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Acupuncture for Chemotherapy-Induced Peripheral Neuropathy (Cipn): A Pilot Study Using Neurography

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Chemotherapy-induced peripheral neuropathy (CIPN) can produce severe neurological deficits and neuropathic pain and is a potential reason for terminating or suspending chemotherapy treatments. Specific and effective curative treatments are lacking. A pilot study was conducted to evaluate the therapeutic effect of acupuncture on CIPN as measured by changes in nerve conduction studies (NCS) in six patients treated with acupuncture for 10 weeks in addition to best medical care and five control patients who received the best medical care but no specific treatment for CIPN. In five of the six patients treated with acupuncture, NCS improved after treatment. In the control group, three of five patients did not show any difference in NCS, one patient improved and one showed impaired NCS. The data suggest that acupuncture has a positive effect on CIPN. The encouraging results of this pilot study justify a randomised controlled trial of acupuncture in CIPN on the basis of NCS.
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Original paper
Schroeder S, Meyer-Hamme G, Epplée S. Acupunct Med (2011). doi:10.1136/acupmed-2011-010034 1 of 4
ABSTRACT
Objectives Chemotherapy-induced peripheral
neuropathy (CIPN) can produce severe neurological
defi cits and neuropathic pain and is a potential
reason for terminating or suspending chemotherapy
treatments. Specifi c and effective curative
treatments are lacking.
Methods A pilot study was conducted to evaluate
the therapeutic effect of acupuncture on CIPN as
measured by changes in nerve conduction studies
(NCS) in six patients treated with acupuncture for
10 weeks in addition to best medical care and fi ve
control patients who received the best medical
care but no specifi c treatment for CIPN.
Results In fi ve of the six patients treated with
acupuncture, NCS improved after treatment. In the
control group, three of fi ve patients did not show any
difference in NCS, one patient improved and one
showed impaired NCS.
Conclusion The data suggest that acupuncture has
a positive effect on CIPN. The encouraging results of
this pilot study justify a randomised controlled trial of
acupuncture in CIPN on the basis of NCS.
INTRODUCTION
Chemotherapy-induced peripheral neuropa-
thy (CIPN) involves damage to the peripheral
nervous system and can produce severe neu-
ropathic pain or gait impairment and may be
a reason to terminate or suspend chemother-
apy treatments. Specifi c and effective curative
treatments are lacking. The major groups of
drugs that induce CIPN include the taxanes,
vinca alkaloids and platinum compounds. The
incidence of CIPN is high and can reach levels
of up to 92%.
1
Publications in English language journals on
acupuncture as a symptomatic treatment for
CIPN have been limited to only a few case
studies, all of which report an improvement
in symptoms.
2 3
A Chinese study described
acupuncture as more effective than cobama-
mide for the treatment of sensory symptoms
in paclitaxel-induced CIPN.
4
We conducted a pilot study in 2006 in 192
patients with peripheral neuropathy diag-
nosed on the basis of nerve conduction studies
(NCS). Patients were evaluated over a period
of 1 year, measured by NCS. The aim of this
Acupuncture for chemotherapy-induced peripheral
neuropathy (CIPN): a pilot study using neurography
Sven Schroeder
1,2,
, Gesa Meyer-Hamme
1
, Susanne Epplée
1
1
HanseMerkur Center for TCM
at the University Medical
Centre, Hamburg, Germany
2
Department of
Neurophysiology, Instituto de
Ciências Biomédicas, Abel
Salazar, University of Porto,
Porto, Portugal
Correspondence to
Sven Schroeder, HanseMerkur
Centre for TCM at the University
Medical Center, UKE-Campus,
House O55, Martinistrasse 52,
20246, Hamburg, Germany;
schroeder@tcm-am-uke.de
Received 22 May 2011
Accepted 11 October 2011
non-randomised non-blinded study was to
determine whether there is evidence of effec-
tive treatment of peripheral neuropathy (PN)
with acupuncture assessed by objective mea-
surements and whether further prospective
studies on the basis of the above criteria are
warranted. We have previously published
data on the treatment of PN of unknown aeti-
ology and diabetic neuropathy with acupunc-
ture, and found an improvement in NCS in
76% of patients after a treatment period of
10 weeks, one treatment per week.
5 6
In this
paper we report our results in patients with
CIPN.
METHODS
A total of 192 consecutive patients with PN of
the lower extremities were diagnosed by NCS
and treated in a neurologist’s outpatient clinic
for a period of 1 year. Patients with PN con-
rmed by neurological examination and NCS
were included in the study. Patients with alco-
hol abuse, drug usage, a history of diabetes,
toxic drugs (except a history of chemother-
apy) or infl ammatory disease documented as
underlying causes for PN were excluded from
the study. This was confi rmed by standard
screening.
5
Of this group, 11 patients had developed
symptoms of PN during the course of chemo-
therapy and were identifi ed as having CIPN.
Chemotherapy had been given for different
types of cancer (table 1).
Acupuncture treatment was offered to all
the patients with CIPN. Six patients agreed
to receive acupuncture treatment and ve
refused owing to personal inconvenience of
the appointments offered. These ve patients
(four men, one woman) of mean age 65 years
who received the best medical care but no spe-
cifi c treatment for PN thus served as a control
group. Six patients (three men, three women)
of mean age 64 years received the best medi-
cal care and additionally were treated with
acupuncture for PN of the lower extremities.
Patients in both groups did not receive any
other treatment for PN except stable doses
of carbamazepine or pregabalin during the
observation period. The characteristics of the
acupuncture and control groups are shown in
table 1.
Copyright 2011 by British Medical Journal Publishing Group.
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Original paper
Schroeder S, Meyer-Hamme G, Epplée S. Acupunct Med (2011). doi:10.1136/acupmed-2011-0100342 of 4
Measurements of nerve conduction velocity (NCV)
were performed with a Neuropack-Sigma, MEB-9400,
EMG/NCV/EP-System (Nihon-Khoden, Tokyo, Japan).
The amplitudes of the motor and sensory responses were
measured to the rst negative peak. All studies of NCV
were done at room temperature (22–24°C). Skin tempera-
ture was measured at the sites of sensory nerve measure-
ments and values were analysed, adjusting for the effects
of temperature. Follow-up NCS data were collected after a
period of 6 months (±2 weeks) by examination of the sural
and tibial nerves in the same calf as in the initial assess-
ment. Standard orthodromic needle recording methods
were used for sural nerve assessment while standard sur-
face recording methods were used for tibial nerve record-
ings.
7 8
A change in NCV in the sural nerve of 2 m/s slower
or faster than the initial measurement was considered sig-
nifi cant. A change in the amplitude of the sensory nerve
action potential of more than 2 µV was defi ned as a signifi -
cant impairment or improvement in the sural nerve.
The patients were asked at the time of the second
NCS to tick one box to indicate whether their condition
had improved, worsened or remained unchanged.
Acupuncture treatment was based on a neurophysi-
ologcial approach to traditional Chinese medicine (TCM)
theory.
9
Point selection followed the training curriculum
at the TCM-Master Education at the Instituto de Ciências
Biomédicas Abel Salazar, University of Porto, Portugal.
The specifi c acupuncture protocols employed in this
study are described below, point location and depth of
insertion were as described in standard textbooks
10
and
disposable sterile steel needles of 0.30×30 mm were used
and left in place for 20 min to a depth of 10–30 mm. Each
patient received a standard 10-week treatment of the
ST34 (Liangqiu) as well as the ve extra points EX–LE12
(Qiduan) and the four extra points EX–LE8 (Bafeng). The
needles were inserted bilaterally. Twenty needles were
inserted per session. Needle stimulation techniques were
not used. We did not employ manipulation in order to
elicit a de qi sensation. Acupuncture was performed in
all cases by the same senior physician who had received
>1000 h of acupuncture training before participating in
the trial and had used acupuncture for 20 years. The six
patients in the acupuncture group were examined by NCS
2–21 months (mean 10.3) after chemotherapy. NCS was
performed before treatment and again 6 months later (ie,
3 months (±2 weeks) after the end of treatment).
The ve patients in the control group were examined
by NCS 1–14 months (mean 10.8) after chemotherapy and
routinely again at 6 months.
RESULTS
All six patients in the acupuncture group had hypoesthesia
in a stocking distribution; three had additional neuropathic
pain. There was no clinical motor involvement and no
motor involvement in NCS. NCS showed mixed damage of
the axon and the myelin sheath of the sensory sural nerve
in all six acupuncture-treated patients. All ve patients in
the control group had hypoesthesia in a stocking contri-
bution; three had additional neuropathic pain. There was
no clinical motor involvement and no motor involvement
in NCS. NCS revealed mixed damage to the axon and
myelin sheath of the sensitive sural nerve in two patients
in the control group while three had pure axonopathy. The
results of the NCS of the sural nerve as well as the subjec-
tive outcomes are shown in table 2. A comparison of the
mean values for the two groups is shown in table 3.
DISCUSSION
This pilot study shows improvement in NCS after acu-
puncture treatment in CIPN. The use of NCS as an
Table 1 Cancer types and chemotherapy of patients with
chemotherapy-induced peripheral neuropathy
Patient groups Chemotherapy
Acupunture group
Breast Docetaxel/doxorubicin/cyclophosphamide
Colon Oxaliplatin
Colon (sigmoid) Cisplatin
Bronchial Cisplatin
Lymphoma Rituximab/fl udarabin/cyclophosphamide
Lymphoma Rituximab/fl udarabin/cyclophosphamide
Control group
Breast Docetaxel/doxorubicin/cyclophosphamide
Colon (sigmoid) Oxaliplatin
Colon 5-fl uorouracil/oxaliplatin
Pleura mesothelioma Alimta/cisplatin
Lymphoma Rituximab/fl udarabin/cyclophosphamide
Table 2 Nerve conduction studies of the sural nerve and subjective outcome in acupuncture-treated and control groups
Acupuncture (10 treatments over 3 months) Control (no specifi c treatment)
Patient no NCV (m/s) Amplitude (µV)
Patients’
evaluation Patient no NCV (m/s) Amplitude (µV)
Patients’
evaluation
Initial After 6 months Initial After 6 months After 6 months Initial After 6 months Initial After 6 months After 6 months
1 0 30.6 0 0.8 Improvement 1 42 42 3.9 3.9 No change
200 00 No change 2 42 42 3.6 3.8 No change
3 36 45 0.2 1.7 Improvement 3 36 42 3.2 3.1 No change
4 0 42 0 1.2 Improvement 4 42 42 2.3 5 Improvement
5 0 42 0 2.2 Improvement 5 37 0 20 Impairment
6 34 45 1.5 2 Improvement
NCV, nerve conduction velocity.
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Original paper
Schroeder S, Meyer-Hamme G, Epplée S. Acupunct Med (2011). doi:10.1136/acupmed-2011-010034 3 of 4
objective parameter is promising for future acupunc-
ture studies, although the number of cases is limited.
Interestingly, an improvement in NCS after acupuncture
was shown in CIPN as well as in previous studies on PN
of undefi ned aetiology and diabetic neuropathy.
5 6
The
results are consistent with previously published case
studies on acupuncture treatment of CIPN.
4
Although PN has numerous causes including genetic,
toxic, metabolic, infectious, infl ammatory, ischaemic and
paraneoplastic disorders, the nerve can be destroyed in
a limited number of ways because the damage can only
occur at the level of the axon or the myelin sheaths.
11 12
Differentiating whether neuropathy is axonal, demyelinat-
ing or both is achieved by NCS.
11–14
It is generally accepted
that compromised nerve conduction in PN mainly depends
on structural changes of the myelin sheaths, while the
amplitude is correlated with the number of functional
axons.
7 8
Consequently, one may speculate that repeated
therapeutic interventions with acupuncture over a period
of 10 weeks improves the symptomatic state of PN and
also induces a normalisation of histological morphology.
It has been shown by Litscher et al
15
that acupuncture may
increase the blood fl ow in the limbs. Increased blood ow
to the vasa nervorum and dependent capillary beds sup-
plying the neurons
16
may contribute to nerve repair with
measurable improvement of axons or myelin sheaths.
Peripheral mechanisms possibly involved may include
other types of bres, such as the small unmyelinised or
thinly myelinised bres commonly believed to be unde-
tected by NCS.
In addition, the symptomatic effect of acupuncture may
refl ect morphological changes in the anatomy of periph-
eral nerves and also complex derangements of central and
peripheral regulation.
17 18
One hypothesis relates to the
enhancement of conduction by the dorsal column
19–21
or
higher centres.
22 23
CONCLUSION
The data suggest that acupuncture has a positive effect
on CIPN as measured by objective parameters (NCS).
The results are comparable to previous studies in dia-
betic neuropathy and PN of undefi ned aetiology. These
ndings are of special signifi cance since PN is otherwise
almost untreatable but seems to respond to treatment by
acupuncture. This pilot study shows encouraging results
for the application of acupuncture in CIPN, justifying a
randomised controlled trial.
Contributors SS designed data collection tools, monitored data collection for the
whole trial, wrote the statistical analysis plan, cleaned and analysed the data and
drafted and revised the paper. MH-G analysed the data and drafted and revised the
paper. ES monitored data collection and revised the draft paper.
Competing interests None
Patient consent Obtained
Ethics approval Ethical approval was obtained from the Ethik Kommission der
Hamburger Ärztekammer
Provenance and peer review Not commissioned; externally peer reviewed
REFERENCES
1. Oxaliplatin Prescribing Information. http://www.drugs.com/pro/oxaliplatin.html
(accessed 3 August 2011).
2. Donald GK, Tobin I, Stringer J. Evaluation of acupuncture in the management of
chemotherapy-induced peripheral neuropathy. Acupunct Med 2011;29:230–3.
3. Wong R, Sagar S. Acupuncture treatment for chemotherapy-induced peripheral
neuropathy–a case series. Acupunct Med 2006;24:87–91.
4. Xu WR, Hua BJ, Hou W, et al. [Clinical randomized controlled study on acupuncture for
treatment of peripheral neuropathy induced by chemotherapeutic drugs]. Zhongguo
Zhen Jiu 2010;30:457–60.
5. Schröder S, Liepert J, Remppis A, et al. Acupuncture treatment improves nerve
conduction in peripheral neuropathy. Eur J Neurol 2007;14:276–81.
6. Schröder S, Rempiss A, Greten T, et al. Quantifi cation of acupuncture effects on
peripheral neuropathy of unknown and diabetic cause by NCS. J Acupunct Tuina Sci
2008;6:312–14.
7. Stoehr M. Atlas der klinischen Elektromyographie und Neurographie. Stuttgart:
Kohlhammer, 1998.
8. Eduardo E, Burke D. The optimal recording electrode confi guration for compound
sensory action potentials. J Neurol Neurosurg Psychiatry 1988;23:1.
9. Greten HJ. Kursbuch Traditionelle Chinesische Medizin. Second edition. Stuttgart-New
York: Thieme Publishing House, 2005
10. Deadman P, Baker K, Al-Khafaji M. A Manual of Acupuncture (2nd edition). East Sussex:
Journal of Chinese Medicine Publications, 2007.
11. Asbury AK, Gilliatt RW. The clinical approach to neuropathy. In: Asbury AK, Gilliatt
RW, eds. Peripheral Nerve Disorders: A Practical Approach. London: Butterworths,
1984:1–20.
12. Bosch EP, Mitsumoto H. Disorders of peripheral nerves. In: Bradley WG, Daroff RB,
Fenichel GM, Marsden CD, eds. Neurology in Clinical Practice. Boston: Butterworth-
Heinemann, 1991:1720–6.
13. Donofrio PD, Albers JW. AAEM minimonograph #34: polyneuropathy:
classification by nerve conduction studies and electromyography. Muscle Nerve
1990;13:889–903.
14. McLeod JG, Tuck RR, Pollard JD, et al. Chronic polyneuropathy of undetermined cause.
J Neurol Neurosurg Psychiatry 1984;47:530–5.
15. Litscher G, Wang L, Huber E, et al. Changed skin blood perfusion in the fi ngertip
following acupuncture needle introduction as evaluated by laser Doppler perfusion
imaging. Lasers Med Sci 2002;17:19–25.
16. Diabetes Control and Complication Trial Group (DCCT). The effect of intense
treatment on the development and progression of long-term complications in
insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–86.
17. Ma S, Cornford ME, Vahabnezhad I, et al. Responses of nitric oxide synthase expression
in the gracile nucleus to sciatic nerve injury in young and aged rats. Brain Res
2000;855:124–31.
Table 3 Mean (SD) differences in nerve conduction studies of the sural nerve in acupuncture-treated and control groups
Acupuncture (10 treatments over 3 months) Control (no specifi c treatment)
Initial After 6 months Paired t test p Value Mean difference Initial After 6 months Paired t test p Value Mean difference
Mean NCV (m/s)
11.67 (18.09) 34.1 (17.54) t=3.0278 df=5 0.03 +22.43 (18.15) 39.8 (3.03) 33.6 (18.78) t=0.7962 df=4 NS 6.20 (17.41)
Mean amplitude (µV)
0.28 (0.60) 1.32 (0.83) t=3.2604 df=5 0.02 +1.03 (0.77) 3.0 (0.88) 3.16 (1.89) t=0.214 df=4 NS +0.06 (1.49)
Product of NCV
and amplitude
9.70 (20.44) 55.55 (37.66) t=3.4289 df=5 0.02 +45.85 (32.75) 120.29 (37.32) 132.72 (79.5) t=0.4163 df=4 NS +12.43 (66.78)
NCV, nerve conduction velocity.
group.bmj.com on December 6, 2011 - Published by aim.bmj.comDownloaded from
Original paper
Schroeder S, Meyer-Hamme G, Epplée S. Acupunct Med (2011). doi:10.1136/acupmed-2011-0100344 of 4
18. Ma SX. Nitric oxide synthase in the gracile nucleus isincreased by stimulus-evoked
excitatory somato-sympatheticrefl exes. FASEB J 1998;2:A691.
19. Al-Chaer ED, Lawand NB, Westlund KN, et al. Pelvic visceral input into the nucleus
gracilis is largely mediated by the postsynaptic dorsal column pathway. J Neurophysiol
1996;76:2675–90.
20. Al-Chaer ED, Lawand NB, Westlund KN, et al. Visceral nociceptive input into the ventral
posterolateral nucleus of the thalamus: a new function for the dorsalcolumn pathway.
J Neurophysiol 1996;76:2661–74.
21. Al-Chaer ED, Westlund KN, Willis WD. Nucleus gracilis: an integrator for visceral and
somatic information. J Neurophysiol 1997;78:521–7.
22. Samso E, Farber NE, Kampine JP, et al. The effects of halothane on pressor
and depressor responses elicited via the somatosympathetic refl ex: a potential
antinociceptive action. Anesth Analg 1994;79:971–9.
23. Sato A, Schmidt RF. Somatosympathetic refl exes: afferent fi bers, central pathways,
discharge characteristics. Physiol Rev 1973;53:916–47.
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doi: 10.1136/acupmed-2011-010034
published online December 5, 2011Acupunct Med
Sven Schroeder, Gesa Meyer-Hamme and Susanne Epplée
using neurography
peripheral neuropathy (CIPN): a pilot study
Acupuncture for chemotherapy-induced
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... Rising evidence has highlighted the effectiveness of acupuncture in reducing neuropathic pain [15]. However, both clinical research and practice suggest that response to acupuncture is variable among patients with persistent CIPN [16][17][18][19][20]. In this threearm placebo-controlled acupuncture study for patients with moderate-to-severe CIPN, we prospectively performed QST testing to determine somatosensory characteristic changes. ...
Article
Full-text available
Purpose Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy. Acupuncture is a promising non-pharmacological intervention for CIPN. However, the physiological effects of acupuncture treatment remain poorly understood. We examined the effects of acupuncture on CIPN using semi-objective quantitative sensory testing (QST). Methods We conducted a randomized controlled trial of real acupuncture (RA) and sham acupuncture (SA) compared to usual care (UC) in cancer survivors with moderate-to-severe CIPN. Treatment response was assessed with QST measures of tactile and vibration detection thresholds in hands and feet, thermal detection, and pain thresholds at weeks 0, 8, and 12. Constrained linear mixed model (cLMM) regression was used for statistical analysis. Results 63 patients completed QST testing. At week 8, vibrational detection thresholds in feet were significantly lower in RA and SA (p = 0.019 and p = 0.046) than in UC, with no difference between RA and SA (p = 0.637). Both RA and SA also showed significantly higher cool thermal detection than UC (p = 0.008 and p = 0.013, respectively), with no difference between RA and SA (p = 0.790). No differences in tactile detection, vibrational detection in hands, warm thermal detection, and thermal pain thresholds were detected among the three arms at weeks 8 and 12. Conclusion QST demonstrated different patterns in RA, SA, and UC. After eight weeks of RA, we observed significant improvements in the vibrational detection threshold in feet and cool thermal detection threshold in hands compared to UC. No significant differences were seen when compared to SA. Trial Registration: ClinicalTrials.gov (NCT03183037); June 9, 2017.
... Participants received a standardised 40-minute, weekly acupuncture session. If a participant was experiencing both lower and upper limb CIPN, a maximum of 26 core points would be needled as follows: Eight bilateral core points (LV3, SP6, ST36, EXLE (Ba Feng) and BL60 for lower limb CIPN, as utilised by Abuaisha et al 1998, Ye 2010 andSchroeder et al 2012. Five bilateral core points EXUE (Ba Xie) and LI4 for upper limb CIPN as previously employed by Bao et al 2012 who used Ll4 as the distal and analgesic point. ...
Article
Full-text available
Purpose Chemotherapy-induced peripheral neuropathy (CIPN) is a dose limiting toxicity posing a major clinical challenge for managing patients receiving specific chemotherapy regimens (e.g., Taxanes). There is a growing body of literature suggesting acupuncture can improve CIPN symptoms. The purpose of the ACUFOCIN trial was to collect preliminary data on the safety, feasibility, acceptability and initial effectiveness of acupuncture as a treatment for CIPN, comparing use of acupuncture plus standard care (Acupuncture) against standard care alone (Control). Method At a tertiary cancer centre, a pragmatic, randomised, parallel group design study was used to investigate the effectiveness of a 10-week course of acupuncture. Participants experiencing CIPN of ≥ Grade II, recording a ‘Most Troublesome’ CIPN symptom score of ≥3 using the "Measure Yourself Medical Outcome Profile" (MYMOP 2), were randomised to ‘Acupuncture’ or ‘Control’ arms. Clinicians were blinded to allocated groups, however as it was not possible to blind participants, it cannot be guaranteed they did not disclose study allocation within their clinic assessments. The primary outcome measure was the number of patients reporting a ≥ 2-point improvement (success) in their MYMOP2 score at week 10. 100 participants (120 to allow for attrition) were required for a hypothesised improvement in success proportions from 30% to 55% using a primary analysis model with logistic regression adjusted for stratification factors and baseline MYMOP2 scores. Feasibility and acceptability of study design was addressed through percentage return of primary outcome, retention rate and a nested qualitative study. Results Primary MYMOP2 outcome data at week 10 was available for 108/120 randomised participants; this is greater than the 100 participants required to adequately power the study. There were 36/53 (68%) successes in ‘Acupuncture’ compared to 18/55 (33%) in ‘Control’. Beneficial effects were seen in the secondary outcome data, including clinicians' grading of neuropathy, EORTC, QLQ-CIPN20, QLQ-C30 summary scores and patient reported pain scores. There were no serious adverse events reported within the study and only 16 acupuncture associated events, none of which required intervention. Conclusion A 10-week course of acupuncture resulted in measurable improvement in participants symptoms of CIPN. The results warrant further investigation.
... However, the effectiveness of these approaches has been shown in the management of peripheral neuropathy due to diabetes and HIV in particular (Nicholas et al. 2007;Ihn 2006;Ho and Roblew 2011), but the number of randomized studies investigating the effectiveness of these approaches is few. In a limited number of studies conducted with cancer patients, the effectiveness of acupuncture (Donald et al. 2011;Schroeder et al. 2012), exercise (Wampler et al. 2005), and massage (Cunningham 2011) was evaluated or presented as case reports. Although these results are not sufficient for conclusive evidence, it is believed that these approaches can be effective in reducing peripheral neuropathy. ...
Chapter
Quality of life is a multidimensional concept. Therefore, its assessment includes many parameters ranging from happiness and well-being of individuals to environmental quality and ecological structures. A good symptom management is associated with less symptom formation and thus with a better quality of life. Non-pharmacological interventions typically include various psychosocial, behavioral and environmental strategies that can complete traditional treatment to increase the quality of life for cancer patients.
... After an initial case series involving five patients treated with acupuncture showed improvement in CIPN symptoms [78], additional trials sought to show the benefits of this therapy in CIPN patients. A small pilot study showed improvement in five of six patients with CIPN treated with acupuncture [79], and a small retrospective study of breast cancer patients also suggested the benefit of this practice for improving CIPN symptoms [80]. A recent randomized controlled pilot trial of forty women treated with taxanes for breast cancer who developed CIPN showed that those who underwent an 8-week acupuncture treatment regimen had significant improvement in neuropathic pain and sensory symptoms [81]. ...
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Opinion statement Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity associated with treatment with platinum-based agents, taxanes, vinca alkaloids, and other specific agents. The long-term consequences of this condition can result in decreased patient quality of life and can lead to reduced dose intensity, which can negatively impact disease outcomes. There are currently no evidence-based preventative strategies for CIPN and only limited options for treatment. However, there are several strategies that can be utilized to improve patient experience and outcomes as more data are gathered in the prevention and treatment setting. Before treatment, patient education on the potential side effects of chemotherapy is key, and although trials have been limited, recommending exercise and a healthy lifestyle before and while undergoing chemotherapy may provide some overall benefit. In patients who develop painful CIPN, our approach is to offer duloxetine and titrate up to 60 mg daily. Chemotherapy doses may also need to be reduced if intolerable symptoms develop during treatment. Some patients may also try acupuncture and physical therapy to help address their symptoms, although this can be limited by cost, time commitment, and patient motivation. Additionally, data on these modalities are currently limited, as studies are ongoing. Overall, approaching each patient on an individual level and tailoring treatment options for them based on overall physical condition, their disease burden, goals of care and co-morbid health conditions, and willingness to trial different approaches is necessary when addressing CIPN.
... Clinical studies have shown that EA can improve the pain, numbness, tingling, and nerve conduction rate of chemotherapy patients. 22,28 Studies have shown that the decrease of spinal GRK2 completely reverses the therapeutic effect of EA on inflammatory pain. 29 In this study, EA increased the expression of GRK2 protein in spinal dorsal horn after cisplatin treatment, and selective downregulation of neuronal GRK2 expression in spinal cord inhibits the regulatory effect of EA on CIPN. ...
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Purpose Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy. Acupuncture is a promising nonpharmacological intervention for CIPN. However, the physiological effects of acupuncture treatment remain poorly understood. We examined the effects of acupuncture on CIPN using semi-objective quantitative sensory testing (QST). Methods We conducted a randomized controlled trial of real acupuncture (RA) and sham acupuncture (SA) compared to usual care (UC) in cancer survivors with moderate to severe CIPN. Treatment response was assessed with QST measures of tactile and vibration detection thresholds in hands and feet, thermal detection, and pain thresholds at weeks 0, 8, and 12. Constrained linear mixed model (cLMM) regression was used for statistical analysis. Results 63 patients completed QST testing. At week 8, vibrational detection thresholds in feet were significantly lower in RA and SA (p = 0.019 and p = 0.046) than in UC, with no difference between RA and SA (p = 0.637). Both RA and SA also showed significantly higher cool thermal detection than UC (p = 0.008 and p = 0.013, respectively), with no difference between RA and SA (p = 0.790). No differences in tactile detection, vibrational detection in hands, warm thermal detection, and thermal pain thresholds were detected among the three arms at weeks 8 and 12. Conclusion QST demonstrated different patterns in RA, SA, and UC. After eight weeks of RA, we observed significant improvements in the vibrational detection threshold in feet and cool thermal detection threshold in hands compared to UC. No significant differences were seen when compared to SA. Trial Registration ClinicalTrials.gov (NCT03183037); June 9, 2017
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When peripheral neuropathy occurs due to chemotherapy treatment, it is referred to as chemotherapy-induced peripheral neuropathy (CIPN). Typically, symptoms are sensory rather than motor and include reduced feeling and heightened sensitivity to pressure, pain, temperature, and touch. The pathophysiology of CIPN is very complex, and it involves multiple mechanisms leading to its development which will be described specifically for each chemotherapeutic class. There are currently no approved or effective agents for CIPN prevention, and Duloxetine is the only medication that is an effective treatment against CIPN. There is an unavoidable necessity to develop preventative and treatment approaches for CIPN due to its detrimental impact on patients' lives. The purpose of this review is to examine CIPN, innovative pharmacological and nonpharmacological therapy and preventive strategies for this illness, and future perspectives for this condition and its therapies.
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Elektromyographische und neurographische Untersuchungen sind in erster Linie bei akuten, intensivpflichtigen neuromuskulären Erkrankungen von Bedeutung. Sie erlauben dabei diagnostische und prognostische Aussagen und können darüber hinaus - z. B. bei der myasthenen Krise therapeutische Hinweise geben. Da die apparative Diagnostik auf der Intensivstation möglichst ohne großen technischen Aufwand und ohne wesentliche Belastung des Patienten erfolgen sollte, werden in diesem Kapitel nicht alle verfügbaren Untersuchungsmethoden besprochen; vielmehr erfolgt eine Beschränkung auf einfache und rasch durchführbare Verfahren, die in der Regel ausreichen, um eine klare Diagnosenstellung zu ermöglichen. Die wichtigsten Indikationen zu elektromyographischen und neurographischen Untersuchungen in der Intensivmedizin sind in Tabelle 8.1 zusammengefaßt.
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