Cell Biochem Biophys DOI 10.1007/s12013-014-9891-x
ORIGINAL PAPER
Emerging New Trends in Neurosurgical Technologies Yang Zhang • Dongxu Zhao • Hongyan Li Ye Li • Xiaobo Zhu • Xiaona Zhang
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Ó Springer Science+Business Media New York 2014
Abstract There has been tremendous progress in the modern day technologies causing a rapid evolution in the field of neurosurgery. The neurosurgeons have been equipped with the latest advancements such as the use of robotics in surgery, the image-guided neurosurgical procedures, and the stereotactic neurosurgery. In addition, the preoperative screening techniques have drastically improved the success of the surgical procedure. Neuronavigation has allowed the precise localization of the deepseated brain structures thereby helping in the accurate operation of the affected regions without stirring the normal brain tissues. Such preciseness has helped in the improvement of the patient outcome. All these aspects
Y. Zhang X. Zhu Department of Neurosurgery, The First Affiliated Hospital of Jilin University, Changchun, China D. Zhao Department of Orthopaedics, China Japan Union Hospital of Jilin University, Changchun, China H. Li Department of Urinary Surgery, China Japan Union Hospital of Jilin University, Changchun, China Y. Li Department of Radiology, The First Affiliated Hospital of Jilin University, Changchun, China X. Zhang (&) Department of Anesthesiology, The First Affiliated Hospital of Jilin University, 71 Xinmin Avenue, Changchun, Jilin 130021, China e-mail: [email protected]
have been discussed in detail in this review with a focus on their developmental background. Keywords Neurosurgical procedures and methods Non-invasive techniques in neurosurgery Robotics and neurosurgery Stereotactic methods in neurosurgery Image guidance in neurosurgery
Introduction The growing need for neurosurgical conditions has laid the foundation for the development of novel tools and technologies in this field. The gadgets used by the neurosurgeons have greatly evolved with regard to screening, diagnosis, and treatment. However, the betterment of the technology is always desired in order to improve patient outcome and satisfaction and the reliability of the physician. In this review, the latest and updated technologies have been discussed with their original versions that have revolutionized the art of neurosurgery. Newer diagnostic tools have made the work of the neurosurgeon all the more easier. Confocal laser endoscopy and the other imaging guidance have vastly improved the way neurosurgery has been conducted with regard to preciseness and accuracy. The computed tomography (CT) and functional stereotaxy has hugely benefitted the neurosurgical patients with better outcome and recovery. The robotics-aided neurosurgery has brought about a paradigm shift in the field. The major changes and modifications brought about in neurosurgical procedures has been a resultant of the pressure on the physician to be effective, quick, and avoid patient misjudgement. Therefore, the emphasis has been on the development of systems that will ensure improved outcome and quality of patient life pre- and post-neurosurgery.
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Trends and Advancements in Intraoperative Image Guidance There has been a steady increase in the use of frameless stereotactic neurosurgery for the deeply placed lesions or the intracranial tumor biopsy or in psychiatric disorders, chronic refractory pain and movement or seizure disorders. It becomes all the more relevant when one considers that under those circumstances anatomic landmarks on the surface can often be misleading [1–4]. Neuronavigational approaches are also involved in the newer biological interventions including tissue and stem cell transplants and gene therapy in the cases of movement impairment. There is a great degree of complexity with these methods and before their application one should be fully aware of the basic principles governing the art of neuronavigation. The prime precaution taken during neurosurgery is to avoid any damage occurring to the subcortical white matter or the eloquent cortex. The diffusion tractography has very quickly gained an important position as a clinical tool that can efficiently segment the white matter subcortical course which is quite critical for the delineation of the white matter tracts that are functionally important and hence forms a crucial part of the surgical planning [5–7]. After the availability of the neuronavigation technology, the essential informations regarding the intraoperative anatomy have been possible by the use of these devices [8–10]. Recently, neuronavigation has undergone modification to be referred to as functional and includes a combinatorial approach of nuclear medicine imaging, image-guided neurosurgery, MR imaging, and physiological examinations. It is faster than its parent technique and allows for a quick time orientation of the functional anatomy to the relative position of the lesion. This is achieved by the incorporation of data regarding localization from the memory areas as also the sensorimotor cortex into the neuronavigation system thereby giving rise to the identification of novel clinical indications and anatomical targets. The system can be further revamped in the future by incorporating neurophysiological and anatomic data from multiple source points that would facilitate a better planned neurosurgical procedure. Other crucial inputs in relation to neurosurgery like brain plasticity and tumor biology could as well be revealed. It is indeed an evolving new process that can accurately integrate anatomical data with the surgical process [11–14]. The three-dimensional image information in addition to the other intraoperative conditions can help the surgeon in simulating, planning, and working out better strategies similar to the one in augmented real or virtual surgery [15, 16]. The co-registration of multimodal patient data and patient data registration into atlases forms the requirements of virtual reality for surgery. Surgery often requires usage over extended period of time
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and hence the interaction style should be comfortable, natural, and easy to use. The virtual reality can have a significant contribution in remote diagnostics where two geographically distant surgeons can share the 3D visualization of a particular case and confer on it. Some of the other applications include robotic surgery-assisted remote operations or assistance to another remote surgeon. In the developed regions or the military settings the inexperienced surgeons can find this technique of telemedicine (teleassistance or teleconsulation) to be highly beneficial [17]. The major drawback is the network delay as remote neurosurgery demands for immediate interactivity and even the slightest delay introduced by the satellite communication is unacceptable.
Confocal Laser Endoscopy The proper diagnosis and therapy form a crucial part of neurosurgical procedures. In particular, the major challenging factor has been the histological diagnosis which helps in the gradation of the tumor type and hence the therapeutic interventions are largely dependent on it. Nearly 5–6 new glioma cases/100,000 per year are observed whose survival rate share a direct correlationship with the WHO gradation. With all the recent advancements in the field of surgery and adjuvant therapies including radiochemotherapy the median survival of the glioblastoma patients is around 18–21 months at the maximum [18]. Although it has been an established fact that surgical resection is unable to cure malignant gliomas, recently it has been observed that a well informed and extended tumor resection can certainly boost up life expectancy [18–20]. Therefore, the ways of resection extent increase has been the focus of neurosurgery that involves methods like fluorescently labeling the tumor cells through 5-aminolaevulinic acid or neuronavigation [21]. The role of neuronavigation may be misleading as it can cause brain shift during surgery although it leads to the clear imaging of the tumor. As a result of this, the tumor borders are often not predicted in accordance with reality [22]. Patients undergoing clinical trials for 5-ALA showed a drastically decreased second resection as compared to the ones who were operated specifically under white light [23]. However, 5-ALA suffers from the drawback that the fluorescent activity is not shown by all the tumor cells. Hence, neither of 5-ALA and neuronavigation could completely solve the intraoperative problem of precisely separating intact brain parenchyma and tumor tissue. Confocal laser endomicroscopy (CLE) is a latest option with regard to optical imaging which has already found successful application in pulmonology and gastroenterology. According to a report as early as 1957, the light from out-of-focus molecules is
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significantly reduced by the confocal microscopy. In confocal laser microscopy, the source emits a very precise beam of light that is in turn emitted by the sample thereby significantly reducing the amount of scattered light. On the other hand, the tissue is widely lit up by the conventional fluorescence microscopes. A clear focussed image is generated by the confocal light which is facilitated by the presence of an interposed pinhole. This pinhole allows the detection of light from only the desired points by cutting off all the remaining scattered light. Thus, this method allows for the microscopic scale visualization of the tissues in conjunction with the device in use. The technique has also made it possible to have real time images at par with the histologic slices and thereby comes up as a highly useful tissue alteration diagnostic tool [24–26]. With all these results, the CLE could potentially establish itself as a promising tool in neurosurgery. Currently, the technique is undergoing evaluation in different settings. The major advantage has been the fact that it can be used in an intraoperative setting. This allows the neurosurgeons for a more precise borderline scanning of the tumors with welldefined resections to improve the outcome in brain tumor patients. Recently, it has been demonstrated that reliable images are provided by the EndoMAG1 combined confocal laser microscopy as seen through tissue cultures and pig brain and human brain tumors. A very well-characterized endoscopic image is seen for all the structures. Potentially, the method could provide a real time diagnostic histology. However, a more detailed correlation study between the histopathological diagnosis and confocal endoscopic imaging needs to be done through further clinical research before its fruitful development and application in the field of neurosurgery.
History of Functional Stereotaxy The physician Robert Henry Clarke who worked with the pioneer British neurosurgeon Victor Mosley since 1880 in the University College, London had originally devised stereotaxy. Their interests particularly revolved in deciphering the role of the cerebellum in relation to movement. In order to investigate the role of cerebellar nuclei in movement they chose apes to place electrodes in the cerebellar nuclei to create electrical stimulations. The localization was controlled with the help of a precise electrolytic lesion free from any collateral damage to the target. It was soon found out that the precise electrode localization was inhibited by the lack of anatomical landmarks. The situation is aggravated by the skull curvature and the variability of the depth that was largely dependent on the varying bone thickness. Subsequently, Clarke was able to design a
procedure free from such altering factors. The basic idea involved the creation of a point of intersection of three perpendicularly placed planes. The distance of the target from each plane was separately measured (very much similar to the x, y, z coordinates of the rectangular Cartesian system). In order to limit the movement of the head while introducing the electrodes a rectangular frame was fixed to the skull. It served a dual role of carrier for the electrodes and a stable holder. Anode current was used to make the electrolytic lesions. The work got published for the first time in 1906 as a short report and then in detail in 1908 and they termed the method as stereotaxis [27]. Later on the system was upgraded by the neurophysiologist Aubrey Mussen to be used as a stereotactic frame for humans that got very limited acceptance [28]. An additional reference point (at the beginning of the calcified pineal body) was introduced to be used in the system by Ernst Adolf Spiegel, the pioneer of human stereotaxy. However, the calcification of the pineal body was not a general process and hence its visibility through radiographic images was limited and accordingly the reference point was changed to the posterior commissure by Spiegel [29]. Ventriculography mediated lateral ventricular images were required for the visualization of the posterior commissure which was initially made possible with diluted contrast media or with air. Henry Wycis, a Philadelphiabased neurosurgeon, was able to put into practice the minimally invasive method designed by Spiegel quite efficiently for functional disorder treatments [30–32]. In the first ever stereotactic surgery performed in 1947, Clarke’s frame was modified to include an additional cast for fixing the head [29]. The first stereotactic neurosurgery was performed by Wycis and Spiegel just a year later when they operated a Parkinson’s disorder patient. This remained to be the only effective therapeutic intervention in Parkinson’s disease until the discovery of L-DOPA. The functional stereotaxis is primarily related to applied neurophysiology and hence its understanding requires an indepth knowledge of neurophysiology in addition to the understanding of imaging technology, sophisticated mechanical equipments, stimulation effects, and topographical anatomy. The anterior commissure was introduced in addition to the posterior commissure by the neurosurgeon Jean Talairach [33]. In 1961, Gerard Guiot and Madame Denise Albe-Fessard successfully introduced microelectrode recordings in the thalamus during stereotactic surgery. This enabled the intraoperative recording of the tremor sensitive cells in Parkinson’s disorder patients [34]. In 1949, a target centered stereotactic frame was designed by Leksell while working at the Karolinska Institute. A higher level of flexibility for the trajectory was made possible by this system as it enabled the surgeon to reach the target from any angle as it positioned the target
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into the isocenter of the frame [35]. In 1951, Leksell in collaboration with the physicist Borje Larson at the Uppsala University devised the first ever stereotactic irradiation apparatus [36]. The isocentrally placed target could be irradiated with a high local dose leaving aside the surrounding normal brain tissues. This is accomplished since around two hundred separate sources are used for irradiation. Freiburg became the central hub for stereotactic surgery in Germany around the fifties of the twentieth century. A polar coordinate system was used by Riechert and Wolff to first make a prototype and then an advanced stereotactic system around the same time [37]. An additional phantom was added to the upgraded version that could check for the trajectory and the coordinates [38]. Until the eighties, the system remained to be the most preferred one due to its preciseness rendered by an advanced mechanical set up and manually subtle electrodes and instruments. One of the major contributors to this success of the Freiburg group was Rolf Hassler. He was an expert in neuroanatomy with speciality in the thalamus anatomy, a highly desirable qualification for the field. A clear and subtle subdivision of the thalamic nuclei was possible mainly because of his anatomical knowledge. It is because of his depth of knowledge and contribution that the basal ganglia was soon replaced by the thalamus to be an integral part of functional stereotaxy and became highly applicable in the treatment of specific cases like the Morbus Parkinson [39]. Hassler later went on to study Morbus Parkinson in detail at the Max Plank Institute, Frankfurt. In Japan, Uchimura and Narabayashi designed a stereotactic frame upon the lines and ideas of Spiegel, Clarke, and Horsley in 1949. In 1951, he became the first successful neurosurgeon to carry out stereotactic pallidotomy. He later went on to develop a famous clinic and well-known research center for movement disorders. The atlases for the fine brain structures were the only support of stereotactic methods with regard to the topographical anatomy. Spiegel and Wycis went on to publish the first ever atlases meant for stereotactic procedures in 1952 and 1962, respectively. However, the 1959 published Schaltenbrand–Bailey atlas become the most frequently used atlas for stereotactic neurosurgery. In 1977, Waldemar Wahren published an enlarged and revised version of the atlas. Generations of neurosurgeons were influenced by the work of Hassler for the detailed thalamic nuclei nomenclature. Around the seventies, L-DOPA was introduced as a therapeutic treatment for Parkinson’s disorder. As a result of this introduction, the functional stereotactic neurosurgery lost its importance and except for a few centers its use was discontinued. However, gradually side effects of the drug were discovered like the on–off phenomenon. In addition, the L-DOPA treatment was found ineffective in countering extrapyramidal problems such as essential tremor. Such negative consequences of L-DOPA
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resulted in the re-popularization of the stereotactic procedures since the eighties. The successful introduction of electrodes without the need to create lesions for stimulation significantly improved the treatment of movement disorders. In the seventies and eighties, intractable pain was also treated by the use of this deep brain stimulation. Later on the technique was successfully used for the treatment of Morbus Parkinson [40]. These earlier works in the field of functional stereotaxy paved the way for the development of modern day technologies in the field of neurosurgery.
Robotics in Neurosurgery Therapeutic interventions have undergone a paradigm shift after the application of robotics in surgery. Intuitive Surgical’s da Vinci system, the most common surgical robot was cleared by the Food and Drug administration of the US in relation to multiple operative categories. Post 9 years of its clearance it has been used in nearly 80 % of prostatectomies in the United States. Subsequently, it has found mention in as many as 4,000 peer reviewed publications [41]. The rapid progress and development of medical robotics have been possible due to a combination of factors that include advanced imaging systems in the medical filed (better resolution, 3D ultrasound, and magnetic resonance imaging), improved technologies (materials, motors, and control theory) and increased acceptance of robotic assistance as well as laparoscopic techniques by both patients and surgeons. As during any technological revolution, the robotics is finding increased usage in the medical field. The robotics with their accurate and precise medical imageaided motions can help in brain surgery which often requires the access to targets that are surrounded by delicate tissues and deeply buried [42, 43]. The first ever use of a robot in brain surgery that used the helps of stereotactic frame and CT was performed for brain biopsy in 1985 [44]. In this case, the probe was oriented toward the target in order to define the biopsy trajectory which the surgeons could easily manipulate. A preoperative CT was registered to determine the orientation through stereotactic fiducials attached to the skull of the patient. However, the project was discontinued later on due to safety concerns. The Minerva robot designed in 1991 facilitates the real time CT-guided tool direction into the brain. This can help in the precise tracking of the targets that are image guided and particularly helpful during brain tissue swelling, shifting or sagging that occurs while operating. Minerva had the limitation of one-dimensional incursions and restricted real time CT and hence was discontinued in 1993 [45]. The recently developed neurosurgery robots are somewhat similar in purpose to that of the historical systems viz. cannulae orientation/image-guided positioning or other
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tools. Currently, in the stage of FDA clearance, the NeuroMate besides its role in biopsy can be beneficial in stereotactic electroencephalography, brain stimulation, neuroendoscopy, transcranial magnetic stimulation, and radiosurgery [46]. In 2004, the FDA cleared yet another robotic system for neurosurgery, the Pathfinder [47]. Based upon preoperative medical image, the surgeon makes use of the system to accurately specify the target and trajectory. The instrument is guided and positioned by the robot with submillimeter precision [48]. Subsequently, the system has been reportedly being used for making burr holes and guiding needles for biopsy [49]. In 2011, Renaissance (Mazor Robotics) received the FDA clearance as well as CE marks for brain operations and spinal surgery [50]. The system comprises of a soda bottle sized robot that guides for various software-based guidance and can be mounted directly onto the spine. The different applications include biopsies, deformity corrections, electrode placements, and minimally invasive surgeries. Renaissance also has the provision for ad-on for fluoroscopy which can be highly beneficial three-dimensional image-based intraoperative verification of the placement of the implants. There are reports to suggest that the spine assist/renaissance have significantly improved the accuracy of the implant placements and they can now be even placed percutaneously [51].
patients. However, recent reports suggest for some negative effects on the brain tissues by intensive insulin therapy [60, 61]. Proper precaution should be taken to analyze the data from clinical studies involving neurosurgical patients for intensive insulin therapy since neuroinjuries often alter brain glucose metabolism. The critical point to ponder is that the lower and upper plasma glucose threshold levels are not well defined. Moreover, consistency relating the glucose levels in brain and peripheral glucose measurements are required. An improved level of perioperative blood glucose level has been found to help prevent a number of the negative consequences of hyperG [60]. A number of factors need to be assessed for patients with other complications like in case of diabetic individuals, related conditions of hypertension, obesity, coronary arterial disease, renal insufficiency, and coronary artery disease can increase the perioperative risk [59]. Surgery often requires readjusted anti-diabetic therapy since it being a stressful event leads to disrupted oral intake [59]. The inpatient glucose response, outpatient treatment, glycemic control, presence of complications, blood glucose control level, surgical process involved and type of anesthesia should be considered in order to reduce metabolic derangements and surgery-associated complications.
PFA-100 as a Screening Technique in Neurosurgery Perioperative Glucose Control in Neurosurgery Adverse outcomes like prolonged hospital stay, increased hospital stay and higher rates of mortality have been found associated with both the non-diabetic and diabetic neurosurgical patients with hyperglycemia (hyperG) as suggested by different independent observations and studies [52–54]. Besides, the patients also suffer from negative effects of the glucose deficit [55, 56]. The subjects with pre-existing diabetes mellitus are at lesser risk than those unknown cases of hyperG [57]. Current reports show that the whole organism including the brain is affected by the deleterious effects of hyperG [58]. Hospital-induced hyperG and undiagnosed diabetes mellitus causes enhanced post-operative complicacies, length of hospital stay and costs [59]. HyperG has been found to be highly associated with the prognosis of various brain injury cases [60]. Notwithstanding its close linkage with the poor outcomes in brain surgery cases, it is hard to say whether hyperG is directly responsible for such results or it is just an epiphenomenon [58, 60]. Therefore, a strict surveillance of blood glucose could result in positive patient outcomes [58]. Subsequently, intensive insulin therapy has been tried out in order to regulate and maintain a tight blood glucose level (within a range of 80–110 mg/dL) in neurocritical
In surgery, the most dreaded and life-threatening complications has been hemorrhage particularly in case of neurosurgery where the patient can meet with devastating consequences due to it. This is because during neurosurgery the surgeon has impaired vision as there is very limited possibility for blood drainage [62, 63]. Therefore, it is mandatory that the diagnostic tools should be evaluated keeping in mind their ultimate influence on the patient outcome. No improvement in the patient outcome was detected after the introduction of PFA-100 in patients who have undergone neurosurgery for their preoperative screening. The PFA group patients received more desmopressin which did not seem to benefit them and hence the treatment of the drug was supposed unnecessary. It has also been established through studies that in case of post-traumatic brain injury the vasopressin receptors play an important role [64, 65]. However, it is assumed that the surgical procedure can be directly influenced by desmopressin. It has been previously found that the patients undergoing surgery often suffer platelet dysfunction and primary hemostasis disorders [66, 67]. Desmopressin has been found effective in the treatment of these disorders [68]. In order to solve such contradictory observations a number of different aspects need to be assessed. One of the crucial questions is the relevance of the PFA-100 in the
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detection of platelet functioning defect. This can provide the valuable information of the role of this defect in the operative and post-operative bleeding complications. The effectiveness of desmopressin in these patients should also be evaluated. The intake of aspirin can last several days on the patients which can result in a high PFA-Epi since it is highly sensitive to the effect of aspirin [69]. Therefore, it can be concluded that many of the surgical patients had aspirin administration before they underwent surgery. However, nothing significant has been associated with the intake of aspirin and increased perioperative bleeding [70]. Nonetheless, an abnormal PFA value can indicate the increased bleeding risk under such circumstances without providing a deterministic prediction for bleeding complications. In addition to the existing known factors perioperative bleeding has often been caused by non-anticipated preoperative factors. The inherent complexity and difficulty associated with surgical method is one such obvious risk factor. Besides, the undetected or preoperative factors like disturbances in the process of coagulation (e.g., increased fibrinolysis) can play a decisive role [71]. As a matter of fact desmopressin induces fibrinolysis and the combinatorial effect of desmopressin and tumor pathophysiology-induced fibrinolytic effect might bring about a hemostatic neutralization. It is therefore assumed that most of the preoperative cases of primary hemostasis are not clinically relevant. There may be other factors that can add on to the bleeding complications. With regard to the diagnosis of the cases of primary hemostatic disorder the PFA-100 shows a limited performance [72]. In particular, the performance has been hampered in patients with low hemoglobin or defect in platelet secretion [73]. Such conditions in the patient group might preclude a favorable preoperative result. Therefore, the PFA screening is carried out for a well-defined patient group where there can be very little subjective effect by the rightful selection of the control group.
100 billion neurons and hence is going to be a huge challenge for the future of neuroscience research. There are fantasies relating to the control of mind which remains largely elusive due to the inability to decode the memory encoding capacity of the brain and its mechanism [75]. Two phases are predicted to be crucial for the developments in BMI: in the first phase the BMI is concentrated for the disabled individuals consisting mainly of therapeutics, while the second phase will be more inclined toward healthy humans to enhance their motor and cognitive skills [75]. McGee and Maguire has predicted for the possibility of a third phase that will involve the transfer of information capabilities with the aid of neural devices [76]. Although the proposed third phase is still a long way from realization, it certainly predicts the enormous future potential of the BMI technology once it is put to practice in its fully developed form. The neurosurgical care can be related to large scale expenditure of the health system resources. As a matter of fact it significantly influences the clinical outcomes and the life quality which has often been found largely disproportionate to the number of encounters and our specialty size. Such interventions are associated with complex social, ethical, and medical dimensions with midlevel providers like nurses, physician assistants for the neurosurgeons. It has been observed that the concentration of the neurosurgical care is often focussed at the extremities of age (the end and beginning of life). The focus should be on the unforgiving nervous system with subspecialty coverage for hydrocephalus, neurotrauma, stroke that tremendously influences the outcome of the healthcare. It is for these reasons that the neurosurgeons have been undergoing updated training, education, and innovation for the advancement and improvement of our specialty and patient outcomes. Neurosurgery has beyond doubt come up as the leader in the field and it should be considered for additional support and care that could enhance the educational practices and provide the necessary goals [77].
Ethical Issues
Conclusion
The last decade has drastically changed our perception of the human brain with the advent of modern technologies in molecular biology, neuroscience, and updated brain imaging methods. A wide array of enhanced cognitive therapeutics development has been worked upon by the neuroscientists. Many such technologies can potentially become the pioneers for our deeper and further understanding of the human brain. It is even predicted that the twenty-first century may be referred to as the century of neuroscience [74]. The complexity of the field comes from the enormity of the neural network of the brain with its huge mesh of nearly 100 trillion synaptic connections and
The field of neurosurgery faces both new challenges as well as opportunities due to rapid advancements in molecular and technological approaches focused toward solving the neurosurgical problems. Our recent technologies in this regard have been a resultant of the transfer of the pressure prevalent on the neurosurgeons to perform an effective, quick, and error free surgical treatment of the patient as well as his effective and favorable post-operative outcome. The neurosurgeons have been able to precisely locate the position of an abnormal tissue in the spinal cord or the brain with the recent technological advancements. This has significantly reduced the surgical trauma of the
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normal tissues. More advances are necessary in the field for safer and successful outcome in the neurosurgical procedures. As a matter of fact the field of neurosurgery will continually feel the pressure of newer technology development.
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ORIGINAL PAPER
Emerging New Trends in Neurosurgical Technologies Yang Zhang • Dongxu Zhao • Hongyan Li Ye Li • Xiaobo Zhu • Xiaona Zhang
•
Ó Springer Science+Business Media New York 2014
Abstract There has been tremendous progress in the modern day technologies causing a rapid evolution in the field of neurosurgery. The neurosurgeons have been equipped with the latest advancements such as the use of robotics in surgery, the image-guided neurosurgical procedures, and the stereotactic neurosurgery. In addition, the preoperative screening techniques have drastically improved the success of the surgical procedure. Neuronavigation has allowed the precise localization of the deepseated brain structures thereby helping in the accurate operation of the affected regions without stirring the normal brain tissues. Such preciseness has helped in the improvement of the patient outcome. All these aspects
Y. Zhang X. Zhu Department of Neurosurgery, The First Affiliated Hospital of Jilin University, Changchun, China D. Zhao Department of Orthopaedics, China Japan Union Hospital of Jilin University, Changchun, China H. Li Department of Urinary Surgery, China Japan Union Hospital of Jilin University, Changchun, China Y. Li Department of Radiology, The First Affiliated Hospital of Jilin University, Changchun, China X. Zhang (&) Department of Anesthesiology, The First Affiliated Hospital of Jilin University, 71 Xinmin Avenue, Changchun, Jilin 130021, China e-mail: [email protected]
have been discussed in detail in this review with a focus on their developmental background. Keywords Neurosurgical procedures and methods Non-invasive techniques in neurosurgery Robotics and neurosurgery Stereotactic methods in neurosurgery Image guidance in neurosurgery
Introduction The growing need for neurosurgical conditions has laid the foundation for the development of novel tools and technologies in this field. The gadgets used by the neurosurgeons have greatly evolved with regard to screening, diagnosis, and treatment. However, the betterment of the technology is always desired in order to improve patient outcome and satisfaction and the reliability of the physician. In this review, the latest and updated technologies have been discussed with their original versions that have revolutionized the art of neurosurgery. Newer diagnostic tools have made the work of the neurosurgeon all the more easier. Confocal laser endoscopy and the other imaging guidance have vastly improved the way neurosurgery has been conducted with regard to preciseness and accuracy. The computed tomography (CT) and functional stereotaxy has hugely benefitted the neurosurgical patients with better outcome and recovery. The robotics-aided neurosurgery has brought about a paradigm shift in the field. The major changes and modifications brought about in neurosurgical procedures has been a resultant of the pressure on the physician to be effective, quick, and avoid patient misjudgement. Therefore, the emphasis has been on the development of systems that will ensure improved outcome and quality of patient life pre- and post-neurosurgery.
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Trends and Advancements in Intraoperative Image Guidance There has been a steady increase in the use of frameless stereotactic neurosurgery for the deeply placed lesions or the intracranial tumor biopsy or in psychiatric disorders, chronic refractory pain and movement or seizure disorders. It becomes all the more relevant when one considers that under those circumstances anatomic landmarks on the surface can often be misleading [1–4]. Neuronavigational approaches are also involved in the newer biological interventions including tissue and stem cell transplants and gene therapy in the cases of movement impairment. There is a great degree of complexity with these methods and before their application one should be fully aware of the basic principles governing the art of neuronavigation. The prime precaution taken during neurosurgery is to avoid any damage occurring to the subcortical white matter or the eloquent cortex. The diffusion tractography has very quickly gained an important position as a clinical tool that can efficiently segment the white matter subcortical course which is quite critical for the delineation of the white matter tracts that are functionally important and hence forms a crucial part of the surgical planning [5–7]. After the availability of the neuronavigation technology, the essential informations regarding the intraoperative anatomy have been possible by the use of these devices [8–10]. Recently, neuronavigation has undergone modification to be referred to as functional and includes a combinatorial approach of nuclear medicine imaging, image-guided neurosurgery, MR imaging, and physiological examinations. It is faster than its parent technique and allows for a quick time orientation of the functional anatomy to the relative position of the lesion. This is achieved by the incorporation of data regarding localization from the memory areas as also the sensorimotor cortex into the neuronavigation system thereby giving rise to the identification of novel clinical indications and anatomical targets. The system can be further revamped in the future by incorporating neurophysiological and anatomic data from multiple source points that would facilitate a better planned neurosurgical procedure. Other crucial inputs in relation to neurosurgery like brain plasticity and tumor biology could as well be revealed. It is indeed an evolving new process that can accurately integrate anatomical data with the surgical process [11–14]. The three-dimensional image information in addition to the other intraoperative conditions can help the surgeon in simulating, planning, and working out better strategies similar to the one in augmented real or virtual surgery [15, 16]. The co-registration of multimodal patient data and patient data registration into atlases forms the requirements of virtual reality for surgery. Surgery often requires usage over extended period of time
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and hence the interaction style should be comfortable, natural, and easy to use. The virtual reality can have a significant contribution in remote diagnostics where two geographically distant surgeons can share the 3D visualization of a particular case and confer on it. Some of the other applications include robotic surgery-assisted remote operations or assistance to another remote surgeon. In the developed regions or the military settings the inexperienced surgeons can find this technique of telemedicine (teleassistance or teleconsulation) to be highly beneficial [17]. The major drawback is the network delay as remote neurosurgery demands for immediate interactivity and even the slightest delay introduced by the satellite communication is unacceptable.
Confocal Laser Endoscopy The proper diagnosis and therapy form a crucial part of neurosurgical procedures. In particular, the major challenging factor has been the histological diagnosis which helps in the gradation of the tumor type and hence the therapeutic interventions are largely dependent on it. Nearly 5–6 new glioma cases/100,000 per year are observed whose survival rate share a direct correlationship with the WHO gradation. With all the recent advancements in the field of surgery and adjuvant therapies including radiochemotherapy the median survival of the glioblastoma patients is around 18–21 months at the maximum [18]. Although it has been an established fact that surgical resection is unable to cure malignant gliomas, recently it has been observed that a well informed and extended tumor resection can certainly boost up life expectancy [18–20]. Therefore, the ways of resection extent increase has been the focus of neurosurgery that involves methods like fluorescently labeling the tumor cells through 5-aminolaevulinic acid or neuronavigation [21]. The role of neuronavigation may be misleading as it can cause brain shift during surgery although it leads to the clear imaging of the tumor. As a result of this, the tumor borders are often not predicted in accordance with reality [22]. Patients undergoing clinical trials for 5-ALA showed a drastically decreased second resection as compared to the ones who were operated specifically under white light [23]. However, 5-ALA suffers from the drawback that the fluorescent activity is not shown by all the tumor cells. Hence, neither of 5-ALA and neuronavigation could completely solve the intraoperative problem of precisely separating intact brain parenchyma and tumor tissue. Confocal laser endomicroscopy (CLE) is a latest option with regard to optical imaging which has already found successful application in pulmonology and gastroenterology. According to a report as early as 1957, the light from out-of-focus molecules is
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significantly reduced by the confocal microscopy. In confocal laser microscopy, the source emits a very precise beam of light that is in turn emitted by the sample thereby significantly reducing the amount of scattered light. On the other hand, the tissue is widely lit up by the conventional fluorescence microscopes. A clear focussed image is generated by the confocal light which is facilitated by the presence of an interposed pinhole. This pinhole allows the detection of light from only the desired points by cutting off all the remaining scattered light. Thus, this method allows for the microscopic scale visualization of the tissues in conjunction with the device in use. The technique has also made it possible to have real time images at par with the histologic slices and thereby comes up as a highly useful tissue alteration diagnostic tool [24–26]. With all these results, the CLE could potentially establish itself as a promising tool in neurosurgery. Currently, the technique is undergoing evaluation in different settings. The major advantage has been the fact that it can be used in an intraoperative setting. This allows the neurosurgeons for a more precise borderline scanning of the tumors with welldefined resections to improve the outcome in brain tumor patients. Recently, it has been demonstrated that reliable images are provided by the EndoMAG1 combined confocal laser microscopy as seen through tissue cultures and pig brain and human brain tumors. A very well-characterized endoscopic image is seen for all the structures. Potentially, the method could provide a real time diagnostic histology. However, a more detailed correlation study between the histopathological diagnosis and confocal endoscopic imaging needs to be done through further clinical research before its fruitful development and application in the field of neurosurgery.
History of Functional Stereotaxy The physician Robert Henry Clarke who worked with the pioneer British neurosurgeon Victor Mosley since 1880 in the University College, London had originally devised stereotaxy. Their interests particularly revolved in deciphering the role of the cerebellum in relation to movement. In order to investigate the role of cerebellar nuclei in movement they chose apes to place electrodes in the cerebellar nuclei to create electrical stimulations. The localization was controlled with the help of a precise electrolytic lesion free from any collateral damage to the target. It was soon found out that the precise electrode localization was inhibited by the lack of anatomical landmarks. The situation is aggravated by the skull curvature and the variability of the depth that was largely dependent on the varying bone thickness. Subsequently, Clarke was able to design a
procedure free from such altering factors. The basic idea involved the creation of a point of intersection of three perpendicularly placed planes. The distance of the target from each plane was separately measured (very much similar to the x, y, z coordinates of the rectangular Cartesian system). In order to limit the movement of the head while introducing the electrodes a rectangular frame was fixed to the skull. It served a dual role of carrier for the electrodes and a stable holder. Anode current was used to make the electrolytic lesions. The work got published for the first time in 1906 as a short report and then in detail in 1908 and they termed the method as stereotaxis [27]. Later on the system was upgraded by the neurophysiologist Aubrey Mussen to be used as a stereotactic frame for humans that got very limited acceptance [28]. An additional reference point (at the beginning of the calcified pineal body) was introduced to be used in the system by Ernst Adolf Spiegel, the pioneer of human stereotaxy. However, the calcification of the pineal body was not a general process and hence its visibility through radiographic images was limited and accordingly the reference point was changed to the posterior commissure by Spiegel [29]. Ventriculography mediated lateral ventricular images were required for the visualization of the posterior commissure which was initially made possible with diluted contrast media or with air. Henry Wycis, a Philadelphiabased neurosurgeon, was able to put into practice the minimally invasive method designed by Spiegel quite efficiently for functional disorder treatments [30–32]. In the first ever stereotactic surgery performed in 1947, Clarke’s frame was modified to include an additional cast for fixing the head [29]. The first stereotactic neurosurgery was performed by Wycis and Spiegel just a year later when they operated a Parkinson’s disorder patient. This remained to be the only effective therapeutic intervention in Parkinson’s disease until the discovery of L-DOPA. The functional stereotaxis is primarily related to applied neurophysiology and hence its understanding requires an indepth knowledge of neurophysiology in addition to the understanding of imaging technology, sophisticated mechanical equipments, stimulation effects, and topographical anatomy. The anterior commissure was introduced in addition to the posterior commissure by the neurosurgeon Jean Talairach [33]. In 1961, Gerard Guiot and Madame Denise Albe-Fessard successfully introduced microelectrode recordings in the thalamus during stereotactic surgery. This enabled the intraoperative recording of the tremor sensitive cells in Parkinson’s disorder patients [34]. In 1949, a target centered stereotactic frame was designed by Leksell while working at the Karolinska Institute. A higher level of flexibility for the trajectory was made possible by this system as it enabled the surgeon to reach the target from any angle as it positioned the target
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into the isocenter of the frame [35]. In 1951, Leksell in collaboration with the physicist Borje Larson at the Uppsala University devised the first ever stereotactic irradiation apparatus [36]. The isocentrally placed target could be irradiated with a high local dose leaving aside the surrounding normal brain tissues. This is accomplished since around two hundred separate sources are used for irradiation. Freiburg became the central hub for stereotactic surgery in Germany around the fifties of the twentieth century. A polar coordinate system was used by Riechert and Wolff to first make a prototype and then an advanced stereotactic system around the same time [37]. An additional phantom was added to the upgraded version that could check for the trajectory and the coordinates [38]. Until the eighties, the system remained to be the most preferred one due to its preciseness rendered by an advanced mechanical set up and manually subtle electrodes and instruments. One of the major contributors to this success of the Freiburg group was Rolf Hassler. He was an expert in neuroanatomy with speciality in the thalamus anatomy, a highly desirable qualification for the field. A clear and subtle subdivision of the thalamic nuclei was possible mainly because of his anatomical knowledge. It is because of his depth of knowledge and contribution that the basal ganglia was soon replaced by the thalamus to be an integral part of functional stereotaxy and became highly applicable in the treatment of specific cases like the Morbus Parkinson [39]. Hassler later went on to study Morbus Parkinson in detail at the Max Plank Institute, Frankfurt. In Japan, Uchimura and Narabayashi designed a stereotactic frame upon the lines and ideas of Spiegel, Clarke, and Horsley in 1949. In 1951, he became the first successful neurosurgeon to carry out stereotactic pallidotomy. He later went on to develop a famous clinic and well-known research center for movement disorders. The atlases for the fine brain structures were the only support of stereotactic methods with regard to the topographical anatomy. Spiegel and Wycis went on to publish the first ever atlases meant for stereotactic procedures in 1952 and 1962, respectively. However, the 1959 published Schaltenbrand–Bailey atlas become the most frequently used atlas for stereotactic neurosurgery. In 1977, Waldemar Wahren published an enlarged and revised version of the atlas. Generations of neurosurgeons were influenced by the work of Hassler for the detailed thalamic nuclei nomenclature. Around the seventies, L-DOPA was introduced as a therapeutic treatment for Parkinson’s disorder. As a result of this introduction, the functional stereotactic neurosurgery lost its importance and except for a few centers its use was discontinued. However, gradually side effects of the drug were discovered like the on–off phenomenon. In addition, the L-DOPA treatment was found ineffective in countering extrapyramidal problems such as essential tremor. Such negative consequences of L-DOPA
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resulted in the re-popularization of the stereotactic procedures since the eighties. The successful introduction of electrodes without the need to create lesions for stimulation significantly improved the treatment of movement disorders. In the seventies and eighties, intractable pain was also treated by the use of this deep brain stimulation. Later on the technique was successfully used for the treatment of Morbus Parkinson [40]. These earlier works in the field of functional stereotaxy paved the way for the development of modern day technologies in the field of neurosurgery.
Robotics in Neurosurgery Therapeutic interventions have undergone a paradigm shift after the application of robotics in surgery. Intuitive Surgical’s da Vinci system, the most common surgical robot was cleared by the Food and Drug administration of the US in relation to multiple operative categories. Post 9 years of its clearance it has been used in nearly 80 % of prostatectomies in the United States. Subsequently, it has found mention in as many as 4,000 peer reviewed publications [41]. The rapid progress and development of medical robotics have been possible due to a combination of factors that include advanced imaging systems in the medical filed (better resolution, 3D ultrasound, and magnetic resonance imaging), improved technologies (materials, motors, and control theory) and increased acceptance of robotic assistance as well as laparoscopic techniques by both patients and surgeons. As during any technological revolution, the robotics is finding increased usage in the medical field. The robotics with their accurate and precise medical imageaided motions can help in brain surgery which often requires the access to targets that are surrounded by delicate tissues and deeply buried [42, 43]. The first ever use of a robot in brain surgery that used the helps of stereotactic frame and CT was performed for brain biopsy in 1985 [44]. In this case, the probe was oriented toward the target in order to define the biopsy trajectory which the surgeons could easily manipulate. A preoperative CT was registered to determine the orientation through stereotactic fiducials attached to the skull of the patient. However, the project was discontinued later on due to safety concerns. The Minerva robot designed in 1991 facilitates the real time CT-guided tool direction into the brain. This can help in the precise tracking of the targets that are image guided and particularly helpful during brain tissue swelling, shifting or sagging that occurs while operating. Minerva had the limitation of one-dimensional incursions and restricted real time CT and hence was discontinued in 1993 [45]. The recently developed neurosurgery robots are somewhat similar in purpose to that of the historical systems viz. cannulae orientation/image-guided positioning or other
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tools. Currently, in the stage of FDA clearance, the NeuroMate besides its role in biopsy can be beneficial in stereotactic electroencephalography, brain stimulation, neuroendoscopy, transcranial magnetic stimulation, and radiosurgery [46]. In 2004, the FDA cleared yet another robotic system for neurosurgery, the Pathfinder [47]. Based upon preoperative medical image, the surgeon makes use of the system to accurately specify the target and trajectory. The instrument is guided and positioned by the robot with submillimeter precision [48]. Subsequently, the system has been reportedly being used for making burr holes and guiding needles for biopsy [49]. In 2011, Renaissance (Mazor Robotics) received the FDA clearance as well as CE marks for brain operations and spinal surgery [50]. The system comprises of a soda bottle sized robot that guides for various software-based guidance and can be mounted directly onto the spine. The different applications include biopsies, deformity corrections, electrode placements, and minimally invasive surgeries. Renaissance also has the provision for ad-on for fluoroscopy which can be highly beneficial three-dimensional image-based intraoperative verification of the placement of the implants. There are reports to suggest that the spine assist/renaissance have significantly improved the accuracy of the implant placements and they can now be even placed percutaneously [51].
patients. However, recent reports suggest for some negative effects on the brain tissues by intensive insulin therapy [60, 61]. Proper precaution should be taken to analyze the data from clinical studies involving neurosurgical patients for intensive insulin therapy since neuroinjuries often alter brain glucose metabolism. The critical point to ponder is that the lower and upper plasma glucose threshold levels are not well defined. Moreover, consistency relating the glucose levels in brain and peripheral glucose measurements are required. An improved level of perioperative blood glucose level has been found to help prevent a number of the negative consequences of hyperG [60]. A number of factors need to be assessed for patients with other complications like in case of diabetic individuals, related conditions of hypertension, obesity, coronary arterial disease, renal insufficiency, and coronary artery disease can increase the perioperative risk [59]. Surgery often requires readjusted anti-diabetic therapy since it being a stressful event leads to disrupted oral intake [59]. The inpatient glucose response, outpatient treatment, glycemic control, presence of complications, blood glucose control level, surgical process involved and type of anesthesia should be considered in order to reduce metabolic derangements and surgery-associated complications.
PFA-100 as a Screening Technique in Neurosurgery Perioperative Glucose Control in Neurosurgery Adverse outcomes like prolonged hospital stay, increased hospital stay and higher rates of mortality have been found associated with both the non-diabetic and diabetic neurosurgical patients with hyperglycemia (hyperG) as suggested by different independent observations and studies [52–54]. Besides, the patients also suffer from negative effects of the glucose deficit [55, 56]. The subjects with pre-existing diabetes mellitus are at lesser risk than those unknown cases of hyperG [57]. Current reports show that the whole organism including the brain is affected by the deleterious effects of hyperG [58]. Hospital-induced hyperG and undiagnosed diabetes mellitus causes enhanced post-operative complicacies, length of hospital stay and costs [59]. HyperG has been found to be highly associated with the prognosis of various brain injury cases [60]. Notwithstanding its close linkage with the poor outcomes in brain surgery cases, it is hard to say whether hyperG is directly responsible for such results or it is just an epiphenomenon [58, 60]. Therefore, a strict surveillance of blood glucose could result in positive patient outcomes [58]. Subsequently, intensive insulin therapy has been tried out in order to regulate and maintain a tight blood glucose level (within a range of 80–110 mg/dL) in neurocritical
In surgery, the most dreaded and life-threatening complications has been hemorrhage particularly in case of neurosurgery where the patient can meet with devastating consequences due to it. This is because during neurosurgery the surgeon has impaired vision as there is very limited possibility for blood drainage [62, 63]. Therefore, it is mandatory that the diagnostic tools should be evaluated keeping in mind their ultimate influence on the patient outcome. No improvement in the patient outcome was detected after the introduction of PFA-100 in patients who have undergone neurosurgery for their preoperative screening. The PFA group patients received more desmopressin which did not seem to benefit them and hence the treatment of the drug was supposed unnecessary. It has also been established through studies that in case of post-traumatic brain injury the vasopressin receptors play an important role [64, 65]. However, it is assumed that the surgical procedure can be directly influenced by desmopressin. It has been previously found that the patients undergoing surgery often suffer platelet dysfunction and primary hemostasis disorders [66, 67]. Desmopressin has been found effective in the treatment of these disorders [68]. In order to solve such contradictory observations a number of different aspects need to be assessed. One of the crucial questions is the relevance of the PFA-100 in the
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detection of platelet functioning defect. This can provide the valuable information of the role of this defect in the operative and post-operative bleeding complications. The effectiveness of desmopressin in these patients should also be evaluated. The intake of aspirin can last several days on the patients which can result in a high PFA-Epi since it is highly sensitive to the effect of aspirin [69]. Therefore, it can be concluded that many of the surgical patients had aspirin administration before they underwent surgery. However, nothing significant has been associated with the intake of aspirin and increased perioperative bleeding [70]. Nonetheless, an abnormal PFA value can indicate the increased bleeding risk under such circumstances without providing a deterministic prediction for bleeding complications. In addition to the existing known factors perioperative bleeding has often been caused by non-anticipated preoperative factors. The inherent complexity and difficulty associated with surgical method is one such obvious risk factor. Besides, the undetected or preoperative factors like disturbances in the process of coagulation (e.g., increased fibrinolysis) can play a decisive role [71]. As a matter of fact desmopressin induces fibrinolysis and the combinatorial effect of desmopressin and tumor pathophysiology-induced fibrinolytic effect might bring about a hemostatic neutralization. It is therefore assumed that most of the preoperative cases of primary hemostasis are not clinically relevant. There may be other factors that can add on to the bleeding complications. With regard to the diagnosis of the cases of primary hemostatic disorder the PFA-100 shows a limited performance [72]. In particular, the performance has been hampered in patients with low hemoglobin or defect in platelet secretion [73]. Such conditions in the patient group might preclude a favorable preoperative result. Therefore, the PFA screening is carried out for a well-defined patient group where there can be very little subjective effect by the rightful selection of the control group.
100 billion neurons and hence is going to be a huge challenge for the future of neuroscience research. There are fantasies relating to the control of mind which remains largely elusive due to the inability to decode the memory encoding capacity of the brain and its mechanism [75]. Two phases are predicted to be crucial for the developments in BMI: in the first phase the BMI is concentrated for the disabled individuals consisting mainly of therapeutics, while the second phase will be more inclined toward healthy humans to enhance their motor and cognitive skills [75]. McGee and Maguire has predicted for the possibility of a third phase that will involve the transfer of information capabilities with the aid of neural devices [76]. Although the proposed third phase is still a long way from realization, it certainly predicts the enormous future potential of the BMI technology once it is put to practice in its fully developed form. The neurosurgical care can be related to large scale expenditure of the health system resources. As a matter of fact it significantly influences the clinical outcomes and the life quality which has often been found largely disproportionate to the number of encounters and our specialty size. Such interventions are associated with complex social, ethical, and medical dimensions with midlevel providers like nurses, physician assistants for the neurosurgeons. It has been observed that the concentration of the neurosurgical care is often focussed at the extremities of age (the end and beginning of life). The focus should be on the unforgiving nervous system with subspecialty coverage for hydrocephalus, neurotrauma, stroke that tremendously influences the outcome of the healthcare. It is for these reasons that the neurosurgeons have been undergoing updated training, education, and innovation for the advancement and improvement of our specialty and patient outcomes. Neurosurgery has beyond doubt come up as the leader in the field and it should be considered for additional support and care that could enhance the educational practices and provide the necessary goals [77].
Ethical Issues
Conclusion
The last decade has drastically changed our perception of the human brain with the advent of modern technologies in molecular biology, neuroscience, and updated brain imaging methods. A wide array of enhanced cognitive therapeutics development has been worked upon by the neuroscientists. Many such technologies can potentially become the pioneers for our deeper and further understanding of the human brain. It is even predicted that the twenty-first century may be referred to as the century of neuroscience [74]. The complexity of the field comes from the enormity of the neural network of the brain with its huge mesh of nearly 100 trillion synaptic connections and
The field of neurosurgery faces both new challenges as well as opportunities due to rapid advancements in molecular and technological approaches focused toward solving the neurosurgical problems. Our recent technologies in this regard have been a resultant of the transfer of the pressure prevalent on the neurosurgeons to perform an effective, quick, and error free surgical treatment of the patient as well as his effective and favorable post-operative outcome. The neurosurgeons have been able to precisely locate the position of an abnormal tissue in the spinal cord or the brain with the recent technological advancements. This has significantly reduced the surgical trauma of the
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normal tissues. More advances are necessary in the field for safer and successful outcome in the neurosurgical procedures. As a matter of fact the field of neurosurgery will continually feel the pressure of newer technology development.
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