Hamstring grafts are tenogenic constructs for ACL reconstruction and Pulsed Electromagnetic Fields improve tendon specific markers expression. An in-vitro study.

Hamstring tendons represent one of the commonest autologous graft used during ACL reconstruction. The harvest of the tendon and the time of tendon processing on the operating table, together with the pretensioning maneuvers and the permanence out of the joint during the time of surgery, might impair tendon derived cells (TCs) viability. The aim of the study was: i) to assess the effective viability of the TCs at the end of the surgical procedure; ii) to investigate if TCs viability and the expression of tendon specific markers may be improved through exposure to prolonged pulsed electromagnetic fields (PEMF) similar to that of clinical practice. Remnants of semitendinosus and gracilis tendons (discarded at the end of the ACL reconstruction) were collected from 13 healthy donors. To isolate TCs, the tendon tissue was minced and digested enzymatically with 0.3% type I collagenase in DMEM with continuous agitation for 15 h at 37°C. The isolated nucleated cells were then plated at 5x103 cells/cm2 in a complete medium composed of DMEM, 10% fetal bovine serum, 50 U/ml Penicillin, 50 mg/ml Streptomycin, 2 mM L-glutamine, and supplemented with 5 ng/ml basic fibroblast growth factor (b-FGF). They were maintained at 37 °C in a humidified atmosphere with 5% CO2, changing culture medium every 3 days. When they reached 80-90% of confluence, the cells were detached by incubation with trypsin/EDTA and then cultured at a density of 5x103 cells/cm2. TCs were cultured in complete medium for 7, 14, 21 days (in chamber slides, to optimize the final immunofluorescence analysis). The following cell cultures were set up: i) TCs cultured with differentiation medium + exposure to PEMF 8 h/day; ii) TCs cultured with differentiation medium without exposure to PEMF. The stimulation with PEMF was generated by a pair of electrical coils, connected with the generator of pulsed electromagnetic fields (PEMF generator system IGEA, Carpi, Italy, intensity of magnetic field = 1.5 mT, frequency = 75 Hz). At day 0, day 7, day 14 and day 21 immunofluorescence analysis was performed to evaluate the expression of tendon specific markers (collagen type I, collagen type VI, scleraxis) and proliferative markers (PCNA, beta-catenin). The TCs from the hamstring tendon fragments at the end of the ACL reconstruction were alive and they expressed markers of proliferation and tendon phenotype at the end of the culture period. The TCs in the presence of PEMF 8h/day showed a greater production of collagen type I, collagen type VI and scleraxis than TCs cultured without PEMF (p<0.05). The expression of these markers increased from 7 to 21 days of culture. The expression of proliferative markers in the presence of PEMF stimulus was significantly lower (p<0.05) than that of TCs cultured without PEMF. Hamstring tendons are not simple "tenoconductive" scaffolds but biologic alive tenogenic constructs rich in cells that can sustain tenogenic behavior and tendon matrix synthesis. Prolonged exposure to PEMF improves their phenotype. Thus, from a clinical perspective, the use of PEMF may represent a possible future strategy to positively influence the early phase of graft remodeling and, ultimately, improve the ligamentization process. Following these concepts, further studies might also exploit the anabolic role of PEMF as an adjunctive postoperative strategy in different tendon pathologies.

CAPACITIVE COUPLING ELECTRIC FIELDS IN THE TREATMENT OF VERTEBRAL COMPRESSION FRACTURES.

Positive effects of Capacitive Coupling Electric Field (CCEF) stimulation are described for several orthopedic indications such as the healing of recent fractures, non-unions and spinal fusion, due to the capacity to involve the up-regulation of osteopromotive factors. In vitro studies on MC3T3-E1 bone cells showed that CCEF acts opening the plasma membrane voltage gated calcium channels, thus increasing the cytosolic calcium concentration and the phospholipase A2 (PLA2) activity. Cytosolic calcium activates the calmodulin pathway, thus resulting in an up-regulated expression of osteogenic genes, such as transforming growth factor-ß superfamily genes (TGF-ß1, -ß2 -ß3, bone morphogenetic protein-2 and -4), fibroblast growth factor (FGF)-2, osteocalcin (BGP) and alkaline phosphatase (ALP). PLA2 acts increasing the synthesis of Prostaglandin E2 (PGE2), which promotes osteogenesis by raising the cellular L-ascorbic acid uptake through the membrane carrier sodium vitamin C transporter-2 (SVCT-2). In vivo, Brighton et al. in a castration-induced osteoporosis animal model, demonstrated that CCEF was able to restore bone mass/unit volume in the rat vertebral body. To investigate the role of CCEF stimulation in vertebral bone marrow edema (VBME) its percentage was assessed in 24 patients with 25 acute vertebral compression fractures (VCFs) conservatively treated with CCEF (group A) or without CCEF (group B) using serial MR imaging follow-up at 0, 30, 60, 90 days. Pain and quality of life were assessed by visual analog scale (VAS) and Oswestry Low Back Disability Index (ODI) in the same periods. At 90 day follow-up the complete resolution of VBME was found only in group A (p=0.0001). A significant improvement of VAS (p=0.007) and ODI (p=0.002) was also observed in group A. This preliminary observational study shows that patients treated with CCEF stimulation present an improvement of clinical symptoms with faster fracture healing and a complete VBME resolution.

Biophysical stimulation and the periprosthetic bone: is there a rationale in the use of Pulsed Electromagnetic Fields after a hip or knee implant?

The biophysical stimulation of bone and cartilage, using Pulsed ElectroMagnetic Fields (PEMF), covers many different aspects of bone formation and/or cartilage repair, such as healing of delayed or non-union of fracture, bone necrosis, osteocartilagineous defects. To date there are no specific data on the effects of PEMFs in osteointegration of prosthetic implants but there are some papers that denote clinical advantages, in terms of early recovery, in patients treated with these procedures. Considering these clinical applications, PEMF stimulation around hip or knee joint implants could be useful to reduce the bone oedema, pain and to reduce excessive bone reabsorption around the femoral stems.

In vitro functional response of human tendon cells to different dosages of low-frequency pulsed electromagnetic field.

PURPOSE: Chronic tendinopathy is a degenerative process causing pain and disability. Current treatments include biophysical therapies, such as pulsed electromagnetic fields (PEMF). The aim of this study was to compare, for the first time, the functional in vitro response of human tendon cells to different dosages of PEMF, varying in field intensity and duration and number of exposures. METHODS: Tendon cells, isolated from human semitendinosus and gracilis tendons (hTCs; n = 6), were exposed to different PEMF treatments (1.5 or 3 mT for 8 or 12 h, single or repeated treatments). Scleraxis (SCX), COL1A1, COL3A1 and vascular endothelial growth factor-A (VEGF-A) expression and cytokine production were assessed. RESULTS: None of the different dosages provoked apoptotic events. Proliferation of hTCs was enhanced by all treatments, whereas only 3 mT-PEMF treatment increased cell viability. However, the single 1.5 mT-PEMF treatment elicited the highest up-regulation of SCX, VEGF-A and COL1A1 expression, and it significantly reduced COL3A1 expression with respect to untreated cells. The treated hTCs showed a significantly higher release of IL-1ß, IL-6, IL-10 and TGF-ß. Interestingly, the repeated 1.5 mT-PEMF significantly further increased IL-10 production. CONCLUSIONS: 1.5 mT-PEMF treatment was able to give the best results in in vitro healthy human tendon cell culture. Although the clinical relevance is not direct, this investigation should be considered an attempt to clarify the effect of different PEMF protocols on tendon cells, in particular focusing on the potential applicability of this cell source for regenerative medicine purpose, both in surgical and in conservative treatment for tendon disorders.

Paratiroidectomía en pacientes renales crónicos en Argentina: estudios prequirúrgicos, tipos de cirugía, recurrencia y persistencia / Parathyroidectomy in chronic kidney disease patients in Argentina: pre surgical studies, types of surgery, recurrence and persistence

La paratiroidectomía (PTx) es el tratamiento de elección en pacientes con HPT 2º severo, refractario al tratamiento médico. Se cuenta con muy poca información en Argentina de este procedimiento, por lo cual se realizó este estudio. Material y Métodos: Se incluyeron 255 pacientes con PTx entre el año 2003 al 2007 de un registro voluntario. Se evaluaron los estudios de localización prequirúrgicos, de laboratorio de metabolismo fosfocálcico previo y posterior a la cirugía y el tipo de técnica quirúrgica utilizada. Se analizó la persistencia y recidiva del HPT postcirugía. Resultados: La tasa de PTx fue de 2,7/1000 pacientes año. 83% de los pacientes tuvieron ecografía de cuello y 59% Sesta Mibi con Tc 99. Hubo una correlación positiva (p<0.001) entre el número de glándulas detectadas por ecografía y Sesta Mibi. La paratiroidectomía realizada fue: subtotal en 77%, total con autoimplante en 14% y total sin autoimplante en 9%. Hubo descensos significativos de Ca y P, fosfatasa alcalina y PTH (1744 ± 788 pg/ml a 247 ±450 pg/ml; p<0.0001) postcirugía. A los 2,4 ±2,5 meses de la PTx, el 72% de los pacientes tenía PTH <250 pg/ml, 19,8% tenía persistencia y 8,3% había recidivado. De acuerdo al tipo de cirugía la persistencia y recidiva fueron para PTx subtotal 22% y 8,3%, PTx total con implante 11% y 11% y PTx total sin autoimplante 13% y 4% respectivamente. La realización de Sesta Mibi no influyó en los resultados de la PTx. No se observaron diferencias entre los centros en relación con persistencia y recidiva. Conclusiones: La tasa de PTx fue muy baja, la ecografía fue el método de localización prequirúrgico preferido y la PTX subtotal la técnica quirúrgica más utilizada. La PTx fue exitosa en la mayoría de los pacientes y la persistencia y recidiva no estuvieron relacionadas con la técnica.

Parathyroidectomy (PTx) is the selecte treatment for patients with severe secondary hyperparathyroidism, refractory to medical treatment. There is not enough information about this procedure in Argentina, that is the reason why we performed this study. Material and Methods: 255 patients with PTx were included from the year 2003 to 2007 on a voluntary register. Studies of pre-surgical localization, phosphocalcic metabolism laboratories before and after surgery were evaluated, and the type of surgical technique used. The persistence and recurrence of post-surgical hyperparathyroidism was analyzed. Results: The PTx rate was 2,7/1000 patients year. 83% of the patients had neck echography and 59% Sestamibi scans with Tc 99. There was a positive correlation (p<0,001) between the number of detected glands by echography and Sestamibi. The parathyroidectomy performed was: subtotal in 77%, total with self-implant in 14% and total without self-implant in 9%. There were significant falls of Ca and P, Alkaline Phosphatase and PTH (1744±788 pg/ml to 247±450 pg/ml; p<0.0001) post-surgical. 2.4 ±2,5 months after the PTx, 72% of patients had PTH <250 pg/ml, 19,8% had persistence and 8,3% had recurrence. According to the type of surgery, the persistence and recurrence were for subtotal PTx 22% and 8,3%, total PTx with implant 11% and 11%, and total PTx without selfimplant 13% and 4% respectively. The performance of the Sestamibi scan did not affect the PTx results. No noticeable differences were observed among the centers for persistence and recurrence. Conclusions: The PTx rate was very low, echography was the preferred method of pre-surgical localization, and subtotal PTx was the most used surgical technique. PTx was successful in most of the patients, and persistence and recurrence were not related to the technique.

In vivo effect of two different pulsed electromagnetic field frequencies on osteoarthritis.

Osteoarthritis (OA) is a joint pathology characterized by fibrillation, reduced cartilage thickness and subchondral bone sclerosis. There is evidence that pulsed electromagnetic fields (PEMFs) counteract OA progression, but the effect of two different PEMF frequencies has not yet been shown. The aim of this study was to test the effectiveness of PEMFs at two different frequencies (37 and 75 Hz) in a late OA stage in 21-month-old Guinea pigs. After 3 months of 6 h/day PEMF stimulation, histological and histomorphometric analyses of the knees were performed. At both frequencies, PEMFs significantly reduced histological cartilage score, fibrillation index (FI), subchondral bone thickness (SBT) and trabecular number (Tb.N) and increased trabecular thickness (Tb.Th) and separation (Tb.Sp) in comparison to the not treated SHAM group. However, PEMFs at 75 Hz produced significantly more beneficial effects on the histological score and FI than 37 Hz PEMFs. At 75 Hz, PEMFs counteracted cartilage thinning as demonstrated by a significantly higher cartilage thickness values than either those of the SHAM or 37 Hz PEMF-treated groups. Although in severe OA both PEMF frequencies were able to limit its progression, 75 Hz PEMF stimulation achieved the better results.

Low frequency pulsed electromagnetic field affects proliferation, tissue-specific gene expression, and cytokines release of human tendon cells.

Low frequency pulsed electromagnetic field (PEMF) has proven to be effective in the modulation of bone and cartilage tissue functional responsiveness, but its effect on tendon tissue and tendon cells (TCs) is still underinvestigated. PEMF treatment (1.5 mT, 75 Hz) was assessed on primary TCs, harvested from semitendinosus and gracilis tendons of eight patients, under different experimental conditions (4, 8, 12 h). Quantitative PCR analyses were conducted to identify the possible effect of PEMF on tendon-specific gene transcription (scleraxis, SCX and type I collagen, COL1A1); the release of pro- and anti-inflammatory cytokines and of vascular endothelial growth factor (VEGF) was also assessed. Our findings show that PEMF exposure is not cytotoxic and is able to stimulate TCs' proliferation. The increase of SCX and COL1A1 in PEMF-treated cells was positively correlated to the treatment length. The release of anti-inflammatory cytokines in TCs treated with PEMF for 8 and 12 h was significantly higher in comparison with untreated cells, while the production of pro-inflammatory cytokines was not affected. A dramatically higher increase of VEGF-A mRNA transcription and of its related protein was observed after PEMF exposure. Our data demonstrated that PEMF positively influence, in a dose-dependent manner, the proliferation, tendon-specific marker expression, and release of anti-inflammatory cytokines and angiogenic factor in a healthy human TCs culture model.

Conservative treatment of spontaneous osteonecrosis of the knee in the early stage: pulsed electromagnetic fields therapy.

HYPOTHESIS: pulsed electromagnetic fields treatment might improve symptoms in the early stage of spontaneous osteonecrosis of the knee. METHODS: Twenty-eight patients (19M/9F, age 49.8±16.4 years) suffering from symptomatic (pain) Koshino stage I spontaneous osteonecrosis of the knee, confirmed by magnetic resonance imaging (MRI) were treated with local pulsed electromagnetic fields therapy (6 h daily for 90 days). Clinical evaluation: baseline, 6- and 24-month follow-up by VAS for pain, knee society score (KSS), Tegner and EQ-5D scales. MRI evaluation: baseline and 6-month follow-up, measuring bone marrow lesion's areas and grading these lesions by WORMS score. Failures: patients undergoing knee arthroplasty. RESULTS: Pain significantly reduced at 6 months (from 73.2±20.7 to 29.6±21.3, p<0.0001), which remained almost unchanged at final follow-up (27.0±25.1). KSS significantly increased in first 6 months (from 34.0±13.3 to 76.1±15.9, p<0.0001) and was slightly reduced at final follow-up (72.5±13.5, p=0.0044). Tegner median level increased from baseline to 6-month follow-up (1(1-1) and 3(3-4), respectively, p<0.0001) and remained stable. EQ-5D improved significantly throughout the 24 months (0.32±0.33, baseline; 0.74±0.23, 6-month follow-up (p<0.0001); 0.86±0.15, 24-month follow-up (p=0.0071)). MRI evaluation: significant reduction of total WORMS mean score (p<0.0001) and mean femoral bone marrow lesion's area (p<0.05). This area reduction was present in 85% and was correlated to WORMS grading both for femur, tibia and total joint (p<0.05). Four failures (14.3%) at 24-month follow-up. CONCLUSIONS: Pulsed electromagnetic fields stimulation significantly reduced knee pain and necrosis area in Koshino stage I spontaneous osteonecrosis of the knee already in the first 6 months, preserving 86% of knees from prosthetic surgery at 24-month follow-up. No correlation was found between MRI and clinical scores. LEVEL OF EVIDENCE: Level IV; case series.

Hangman's fracture: a historical and biomechanical perspective.

The execution technique of hanging, introduced by the Angle, Saxon, and Jute Germanic tribes during their invasions of the Roman Empire and Britain in the 5th century, has remained largely unchanged over time. The earliest form of a gallows was a tree on which prisoners were hanged. Despite the introduction of several modifications such as a trap door, the main mechanism of death remained asphyxiation. This created the opportunity for attempted revival after the execution, and indeed several well-known cases of survival following judicial hanging have been reported. It was not until the introduction of the standard drop by Dr. Samuel Haughton in 1866, and the so-called long drop by William Marwood in 1872 that hanging became a standard, humane means to achieve instantaneous death. Hangmen, however, fearing knot slippage, started substituting the subaural knot for the traditional submental knot. Subaural knots were not as effective, and cases of decapitation were recorded. Standardization of the long drop was further propagated by John Berry, an executioner who used mathematical calculations to estimate the correct drop length for each individual to be hanged. A British committee on capital sentences, led by Lord Aberdare, studied the execution method, and advocated for the submental knot. However, it was not until Frederic Wood-Jones published his seminal work in 1913 that cervical fractures were identified as the main mechanism of death following hanging in which the long drop and a submental knot were used. Schneider introduced the term "hangman's fracture" in 1965, and reported on the biomechanics and other similarities of the cervical fractures seen following judicial hangings and those caused by motor vehicle accidents.

Thoracolumbar spinal deformity: Part I. A historical passage to 1990: historical vignette.

Seven millennia of anthropological artifacts and historical tales reference human spinal deformity, its diagnosis, and treatment-many of the latter of which turned out to be worse than the deformity itself. From Hippocrates to Harrington to the 21st century, the literature base has expanded in exponential fashion to yield an imperfect but constantly improving body of evidence, experience, and understanding of this challenging disease phenomenon. This review details the pre-1990 innovations, whose failures and successes have equally contributed to the advancement and dissemination of the increasingly evidence-based field of spinal deformity.

Development of anatomic science in the late middle ages: the roles played by Mondino de Liuzzi and Guido da Vigevano.

Medical historians generally consider anatomic science, as we know it today, to have been established through the pioneering work of Vesalius during the Renaissance. Although this is largely true, detailed assessment of the scientific advances made in the late Middle Ages, though not as spectacular as those made during the Renaissance period, did pave the way and form a foundation for subsequent progress. During the two centuries of AD 1300 to 1500, several worthwhile advances occurred. Many universities, centers of learning excellence, were established throughout Europe, most notably in Italy. King Frederick II, the Holy Roman Emperor, established guidelines for medical education and practice that seem to parallel current regulations. Human cadaveric dissection was performed, after a hiatus of over 1700 years, as the foundation for the study of anatomy. Observation of human dissection became a requirement for medical students. A manual for anatomic dissection was written, printed, and published for the first time in history by Mondino de Liuzzi. His student, Guido da Vigevano, who also had an engineering background, established two "firsts" of his own: providing illustrations of anatomy and designing the first automobile in history. The authors believe that the contributions of these two key anatomists in the late Middle Ages should not be forgotten.

Does exposure to extremely low frequency magnetic fields produce functional changes in human brain?

Behavioral and neurophysiological changes have been reported after exposure to extremely low frequency magnetic fields (ELF-MF) both in animals and in humans. The physiological bases of these effects are still poorly understood. In vitro studies analyzed the effect of ELF-MF applied in pulsed mode (PEMFs) on neuronal cultures showing an increase in excitatory neurotransmission. Using transcranial brain stimulation, we studied noninvasively the effect of PEMFs on several measures of cortical excitability in 22 healthy volunteers, in 14 of the subjects we also evaluated the effects of sham field exposure. After 45 min of PEMF exposure, intracortical facilitation produced by paired pulse brain stimulation was significantly enhanced with an increase of about 20%, while other parameters of cortical excitability remained unchanged. Sham field exposure produced no effects. The increase in paired-pulse facilitation, a physiological parameter related to cortical glutamatergic activity, suggests that PEMFs exposure may produce an enhancement in cortical excitatory neurotransmission. This study suggests that PEMFs may produce functional changes in human brain.

Albert Wojciech Adamkiewicz (1850-1921): unsung hero behind the eponymic artery.

The artery of Adamkiewicz is an important radiculomedullary artery supplying the spinal cord, especially the lumbar enlargement. Anatomical knowledge of this artery is important for avoiding serious neurological complications during surgery performed in this region--for neurosurgeons and interventional radiologists treating intramedullary tumors and spinal arteriovenous malformations, traumatologists performing spinal fusions, thoracic surgeons treating aortic aneurysms, and urologists and pediatric surgeons conducting retroperitoneal dissections. However, the biography of the talented Polish pathologist Albert Adamkiewicz, after whom the landmark artery is named, has not been described adequately in the existing neurosurgical literature. The authors bring to light the historical perspective of the eponymic artery and provide a recapitulation of other significant contributions made by Adamkiewicz, mostly involving the nervous system. His research papers on the histology of neuronal tissues and neurodegenerative diseases had high scientific merit, but the discovery of the anticancer antitoxin "cancroin" and his postulation of a cancer-causing parasite he named "Coccidium sarcolytus" met with harsh criticism and eventually led to his ill fame. The biography is supplemented with a brief overview of the important surgical implications of the artery of Adamkiewicz.

Contributions of Johann jacob Huber to the surface anatomy of the spinal cord and meninges.

From prehistoric times, man has been aware that injury to the spine may result in paralysis of the limbs; this is reflected in bas-relief figures found at Nineweh in ancient Mesopotamia, in a hunting scene that depicts a lioness wounded by King Ashurbanipal. The Edwin Smith papyrus gives many case illustrations of spinal cord injury resulting in paralysis, yet early physicians were unaware of the anatomy of the spinal cord. Galen performed prospective studies in animals by sectioning the spinal cord at varying levels and observing the commensurate paralysis and sensory loss. Real advances in the understanding of spinal cord anatomy did not occur until human cadaveric dissections were undertaken; even then, the knowledge of the anatomy of the spinal cord lagged behind that of other body structures. Johann Jacob Huber appears to be the first anatomist to focus on the spinal cord almost exclusively. His descriptions, and especially his illustrations that depict spinal cord surface anatomy, are impressive with regard to their accuracy and their sense of photorealism. Indeed, his illustrations seem to compare well with the anatomic drawings in contemporary anatomic texts. Yet, we were unable to find a single article in the entire English-language literature depicting his illustrations. We conclude that the description and anatomic illustrations by Johann Jacob Huber remain a hidden gem in the history of human spinal anatomy.

The legendary contributions of Thomas Willis (1621-1675): the arterial circle and beyond.

Thomas Willis established neurology as a distinct discipline and made significant original contributions to many related fields including anatomy, pathology, cardiology, endocrinology, and gastroenterology. He is most remembered for his work in elucidating the function and anatomy of the circle of Willis. Willis' accomplishments and research methods can be credited in large part to his unconventional medical education which did not include traditional teachings, but rather emphasized learning through clinical practice. Although Willis was not the first to describe the arterial circle, he was the first to describe its function and provide a complete, undisputed illustration through his own innovative use of dye studies. The Willis classification of cranial nerves was still in use over 100 years after its original description. He has also described several disease entities and named many brain structures. Willis' accomplishments in comparative anatomy and understanding the pathophysiology of various diseases through original multidisciplinary experimental work in a clinical setting reveal that he was a true pioneer in translational research.

Medicosocial problems engendered with the discovery of the Bell-Magendie Law.

The discovery of the Bell-Magendie Law, which states that the ventral spinal roots transmit motor impulses and the posterior roots sensory impulses, established a major landmark in the history of neuroscience. It led to further elucidation of brain function and served as a starting point for virtually all of electrophysiology. During the past two centuries, there has been an intense debate as to which of the two scientists deserves the credit for the discovery itself and the prominent claim to the discovery. Extensive literature exists in this regard, and the goal of the authors is not to dwell on it further but rather to summarize the arguments. The major objective of this work, however, is to elaborate on the two medicosocial issues that were brought into focus by the discovery of the Bell-Magendie Law, namely, the provision of adequate numbers of cadavers for the sound anatomic education of medical students, so that the despicable practice of "body-snatching" could be abolished, and the prevention of cruelty to the experimental animals used for biomedical research. Public opinion prevailing at the time of the postulation of the Bell-Magendie Law promoted the establishment of the Royal Society for the Prevention of Cruelty to Animals, and other similar societies were established worldwide. The authors summarize the current status of these two issues.

Charles-Edouard Brown-Séquard: an eccentric genius.

Brown-Sequard is known eponymously for the syndrome of hemisection of the spinal cord, but most clinicians are not familiar with his colorful, quixotic, and eccentric life history. His contributions to medicine and neuroscience reached much further than his discovery of the spinal hemisection syndrome. He lived in five countries on three continents and crossed the Atlantic 60 times, spending a total of almost 6 years on the sea. He contributed more than 500 papers in his lifetime, was even the editor of many prestigious journals, and spent his last years as Professeur au Collége de France, a most coveted position for a French neuroscientist. Many are not aware of his contributions to endocrinology and hormone replacement therapy, even those who consider him the father of modern endocrinology. Brown-Séquard was a skillful experimentalist. He pioneered the concept of the advancement of neuroscience through experimental physiological observation. He was devoted to science. He was not interested in monetary gains through his inventions or patient care. Although he may be criticized for arriving at some incorrect conclusions from his experiments, his visionary ideas and prescient statements have stood the test of time; he truly was an eccentric genius. This article highlights Brown-Séquard's life history, specifically his time in France and North America, and his contributions to neuroscience and endocrinology.