Autonomic and Sleep Disturbances

Questions

1. Which of the following is a common feature of orthostatic intolerance?

A. Bradykinesia

B. Episodic supraventricular tachycardia

C. Low serum catecholamine levels

D. Neurogenic orthostatic hypotension

E. Vasovagal or reflex syncope

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1. Answer E. (MN-116) Reflex or vasovagal syncope is present in about 40% of patients with orthostatic intolerance or postural orthostatic tachycardia syndrome (POTS). Patients may have multiple symptoms but do not have neurogenic orthostatic hypotension and will not have parkinsonism on examination. Tachycardia may occur, but various primary arrhythmias such as supraventricular tachycardia would be considered a separate condition. Patients with POTS often have normal or high serum catecholamine levels.

2. Severe autonomic failure is most associated with which condition?

A. Acquired amyloidosis

B. Alzheimer disease

C. Chronic inflammatory demyelinating polyneuropathy (CIDP)

D. Myelin-associated protein neuropathy (Anti-MAG)

E. Progressive supranuclear palsy

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2. Answer A. (MN-116) Acquired amyloidosis often causes severe autonomic neuropathy and related neurogenic orthostatic hypotension. This diagnosis may be initially identified through consultation with a hematologist and elevated serum light chains. The other neuropathic and central degenerative cases listed have minimal to no autonomic involvement.

3. Pure autonomic failure shares pathological features with which condition?

A. Fabry disease

B. Familial amyloid polyneuropathy

C. Multiple system atrophy (MSA)

D. Parkinson disease

E. Progressive supranuclear palsy

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3. Answer D. (MN-116) The pathological hallmark of pure autonomic failure is of Lewy bodies identified in peripheral autonomic and enteric ganglia. Lewy bodies are alpha-synuclein neuronal inclusions and are also a primary recognized pathology in the spectrum of central nervous system Lewy body diseases (LBD), which includes Parkinson disease, dementia with Lewy bodies, and a Lewy body variant of Alzheimer disease. Autonomic failure is also common in patients with MSA; however, pathologically synuclein deposition in MSA occurs in glial cytoplasm rather than in neurons, and without development of distinct Lewy body inclusions.

4. Which of the following is the most common cause of autonomic neuropathy?

A. Chronic alcoholism

B. Diabetes mellitus

C. Fabry disease

D. Familial amyloidosis

E. Sjögren syndrome

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4. Answer B. (MN-116) Diabetic autonomic neuropathy is the most common cause of autonomic neuropathy in most populations, and diabetes is the leading cause of peripheral neuropathy. The other causes listed also cause autonomic neuropathy but at much lower frequencies in the population.

5. Familial dysautonomia, also known as hereditary sensory and autonomic neuropathy type III, is inherited in which pattern?

A. Autosomal dominant

B. Autosomal recessive

C. Sporadic

D. X-linked dominant

E. X-linked recessive

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5. Answer B. (MN-116) This disease is an autosomal recessive condition. The carrier state in eastern European (Ashkenazi) Jewish populations is approximately 1 in 25 and has led to prenatal screening programs in at-risk populations.

6. Which agent is US FDA-approved for the treatment of symptomatic neurogenic orthostatic hypotension (NOH)?

A. 3,4 Diaminopyridine

B. Droxidopa

C. Fludrocortisone

D. Pyridostigmine

E. Yohimbine

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6. Answer B. (MN-116) In addition to midodrine, droxidopa is the only other medication that is FDA approved for treatment of neurogenic orthostatic hypotension (NOH) in the United States. However, droxidopa is not approved for treatment of patients with diabetic autonomic neuropathy. Midodrine is approved for all underlying causes of NOH.

7. A 34-year-old man suffered a severe brain injury after a head-on automobile collision. He has been in the neurologic intensive care unit for 2 weeks, and his course has been complicated by urinary tract infection and pneumonia. His intracranial monitor has been discontinued, and while weaning down his sedative medications he is noted to have episodes of fever, hypertension, tachycardia, tachypnea, and flexion posturing. Episodes last 20 minutes and occur 5 to 6 times a day. What is the most appropriate next step in management?

A. Continue with intravenous medications for sedation so as to not aggravate ICP during the episodes

B. Give paralytics to stop the posturing movements

C. Place patient on a cooling device to control fevers

D. Rule out infectious etiology for episodes

E. Start IV dantrolene

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7. Answer D. (MN-117) Paroxysmal sympathetic hyperactivity is an episodic syndrome seen after acute brain injury characterized by hyperthermia, tachycardia, tachypnea, diaphoresis, and motor posturing. Although this patient’s description fits the diagnosis, the most important first step is to exclude other etiologies for the symptoms. Infectious etiologies are the most common cause of fever and tachycardia, and need to be ruled out.

8. A 24-year-old woman experienced a severe traumatic brain injury 2 months ago. For the last month she has been having episodes of fever, tachycardia, tachypnea, and hypertension with episodes of tonic posturing. These episodes last 10 minutes and occur several times a day, often brought on during routine nursing care. She is bedbound, incontinent of bowel and bladder, and unable to communicate. She is being fed through a gastric tube and resides in a skilled nursing facility. Which of the following is the pathophysiology of this disorder?

A. An imbalance between the inhibitory cortical pathways and autonomic nervous system centers

B. Cardiac imbalance causing arrhythmias

C. Bacteremia secondary to an occult abscess

D. Intermittent loss of cerebral autoregulation functions from loss of inhibitory cortical pathways

E. Recurrent difficult-to-control posttraumatic seizures

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8. Answer A. (MN-117) The Excitatory:Inhibitory Ratio (EIR) Model has been used to explain the pathophysiology of paroxysmal sympathetic hyperactivity, and it takes into account the hypersensitive, overreactive nature of the responses to normal stimuli. Autonomic efferents at the level of the spinal cord are modulated centrally by a balance of sympathetic and parasympathetic inputs from higher brainstem nuclei. Afferents from the spinal cord can modulate this balance in response to stimuli from the environment. Damage to these central inhibitory centers may cause sympathetic overactivity to afferent stimuli. Thus nonnoxious stimuli can become a very noxious stimuli associated with an uncontrolled sympathetic response.

9. A 32-year-old man has been having episodes consistent with paroxysmal sympathetic hyperactivity (PSH). He has episodes of fever, tachycardia, and posturing. Which statement is true about the treatment of PSH?

A. Antihistamines are a preferred agent to decrease the associated symptoms related to histamine release in this disorder

B. Antipsychotic medication including haloperidol should be used for the control of agitation and as abortive therapy

C. Benzodiazepines and opioids including morphine should be used for abortive agents and as maintenance medications

D. Beta blockers are the most effective first-line drugs for abortive treatment

E. The first line of treatment is intravenous propofol to control the fluctuations in sympathetic tone

View Answer

9. Answer C. (MN-117) Benzodiazepines and opioids, especially morphine, are recommended agents for the treatment of paroxysmal sympathetic hyperactivity (PSH). Antipsychotics and antihistamines have no role in the treatment of PSH. Intravenous sedatives such as propofol may control PSH symptoms but are not considered a viable long-term treatment option. Beta blockers are useful for maintenance treatment and suppression of tachycardia and hypertension but do not target the primary pathophysiologic mechanism of PSH. Figure 16.9.1 details the approach to treatment of PSH.

FIGURE 16.9.1 (Reprinted with permission from Louis ED, Mayer SA, Noble JM, eds. Merritt’s Neurology. 14th ed. Wolters Kluwer; 2022.)

10. A 19-year-old man has intermittent fever, tachycardia, hypertension, and pupillary dilatation with stereotype posturing extents 1 week after a severe traumatic brain injury. Which of the following set of clinical findings are supportive of the diagnosis of paroxysmal sympathetic hyperactivity?

A. Fever, tachycardia, hypertension, and posturing

B. Fever, tachycardia, hypertension, posturing, and pupillary dilation

C. Fever, bradycardia, hypotension, and posturing

D. Fever, tachycardia, hypotension, and posturing

E. Hypothermia, tachycardia, hypertension, and posturing

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10. Answer A. (MN-117) The consensus diagnosis of paroxysmal sympathetic hyperactivty (PSH) includes elevations in heart rate, respiratory rate, systolic blood pressure, temperature, sweating, and posturing during episodes (Table 16.10.1). Diagnostic criteria require exclusion of an alternative diagnosis such as infection. Pupillary dilation can be a reaction to sympathetic tone, but it is not included in the diagnostic criteria. Additionally, one must rule out other reasons for a dilated pupil before diagnosis of PSH is made.

TABLE 16.10.1 Paroxysmal Sympathetic Hyperactivty-Assessment Measure

Clinical Feature Scale
	0	1	2	3	Score
Heart rate (BPM)	<100	100-119	120-139	≥140
Respiratory rate (breaths/min)	<18	18-23	24-29	≥30
Systolic blood pressure (mm Hg)	<140	140-159	160-179	≥180
Temperature (°C)	<37	37-37.9	38-38.9	≥39
Sweating	Nil (none)	Mild (moist skin)	Moderate (beads of sweat)	Severe (profuse generalized sweating)
Posturing during episodes	Nil (none)	Mild (increased tone but not requiring treatment)	Moderate (increased tone requiring treatment)	Severe (very increased tone refractory to treatment)
				CFS subtotal =
Diagnosis Likelihood Tool (DLT)
*Score as “1” if present*					Score
Clinical features occur simultaneously
Episodes are paroxysmal in nature
Over-reactivity to normally nonpainful stimuli
Features persist ≥3 consecutive days
Features persist ≥2 weeks post-brain injury
Features persist despite treatment of differential diagnoses
Medication administered to decrease sympathetic features
≥2 episodes daily
Absence of parasympathetic features during episodes
Absence of other presumed cause of features
Antecedent acquired brain injury
DLT subtotal =
Combined total (CFS + DLT) =
Use CFS + DLT for diagnosis:
<8 = PSH unlikely
8 to 16 = PSH possible
≥17 = PSH probable
If total score 8 or greater, then use the CFS scale for monitoring of evolution (document daily maximal score).
BPM, beats per minute; PSH, paroxysmal sympathetic hyperactivity.
Adapted with permission from Baguley IJ, Perkes IE, Fernandez-Ortega JF, et al. Paroxysmal sympathetic hyperactivity after acquired brain injury: consensus on conceptual definition, nomenclature, and diagnostic criteria. J Neurotrauma. 2014;31(17):1515-1520. Copyright © 2014 Mary Ann Liebert, Inc. The publisher for this copyrighted material is Mary Ann Liebert, Inc. publishers.