Brief Communications

Vagal nerve Article abstract—Vagal nerve stimulation is an approved adjunctive treat-

ment for medically intractable epilepsy. Although it is generally well toler-
stimulation: ated, some patients experience pain, coughing, or hoarseness during
Adjustments to reduce stimulation. Lowering the pulse width in these patients alleviates pain and
reduces voice alteration without loss of efficacy. This allows more optimal
painful side effects programming of stimulation intensities.
NEUROLOGY 2001;57:885–886

J. Liporace, MD; D. Hucko, RN, BSN; R. Morrow, MD; G. Barolat, MD; M. Nei, MD;
J. Schnur, BA; and M. Sperling, MD

Vagal nerve stimulation (VNS) was approved in 1997
by the US Food and Drug Administration for adjunc-
tive use in the treatment of patients with medically
refractory epilepsy. Currently, 9,600 patients have
had the device implanted in the United States (B.
Tarver [Corporate Studies, Cyberonics, Devices for
Epilepsy], personal communication, February 12,
2001). Although VNS is typically well tolerated,
some patients experience pain, coughing, or voice al-
teration during stimulation. For some, these effects
are distressing and may disrupt activities of daily
life. These side effects can also interfere with pro-
gramming optimal stimulation intensities for maxi-
mal seizure benefit. Currently, there are no
guidelines concerning program adjustments to re-
lieve these side effects. We sought to determine if
lowering the pulse width would alleviate the side
effects of VNS.
Methods. VNS devices were activated 2 weeks after im-
plantation and adjusted periodically at the Jefferson Com-
prehensive Epilepsy Center. During visits, the VNS was
interrogated and the output current intensity was in-
creased by 0.25 to 0.5 mA as tolerated toward a goal of 2.0
to 3.0 mA with the typical cycling rate of 30 seconds of
stimulation every 5.5 minutes. Rapid cycling (typically 7
seconds on, 21 seconds off) was programmed in some pa-
tients who failed to respond to slower cycling rates. Side
effects were assessed at each visit. If a patient had pain
(throat, jaw, neck, or tooth) or coughing, the pulse width
was reduced from the preprogrammed level of 500 to 250
or 130 microseconds to see if these symptoms could be
reduced.
From the Jefferson Comprehensive Epilepsy Center (Drs. Liporace, Mor-
row, Barolat, and Sperling, and D. Hucko and J. Schnur) and Departments
of Neurology (Drs. Liporace, Nei, and Sperling, and J. Schnur) and Neuro-
surgery (Dr. Barolat), Thomas Jefferson University Hospital; and Depart-
ment of Neuroscience, Sacred Heart Hospital (Dr. Morrow and D. Hucko),
Philadelphia, PA.
Presented at the 53rd annual meeting of the American Academy of Neurol-
ogy; Philadelphia, PA; May 9, 2001.
Received February 13, 2001. Accepted in final form April 15, 2001.
Address correspondence and reprint requests to Dr. J. Liporace, Jefferson
Comprehensive Epilepsy Center, 4150 Gibbon Bldg., Philadelphia, PA
19107; e-mail: Joyce.Liporace@mail.tju.edu
Seizure frequency was assessed by monthly seizure
counts. These were averaged over 3 months whenever pos-
sible. Three time periods were evaluated, including a base-
line before VNS implantation, after VNS programming
(pulse width 500 microseconds), and after pulse width ad-
justment (pulse width 130 to 250 microseconds).
Results. Forty-eight patients had the VNS device im-
planted between 1997 and 2001 (30 men, 18 women). Mean
age at surgery was 41.0 ⫾ 12.5 years (range 20.4 to 77.6
years). Duration of epilepsy was 29.8 ⫾ 12.1 years. Four-
teen of 48 patients (29%) had pain or coughing at a range
of stimulation intensities from 1.0 to 3 mA (mean 2.0 mA)
(figure). Ten had neck pain, two noted throat pain, one had
neck pain and cough, and one had jaw and tooth pain. One
patient who had neck pain also noted muscular contraction
of the neck with activation. Ten of 14 patients had com-
plete and immediate resolution of pain with a reduction of
pulse width from 500 to 250 microseconds, whereas 4 of 14
required further reduction to 130 microseconds. All 14 pa-
tients were pain-free and able to have their output current
intensities increased (mean increase from 2.0 to 2.5 mA).
Two patients noted the added benefit of reduced voice al-
teration with stimulation.
Overall, 18 of 48 (39%) patients had a ⱖ50% reduction
in seizure frequency with VNS implantation. Mean
follow-up was 1.21 ⫾ 0.8 years. For those with altered
pulse width, 6 of 14 (43%) had a ⱖ50% reduction in seizure
frequency with VNS at 500-microsecond pulse width. After
lowering of the pulse width, 6 of 14 (43%) had ⱖ50% sei-
zure reduction. Seizure control was not adversely affected
in any of the patients with adjustments in pulse width. In
two patients, coincident with programming higher stimu-
lation intensities after pulse width adjustment, seizure
control improved. All patients had a minimum of 3 months
of follow-up after pulse width adjustment.
Discussion. VNS is a novel nonpharmacologic
treatment for medically refractory epilepsy. It is a
palliative procedure, resulting in a 50% decrease in
seizures for 30 to 35% of patients.1 Chronic adverse
effects include hoarseness, cough, pain, or choking
sensation, which increase during the time of stimula-
tion. These effects may limit attainment of higher
stimulation intensities and may restrict its effective-
ness. Although many physicians utilize VNS, there
Copyright © 2001 by AAN Enterprises, Inc. 885

Figure. Stimulation intensities associated with side ef-
fects, given as percentage of patients (n ⫽ 14).
are no guidelines to follow concerning adjustments of
program parameters to enhance tolerability. We
found that reducing the pulse width successfully
eliminated pain associated with stimulation.
The vagus nerve carries both motor and sensory
(visceral afferent) fibers. The motor fibers arise from
the nucleus ambiguus to innervate the somatic mus-
cles of the pharynx and larynx and from the dorsal
motor nucleus to supply autonomic innervation to
the heart, lungs, esophagus, and stomach. Unilateral
stimulation may lead to dysarthria or hoarseness.
Sensory fibers from the oropharynx, upper gastroin-
886 NEUROLOGY 57 September (1 of 2) 2001
testinal tract, and thoracic and abdominal organs
send information along the vagus to the tractus soli-
tarius. These pathways carry fibers for nociception.
For our patients, symptoms were largely local, sug-
gesting that local nociceptive fibers were important.
We found that lowering pulse width reduced this
local nociceptive effect. The effects of lowering pulse
width were immediate and easily discernible at the
time of pulse width adjustment.
Lowering the pulse width did not adversely affect
seizure control. One report noted similar findings.
Twenty patients with newly implanted VNS devices
were randomly assigned to either high (500-
microsecond) or low (250-microsecond) pulse width.
There were no group differences in seizure control at
6 or 12 months.2
We suggest using a pulse width of 250 microsec-
onds in VNS patients. Shorter pulse widths are bet-
ter tolerated while seizure control is not adversely
affected. Additionally, this adjustment reduces voice
alteration and helps preserve battery life.
References
1. Ben-Menachem E, Manon-Espaillat R, Ristanovic R, et al. Va-
gus nerve stimulation for treatment of partial seizures: 1. A
controlled study of effect on seizures. Epilepsia 1994;35:616 –
626.
2. Labiner D, Schwirtz D, Ahern G, MacDonald J, Weinard M.
Shorter pulse width of vagus nerve stimulation is as effective
in reducing seizure frequency as standard stimulation and is
better tolerated. Epilepsia 1999;40:141. Abstract.
 Vagal nerve stimulation: Adjustments to reduce painful side effects
J. Liporace, D. Hucko, R. Morrow, et al.
Neurology 2001;57;885-886
DOI 10.1212/WNL.57.5.885

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