Acupuncture in PD 2021

Inspired by Brandín-de la Cruz et al 2021,[1] Pereira et al 2021,[2] and Park et al 2021.[3]

Dopamine – carbon (yellow), oxygen (red), nitrogen (blue) and hydrogen (gold).

PD – Parkinson’s disease
RCT – randomised controlled trial
DN – dry needling
TrP – trigger point
1Hz DN – insertion of the needle once every second
TUG – timed up and go (test)
10MWT – 10m walking test
6MWT – 6 minute walking test
UPDRS – universal Parkinson’s disease rating scale
APs – acupuncture points
RNA – ribose nucleic acid (transcribed sequences from DNA, hence transcriptome)
qPCR – quantitative real-time polymerase chain reaction
SYN1 – synapsin 1 (a phosphoprotein in synaptic vesicles)
ANKRD22 – ankyrin repeat domain 22 (ankyra is Greek for anchor)

key to acronyms

This is now my fourth blog including PD, so I have created a category – PD.

As I have said before, I am not hopeful that acupuncture has either substantial or useful effects in this condition, but I am more open to the possibility of modest effects beyond expectation alone. Expectation appears to have substantial effects in some patients, as I have noted in: Acupuncture in PD 2020.

The three papers I am highlighting all came out in September 2021, and none of them inspired me sufficiently on their own, but on review of my list of recent potentially interesting papers, 3 in the same fortnight on PD made the topic worth another mention here.

The first of these 3 papers comes from Zaragoza in Spain. It is a small parallel arm RCT of a single session of DN versus a non-penetrating sham. Interestingly the sham method is almost identical to one I discussed with Thomas Lundeberg at a conference nearly 20 years ago. At the time I was considering the idea of engaging in primary research and did not want to ‘miss the point’ in my control group.

My idea was to simply snip the sharp end off a standard needle and press it gently into the skin over a TrP repeatedly in the same way as I would when performing real DN.

In this case they used a long metal handled needle, snipped off the whole of the needle shaft and then sanded down any rough edges.[4] I guess there would be less chance of skin penetration with this method.

37 patients with PD were randomised to either real or sham DN and after baseline measures received a minute of 1Hz DN at TrPs in four muscles of each lower limb: semitendinosus, medial gastrocnemius, soleus and rectus femoris.

TUG – timed up and go (test)

The outcome measures included functional tests (TUG, 10MWT, 6MWT), myotonometry and a rating scale for PD (UPDRS).

There were no between group differences, although there were a few significant within group changes in the real DN group, but none of these reached a size that would be considered clinically relevant.

The second paper comes from Porto in Portugal. This is similar in that it measured the immediate effect of needling compared with a sham, but the needling was performed at APs rather than TrPs and the sham was superficial needling away from known APs. This was a small (n=7) cross-over trial with a 15-day washout period, and the outcomes were measured with a gait analysis tool. Cross-over trials have advantages in terms of statistical power, but drawbacks in terms of possible long-term effects and unblinding. The latter in this case through an individual patient spotting the difference between the two needling approaches. There was no mention of any test for blinding in the participants, and the paper acknowledges that the results were evaluated by an unblinded researcher.

There were several highly statistically significant changes following real acupuncture, but these were presented as within group changes with no mention of any statistical correction for multiple testing. Whilst there was the potential for both performance and detection bias, the main outcomes were objective measurements from a gait analysis device, so the unblinded observer may have had less potential to influence proceedings than the motivation of an unblinded individual patient.

We have to be very cautious about drawing any conclusions from these rather small trials, apart from noting that the better-quality trial was not able to demonstrate a clear effect.

Turning to the last paper for something different, this one comes from Korea, and is an exploratory study using gene transcriptome analysis on blood samples from patients in a previous trial of acupuncture for PD.[5] The previous trial was mentioned here before: Acupuncture in PD 2020. Eight sessions of acupuncture were performed, and blood samples were collected before treatment, and after both 5 and 8 sessions. Whilst there were 26 PD patients in the trial, only 6 had blood samples at each time point that met the parameters required for the study ie sufficient RNA to perform an analysis.

Of those 6, one patient was chosen based on functional outcomes from the trial and full RNA sequencing was performed. This was done to identify potential targets of interest in the transcriptome, which were then used for quantitative (qPCR) assessment of changes in the blood of the other 5 patients. Finally these changes were correlated with the functional improvements in the same patients at the 2 follow-up time points after 5 and 8 sessions.

In summary, 3 targets in the transcriptome that are consistently downregulated in PD were shown to be increased in the transcriptome of the chosen patient, and a further target of interest was identified based on it being a post-mortem biomarker for PD that increased dramatically in the transcriptome of the chosen patient. The increases in 2 of these 4 biomarkers (SYN1 & ANKRD22) in the qPCR of the 5 other patients correlated positively with their functional changes following acupuncture treatment.

functional benefits in PD patients are rather modest

That all sounds quite encouraging, and perhaps not surprising, but it is merely observational, with no inferences on causality possible. We should also remember that the functional changes measured in PD patients are rather modest and probably don’t reach the level of clinical relevance.

The bottom line for me is that I will be continuing my policy of not offering acupuncture treatment to patients with PD, at least not for the PD symptoms.

References

1          Brandín-de la Cruz N, Calvo S, Rodríguez-Blanco C, et al. Effects of dry needling on gait and muscle tone in Parkinson’s disease: a randomized clinical trial. Acupunct Med Published Online First: 19 September 2021. doi:10.1177/09645284211039232

2          Pereira CR, Criado MB, Machado J, et al. Acute effects of acupuncture in balance and gait of Parkinson disease patients – A preliminary study. Complement Ther Clin Pract 2021;45:101479. doi:10.1016/j.ctcp.2021.101479

3          Park S, Kim A, Park G, et al. Investigation of Therapeutic Response Markers for Acupuncture in Parkinson’s Disease: An Exploratory Pilot Study. Diagnostics 2021;11:1697. doi:10.3390/diagnostics11091697

4          Mitchell UH, Stoneman P, Larson RE, et al. The Construction of Sham Dry Needles and Their Validity. Evid-Based Complement Altern Med ECAM 2018;2018:9567061. doi:10.1155/2018/9567061

5          Jang J-H, Park S, An J, et al. Gait Disturbance Improvement and Cerebral Cortex Rearrangement by Acupuncture in Parkinson’s Disease: A Pilot Assessor-Blinded, Randomized, Controlled, Parallel-Group Trial. Neurorehabil Neural Repair 2020;34:1111–23. doi:10.1177/1545968320969942


Declaration of interests MC