At this time, no clear consensus on the duration of therapy necessary to produce analgesic rebound is reported. As a general rule, it is best to limit the use of analgesic medications to no more than 2- to 3-headache days per week. In addition, limit the patient's analgesic use to no more than 2 to 3 weeks per month. Patient education is the most important part of therapy in treating analgesic rebound or medication-overuse headaches.

Question 18.4.7 Which of the following medications would be the LEAST appropriate for the preventative treatment of your patient's migraine headaches?

A) Verapamil

B) Propranolol

C) Amitriptyline

D) Clonazepam

Answer 18.4.7 The correct answer is "D." Clonazepam is not used as a preventive treatment for migraine headaches. Keep in mind the common side effects of these medications and the appropriateness in your specific patient. For example, valproate would be a bad choice for many patients secondary to weight gain or teratogenicity. Propranolol may cause hypotension. Amitriptyline may cause cardiac arrhythmia in certain patients, while constipation and urinary retention are relatively common in elderly patients. Topiramate (Topamax) may actually cause weight loss, and impaired cognition is common.

Question 18.4.8 Which one of the following medications is rated Class B or better in pregnancy?

A) Phenergan (promethazine)

B) Imitrex (sumatriptan)

C) Codeine

D) Amitriptyline

E) None of the above

Answer 18.4.8 The correct answer is "E." Headache treatment in pregnancy remains a difficult problem. Although numerous medications are available for headache treatment, their safety in pregnancy has not been established. Amitriptyline and valproic acid are class D in pregnancy. Other commonly used tricyclics include imipramine (Class C) and nortriptyline (Class D); venlafaxine is Class C. Promethazine, prochlorperazine, codeine, hydrocodone, and meperidine are all Class C. Ergotamine (DHE 45) is Class X. The triptan class of medications, including sumatriptan, remains Class C, though pregnancy registries, retrospective, and observational studies suggest that sumatriptan is safe.

Question 18.4.9 In which of the following patients is neuroimaging LEAST likely to be useful?

A) A 30-year-old woman with a headache typical of a migraine

B) A 23-year-old woman with a history of migraine headaches that is very concerned because her current headache of 1-week duration is more severe than her typical migraine headaches. She has been unable to sleep or concentrate at work because of her "headache anxiety."

C) A 60-year-old man with new headache, worse in the morning and of 6 weeks duration

D) A 40-year-old man with a headache and right arm weakness

Answer 18.4.9 The correct answer is "A." According to the U.S. Headache Consortium, neuroimaging is not typically recommended in migraine patients with a normal neurologic examination. Imaging may be considered in patients who are disabled by their fear of serious pathology or if the provider is suspicious about underlying pathology. Factors that may lead one to consider neuroimaging include a nonacute, atypical headache or unexplained abnormal neurologic examination.

Objectives: Did you learn to…

• Recognize and diagnose migraine headaches?

• Initiate appropriate acute therapy for migraine headaches?

• Identify contraindications and adverse reactions of the triptan medications?

• Recognize and treat analgesic-related headaches?

• Identify appropriate preventive therapy for chronic headaches?

A 30-year-old woman presents to your office with a 2-day history of progressive, unilateral arm (proximal and distal) numbness without weakness. She has been diagnosed with fibromyalgia in the past. She is taking fluoxetine for depression and has a history of previous hospitalizations for depression.

Question 18.5.1 Which of the following is the most appropriate next step?

A) Monitor her symptoms and reassure that her numbness is likely related to her fibromyalgia

B) Order nerve conduction velocity (NCV) studies

C) Order a head CT

D) Get additional history; ask about previous similar episodes or other neurological concerns

E) Order a chest radiograph (CXR) and complete blood cell count (CBC)

Answer 18.5.1 The correct answer is "D." Of course, the answer is "more history." With a progressive neurological deficit, the first step in the workup is to further explore the history. Frequently, patients will not mention previous neurological symptoms because they— the symptoms, not the patients—are vague (although, to be fair, some patients are vague).

When you ask about previous spells, she notes that she had an episode of left leg numbness that lasted about 1-week several years ago, but she thought nothing of it, as it was mild. Six months ago, she had a 3-day visual disturbance in her right eye, during which she found it difficult to read and focus on objects; no blind spot was noticed. However, she had pain in the eye, especially when moving it.

Question 18.5.2 What is the most likely diagnosis based on the history given?

A) Multiple sclerosis (MS)

B) Fibromyalgia

C) Conversion disorder

D) Atypical migraine

E) Transient ischemic attacks

Answer 18.5.2 The correct answer is "A." MS would be the most likely diagnosis based on the history related above. MS most commonly presents in women 20 to 35 years old and in men 35 to 45 years old. It is almost five times more prevalent among women than among men and is more common in the Caucasian population. MS is a CNS demyelinating disease that is thought to occur by an immune mediated process. The demyelinating lesions of MS can occur anywhere in the CNS including the brain stem and spinal cord. The presenting symptoms of MS vary, but common symptoms are visual complaints, weakness, and sensory deficits. Although migraine can be associated with neurologic symptoms, one would expect more stereotypic events and a history of previous headaches. Fibromyalgia is associated with numerous somatic complaints, but is not typically associated with sensory deficits or visual problems. Conversion disorder can produce all of the symptoms described earlier but is a diagnosis of exclusion. TIAs would be unusual in a patient of this age, though not impossible by any means, and would typically present with stroke-like symptoms (dysarthria, vertigo, hemiparesis, etc.).

Question 18.5.3 If your patient indeed does have MS, which type is most likely?

A) Devic disease

B) Relapsing–remitting

C) Primary progressive

D) All of the above are equally likely

Answer 18.5.3 The correct answer is "B." The two common forms of MS are primary progressive and relapsing–remitting. The diagnosis of relapsing–remitting MS is based on clinical grounds and laboratory data. Clinically, symptoms of CNS dysfunction develop over hours to days, stabilize, and then improve. It is important to identify clinical events disseminated in space and time. In this case, your patient had a prior history of optic neuritis and lower extremity numbness and now has arm numbness. "A," Devic disease (neuromyelitis optica), is a CNS demyelinating illness that is characterized by bilateral optic neuritis (simultaneous or occurring at different times) and spinal cord demyelination.

Question 18.5.4 Which of the following tests would NOT be helpful in further diagnosing MS?

A) MRI brain

B) Lumbar puncture

C) Nerve conduction studies

D) Visual evoked potentials

E) MRI spine

Answer 18.5.4 The correct answer is "C." MS is a central demyelinating process and does not produce abnormalities that would be seen on nerve conduction studies. "A" and "E," MRI of the brain and/or spine, would be helpful. Brain MRI is 85% to 97% sensitive in detecting MS plaques. Multiple areas of increased signal in the periventricular area are suggestive of, but not specific for, MS. Gadolinium-enhancing lesions suggest active disease. "B," lumbar puncture, can also be useful. Cerebrospinal fluid (CSF) abnormalities suggestive of MS include oligoclonal bands and increased synthesis of IgG. A spinal fluid examination may be considered if the clinical diagnosis of MS is suspected but is not definite. However, the positive and negative predictive value of CSF oligoclonal bands is inadequate to do more than support the clinical diagnosis. Recent evidence for serum antibody testing to other myelin components has yielded promising initial results as a supportive diagnostic tool. Finally, "D," visual evoked potentials, may be helpful. Evoked potential may be used to aid in the diagnosis of MS by indicating prior demyelination of the optic tract (optic neuritis) if the clinical history is vague (e.g., eye pain without vision loss or no recollection of symptoms). This will aid in proving the occurrence of different events separated by space and time.

Question 18.5.5 Which of the following is not a recognized therapy for MS?

A) Corticosteroids

B) Interferon-β

C) Glatiramer acetate

D) Sulfasalazine

E) Amantadine

Answer 18.5.5 The correct answer is "D." Sulfasalazine is not useful in the treatment of MS. Immune-modulating therapy reduces the number of exacerbations and active lesions on MRI. These include interferon-β-1a (Avonex and Rebif) and interferon-β-1b (Betaseron), as well as glatiramer acetate (Copaxone). These medications are more efficacious if started early in the course of the disease. Common adverse effects of interferon include fatigue, depression, and myalgias. Amantadine is given commonly as monotherapy and in combination with immunomodulatory therapy to treat fatigue associated with MS. Corticosteroids have a role in treating severe acute exacerbations (e.g., optic neuritis, severe neurological impairments limiting activities of daily living) in the form of a short burst and taper (typically methylprednisolone, 1 g/day often followed by an oral prednisone taper). Steroid use does not appear to offer long-term functional benefit, excluding the possible exception of IV pulsed steroid dosing. Currently, oral immunosuppressive therapies (mycophenolate mofetil, azathioprine, and cyclosporin) are being considered in treating refractory MS, but their long-term efficacy and safety are not known. Similarly, the value of IVIG and plasma exchange has not been conclusively demonstrated and use of these treatment modalities is reserved for refractory patients.

Question 18.5.6 Which of the following treatments would you most likely choose for this patient, given her history of depression?

A) Avonex (interferon-β-1a)

B) Amantadine

C) Copaxone (glatiramer acetate)

D) Betaseron (interferon-β-1b)

Answer 18.5.6 The correct answer is "C." The interferon agents (Avonex, Rebif, and Betaseron) and amantadine are associated with worsening of depression. Given this patient's history of severe depression requiring hospitalization, one would favor Copaxone as an initial therapy, although treatment with interferon is not absolutely contraindicated.

The patient is wondering what she can do to prevent exacerbations.

Question 18.5.7 Which of the following is associated with exacerbation of MS symptoms?

A) Cold temperatures (you could recommend she move to Florida)

B) Urinary tract infection

C) Influenza vaccination

D) Trauma

Answer 18.5.7 The correct answer is "B." Urinary tract infections can exacerbate MS. Unfortunately, urinary tract infections are particularly common in those with MS because of the frequent occurrence of neurogenic bladder. Systemic infection has also been reported to provoke MS exacerbations. "A" is of special note. Cold is not associated with exacerbations, but heat is notorious, and this phenomenon actually has a name—Uhthoff phenomenon. Patients with MS should be instructed to avoid hot tubs, saunas, steam rooms, etc. "C," vaccinations, including influenza vaccine, had been posited as a cause of exacerbations. However, a review of multiple clinical trials showed no increased risk of exacerbations in patients with MS receiving the influenza, hepatitis B, or tetanus vaccinations. Note that we do not have experience with nasal influenza vaccine and MS. Since the nasal vaccine contains live virus, it should probably be avoided in patients with MS. "D," trauma, has been suggested as a possible exacerbation trigger, but the American Academy of Neurology clinical practice guidelines state that the majority of class II evidence available on this issue supports no connection.

Objectives: Did you learn to…

• Identify epidemiologic characteristics of MS?

• Identify appropriate workup for patients with possible MS?

• Diagnose MS?

• Discuss potential treatment options available for long-term disease modification as well as acute exacerbations?

• Recognize factors that might result in exacerbations of MS?

A 43-year-old woman with a history of myasthenia gravis presents to the ED while on vacation. She reports she is feeling tired and rundown and endorses flu-like symptoms in addition to some worsening of her proximal lower extremity weakness. On examination, she is afebrile with a respiratory rate of 18. She has mild diplopia with lateral gaze. Her strength is 4/5 proximally and 4+/5 distally bilaterally. Her sensory examination is normal. Plantar responses are down-going bilaterally.

Question 18.6.1 In determining this patient's further disposition, what is the most important test?

A) Arterial blood gas

B) CXR

C) Head CT

D) Spirometry (forced vital capacity [FVC] and negative inspiratory force [NIF])

E) CBC

Answer 18.6.1 The correct answer is "D." This patient is experiencing an exacerbation of myasthenia gravis. This could be occurring for any number of reasons including concurrent illness or possibly noncompliance with her regimen. The greatest morbidity and mortality for this patient lies in the potential for respiratory failure and arrest. In primary neuromuscular respiratory failure (e.g., myasthenia gravis, acute inflammatory demyelinating polyradiculoneuropathy, GBS), the arterial blood gas may remain normal despite impending respiratory collapse. The best way to evaluate respiratory status is with the FVC and NIF. If the FVC is less than 15 mL/kg or NIF less than –20 cm H₂O, elective intubation is recommended, although some centers will choose to monitor these patients closely in an intensive care setting. Once a myasthenic patient has been intubated, you should stop their pyridostigmine as it will increase respiratory secretions and GI motility leading to diarrhea. Neither of these is desirable in an intubated ICU patient (the nurses will love you for this one) and the pyridostigmine will not liberate them from the ventilator. Monitoring the FVC/NIF should be done regularly throughout the hospital course until the patient is clinically improved and stable.

You decide to give this patient a dose of edrophonium trying to reverse her symptoms. When you do this, she becomes increasingly weak, requiring intubation.

Question 18.6.2 The BEST explanation of this is:

A) Since she has missed multiple doses of her pyridostigmine, she has become desensitized and will have an overwhelming response to small doses of IV edrophonium

B) Influenza has made her particularly susceptible to edrophonium

C) The patient has taken too much pyridostigmine by accident

D) The alcohol that she has had on vacation has changed her pyridostigmine requirement

Answer 18.6.2 The correct answer is "C." Myasthenic crisis can be due to two causes. First, the patient may have not taken enough medication or may have missed doses. In this case, edrophonium will improve symptoms. The second cause is too much pyridostigmine. This will also cause weakness. In this case, the edrophonium will worsen the patient's symptoms. Here's how it works. Pyridostigmine and edrophonium are both cholinesterase inhibitors similar to organophosphates. They act by binding to acetylcholinesterase and preventing the breakdown of acetylcholine. Too much of either drug (or a combination of the drugs) will cause weakness and an organophosphate toxicity-like syndrome (salivation, lacrimation, defecation, urination, weakness, etc.).

Question 18.6.3 Which of the following IS NOT likely to contribute to the diagnosis of myasthenia gravis?

A) Tensilon (edrophonium) test

B) Nerve conduction studies

C) Antithymocyte antibodies

D) Antiacetylcholine receptor antibodies

Answer 18.6.3 The correct answer is "C." Antithymocyte antibodies are used to treat renal rejection and have also been used in aplastic anemia, red cell aplasia, and other disorders. They have no relationship at all to myasthenia gravis … sorry. All of the others can be used in the diagnosis of myasthenia gravis. The edrophonium test is a functional test. One must be ready to intubate the patient when performing an edrophonium test, as weakness may get worse. Nerve conduction studies show a reduction in the amplitude of the response to repeated stimulation (thus, patients get weaker with repeated muscle use). Antiacetylcholine receptor antibodies are found in the majority (80–90%) of patients with myasthenia gravis. In fact, when an ultrasensitive test is done, it is found in 70% of "antibody negative" cases of myasthenia gravis.

Question 18.6.4 Which of the following is LEAST likely to be confused with myasthenia gravis on the basis of its neurologic symptoms?

A) Eaton–Lambert syndrome

B) Guillain–Barré syndrome (GBS)

C) Amyotrophic lateral sclerosis

D) Botulism toxicity

E) Penicillamine-induced myasthenia gravis

Answer 18.6.4 The correct answer is "B." Remember that myasthenia gravis has no sensory findings. GBS includes sensory findings of pain, paresthesias, numbness, etc. that are generally absent in the other syndromes. "A," Eaton–Lambert syndrome, is a paraneoplastic process, which consists of weakness that gets better with repetitive movement. This is the exact opposite of what is seen with myasthenia gravis where repetitive tasks lead to increased weakness. Thus, Eaton–Lambert syndrome is often worse in the morning and better toward the afternoon—the reverse of what is seen with myasthenia gravis. Patients with amyotrophic lateral sclerosis, botulism, and penicillamine-induced myasthenia gravis do not have sensory symptoms. Thus, these can be confused with myasthenia gravis.

The patient and her husband have some questions about myasthenia gravis and are wondering if there are any medications that might exacerbate this patient's weakness.

Question 18.6.5 Which of the following can worsen myasthenia gravis?

A) Fluoroquinolones

B) Verapamil

C) β-blockers

D) Oral contraceptives

E) All of the above

Answer 18.6.5 The correct answer is "E." All of the above can worsen myasthenia gravis. Other drugs of note include aminoglycosides, anesthetic and paralytic agents, diuretics, tetracyclines, and magnesium, among many others.

You decide to add to the treatment of this patient.

Question 18.6.6 Which of the following is considered a standard therapy for myasthenia gravis?

A) Plasmaphoresis for an acute myasthenic crisis

B) IVIG

C) Prednisone

D) Azathioprine

E) All of the above are used for myasthenia gravis

Answer 18.6.6 The correct answer is "E." Do you see a pattern here? All of the treatments are immunomodulators. Most people will start with prednisone and azathioprine. Other options are cyclosporin and mycophenolate. The idea here is to reduce antiendplate antibodies (although nobody is quite sure how IVIG works). Prednisone is generally considered first-line therapy for an exacerbation. It may be that immunomodulators will become first line (many neurologists are already using them as first line and using pyridostigmine only as a bridge until the immunomodulator kicks in). Plasma exchange can be used to treat an acute exacerbation. Remember thymectomy as this may be a cure if a thymoma is present.

Objectives: Did you learn to…

• Manage a patient with an exacerbation of myasthenia gravis?

• Understand the use of diagnostic tests in myasthenia gravis?

• Recognize diagnoses that can be confused with myasthenia gravis?

A 29-year-old woman presents to the ED with sudden onset of a severe headache involving bilateral occipital pain associated with nausea. The headache has not responded to her sumatriptan (Imitrex) injection. She has a history of migraine headaches consisting of right-sided throbbing pain that typically respond to sumatriptan but occasionally require IV ketorolac and metoclopramide. She appears to be in moderate pain but otherwise has a normal general and neurological examination. This is the worst headache of her life.

Question 18.7.1 What is the next step in the management of this patient?

A) Ketorolac (Toradol) and metoclopramide IV

B) Hot tea and soft pillow

C) Dihydroergotamine (DHE) IV

D) Head CT

E) Lumbar puncture

Answer 18.7.1 The correct answer is "D." Although this patient has a history of migraines, she is reporting a sudden onset headache that is markedly changed from her typical pattern of headache. In this setting—especially with the "worst headache of her life"—the diagnosis of subarachnoid hemorrhage (SAH) must be ruled out. None of the other answers are correct. While pain management can be given before CT (e.g., IV morphine or fentanyl), ketorolac, aspirin, and DHE are inappropriate if there is a question of SAH. Ketorolac and aspirin have antiplatelet effects, which can increase bleeding. DHE can cause vasospasm and worsen brain ischemia. Finally, if you recall, this patient tried her sumatriptan. One should not use DHE within 24 hours of a triptan. Note that in a patient with a nonfocal examination who is immunologically intact LP may be done before CT.

The patient's head CT is negative.

Question 18.7.2 What next?

A) Lumbar puncture

B) IV hydroxyzine and meperidine and discharge when she is comfortable

C) IV hydroxyzine and promethazine (Phenergan) and discharge when she is comfortable

D) Discharge home with prescription for acetaminophen and oxycodone (Percocet)

E) Discharge home with prescription for rizatriptan (Maxalt)

Answer 18.7.2 The correct answer is "A." In the setting of a "worst headache of life" a CT scan to rule out SAH is required. The sensitivity of CT scan of the brain for hemorrhage in the setting of SAH is 90–95% within 24 hours of the event (decreases to 80% at 72 hours). CT only picks up 50% of warning leaks. As a result, a negative head CT does not adequately rule out SAH and should be followed with a lumbar puncture. The CSF from the lumbar puncture must be spun down immediately to examine for xanthochromia; delay in examining the CSF may result in false-positive results. Xanthochromia is a yellow discoloration of the normally clear CSF resulting from degradation of hemoglobin. In addition to xanthochromia, markedly elevated RBC counts are indicative of SAH. If either the CT or LP is positive for SAH, an emergent four-vessel cerebral angiogram (or MR angiogram or CT angiogram) is indicated.

You complete the LP, and it is normal. Apparently, this was just the worst migraine of her life. After loading her up on some good drugs, her pain subsides. Problem solved!

Objective: Did you learn to…

• Identify a patient presenting with SAH symptoms and perform an appropriate workup?

A 40-year-old man presents with a complaint of low-back pain that is dull in nature, which started 2 days ago. This morning he woke up with a feeling of numbness and tingling in his feet, which gradually seemed to worsen. By noon, he noted difficulty walking and decided to come to the ED. He denies bowel or bladder incontinence. On examination, he is in no acute distress and has a respiratory rate of 12. He has strength of 5/5 in his upper extremities, and in his lower extremities, strength is 4/5 proximally and 3/5 distally. Sensory examination reveals a mild decrease in pinprick and light touch in a stocking distribution to the mid-calf. Reflexes in the upper extremities are 2+/4 and in the lower extremities are trace at the knees and absent at the Achilles. Plantar response is down-going bilaterally.

Question 18.8.1 What is the most likely diagnosis?

A) Diabetic polyneuropathy

B) Guillain–Barré syndrome (GBS)

C) Diabetic amyotrophy

D) Stroke

E) Conversion reaction

Answer 18.8.1 The correct answer is "B." Of the choices given above, the most likely diagnosis is acute inflammatory demyelinating polyradiculoneuropathy (GBS). With an acute onset of bilateral lower extremity weakness and sensory deficits, the diagnosis of an acute cord-compressing lesion (e.g., tumor and epidural abscess) should also be considered and ruled out, especially when back pain is also present. The time course described above is not consistent with diabetic polyneuropathy nor would one expect to see weakness as a prominent symptom. Diabetic amyotrophy is characterized by painful proximal muscle weakness with minor sensory loss. The onset of diabetic amyotrophy can be subacute or acute. The time course described above of gradually progressing deficits is not consistent with stroke. Additionally, the findings of a stroke should not be bilateral.

Question 18.8.2 Which of the following is/are associated with GBS?

A) Campylobacter jejuni infection

B) Lyme disease

C) Epstein–Barr virus

D) CMV virus

E) All of the above

Answer 18.8.2 The correct answer is "E." All of these infectious agents are associated with GBS, especially Campylobacter Other associations include viral URIs, HIV, immunizations (rare), mycoplasma, epidural anesthesia, sarcoid, lupus, etc. Add to this the Zika virus and the West Nile virus. The point here is that one should look for an underlying illness in patients with GBS.

Question 18.8.3 Which of the following actions would NOT be appropriate for additional diagnosis and/or management of this patient with progressive weakness?

A) Cardiac monitoring

B) Forced vital capacity (FVC)

C) Discharge to home on steroids with a follow-up in the morning

D) EMG/NCV

Answer 18.8.3 The correct answer is "C." This patient should not be sent home. Did you even consider it? Discharge is a particularly bad idea because his disease has worsened rapidly over the last 12 hours. As with other potential causes of neuromuscular respiratory failure, an FVC and NIF are necessary to determine adequate respiratory reserve. The FVC and NIF should be monitored closely during the acute illness. GBS can have a rapid and catastrophic worsening that necessitates monitoring during the acute phase of illness. Typically, patients reach the peak of severity about 2 weeks into the illness. Autonomic dysfunction is associated with GBS, and close cardiovascular monitoring is important. EMG/NCV can be of value in diagnosing GBS—although early on in the course of the disease, these tests may be normal.

A diagnosis of GBS is made.

Question 18.8.4 Which of the following is NOT an appropriate treatment modality?

A) IVIG

B) Plasma exchange

C) Elective intubation if FVC is <15 cc/kg

D) Corticosteroids

Answer 18.8.4 The correct answer is "D." Corticosteroids are not used in the treatment of GBS. Multiple studies have shown no benefit to corticosteroids in this disease. Treatment options for GBS include careful monitoring of disease and supportive therapy with no intervention. Some experts recommend initiating IVIG or plasma exchange. If a patient requires ventilatory support or has weakness that precludes ambulation, treatment should be started immediately. Elective intubation is appropriate if the FVC is less than 15 cc/kg or the NIF is –20 cm H₂O. As discussed in regard to neuromuscular respiratory failure with myasthenia gravis, arterial blood gases are not reliable markers of impending failure, and the FVC must be closely monitored.

The family would like to know what the outcome in this patient with GBS will be, so you pull out your crystal ball.

Question 18.8.5 Well, instead of sarcasm, you actually opt for compassion and tell them that FULL RECOVERY can be expected in __________ percent of patients.

A) 15%

B) 50%

C) 80%

D) Greater than 95%

Answer 18.8.5 The correct answer is "A." Fifteen percent of all patients with GBS will have complete resolution of their symptoms. Sixty-five percent will be left with minor deficits, and about 10% will become disabled. Despite excellent care, some patients still die.

Objectives: Did you learn to…

• Recognize the clinical presentation of GBS?

• Identify underlying illnesses that are associated with GBS?

• Manage a patient with GBS?

A 38-year-old woman is brought to the ED by her husband who expresses concerns over changes in her mental status over the past 2 days. She has become confused, forgetting the names of persons well-known to her, and forgetting what she is doing. Her conversations have become increasingly more difficult to follow, and over the past 12 hours, she has gradually become sleepier. On examination, she has a temperature of 38.0°C. She is drowsy but can be aroused. She has no meningismus. She is oriented only to person. She responds to questions slowly and incorrectly and follows only simple commands ("stick out your tongue"). The remainder of her neurological examination is essentially normal, given her limited ability to cooperate. CBC, coagulation studies, and electrolytes (including calcium, magnesium, and phosphorous) are normal.

Question 18.9.1 What is the best next step in evaluating this patient?

A) Lumbar puncture

B) Head CT

C) Electroencephalogram (EEG)

D) Chest x-ray (CXR)

Answer 18.9.1 The correct answer is "B." Although performing all of the above tests will be helpful in evaluating this patient, the most important test to do at this time is a head CT to rule out any mass lesion or hemorrhage. You could argue that "A," an LP, could be done first, and some experts would agree with that decision. However, the standard in the United States is to do the CT scan first if there is any possibility of a mass lesion. There is a possibility that nonconvulsive status epilepticus is causing these mental status changes. However, even if the EEG showed nonconvulsive status epilepticus, a head CT and lumbar puncture would remain necessary. Although pneumonia could cause confusion, a CXR is unlikely to be of high yield in this setting.

Her head CT is normal. You perform a lumbar puncture, which reveals 18 WBCs (all lymphocytes), 12 RBCs, CSF protein 67 mg/dL (elevated), and CSF glucose 70 mg/dL (normal). An EEG is normal.

Question 18.9.2 What is the next step in managing this patient?

A) Admit for viral encephalitis with close monitoring

B) Admit for viral encephalitis and start acyclovir and antibiotics

C) Admit for bacterial meningitis and start antibiotics

D) Discharge to home with close follow-up tomorrow at 8 am

Answer 18.9.2 The correct answer is "B." The probable diagnosis in this setting is herpes simplex encephalitis. Her CSF results are consistent with a viral process and are not consistent with bacterial meningitis (due to the normal glucose and only lymphocytes in the differential). Given the mortality of herpes simplex encephalitis (30–70%), all patients in whom the diagnosis is suspected should be started on acyclovir 10 mg/kg every 8 hours IV empirically (with appropriate dosage adjustments for renal failure), while further confirmatory testing is pending (CSF PCR for the herpes simplex virus). Treatment should be for a minimum of 10 days and has been advocated (with little evidence to support it) to be as long as 21 days. It is important to recognize that the EEG and CT may be normal in herpes simplex encephalitis, particularly early in the disease. However, on CT, one may see evidence of temporal lobe hemorrhage and/or hypodensity in the temporal lobes. EEG can show either periodic lateralized epileptiform discharges or focal slowing in the temporal lobes. Temporal lobe changes may be even more prominently visualized on MRI, and this may be of benefit in cases in which the diagnosis remains unclear. Even with prompt, appropriate treatment, only 38% of patients returned to normal or near-normal neurologic functioning at 2 years. "B" includes antibiotics because most clinicians would cover for bacterial meningitis until the CSF cultures come back negative.

Objectives: Did you learn to…

• Recognize the clinical presentation of and the laboratory findings in viral encephalitis?

• Initiate appropriate treatment in a patient with a presumptive diagnosis of herpes encephalitis?

A 70-year-old male presents to your office as a new patient. He is with his wife, who assists in providing the history. His appetite is reduced, and he has lost 10 lb in the past 6 months. His only medication is aspirin, and he has no significant past medical history.

On examination, his vital signs are normal, and he is in no acute distress. His gait is slow, and he takes eight steps to turn. He has retropulsion (takes two steps backward when you pull him from behind). There is a resting tremor in both hands but more prominently in the right. You find cogwheel rigidity in both arms as well, but again more prominently displayed on the right. His cognitive screening tests are normal.

Question 18.10.1 The most likely diagnosis is:

A) Essential tremor

B) Parkinson disease

C) Normal pressure hydrocephalus (NPH)

D) Progressive supranuclear palsy

E) Stroke

Answer 18.10.1 The correct answer is "B." This patient most likely has Parkinson disease. "A" is incorrect because essential tremor is typically worsened by activity and is not associated with the other neurologic findings seen in this patient. "C" is incorrect. The classic triad of NPH includes urinary incontinence, gait ataxia, and dementia. "D" might be a consideration, but there is no specific finding of progressive supranuclear palsy here (e.g., aggressive course, more severe axial rigidity, dysarthria, dysphagia, and downward gaze paresis). Stroke is quite unlikely to present in this insidious fashion with generalized findings.

Question 18.10.2 Which of the following is NOT a common feature of idiopathic Parkinson disease?

A) Rigidity

B) Extraocular movement paresis

C) Bradykinesia

D) Loss of postural reflexes or gait disturbance

E) Asymmetric tremor

Answer 18.10.2 The correct answer is "B." There are four cardinal features of Parkinson disease: tremor, bradykinesia, rigidity, and postural instability. Two or more of these features should be present to make the diagnosis. The tremor of Parkinsonism is a resting tremor (as opposed to the postural, intention, or action tremor) and is most common in the hands, typically with one side affected more than another. Rigidity ("A") is described as increased resistance to passive movement and may be reinforced by having the patient open and close the fist on the opposite hand. Cogwheel rigidity is a ratchet-like sensation noted when testing a limb with concurrent tremor. Bradykinesia ("C") may be observed by monitoring the speed and amplitude of movements. Gait disturbance ("D") with reduced stride length and stooped posture is a common finding but generally occurs later in the course of the disease. Postural reflexes and ability to rise from a chair are also impaired. Postural reflexes may be tested by retropulsion.

You are fairly certain that your patient has Parkinson disease.

Question 18.10.3 What else might you find with idiopathic Parkinson disease?

A) Micrographia

B) Urinary incontinence

C) Apraxia

D) Autonomic dysfunctions

E) Alien limb phenomenon

Answer 18.10.3 The correct answer is "A." Micrographia, writing in small letters, is associated with Parkinson disease. The others are not. This is important because there are a number of neurologic syndromes that can mimic Parkinson disease, and knowing the additional features of Parkinson disease will help you to differentiate it from other diseases. Decreased facial expression (hypomimia) with decreased rate of eye blink and diminished vocal volume (hypophonia) are also common with Parkinson disease. Other conditions that occur in patients with Parkinson disease include depression, cognitive impairment, and REM sleep behavioral disorder (e.g., kicking and screaming during REM sleep in response to vivid, disturbing dreams).

Question 18.10.4 The diagnosis of Parkinson disease is most appropriately made:

A) With a brain MRI

B) By CSF analysis

C) Clinically

D) By a neurologist

E) At autopsy

Answer 18.10.4 The correct answer is "C." The diagnosis is based on a history and physical examination that are consistent with Parkinson disease. Additionally, a response to dopaminergic agents is virtually diagnostic of Parkinson disease. If the patient does not have some response to a dopaminergic agent, reconsider your diagnosis. "A" is incorrect because there are no findings on neuroimaging that are specific for the diagnosis of Parkinson disease. Likewise, "B" is wrong because CSF analysis cannot provide the diagnosis. "D" is clearly wrong—do you really need a neurologist for this? The "gold standard" for diagnosis is neuropathologic examination, but you would rather not wait for the autopsy to diagnose Parkinson disease.

Your patient takes only aspirin, which you know does not cause parkinsonism.

Question 18.10.5 Which of the following medications is frequently associated with a Parkinson-like syndrome in the elderly?

A) ACE inhibitors

B) HMG-CoA reductase inhibitors