Sergio Canavero's research while affiliated with First Affiliated Hospital of China Medical University and other places

Publications (169)

Chapter
There is at present no biological cure for chronic paralysis following spinal cord injury (SCI). Work conducted by U.S. neurosurgeon L. Walter Freeman in the 1960s suggests that a permanent, biological cure is possible, at least in several cases of chronic SCI, by removing the most damaged portion of the spinal cord en bloc, and connecting the two...
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Aim Despite animal evidence of a role of calcium in the pathogenesis of spinal cord injury, several studies conducted in the past found calcium blockade ineffective. However, those studies involved oral or parenteral administration of Ca++ antagonists. We hypothesized that Ca++ blockade might be effective with local/immediate application (LIA) at t...
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Background: Our study shows that a membrane sealant/fiber fusogen polyethylene glycol (PEG) applied immediately on a sharp section of the spinal cord can mend the cord and lead to exceptional levels of motor recovery, with some animals almost normal. Materials and methods: Before deploying such technology in man, long-term data in large mammals...
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A sharply transected spinal cord has been shown to be fused under the accelerating influence of membrane fusogens such as polyethylene glycol (PEG) (GEMINI protocol). Previous work provided evidence that this is in fact possible. Other fusogens might improve current results. In this study, we aimed to assess the effects of PEGylated graphene nanori...
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The reader is referred to Canavero [1–3] for an in-depth discussion.
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Transcranial magnetic stimulation (TMS) (Table 19.1): TMS in a repetitive mode (rTMS) is a noninvasive technique with a benign side effect profile and is easy to administer (for an in-depth description, see [38]). Patients are awake, are alert, and sit in a comfortable chair during treatment sessions, which are roughly 20–30 min in duration. Cardia...
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SCS (aka dorsal column stimulation) can be applied via surgical or percutaneous implantation of stimulating electrodes. Stimulation can be in tonic low-frequency (generally 50–100 Hz), high-frequency (up to 10 kHz; pulsed, 500 kHz; [1]), or burst (paresthesia-free) mode. A definitive pacemaker is applied after a suitable test period, in the abdomen...
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When one considers neuropathic pain globally, 6.9%–10% of the entire population is affected [1].
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Brain central pain (BCP) has been caused by all kinds of lesions at any level along the spinothalamoparietal path, from brainstem to cortex. These include rapidly or slowly developing processes, compressive or disruptive/distractive. Minor indirect trauma can also cause BCP [1, 2]. Stroke, either ischemic or hemorrhagic, is the commonest cause of B...
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The evidence reviewed in the genesis chapter makes a strong case for CP being the result of a localized “locked” reverberating loop between the somatosensory cortex and the sensory thalamus (Dynamic Reverberation). In those cases with complete S1 or thalamic destruction, the reverberant loop is activated in the opposite hemisphere. In this model, t...
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A placebo is an inert treatment, be it pharmacological or nonpharmacological, with no specific therapeutic properties for the condition being treated. A placebo effect, i.e., a positive effect on the therapeutic outcome, may follow the administration of such inert treatment. This is different from spontaneous remission or regression to the mean. On...
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The first recorded treatment of neuropathic pain with a sodium (Na+) channel blocker is probably Sigmund Freud’s treatment of Ernst von Fleischl’s trigeminal neuralgia with cocaine injections. Deisenhammer et al. [1] published the first Medline-indexed paper detailing the use of a Na+ channel blocker (carbamazepine) for CP (Tables 13.1, 13.2, 13.3,...
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Transcutaneous electrical nerve stimulation (TENS) is applied at high frequency (80–100 Hz) (also known as conventional TENS) aimed at activation of myelinated cutaneous sensory fibers or low-frequency stimulation (short trains of impulses at 1–4 Hz, known as acupuncture-like TENS) and aimed at activation of small-diameter nonnoxious muscle afferen...
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Antiglutamatergic agents, despite many initial hopes and several compounds tested, are not a mainstay of treatment of CP and are only infrequently used. The antiglutamatergic drug of choice remains parenteral ketamine. However, ketamine is a drug of addiction with neurotoxic (particularly with intrathecal/epidural administration) effects and unplea...
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Several approaches have been tested and can be integrated into a comprehensive palliative program for CP. These are discussed alphabetically (Table 27.1).
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Inhaled cannabis (Cannabis sativa) may provide short-term (2 weeks) relief with an NNT of 5.6 (3.4–14) in patients with peripheral neuropathic pain [1], as compared with an NNT of gabapentin of 5.9 (4.6–8.3) for the same population. Thus, both drugs are not very effective. More relevant, the toxicity profile is not benign, militating against long-t...
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Electroconvulsive therapy (ECT) has also been employed for pain control [1].
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This chapter describes conditions that do not fit the definition of central pain as given in the introduction chapter but have central mechanisms.
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Central pruritus (CP) following CNS damage (Tables 5.1 and 5.2) has not received adequate recognition as part of the spectrum of CP (while it is well known as a consequence of PNP). Pruritus can blend with pain or dysesthesias or present singly (note that pain-insensitive patients are also itch-insensitive: [38]). Most likely, patients may complain...
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Deep brain stimulation (DBS) involves the insertion of suitable electrodes into the brain.
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Opioids (including tramadol and, pending confirmation, cebranopadol) are not indicated in the routine management of CP, alone or in combination (e.g., with aminergics) [1, 2]. The first patient in history to be diagnosed with CP was also opioid unresponsive [3]. Most chronic pain patients on long-term opioids report strong or very strong pain, high...
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These drugs modulate the release of aminergic and non-aminergic neurotransmitters from brainstem (e.g., locus coeruleus, raphe nuclei, etc.) and basal forebrain (e.g., Meynert’s nucleus) nuclei. Fibers leaving these nuclei fan out both upward into the brain and downward to the cord. These regulate the function and activation state of the brain, bot...
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A wide spectrum of sensory abnormalities can be found among patients with CP. They range from a slightly raised threshold for one of the submodalities to complete loss of all somatic sensibility in the painful region or a very painful hyperesthesia. However, pain distribution is usually well correlated with sensory abnormalities (Tables 4.1 and 4.2...
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Several other molecules have been tried for CP. NSAIDs are useless, but tried by the vast majority of patients. Botulinum, which has pleiotropic actions (substance P/CGRP and glutamate block), and may have unexpected central effects, is interesting, but its effects are modest at best. Cholinergics (e.g., donepezil) have not been adequately tested,...
Chapter
CP is pain/dysesthesia/pruritus due to a CNS lesion along the spinothalamoparietal (STP) path. Thus, an appropriate lesion must be demonstrated in such a location. Bilateral pain and dysesthesia referred to the limbs, although usually pointing to a spinal cord lesion, may rarely be observed after unilateral brain lesions.
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Psychological treatment is targeted on pain cognition, e.g., catastrophizing, pain-related beliefs and coping, and social factors. In particular, catastrophizing is a predictor of a worse outcome for neuropathic pain, including CP [1]. Emotional and cognitive factors (e.g., anxiety, depression, and anger or, vice versa, positive emotions) are known...
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Central pain (CP) remains one of the most ill-treated entities among chronic pain syndromes. No drug is substantially effective in a majority of patients, despite claims to the contrary by the pharma industry and regulatory agencies. Apparently, significant treatment effects reported in pharma-sponsored trials would have been much smaller or absent...
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Despite regulatory approval, gabapentinoids are not superior to much cheaper agents. Clinically meaningful pain relief with gabapentinoids is achieved in fewer than 20% of patients with discrete diagnoses, and patients with poorly defined disorders such as fibromyalgia fare even worse, with reductions in pain intensity across a number of conditions...
Chapter
The anatomophysiological “engine” of CP is a focal, self-sustaining, reverberating loop between the sensory cortex and the sensory thalamus (Dynamic Reverberation, DR) ([1], Figs. 8.1 and 8.2), following the establishment of an intracortical S1 attractor state (locked S1) (e.g., layer 4⇒ (layer 2/3⇒) layer 5⇒ layer 6⇒ layer 4+corticothalamic outflo...
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Several drugs have been administered intrathecally (IT) in attempting to treat CP. Unfortunately, no well-designed studies with homogeneous groups of patients and long-term follow-up are available for definite conclusions. However, drug combinations (e.g., midazolam/clonidine/bupi- or ropivacaine or baclofen/clonidine/bupi- or ropivacaine) may be m...
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Published guidelines from different organizations are biased by heavy interference from pharma companies and as such totally unreliable. In putting together our conflict-of-interest-free recommendations, we hewed firstly to the Hippocratic Oath, i.e., primum non nocere, and secondly to cost containment. The reader will notice how different are our...
Chapter
Inflammation has been linked to chronic pain, including peripheral neuropathic pain. CCP is often associated with root injury, i.e., PNP: this triggers local inflammation and supraspinal changes in cytokine or chemokine expression (neuroinflammation) [1]. Since inflammation has been associated, among many others, with depression, aggressively targe...
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GABA receptors are pentameric heterooligomers; at least 19 distinct GABA-A receptor subunit genes exist, classified into eight classes (α1–6, β1–3, γ1–3, δ, ε, θ, π, and ρ1–3). GABA-A receptor assembly can be derived from a permutation and combination of two, three, four, or even five different subunits. Distribution of the major subunits in variou...
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Traditional acupuncture has been used for millennia in China and has been widely adopted in the West only in the second half of the twentieth century. However, in the nineteenth century, Sir William Osler [1] in his highly acclaimed textbook wrote in the section on treatment of neuralgia (pp. 962–963) “acupuncture may be used” (Table 29.1).
Book
This book sheds new light on central pain, a field that is largely obscured by lack of knowledge among pain professionals at all levels, including high-end pain centers. As a matter of fact, central pain, classified as a form of neuropathic pain, remains too often a scourge for those affected due to the ignorance of pain therapists worldwide and en...
Article
Background: Cephalosomatic anastomosis or what has been called a "head transplantation" requires full reconnection of the respective transected ends of the spinal cords. The GEMINI spinal cord fusion protocol has been developed for this reason. Here, we report the first randomized, controlled study of the GEMINI protocol in large animals. Methods...
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Background Cephalosomatic anastomosis (CSA) has never been attempted before in man as the transected spinal cords of the body donor and body recipient could not be “fused” back together. Recent advances made this possible. Here, we report on the surgical steps necessary to reconnect a head to a body at the cervical level. Methods Full rehearsal of...
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A sound ethical debate in biomedicine calls for (1) equipoise and (2) knowledge. The debate surrounding HEAVEN, the head transplant initiative, has been based on the exact opposite. Here we show that (1) HEAVEN is technically feasible and (2) HEAVEN can help patients with no other course of curative treatment available. At the same time we highligh...
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Aims: Despite more than a century of research, spinal paralysis remains untreatable via biological means. A new understanding of spinal cord physiology and the introduction of membrane fusogens have provided new hope that a biological cure may soon become available. However, proof is needed from adequately powered animal studies. Methods and resu...
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Aims: A successful cephalosomatic anastomosis ("head transplant") requires, among others, the ability to control long-term immune rejection and avoidance of ischemic events during the head transference phase. We developed a bicephalic model of head transplantation to study these aspects. Methods and results: The thoracic aorta and superior vena...
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In June 2013, the world was taken by storm by the announcement that a full head (or body) transplant was possible.[1] This key achievement would have been made possible by the GEMINI spinal cord fusion protocol.
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The HEAVEN head transplant initiative needs human data concerning the acute restoration of motor transmission after application of fusogens to the severed cord in man. Data from two centuries ago prove that a fresh cadaver, after hanging or decapitation, can be mobilized by electrical stimulation for up to 3 hours. By administering spinal cord stim...
Article
Cephalosomatic anastomosis has been carried out in both monkeys and mice with preservation of brain function. Nonetheless the spinal cord was not reconstructed, leaving the animals unable to move voluntarily. Here we review the details of the GEMINI spinal cord fusion protocol, which aims at restoring electrophysiologic conduction across an acutely...
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Cephalosomatic anastomosis requires neuroprotective techniques, such as deep hypothermia, to preserve brain activity. Despite the failure of pharmacologic neuroprotection, new strategies, including ischemic pre- and postconitioning and the use of Perftoran, have to be explored to complement hypothermia. This article summarizes the field of brain pr...
Article
One of the key obstacles to a successful head transplant is the possible onset of central pain, a chronic pain condition that would impair the quality of life of the transplantee. In this review, we provide the reader with a knowledge of this neglected aspect of the head transplant initiative and outline the management should this eventuality occur...
Article
Despite clear advancements in our understanding of the genesis of central pain (CP) [1,2], four notions continue to stand out in the neuropathic pain literature that—we will argue—must be thoroughly revised, if not discarded. We will refer to them as Pain Myths. In light of the supposed failures of cortectomies or thalamotomies to relieve phantom...
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In 1970, the first cephalosomatic linkage was achieved in the monkey. However, the technology did not exist for reconnecting the spinal cord, and this line of research was no longer pursued. In this paper, an outline for the first total cephalic exchange in man is provided and spinal reconnection is described. The use of fusogens, special membrane-...
Chapter
Central pain can easily be described as hallucinatory pain, being couched as a disturbance of sensory information transfer along an uninhibited reverberating corticothalamocortical sensory channel. This generator alters the widely distributed small-world architecture of the brain, which can be neuroimaged, for instance, as an alteration of brain rh...
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This chapter explains how cortical stimulation (CS) aims at changing the excitability or activity of cortical and related subcortical networks involved in pathophysiological processes. The cortex accommodates pyramidal and non-pyramidal cells, with a total number of neocortical synapses numbering at about 300 000 billion. In view of variations in l...
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A fully updated new edition of this definitive, unrivalled, no-nonsense textbook, Central Pain Syndrome: Pathophysiology, Diagnosis and Management provides new treatment guidelines that aid the reader in effective management. • Encyclopedic coverage of all drug and surgical therapies, including the hot field of non-invasive and invasive cortical st...
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It is debatable as to whether the spontaneous blood-oxygen-level dependent fluctuations that are observed in the resting brain in turn reflect consciously directed mental activity or, alternatively, constitute an intrinsic property of functional brain organisation persisting in the absence of consciousness. This report shows for the first time, in...
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The spontaneous component of neuropathic pain (NP) has not been explored sufficiently with neuroimaging techniques, given the difficulty to coax out the brain components that sustain background ongoing pain. Here, we address for the first time the correlates of this component in an fMRI study of a group of eight patients suffering from diabetic neu...
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Extradural motor cortex stimulation has been employed in cases of Parkinson's disease (PD), fixed dystonia (FD) and spastic hemiparesis (SH) following cerebral stroke. Symptoms of PD are improved by EMCS: results were evaluated on the basis of the UPDRS and statistically analysed. In PD EMCS is less efficacious than bilateral subthalamic nucleus (S...
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Full-text available
Extradural motor cortex stimulation has been employed in cases of Parkinson’s disease (PD), fixed dystonia (FD) and spastic hemiparesis (SH) following cerebral stroke. Symptoms of PD are improved by EMCS: results were evaluated on the basis of the UPDRS and statistically analysed. In PD EMCS is less efficacious than bilateral subthalamic nucleus (S...
Article
Central pain (CP), namely, pain or allied symptoms that follow damage to the CNS, has remained an obscure neurological syndrome with no explanation or effective treatment since Edinger's description in 1891. Once believed to be rare, CP is now known to affect several millions of people worldwide, making it at least as frequent as, for example, Park...
Article
Extradural cortical stimulation is a recent addition to the armamentarium of operative neuromodulation. Motor cortex stimulation (MCS) is offered by positioning a stimulating plate extradurally on the primary motor cortex. It is a minimally invasive technique that was originally proposed for the control of central neuropathic pain. Currently, its u...
Article
Central pain results from a central nervous system injury and represents a challenge for the pain therapist. Human studies have shown that motor cortex stimulation (MCS), i.e. the placement of a stimulating plate on the dura overlying the motor cortex can relieve brain central pain. Studies suggest that MCS directly affects activity in the first an...
Chapter
Central pain results from a central nervous system injury and represents a challenge for the pain therapist. Human studies have shown that motor cortex stimulation (MCS), i.e. the placement of a stimulating plate on the dura overlying the motor cortex can relieve brain central pain. Studies suggest that MCS directly affects activity in the first an...
Chapter
Extradural cortical stimulation is a recent addition to the armamentarium of operative neuromodulation. Motor cortex stimulation (MCS) is offered by positioning a stimulating plate extradurally on the primary motor cortex. It is a minimally invasive technique that was originally proposed for the control of central neuropathic pain. Currently, its u...
Article
The pharmacological treatment of neuropathic pain remains unsatisfactory. This is partly owing to poor knowledge of available drugs on the part of treating physicians, but equally important is the poor correlation between animal models and clinical effects. In this review, we survey the field and draw several conclusions, particularly that current...
Article
Trigeminal neuralgia is a chronic pain syndrome of still unestablished origin. Its diagnosis depends on clinical grounds. Drug therapy initially helps a great majority of patients. The choice of drugs is quite large, but truly effective compounds with a tolerable side effect profile remain few. Carbamazepine (or oxcarbazepine) and lamotrigine appea...
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Objective. We assessed the effects of bilateral extradural motor cortex stimulation (ECS) to areas of maximal functional MRI (fMRI) activation in a male patient with plegic stroke by using multiple sequential 1-month blocks of stimulation with single-blind design in a tertiary referral hospital. Measurements. Assessments included the European Strok...
Article
Transcranial magnetic stimulation recently has emerged as a therapeutic tool in neurology and psychiatry, with contradictory results. Central pain, a major chronic pain syndrome affecting millions of people worldwide, has been the focus of a few studies. Although transcranial magnetic stimulation has no role in the chronic management of such pain,...
Article
To validate IV subhypnotic propofol, a gamma-aminobutyric acid A (GABA-A) agonist, as a diagnostic test for central pain. The efficacy of systemic propofol (0.2 mg/kg IV bolus) was evaluated in a double-blind, placebo-controlled and crossover fashion on both spontaneous ongoing pain and allodynia in 44 patients with chronic central pain of both bra...
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In a recent issue of the ARCHIVES, Kleiner-Fisman et al1 reported the use of motor cortical stimulation for multiple system atrophy (MSA)–related parkinsonism. A few comments are in order. We introduced extradural motor cortical stimulation for Parkinson disease (PD) in 1998 and have since reported 3 cases.2- 4 We observed that low-frequency but no...
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Central pain, which follows brain and spinal cord injury remains an ill-treated entity affecting approximately 1-2 million people worldwide. When oral drugs fail, either immediately or in the long run, the only therapeutic option is neuromodulation, via either electrical or chemical means. The whole spectrum of neuromodulatory techniques for centra...
Article
Neuroprotection in the setting of severe head injury (SHI) remains an unsettled problem. We tested a combination of high-dose magnesium and low-dose lidocaine, infused over 3 days, in a pilot study to assess safety. This combination appears indicated to protect both gray and white matter from secondary injury following SHI. We studied 32 consecutiv...
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pathic pain is clinically unresponsive to oral opioids, even at high doses. Only 30 percent of the patients who had central pain after stroke or a focal brain le- sion were able to complete the study, reporting only a 20 percent reduction in pain from base line. Other controlled studies support this assumption. In two studies of patients with centr...
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Only about 50% of central pain patients respond to motor cortex stimulation in the long run. There is a need for prognostic factors. Here we show that propofol test and TMS both predict short-term effect in nine patients with central pain. This may help reduce the number of failures.
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Extradural motor cortex stimulation was introduced in 1989 for control of central pain. In recent years this has been found useful in several patients with movement disorders. This paper attempts to bring together all the relevant literature, discuss mechanisms and lay out guidelines for future research and clinical applications.
Article
A case of simultaneous trigeminal and vagoglossopharyngeal neuralgia is described. No microvascular compression was seen at the trigeminal complex while the origin of vagoglossopharyngeal pain could have been due either to Chiari malformation or microvascular compression of the IX-X nerve complex. Decompressive surgery was ineffective. The patient...