A shock to the system

Researchers at McGill University in Montreal have reported improvement in gait speed in a woman with PSP using transcranial direct current stimulation (tDCS). 

The research findings that I pass along here are generally of high scientific quality.  This one is only a single case report and was published only as a letter to the editor, which typically meets a lower standard in the peer-review process.  But it’s in a good journal and from a well-reputed group with a long record of accomplishment in a closely related field.  Plus, it’s about a low-risk potential treatment of PSP — a disease without much other treatment.  So – good enough for me.

The paper’s first author is Carlos Roncero, MD, PhD, a psychiatrist and psychologist and the senior (i.e., last-named) author is Howard Chertkow, MD.  Both McGill professors have long and distinguished research records.  Dr. Chertkow has worked extensively on tDCS for Alzheimer’s disease and is perhaps most famous for having developed, along with two colleagues, the Montreal Cognitive Assessment (MoCA), a quick test of general cognition that works very well in PSP and other frontal lobe conditions and is used world-wide. 

There has been research before in both tDCS and in transcranial magnetic stimulation for movement disorders, including a bit in PSP.  But the previous work has used arcane physiological variables or speech as their outcome measures rather than gait or balance.

The methods

The procedure consists of passing a weak electric current through the brain, in this case from two electrically negative electrodes (“anodes”) on the skin, one over each deltoid muscle (at the shoulder), to a single positive electrode (“cathode”) atop the center of the head, where the left and right “primary motor cortices” nearly touch.  Nothing pierced the skin – these were just wires ending in 5 x 7-cm (2 x 3- inch) patches held by adhesive. Each deltoid received 2 milliamps of current over 20 minutes per day for 4 consecutive days per week for 3 weeks.  The patient’s gait was tested during the fourth stimulation of the third week and then monthly for 5 months after the stimulation sessions had ended.  As a placebo control, before the first week of stimulation, they gave the patient a week of sham stimulation, with the apparatus in place but the switch off, and considered the gait result at that point to be her baseline.  The nature of the gait test was the time required to walk 24 meters (26 yards) using the same walker that the patient was using at home.  Three clinicians flanked her to prevent falls but did not touch her or the walker.

Here are the results:

Note that the “interval time” on the vertical axis is the time to cover 3 meters, calculated by timing the patient for the 24 meters and dividing by 8.  The average healthy woman of that age (61) walking at maximum speed covers 3 meters in about 1.6 seconds and walking comfortably in 2.3 seconds. (I calculated those times from the reference data in this publication.)  With only sham stimulation, the patient’s time for 3 meters was 11.92 seconds.  It sped up to 9.46 seconds by the end of the third week. The time improved further a month later and further still a month after that, to 7.47 seconds.  After another month, it started to return to baseline and returned a bit further a month later, but then stabilized at about 9.8 seconds for 3 weeks.  So they resumed the stimulation and the next week brought improvement to 8.72 seconds. 

There are some methodological issues. 

Unfortunately, the gait was not tested pre-sham and the patient was not asked if she knew that she had received a sham treatment and when it was given.  If the real stimulation had produced a bit of an electrical sensation in her skin, that could have had a placebo effect with a resulting false-positive result.

Secondly, we don’t know how much, if at all, the speed would have improved beyond that 8.72 seconds if after 5 months had they had given the treatment for the same 3 weeks as the first time.  We also don’t know if this degree of improvement made a difference to the patient’s activities of daily living; nor if it was accompanied by an increased risk of falling not observable over the short time sample of the tests. 

Another caveat is that the gait was assessed using a simple timing of gait speed with a walker rather than with an automated gait analysis system.  Such devices are available commercially and typically have the patient placed in a harness to prevent falls and monitor dozens of variables transduced through electronic contacts embedded in a long walking mat. 

The clinicians with the patient during her walking tests were aware of whether she was receiving sham or real treatment and could have unconsciously influenced her performance. 

Bottom line

In summary, this harmless electrical stimulation procedure may eventually prove to give moderate improvement in gait speed in people with PSP, with long-term retention of benefit.  This result could serve as justification for a grant to study the issue in a larger group of patients and using more rigorous procedures and an assessment of improvement in the patients’ activities of daily living.

The methodologic informalities I’ve complained about are standard in exploratory research, which I’m sure is why this prestigious journal’s editor accepted the manuscript.  This is a good example of how science doesn’t just come up with new knowledge, “eureka!”-style.  The process is full of fits and starts, blind alleys, disagreements, human error, and lots of sweat, with one piece providing a toehold for the next until something useful emerges and is confirmed by others.   

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