Brown-Séquard syndrome - a serious blow to the spinal cord

888 11 min.

72-year-old Collège de France professor Charles Brown-Séquard reported his feelings in 1889 at a meeting of the Societe de Biologie (Scientific Biological Society of Paris). The sensations, he said, were short-lived, but strong: enlightenment of the mind, an increase in physical strength and potency. The reaction of his colleagues in the scientific society was also strong: “Lecture (Brown-Sequard. - Kommersant-Science"

) once again proves that it’s time for professors to retire after 70 years.”

Photo: DeAgostini/Getty Images

Photo: DeAgostini/Getty Images

Placebo effect

Professor Brown-Séquard was an authoritative scientist of his time. Member of the Royal Society of London, successor to the famous Claude Bernard at the Societe de Biologie, his experiments on partial excision of the spinal cord (Brown-Séquard syndrome) are still considered classic in the history of surgery, and in the history of science he is considered one of the founders of endocrinology and hormonal therapy. However, his simple experiment with injecting himself with an aqueous suspension of animal germ cells was ridiculed by scientists. The solution to man’s age-old dream of regaining youth and ultimately achieving immortality seemed too simple to them. The professor's misconception about the enlightenment of the mind and potency was attributed to his self-hypnosis, as happens when taking a placebo (dummy pill): a person sincerely believes that it will help, and it helps.

Nevertheless, Brown-Séquard gained followers. In the first decades of the last century, in different countries, including Soviet Russia, experiments were conducted on transplantation of gonadal cells in animals and humans. The most famous “rejuvenator” of that time was the French surgeon Sergei Voronov, whose Michurin method of grafting fragments of chimpanzee and baboon testicles onto human testicles received official approval from both the world medical community and the French authorities. True, the clinic through which the main flow of Voronov’s patients passed was, just in case, moved from continental France to French Algeria. There he began grafting monkey gonads into women. Doctor Voronov’s patients were wealthy, and Voronov himself quickly became quite wealthy.

Over time, it became clear that “monkey Viagra” did not produce results. The flow of wealthy and, most importantly, influential patients dried up, and immediately Dr. Voronov’s scientific colleagues began to doubt his method. As in the case of Professor Brown-Séquard, they explained Voronov’s dubious successes by the placebo effect, and then completely declared him a “swindler.” In the 1940s, his method was banned in France.

Symptoms

Depending on the mechanism of occurrence, the pathology is manifested by a number of characteristic signs. Changes are noticeable not only on the affected part of the body, but also on the healthy one. Patients note the following changes in the body:

• Paralysis of the body below the level of the vertebral lesion.
• Loss of touch, temperature, or pain sensation.
• The patient is unable to feel his body weight, vibrations, or passive movements.
• The skin is bright red and cold to the touch.
• Trophic disorders of varying severity.

Pathology can be recognized by decreased sensitivity or limited motor activity on one side of the body. Some people have no symptoms, this is due to the individual characteristics of the body.

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Affects the manifestation of the disease, localization zone:

• 1-2 cervical vertebrae. Paralysis of the arm, decreased sensitivity of the facial skin, loss of muscle sensitivity to irritants. A limb on the opposite side of the body begins to fail, and the normal sensation when touching the face, shoulders or neck disappears.
• 3-4 cervical vertebrae. Spastic paralysis on the injured side of the limb, dysfunction of the diaphragmatic muscles. On the part of the healthy part of the body, there is only a slight decrease in the susceptibility of the limbs to external stimuli.
• 5th cervical – 1st thoracic vertebra. Paralysis of the affected part, the patient loses the ability to move normally, and deep sensitivity disappears. On the second part of the body, the ability to superficially sense irritating factors disappears.
• Thoracic region from 2 to 7 vertebrae. The patient loses the ability to move the leg on the side of the ridge injury, and tendon reflexes disappear. Deep sensitivity disappears in the lower part of the body. The same applies to the skin of the leg, buttocks and lumbar region on the healthy side.
• Lumbar and sacrum. Motor function is lost, as well as deep sensitivity of the lower limb. Sensation disappears in the perineal area.

One of the important diagnostic indicators is the absence of dysfunction of the pelvic organs. Even if one side is paralyzed, the other ensures normal bladder emptying and defecation. Only in this case can the doctor suspect unilateral spinal cord injury.

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Sheep spring

It was no longer so easy for scientists to dismiss the experiment of Swiss doctor Paul Niehans. In 1931, Niehans injected a suspension of calf parathyroid gland cells into a woman dying on the operating table, whose surgeon, when removing the thyroid gland (in those years, a routine operation), also mistakenly removed two pairs of small parathyroid glands adjacent to the thyroid gland from behind. The woman fell into a state of tetanus, that is, all her muscles tensed and did not relax. After Dr. Niehans' injection, they relaxed and the patient was saved.

The placebo effect was excluded here, but the simplicity of the method remained. The doctor continued his experiments, but with cells from sheep embryos, that is, embryonic stem cells in modern terminology. He also had no shortage of patients, mostly cancer patients. Dr. Niehans charged dearly for treatment and also became rich. In 1953, Pope Pius XII appointed him to the Pontifical Academy of Sciences. But over time, it became clear that the Niehans method did not give more significant results than the one-time removal of tetanus and, as is now clear, could not give. In the 1980s, his methods were banned, first in the United States and then in other developed countries.

Today, Niehans and Voronov are often included in lists of “the most famous charlatan doctors,” which is clearly unfair. Then it is necessary to include in these lists a good hundred outstanding scientists from different times and peoples who tried, at the level of knowledge of their time, using different methods to stop the aging process of the body and restore damaged or lost organs and tissues of patients as a result of diseases and injuries. Some methods, such as blood transfusions and bone marrow transplants, have given brilliant results and have become part of the practice of modern medicine.

Reasons for the development of the disorder

A variety of factors can provoke the development of diseases of the spinal cord and spine, but among the entire list, special attention is given to the following:

1. The most common causes of the disease are various bruises, fractures and dislocations of the spine and spinal cord . Usually a person gets them as a result of a traffic accident, while playing sports or performing heavy physical work.
2. The presence of a neoplasm in the spinal cord or spine (it does not matter whether it is benign or malignant).
3. Development of infectious or inflammatory myelopathy .
4. Radiation damage to the spinal cord .
5. A change in the normal level of blood circulation in the spinal cord (becomes a consequence of a stroke or epidural hematoma).
6. Contusion of the spinal cord (spinal cord).
7. Progression of multiple sclerosis.

Regardless of the influence of unfavorable factors that provoked the development of pathology, there are risk factors that, in turn, also pose a danger to human health. These include:

• traumatic syndrome;
• the presence of tumors and neoplasms;
• hematogenous syndrome;
• infectious and inflammatory processes in the body.

The further treatment and recovery of the patient depends on how correctly the specialist determines the causes and types of the disease.

The Birth of Regenerative Medicine

Another thing is a universal remedy for the regeneration of the human body. He didn’t exist and still doesn’t exist to this day. But this does not mean that his search has stopped. On the contrary, they constantly went and are going now. At the turn of the 1970s and 1980s, what happened in the finale of Karel Capek’s comedy “The Makropoulos Remedy” happened. There, the young heroine resolutely burns the recipe for the elixir of eternal youth of the medieval alchemist Hieronymus Makropoulos. Against the backdrop of accumulated scientific data, it finally became clear to scientists that direct cell transplantation is a dead end. Cells require special preparation before transplantation for it to be successful and produce results. In short, everything that happened before had to be forgotten and started from scratch.

Thus, modern cell therapy was born, and a short time later a whole new field of medicine emerged, where cell therapy occupies a central place. Only now tissue engineering has been added to it, when a tissue or organ is created using 3D bioprinting from synthetic or natural materials (for example, collagen protein, the main structural element of connective tissue). Gene therapy has also been added - the same cell therapy, but using genetically modified cells. Finally, drugs based on natural molecules of cytokines and nerve growth factors (NGF) and skin epidermal growth factors (EGF) have appeared. They called the new science regenerative medicine.

Treatment of the disease

For comprehensive treatment of the syndrome, it is important to establish the cause of its development. If it is a hematoma or tumor, surgery is prescribed to eliminate it. It is important to restore the integrity of the spinal column, as well as eliminate the possibility of compression or damage to the spinal cord and nerve endings. Treatment is carried out only surgically, and the earlier the manipulation is prescribed, the lower the risk of complications.

The main goal of surgery is to eliminate compression and all factors affecting the brain, nerve endings, and blood vessels. The type of operation is selected individually, based on the cause of the disease. After the procedure, a rehabilitation course is selected for the patient. Typically it includes:

• Taking medications - these can be vitamin complexes, drugs that improve blood circulation in the brain tissue, as well as tablets to prevent thrombosis.
• Therapeutic exercise – performing special exercises allows you to get rid of pain, normalize blood circulation, improve the elasticity and mobility of the spine.
• Physiotherapy can be various techniques that improve metabolic processes in tissues through the effects of current, laser or magnetic fields. They are carried out using special equipment and only under the supervision of specialists. The most popular manipulations are ultrasound, electrophoresis, UHF therapy, paraffin baths and magnetic therapy.
• Massage – by influencing soft tissues, it is possible to improve blood circulation in the affected area, normalize the movement of biological fluids, and speed up metabolism. The session should only be performed by an experienced, qualified specialist so as not to harm the patient.
• Diets – Proper nutrition is an important part of restoring cartilage health. The menu is developed individually, taking into account individual characteristics and the presence of chronic pathologies.

The pathology is dangerous due to its complications, therefore it is strictly forbidden to self-medicate, change the dosage of drugs, or the number of approaches when performing physical therapy exercises. Only strict adherence to all recommendations allows you to maintain normal motor activity and slow down the progression of pathology.

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Expensive medicine

Modern methods of regenerative medicine (RM) are figuratively “licensed” by the dozen or so Nobel Prizes in Physiology or Medicine received by their authors between the 1980s and 2012. But the first cell therapy drugs licensed and approved for use by the national regulator appeared only in 2001–2002 in South Korea and Singapore. These were Chondron from the South Korean company Sewon Cellontec and Cartogen from the Singaporean company Mercy Tissue Engineering, both drugs were almost identical and contributed to the restoration of knee cartilage.

In the first decade of this century, South Korean companies introduced five more drugs to the market, which had no competitors on the market, except for one already mentioned Singaporean and one Japanese drug JACE from J-TEC for the treatment of burns and skin scars (2007). The monopoly of the countries of Southeast Asia in this area was associated with the peculiarities of their legislation, which created a most favored regime for the national industries of the Republic of Moldova.

The situation changed at the beginning of the current decade; in 2010–2012, four drugs from American companies approved by the US Food and Drug Administration (FDA) entered the market: Provenge from Dendreon Corp. (treatment of prostate cancer), Laviv by Fibrocell Technologies (an aesthetic medicine drug for eliminating nasolabial folds, essentially “Botox” for the rich), MACI by Vericel Corp. (knee cartilage repair) and Gintuit from Organogenesis Inc. (restoration of the oral mucosa).

This was a turning point in the attitude of big business towards the Republic of Moldova. As The Economist magazine wrote in 2013, “after many years of promises, the Republic of Moldova is getting closer to delivering results (profit for investors. - Kommersant-Science”

)". Large pharmaceutical and biotechnological companies are entering the Moldovan market to replace private investors and speculators. In addition, in the United States, $2 billion was allocated from the Federal Reserve to financially support the development of PM drugs. After the 2008 crisis, the market in the Republic of Moldova and in the EU began to grow. Here, the UK and Germany are leading in attracting capital.

Today, 44 cellular, tissue-engineering and gene therapy drugs have been approved for use in the world. It is difficult to keep track of all the new products of the Republic of Moldova: the situation is changing very dynamically. But one thing is for sure: even such drugs as Kymriah and Yescarta are in demand, the course of treatment of which costs from $364 thousand to $475 thousand.

Effective patient rehabilitation

Patients with this symptom complex require a certain amount of time to recover after undergoing surgery.

During the rehabilitation period it is shown:

• performing special exercises;
• undergoing physiotherapeutic procedures;
• following a well-planned diet;
• calmness and avoidance of stress.

An important role is played by physical therapy exercises. Its effectiveness cannot be underestimated.

Thanks to exercise therapy:

1. Metabolic processes are being improved.
2. Blood microcirculation is activated.
3. The muscle frame is strengthened.

The doctor determines individually how many exercises should be performed and in what sequence. To achieve a speedy recovery, the patient requires physical therapy.

Rehabilitation includes:

• paraffin applications;
• heating with ozokerite;
• electrophoresis using potassium iodide;
• diadynamic currents;
• ultrasound;
• UHF therapy.

In the long term, patients often experience partial or complete neurological recovery.

Ours and others

Modern RM has one more specificity that distinguishes it from classical therapy. All PM products are divided into autologous (personalized, obtained from the material of a specific patient and intended for use only by him and no one else) and allogeneic (donor, such as Brown-Séquard, Voronov and Niehans used, only their donors were animals).

A priori, it was believed that autologous products are more effective (the stem and other cells in them are, after all, their own, native). Today, among the PM drugs approved by regulators, approximately three quarters are autologous and only a quarter are allogeneic. But no evidence of greater effectiveness of autologous drugs and products has yet been obtained.

Allogeneic cells, meanwhile, have a number of significant advantages. They require less labor in production, to obtain a cell preparation, you can use material from young donors or perinatal sources (with age, the number of target cells and their regenerative potential decrease), and - most importantly - they can be produced off the shelf (directly from the pharmacy shelf ), that is, a ready-to-use product.

Medical tourism for the rich

The global market for regenerative medicine is estimated at $13 billion. Against the backdrop of a 1.5 trillion market for traditional medicines, the market share of RM products in monetary terms barely reaches 0.002%, which can be compared with the sales of one “blockbuster” drug. But the point is not in the numbers, the main thing is that large pharmaceutical and bioengineering companies seem to have finally believed in its future.

The US PM market is leading, and the key players in it are Kite Pharma, Novartis, Vericel Corporation, Integra LifeSciences, Wright Medical, MiMedx, Osiris Therapeutics, Stryker Corporation and Spark Therapeutics. All of them, with the exception of the Swiss Novartis, are originally American.

What stands out are the products of the so-called hospital production, that is, those used within one hospital for a specific patient. For them, national regulators make exceptions (hospital exemptions), although they use products that sometimes have not even passed preclinical tests. The leader in hospital production of RM today is Germany. This practice increases the availability of medical treatment for patients, and in some countries, for example, Germany, Israel, China, stimulates medical tourism.

Diagnosis of the disorder

When visiting a medical facility, specialists first collect the patient’s medical history. They are interested in how long ago the symptoms began to manifest themselves and with what intensity they develop.

It is also important to check the presence of various reflexes and sensitivity of all limbs. In order for the diagnosis to be made correctly, with full confidence and confirmation from the doctor, the patient will need to undergo a special course of medical examinations, which will allow them to establish a clear picture of the disease and prescribe competent treatment.

The examination includes:

• X-ray examination (makes it possible to detect spinal damage in the early stages);
• Computed tomography allows you to identify problems not only in bone tissue, but also in muscles, nerve endings and blood vessels;
• MRI (magnetic resonance imaging) today is considered the most informative, as it combines a lot of additional information that cannot be obtained using previously described methods.

Large caliber weapons

In our country, everything, as usual, comes down to bureaucracy and money. RM is an expensive branch of medicine, not only because it is new, but because its modern technologies are still very expensive for their developer, for the manufacturer of the product, and for the consumer.

“Cell products are a “large-caliber” weapon,” says the head of the laboratory of gene cell therapy at the Institute of Regenerative Medicine of Moscow State University. M.V. Lomonosov Pavel Makarevich. — We can’t talk about its mass use yet, these will be quite expensive products. Globally, their prices are very high, reaching several million euros or dollars for the treatment of one patient.”

It is clear that in the current economic situation, it is extremely problematic for domestic producers to rely on raising capital on the open market or borrowed capital; they require government support in one form or another. For the same reason, the domestic consumer is not ready to pay several tens or hundreds of thousands of rubles out of his own pocket for generally routine RM procedures.

In the West, insurance companies also do not always cover the full cost of RM procedures. For example, in Japan, insurance covers only half the cost of autologous skin regeneration for burns using J-TEC's JACE technology (20 epidermal sheets are free for the patient, while for severe burns 40 sheets are usually required).

No stupider than others

The situation in Russia is better in the research area of ​​the Republic of Moldova. “As for financing, everything is simple: a scientist always lacks money. Because ideas are beyond the horizon, and their implementation and receiving grants is a very mundane and even cynical thing, you have to weigh desires and possibilities,” says Pavel Makarevich. “Research is financed by government assignments, funds from the Ministry of Education and Science, grants from scientific foundations and federal targeted programs ( which are currently calculated until 2021 and should be extended). There are also national projects now, but they are still at the launch stage and scientists have not yet “gotten there”.”

The scientific background of the Republic of Moldova in Russia is quite representative by international standards. According to Pavel Makarevich, most of the products that were created by Russian science are intended to restore bone tissue, stimulate the growth of nerves and blood vessels, and there is a separate segment that is dedicated to the regeneration of damaged skin - the treatment of wounds, burns, ulcers.

“In Russia there are also promising developments in the field of cardiology, neurology, treatment of ophthalmological diseases, that is, serious conditions from almost any branch of modern medicine,” says Pavel Makarevich. “For example, at Moscow University, prototypes of cellular products have been developed for the treatment of soft tissue defects, and for this we want to use not just cells in suspension, where they quickly die, but in the form of “layers,” that is, a kind of biological patch.”

Among the leaders in the field of RM, according to Makarevich, one can also highlight the Research Institute of Cytology (St. Petersburg), the Institute of Developmental Biology (Moscow), where work is underway to create unique products for the regeneration of skin and cartilage. At the Almazov Center and the National Medical Research Center of Cardiology (including in joint projects with Moscow State University), experimental developments have been carried out for the treatment of limb ischemia, myocardial infarction and chronic heart failure. In CITO im. N.N. Priorova has a wealth of experience in the regeneration of bones, ligaments, and cartilage.

“Today, three main organizations play a key role in research in the field of PM. This is the Russian Academy of Sciences, Moscow State University. M. V. Lomonosov and the First Moscow State Medical University named after. I. M. Sechenov. However, despite the high centralization, there are active scientific groups in Tomsk and Novosibirsk,” says the director of the Institute of Regenerative Medicine of Moscow State Medical University. I. M. Sechenov Petr Timashev. According to him, the first research stages of developing a biomedical cell product are being successfully carried out by research institutes and universities and are well supported by the Russian Science Foundation and the Russian Foundation for Basic Research.

“But the most difficult stages - transferring technology into production and conducting preclinical and clinical trials - fall almost entirely on the shoulders of the manufacturer. If government support measures were developed, we could talk about accelerating the translation of cellular products into clinical practice. So, most likely, we should expect the appearance of domestic biomedical cell products on the Russian market no earlier than in eight to ten years,” says Petr Timashev.

In other words, in the field of regenerative medicine we are not dumber than others, we are just poorer.

Possible forecast

Doctors cannot give accurate predictions when making such a diagnosis. It is possible to prevent the progression of the disease only if all medical recommendations are strictly followed. In this case, the prognosis is almost always favorable. Approximately 90% of patients retain the ability to move independently and control the functioning of the pelvic organs. Untimely treatment of the pathology threatens the patient with the following pathological conditions:

• dysfunction of the genitourinary organs;
• hematomyelia;
• intense pain in the back and head;
• hemorrhages in the spinal cord;
• chronic migraines;
• spinal cord rupture;
• spinal shock.

In addition, the patient may have problems with potency, reproductive function, urinary or fecal incontinence, and chronic constipation. When an arteriovenous aneurysm ruptures in the spine, acute unbearable pain is observed that cannot be relieved by pills.

Vicious circle

Currently, about a thousand clinical trials (CTs) of PM drugs are being conducted in the world, more than 40% of them are antitumor. The range of pathologies in which PM drugs and agents will be present will expand significantly. At the final stages of CI there are about 90 RM drugs for the treatment of diseases of the nervous system and cardiovascular pathologies, endocrine, metabolic and genetic disorders, hematological pathologies, diseases of the digestive system, genitourinary, respiratory systems, diseases of the ENT organs, lymphatic system, radiation injuries, as well as products for use in surgery and dentistry. In other words, drugs and means of RM will be present in almost all areas of modern medicine and over time will occupy their own niche there, appropriate to their real benefits.

In general, the prospect of regenerative medicine that is foreseeable today is the same as it has always been—since the time of Macropolus and other mythical and real inventors of the “elixir of eternal youth.” A surge of interest, first results, disappointment, search for a solution and, finally, an understanding of the real possibilities of the next version of rejuvenating apples.

Sergey Petukhov