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F wave, A wave, H reflex, and blink reflex
Handbook of Clinical Neurology, Vol. 160 (3rd series) Clinical Neurophysiology: Basis and Technical Aspects K.H. Levin and P. Chauvel, Editors https://doi.org/10.1016/B978-0-444-64032-1.00015-1 Copyright © 2019 Elsevier B.V. All rights reserved
Chapter 15
F wave, A wave, H reflex, and blink reflex NIVEDITA JERATH* AND JUN KIMURA Department of Neurology, University of Iowa, Iowa City, IA, United States
Abstract Late responses include F waves, A waves, H reflex, and the blink reflex. These responses help enhance routine nerve conduction studies. Despite the use of F waves in multiple clinical applications, their studies can technically challenge even the most experienced electromyographers. They vary in latency, amplitude, and configuration, whereas A waves show no change in latency or morphology. Electrical stimulation of the supraorbital branch of the trigeminal nerve on one side results in a reflexive activation of the facial nucleus causing contraction of the orbicularis oculi muscle, short latency R1 ipsilaterally, and long latency R2 bilaterally. F waves can help determine the presence of a polyneuropathy. A waves can reflect axonal damage. H reflexes provide nerve conduction measurements along the entire length of the nerve, demonstrating abnormalities in neuropathies and radiculopathies. Abnormalities in the blink reflex can suggest the presence of an acoustic neuroma or a demyelinating polyneuropathy, which can affect the cranial nerves. This reflex, which also needs appropriate technical expertise, helps to assess cranial nerves V and VII along with their connections in the pons and medulla. The blink reflex, the electrical version of the corneal reflex, represents a polysynaptic reflex.
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX Introduction Routine nerve conductions can be enhanced with late responses such as F waves, A waves, H reflex, and the blink reflex. This chapter describes techniques to elicit these responses as well as their usage to delineate physiological and pathological processes.
F WAVE Introduction The F wave, a compound muscle action potential (CMAP) from a single or a small number of motor units, results from antidromic activation of the anterior horn cells. Its measurement helps determine motor nerve
conduction along the entire length of a peripheral axon, including the most proximal segment. First explored in patients with Charcot–Marie–Tooth disease (Kimura, 1974) and motor neuron disease (Argyriou et al., 2006), it has now become a routine component of nerve conduction studies (NCSs), primarily for assessment of a neuropathy (Young and Shahani, 1978). F waves have inherent variability in their latency and configuration, because each stimulus activates variable motor units thus making it technically more demanding than a CMAP elicited by orthodromic motor impulse or M response. Despite this technical challenge, F-wave studies contribute substantially in clinical assessments. Its latencies allow for evaluation of polyneuropathies, and its persistence provides a measure of motor neuron excitability, which controls the probability of backfiring of individual axons (Rivner, 2008). This section reviews F waves and their clinical application.
*Correspondence to: Nivedita Jerath, M.D., M.S., Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, United States. Tel: +1-706-691-9066, E-mail: [email protected]
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Physiology of the F wave
stimulus; thus the F wave appears much lower in amplitude than an M response. Repeater F waves identical in latency, size, and shape probably indicate the presence of hyperexcitable motor axons (Chroni et al., 2016).
A supramaximal stimulus to a nerve results in a late muscle response that follows the direct motor potential, or M response. The F-wave response must travel away from the recording electrodes toward the spinal cord before it returns toward distal muscles. It could theoretically result from a reflex (Hagbarth, 1960; Liberson et al., 1966) or from recurrent discharge of antidromically activated motor neurons (Mayer and Feldman, 1967) or from both (Kimura, 2013). Most investigators now believe it originates from recurrent discharge or backfiring of motor neurons because of its presence in deafferented limbs (McLeod and Wray, 1966) and after transverse myelotomy (Kimura, 2013).
F waves appear after stimulation of any motor nerves, but we prefer stimulating the tibial nerve and recording from the foot muscles. Recording electrodes placed in the standard locations for a motor NCS suffice for studying this late response. The F wave shows the highest persistence for the tibial nerve and the lowest for the fibular nerve, as expected from the number of intrinsic foot muscles available for recurrent discharges.
F-wave latency and amplitude
Stimulation
A supramaximal stimulus applied at any point of a nerve results in an F wave. Its latency consists of the time required for the action potential to travel antidromically from stimulation to the spinal cord and the time required traveling back orthodromically from the spinal cord to the muscle (Fig. 15.1). The point of stimulation, if moved proximally across a limb, causes F-wave latency to decrease, because the distance it travels shortens, and eventually the F wave and M wave can merge. Thus F waves are elicited by distal stimulation to maintain clear separation from the M wave. With more proximal stimulation, the M response latency increases but that of the F wave decreases by the same amount, so the sum of both remains the same regardless of the site of stimulation (Fig. 15.2). F waves comprise only a small number of motor units activated antidromically despite the use of a supramaximal
Stimulation applied to the median, ulnar, tibial, or fibular nerve at the wrist or ankle elicits an F wave with a latency much longer than the M wave. The cathode placed distal to the anode with the two poles separated by 2–3 cm can induce effective supramaximal antidromic activation (Daube and Rubin, 2009). After a maximal M response, distal stimulation for a routine motor NCS also elicits F waves recorded with higher amplification and slower sweep speed. We use gains of 200 or 500 mV/cm and a sweep of 5 or 10 ms/cm, depending on the nerve length and stimulus location. A high amplification and slow sweep allow for the M response to appear in the initial part of the tracing. Muscle contraction can make F waves more difficult to recognize, necessitating immobilization of the limb and relaxation maneuvers, which may help to elicit them. A series of stimuli applied consecutively should
Recording
Fig. 15.1. F waves and M waves recorded from the ulnar and peroneal nerves after eight consecutive stimulations (Kimura, 2013).
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Fig. 15.2. F waves from the left median nerve and left tibial nerve. Normal M response (horizontal brackets) and F wave (small arrows) recorded from the thenar muscles and abductor hallucis muscles after supramaximal stimulation of the median nerve and tibial nerves. More proximal stimulus increases the latency of the M response and decreases that of the F wave (Kimura, 2013).
induce a sufficient number of F waves for reliable measurement of minimal, mean, and maximal latencies despite inherent variability.
latencies obtained in normal subjects in the United States. Normative data has also been obtained for those from China (Pan et al., 2013).
Measurement
Distal vs proximal stimulation
F-wave latency, measured from the stimulus artifact to the beginning of the evoke potential, varies slightly by a few milliseconds from one stimulus to the next (Fig. 15.1). Normal values of each F wave relate to arm and leg measurements corrected for distance (Fig. 15.3) (Kimura, 2013; Nobrega et al., 2004). We use a heightlatency nomogram, normative data of F-wave latencies based on patient height, which reflects limb length (Nobrega et al., 2004). Table 15.1 summarizes F-wave
The F wave elicited by distal stimulation at the wrist or ankle serves as a measure of motor conduction time of the entire nerve length, which may show an increased latency from a lesion anywhere along the course of the nerve. Comparing F-wave and M-wave latencies when stimulating at the elbow and knee could differentiate between distal and proximal slowing. We measure minimal F-wave latency, mean F-wave latency, and maximal F-wave latency.
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N. JERATH AND J. KIMURA 32
Ulnar nerve
59 57 Minimum latency 55 53 51 49 47 45 43 41 39 37 35 150 155 160 165 170 175 180 185 190 195
Tibial nerve
Minimum latency 30
Latency
Latency
28 26 24 22 20 150 155 160 165 170 175 180 185 190 195
A
A
Height
34 Mean latency
30
Latency
Latency
32
28 26 24 22 150 155 160 165 170 175 180 185 190 195
B
150 155 160 165 170 175 180 185 190 195
38 Maximum latency 36
Latency
34 Latency
Mean latency
B
Height
32 30 28 26 24 150 155 160 165 170 175 180 185 190 195
C
Height
64 62 60 58 56 54 52 50 48 46 44 42 40 38 36
C
Height
Height
68 66 Maximum latency 64 62 60 58 56 54 52 50 48 46 44 42 40 150 155 160 165 170 175 180 185 190 195 Height
Fig. 15.3. Height-latency nomograms of ulnar and tibial F-wave minimal, mean, and maximum latencies (Nobrega et al., 2004; Kimura, 2013).
Table 15.1 Normal values of F-wave minimal latencies, F-wave conduction velocity, and F ratio mean and standard deviation (Kimura, 2013)
Number of nerves tested 122 Median nerves from 61 subjects 130 Ulnar nerves from 56 subjects 120 Peroneal nerves from 60 subjects 118 Tibial nerves from 59 subjects
Site of stimulation
F-wave minimal latency to recording site (ms)
Conduction velocity to and from spinal cord (m/s)a
F ratios between distal and proximal segments
Wrist Elbow Axilla Wrist Elbow Axilla Ankle Above knee Ankle Knee
26.2 2.2 22.8 1.9 20.4 1.9 27.6 2.2 23.1 1.7 20.3 1.6 48.4 4.0 39.9 3.2 47.7 5.0 39.6 4.4
65.3 4.7 67.8 5.8
0.098 0.08 (0.82–1.14)
65.3 4.8 65.7 5.3 49.8 3.6 55.1 4.6 52.6 4.3 53.7 4.8
1.05 0.09 (0.87–1.23)
1.05 0.09 (0.87–1.23) 1.11 0.11 (0.89–1.33)
Conduction velocity ¼ 2D/(F M 1), where D indicates the distance from the stimulus point to C7 or T12 spinous process.
a
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX
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Another method compares the actual F-wave latencies with an estimated F-wave latency, F estimate, based on the distance and conduction velocity in the distal segment using the following formula: Fest ¼ ½ð2 distanceÞ=conduction velocity + distal latency
Clinical applications of the F wave F waves, which travel a long distance over the entire segments of nerve, provide very sensitive measures of diffuse nerve disease. Sensory or motor NCSs do not allow for evaluation of the long proximal segments of a nerve (Khoshbin and Hallett, 1981). In fact, F-wave latencies clearly exceed the normal range in patients with a conduction abnormality as the best predictor of a polyneuropathy (Jerath et al., 2015). In addition, calculation of F-wave velocities and F ratios allows for comparison of conduction in the proximal vs distal nerve segments (Fig. 15.4). Clinical applications of F-wave minimal latencies include detection of abnormalities in patients with hereditary neuropathies, demyelinating neuropathies, diabetic neuropathies (Pan et al., 2014), uremic neuropathies, and alcoholic neuropathies, as well as other neuropathies (Fig. 15.5) (Jerath et al., 2015). F waves also provide an important prognostic factor in the Guillain-Barre syndrome in children (Lee et al., 2016). In juvenile spinal muscular atrophy, unlike in ALS and healthy subjects, the dynamic F waves during neck flexion showed a significantly greater incidence of repeater F waves of the ulnar and median nerves on the symptomatic side (Zheng et al., 2016). In a study analyzing F-wave amplitudes, giant F waves occurred significantly more often in those with spinobulbar muscular atrophy than in those with ALS or normal controls (Fang et al., 2016). Additionally, F waves can be used in some instances for stroke prognosis; reappearance of F waves after a conus medullaris infarct may serve as a good prognostic sign for ambulation (Alanazy, 2016). Sustained muscle relaxation diminishes amplitude and persistence of F waves, which motor imagery can counter in healthy subjects and hemiparetic stroke survivors; this as well as other studies suggest that motor imagery can help restore motor neuron excitability (Taniguchi et al., 2008; Hara et al., 2010; Fujisawa et al., 2011; Naseri et al., 2015).
A WAVE Introduction The A wave, a late potential seen when assessing the F responses, usually signifies an acute or chronic axonal damage. In the presence of a collateral sprouting, a submaximal stimulus excites one axon branch but not the
Fig. 15.4. The F-wave and M response latency difference reflects the motor impulse relay to and from the spinal cord and proximal segment. With an estimated minimal delay of 1.0 ms at the motor neuron pool, the proximal latency from the stimulus site to the cord equals (F M 1)/2, where F and M are latencies of the F wave and M response. The F-wave conduction velocity, FWCV ¼ (D 2)/(F M 1), where D is the distance from the stimulus site to the cord, and (F M 1)/2 is the time required to cover the length D. Dividing the conduction time in the proximal segment to the cord by that of the remaining distal segment to the muscle, the F ratio¼ (F M 1)/2M, where (F M 1)/2 and M are proximal and distal latencies (Kimura, 2013).
other. The antidromic impulse turns around at the branching point and then propagates distally along a second branch, resulting in a constant late response called the A wave. This type of A wave, also called an intermediate latency response, usually but not always appears between the M response and the F wave (Fig. 15.6) (Fullerton and Gilliatt, 1965). Mechanisms of the A wave include not only the collateral sprouting described previously, but also ephaptic or ectopic discharges from a hyperexcitable lesion in the proximal nerve segment (Magistris and Roth, 1992; Bischoff et al., 1996).
Recording Distal stimulation evokes an A wave, whereas proximal stimulation above the origin of a collateral nerve axon or the site of ephaptic transmission or ectopic discharge produces only an M response. Similar to the F wave, A-wave latencies decrease when stimulation occurs proximally, suggesting antidromic passage of the initial impulse. As opposed to F waves, which vary in latency, amplitude, and configuration but occur as a group within a range of latencies, A waves show no change in latency or morphology. They result from a proximal site where
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Frequency of abnormality (%)
Sural NCS
Tibial F-wave minimal latency
***
*** 95%
97%
***
*
97%
** 90%
63%
* 100% 89%
62%
56%
100%
94%
55%
58%
31%
All
Diabetes
Alcohol
Vitamin B-12 deficiency
CIDP/AIDP
HIV
Demyelinating CMT
* P < 0.05 for F-wave minimal latencies vs equivalent NCS ** P< 0.01 for F-wave minimal latencies vs equivalent NCS *** P< 0.001 for F-wave minimal latencies vs equivalent NCS
Fig. 15.5. Frequency of abnormality comparing the sural NCS to tibial F waves in different types of polyneuropathy.
Fig. 15.6. A waves seen with stimulation of the left peroneal nerve (black arrow).
the axonal branches originate from a hyperexcitable portion of a single motor unit, either by ephaptic or ectopic mechanisms. Supramaximal stimulus normally eliminates the collateral A wave unless a structural abnormality prevents
the current from reaching the branches, but not ephaptic or ectopic Awaves (Fig. 15.7). Ephaptic Awaves involve a cross-talk from a neighboring axon, and ectopic A waves result from a hyperexcitable motor axon after transmission of an impulse (Fig. 15.7) (Kimura, 2013).
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX 3
2
1
231
extinction with increased stimulus intensity include possible collision of the antidromic activity and the reflex impulse in the alpha motor neuron, axon hillock refractoriness after the antidromic impulse, and Renshaw inhibition of the motor neuron axon collaterals via internuncial cells and neighboring alpha motor neurons (Eccles, 1967; Jabre and Stalberg, 1989; Kimura, 2013).
Recording procedure of the H reflex off the soleus muscle
Collateral innervation
Ectopic discharge
Ephaptic activation
Fig. 15.7. Ectopic and ephaptic A waves. Pathophysiological mechanisms for three types of A waves: (1) ephaptic activation of a hyperexcitable nerve segment from a neighboring axon, (2) a propagating impulse triggering an ectopic discharge, and (3) a turnaround at a branching point of collateral innervation.
Clinical applications of the A wave A waves occur in patients with peripheral nerve disorders during both acute and chronic stages and also in some, usually elderly, healthy individuals. Diseases commonly associated with the A wave include entrapment syndromes, ulnar neuropathies, brachial plexus lesions, diabetic neuropathy, hereditary neuropathies, motor neuron disease, acute or chronic inflammatory demyelinating polyneuropathy, or even cervical radiculopathies (Sawhney and Kayan, 1970). They commonly arise as a result of ephaptic spread from one nerve fiber to another in an inflamed or demyelinated nerve during the acute phase of the Guillain-Barre syndrome (Preston and Shapiro, 2013).
H REFLEX Introduction The H reflex is an electrically elicited spinal monosynaptic reflex, named after Paul Hoffman, who first described it (Burke, 2016). Although it bypasses the muscle spindles, it is identical to the stretch reflex elicited by a mechanical tap of the tendon (Kimura, 2013). The H reflex results in one impulse as opposed to the mechanical tap, which can result in multiple impulses (Burke, 2016). Electrical stimulation elicits an H reflex in the median and tibial nerves in healthy adults. The H reflex diminishes with increased stimulus intensity, unlike the F wave (Fig. 15.8). Potential reasons for H-reflex
The H reflex is recorded with the patient lying down supine or prone. The active electrode (G1) is placed 2 cm distal to the insertion of the gastrocnemius on the Achilles tendon and the reference electrode (G2) is 3 cm further distally with a ground electrode located between the stimulating and recording electrodes (Kimura, 2013). A second pair of electrodes is placed on the tibialis anterior muscle 3 cm apart along the midline, monitoring the antagonistic muscles (Kimura, 2013). The H reflex will vary in amplitude and waveform, depending on the placement of the recording electrodes. It will appear as a triphasic potential with initial positivity when placed over the gastrocnemius and a diphasic potential with initial negativity when placed over the soleus (Kimura, 2013). The H reflex can be technically difficult to obtain, which can limit its diagnostic value.
Clinical applications The H reflex provides a measure of nerve conduction along the entire length of the tibial/S1 pathway, providing information along proximal nerve segments, including the plexus and roots (Burke, 2016). Clinical conditions with a depressed ankle reflex, such as polyneuropathy, sciatic neuropathy, or S1 radiculopathy, will show a diminished or absent H reflex. Diabetic polyneuropathy is known to increase the H-reflex latency. Table 15.2 summarizes normal values in healthy adults. In evaluating radiculopathy, a unilateral absent H reflex or a side-to-side latency difference greater than 2.0 ms supports a diagnosis of an S1 radiculopathy (Kimura, 2013).
BLINK REFLEX Introduction In addition to visual and brainstem evoked potentials, the blink reflex helps assess cranial nerves V and VII along with their connections in the pons and medulla. The blink reflex, the electrical version of the corneal reflex, represents a polysynaptic reflex. Electrical stimulation of the supraorbital branch of the trigeminal nerve on one side results in a reflexive activation of the facial nucleus, causing contraction of the orbicularis oculi muscle bilaterally.
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Fig. 15.8. (A) Representation of soleus H reflex elicited by electrical stimulation of the S1 root at the S1 foramen and of the tibial nerve at the popliteal fossa. (B) The H reflex and M response elicited by magnetic stimulation (upper trace) and electrical stimulation (lower trace) of the S1 nerve root at the S1 foramen. The intensity is depicted on the right of the traces. Zhu Y, Starr A, Haldeman S et al. (1998). Soleus H-reflex to S1 nerve root stimulation. Electroencephalogr Clin Neurophysiol 109: 10–14.
Table 15.2 a
H reflex normal values (Kimura, 2013)
Amplitude (mV)b
Difference between right and left (mV)
Latency to recording Site (ms)b
Difference between right and left (ms)
2.4 1.4
1.2 1.2
29.5 2.4
0.6 0.4
Mean standard deviation. Amplitude of the evoked response measured from baseline to negative peak; latency measured to the onset of the evoked response.
a
b
The blink reflex consists of two responses: R1, a synchronized response occurring ipsilateral to the stimulus with a disynaptic pathway between the main sensory nucleus of the trigeminal nerve in the mid-pons and the ipsilateral facial nucleus in the lower pontine tegmentum; and R2, a bilateral response with a longer latency mediated by multisynaptic pathways between the nucleus of the spinal tract of the trigeminal nerve in
the ipsilateral pons and medulla with interneurons forming connections to the ipsilateral and contralateral facial nuclei. The afferent impulse transmitted from the trigeminal nerve specifically propagates through the ophthalmic division with the nerve cell body in the gasserian ganglion. The efferent impulse involves the facial nerve axons innervating the orbicularis oculi muscles. Of the two, R1, a reproducible response, serves as a reliable measure of nerve conduction on reflexive pathways. In contrast, R2, a polyphasic response, varies considerably from one stimulation to the next and tends to habituate with repeated shocks. Nonetheless, R2 analysis helps localize lesions to the trigeminal nerve, facial nerve, or brainstem (Kimura and Lyon, 1972; Ongerboer De Visser and Goor, 1976). Involvement of the trigeminal nerve causes an afferent pattern of abnormality with delay or reduced amplitude of the R2 bilaterally after stimulation on the affected side. In diseases of the facial nerve, the pattern indicates an efferent abnormality with an R2 abnormality only on the affected side of the face, regardless of the side of stimulation.
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX
DIRECT VS REFLEX RESPONSES Facial nerve Nerve excitability, tested by applying shocks to the facial nerve, depends on observing facial muscle contraction as well as recording muscle action potentials. Visualizing the muscle contraction during this stimulation helps exclude a volume conducted potential from the masseter muscle, which could suggest a favorable prognosis in error despite the total degeneration of facial nerve axon (Kimura, 2013). A complete proximal site lesion of the nerve results in loss of excitability within 5–10 days of onset; thus a normal distal response at the end of the first week suggests a good prognosis (Gilliatt and Taylor, 1959; Kimura, 2013).
Stimulation procedure Recording electrodes consist of E1 placed on the orbicularis oculi, orbicularis oris, quadratus labii, or nasalis, and E2 on the same muscle on the opposite side. Normal values for facial nerve amplitude range from 3.0 to 8.0 mV with side-to-side differences not exceeding 2.0 mV (Kimura, 2013). Facial nerve latencies range from 3.4 0.8 to 4.0 0.5 ms. Table 15.3 summarizes the normal onset latency measured to the negative or positive deflection of the evoked potential from the baseline in 78 subjects (Waylonis and Johnson, 1964; Kimura, 2013).
Trigeminal nerve Trigeminal nerve stimulation results in a reflexive contraction of the orbicularis oculi. In contrast to a direct response used to assess the distal nerve segment, the blink reflex can evaluate both afferent and efferent pathways, including the proximal facial nerve segment. Of the two components, the more Table 15.3 Facial nerve latency in 78 subjects divided into different age groups (Waylonis and Johnson, 1964; Kimura, 2013) Age
Mean (ms)
Range (ms)
0–1 month 1–12 months 1–2 years 2–3 years 3–4 years 4–5 years 5–7 years 7–16 years
10.1 7.0 5.1 3.9 3.7 4.1 3.9 4.0
6.1–12.0 5.0–10.0 3.5–6.3 3.8–4.5 3.4–4.0 3.5–5.0 3.2–5.0 3.0–5.0
233
reliable R1 latency consists of the conduction time along the trigeminal nerve and facial nerves as well as pontine relay. In contrast, R2 has an inherently variable latency, making it less reliable for diagnostic purposes as it reflects the excitability of interneurons and delay of synaptic transmission in addition to the axonal conduction time.
Stimulation procedure for blink reflex The patient lies supine with the eyes open or gently closed for stimulation, with the cathode placed over the supraorbital foramen and anode placed 2 cm rostrally (Kimura et al., 1969). Applying shocks in this position results in R1 and R2, with a pair of recording electrodes, E1, E2, placed 2 cm apart on the lower part of the orbicularis oculi muscle on each side, with a ground electrode under the chin or on the arm. The R2 response correlates with the corneal reflex tested in neurological examination, showing similar latency and duration. The R1 response has no known clinical counterpart. Use of a two-channel device allows simultaneous recording from both sides with the sweep speed set at 5 or 10 ms per division and gain at 100–200 mV per division to record small amplitude R1 and R2 responses. The filter settings range from 10 Hz to 10 kHz, similar to motor NCSs. Unilateral stimulation of the supraorbital nerve with a small bipolar prong or bar electrode elicits ipsilateral R1 and bilateral R2 responses. The recording electrodes, E1 and E2, lie only a few centimeters away from the cathode. Thus, the short latency R1 could overlap with the stimulus artifact, interfering with accurate measurements. Rotating the anode around the cathode often helps to reduce the surface spread of the stimulus current to accomplish optimal recording. Each side should have four to six stimuli with the probe placed on the superior orbital fissure palpable over the medial supraorbital ridge in the eyebrow. An electrical pulse of 0.1 ms duration and current intensity up to 10 mA usually suffice as a supramaximal stimulation, resulting in the shortest latency and high-amplitude reflex potentials. Additional procedures include stimulation of the infraorbital and mental nerve with the cathode placed over the foramen on one side and recording from the orbicularis oculi on both sides (Kimura, 2013). Facial synkinesis assessment requires two pairs of recording electrodes on the same side of the face, one over the orbicularis oculi and the other over the orbicularis oris or platysma muscle (Kimura et al., 1975). Shocks of 0.1 ms in duration ranging in intensity from 50 to 100 V or 5 to 10 mA elicit a stable R1 response after
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multiple trials. In 5%–10% of individuals, a mild contraction of the orbicularis oculi may help evoke a stable response, which otherwise escapes detection. A higher shock intensity may result in more patient discomfort without reliable results. Applying paired stimuli with intervals of 3–5 ms usually gives rise to a good response in a sedated or comatose patient showing reduced excitability. R1 latency measured to the initial deflection of the evoked potential corresponds to the minimal conduction time for the reflex pathway. Several trials will ensure recording the shortest latency response. The latency ratios of R1 to the direct response (R/D ratio) provide a comparison of the conduction through the distal segment of the facial nerve with that of the entire reflex arc, which includes the trigeminal nerve and the proximal segment of the facial nerve (Fig. 15.9). Bilateral R3 responses can occur in some healthy subjects. With slowly increasing stimulation intensity, R2 responses may appear before R1. In these cases, a paired stimulus with an interstimulus interval of 5 ms may help elicit a stable R1 response. The stimulating electrode placed too close to the midline may elicit a contralateral R1 response with spread of stimulating current to the opposite trigeminal nerve. Table 15.6 summarizes normal values and ipsilateral/contralateral differences in milliseconds.
Lt.
Normal values in adults and infants Tables 15.4 and 15.5 summarize latencies of the direct and reflex responses and R/D ratio in normal subjects and in patients with a bilateral or unilateral neurological disease (Kimura, 1975, 2013). Although neonates have a shorter reflex arc for the blink reflex, they have a significantly greater latency than adults, reflecting the maturational process. Supraorbital nerve stimulation elicited R2 bilaterally in all adults but in only two-thirds of neonates ipsilateral to the stimulus (Clay and Ramseyer, 1977; Kimura et al., 1977; Blank et al., 1983).
Rt.
1 3
V 2
Constant current unit
Stimulus isolation unit
Amplifier
Oscilloscope
Stimulator
VII
VII
1. R1
ude
The R1 latency in children reaches adult values by the age of 2 years. The R2 response, similar to the adult pattern at 5–6 years of age, varies substantially in children less than 6 years of age and is often absent in children less than 2 years. With maxillary and mandibular lesions, the supraorbital nerve stimulation reveals no abnormality; in this situation, the infraorbital branch can be stimulated to assess the function of the maxillary division. Stimulation of the infraorbital nerve can elicit R2 responses normally, but the R1 response is absent. Mental nerve stimulation can elicit R2 responses, but the R1 response is not seen.
Camera
2. Ipsilateral R2
Average amplitude
Rt. Latency
Duration Latency
Average amplitude
Lt. Stimulus artifact
3. Contralateral R2
Fig. 15.9. Top: Presumed pathway of R1 through the pons (1), and ipsilateral and contralateral R2 through the pons and lateral medulla (2 and 3). Bottom: A routine blink reflex after ride sided stimulation with an ipsilateral R1 response and subsequent bilateral R2 responses (Kimura, 2013).
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Table 15.4 Blink reflex results with supraorbital nerve stimulation in normal subjects and in patients with bilateral neurological disease (mean SD) (Kimura, 2013)
Category Normal Guillain-Barre syndrome Chronic inflammatory polyneuropathy Fisher syndrome Hereditary motor sensory neuropathy type 1 Hereditary motor sensory neuropathy type II Diabetic polyneuropathy Multiple sclerosis
Number of patients
Direct response right and left R1 right and left combined combined Direct response R1 (ms) Abs Delay Nl Abs Delay Nl (ms)
83 (Glabellar tap 21)a 90
0
0
12
63
4
13
166
0
105 20 11
7
0 160 78
82
13
8
14 4
0 9
0 88
8 27
0 0
1 105
0
34
1
0
62
10.5 0.8 3.6 0.5 30.5 3.4 30.5 4.4 (12.5 1.4)a
4.2 2.1 15.1 5.9
3.9 1.3 37.4 8.9 37.7 8.4
5.8 2.6 16.4 6.4
3.1 0.5 39.5 9.4 42.0 10.3 3.9 0.4 31.8 1.3 31.4 1.9
6.7 2.7 17.0 3.7
2.8 0.9 39.5 5.7 39.3 6.4
2.9 0.4 10.1 0.6
3.6 0.6 30.1 3.8 30.1 3.7
3.4 0.6 11.4 1.2
3.4 0.5 33.7 4.6 34.8 5.3
79 2.9 0.5 12.3 2.7
4.3 0.9 35.8 8.4 37.7 8.0
33
17
86
Ipsilateral Contralateral R2 (ms) R2 (ms)
7 2.7 0.2 10.7 0.8 19
62 0
2.9 0.4
R/D ratio
2
20
150
1
17 154
0
0
124
1
44
a
R1 elicited bilaterally by a midline glabellar tap in another group of 21 healthy subjects. Abs, absent response; Nl, normal.
Table 15.5 Blink reflex results with supraorbital nerve stimulation in normal subjects in patients with unilateral neurological disease (mean SD) (Kimura, 2013) Category and side of stimulation
Number of patients
Trigeminal neuralgia Affected side 89 Normal side 89 Compressive lesion of the trigeminal nerve Affected side 17 Normal side 17 Bell’s palsy Affected side 100 Normal side 100 Acoustic neuroma Affected side 26 Normal side 26 Wallenberg syndrome Affected side 23 Normal side 23
Direct response (ms)
R1 (ms)
R/D ratio
Ipsilateral R2 (ms)
Contralateral R2 (ms)
2.9 0.4 2.9 0.5
10.6 1.0 10.5 0.9
3.7 0.6 3.7 0.6
30.4 4.4 30.5 4.2
31.6 4.5 31.1 4.7
3.1 0.5 3.2 0.6
11.9 1.8 10.3 1.1
3.9 1.0 3.4 0.6
36.0 5.5 33.7 3.5
37.2 5.7 34.8 4.1
2.9 0.6 2.8 0.4
12.8 1.6 10.2 1.0
4.4 0.9 3.7 0.6
33.9 4.9 30.5 4.3
30.5 4.9 34.0 5.4
3.2 0.7 2.9 0.4
14.0 2.7 10.9 0.9
4.6 1.7 3.8 0.5
38.2 8.2 33.1 3.5
36.6 8.2 35.3 4.5
3.2 0.6 3.2 0.4
10.9 0.7 10.7 0.5
3.6 0.6 3.4 0.4
40.7 4.6 34.0 5.7
38.4 7.1 35.1 5.8
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N. JERATH AND J. KIMURA
The upper limits of normal, defined as the mean latency plus 3 standard deviations, include 4.1 ms for a direct response, 13.0 ms for an electrically elicited R1, and 16.7 ms for mechanically evoked R1. The latency difference between the two sides should not exceed 0.6 ms for direct response, 1.2 ms for electrically elicited R1, and 1.6 ms for mechanically evoked R1 (Kimura, 2013). The R/D latency ratio should not fall outside the range of 2.6–4.6 (Kimura, 2013). With stimulation of the supraorbital nerve, the R2 latency should not exceed 40ms on the side of the stimulus and 41ms on the contralateral side (Kimura, 2013). Also, the ipsilateral and contralateral R2 simultaneously evoked by stimulation on one side should not differ more than 4.5 ms in latency. A latency difference between R2 evoked Table 15.6 Normal values of a blink reflex and side-to-side difference in milliseconds Side-to-side difference (ms)
Normal values (ms) Ipsilateral R1 <13 Ipsilateral R2 < 41 Contralateral R2 < 44
R1 <1.2 R2 < 8
by either side of stimulation can show a slightly greater value but should remain less than 7 ms (Table 15.6) (Kimura, 2013).
Additional nerves tested with the blink reflex Stimulation of the infraorbital nerve can evoke R1 and R2 in some subjects. Both R1 and R2 have similar latencies regardless of nerve tested. Stimulation of the mental nerve elicited R1 rarely and R2 inconsistently, showing considerably prolonged latency. With infraorbital nerve stimulation, the upper limit is 41 ms on the side of the stimulus and 42 ms on the contralateral side (Kimura, 2013). Studies of the mental nerve provide less consistent results, but R2 responses rarely exceed 50 ms in latency (Kimura, 2013). Stimulation of the lingual nerve can elicit R2 in the orbicularis oculi bilaterally as a possible test for lingual neuropathy (Montagna, 1996).
Applications Table 15.7 and Figs. 15.10 and 15.11 illustrate examples of blink reflex abnormalities. Increased R1 latencies usually involve an abnormal reflex arc, whereas a reduced R1 or R2 amplitude may result either from lesions directly affecting the reflex pathway or indirect lesions
Table 15.7 Patterns of R1 and R2 abnormalities in specific disease conditions (Kimura, 2013) Disorders
Direct response
R1
R2
Trigeminal neuralgia
Normal
Normal (95%)
Compressive lesion of the trigeminal nerve
Normal
Abnormal on the affected side (59%)
Bell’s palsy
Normal unless distal segment degenerated
Abnormal on the affected side (99%)
Normal Abnormal on both sides when affected side stimulated (afferent type) Abnormal on the affected side regardless of the side of stimulus (efferent type)
Acoustic neuroma Guillain-Barre syndrome Hereditary motor sensory neuropathy type I Diabetic polyneuropathy
Normal unless distal segment degenerated Abnormal (42%)
Abnormal on the affected side (85%)
Afferent and/or efferent type
Abnormal (54%)
Afferent and/or efferent type
Abnormal (78%)
Abnormal (85%)
Afferent and/or efferent type
Abnormal (13%)
Abnormal (10%) Abnormal with pontine lesion, variable incidence determined by patient’s selection Normal or borderline Abnormal with lesions of the trigeminal nerve or pons Abnormal with pontine lesion; reduced excitability in acute supratentorial lesion
Afferent and/or efferent type
Multiple sclerosis
Normal
Wallenberg syndrome
Normal
Facial hypesthesia
Normal
Comatose state, akinetic mutism, locked-in syndrome
Normal
Afferent and/or efferent type Afferent type Afferent type Absent on both sides regardless of side of stimulus
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX
●
●
●
●
●
Fig. 15.10. Five basic types of blink reflex abnormalities (Kimura, 2013). From top to bottom, 1: Trigeminal nerve abnormality (afferent pathway). 2: Facial nerve abnormality (efferent pathway). 3: Pathway between the main sensory nucleus or pontine interneurons relaying to the ipsilateral facial nucleus. 4: Pathway between the spinal tract and nucleus or medullary interneuronal pathways to the facial nuclei on both sides. 5: Pathway involving uncrossed medullary interneurons to the ipsilateral facial nucleus. 6: Pathway from crossed medullary interneurons to the contralateral facial nucleus.
influencing interneuron or motor neuron excitability. The following list describes typical applications. ●
●
Unilateral trigeminal nerve lesions. Stimulating the affected side will reveal a delay or absence in all potentials. Stimulating the unaffected side will result in normal potentials, including the ipsilateral R1, R2, and contralateral R2. Unilateral facial nerve lesions. Stimulating the affected side results in a delay or absence of the ipsilateral R1 and R2, but a normal contralateral R2. Stimulating the unaffected side results in a normal ipsilateral R1 and R2, but a delayed or absent contralateral R2. In this pattern, all potentials
●
●
●
237
on the affected side are abnormal regardless of stimulation site. Synkinesis of facial muscles. R1 and R2 components of the blink reflex recorded in facial muscles other than the orbicularis oculi indicate aberrant reinnervation. The blink reflex will show time-locked discharges involving two independent muscles showing synkinesis. In contrast, volitional associated movements show no time relationship to the reflexive discharges. Hemifacial spasm. Patients with idiopathic hemifacial spasms can also exhibit synkinetic movements, which, however, vary in latency and waveform from one stimulus to the next, probably reflecting an ephaptic transmission (Auger, 1979; Kameyama et al., 2016). Acoustic neuroma. A tumor in this location can affect the trigeminal nerve, facial nerve, and at times the brainstem. An abnormal blink reflex can often identify the involved structure, showing an absent or delayed R1, R2, or both. Demyelinating polyneuropathy. As expected, demyelination may abolish either R1 or R2 or markedly delay them as a result of slowing of either motor or sensory pathways or both. Multiple sclerosis. In patients with brainstem lesions, both R1 and R2 show various abnormalities, worse with a longer history of clinical symptoms. A delayed R1 usually indicates (Khoshbin and Hallett, 1981) the effect of pontine demyelination, often involving the intraaxial portion of the facial nerve. Wallenberg syndrome. This abnormality in the lateral medulla can typically result in no R2 on either side with stimulation on the affected side (Fitzek et al., 1999). Other patterns of changes include lowamplitude R2 on the side of stimulation, delayed R2 ipsilateral on the side of the lesion (Vila et al., 1997), and, if present, unpredictable patterns of abnormalities of R2 (Meincke and Ferbert, 1993). Migraine headaches. In migraines, the attacks may prolong R1 and R2 latencies on both ipsilateral and contralateral sides, with a longer latency found on the symptomatic side during an attack (Avramidis et al., 2017). A longer R1 and R2 latency found on the symptomatic headache side during the attack could potentially support the theory of increased sensitization of the trigeminal nucleus (on the symptomatic side) of migraines (Unal et al., 2016; Avramidis et al., 2017). Tetanus. A reported case showed absent bilateral blink reflex in a severe case of tetanus (Neumann et al., 2017).
238
N. JERATH AND J. KIMURA Left Normal
1 2
Right 1 2
GBS 1 Case 2 1
1 2
1 Case 2 2
1 2
1 Case 2 3
1 2
1 Case 2 4
1 2
CMT 1 Case 2 5
1 2
A
1 Case 2 6
1
Case 1 2 7
1
Case 1 2 8
1 2
Stimulation
2
2
0.5 mV 5 ms
Fig. 15.11. Clinical example of a blink reflex. Bilateral delay of R1 in four patients with Guillain-Barre syndrome and four patients with Charcot–Marie–Tooth disease type 1A. The top tracings are from a healthy subject and serve as controls; shaded areas indicate normal range.
REFERENCES Alanazy MH (2016). Conus medullaris stroke. Does F wave predict return of ambulation? Neurosciences (Riyadh) 21: 260–263. Argyriou AA, Polychronopoulos P, Talelli P et al. (2006). F wave study in amyotrophic lateral sclerosis: assessment of balance between upper and lower motor neuron involvement. Clin Neurophysiol 117: 1260–1265. Auger RG (1979). Hemifacial spasm: clinical and electrophysiologic observations. Neurology 29: 1261–1272. Avramidis T, Bougea A, Hadjigeorgiou G et al. (2017). Blink reflex habituation in migraine and chronic tension-type headache. Neurol Sci 38: 993–998. Bischoff C, Stalberg E, Falck B et al. (1996). Significance of A-waves recorded in routine motor nerve conduction studies. Electroencephalogr Clin Neurophysiol 101: 528–533. Blank A, Ferber I, Shapira Y et al. (1983). Electrically elicited blink reflex in children. Arch Phys Med Rehabil 64: 558–559. Burke D (2016). Clinical uses of H reflexes of upper and lower limb muscles. Clin Neurophysiol Pract 1: 9–17.
Chroni E, Veltsista D, Papapaulou C et al. (2016). Generation of repeater F waves in healthy subjects. J Clin Neurophysiol 34: 236–242. Clay SA, Ramseyer JC (1977). The orbicularis oculi reflex: pathologic studies in childhood. Neurology 27: 892–895. Daube JR, Rubin DI (2009). Clinical neurophysiology, Oxford University Press, Oxford; New York. Eccles JC (1967). The inhibitory control of spinal reflex action. Electroencephalogr Clin Neurophysiol Suppl 25: 20–34. Fang J, Cui L, Liu M et al. (2016). Differences in F-wave characteristics between spinobulbar muscular atrophy and amyotrophic lateral sclerosis. Front Aging Neurosci 8: 50. Fitzek S, Fitzek C, Marx J et al. (1999). Blink reflex R2 changes and localisation of lesions in the lower brainstem (Wallenberg’s syndrome): an electrophysiological and MRI study. J Neurol Neurosurg Psychiatry 67: 630–636. Fujisawa R, Kimura J, Taniguchi S et al. (2011). Effect of volitional relaxation and motor imagery on F wave and MEP: do these tasks affect excitability of the spinal or cortical motor neurons? Clin Neurophysiol 122: 1405–1410.
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX Fullerton PM, Gilliatt RW (1965). Axon reflexes in human motor nerve fibres. J Neurol Neurosurg Psychiatry 28: 1–11. Gilliatt RW, Taylor JC (1959). Electrical changes following section of the facial nerve. Proc R Soc Med 52: 1080–1083. Hagbarth KE (1960). Spinal withdrawal reflexes in the human lower limbs. J Neurol Neurosurg Psychiatry 23: 222–227. Hara M, Kimura J, Walker DD et al. (2010). Effect of motor imagery and voluntary muscle contraction on the F wave. Muscle Nerve 42: 208–212. Jabre JF, Stalberg EV (1989). Single-fiber EMG study of the flexor carpi radialis H reflex. Muscle Nerve 12: 523–527. Jerath NU, Aul E, Reddy CG et al. (2015). Prolongation of F-wave minimal latency: a sensitive predictor of polyneuropathy. Int J Neurosci 126: 520–525. Kameyama S, Masuda H, Shirozu H et al. (2016). Ephaptic transmission is the origin of the abnormal muscle response seen in hemifacial spasm. Clin Neurophysiol 127: 2240–2245. Khoshbin S, Hallett M (1981). Multimodality evoked potentials and blink reflex in multiple sclerosis. Neurology 31: 138–144. Kimura J (1974). F-wave velocity in the central segment of the median and ulnar nerves. A study in normal subjects and in patients with Charcot-Marie-Tooth disease. Neurology 24: 539–546. Kimura J (1975). Electrically elicited blink reflex in diagnosis of multiple sclerosis. Review of 260 patients over a sevenyear period. Brain 98: 413–426. Kimura J (2013). Electrodiagnosis in diseases of nerve and muscle: principles and practice, OUP, USA. Kimura J, Lyon LW (1972). Orbicularis oculi reflex in the Wallenberg syndrome: alteration of the late reflex by lesions of the spinal tract and nucleus of the trigeminal nerve. J Neurol Neurosurg Psychiatry 35: 228–233. Kimura J, Powers JM, Van Allen MW (1969). Reflex response of orbicularis oculi muscle to supraorbital nerve stimulation. Study in normal subjects and in peripheral facial paresis. Arch Neurol 21: 193–199. Kimura J, Rodnitzky RL, Okawara SH (1975). Electrophysiologic analysis of aberrant regeneration after facial nerve paralysis. Neurology 25: 989–993. Kimura J, Bodensteiner J, Yamada T (1977). Electrically elicited blink reflex in normal neonates. Arch Neurol 34: 246–249. Lee EB, Lee YY, Lee JM et al. (2016). Clinical importance of F-waves as a prognostic factor in Guillain-Barre syndrome in children. Korean J Pediatr 59: 271–275. Liberson WT, Gratzer M, Zalis A et al. (1966). Comparison of conduction velocities of motor and sensory fibers determined by different methods. Arch Phys Med Rehabil 47: 17–23.
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Magistris MR, Roth G (1992). Motor axon reflex and indirect double discharge: ephaptic transmission? A reappraisal. Electroencephalogr Clin Neurophysiol 85: 124–130. Mayer RF, Feldman RG (1967). Observations on the nature of the F wave in man. Neurology 17: 147–156. McLeod JG, Wray SH (1966). An experimental study of the F wave in the baboon. J Neurol Neurosurg Psychiatry 29: 196–200. Meincke U, Ferbert A (1993). Blink reflex in patients with an ischaemic lesion of the brain-stem verified by MRI. J Neurol 241: 37–44. Montagna P (1996). Lingual neuropathy after a dental procedure. Muscle Nerve 19: 111–112. Naseri M, Petramfar P, Ashraf A (2015). Effect of motor imagery on the F-wave parameters in hemiparetic stroke survivors. Ann Rehabil Med 39: 401–408. Neumann B, Schulte-Mattler W, Fuchs K et al. (2017). Misleading bilateral blink reflex loss in a severe tetanus case. Clin Case Rep 5: 85–88. Nobrega JA, Pinheiro DS, Manzano GM et al. (2004). Various aspects of F-wave values in a healthy population. Clin Neurophysiol 115: 2336–2342. Ongerboer De Visser BW, Goor C (1976). Jaw reflexes and masseter electromyograms in mesencephalic and pontine lesions: an electrodiagnostic study. J Neurol Neurosurg Psychiatry 39: 90–92. Pan H, Lin J, Chen N et al. (2013). Normative data of F-wave measures in China. Clin Neurophysiol 124: 183–189. Pan H, Jian F, Lin J et al. (2014). F-wave latencies in patients with diabetes mellitus. Muscle Nerve 49: 804–808. Preston DC, Shapiro BE (2013). Electromyography and neuromuscular disorders: clinical-electrophysiologic correlations, Elsevier Saunders, London; New York. Rivner MH (2008). The use of F-waves as a probe for motor cortex excitability. Clin Neurophysiol 119: 1215–1216. Sawhney BB, Kayan A (1970). A study of axon reflexes in some neurogenic disorders. Electromyography 10: 297–305. Taniguchi S, Kimura J, Yamada T et al. (2008). Effect of motion imagery to counter rest-induced suppression of F-wave as a measure of anterior horn cell excitability. Clin Neurophysiol 119: 1346–1352. Unal Z, Domac FM, Boylu E et al. (2016). Blink reflex in migraine headache. North Clin Istanb 3: 1–8. Vila N, Valls-Sole J, Obach V et al. (1997). Blink reflex in patients with Wallenberg’s syndrome. J Neurol 244: 30–34. Waylonis GW, Johnson EW (1964). Facial nerve conduction delay. Arch Phys Med Rehabil 45: 539–547. Young RR, Shahani BT (1978). Clinical value and limitations of f-wave determination. Muscle Nerve 1: 248–250. Zheng C, Zhu Y, Yang S et al. (2016). A study of dynamic F-waves in juvenile spinal muscular atrophy of the distal upper extremity (Hirayama disease). J Neurol Sci 367: 298–304.
Chapter 15
F wave, A wave, H reflex, and blink reflex NIVEDITA JERATH* AND JUN KIMURA Department of Neurology, University of Iowa, Iowa City, IA, United States
Abstract Late responses include F waves, A waves, H reflex, and the blink reflex. These responses help enhance routine nerve conduction studies. Despite the use of F waves in multiple clinical applications, their studies can technically challenge even the most experienced electromyographers. They vary in latency, amplitude, and configuration, whereas A waves show no change in latency or morphology. Electrical stimulation of the supraorbital branch of the trigeminal nerve on one side results in a reflexive activation of the facial nucleus causing contraction of the orbicularis oculi muscle, short latency R1 ipsilaterally, and long latency R2 bilaterally. F waves can help determine the presence of a polyneuropathy. A waves can reflect axonal damage. H reflexes provide nerve conduction measurements along the entire length of the nerve, demonstrating abnormalities in neuropathies and radiculopathies. Abnormalities in the blink reflex can suggest the presence of an acoustic neuroma or a demyelinating polyneuropathy, which can affect the cranial nerves. This reflex, which also needs appropriate technical expertise, helps to assess cranial nerves V and VII along with their connections in the pons and medulla. The blink reflex, the electrical version of the corneal reflex, represents a polysynaptic reflex.
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX Introduction Routine nerve conductions can be enhanced with late responses such as F waves, A waves, H reflex, and the blink reflex. This chapter describes techniques to elicit these responses as well as their usage to delineate physiological and pathological processes.
F WAVE Introduction The F wave, a compound muscle action potential (CMAP) from a single or a small number of motor units, results from antidromic activation of the anterior horn cells. Its measurement helps determine motor nerve
conduction along the entire length of a peripheral axon, including the most proximal segment. First explored in patients with Charcot–Marie–Tooth disease (Kimura, 1974) and motor neuron disease (Argyriou et al., 2006), it has now become a routine component of nerve conduction studies (NCSs), primarily for assessment of a neuropathy (Young and Shahani, 1978). F waves have inherent variability in their latency and configuration, because each stimulus activates variable motor units thus making it technically more demanding than a CMAP elicited by orthodromic motor impulse or M response. Despite this technical challenge, F-wave studies contribute substantially in clinical assessments. Its latencies allow for evaluation of polyneuropathies, and its persistence provides a measure of motor neuron excitability, which controls the probability of backfiring of individual axons (Rivner, 2008). This section reviews F waves and their clinical application.
*Correspondence to: Nivedita Jerath, M.D., M.S., Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, United States. Tel: +1-706-691-9066, E-mail: [email protected]
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Physiology of the F wave
stimulus; thus the F wave appears much lower in amplitude than an M response. Repeater F waves identical in latency, size, and shape probably indicate the presence of hyperexcitable motor axons (Chroni et al., 2016).
A supramaximal stimulus to a nerve results in a late muscle response that follows the direct motor potential, or M response. The F-wave response must travel away from the recording electrodes toward the spinal cord before it returns toward distal muscles. It could theoretically result from a reflex (Hagbarth, 1960; Liberson et al., 1966) or from recurrent discharge of antidromically activated motor neurons (Mayer and Feldman, 1967) or from both (Kimura, 2013). Most investigators now believe it originates from recurrent discharge or backfiring of motor neurons because of its presence in deafferented limbs (McLeod and Wray, 1966) and after transverse myelotomy (Kimura, 2013).
F waves appear after stimulation of any motor nerves, but we prefer stimulating the tibial nerve and recording from the foot muscles. Recording electrodes placed in the standard locations for a motor NCS suffice for studying this late response. The F wave shows the highest persistence for the tibial nerve and the lowest for the fibular nerve, as expected from the number of intrinsic foot muscles available for recurrent discharges.
F-wave latency and amplitude
Stimulation
A supramaximal stimulus applied at any point of a nerve results in an F wave. Its latency consists of the time required for the action potential to travel antidromically from stimulation to the spinal cord and the time required traveling back orthodromically from the spinal cord to the muscle (Fig. 15.1). The point of stimulation, if moved proximally across a limb, causes F-wave latency to decrease, because the distance it travels shortens, and eventually the F wave and M wave can merge. Thus F waves are elicited by distal stimulation to maintain clear separation from the M wave. With more proximal stimulation, the M response latency increases but that of the F wave decreases by the same amount, so the sum of both remains the same regardless of the site of stimulation (Fig. 15.2). F waves comprise only a small number of motor units activated antidromically despite the use of a supramaximal
Stimulation applied to the median, ulnar, tibial, or fibular nerve at the wrist or ankle elicits an F wave with a latency much longer than the M wave. The cathode placed distal to the anode with the two poles separated by 2–3 cm can induce effective supramaximal antidromic activation (Daube and Rubin, 2009). After a maximal M response, distal stimulation for a routine motor NCS also elicits F waves recorded with higher amplification and slower sweep speed. We use gains of 200 or 500 mV/cm and a sweep of 5 or 10 ms/cm, depending on the nerve length and stimulus location. A high amplification and slow sweep allow for the M response to appear in the initial part of the tracing. Muscle contraction can make F waves more difficult to recognize, necessitating immobilization of the limb and relaxation maneuvers, which may help to elicit them. A series of stimuli applied consecutively should
Recording
Fig. 15.1. F waves and M waves recorded from the ulnar and peroneal nerves after eight consecutive stimulations (Kimura, 2013).
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX
227
Fig. 15.2. F waves from the left median nerve and left tibial nerve. Normal M response (horizontal brackets) and F wave (small arrows) recorded from the thenar muscles and abductor hallucis muscles after supramaximal stimulation of the median nerve and tibial nerves. More proximal stimulus increases the latency of the M response and decreases that of the F wave (Kimura, 2013).
induce a sufficient number of F waves for reliable measurement of minimal, mean, and maximal latencies despite inherent variability.
latencies obtained in normal subjects in the United States. Normative data has also been obtained for those from China (Pan et al., 2013).
Measurement
Distal vs proximal stimulation
F-wave latency, measured from the stimulus artifact to the beginning of the evoke potential, varies slightly by a few milliseconds from one stimulus to the next (Fig. 15.1). Normal values of each F wave relate to arm and leg measurements corrected for distance (Fig. 15.3) (Kimura, 2013; Nobrega et al., 2004). We use a heightlatency nomogram, normative data of F-wave latencies based on patient height, which reflects limb length (Nobrega et al., 2004). Table 15.1 summarizes F-wave
The F wave elicited by distal stimulation at the wrist or ankle serves as a measure of motor conduction time of the entire nerve length, which may show an increased latency from a lesion anywhere along the course of the nerve. Comparing F-wave and M-wave latencies when stimulating at the elbow and knee could differentiate between distal and proximal slowing. We measure minimal F-wave latency, mean F-wave latency, and maximal F-wave latency.
228
N. JERATH AND J. KIMURA 32
Ulnar nerve
59 57 Minimum latency 55 53 51 49 47 45 43 41 39 37 35 150 155 160 165 170 175 180 185 190 195
Tibial nerve
Minimum latency 30
Latency
Latency
28 26 24 22 20 150 155 160 165 170 175 180 185 190 195
A
A
Height
34 Mean latency
30
Latency
Latency
32
28 26 24 22 150 155 160 165 170 175 180 185 190 195
B
150 155 160 165 170 175 180 185 190 195
38 Maximum latency 36
Latency
34 Latency
Mean latency
B
Height
32 30 28 26 24 150 155 160 165 170 175 180 185 190 195
C
Height
64 62 60 58 56 54 52 50 48 46 44 42 40 38 36
C
Height
Height
68 66 Maximum latency 64 62 60 58 56 54 52 50 48 46 44 42 40 150 155 160 165 170 175 180 185 190 195 Height
Fig. 15.3. Height-latency nomograms of ulnar and tibial F-wave minimal, mean, and maximum latencies (Nobrega et al., 2004; Kimura, 2013).
Table 15.1 Normal values of F-wave minimal latencies, F-wave conduction velocity, and F ratio mean and standard deviation (Kimura, 2013)
Number of nerves tested 122 Median nerves from 61 subjects 130 Ulnar nerves from 56 subjects 120 Peroneal nerves from 60 subjects 118 Tibial nerves from 59 subjects
Site of stimulation
F-wave minimal latency to recording site (ms)
Conduction velocity to and from spinal cord (m/s)a
F ratios between distal and proximal segments
Wrist Elbow Axilla Wrist Elbow Axilla Ankle Above knee Ankle Knee
26.2 2.2 22.8 1.9 20.4 1.9 27.6 2.2 23.1 1.7 20.3 1.6 48.4 4.0 39.9 3.2 47.7 5.0 39.6 4.4
65.3 4.7 67.8 5.8
0.098 0.08 (0.82–1.14)
65.3 4.8 65.7 5.3 49.8 3.6 55.1 4.6 52.6 4.3 53.7 4.8
1.05 0.09 (0.87–1.23)
1.05 0.09 (0.87–1.23) 1.11 0.11 (0.89–1.33)
Conduction velocity ¼ 2D/(F M 1), where D indicates the distance from the stimulus point to C7 or T12 spinous process.
a
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX
229
Another method compares the actual F-wave latencies with an estimated F-wave latency, F estimate, based on the distance and conduction velocity in the distal segment using the following formula: Fest ¼ ½ð2 distanceÞ=conduction velocity + distal latency
Clinical applications of the F wave F waves, which travel a long distance over the entire segments of nerve, provide very sensitive measures of diffuse nerve disease. Sensory or motor NCSs do not allow for evaluation of the long proximal segments of a nerve (Khoshbin and Hallett, 1981). In fact, F-wave latencies clearly exceed the normal range in patients with a conduction abnormality as the best predictor of a polyneuropathy (Jerath et al., 2015). In addition, calculation of F-wave velocities and F ratios allows for comparison of conduction in the proximal vs distal nerve segments (Fig. 15.4). Clinical applications of F-wave minimal latencies include detection of abnormalities in patients with hereditary neuropathies, demyelinating neuropathies, diabetic neuropathies (Pan et al., 2014), uremic neuropathies, and alcoholic neuropathies, as well as other neuropathies (Fig. 15.5) (Jerath et al., 2015). F waves also provide an important prognostic factor in the Guillain-Barre syndrome in children (Lee et al., 2016). In juvenile spinal muscular atrophy, unlike in ALS and healthy subjects, the dynamic F waves during neck flexion showed a significantly greater incidence of repeater F waves of the ulnar and median nerves on the symptomatic side (Zheng et al., 2016). In a study analyzing F-wave amplitudes, giant F waves occurred significantly more often in those with spinobulbar muscular atrophy than in those with ALS or normal controls (Fang et al., 2016). Additionally, F waves can be used in some instances for stroke prognosis; reappearance of F waves after a conus medullaris infarct may serve as a good prognostic sign for ambulation (Alanazy, 2016). Sustained muscle relaxation diminishes amplitude and persistence of F waves, which motor imagery can counter in healthy subjects and hemiparetic stroke survivors; this as well as other studies suggest that motor imagery can help restore motor neuron excitability (Taniguchi et al., 2008; Hara et al., 2010; Fujisawa et al., 2011; Naseri et al., 2015).
A WAVE Introduction The A wave, a late potential seen when assessing the F responses, usually signifies an acute or chronic axonal damage. In the presence of a collateral sprouting, a submaximal stimulus excites one axon branch but not the
Fig. 15.4. The F-wave and M response latency difference reflects the motor impulse relay to and from the spinal cord and proximal segment. With an estimated minimal delay of 1.0 ms at the motor neuron pool, the proximal latency from the stimulus site to the cord equals (F M 1)/2, where F and M are latencies of the F wave and M response. The F-wave conduction velocity, FWCV ¼ (D 2)/(F M 1), where D is the distance from the stimulus site to the cord, and (F M 1)/2 is the time required to cover the length D. Dividing the conduction time in the proximal segment to the cord by that of the remaining distal segment to the muscle, the F ratio¼ (F M 1)/2M, where (F M 1)/2 and M are proximal and distal latencies (Kimura, 2013).
other. The antidromic impulse turns around at the branching point and then propagates distally along a second branch, resulting in a constant late response called the A wave. This type of A wave, also called an intermediate latency response, usually but not always appears between the M response and the F wave (Fig. 15.6) (Fullerton and Gilliatt, 1965). Mechanisms of the A wave include not only the collateral sprouting described previously, but also ephaptic or ectopic discharges from a hyperexcitable lesion in the proximal nerve segment (Magistris and Roth, 1992; Bischoff et al., 1996).
Recording Distal stimulation evokes an A wave, whereas proximal stimulation above the origin of a collateral nerve axon or the site of ephaptic transmission or ectopic discharge produces only an M response. Similar to the F wave, A-wave latencies decrease when stimulation occurs proximally, suggesting antidromic passage of the initial impulse. As opposed to F waves, which vary in latency, amplitude, and configuration but occur as a group within a range of latencies, A waves show no change in latency or morphology. They result from a proximal site where
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Frequency of abnormality (%)
Sural NCS
Tibial F-wave minimal latency
***
*** 95%
97%
***
*
97%
** 90%
63%
* 100% 89%
62%
56%
100%
94%
55%
58%
31%
All
Diabetes
Alcohol
Vitamin B-12 deficiency
CIDP/AIDP
HIV
Demyelinating CMT
* P < 0.05 for F-wave minimal latencies vs equivalent NCS ** P< 0.01 for F-wave minimal latencies vs equivalent NCS *** P< 0.001 for F-wave minimal latencies vs equivalent NCS
Fig. 15.5. Frequency of abnormality comparing the sural NCS to tibial F waves in different types of polyneuropathy.
Fig. 15.6. A waves seen with stimulation of the left peroneal nerve (black arrow).
the axonal branches originate from a hyperexcitable portion of a single motor unit, either by ephaptic or ectopic mechanisms. Supramaximal stimulus normally eliminates the collateral A wave unless a structural abnormality prevents
the current from reaching the branches, but not ephaptic or ectopic Awaves (Fig. 15.7). Ephaptic Awaves involve a cross-talk from a neighboring axon, and ectopic A waves result from a hyperexcitable motor axon after transmission of an impulse (Fig. 15.7) (Kimura, 2013).
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX 3
2
1
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extinction with increased stimulus intensity include possible collision of the antidromic activity and the reflex impulse in the alpha motor neuron, axon hillock refractoriness after the antidromic impulse, and Renshaw inhibition of the motor neuron axon collaterals via internuncial cells and neighboring alpha motor neurons (Eccles, 1967; Jabre and Stalberg, 1989; Kimura, 2013).
Recording procedure of the H reflex off the soleus muscle
Collateral innervation
Ectopic discharge
Ephaptic activation
Fig. 15.7. Ectopic and ephaptic A waves. Pathophysiological mechanisms for three types of A waves: (1) ephaptic activation of a hyperexcitable nerve segment from a neighboring axon, (2) a propagating impulse triggering an ectopic discharge, and (3) a turnaround at a branching point of collateral innervation.
Clinical applications of the A wave A waves occur in patients with peripheral nerve disorders during both acute and chronic stages and also in some, usually elderly, healthy individuals. Diseases commonly associated with the A wave include entrapment syndromes, ulnar neuropathies, brachial plexus lesions, diabetic neuropathy, hereditary neuropathies, motor neuron disease, acute or chronic inflammatory demyelinating polyneuropathy, or even cervical radiculopathies (Sawhney and Kayan, 1970). They commonly arise as a result of ephaptic spread from one nerve fiber to another in an inflamed or demyelinated nerve during the acute phase of the Guillain-Barre syndrome (Preston and Shapiro, 2013).
H REFLEX Introduction The H reflex is an electrically elicited spinal monosynaptic reflex, named after Paul Hoffman, who first described it (Burke, 2016). Although it bypasses the muscle spindles, it is identical to the stretch reflex elicited by a mechanical tap of the tendon (Kimura, 2013). The H reflex results in one impulse as opposed to the mechanical tap, which can result in multiple impulses (Burke, 2016). Electrical stimulation elicits an H reflex in the median and tibial nerves in healthy adults. The H reflex diminishes with increased stimulus intensity, unlike the F wave (Fig. 15.8). Potential reasons for H-reflex
The H reflex is recorded with the patient lying down supine or prone. The active electrode (G1) is placed 2 cm distal to the insertion of the gastrocnemius on the Achilles tendon and the reference electrode (G2) is 3 cm further distally with a ground electrode located between the stimulating and recording electrodes (Kimura, 2013). A second pair of electrodes is placed on the tibialis anterior muscle 3 cm apart along the midline, monitoring the antagonistic muscles (Kimura, 2013). The H reflex will vary in amplitude and waveform, depending on the placement of the recording electrodes. It will appear as a triphasic potential with initial positivity when placed over the gastrocnemius and a diphasic potential with initial negativity when placed over the soleus (Kimura, 2013). The H reflex can be technically difficult to obtain, which can limit its diagnostic value.
Clinical applications The H reflex provides a measure of nerve conduction along the entire length of the tibial/S1 pathway, providing information along proximal nerve segments, including the plexus and roots (Burke, 2016). Clinical conditions with a depressed ankle reflex, such as polyneuropathy, sciatic neuropathy, or S1 radiculopathy, will show a diminished or absent H reflex. Diabetic polyneuropathy is known to increase the H-reflex latency. Table 15.2 summarizes normal values in healthy adults. In evaluating radiculopathy, a unilateral absent H reflex or a side-to-side latency difference greater than 2.0 ms supports a diagnosis of an S1 radiculopathy (Kimura, 2013).
BLINK REFLEX Introduction In addition to visual and brainstem evoked potentials, the blink reflex helps assess cranial nerves V and VII along with their connections in the pons and medulla. The blink reflex, the electrical version of the corneal reflex, represents a polysynaptic reflex. Electrical stimulation of the supraorbital branch of the trigeminal nerve on one side results in a reflexive activation of the facial nucleus, causing contraction of the orbicularis oculi muscle bilaterally.
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Fig. 15.8. (A) Representation of soleus H reflex elicited by electrical stimulation of the S1 root at the S1 foramen and of the tibial nerve at the popliteal fossa. (B) The H reflex and M response elicited by magnetic stimulation (upper trace) and electrical stimulation (lower trace) of the S1 nerve root at the S1 foramen. The intensity is depicted on the right of the traces. Zhu Y, Starr A, Haldeman S et al. (1998). Soleus H-reflex to S1 nerve root stimulation. Electroencephalogr Clin Neurophysiol 109: 10–14.
Table 15.2 a
H reflex normal values (Kimura, 2013)
Amplitude (mV)b
Difference between right and left (mV)
Latency to recording Site (ms)b
Difference between right and left (ms)
2.4 1.4
1.2 1.2
29.5 2.4
0.6 0.4
Mean standard deviation. Amplitude of the evoked response measured from baseline to negative peak; latency measured to the onset of the evoked response.
a
b
The blink reflex consists of two responses: R1, a synchronized response occurring ipsilateral to the stimulus with a disynaptic pathway between the main sensory nucleus of the trigeminal nerve in the mid-pons and the ipsilateral facial nucleus in the lower pontine tegmentum; and R2, a bilateral response with a longer latency mediated by multisynaptic pathways between the nucleus of the spinal tract of the trigeminal nerve in
the ipsilateral pons and medulla with interneurons forming connections to the ipsilateral and contralateral facial nuclei. The afferent impulse transmitted from the trigeminal nerve specifically propagates through the ophthalmic division with the nerve cell body in the gasserian ganglion. The efferent impulse involves the facial nerve axons innervating the orbicularis oculi muscles. Of the two, R1, a reproducible response, serves as a reliable measure of nerve conduction on reflexive pathways. In contrast, R2, a polyphasic response, varies considerably from one stimulation to the next and tends to habituate with repeated shocks. Nonetheless, R2 analysis helps localize lesions to the trigeminal nerve, facial nerve, or brainstem (Kimura and Lyon, 1972; Ongerboer De Visser and Goor, 1976). Involvement of the trigeminal nerve causes an afferent pattern of abnormality with delay or reduced amplitude of the R2 bilaterally after stimulation on the affected side. In diseases of the facial nerve, the pattern indicates an efferent abnormality with an R2 abnormality only on the affected side of the face, regardless of the side of stimulation.
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX
DIRECT VS REFLEX RESPONSES Facial nerve Nerve excitability, tested by applying shocks to the facial nerve, depends on observing facial muscle contraction as well as recording muscle action potentials. Visualizing the muscle contraction during this stimulation helps exclude a volume conducted potential from the masseter muscle, which could suggest a favorable prognosis in error despite the total degeneration of facial nerve axon (Kimura, 2013). A complete proximal site lesion of the nerve results in loss of excitability within 5–10 days of onset; thus a normal distal response at the end of the first week suggests a good prognosis (Gilliatt and Taylor, 1959; Kimura, 2013).
Stimulation procedure Recording electrodes consist of E1 placed on the orbicularis oculi, orbicularis oris, quadratus labii, or nasalis, and E2 on the same muscle on the opposite side. Normal values for facial nerve amplitude range from 3.0 to 8.0 mV with side-to-side differences not exceeding 2.0 mV (Kimura, 2013). Facial nerve latencies range from 3.4 0.8 to 4.0 0.5 ms. Table 15.3 summarizes the normal onset latency measured to the negative or positive deflection of the evoked potential from the baseline in 78 subjects (Waylonis and Johnson, 1964; Kimura, 2013).
Trigeminal nerve Trigeminal nerve stimulation results in a reflexive contraction of the orbicularis oculi. In contrast to a direct response used to assess the distal nerve segment, the blink reflex can evaluate both afferent and efferent pathways, including the proximal facial nerve segment. Of the two components, the more Table 15.3 Facial nerve latency in 78 subjects divided into different age groups (Waylonis and Johnson, 1964; Kimura, 2013) Age
Mean (ms)
Range (ms)
0–1 month 1–12 months 1–2 years 2–3 years 3–4 years 4–5 years 5–7 years 7–16 years
10.1 7.0 5.1 3.9 3.7 4.1 3.9 4.0
6.1–12.0 5.0–10.0 3.5–6.3 3.8–4.5 3.4–4.0 3.5–5.0 3.2–5.0 3.0–5.0
233
reliable R1 latency consists of the conduction time along the trigeminal nerve and facial nerves as well as pontine relay. In contrast, R2 has an inherently variable latency, making it less reliable for diagnostic purposes as it reflects the excitability of interneurons and delay of synaptic transmission in addition to the axonal conduction time.
Stimulation procedure for blink reflex The patient lies supine with the eyes open or gently closed for stimulation, with the cathode placed over the supraorbital foramen and anode placed 2 cm rostrally (Kimura et al., 1969). Applying shocks in this position results in R1 and R2, with a pair of recording electrodes, E1, E2, placed 2 cm apart on the lower part of the orbicularis oculi muscle on each side, with a ground electrode under the chin or on the arm. The R2 response correlates with the corneal reflex tested in neurological examination, showing similar latency and duration. The R1 response has no known clinical counterpart. Use of a two-channel device allows simultaneous recording from both sides with the sweep speed set at 5 or 10 ms per division and gain at 100–200 mV per division to record small amplitude R1 and R2 responses. The filter settings range from 10 Hz to 10 kHz, similar to motor NCSs. Unilateral stimulation of the supraorbital nerve with a small bipolar prong or bar electrode elicits ipsilateral R1 and bilateral R2 responses. The recording electrodes, E1 and E2, lie only a few centimeters away from the cathode. Thus, the short latency R1 could overlap with the stimulus artifact, interfering with accurate measurements. Rotating the anode around the cathode often helps to reduce the surface spread of the stimulus current to accomplish optimal recording. Each side should have four to six stimuli with the probe placed on the superior orbital fissure palpable over the medial supraorbital ridge in the eyebrow. An electrical pulse of 0.1 ms duration and current intensity up to 10 mA usually suffice as a supramaximal stimulation, resulting in the shortest latency and high-amplitude reflex potentials. Additional procedures include stimulation of the infraorbital and mental nerve with the cathode placed over the foramen on one side and recording from the orbicularis oculi on both sides (Kimura, 2013). Facial synkinesis assessment requires two pairs of recording electrodes on the same side of the face, one over the orbicularis oculi and the other over the orbicularis oris or platysma muscle (Kimura et al., 1975). Shocks of 0.1 ms in duration ranging in intensity from 50 to 100 V or 5 to 10 mA elicit a stable R1 response after
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multiple trials. In 5%–10% of individuals, a mild contraction of the orbicularis oculi may help evoke a stable response, which otherwise escapes detection. A higher shock intensity may result in more patient discomfort without reliable results. Applying paired stimuli with intervals of 3–5 ms usually gives rise to a good response in a sedated or comatose patient showing reduced excitability. R1 latency measured to the initial deflection of the evoked potential corresponds to the minimal conduction time for the reflex pathway. Several trials will ensure recording the shortest latency response. The latency ratios of R1 to the direct response (R/D ratio) provide a comparison of the conduction through the distal segment of the facial nerve with that of the entire reflex arc, which includes the trigeminal nerve and the proximal segment of the facial nerve (Fig. 15.9). Bilateral R3 responses can occur in some healthy subjects. With slowly increasing stimulation intensity, R2 responses may appear before R1. In these cases, a paired stimulus with an interstimulus interval of 5 ms may help elicit a stable R1 response. The stimulating electrode placed too close to the midline may elicit a contralateral R1 response with spread of stimulating current to the opposite trigeminal nerve. Table 15.6 summarizes normal values and ipsilateral/contralateral differences in milliseconds.
Lt.
Normal values in adults and infants Tables 15.4 and 15.5 summarize latencies of the direct and reflex responses and R/D ratio in normal subjects and in patients with a bilateral or unilateral neurological disease (Kimura, 1975, 2013). Although neonates have a shorter reflex arc for the blink reflex, they have a significantly greater latency than adults, reflecting the maturational process. Supraorbital nerve stimulation elicited R2 bilaterally in all adults but in only two-thirds of neonates ipsilateral to the stimulus (Clay and Ramseyer, 1977; Kimura et al., 1977; Blank et al., 1983).
Rt.
1 3
V 2
Constant current unit
Stimulus isolation unit
Amplifier
Oscilloscope
Stimulator
VII
VII
1. R1
ude
The R1 latency in children reaches adult values by the age of 2 years. The R2 response, similar to the adult pattern at 5–6 years of age, varies substantially in children less than 6 years of age and is often absent in children less than 2 years. With maxillary and mandibular lesions, the supraorbital nerve stimulation reveals no abnormality; in this situation, the infraorbital branch can be stimulated to assess the function of the maxillary division. Stimulation of the infraorbital nerve can elicit R2 responses normally, but the R1 response is absent. Mental nerve stimulation can elicit R2 responses, but the R1 response is not seen.
Camera
2. Ipsilateral R2
Average amplitude
Rt. Latency
Duration Latency
Average amplitude
Lt. Stimulus artifact
3. Contralateral R2
Fig. 15.9. Top: Presumed pathway of R1 through the pons (1), and ipsilateral and contralateral R2 through the pons and lateral medulla (2 and 3). Bottom: A routine blink reflex after ride sided stimulation with an ipsilateral R1 response and subsequent bilateral R2 responses (Kimura, 2013).
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX
235
Table 15.4 Blink reflex results with supraorbital nerve stimulation in normal subjects and in patients with bilateral neurological disease (mean SD) (Kimura, 2013)
Category Normal Guillain-Barre syndrome Chronic inflammatory polyneuropathy Fisher syndrome Hereditary motor sensory neuropathy type 1 Hereditary motor sensory neuropathy type II Diabetic polyneuropathy Multiple sclerosis
Number of patients
Direct response right and left R1 right and left combined combined Direct response R1 (ms) Abs Delay Nl Abs Delay Nl (ms)
83 (Glabellar tap 21)a 90
0
0
12
63
4
13
166
0
105 20 11
7
0 160 78
82
13
8
14 4
0 9
0 88
8 27
0 0
1 105
0
34
1
0
62
10.5 0.8 3.6 0.5 30.5 3.4 30.5 4.4 (12.5 1.4)a
4.2 2.1 15.1 5.9
3.9 1.3 37.4 8.9 37.7 8.4
5.8 2.6 16.4 6.4
3.1 0.5 39.5 9.4 42.0 10.3 3.9 0.4 31.8 1.3 31.4 1.9
6.7 2.7 17.0 3.7
2.8 0.9 39.5 5.7 39.3 6.4
2.9 0.4 10.1 0.6
3.6 0.6 30.1 3.8 30.1 3.7
3.4 0.6 11.4 1.2
3.4 0.5 33.7 4.6 34.8 5.3
79 2.9 0.5 12.3 2.7
4.3 0.9 35.8 8.4 37.7 8.0
33
17
86
Ipsilateral Contralateral R2 (ms) R2 (ms)
7 2.7 0.2 10.7 0.8 19
62 0
2.9 0.4
R/D ratio
2
20
150
1
17 154
0
0
124
1
44
a
R1 elicited bilaterally by a midline glabellar tap in another group of 21 healthy subjects. Abs, absent response; Nl, normal.
Table 15.5 Blink reflex results with supraorbital nerve stimulation in normal subjects in patients with unilateral neurological disease (mean SD) (Kimura, 2013) Category and side of stimulation
Number of patients
Trigeminal neuralgia Affected side 89 Normal side 89 Compressive lesion of the trigeminal nerve Affected side 17 Normal side 17 Bell’s palsy Affected side 100 Normal side 100 Acoustic neuroma Affected side 26 Normal side 26 Wallenberg syndrome Affected side 23 Normal side 23
Direct response (ms)
R1 (ms)
R/D ratio
Ipsilateral R2 (ms)
Contralateral R2 (ms)
2.9 0.4 2.9 0.5
10.6 1.0 10.5 0.9
3.7 0.6 3.7 0.6
30.4 4.4 30.5 4.2
31.6 4.5 31.1 4.7
3.1 0.5 3.2 0.6
11.9 1.8 10.3 1.1
3.9 1.0 3.4 0.6
36.0 5.5 33.7 3.5
37.2 5.7 34.8 4.1
2.9 0.6 2.8 0.4
12.8 1.6 10.2 1.0
4.4 0.9 3.7 0.6
33.9 4.9 30.5 4.3
30.5 4.9 34.0 5.4
3.2 0.7 2.9 0.4
14.0 2.7 10.9 0.9
4.6 1.7 3.8 0.5
38.2 8.2 33.1 3.5
36.6 8.2 35.3 4.5
3.2 0.6 3.2 0.4
10.9 0.7 10.7 0.5
3.6 0.6 3.4 0.4
40.7 4.6 34.0 5.7
38.4 7.1 35.1 5.8
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The upper limits of normal, defined as the mean latency plus 3 standard deviations, include 4.1 ms for a direct response, 13.0 ms for an electrically elicited R1, and 16.7 ms for mechanically evoked R1. The latency difference between the two sides should not exceed 0.6 ms for direct response, 1.2 ms for electrically elicited R1, and 1.6 ms for mechanically evoked R1 (Kimura, 2013). The R/D latency ratio should not fall outside the range of 2.6–4.6 (Kimura, 2013). With stimulation of the supraorbital nerve, the R2 latency should not exceed 40ms on the side of the stimulus and 41ms on the contralateral side (Kimura, 2013). Also, the ipsilateral and contralateral R2 simultaneously evoked by stimulation on one side should not differ more than 4.5 ms in latency. A latency difference between R2 evoked Table 15.6 Normal values of a blink reflex and side-to-side difference in milliseconds Side-to-side difference (ms)
Normal values (ms) Ipsilateral R1 <13 Ipsilateral R2 < 41 Contralateral R2 < 44
R1 <1.2 R2 < 8
by either side of stimulation can show a slightly greater value but should remain less than 7 ms (Table 15.6) (Kimura, 2013).
Additional nerves tested with the blink reflex Stimulation of the infraorbital nerve can evoke R1 and R2 in some subjects. Both R1 and R2 have similar latencies regardless of nerve tested. Stimulation of the mental nerve elicited R1 rarely and R2 inconsistently, showing considerably prolonged latency. With infraorbital nerve stimulation, the upper limit is 41 ms on the side of the stimulus and 42 ms on the contralateral side (Kimura, 2013). Studies of the mental nerve provide less consistent results, but R2 responses rarely exceed 50 ms in latency (Kimura, 2013). Stimulation of the lingual nerve can elicit R2 in the orbicularis oculi bilaterally as a possible test for lingual neuropathy (Montagna, 1996).
Applications Table 15.7 and Figs. 15.10 and 15.11 illustrate examples of blink reflex abnormalities. Increased R1 latencies usually involve an abnormal reflex arc, whereas a reduced R1 or R2 amplitude may result either from lesions directly affecting the reflex pathway or indirect lesions
Table 15.7 Patterns of R1 and R2 abnormalities in specific disease conditions (Kimura, 2013) Disorders
Direct response
R1
R2
Trigeminal neuralgia
Normal
Normal (95%)
Compressive lesion of the trigeminal nerve
Normal
Abnormal on the affected side (59%)
Bell’s palsy
Normal unless distal segment degenerated
Abnormal on the affected side (99%)
Normal Abnormal on both sides when affected side stimulated (afferent type) Abnormal on the affected side regardless of the side of stimulus (efferent type)
Acoustic neuroma Guillain-Barre syndrome Hereditary motor sensory neuropathy type I Diabetic polyneuropathy
Normal unless distal segment degenerated Abnormal (42%)
Abnormal on the affected side (85%)
Afferent and/or efferent type
Abnormal (54%)
Afferent and/or efferent type
Abnormal (78%)
Abnormal (85%)
Afferent and/or efferent type
Abnormal (13%)
Abnormal (10%) Abnormal with pontine lesion, variable incidence determined by patient’s selection Normal or borderline Abnormal with lesions of the trigeminal nerve or pons Abnormal with pontine lesion; reduced excitability in acute supratentorial lesion
Afferent and/or efferent type
Multiple sclerosis
Normal
Wallenberg syndrome
Normal
Facial hypesthesia
Normal
Comatose state, akinetic mutism, locked-in syndrome
Normal
Afferent and/or efferent type Afferent type Afferent type Absent on both sides regardless of side of stimulus
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX
●
●
●
●
●
Fig. 15.10. Five basic types of blink reflex abnormalities (Kimura, 2013). From top to bottom, 1: Trigeminal nerve abnormality (afferent pathway). 2: Facial nerve abnormality (efferent pathway). 3: Pathway between the main sensory nucleus or pontine interneurons relaying to the ipsilateral facial nucleus. 4: Pathway between the spinal tract and nucleus or medullary interneuronal pathways to the facial nuclei on both sides. 5: Pathway involving uncrossed medullary interneurons to the ipsilateral facial nucleus. 6: Pathway from crossed medullary interneurons to the contralateral facial nucleus.
influencing interneuron or motor neuron excitability. The following list describes typical applications. ●
●
Unilateral trigeminal nerve lesions. Stimulating the affected side will reveal a delay or absence in all potentials. Stimulating the unaffected side will result in normal potentials, including the ipsilateral R1, R2, and contralateral R2. Unilateral facial nerve lesions. Stimulating the affected side results in a delay or absence of the ipsilateral R1 and R2, but a normal contralateral R2. Stimulating the unaffected side results in a normal ipsilateral R1 and R2, but a delayed or absent contralateral R2. In this pattern, all potentials
●
●
●
237
on the affected side are abnormal regardless of stimulation site. Synkinesis of facial muscles. R1 and R2 components of the blink reflex recorded in facial muscles other than the orbicularis oculi indicate aberrant reinnervation. The blink reflex will show time-locked discharges involving two independent muscles showing synkinesis. In contrast, volitional associated movements show no time relationship to the reflexive discharges. Hemifacial spasm. Patients with idiopathic hemifacial spasms can also exhibit synkinetic movements, which, however, vary in latency and waveform from one stimulus to the next, probably reflecting an ephaptic transmission (Auger, 1979; Kameyama et al., 2016). Acoustic neuroma. A tumor in this location can affect the trigeminal nerve, facial nerve, and at times the brainstem. An abnormal blink reflex can often identify the involved structure, showing an absent or delayed R1, R2, or both. Demyelinating polyneuropathy. As expected, demyelination may abolish either R1 or R2 or markedly delay them as a result of slowing of either motor or sensory pathways or both. Multiple sclerosis. In patients with brainstem lesions, both R1 and R2 show various abnormalities, worse with a longer history of clinical symptoms. A delayed R1 usually indicates (Khoshbin and Hallett, 1981) the effect of pontine demyelination, often involving the intraaxial portion of the facial nerve. Wallenberg syndrome. This abnormality in the lateral medulla can typically result in no R2 on either side with stimulation on the affected side (Fitzek et al., 1999). Other patterns of changes include lowamplitude R2 on the side of stimulation, delayed R2 ipsilateral on the side of the lesion (Vila et al., 1997), and, if present, unpredictable patterns of abnormalities of R2 (Meincke and Ferbert, 1993). Migraine headaches. In migraines, the attacks may prolong R1 and R2 latencies on both ipsilateral and contralateral sides, with a longer latency found on the symptomatic side during an attack (Avramidis et al., 2017). A longer R1 and R2 latency found on the symptomatic headache side during the attack could potentially support the theory of increased sensitization of the trigeminal nucleus (on the symptomatic side) of migraines (Unal et al., 2016; Avramidis et al., 2017). Tetanus. A reported case showed absent bilateral blink reflex in a severe case of tetanus (Neumann et al., 2017).
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N. JERATH AND J. KIMURA Left Normal
1 2
Right 1 2
GBS 1 Case 2 1
1 2
1 Case 2 2
1 2
1 Case 2 3
1 2
1 Case 2 4
1 2
CMT 1 Case 2 5
1 2
A
1 Case 2 6
1
Case 1 2 7
1
Case 1 2 8
1 2
Stimulation
2
2
0.5 mV 5 ms
Fig. 15.11. Clinical example of a blink reflex. Bilateral delay of R1 in four patients with Guillain-Barre syndrome and four patients with Charcot–Marie–Tooth disease type 1A. The top tracings are from a healthy subject and serve as controls; shaded areas indicate normal range.
REFERENCES Alanazy MH (2016). Conus medullaris stroke. Does F wave predict return of ambulation? Neurosciences (Riyadh) 21: 260–263. Argyriou AA, Polychronopoulos P, Talelli P et al. (2006). F wave study in amyotrophic lateral sclerosis: assessment of balance between upper and lower motor neuron involvement. Clin Neurophysiol 117: 1260–1265. Auger RG (1979). Hemifacial spasm: clinical and electrophysiologic observations. Neurology 29: 1261–1272. Avramidis T, Bougea A, Hadjigeorgiou G et al. (2017). Blink reflex habituation in migraine and chronic tension-type headache. Neurol Sci 38: 993–998. Bischoff C, Stalberg E, Falck B et al. (1996). Significance of A-waves recorded in routine motor nerve conduction studies. Electroencephalogr Clin Neurophysiol 101: 528–533. Blank A, Ferber I, Shapira Y et al. (1983). Electrically elicited blink reflex in children. Arch Phys Med Rehabil 64: 558–559. Burke D (2016). Clinical uses of H reflexes of upper and lower limb muscles. Clin Neurophysiol Pract 1: 9–17.
Chroni E, Veltsista D, Papapaulou C et al. (2016). Generation of repeater F waves in healthy subjects. J Clin Neurophysiol 34: 236–242. Clay SA, Ramseyer JC (1977). The orbicularis oculi reflex: pathologic studies in childhood. Neurology 27: 892–895. Daube JR, Rubin DI (2009). Clinical neurophysiology, Oxford University Press, Oxford; New York. Eccles JC (1967). The inhibitory control of spinal reflex action. Electroencephalogr Clin Neurophysiol Suppl 25: 20–34. Fang J, Cui L, Liu M et al. (2016). Differences in F-wave characteristics between spinobulbar muscular atrophy and amyotrophic lateral sclerosis. Front Aging Neurosci 8: 50. Fitzek S, Fitzek C, Marx J et al. (1999). Blink reflex R2 changes and localisation of lesions in the lower brainstem (Wallenberg’s syndrome): an electrophysiological and MRI study. J Neurol Neurosurg Psychiatry 67: 630–636. Fujisawa R, Kimura J, Taniguchi S et al. (2011). Effect of volitional relaxation and motor imagery on F wave and MEP: do these tasks affect excitability of the spinal or cortical motor neurons? Clin Neurophysiol 122: 1405–1410.
F WAVE, A WAVE, H REFLEX, AND BLINK REFLEX Fullerton PM, Gilliatt RW (1965). Axon reflexes in human motor nerve fibres. J Neurol Neurosurg Psychiatry 28: 1–11. Gilliatt RW, Taylor JC (1959). Electrical changes following section of the facial nerve. Proc R Soc Med 52: 1080–1083. Hagbarth KE (1960). Spinal withdrawal reflexes in the human lower limbs. J Neurol Neurosurg Psychiatry 23: 222–227. Hara M, Kimura J, Walker DD et al. (2010). Effect of motor imagery and voluntary muscle contraction on the F wave. Muscle Nerve 42: 208–212. Jabre JF, Stalberg EV (1989). Single-fiber EMG study of the flexor carpi radialis H reflex. Muscle Nerve 12: 523–527. Jerath NU, Aul E, Reddy CG et al. (2015). Prolongation of F-wave minimal latency: a sensitive predictor of polyneuropathy. Int J Neurosci 126: 520–525. Kameyama S, Masuda H, Shirozu H et al. (2016). Ephaptic transmission is the origin of the abnormal muscle response seen in hemifacial spasm. Clin Neurophysiol 127: 2240–2245. Khoshbin S, Hallett M (1981). Multimodality evoked potentials and blink reflex in multiple sclerosis. Neurology 31: 138–144. Kimura J (1974). F-wave velocity in the central segment of the median and ulnar nerves. A study in normal subjects and in patients with Charcot-Marie-Tooth disease. Neurology 24: 539–546. Kimura J (1975). Electrically elicited blink reflex in diagnosis of multiple sclerosis. Review of 260 patients over a sevenyear period. Brain 98: 413–426. Kimura J (2013). Electrodiagnosis in diseases of nerve and muscle: principles and practice, OUP, USA. Kimura J, Lyon LW (1972). Orbicularis oculi reflex in the Wallenberg syndrome: alteration of the late reflex by lesions of the spinal tract and nucleus of the trigeminal nerve. J Neurol Neurosurg Psychiatry 35: 228–233. Kimura J, Powers JM, Van Allen MW (1969). Reflex response of orbicularis oculi muscle to supraorbital nerve stimulation. Study in normal subjects and in peripheral facial paresis. Arch Neurol 21: 193–199. Kimura J, Rodnitzky RL, Okawara SH (1975). Electrophysiologic analysis of aberrant regeneration after facial nerve paralysis. Neurology 25: 989–993. Kimura J, Bodensteiner J, Yamada T (1977). Electrically elicited blink reflex in normal neonates. Arch Neurol 34: 246–249. Lee EB, Lee YY, Lee JM et al. (2016). Clinical importance of F-waves as a prognostic factor in Guillain-Barre syndrome in children. Korean J Pediatr 59: 271–275. Liberson WT, Gratzer M, Zalis A et al. (1966). Comparison of conduction velocities of motor and sensory fibers determined by different methods. Arch Phys Med Rehabil 47: 17–23.
239
Magistris MR, Roth G (1992). Motor axon reflex and indirect double discharge: ephaptic transmission? A reappraisal. Electroencephalogr Clin Neurophysiol 85: 124–130. Mayer RF, Feldman RG (1967). Observations on the nature of the F wave in man. Neurology 17: 147–156. McLeod JG, Wray SH (1966). An experimental study of the F wave in the baboon. J Neurol Neurosurg Psychiatry 29: 196–200. Meincke U, Ferbert A (1993). Blink reflex in patients with an ischaemic lesion of the brain-stem verified by MRI. J Neurol 241: 37–44. Montagna P (1996). Lingual neuropathy after a dental procedure. Muscle Nerve 19: 111–112. Naseri M, Petramfar P, Ashraf A (2015). Effect of motor imagery on the F-wave parameters in hemiparetic stroke survivors. Ann Rehabil Med 39: 401–408. Neumann B, Schulte-Mattler W, Fuchs K et al. (2017). Misleading bilateral blink reflex loss in a severe tetanus case. Clin Case Rep 5: 85–88. Nobrega JA, Pinheiro DS, Manzano GM et al. (2004). Various aspects of F-wave values in a healthy population. Clin Neurophysiol 115: 2336–2342. Ongerboer De Visser BW, Goor C (1976). Jaw reflexes and masseter electromyograms in mesencephalic and pontine lesions: an electrodiagnostic study. J Neurol Neurosurg Psychiatry 39: 90–92. Pan H, Lin J, Chen N et al. (2013). Normative data of F-wave measures in China. Clin Neurophysiol 124: 183–189. Pan H, Jian F, Lin J et al. (2014). F-wave latencies in patients with diabetes mellitus. Muscle Nerve 49: 804–808. Preston DC, Shapiro BE (2013). Electromyography and neuromuscular disorders: clinical-electrophysiologic correlations, Elsevier Saunders, London; New York. Rivner MH (2008). The use of F-waves as a probe for motor cortex excitability. Clin Neurophysiol 119: 1215–1216. Sawhney BB, Kayan A (1970). A study of axon reflexes in some neurogenic disorders. Electromyography 10: 297–305. Taniguchi S, Kimura J, Yamada T et al. (2008). Effect of motion imagery to counter rest-induced suppression of F-wave as a measure of anterior horn cell excitability. Clin Neurophysiol 119: 1346–1352. Unal Z, Domac FM, Boylu E et al. (2016). Blink reflex in migraine headache. North Clin Istanb 3: 1–8. Vila N, Valls-Sole J, Obach V et al. (1997). Blink reflex in patients with Wallenberg’s syndrome. J Neurol 244: 30–34. Waylonis GW, Johnson EW (1964). Facial nerve conduction delay. Arch Phys Med Rehabil 45: 539–547. Young RR, Shahani BT (1978). Clinical value and limitations of f-wave determination. Muscle Nerve 1: 248–250. Zheng C, Zhu Y, Yang S et al. (2016). A study of dynamic F-waves in juvenile spinal muscular atrophy of the distal upper extremity (Hirayama disease). J Neurol Sci 367: 298–304.