By Jonathan Moens June 1, 2022
The visual display of the Neurolith device helps clinicians know what brain regions they are targeting using sound waves. STORZ MEDICAL
BERLIN — Looking more like a barber than a doctor, orthopedic surgeon Musa Citak squirted gel on his patient’s head and massaged the gooey substance into his scalp as though it were shampoo. He then pulled out a handheld device and began sliding it across the side of the elderly man’s head.
“This is shockwave therapy,” Citak explained. As he moved the device, it made rapid clicking sounds, each click a high-frequency sound wave intended to stimulate brain regions and, according to Citak, help regenerate cells and halt the rapid deterioration of the patient’s brain.
Manfred Sköries, 80, has been living with a mixed diagnosis of Alzheimer’s disease, Parkinson’s, and Lewy body dementia since 2012, leaving him with significant memory loss, difficulty walking, and slurred speech. After trying several drug treatments and showing no significant improvements, his family reached out to Citak’s clinic in Berlin, TPS Nord. The clinic’s website promised “a causal treatment of symptoms” and “permanent stopping” of Alzheimer’s disease.
With no cure for Alzheimer’s, Sköries is one of hundreds of patients who have come to Citak in the past year, desperate for help. The treatment, known as “transcranial pulse stimulation,” is largely unproven, but it has exploded far beyond German borders: In just two years, around 85 clinics across Europe, Asia, the Middle East, and the United States have begun offering the therapy. Storz Medical, the Swiss-based manufacturer of the device, said at least 1,500 patients in 23 countries have undergone a total of about 10,000 treatment sessions.
Twenty minutes and 6,000 pulses later, Sköries’ therapy was complete. He looked exhausted, but his family was thrilled. This was his ninth session and his family said they have witnessed stunning results: Before the treatment, Sköries was silent, unresponsive, and moved mostly in a wheelchair; now he sometimes walks up and down stairs, bursts into conversations, and has regained a sense of humor, they said.
“We are really convinced by the results,” said Maik Sköries, Manfred’s grandchild. “For us, this is the real deal.”
Yet anecdotes aren’t sound evidence, and the science behind TPS is far from convincing, experts say. Studies of its efficacy are limited and their methods questionable, and there’s no real understanding of how the technology acts on the brain beyond speculative theories, experts say. The treatment is also largely unregulated and expensive, costing thousands of dollars that patients have to pay out of pocket. Critics accuse clinicians adopting the technology and Storz Medical of taking advantage of families desperate for help.
“They’re raising false hopes,” said Robert Howard, professor of old age psychiatry at University College London. “I hesitate to use the word quackery, but this is not scientific evidence-based medicine.”
Major Alzheimer’s organizations are also skeptical. “It’s concerning that claims are being made which describe TPS as ‘clinically proven’ to reduce the symptoms of dementia. To our knowledge there is no convincing evidence to justify this,” said Tim Beanland, head of knowledge management at the Alzheimer’s Society, a leading dementia charity based in the United Kingdom.
TPS has its roots in “shockwave therapy”— repetitive acoustic pulses that generate pressure waves — which was first used at high energy levels in medicine to pulverize kidney stones. With the advent of lower-energy pulses, the technology quickly became an all-purpose therapy, with uses ranging from joint and back pain to erectile dysfunction. More recently, Storz Medical devised a new shockwave device, which it calls Neurolith, that can target another organ: the brain.
Many of the brain regions most affected by Alzheimer’s and Parkinson’s lie deep inside, but Storz says its shockwaves can penetrate up to 2 to 3 inches beneath the skull.
The key research cited by proponents of the therapy was led by Roland Beisteiner, an associate professor of neurology at the Medical University of Vienna, who conducted a series of experiments that were partly funded by Storz Medical and sometimes in collaboration with company researchers.
In a pilot study with no control group, Beisteiner reported in 2019 that after two to four weeks of TPS treatment, 35 Alzheimer’s disease patients showed significant improvements on a test of memory and speaking abilities. The effects lasted at least three months. A follow-up study analyzing 17 of these patients’ brain scans showed that these improvements were associated with a reduction in degeneration in brain networks implicated in Alzheimer’s disease. And in a paper published this past February, the team found that these same patients’ depression scores dipped after two to four weeks of TPS treatment.
But critics say the science is still premature. Only a handful of studies have looked at the effects of transcranial pulse stimulation specifically on Alzheimer’s patients. None was a double-blind randomized controlled trial — the gold-standard scientific method used to evaluate whether a treatment is effective — nor did any look at its long-term effects beyond three months.
Typically, such studies would control for the placebo effect by, for example, probing some patients with a real device and another group with a fake or “sham” device that mimics the sound and feel of TPS. But the studies so far have not done this in clinical trials, said Peter Whitehouse, professor of neurology at the University of Toronto.
The studies also reuse a small group of Alzheimer’s patients that vary wildly in the severity and nature of their conditions, making it hard to discern the true benefits of the treatment. Many patients in the 2019 study, for instance, had comorbidities like depression, panic disorder, coronary heart disease, and suspected epilepsy.
“This technology may turn out to be very effective. It may turn out to be terrific,” said Michael Gusmano, a professor of health policy at Lehigh University in Pennsylvania and author of a book on medical devices. “But at this stage, I don’t think we have adequate evidence.”
“This technology may turn out to be very effective. It may turn out to be terrific. But at this stage, I don’t think we have adequate evidence.”
MICHAEL GUSMANO, PROFESSOR OF HEALTH POLICY AT LEHIGH UNIVERSITY
Beisteiner and Storz Medical reject these criticisms, saying the evidence is already sufficiently strong to warrant selling the product widely, especially since Alzheimer’s patients have no viable alternatives. “The safety is proven and the clinical effectiveness of the treatment is proven,” said Thi-Lan Freedman, a management trainee for Storz Medical.
While she acknowledged that the studies are imperfect, she said that larger-scale clinical trials using more rigorous methods are ongoing and that the company gets regular feedback from clinicians that patients are showing great benefits. Freedman contended that obtaining “CE marking” in 2018 — a designation that allows medical devices to be commercially sold in Europe — also testifies to the technology’s clinical efficacy.
“CE marking,” however, hardly constitutes a guarantee of clinical efficacy, experts say. The evaluation process is focused on safety and is conducted by private organizations accredited by an EU country known as “notified bodies.” They have notoriously low standards for evaluating whether a treatment works for medical devices, said Tom Joyce, professor of orthopedic engineering at Newcastle University in the U.K. The evaluation process is also largely invisible to the public, meaning manufacturers cannot be held accountable.
“We know very little about the CE mark,” said Joyce. “The product gets it and, on what evidence it got the CE mark in Europe, we know virtually nothing.
The lack of stringent regulations on medical devices has led to major scandals in Europe. In one case, TÜV Rheinland, the notified body in Germany that granted CE marking to Neurolith, certified faulty breast implants filled with cheap, industrial-grade silicone that affected 400,000 women, many of whom suffered from infections and had to have the implants removed.
TÜV Rheinland did not respond to questions about its evaluation process with Neurolith, citing client confidentiality.
“This is just not a treatment that’s got a demonstrated clinical efficacy base,” said University College London’s Howard, who is convinced that the alleged benefits of the treatment could simply be attributable to a placebo effect, which tends to be particularly strong in Alzheimer’s patients desperate for an effective treatment.
Some clinicians who offer TPS readily admit that the science is lacking. Mohamed Abdelghani, a consultant psychiatrist who offers the treatment at his private clinic, Dyad Medical, in London, said the evidence is “limited.” But he and others justify offering the treatment largely because CE marking confirms its safety and the intervention lasts only about two weeks, so patients can stop immediately if they don’t see any benefits.
Of the around 10,000 sessions conducted since Neurolith’s release in 2018, there have been no reports of serious adverse effects, according to Storz Medical. Beisteiner’s studies also showed that only a small proportion of patients experienced minor side effects like headaches and mood decreases, and that rat brains stimulated at energy levels up to 150 times that used in humans showed no brain damage.
“The good thing is that either it works or it does not — you don’t damage [the brain]. There is no real disadvantage to the patient,” said Citak, of TPS Nord.
Howard, however, said that studies on patients lasting only three months aren’t long enough to ensure the treatment is safe for patients. There may be a cumulative effect of TPS that harms the brain, added Whitehouse.
Surgeon Musa Citak treats Manfred Sköries with the Neurolith device in his Berlin clinic. JONATHAN MOENS FOR STAT
Even if the risks of physical harm turn out to be negligible, experts say patients face other kinds of harm. The full treatment generally costs between $3,000 and $6,000, depending on the clinic, and there is currently no health insurance — public or private — that covers these costs, said Manfred Schulz, director of business development and neurology at Storz Medical. Storz Medical is negotiating with German insurance companies to try and convince them to cover the treatment. Patients pay hundreds of dollars more for additional “booster” sessions if they are deemed necessary.
For a disease that is already highly burdensome, it would be wiser to use that money to improve the patient’s quality of life, said Thomas Fischer, professor of aged care nursing at the Protestant University of Dresden, in Germany. That may mean remodeling a patient’s home to make it easier to live in, going on a holiday, or hiring a nurse to take care of them.
Beisteiner responded that a “large part of patients ask for treatment repeats, indicating that they judge TPS as good value for their money.”
The Neurolith is largely unregulated in the countries where it’s used. The device is sold to private clinics with an accompanying instruction manual, but clinicians don’t get training and sometimes go off-script.
This is the case with Citak, who uses TPS as an “off-label” treatment for patients with Parkinson’s disease and depression, despite there being no published evidence for its use in these conditions. He said he stimulates brain regions that he has personally mapped out and keeps confidential to prevent competition from other clinicians. “We don’t tell,” he said. “Secret.”
Until this week, his clinic’s website stated that TPS has been approved by the Federal Institute for Drugs and Medical Devices, Germany’s regulatory body for health products, and that private insurers were therefore required to cover the costs, when in fact it merely was granted the CE mark by TÜV Rheinland, a private entity.
After the misstatements were pointed out by STAT, Citak’s clinic agreed that the information was incorrect and they were taken down on Monday. “Musa is a doctor and not an expert in licensing — he does not have to be,” said Katja Schmidt, project manager at the clinic.
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The operator of a Florida clinic offering TPS uses a similarly broad approach to using the technology. Boris Kawliche, a psychiatrist who has been offering TPS at Brandon TMS and Psychiatry since November, said he is the only clinician in the U.S. to own a Neurolith and has treated about 10 patients with various conditions, including Alzheimer’s, traumatic brain injury, aphasia, depression, and Parkinson’s. All patients were treated in exactly the same way, despite significant differences in the underlying causes of their illnesses and their symptoms.
His results, which haven’t been published or peer-reviewed, have been mixed, he said: Some patients show virtually no sign of change. Others, like a Parkinson’s patient in his mid-70s, showed remarkable, though temporary, improvements; before treatment he was withdrawn and unable to walk. After a couple of sessions, he was greeting people and walking long distances, the doctor claimed.
“Unfortunately, he got home and the effects lasted only two weeks,” Kawliche told STAT.
Neurolith is not approved by the U.S. Food and Drug Administration. Schulz said Storz Medical is working with its New York-based distributor, Soterix Medical, to apply to the FDA to use the device for investigational purposes in the U.S., and to obtain approval of an institutional review board (IRB).
Nevertheless, Kawliche said Soterix sold him the device for around $100,000, with Storz Medical’s approval, and told him that the FDA would allow him to treat patients if he conducted a study that followed Beisteiner’s methods and worked toward obtaining approval of the study from an IRB. He didn’t have the resources to carry out this study, Kawliche said, but he began treating patients after consulting a lawyer. (The lawyer denied telling Kawliche he could treat patients with TPS.)
Study sponsors typically have to get IRB approval before studying medical devices on patients to ensure that experiments are conducted ethically and that patients are properly informed of the potential risks and consent to participate in a study. Proceeding without such approval “is not permitted,” said Diana Zuckerman, president of the National Center for Health Research.
An FDA spokesperson said the agency typically does not comment on the use of a device that has not been approved or cleared.
Storz Medical initially told STAT it shipped one Neurolith to the U.S., to Soterix, so that it could be used for demonstration purposes. Schulz later acknowledged that Kawliche may have purchased this device when STAT pointed out that Kawliche had posted multiple images of himself on LinkedIn posing with a Neurolith at his Florida clinic over the past year.
Schulz said the company has many users of its devices across the world so “it’s impossible to know what everyone is doing. But he [Kawliche] seems to be a special case.”
Storz Medical and Soterix claim they were not aware that Kawliche was treating patients and that he shouldn’t have done so. Yet both were in regular contact with Kawliche and multiple Storz Medical employees reacted to and commented on social media posts of the Florida clinician describing his experience using the device on patients.
Not all clinics have been so loose with how they use TPS. Abdelghani, the London psychiatrist, said his clinic has had 20 inquiries in the past year, but only one patient has started treatment with the technology after screening. People with severe Alzheimer’s aren’t eligible to ensure they have the capacity to consent. The consent form includes information that highlights the lack of clinical evidence behind the treatment and the possibility that any benefits experienced may be due to a placebo effect.
Not being cautious like this risks backfiring, he said. “I think this should be done not only to protect patients, but to protect the technology.”
But others say caution and transparency are not enough. Under the current system, medical devices in Europe can enter the market with little to no scrutiny of their clinical efficacy. Joyce, of Newcastle University, said the process needs to be more transparent so that patients and policymakers can evaluate the evidence themselves. A framework for this sort of transparency already exists, but it won’t make posting information in the database mandatory until late 2023.
The European Union’s lax medical-device regulations are underpinned by a moral duty to provide seriously ill patients with new technologies as soon as possible, especially if there are no alternatives. However, a slower, more deliberative approach may actually be more conducive to helping these patients in the long run, said Lehigh’s Gusmano.
“New isn’t always better,” he said. “This isn’t about trying to inappropriately slow the use of technology. It’s about trying to most appropriately select and use those technologies that are actually good value.”
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