- Email: [email protected]
Acupuncture in the Management of Medication Overuse and Drug-Induced Aseptic Meningitis Headache
Journal Pre-proof Acupuncture in the Management of Medication Overuse and Drug-Induced Aseptic Meningitis Headache Renuka T. Rudra, M.D., M.S., Vitaly Gordin, M.D, Lihua Xu, M.D PII:
S2005-2901(20)30001-7
DOI:
https://doi.org/10.1016/j.jams.2020.01.001
Reference:
JAMS 465
To appear in:
Journal of Acupuncture and Meridian Studies
Received Date: 12 October 2018 Revised Date:
16 December 2019
Accepted Date: 8 January 2020
Please cite this article as: Rudra RT, Gordin V, Xu L, Acupuncture in the Management of Medication Overuse and Drug-Induced Aseptic Meningitis Headache, Journal of Acupuncture and Meridian Studies, https://doi.org/10.1016/j.jams.2020.01.001. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Medical Association of Pharmacopuncture Institute, Publishing services by Elsevier B.V. All rights reserved.
Case Report Acupuncture in the Management of Medication Overuse and Drug-Induced Aseptic Meningitis Headache
Running Title: Acupuncture in Medication Overuse Headache Renuka T. Rudra1, M.D., M.S., [email protected], 717-531-0003 Vitaly Gordin2, M.D., [email protected], 717-531-0003 Lihua Xu3, M.D., [email protected], 717-531-0003
1. Department of Physical Medicine and Rehabilitation, Penn State Milton S. Hershey Medical Center and Penn State College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033 2. Department of Anesthesiology, Penn State Milton S. Hershey Medical Center and Penn State College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033 3. Department of Gastroenterology, Penn State Milton S. Hershey Medical Center and Penn State College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033
Correspondence to: Renuka T. Rudra, M.D., M.S. Department of Physical Medicine and Rehabilitation Penn State Milton S. Hershey Medical Center Penn State College of Medicine 500 University Drive P.O. Box 850, Mail Code HP28
Hershey, Pennsylvania 17033 United State of America Phone: 717-531-0003, x282045 Fax: 717-566-8202 Email: [email protected]
Declaration: No financial or personal conflicts of interest exist for the authors of this case report. All authors contributing to this paper have never submitted this manuscript, in whole or in part, to other journals.
Suggested Reviewers: 1. Andrew J Vickers, DPhil, Memorial Sloan Kettering Cancer Center, 485 Lexington Ave, New York, NY 10017 Email: [email protected], Phone: 646-888-8233 2. Denise M Millstine, MD, Mayo Clinic 13737 N 92nd St, Scottsdale, AZ 85260 Phone: 480-860-4800 3. Arthur Yin Fan, The American TCM Association, Vienna, VA 22182, USA Phone: 703-499-4428, email: [email protected]
1
Acupuncture in the Management of Medication Overuse and Drug-Induced Aseptic Meningitis
2
Headache: A Case Report.
3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
1
24
Abstract
25
Headache disorders are burdensome, both in terms of the number of people they affect, and in
26
terms of associated healthcare spending. This report presents a 36-year-old female admitted to a
27
tertiary university hospital with a primary complaint of intractable headache, caused by a
28
combination of Medication Overuse Headache (MOH), and headache secondary to aseptic
29
meningitis. During her hospital stay, opioid analgesic doses were initially increased without
30
success in an attempt to control her headache. Despite multiple medication trials the patient’s
31
headache failed to improve. On day ten of her hospitalization, she underwent a thirty-minute
32
acupuncture session which resulted in immediate relief of her headache. She received one more
33
acupuncture treatment the following day and was discharged to an acute inpatient rehabilitation
34
facility on a vastly reduced dose of opioids. Instructions on how to taper the remaining opioids
35
were provided, and the patient was scheduled for outpatient acupuncture therapy sessions for
36
further headache management. This report demonstrates the importance of recognizing
37
acupuncture as a viable treatment option for MOH and for headache secondary to systemic
38
diseases such as aseptic meningitis. Furthermore, acupuncture should also be considered as a
39
nonpharmacological modality to be utilized when tapering a patient off of high doses of opioids.
40 41 42 43 44 45 46 47 48 49 50 51 52 53
Key words: Acupuncture, Aseptic meningitis, Headache, Medication Overuse Headache, Opioids
2
54
Introduction
55
Acupuncture has been used in the management of headaches with variable success. The best
56
evidence of its effectiveness is for migraine headache. [1-3] While the International
57
Classification of Headache Disorders 3rd Edition includes multiple types of headaches, this case
58
report presents a patient suffering from both medication overuse headache (MOH) and headache
59
attributed to aseptic meningitis. [4] MOH is a characterized by chronic headache due to overuse
60
of various analgesics and abortive headache medications. Overuse of abortive headache
61
medications can worsen headache symptoms and transform episodic headaches into chronic
62
daily headaches. [5]
63 64
Meningitis is the inflammation of the meninges of the brain and spinal cord. Aseptic meningitis
65
presents with characteristic meningeal symptoms (fever, headache, neck stiffness, nausea,
66
vomiting, and photophobia amongst others), however cerebral spinal fluid (CSF) testing is
67
negative for an identifiable bacterial pathogen, and usually accompanied by a lymphocytic
68
pleocytosis. [6] The most common causes of aseptic meningitis include viral infections,
69
mycobacteria, spirochetes, fungi, malignancy, or can be drug induced. Drug induced meningitis
70
occurs either via direct meningeal irritation caused by intrathecal administration of drugs, or via
71
hypersensitivity reaction after systemic administration. [7]
72 73
Patients suffering from headaches are often treated with a multi-drug regimen, both prophylactic
74
and abortive. When standard pharmacologic agents fail to provide relief, physicians may resort
75
to opioids. As in other chronic pain conditions, a multi-modal approach has been recommended
3
76
for therapy, which includes a number of nonpharmacological modalities such as cognitive
77
behavioral therapy, massage, biofeedback, meditation, physical therapy and acupuncture. [8]
78 79
In light of the opioid epidemic, it is especially important to determine the role of
80
nonpharmacologic modalities such as acupuncture in treating patients who have been using high
81
doses of opioid analgesics for pain secondary to noncancerous conditions, and in patients who
82
are being tapered to lower doses or completely off of opioid analgesics.
83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98
4
99
Case Presentation
100
A 36-year-old Caucasian female with past medical history of migraines, anxiety, and bipolar
101
disorder, presented to a tertiary medical center with a primary complaint of headaches and low
102
back pain that had been present intermittently for about a year, but were worsening in intensity
103
and frequency over the month preceding her admission. These headaches were associated with
104
nausea, vomiting, photophobia, phonophobia, neck stiffness, low grade fevers, and low back
105
pain. The headache intensity did not change with position, nor were there any features of
106
increased intracranial pressure such as changes in visual acuity, issues with balance, or increased
107
intensity of headache with Valsalva. She had no history of receiving spinal injections for her low
108
back pain. There was no history of traumatic brain injury, concussion, meningitis, encephalitis,
109
or immunosuppression in this patient. Her family history was relevant for migraines in her
110
mother. The patient, who previously worked as an aerobics instructor, began declining in
111
functional ability over the 18 months preceding admission. In the three months preceding
112
admission she had lost 30 pounds and was mostly bedridden requiring assistance from her
113
husband who took family medical leave to help care for the family. The patient’s home
114
medications included lamotrigine 200mg PO daily for bipolar disorder, and opioid analgesics for
115
headache management. Approximately a month prior to admission, the patient’s primary care
116
provider was prescribing her oxycodone 20mg at bedtime PRN. However, over the course of a
117
month, her opioid regimen escalated to oxycodone immediate release 20mg PO at bedtime PRN,
118
oxycodone 10mg q4h PRN, and oxycodone extended release 30mg q12h. The patient had trialed
119
and failed a combination of acetaminophen, butalbital and caffeine (Fioricet) and sumatriptan in
120
the past.
121
5
122
On initial physical examination, the patient was awake, alert and oriented times three. Her
123
speech was fluent and cognition intact. She was applying ice packs to her head, neck and back,
124
and mild neck stiffness was evident, with no other meningeal signs present. She had no focal
125
neurological deficits.
126 127
On admission, the infectious disease team who was already seeing this patient in the outpatient
128
setting, was consulted. Initial evaluation was notable for documented low-grade fevers up to
129
37.8°C, and leukopenia of 3.3 x 10^9 cells/L (normal = 4.0 – 10.4 x 10^9). A lumbar puncture
130
was performed which was significant only for a lymphocytic pleocytosis, believed to be
131
secondary to drug induced aseptic meningitis caused by lamotrigine. The patient reported having
132
been on lamotrigine at the same dose for “years”. The infectious disease team noted that while
133
this made implication of lamotrigine as the causal agent for aseptic meningitis more difficult, it
134
was still a plausible explanation. MRI and MRA of the head and neck, and MRI of the lumbar
135
spine, were all done and within normal limits.
136 137
On day five of admission, a consult was placed to the Chronic Pain Medicine team as the patient
138
was on high doses of extended release and short acting opioid analgesics without adequate pain
139
relief. With the addition of breakthrough doses of oxycodone for additional pain relief, her total
140
daily dose was 140mg of oxycodone. The Pain Medicine team proposed that the patient’s
141
headache worsened from chronic opioid overuse, in addition to aseptic meningitis. It was the
142
recommendation of the Pain Medicine team that the patient be tapered off of opioids, starting
143
with discontinuation of oxycodone extended release 30mg q12h, and use of oxycodone
144
immediate release 30mg four times daily as needed. The primary team did make this change,
6
145
however was unable to taper dosing due to poor pain control, and continued to give the patient
146
additional breakthrough doses of narcotics. Finally, on day ten of admission a multidisciplinary
147
team meeting was held in which the Pain medicine team offered the services of a physician
148
trained in acupuncture to the patient. The patient was agreeable to trialing acupuncture as she
149
was unable to achieve any pain relief in spite of multiple medication trials.
150 151
At the beginning of the acupuncture session, the patient rated headache intensity at 10/10 with
152
associated photophobia, phonophobia and nausea. The patient underwent a thirty-minute
153
session with the following points stimulated with needles: First group: HN-1 point in four sites
154
and HN-3 point at the glabella. Second group: BL-10, LI-4, GB-20, GB-44, GB-2, and HN-5 on
155
both sides. During this session, the patient’s pain improved drastically from 10/10 to 1/10 and
156
her photophobia resolved. She reported feeling tired after the procedure, however was more
157
interactive with the staff and her family members. The following morning the patient reported
158
the best night’s sleep she had had during the hospitalization and reported no headache. She
159
underwent another 30-minute acupuncture session with the points above re-stimulated. Her
160
opioid regimen was reduced by 50% following the first acupuncture session, and she was
161
discharged home the following day, still headache free. At the time of discharge, her opioid
162
requirement decreased by 72% from her prior baseline. Her discharge plan included instructions
163
on how to taper the remaining dose of opioids, the discontinuation of lamotrigine, and follow-up
164
for repeat acupuncture treatments in the outpatient setting.
165 166 167
7
168
Discussion
169
According to the WHO global burden of disease, headache disorders rank as the leading cause of
170
years lived with disability worldwide. [9] In the United States, about one in six Americans are
171
affected by at least one migraine and/or a severe headache of a different etiology over a three-
172
month period. These disorders are a public health concern due to prevalence, associated
173
disability, and financial cost. [10] Treatment for headaches often involves the use of analgesics
174
and abortive anti-migraine drugs. The frequent use of analgesics or anti-migraine drugs for
175
primary headache syndromes may then lead to a MOH, which is a secondary headache
176
syndrome. [11] In light of the opioid epidemic, the U.S. FDA now recommends consideration of
177
non-pharmacologic options for pain control in patients on high doses of opioid analgesics, and
178
for those whose pain and ability to function are adversely affected by opioid use. [12]
179 180
Acupuncture has been used in China for two thousand years as a non-pharmacologic treatment of
181
headaches. Our patient underwent manual acupuncture, in which acupuncture needles are
182
inserted into acupoints followed by manipulation of the needles up and down by hand. [13]
183
While mechanisms of analgesia from acupuncture are still being studied, multiple mechanisms
184
have been proposed: post-stimulatory sympathetic inhibition, stimulation induced release of
185
endogenous opioids, and deformation of localized tissue eliciting a systemic response. [14-16]
186 187
In the presented case, the patient had tried and failed anti-migraine medications, and was
188
requiring opioids for migraine headaches. Her headache symptoms became more frequent as
189
time progressed, and she was subsequently diagnosed with MOH. This case supports the existing
190
data in showing that the use of non-opioid and opioid analgesics and anti-migraine agents,
8
191
intended to provide relief, can contribute towards the global burden of headache disorders.
192
Therefore, it is imperative that we consider alternative non-pharmacologic methods of treatment,
193
such as acupuncture. Studies have shown acupuncture in particular to be safe, cost-effective, and
194
successful in cases of opioid abuse and overuse. [17] In this case, acupuncture resulted in the
195
dramatic improvement of the patient’s condition and decreased her opioid requirement by 50%
196
within 24 hours of the first acupuncture session. The use of non-pharmacologic therapies in place
197
of opioids can help lessen the healthcare burden that the opioid crisis has caused. A second
198
etiology potentially contributing towards this patient’s headaches was aseptic meningitis
199
secondary to lamotrigine use. Given that the patients symptoms completely resolved following
200
manual acupuncture, it may be worthwhile to not only further investigate the use of acupuncture
201
in MOH, but also in headache symptoms secondary to systemic diseases, such as aseptic
202
meningitis.
203 204 205 206 207 208 209 210 211 212 213
9
214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258
References 1. Vickers, Andrew J., Rebecca W. Rees, Catherine E. Zollman, Rob McCarney, Claire M. Smith, et al. “Acupuncture for Chronic Headache in Primary Care: Large, Pragmatic, Randomised Trial.” BMJ 328, no. 7442 (March 25, 2004): 744. https://doi.org/10.1136/bmj.38029.421863.EB. 2. Li, Ying, Fanrong Liang, Xuguang Yang, Xiaoping Tian, Jie Yan, et al. “Acupuncture for Treating Acute Attacks of Migraine: A Randomized Controlled Trial.” Headache 49, no. 6 (June 2009): 805–16. https://doi.org/10.1111/j.1526-4610.2009.01424.x. 3. Gu, Tao, Lei Lin, Yun Jiang, Juan Chen, Ryan Cn D’Arcy, et al. 2018. “Acupuncture Therapy in Treating Migraine: Results of a Magnetic Resonance Spectroscopy Imaging Study.” Journal of Pain Research 11: 889–900. https://doi.org/10.2147/JPR.S162696. 4. Ihsclassification. “ICHD-3 The International Classification of Headache Disorders 3rd Edition.” ICHD-3 The International Classification of Headache Disorders 3rd edition. Accessed May 22, 2018. https://www.ichd-3.org/. 5. Kristoffersen, Espen Saxhaug, and Christofer Lundqvist. “Medication-Overuse Headache: A Review.” Journal of Pain Research 7 (June 26, 2014): 367–78. https://doi.org/10.2147/JPR.S46071. 6. Irani, David N. “Aseptic Meningitis and Viral Myelitis.” Neurologic Clinics 26, no. 3 (August 2008): 635–viii. https://doi.org/10.1016/j.ncl.2008.03.003. 7. Yelehe-Okouma, Melissa, Julie Czmil-Garon, Elise Pape, Nadine Petitpain, and Pierre Gillet. “Drug-Induced Aseptic Meningitis: A Mini-Review.” Fundamental & Clinical Pharmacology, January 24, 2018. https://doi.org/10.1111/fcp.12349. 8. Millstine, Denise, Christina Y. Chen, and Brent Bauer. 2017. “Complementary and Integrative Medicine in the Management of Headache.” BMJ (Clinical Research Ed.) 357 (May): j1805. 9. Saylor, Deanna, and Timothy J. Steiner. “The Global Burden of Headache.” Seminars in Neurology 38, no. 2 (April 2018): 182–90. https://doi.org/10.1055/s-0038-1646946. 10. Burch, Rebecca, Paul Rizzoli, and Elizabeth Loder. “The Prevalence and Impact of Migraine and Severe Headache in the United States: Figures and Trends From Government Health Studies.” Headache: The Journal of Head and Face Pain 58, no. 4 (n.d.): 496–505. https://doi.org/10.1111/head.13281. 11. Ärzteblatt, Deutscher Ärzteverlag GmbH, Redaktion Deutsches. “Chronic Headache Due to Overuse of Analgesics and Anti-Migraine Agents (01.06.2018).” Accessed June 30, 2018. https://www.aerzteblatt.de/int/archive/article?id=198145.
10
259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286
12. The Food and Drug Administration. Introduction for the FDA blueprint for prescriber education for extended-release and long-acting opioid analgesics. (2017-05) [2017-0819].https://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM51 5636.pdf. 13. Zhao, Zhi-Qi. “Neural Mechanism Underlying Acupuncture Analgesia.” Progress in Neurobiology 85, no. 4 (August 2008): 355–75. https://doi.org/10.1016/j.pneurobio.2008.05.004. 14. Huang, Meng, Xuezhi Wang, Beibei Xing, Hongwei Yang, Zheyan Sa, et al. “Critical Roles of TRPV2 Channels, Histamine H1 and Adenosine A1 Receptors in the Initiation of Acupoint Signals for Acupuncture Analgesia.”Scientific Reports 8, no. 1 (April 25, 2018): 6523. https://doi.org/10.1038/s41598-018-24654-y. 15. Andersson, S., and T. Lundeberg. “Acupuncture — from Empiricism to Science: Functional Background to Acupuncture Effects in Pain and Disease Pain and Disease.” Medical Hypotheses 45, no. 3 (September 1, 1995): 271–81. https://doi.org/10.1016/0306-9877(95)90117-5. 16. Carlsson, C. “Acupuncture Mechanisms for Clinically Relevant Long-Term Effects – Reconsideration and a Hypothesis | Acupuncture in Medicine.” Accessed September 3, 2018. https://aim.bmj.com/content/20/2-3/82.long. 17. Fan, Arthur Yin, David W. Miller, Bonnie Bolash, Matthew Bauer, John McDonald, et al. 2017. “Acupuncture’s Role in Solving the Opioid Epidemic: Evidence, CostEffectiveness, and Care Availability for Acupuncture as a Primary, Non-Pharmacologic Method for Pain Relief and Management–White Paper 2017.” Journal of Integrative Medicine 15 (6): 411–25. https://doi.org/10.1016/S2095-4964(17)60378-9.
11
S2005-2901(20)30001-7
DOI:
https://doi.org/10.1016/j.jams.2020.01.001
Reference:
JAMS 465
To appear in:
Journal of Acupuncture and Meridian Studies
Received Date: 12 October 2018 Revised Date:
16 December 2019
Accepted Date: 8 January 2020
Please cite this article as: Rudra RT, Gordin V, Xu L, Acupuncture in the Management of Medication Overuse and Drug-Induced Aseptic Meningitis Headache, Journal of Acupuncture and Meridian Studies, https://doi.org/10.1016/j.jams.2020.01.001. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Medical Association of Pharmacopuncture Institute, Publishing services by Elsevier B.V. All rights reserved.
Case Report Acupuncture in the Management of Medication Overuse and Drug-Induced Aseptic Meningitis Headache
Running Title: Acupuncture in Medication Overuse Headache Renuka T. Rudra1, M.D., M.S., [email protected], 717-531-0003 Vitaly Gordin2, M.D., [email protected], 717-531-0003 Lihua Xu3, M.D., [email protected], 717-531-0003
1. Department of Physical Medicine and Rehabilitation, Penn State Milton S. Hershey Medical Center and Penn State College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033 2. Department of Anesthesiology, Penn State Milton S. Hershey Medical Center and Penn State College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033 3. Department of Gastroenterology, Penn State Milton S. Hershey Medical Center and Penn State College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033
Correspondence to: Renuka T. Rudra, M.D., M.S. Department of Physical Medicine and Rehabilitation Penn State Milton S. Hershey Medical Center Penn State College of Medicine 500 University Drive P.O. Box 850, Mail Code HP28
Hershey, Pennsylvania 17033 United State of America Phone: 717-531-0003, x282045 Fax: 717-566-8202 Email: [email protected]
Declaration: No financial or personal conflicts of interest exist for the authors of this case report. All authors contributing to this paper have never submitted this manuscript, in whole or in part, to other journals.
Suggested Reviewers: 1. Andrew J Vickers, DPhil, Memorial Sloan Kettering Cancer Center, 485 Lexington Ave, New York, NY 10017 Email: [email protected], Phone: 646-888-8233 2. Denise M Millstine, MD, Mayo Clinic 13737 N 92nd St, Scottsdale, AZ 85260 Phone: 480-860-4800 3. Arthur Yin Fan, The American TCM Association, Vienna, VA 22182, USA Phone: 703-499-4428, email: [email protected]
1
Acupuncture in the Management of Medication Overuse and Drug-Induced Aseptic Meningitis
2
Headache: A Case Report.
3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
1
24
Abstract
25
Headache disorders are burdensome, both in terms of the number of people they affect, and in
26
terms of associated healthcare spending. This report presents a 36-year-old female admitted to a
27
tertiary university hospital with a primary complaint of intractable headache, caused by a
28
combination of Medication Overuse Headache (MOH), and headache secondary to aseptic
29
meningitis. During her hospital stay, opioid analgesic doses were initially increased without
30
success in an attempt to control her headache. Despite multiple medication trials the patient’s
31
headache failed to improve. On day ten of her hospitalization, she underwent a thirty-minute
32
acupuncture session which resulted in immediate relief of her headache. She received one more
33
acupuncture treatment the following day and was discharged to an acute inpatient rehabilitation
34
facility on a vastly reduced dose of opioids. Instructions on how to taper the remaining opioids
35
were provided, and the patient was scheduled for outpatient acupuncture therapy sessions for
36
further headache management. This report demonstrates the importance of recognizing
37
acupuncture as a viable treatment option for MOH and for headache secondary to systemic
38
diseases such as aseptic meningitis. Furthermore, acupuncture should also be considered as a
39
nonpharmacological modality to be utilized when tapering a patient off of high doses of opioids.
40 41 42 43 44 45 46 47 48 49 50 51 52 53
Key words: Acupuncture, Aseptic meningitis, Headache, Medication Overuse Headache, Opioids
2
54
Introduction
55
Acupuncture has been used in the management of headaches with variable success. The best
56
evidence of its effectiveness is for migraine headache. [1-3] While the International
57
Classification of Headache Disorders 3rd Edition includes multiple types of headaches, this case
58
report presents a patient suffering from both medication overuse headache (MOH) and headache
59
attributed to aseptic meningitis. [4] MOH is a characterized by chronic headache due to overuse
60
of various analgesics and abortive headache medications. Overuse of abortive headache
61
medications can worsen headache symptoms and transform episodic headaches into chronic
62
daily headaches. [5]
63 64
Meningitis is the inflammation of the meninges of the brain and spinal cord. Aseptic meningitis
65
presents with characteristic meningeal symptoms (fever, headache, neck stiffness, nausea,
66
vomiting, and photophobia amongst others), however cerebral spinal fluid (CSF) testing is
67
negative for an identifiable bacterial pathogen, and usually accompanied by a lymphocytic
68
pleocytosis. [6] The most common causes of aseptic meningitis include viral infections,
69
mycobacteria, spirochetes, fungi, malignancy, or can be drug induced. Drug induced meningitis
70
occurs either via direct meningeal irritation caused by intrathecal administration of drugs, or via
71
hypersensitivity reaction after systemic administration. [7]
72 73
Patients suffering from headaches are often treated with a multi-drug regimen, both prophylactic
74
and abortive. When standard pharmacologic agents fail to provide relief, physicians may resort
75
to opioids. As in other chronic pain conditions, a multi-modal approach has been recommended
3
76
for therapy, which includes a number of nonpharmacological modalities such as cognitive
77
behavioral therapy, massage, biofeedback, meditation, physical therapy and acupuncture. [8]
78 79
In light of the opioid epidemic, it is especially important to determine the role of
80
nonpharmacologic modalities such as acupuncture in treating patients who have been using high
81
doses of opioid analgesics for pain secondary to noncancerous conditions, and in patients who
82
are being tapered to lower doses or completely off of opioid analgesics.
83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98
4
99
Case Presentation
100
A 36-year-old Caucasian female with past medical history of migraines, anxiety, and bipolar
101
disorder, presented to a tertiary medical center with a primary complaint of headaches and low
102
back pain that had been present intermittently for about a year, but were worsening in intensity
103
and frequency over the month preceding her admission. These headaches were associated with
104
nausea, vomiting, photophobia, phonophobia, neck stiffness, low grade fevers, and low back
105
pain. The headache intensity did not change with position, nor were there any features of
106
increased intracranial pressure such as changes in visual acuity, issues with balance, or increased
107
intensity of headache with Valsalva. She had no history of receiving spinal injections for her low
108
back pain. There was no history of traumatic brain injury, concussion, meningitis, encephalitis,
109
or immunosuppression in this patient. Her family history was relevant for migraines in her
110
mother. The patient, who previously worked as an aerobics instructor, began declining in
111
functional ability over the 18 months preceding admission. In the three months preceding
112
admission she had lost 30 pounds and was mostly bedridden requiring assistance from her
113
husband who took family medical leave to help care for the family. The patient’s home
114
medications included lamotrigine 200mg PO daily for bipolar disorder, and opioid analgesics for
115
headache management. Approximately a month prior to admission, the patient’s primary care
116
provider was prescribing her oxycodone 20mg at bedtime PRN. However, over the course of a
117
month, her opioid regimen escalated to oxycodone immediate release 20mg PO at bedtime PRN,
118
oxycodone 10mg q4h PRN, and oxycodone extended release 30mg q12h. The patient had trialed
119
and failed a combination of acetaminophen, butalbital and caffeine (Fioricet) and sumatriptan in
120
the past.
121
5
122
On initial physical examination, the patient was awake, alert and oriented times three. Her
123
speech was fluent and cognition intact. She was applying ice packs to her head, neck and back,
124
and mild neck stiffness was evident, with no other meningeal signs present. She had no focal
125
neurological deficits.
126 127
On admission, the infectious disease team who was already seeing this patient in the outpatient
128
setting, was consulted. Initial evaluation was notable for documented low-grade fevers up to
129
37.8°C, and leukopenia of 3.3 x 10^9 cells/L (normal = 4.0 – 10.4 x 10^9). A lumbar puncture
130
was performed which was significant only for a lymphocytic pleocytosis, believed to be
131
secondary to drug induced aseptic meningitis caused by lamotrigine. The patient reported having
132
been on lamotrigine at the same dose for “years”. The infectious disease team noted that while
133
this made implication of lamotrigine as the causal agent for aseptic meningitis more difficult, it
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was still a plausible explanation. MRI and MRA of the head and neck, and MRI of the lumbar
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spine, were all done and within normal limits.
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On day five of admission, a consult was placed to the Chronic Pain Medicine team as the patient
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was on high doses of extended release and short acting opioid analgesics without adequate pain
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relief. With the addition of breakthrough doses of oxycodone for additional pain relief, her total
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daily dose was 140mg of oxycodone. The Pain Medicine team proposed that the patient’s
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headache worsened from chronic opioid overuse, in addition to aseptic meningitis. It was the
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recommendation of the Pain Medicine team that the patient be tapered off of opioids, starting
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with discontinuation of oxycodone extended release 30mg q12h, and use of oxycodone
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immediate release 30mg four times daily as needed. The primary team did make this change,
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however was unable to taper dosing due to poor pain control, and continued to give the patient
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additional breakthrough doses of narcotics. Finally, on day ten of admission a multidisciplinary
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team meeting was held in which the Pain medicine team offered the services of a physician
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trained in acupuncture to the patient. The patient was agreeable to trialing acupuncture as she
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was unable to achieve any pain relief in spite of multiple medication trials.
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At the beginning of the acupuncture session, the patient rated headache intensity at 10/10 with
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associated photophobia, phonophobia and nausea. The patient underwent a thirty-minute
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session with the following points stimulated with needles: First group: HN-1 point in four sites
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and HN-3 point at the glabella. Second group: BL-10, LI-4, GB-20, GB-44, GB-2, and HN-5 on
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both sides. During this session, the patient’s pain improved drastically from 10/10 to 1/10 and
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her photophobia resolved. She reported feeling tired after the procedure, however was more
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interactive with the staff and her family members. The following morning the patient reported
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the best night’s sleep she had had during the hospitalization and reported no headache. She
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underwent another 30-minute acupuncture session with the points above re-stimulated. Her
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opioid regimen was reduced by 50% following the first acupuncture session, and she was
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discharged home the following day, still headache free. At the time of discharge, her opioid
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requirement decreased by 72% from her prior baseline. Her discharge plan included instructions
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on how to taper the remaining dose of opioids, the discontinuation of lamotrigine, and follow-up
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for repeat acupuncture treatments in the outpatient setting.
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Discussion
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According to the WHO global burden of disease, headache disorders rank as the leading cause of
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years lived with disability worldwide. [9] In the United States, about one in six Americans are
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affected by at least one migraine and/or a severe headache of a different etiology over a three-
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month period. These disorders are a public health concern due to prevalence, associated
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disability, and financial cost. [10] Treatment for headaches often involves the use of analgesics
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and abortive anti-migraine drugs. The frequent use of analgesics or anti-migraine drugs for
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primary headache syndromes may then lead to a MOH, which is a secondary headache
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syndrome. [11] In light of the opioid epidemic, the U.S. FDA now recommends consideration of
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non-pharmacologic options for pain control in patients on high doses of opioid analgesics, and
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for those whose pain and ability to function are adversely affected by opioid use. [12]
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Acupuncture has been used in China for two thousand years as a non-pharmacologic treatment of
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headaches. Our patient underwent manual acupuncture, in which acupuncture needles are
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inserted into acupoints followed by manipulation of the needles up and down by hand. [13]
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While mechanisms of analgesia from acupuncture are still being studied, multiple mechanisms
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have been proposed: post-stimulatory sympathetic inhibition, stimulation induced release of
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endogenous opioids, and deformation of localized tissue eliciting a systemic response. [14-16]
186 187
In the presented case, the patient had tried and failed anti-migraine medications, and was
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requiring opioids for migraine headaches. Her headache symptoms became more frequent as
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time progressed, and she was subsequently diagnosed with MOH. This case supports the existing
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data in showing that the use of non-opioid and opioid analgesics and anti-migraine agents,
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intended to provide relief, can contribute towards the global burden of headache disorders.
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Therefore, it is imperative that we consider alternative non-pharmacologic methods of treatment,
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such as acupuncture. Studies have shown acupuncture in particular to be safe, cost-effective, and
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successful in cases of opioid abuse and overuse. [17] In this case, acupuncture resulted in the
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dramatic improvement of the patient’s condition and decreased her opioid requirement by 50%
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within 24 hours of the first acupuncture session. The use of non-pharmacologic therapies in place
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of opioids can help lessen the healthcare burden that the opioid crisis has caused. A second
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etiology potentially contributing towards this patient’s headaches was aseptic meningitis
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secondary to lamotrigine use. Given that the patients symptoms completely resolved following
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manual acupuncture, it may be worthwhile to not only further investigate the use of acupuncture
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in MOH, but also in headache symptoms secondary to systemic diseases, such as aseptic
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meningitis.
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214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258
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