Special Neurologic Tests and Procedures

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Chapter 61

Special Neurologic Tests and Procedures

J. Stephen Huff

Neuro-otologic tests and procedures are used in a variety of clinical scenarios ranging from evaluation of a dizzy patient to diagnosing brain death. Some of these procedures have become less common with the advent of advanced neuroimaging and electrophysiologic testing; nonetheless, their simplicity and effectiveness give them continued relevance, especially in practice environments with limited resources.¹

Caloric Testing

Accurate assessment of a comatose patient requires a thorough neurologic examination, including careful evaluation of the patient’s responses to a variety of external stimuli. In a comatose individual with normal brainstem and cranial nerve function, stimulation of the vestibular labyrinth results in well-described and reproducible extraocular movements. This response is known as the vestibulo-ocular reflex (VOR) and forms the physiologic basis for caloric testing. Caloric testing (calor from Latin, meaning heat) involves delivering a thermal stimulus to the external auditory canal to activate the labyrinth. Pathologic conditions involving either the vestibular or the oculomotor reflex pathways will alter or abolish the usual response to caloric stimulation.

Caloric tests may be performed in either conscious or unconscious patients, depending on the diagnostic circumstances. Quantitative caloric examination is conducted in awake ambulatory patients for evaluation of possible vestibular dysfunction. This type of testing requires precisely controlled irrigation temperatures and specialized recording devices and is best undertaken in a properly equipped laboratory under the supervision of an experienced neuro-otologist. However, a neurologist, neurosurgeon, or emergency clinician may perform qualitative caloric testing in a comatose patient to detect gross disruption of the VOR pathways that may indicate structural lesions or metabolic abnormalities affecting the labyrinth, vestibulocochlear nerve, or brainstem. In this clinical setting, ice water is used to provide stimulation of the vestibular system. Such testing needs no special expertise and can be done at the bedside with equipment readily available in the emergency department (ED). This simple procedure can provide valuable diagnostic and prognostic information necessary for the management of a comatose patient.

Brown-Séquard ² first described the effects of introducing cold water into the ear canal in the mid-19th century. The clinical importance of the phenomenon was first realized in 1906 by Bárány,³ who developed a caloric procedure involving an ice water stimulus. He postulated, correctly, that caloric stimulation of the auditory canal induces the formation of convection currents within the semicircular canals of the vestibular labyrinth.

Standardization of the procedure awaited introduction of the Fitzgerald-Hallpike technique in 1942. This technique used both warm and cool water stimuli under rigidly specified conditions, which permitted quantification of normal and abnormal caloric responses. Today, most formal caloric testing of conscious patients is based on variations of the original Fitzgerald-Hallpike procedure.⁴

The value of caloric testing in the assessment of comatose patients was emphasized by the work of Klingon ⁵ and Bender and associates.⁶ Electronystagmography (ENG) can provide a graphic record of reflex eye movements and permit precise determination of the intensity of the caloric response.

Physiology and Functional Anatomy

Proper performance and interpretation of a caloric test requires a basic understanding of the structure and function of both the vestibular and oculomotor systems. The anatomic pathways underlying the VOR begin in the posterior portion of the labyrinth of the inner ear. The peripheral vestibular apparatus is located within the temporal bone and consists of the utricle, the saccule, and the lateral, anterior, and posterior semicircular canals. Because of its proximity to the external ear canal, the lateral or horizontal canal is of principal interest in caloric testing. The lateral canal is oriented at a 30-degree angle to the horizontal plane. Deflections of the cupola because of movement of endolymphatic fluid within the canal result in changes in polarization in the underlying hair cells, which in turn are relayed to the afferent limb of the primary vestibular neuron.

Impulses of the primary neuron travel via Scarpa’s ganglion and cranial nerve VIII to the brainstem and synapse with secondary vestibular neurons in the superior and medial vestibular nuclei of the upper medulla and lower pons (Fig. 61-1). Although the connections between the vestibular and oculomotor nuclei in the brainstem are quite complex, two main pathways exist. The direct projection runs from the vestibular complex to the nuclei of cranial nerves III and VI via the medial longitudinal fasciculus (MLF) and involves only three neurons: (1) primary vestibular, (2) secondary vestibular, and (3) oculomotor. The indirect projection between these nuclei occurs over multisynaptic circuits in the tegmental reticular formation. Another brainstem structure that contributes to the vestibulo-ocular interaction is the paramedian pontine reticular formation (PPRF), a poorly characterized group of pontine neurons that coordinate both voluntary and involuntary lateral gaze. The PPRF receives multiple inputs. Including projections from the vestibular system and the contralateral frontal cortex, and sends output to oculomotor neurons through both direct and indirect pathways. Excitatory impulses originating in the lateral canal finally travel via the oculomotor and abducens nerves to the ipsilateral medial rectus and contralateral lateral rectus muscles.⁷

Figure 61-1 Vestibulo-ocular reflex and its contribution to horizontal eye movements. The semicircular canals respond to rotational acceleration of the head by driving the vestibulo-ocular reflex to maintain the eyes in the same direction in space during head movement. Fibers from the horizontal semicircular canal travel first to the vestibular nuclei and then to each paramedian pontine reticular formation. Excitatory projections that travel to the contralateral sixth cranial nerve nucleus and, via the medial longitudinal fasciculus, to the ipsilateral medial rectus subnucleus cause gaze to the left. In a similar manner, inhibitory projections are sent to the antagonist ipsilateral lateral rectus and contralateral medial rectus. (Adapted from Lavin PJ, Donahue SP. Disorders of supranuclear control of ocular motility. In: Yanoff M, Duker JS, eds. Ophthalmology. 3rd ed. St. Louis: Mosby; 2008.)

Rotation of the head generates flow of endolymphatic fluid within the semicircular canals. The firing rate of the primary vestibular neuron is dependent on the direction of flow. For example, in the lateral canal, flow toward the ampulla (ampullopetal) increases the firing rate, whereas flow away from the ampulla (ampullofugal) decreases the firing rate. Increased firing on one side results in conjugate deviation of the eyes toward the opposite side, whereas decreased firing causes deviation to the same side. This principle forms the physiologic basis of caloric testing. When the lateral canal is in the vertical position (patient placed supine) and ice water is infused into the ear, the endolymph nearest the canal cools and sinks, which results in ampullofugal flow (Fig. 61-2). As the firing rate decreases, the eyes deviate conjugately toward the side of irrigation. When warm water is used in the same position or when the canal is inverted 180 degrees, the opposite occurs.

Figure 61-2 Convective flow mechanism of the caloric response. Irrigation with warm or cold water (or air) results in a temperature gradient across the horizontal semicircular canal. With the horizontal canal oriented in the earth-vertical plane, gravity induces convective flow of endolymph from the cooler area of the canal, in which endolymph is more dense, into the warmer area of the canal, in which endolymph is less dense. For the warm caloric irrigation shown in this diagram, an ampullopetal deflection of the cupula results from this flow of endolymph. Vestibular nerve afferents innervating the horizontal semicircular canal are excited, and a horizontal nystagmus with slow-phase components directed toward the opposite ear is produced. A cold caloric stimulus results in an oppositely directed response, with ampullofugal deflection of the cupula, inhibition of horizontal canal afferents, and nystagmus with slow-phase components directed toward the ear to which the cold caloric stimulus is applied. (Adapted from Baloh RW, Honorubia V, eds. Clinical Neurophysiology of the Vestibular System. 3rd ed. Philadelphia: Davis; 2001.)

The eye movements induced by caloric stimulation in conscious, neurologically normal individuals are more complex. Ice water infusion induces a rhythmic jerking of the eyes that includes a slow deviation toward the irrigated side followed by a quick compensatory saccade toward the midline. This is known as caloric nystagmus. By convention, caloric nystagmus is named for the fast component, thus the popular mnemonic “fast COWS” (Cold irrigation—Opposite beating nystagmus; Warm irrigation—Same-sided beating nystagmus). Most sources attribute the slow phase of nystagmus to vestibular activity transmitted over the direct pathway, whereas the fast phase is believed to be generated by the PPRF in conjunction with cortical activity and carried over indirect pathways within the reticular formation. Numerous factors, including physiologic, pharmacologic, and pathologic, can alter caloric-induced eye movements.

Second Phase of Interpretation

After irrigation, ocular movements should be observed for any response to the stimulus. Again, typically there is a latency of response of 10 to 40 seconds. Reactions to ice water irrigation may be divided into four categories: (1) caloric nystagmus, (2) conjugate deviation, (3) dysconjugate deviation, and (4) absent responses (Fig. 61-3). The first reaction, caloric nystagmus with the fast component beating away from the side of ice water irrigation, is seen in normal, alert individuals, in cases of psychogenic unresponsiveness, and in those who have very mild organic disturbances in consciousness. The intensity of nystagmus is highly variable in conscious subjects and depends on the degree of visual fixation and the level of mental alertness. The response is present in more than 90% of children by 6 months of age and declines in magnitude only after the seventh decade of life.¹³

Figure 61-3 A, The four types of caloric responses seen with unilateral and bilateral irrigation. 1, Normal nystagmus. 2, Conjugate deviation. 3, Disconjugate deviation. The most common type, internuclear ophthalmoplegia, is shown here. Vertical eye movements usually remain intact in this lesion. 4, Absent caloric responses. MLF, medial longitudinal fasciculus. B, Oculocephalic and oculovestibular testing in patients with selected clinical conditions. (A, Modified from Plum F, Posner JB, eds. The Diagnosis of Stupor and Coma. 3rd ed. Philadelphia: Davis; 1980:55; B, from Smith M, Bleck T. Techniques for evaluating the cause of coma. J Crit Illness. 1987;2:51.)

Caloric-induced nystagmus after cold water irritation in an apparently comatose individual usually occurs when testing individuals with psychogenic unresponsiveness as a result of catatonia, conversion reactions, schizophrenia, or feigned coma. Hyperactive caloric responses may result from testing in the presence of tympanic perforation or mastoid disease. Hypoactive caloric responses are recorded in patients with a wide variety of vestibular and neurologic disorders.

Hypoactive or abnormal caloric responses may be further evaluated with quantitative caloric testing, ENG, or other techniques such as auditory evoked responses. Caloric-induced nystagmus may be inverted (beating to the wrong side) or perverted (beating in the wrong plane); both responses may be seen with brainstem lesions. Pseudocaloric nystagmus is a preexisting latent nystagmus that is brought out by the general arousal of ice water irrigation; it can be distinguished from true nystagmus by its failure to reverse direction with warm water irrigation.

As the level of coma deepens, the fast phase of nystagmus becomes intermittent and then disappears, probably because of decreased activity in the cerebral cortex.

In the second type of response to cold caloric stimulation, the eyes deviate conjugately toward the side of ice water stimulation (they “look” toward the source of irritation). When present, this reaction indicates intact brainstem function, as well as intact afferent and efferent limbs of the reflex. This is seen during general anesthesia, in supratentorial lesions without brainstem compression, and with many metabolic and drug-induced comas. In such situations, bilateral simultaneous irrigation with ice water might result in conjugate downward deviation, thus implying that the brainstem centers for vertical gaze are functional.

Dysconjugate reactions constitute the third type of caloric response to ice water stimuli. The most common dysconjugate reaction is internuclear ophthalmoplegia, in which a lesion of the MLF causes weakness or paralysis of the adducting eye after caloric irrigation. Internuclear ophthalmoplegia might be due to acute damage to the rostral pons or could be seen as a manifestation of multiple sclerosis or stroke.

With acute supratentorial lesions, the development of dysconjugate caloric responses is a significant sign that may indicate compression of the brainstem and impending herniation. Caloric responses of this type are less common with metabolic and drug-induced coma; when present in metabolic coma, their significance is less ominous. Reversible internuclear ophthalmoplegia has been reported in patients with hepatic coma and may occur during toxic responses to phenytoin, barbiturates, or amitriptyline. Forced downward deviation of the eyes, either conjugate or dysconjugate, may be seen in sedative-hypnotic drug–induced coma when unilateral caloric testing is performed.¹⁴

Palsies of the oculomotor nerves are another cause of dysconjugate reactions, although most should be apparent before irrigation. Causes include diabetic neuropathy, increased intracranial pressure, and Wernicke’s encephalopathy. Finally, Plum and Posner ¹⁰ reported that unusual and poorly characterized caloric responses may be obtained when testing comatose patients with long-standing severe brain injury.

Absent caloric response is the fourth category of reactions to ice water stimuli. As a general rule, the VOR is preserved more than other brainstem reflexes; however, the oculocephalic, or doll’s eye, response may persist in the absence of caloric responses. Loss of caloric responses in comatose patients with structural lesions is usually a sign of brainstem damage. With supratentorial lesions, progressive loss of caloric responses may be seen in the final stages of transtentorial herniation. The VOR may also be transiently absent or decreased on the side opposite massive supratentorial damage during the first hours after injury.¹⁵ Absent caloric responses may occur with any subtentorial lesion that affects the vestibular reflex pathways, including pontine hemorrhage, basilar artery occlusion, cerebellar hemorrhage, or infarction with encroachment on the brainstem, and with any expanding mass lesion within the posterior fossa. Caloric responses may disappear in patients with deep coma resulting from subarachnoid hemorrhage, perhaps because of pressure on the brainstem.

The VOR is usually retained until the late stages of metabolic coma. Nevertheless, caloric responses may be transiently absent in certain types of drug-induced coma, with eventual complete recovery of the patient. The VOR seems to be particularly sensitive to the effects of sedative-hypnotic drugs, antidepressants (e.g., amitriptyline, doxepin), and anticonvulsants (e.g., phenytoin, carbamazepine).16,17 As one would expect, neuromuscular blocking agents (e.g., succinylcholine) will abolish caloric-induced ocular movements.

Finally, the caloric response may be absent for reasons other than the neurologic causes responsible for the coma. Inadequate irrigation because of excessive cerumen or poor technique and unilateral or bilateral dysfunction of the peripheral vestibular apparatus must be considered. Bilateral loss of the caloric response (areflexia vestibularis) is uncommon in conscious patients, constituting 1.7% and 0.2% of the ENG clinical population in two large series of patients.18,19

The VOR has prognostic as well as diagnostic significance in comatose patients. In a study of 100 patients who were comatose as a result of head trauma, absence of caloric responses 1 to 3 days after injury was associated with extremely high mortality.²⁰ Testing in the immediate posttraumatic period may yield inconsistent responses and is of considerably less prognostic value. Levy and coworkers²¹ studied 500 cases of nontraumatic, non–drug-induced coma in a large multicenter study. Absence of the VOR correlated with less than a 5% chance of achieving functional recovery within 1 year when tested within 6 to 24 hours of the onset of coma. In one study of comatose patients, the combination of absent VOR and absent pupillary light reflex at 24 hours was associated with 100% mortality.²² Complete loss of caloric responses is part of the criteria for the diagnosis of brain death and correlates with irreversible cessation of cerebral function at least as well as an isoelectric electroencephalogram (EEG) does.²³ Excessive reliance on a single clinical sign must be avoided during consideration of brain death and in decisions regarding neurologic prognosis, and therapy should be based on complete evaluation of all the evidence available (see the later section “Brain Death Testing”).

Summary

Caloric testing is a simple, easily performed bedside procedure that may enhance the neurologic assessment of comatose patients. When reliably interpreted, caloric testing may furnish valuable diagnostic and prognostic information. Even if the cause of the coma is known, the test may provide a baseline for the evaluation of changes in the patient’s status. In the ED this test should be reserved for stable patients undergoing secondary assessment. The examination requires minimal equipment and can be conducted in a few minutes while awaiting the results of laboratory testing or neuroimaging. Complications are few if patients are properly selected and correct technique is used.

DIX-Hallpike Test For The Diagnosis of Positional Vertigo

Vertigo occurring only and repeatedly with change in position is probably benign paroxysmal positional vertigo (BPPV); the head-hanging positioning maneuver (Dix-Hallpike test, sometimes referred to as the Nylen-Báràny maneuver) is useful in confirming clinical suspicion of BPPV because the abnormal nystagmus provoked is characteristic of the disorder.24,25 In BPPV, it is thought that calcium crystal material displaced from the vestibule floats within the endolymph of the posterior semicircular canal. Head movement induces bidirectional forces in the fluid acting on the cupula that trigger the attack of BPPV.^26–29 The posterior semicircular canal is most commonly affected,^25,28 but at times the horizontal canal is thought to be involved, thereby leading to variants of typical BPPV.^30–32

Background

BPPV is a common mechanical disorder of the inner ear in which vertigo is precipitated by certain head movements; nystagmus and autonomic symptoms such as nausea and vomiting commonly accompany the vertigo. Although patients may have quite dramatic findings with severe autonomic symptoms, the actual episodes of vertigo are extremely brief and typically last less than 1 minute. Syndromes of positional vertigo and provocative maneuvers have been described by clinicians for more than 100 years; the description of BPPV has been attributed to Adler, Báràny, Nylèn, Bruns, Borries, Dix, and Hallpike.³³ Dix and Hallpike most fully defined the disorder, and the provocative technique that they described is superior; thus it most accurately should bear the eponym Dix-Hallpike positioning test or the Dix-Hallpike test.^25–33 Rarely, paroxysmal positional vertigo from a central cause has also been described in patients with small cerebellar hemorrhages.³⁴

Indications and Contraindications

The Dix-Hallpike test may be a useful diagnostic test in confirming BPPV by provoking a specific type of nystagmus and in selecting patients suitable for positional therapy (discussed later). The maneuver should not be performed on patients with severe cervical spine disease, unstable spinal injury, high-grade carotid stenosis, or unstable heart disease.²⁵ Patient discomfort and physical infirmity are relative contraindications; some elderly patients or those with ongoing nausea or vertigo may not tolerate the changes in body position necessary for performance of the procedure. If nystagmus is present at rest without any provocation or if associated neurologic signs or symptoms exist, the diagnosis of BPPV is probably excluded and the maneuver is not clinically indicated.

Procedure

The Dix-Hallpike maneuver is illustrated in Figure 61-4. Place the patient initially in the seated position on the stretcher with the head turned 45 degrees to one side. With the patient instructed to keep the eyes open and focused on the examiner, quickly lay the patient down flat with the head hanging over the edge of the bed and observe the eyes for induced nystagmus. Repeat the entire maneuver with the head turned 45 degrees toward the opposite side.²⁵

Figure 61-4 The Dix-Hallpike test for evaluating a patient complaining of dizziness for benign paroxysmal positional vertigo (BPPV) affecting the right ear. (Adapted from Furman C. Benign paroxysmal positional vertigo. N Engl J Med. 1999;341:1590.)

Interpretation

The Dix-Hallpike head-hanging positioning maneuver produces vertigo in patients with positional vertigo that is most commonly characterized as BPPV. The stereotypic positive response in BPPV is provoked vertigo developing after a brief delay (1 to 10 seconds), lasting less than a minute, and with direction-fixed rotary nystagmus. Nausea or other systemic symptoms are often present.24,25 The eye movements are mixed torsional and vertical nystagmus of both eyes with the upper pole of the eye beating toward the dependent ear and the vertical nystagmus beating toward the forehead. The side with the ear in the downward position during the Dix-Hallpike test that elicits greater nystagmus usually identifies the affected ear. After the patient is returned to the sitting position, the nystagmus may again be transiently observed in a reverse direction. If the positional nystagmus is atypical or if the maneuver fails to elicit nystagmus in a patient with ongoing symptoms of vertigo, another diagnostic possibility should be considered.^25,35

Complications

The maneuver may precipitate brief vertigo and nausea in patients with BPPV.

Summary

The Dix-Hallpike test may be useful in confirming the diagnosis of BPPV and in localizing the abnormality to one ear. Accurate identification of BPPV is of interest because of the possibility of canalith-repositioning maneuvers, as described next.

Canalith-Repositioning Maneuvers

If the clinical evaluation of a patient with vertigo is consistent with the diagnosis of BPPV and the Dix-Hallpike test is supportive of the diagnosis and lateralizes to one ear, the patient may be a candidate for attempted canalith-repositioning maneuvers. These techniques have largely been described in the otologic and neurologic literature and have recently been described in the ED setting. Success rates of 44% to 100% are reported.²⁵ One small ED-based study concluded that the Epley maneuver was more efficacious than a placebo maneuver.³⁶

Background

With theory suggesting that stray material in the posterior semicircular canal causes the symptoms of BPPV, maneuvers were designed that involved sequential head movements to reposition the debris to the vestibule.25,29,37,38 Manipulation of head position theoretically allows the debris (“canaliths”) to sequentially fall from the problematic location in the semicircular canal to the vestibule of the labyrinth, where they presumably adhere. The currently recommended maneuver was introduced by Epley.²⁹ Other maneuvers are described but require repeated trials or are more difficult to perform and perhaps more uncomfortable for the patient.^25,37,39 The Semont maneuver is also described because it may be performed at the bedside. In theory, the Semont maneuver would be effective primarily in patients in whom the displaced canaliths were adhering to the cupola of the posterior semicircular canal (Schuknecht cupolith theory), although it might be effective as well when the debris are free floating in the long arm of the semicircular canal; the Epley maneuver would be effective only in patients with debris floating in the long arm of the posterior semicircular canal (canalith theory).⁴⁰ In one small trial comparing the efficacy of either the Semont or the Epley maneuver in a carefully selected outpatient otolaryngology population, the maneuvers were found to be of roughly the same effectiveness (90%) in relieving or improving symptoms of BPPV.⁴⁰

Indications and Contraindications

The indication for any canal-clearing or “liberatory” procedure is the clinical diagnosis of BPPV as confirmed by the history and physical examination, including the Dix-Hallpike maneuver. Careful patient selection is probably a key point in the success of any of these maneuvers, as well as correct identification of the impaired ear, which will govern the initial position and movement of the patient. Contraindications are the same as for the Dix-Hallpike maneuver, as noted earlier.

Procedure

The Epley procedure is illustrated in Figure 61-5. Briefly, as in the Dix-Hallpike maneuver, place the patient initially in the seated position on the stretcher with the head turned 45 degrees toward the affected side. Lay the patient down flat with the head hanging over the edge of the bed. After 20 seconds or after the symptoms subside, rotate the patient’s head so that it faces the opposite shoulder while maintaining the head-hanging orientation. Roll the patient further onto the side and rotate the head further into a face-down position. Again, after 20 seconds or after any symptoms subside, return the patient to a seated position.^26,35,39 Some authors suggest keeping the patient’s head in each position long enough for any provoked symptoms of nystagmus or vertigo to resolve.²⁵ Others suggest a period of 4 minutes after the head is placed in the hanging position and again after rotation of the head (“modified Epley maneuver”).⁴⁰ The maneuver may be repeated a few times until some improvement in symptoms occurs, although this is not typically described in the literature.⁴⁰ After a successful procedure, advise the patient to remain in a head-upright position for 24 hours.

Figure 61-5 The Epley procedure, a bedside maneuver for the treatment of a patient with benign paroxysmal positional vertigo affecting the right ear. The presumed position of debris within the labyrinth during the maneuver is shown in each panel. (Adapted from Furman C. Benign paroxysmal positional vertigo. N Engl J Med. 1999;341:1590.)

The Semont maneuver involves larger and more abrupt body movements. Identify the affected ear by the Dix-Hallpike maneuver. With the patient seated on the side of an examination table or bed, turn the patient’s head toward the unaffected side. Quickly lay the patient down into a side-lying position (Fig. 61-6) and keep the patient there until the symptoms subside. Move the patient abruptly through the sitting position to the opposite side-lying position and keep the patient there until the symptoms subside. Return the patient to the upright position.^39,40 Advise the patient to remain in a head-upright position for 24 hours after a successful procedure.

Figure 61-6 Semont’s maneuver.

Complications

Exacerbation of vertigo occurs occasionally and is thought to result from displacement or dislodgment of canal debris. Repeating the procedure is recommended for relief. Similar symptoms may recur in as many as 50% of patients and in up to 20% in the first 2 weeks.²⁶

Summary

In patients with correctly identified BPPV, canalith repositioning may bring immediate relief or improvement of symptoms. Experience in the ED setting is limited but growing.³⁶

Tests to Distinguish Central From Peripheral Lesions in Patients with AVS

Background

Vertigo that is not limited to very brief episodes and triggered by a change in position is not BPPV. Acute vestibular syndrome (AVS) refers to another group of disorders characterized by an acute onset of vertigo, nausea, vomiting, and gait instability that lasts for days to weeks. The majority of these conditions are the result of a peripheral neuropathy, either acute labyrinthitis or vestibular neuritis. Auditory function is preserved in pure vestibular neuritis. The condition is called labyrinthitis when this syndrome is combined with unilateral hearing loss. Both are often preceded by a viral illness.

Unfortunately, a certain percentage of patients with AVS (as many as 25% in some series) harbor a more sinister central pathology such as a brainstem or cerebellar stroke.⁴¹ Moreover, unlike BPPV, which tends to be very specific in its findings, it can be very difficult to distinguish a peripheral from a central process in patients with AVS. Traditional teaching has emphasized a careful neurologic examination in an attempt to find other cranial nerve, cerebellar, or long-tract (descending motor or sensory) findings to corroborate the presence of a central lesion. However, in some patients with stroke involving the posterior circulation, the vertigo is isolated and routine neurologic examination will reveal none of these findings. Magnetic resonance imaging (MRI) may help unravel such cases, but it is not standard to routinely perform MRI in patients with AVS simply because of the rare incidence of occult stroke. Stroke mimicking AVS is rare in young healthy patients, but a stroke causing AVS symptoms may be considered in the elderly or in patients with hypertension, diabetes, previous stroke, atherosclerotic vascular disease, or other vasculopathies.

In 1988, Halmagyi and Curthoys ⁴² described the horizontal head impulse test (h-HIT), a test of the VOR, as a bedside evaluation to detect peripheral vestibular disease. Subsequent studies have revealed that although a normal finding on the h-HIT is able to reliably identify patients with a central cause of vertigo, it is not as reliable in ruling out central pathology; a positive (abnormal) h-HIT may also occur in patients with lateral pontine and cerebellar stroke syndromes.⁴³

The ability of the h-HIT to exclude stroke may be enhanced by the addition of two bedside maneuvers, an examination of nystagmus and a test of skew. The nystagmus that results from a peripheral lesion is unidirectional; its fast or corrective phase beats away from the affected side when the head is rapidly rotated toward that side. Nystagmus that changes its direction (the fast beating phase) with horizontal gaze to either side is highly predictive of a central lesion, as is spontaneous vertical and multidirectional nystagmus.⁴⁴ Skew deviation refers to a misalignment of the eyes in the vertical plane; it is usually associated with a central lesion. Although skew deviation can be quite subtle, it can be unmasked by alternately covering each eye in rapid succession while the patient fixes his gaze on the examiner.⁴⁵

Using the h-HIT, Newman-Toker and colleagues ⁴³ were able to distinguish central vertigo from peripheral vertigo in most cases. However, the test is far from perfect; in one study of 43 patients with AVS, 3 patients with stroke (9%) had a positive result on the h-HIT. In a more recent study, when an examination for bidirectional nystagmus and test of skew were added, diagnostic accuracy improved.⁴⁶ In 108 patients with chronic risk factors for cerebrovascular disease and a new onset of AVS, the presence of either a normal h-HIT result, direction-changing nystagmus on eccentric gaze, or skew deviation was 100% sensitive and 96% specific for stroke. In this series, 25 peripheral and 76 central lesions were diagnosed by using a combination of MRI and clinical follow-up. Consistent with previous studies, the h-HIT erroneously suggested a peripheral lesion in a small minority (two) of cases. Interestingly, initial diffusion-weighted MRI was falsely negative in 12% of patients in whom a central lesion was ultimately diagnosed.

Indications and Contraindications

Like the Dix-Hallpike maneuver, the h-HIT should not be performed in patients with severe cervical spine disease, unstable spinal injury, high-grade carotid stenosis, or unstable heart disease. Patient discomfort is also a relative contraindication. If nystagmus is present at rest without any provocation (especially if it is vertical or bidirectional), if vertical skew is present, or if any other associated neurologic signs or symptoms exist, a central origin of the vertigo should be suspected and the maneuver is not clinically indicated. There are no absolute contraindications to examination for bidirectional nystagmus or testing for skew.

Procedure

Have the patient seated in a comfortable position. Ask the patient to gaze directly on the examiner’s eyes at all times. Quickly rotate the patient’s head to each side while carefully observing the eyes for nystagmus. A negative and positive h-HIT maneuver is simulated in Figure 61-7. Next, note any spontaneous vertical nystagmus or nystagmus that is bidirectional with horizontal gaze to both sides. To test for skew, alternately cover each eye in rapid succession while the patient looks directly ahead—note any vertical misalignment that occurs.

Figure 61-7 The horizontal head impulse test (h-HIT). In the setting of a sudden onset of isolated vertigo, a normal h-HIT result strongly suggests a central origin (e.g., brainstem or cerebellar stroke). Top row, The intact vestibular-ocular reflex causes the subject’s eyes to smoothly track the examiner as his head is quickly turned to one side. Bottom row, A patient with a peripheral vestibular lesion does not track the examiner when the head is turned to the affected side and requires a quick, corrective saccade back to the examiner.

Interpretation

A positive h-HIT occurs when the head is rotated toward the side of a peripheral vestibular lesion; loss of afferent input from the affected side results in an inability to maintain fixation during head rotation. This requires a corrective saccade (fast jerking movement) back toward the examiner. A negative or normal h-HIT result in the setting of AVS is strongly suggestive of a central origin. A positive h-HIT is consistent with but not diagnostic of a peripheral vestibular lesion. In patients with a positive h-HIT result, diagnostic confidence of a peripheral lesion may be increased if there is an absence of bidirectional nystagmus on lateral gaze and a negative test of skew.

Complications

The h-HIT may exacerbate injury in improperly selected patients with unstable cervical spinal injury or, theoretically, with severe carotid atherosclerotic disease, although no reports of such complications have been reported.

Summary

The h-HIT, along with examination for vertical and bidirectional nystagmus and a test of skew, may be useful in identifying patients with a central cause of vertigo. Although early investigations appear to confirm their role in differentiating central from peripheral vertigo, they should be used with caution and in conjunction with other diagnostic data until further studies confirm their reliability in the ED setting.

Brain Death Testing

A textbook of emergency medicine from 1988 once stated that because emergency medicine is a life support–oriented specialty, determination of brain death was outside the practice of the emergency clinician.⁴⁷ The date of publication reflects practice at that time; neuroimaging was not often performed while patients were in the ED, and delays for inpatient beds were less common. With increased use of neuroimaging in the ED and general trends toward increased ED length of stay, the occasion may arise for emergency clinicians to be involved in the assessment of brain death. The duty to identify potential organ and tissue donors is another consideration in identifying patients with irreversible loss of brain function. Local practices, policies, regulations, and laws differ, and these remarks are general; the clinician is urged to be familiar with local practices and administrative policies regarding the issue of brain death. Brain death determination has been considered in court cases in the United States, and court rulings have upheld the medical practice of determination of brain death.⁴⁸

For purposes of this discussion, brain death is defined as irreversible loss of functioning of the cerebral hemispheres and brainstem consistent with definitions in the literature.49–52 The cause of the brain injury should be known or identified because some toxicologic syndromes, notably barbiturate toxicity, exactly duplicate the clinical syndrome of brain death. This section focuses on clinical procedures commonly used to delineate brain death. Radiologic, electrophysiologic, and other tests that are sometimes used are not covered in detail. It should also be noted that in most cases a determination of brain death is not necessary for withdrawal of life-supporting measures. If a cause of coma or severe neurologic injury is identified and a poor prognosis is shared with the family, the option of withholding or withdrawing life support is often exercised. This is entirely within the realm of the patient, family, and clinician, and formal determination of brain death need not occur in these circumstances.

Background

With the advancement of intensive care techniques, patients were identified with continuing spontaneous cardiovascular function while on ventilatory support but without evidence of CNS activity. Observation of these patients revealed that cardiovascular function would eventually fail, although rare prolonged survival has been reported.53,54 Criteria to reliably identify these patients have been sought for multiple reasons, including to help in family counseling, improve resource allocation, and identify potential organ donors. Part of the impetus for a reliable set of criteria for brain death was legal; a legal pronouncement of death allows discontinuation of advanced life support in cases in which disagreement about continued life support measures may exist.

Death had long been defined as cessation of cardiac function; deeply comatose patients with persistent cardiac activity but without demonstrable brain function challenged the traditional definition of death. The concept of brain death has been entangled in continuing ethical, legal, and policy discussions roughly since the advent of the clinical application of mechanical ventilation in the 1960s.49,55,56

Indications and Contraindications

Evaluation for brain death implies that severe CNS dysfunction has been identified, that the cause of the CNS dysfunction is known, and that reversible causes of profound coma have been confidently excluded.50,52 Formal assessment of brain death is made in preparation for pronouncement of death to allow organ harvest or in uncommon cases of disparate family or caregiver convictions regarding prognosis of the patient. Complex medical issues that may confound the assessment should be considered and ruled out, including severe electrolyte disturbances, hypothermia (defined as a core temperature < 32°C), hypotension, drug intoxication or poisoning, and pharmacologic neuromuscular blockade.⁵² Neuroimaging studies should be carefully reviewed.

Procedure

Establishment of Coma and Cortical Assessment

By definition, a patient under evaluation for brain death will be in a coma without spontaneous respirations. Certain examination techniques are used to establish loss of function of the cerebral cortex and brainstem; clinical neurologic examination remains the standard for determination of brain death.⁵² It typically involves assessment for cortical function and brainstem reflexes, including respiratory drive.

While holding the patient’s eyes open, give loud verbal commands such as “Look up!” and assess for voluntary eye movements, particularly important for patients with the locked-in syndrome. Additionally, deliver a strong painful stimulus by forcefully pressing on the brow, sternum, or nail bed. Should any cerebral or brainstem function be discovered, the patient is not by definition brain-dead even if severe brain injury is present. Some institutions require evaluation by two clinicians with particular specialty training or repeated examinations several hours apart. The need for a second brain death determination has recently been questioned.57,58 The clinician must be familiar with local practices and policies, which may also require an ancillary EEG, nuclear angiography, or other techniques. Brain death in the pediatric population is more complex, with varying recommendations for repeated examinations and ancillary tests; such discussion is outside the scope of this chapter but is summarized elsewhere.^52,59

Brainstem Reflex Testing

Pupillary Response: The pupils in brain-dead patients are unreactive and midposition to dilated. Shine a bright light into the pupil and observe for a reaction; none will be seen in a brain-dead patient. Should any reactivity be noted, the patient is not brain-dead.

Auditory Reflex: Deliver a loud handclap into each ear. Observe for eye blink or other reaction. Any reaction establishes that some brainstem function remains and excludes brain death.

Caloric Testing: Perform cold water irrigation of the external auditory canals with large volumes (≥100 mL) to elicit any eye movements through the VOR (described in detail earlier in this chapter). In a brain-dead patient, there will be no movement of the eyes in response to irrigation. Any eye movement excludes brain death.

Corneal Reflex: Stimulate the cornea with a cotton wisp or applicator. Observe for any eye closure, which indicates that the cranial nerve V to VII reflex arc remains intact and excludes the diagnosis of brain death.

Cough Reflex: Stimulate the trachea or main stem bronchi by deep suctioning and observe for coughing. A cough excludes brain death.

Apneic Oxygenation Test: CNS control of respiratory drive resides in the medulla. Establishing apnea is necessary to confirm medullary failure. Mechanical hyperventilation may artificially depress respiratory effort. It is hypercapnia, not hypoxia, that triggers respiratory effort. Simply disconnecting the ventilator to allow the development of hypercapnia for apnea testing may lead to hypoxia.⁶⁰ A variety of techniques have been described that allow adequate hypercapnia for medullary stimulation to develop but ensure that oxygenation is adequate during the test. The most commonly described technique is to disconnect the patient from the ventilator and deliver oxygen at 10 to 15 L/min through a catheter inserted into the trachea and then observe for respiratory effort for 8 minutes. Any observed excursion of the abdomen or chest sufficient to produce a tidal volume suggests that brain death is not present. If no respiratory excursions are observed, arterial blood gas analysis is obtained and the patient is reconnected to the ventilator pending results. An arterial partial carbon dioxide pressure (Pco₂) of 60 mm Hg or higher and the absence of respiratory excursions are the criteria for a positive apnea test.⁵¹ Others suggest that a possibly safer technique is to simply set the ventilator rate to zero while allowing continuous oxygen flow to continue and maintaining any necessary continuous positive pressure through the ventilator.⁶¹

Declaration of Death

If the criteria for brain death are satisfied, the family and all clinicians involved in patient care should be informed to allow further management decisions. At some institutions the patient is declared dead at the time that the criteria are met, and further care is assumed by the transplant services if that is the anticipated course. Per institutional protocol, confirmation of brain death by two clinicians may be required. Families are generally given the option of being present at the bedside while mechanical ventilation is discontinued, although some advise against this policy because spontaneous reflex movements such as the Lazarus sign (discussed below) may occur and disturb the family.⁸ For patients 18 years of age or younger, particularly infants, repeated examinations and confirmatory tests are generally recommended.^52,56,59 A model for direct family conversation in this sensitive interaction has been described and includes a sample script and procedure.⁶²

Complications

Carefully following the physical examination protocol reliably identifies the majority of patients with irreversible loss of brain function. Two basic types of error are possible: either erroneously declaring a patient brain-dead when in fact some CNS function is retained or failing to correctly identify brain death.

Profound barbiturate intoxication may simulate the picture of brain death at times. To guard against the error of failing to detect surreptitious pharmacologic coma, some protocols include toxicologic screening tests for barbiturates as part of the process of assessment for brain death. Ancillary techniques for assessing intracranial blood flow would also prevent this error. Two examinations both confirming brain death performed several hours apart have been part of some protocols with the idea that toxicologic coma might improve during this period of observation. Again, familiarity with local policies and practices is necessary.

A variety of movements have been observed in brain-dead patients; at times these spinal level–mediated reflexes may be dramatic and erroneously lead observers to believe that the brain-dead patient is demonstrating voluntary movements or brain-mediated reflex movements. Finger jerks and facial myokymia (spontaneous, fine fascicular muscular contractions) have been reported to be spontaneously present in brain-dead patients. Decerebrate-like extensor posturing, the Lazarus sign (flexion of the arms at the elbows, shoulder adduction, lifting the arms, dystonic posturing of the hands with crossing of the hands), undulating toe flexion, triple-flexion response in the lower extremities, and flexion of the trunk (giving the appearance of sitting up) are among the signs described during apnea testing and after the termination of ventilation or triggered by tactile stimuli.11,63–67

Summary

The emergency clinician may become involved in the assessment of patients for brain death in the course of current practice. The cause of irreversible coma should be known. The clinician is urged to be familiar with local practices and regulations in this sometimes complex medicolegal process.

MG Testing

Background

Myasthenia gravis (MG) is the most common disease of neuromuscular transmission, but the incidence is just 1 in 20,000 in the general population. Patients with MG may be grouped into two major categories. The first group shows weakness in the proximal muscles that increases with activity and improves with rest. The other group has ocular complaints of diplopia or ptosis. Patients in the ocular weakness group may or may not have generalized symptoms as well. Fatigue is the hallmark of the disease; the symptoms typically wax and wane. Patients often see a number of clinicians before a correct diagnosis is made.68,69

MG results from immune-mediated destruction of postsynaptic acetylcholine (ACh) receptors, with variable failure of neuromuscular transmission.68,69 ACh is the transmitter at the neuromuscular junction. When the nerve terminal is stimulated, ACh is released in a quantity far in excess of that needed for effective activation of the ACh receptor. ACh diffuses across the synaptic cleft to transiently interact with the ACh receptor, and an electrical potential is generated at the myoneural end plate. If of sufficient magnitude, the end plate potential initiates an action potential that is propagated along the muscle membrane, and muscle fiber contraction follows. The ACh is rapidly hydrolyzed by acetylcholinesterase in the synaptic cleft. Figure 61-8 summarizes neurotransmitter action at the neuromuscular junction. Of the millions of receptors at each myoneural junction, only a fraction must depolarize to stimulate muscle fiber contraction. Any factor that decreases the interaction of ACh with ACh receptors decreases the probability of an action potential being generated and may lead to failure of neuromuscular transmission with resulting weakness. Acetylcholinesterase inhibitors (anticholinesterases) have been the mainstay of therapy for MG for years, but they have been supplemented by immunosuppressive regimens and thymectomy. Failure of neuromuscular transmission may also occur with excessive inhibition of acetylcholinesterase; persistence of ACh in the synaptic cleft leads to continuous depolarization of the receptor.

Figure 61-8 Neuromuscular junctions. In myasthenia gravis, acetylcholine is released from presynaptic vesicles and diffuses across the synaptic cleft to the postsynaptic receptors. Acetylcholinesterase, located deep within the synaptic folds, hydrolyzes acetylcholine. There is also a simplification of the postsynaptic site with a reduced number of receptors.

Bedside diagnostic testing for MG has been described in patients seen in the ED with two different clinical pictures. The first involves a known patient with MG and increased weakness who is being treated with cholinesterase inhibitor therapy; pharmacologic testing in this setting is controversial. The second involves a previously undiagnosed patient in whom the diagnosis of MG is suspected because of ptosis, diplopia, or fluctuating muscular weakness; bedside testing may be helpful in selected patients in this group.

A battery of tests can be used for the assessment of a patient with suspected MG, but only a few are available to the emergency clinician.70,71 ACh receptor antibody assay is positive in more than 80% of patients with MG but has a turnaround time of several days.^72,73 Repetitive nerve stimulation and single-fiber electromyography tests are available in the electrophysiology laboratory.⁷⁴ Several pharmacologic tests have been used to aid in the diagnosis of suspected MG, including parenteral administration of edrophonium chloride (Tensilon), neostigmine, or curare. Administration of edrophonium chloride for the diagnosis of MG (Tensilon test) is described in detail because of the drug’s rapid onset, short duration of action, and widespread acceptance for this diagnostic challenge; the emergency clinician may find occasion to use this test. The ice pack test is discussed because of favorable reports of its utility and noninvasive nature.^71,75,76 Other noninvasive tests such as the “sleep test” (improvement in ptosis after 30 minutes of rest) and the “peek sign” (failure of the patient to maintain gentle eye closure) have been described.⁷¹ Both systemic and regional administration of curare has also been reported to aid in the diagnosis of MG. A technique is described for administration of curare into an ischemic arm; this modification is known as the regional curare test.⁷⁴ The use of curare in this setting is outside the realm of practice of the emergency clinician.

Edrophonium (Tensilon) Test

Background

Edrophonium chloride (Tensilon) is an acetylcholinesterase inhibitor that has been used for the diagnosis of MG since the 1960s. The short duration of action of edrophonium that made it unsatisfactory as a therapeutic agent for MG makes it useful as a diagnostic agent. The drug’s onset of action is rapid, and the duration of maximal effect is short, usually less than 2 minutes. Any effect resolves within 5 to 10 minutes.⁷⁷

Edrophonium administration has also been recommended in the past to monitor acetylcholinesterase inhibitor therapy.78,79 However, edrophonium is not sufficiently reliable for titrating the effect of anticholinesterase medication.⁸⁰ Use of the Tensilon test in a patient with known MG is controversial and should be done only in consultation with or in the presence of the treating neurologist, if at all.

Myasthenic crisis may be defined as respiratory distress in a patient with MG. In a myasthenic patient with respiratory distress, airway management and assisted ventilation are top priorities. Administration of edrophonium should not be viewed as a possible alternative to intubation and mechanical ventilation.

Earlier types of crises described included “myasthenic” crisis from insufficient drug administration, “cholinergic” crisis from overdosage of a cholinesterase inhibitor, and the “brittle” patient with rapidly changing drug requirements,81,82 but terminology in this setting remains controversial.⁸³ Even the clinical existence of the different types of crises has been debated.⁸⁰ Several authorities advocate withdrawing all cholinesterase inhibitors in patients with worsening symptoms because most patients show increased responsiveness to cholinesterase inhibitors after several days without taking the drug.^80,83 Others advocate a trial of edrophonium chloride at reduced dosage (1 to 2 mg) only after ventilator support.^81,84

Indications and Contraindications

The bedside Tensilon test is indicated for the diagnosis of patients with suspected MG when there is a clinical need to make this diagnosis immediately. If other bedside tests such as the ice pack test (discussed later) are conclusive or if eyelid fatigue on prolonged upgaze can be demonstrated, there is no need to administer edrophonium.⁸⁵ If the tempo of the clinical scenario is such that consultation or admission and performing specialized electromyelograms or serologic testing are feasible, deferring the Tensilon test in the ED may be preferred in recognition of the fact that serologic and neurophysiologic testing will not be completed for several days.

Administration of edrophonium is commonly performed in office settings by neuro-ophthalmologists, and occasionally complications of bradycardia occur that at times may be symptomatic with hypotension and loss of consciousness.86,87 One study reported the complication rate in office settings to be 0.16%.⁸⁶ A history of asthma or cardiac dysrhythmias is a relative contraindication to the administration of cholinesterase inhibitors. Complications reported in the literature from edrophonium testing largely date from the era when it was used in cardiology to differentiate supraventricular rhythms.⁸⁵ Reported complications include disturbances in cardiac rhythm and even death; several of these patients were taking digoxin or β-blockers.^88–91 One report noted transient asystole after the administration of edrophonium in a patient with suspected MG; the patient was critically ill and had been receiving intravenous labetalol.⁸⁵ Hence, caution is advised in administering edrophonium to patients receiving β-blocking agents, digoxin, or other drugs with atrioventricular-blocking properties.

Administration of edrophonium to a patient with MG being treated with cholinesterase inhibitors is controversial. Many investigators consider myasthenic crisis to be a contraindication to edrophonium administration, although in series of patients with myasthenic crisis, its use continues to be reported.81,84

A muscle that is clearly weak must be identified to monitor during Tensilon testing; ptosis is a commonly monitored sign. If a specific muscle cannot be isolated for objective testing, administration of edrophonium should be deferred and other approaches to diagnosis pursued.

Equipment

The following material is needed for testing an adult. Intravenous access should be secured with a saline lock. Ten milligrams of edrophonium chloride should be drawn up in a tuberculin syringe. Edrophonium chloride is supplied in 1- and 10-mL vials at a concentration of 10 mg/mL. A second syringe of normal saline should be available to administer as placebo, although some clinicians have recommended nicotine, calcium chloride, or atropine for this purpose.⁷⁹ Atropine and other cardiovascular drugs and resuscitative equipment should be readily available. Cardiac monitoring is generally recommended. Photographic recording equipment is desirable to objectively document any improvement in motor function.

Procedure

Identify a muscle that is clearly weak. A clinically evident extraocular muscle weakness or the presence of ptosis allows direct observation of a single weak muscle becoming stronger in response to the drug. Simple grip dynamometry does not aid in evaluation; a repetitive measure of grip strength (ergogram) is necessary. Ideally, one person is available to administer the edrophonium or placebo and a second person is free to observe the effect of medication on the patient. It is best if both the observer and the patient do not know which syringe contains edrophonium and which contains saline, thus creating a double-blind testing situation.

Again, ptosis is an easy sign to test and is generally used if present (Fig. 61-9). The principles involved in assessing the effect of edrophonium on ptosis may be extended to testing other muscles. Ask the patient to look upward for several moments to fatigue the levator muscles. Note the degree of ptosis and document it by measurements or photographs. After a moment’s rest, ask the patient to look straight ahead. Inject 0.2 mL of the test substance in one syringe (2 mg of edrophonium or saline). If no response is seen within 1 minute, inject further increments of 2 mg up to a maximum of 10 mg. Note any increase in strength as reflected by an increase in size of the palpebral fissure. Repeat the procedure with the other test substance. Any improvement should occur within 30 seconds and disappear in 5 minutes.

Figure 61-9 Tensilon test. A, Bilateral asymmetric ptosis and defective upgaze. B, Improvement of ptosis and left upgaze following the intravenous injection of Tensilon. (From Kanski JJ. Clinical Diagnosis in Ophthalmology. St. Louis: Mosby; 2006.)

Complications

A small percentage of individuals are hypersensitive to even the initial small dose of edrophonium and exhibit the cholinergic side effects of salivation, lacrimation, and miosis. These effects are transient. Atropine, 0.5 mg, may be given intravenously if necessary to counteract these symptoms. A smaller number of patients may experience symptomatic bradycardia that responds to atropine. As described earlier, rare cardiac arrhythmias and death have been reported, usually in patients taking digoxin or β-blockers.

Interpretation

The key to the procedure is its interpretation. If a clearly paretic muscle has been identified, objective signs of improvement in the strength of that muscle within a moment of administration of edrophonium and fading of that improvement over the next 5 minutes are the criteria for a positive test result. Up to 90% of patients with MG have a positive test result under ideal circumstances.78,79 False-negative results do occur consistently, however.

For evaluating the effect of edrophonium on ptosis, a positive test consists of the patient having increased ability to elevate the eyelids after the administration of 5 to 10 mg of edrophonium. The ptosis returns within 5 minutes. Subjective increases in general strength or relief of fatigue do not constitute a positive test. Fasciculations, or brief twitches of muscles, are not usually observed in a patient with MG who has received edrophonium, in contrast to normal subjects. The Tensilon test may be repeated in 30 minutes if desired.

Normal subjects have no change in muscle strength. They may transiently experience the side effects of salivation, lacrimation, and diaphoresis. Perioral, periocular, or lingual fasciculations are almost always noted in normal patients after edrophonium administration.

Reproducible and unequivocal reversal of weakness in a specific muscle is extremely specific for MG.92,93 False-positive test results have been reported in patients with Eaton-Lambert syndrome and rarely in patients with intracranial lesions.^94–96 Other rare reports of positive test results involve patients with amyotrophic lateral sclerosis. A “perverse” reaction in which a paretic extraocular muscle, weak from other causes, becomes even weaker with edrophonium administration has been noted rarely.⁹⁷

Ice Pack Test

Background

It has been observed clinically that myasthenic patients have exacerbations of weakness with environmental heat and improvement in strength with cold temperatures. A simple bedside test uses these observations to evaluate ptosis.71,75,76 Ice placed in a surgical glove or wrapped in a towel is placed lightly over the eyelid of the patient. Cooling of the eyelid below 29°C is accomplished within 2 minutes. Ptosis has been noted to improve in 80% or more of patients tested and may be more sensitive than the edrophonium test in detecting ocular MG. Although the reported number of patients evaluated by this method continues to be small, the test is included here because of its potential application in the ED, its lack of side effects, and its noninvasive nature.