Optimization of Radiofrequency Needle Placement in Percutaneous Cordotomy Using Electromyography in the Deeply Sedated Patient.

BACKGROUND AND OBJECTIVES: Cordotomy, the selective disconnection of the nociceptive fibers in the spinothalamic tract, is used to provide pain palliation to oncological patients suffering from intractable cancer-related pain. Cordotomies are commonly performed using a cervical (C1-2) percutaneous approach under imaging guidance and require patients' cooperation to functionally localize the spinothalamic tract. This can be challenging in patients suffering from extreme pain. It has recently been demonstrated that intraoperative neurophysiology monitoring by electromyography may aid in safe lesion positioning. The aim of this study was to evaluate the role of compound muscle action potential (CMAP) in deeply sedated patients undergoing percutaneous cervical cordotomy (PCC). METHODS: A retrospective analysis was conducted of all patients who underwent percutaneous cordotomy while deeply sedated between January 2019 and November 2022 in 2 academic centers. The operative report, neuromonitoring logs, and clinical medical records were evaluated. RESULTS: Eleven patients underwent PCC under deep sedation. In all patients, the final motor assessment prior to ablation was done using the electrophysiological criterion alone. The median threshold for evoking CMAP activity at the lesion site was 0.9 V ranging between 0.5 and 1.5 V (average 1 V ± 0.34 V SD). An immediate, substantial decrease in pain was observed in 9 patients. The median pain scores (Numeric Rating Scale) decreased from 10 preoperatively (range 8-10) to a median 0 (range 0-10) immediately after surgery. None of our patients developed motor deficits. CONCLUSION: CMAP-guided PCC may be feasible in deeply sedated patients without added risk to postoperative motor function. This technique should be considered in a group of patients who are not able to undergo awake PCC.

Open Thoracic Cordotomy for Cancer Pain with Intraoperative Neuromonitoring: A Case Series and Critical Review of the Literature.

OBJECTIVE: Cordotomy is a viable option for patients with intractable cancer pain and limited survival. Open thoracic cordotomy is offered when patients are not candidates for percutaneous cordotomy. After the open procedure, traditionally performed purely based on anatomic landmarks, up to 22% of patients experience postoperative limb weakness. The objective of this study is to report our experience with neurophysiology-guided open cordotomy along with a critical review of the literature. METHODS: Between 2019 and 2022, 5 open thoracic cordotomies were performed in our center. Intraoperative neurophysiologic monitoring was used in all cases to guide the lesion and standard single-level laminectomy or hemilaminectomy was performed for exposure. Outcome measures were retrospectively reviewed focusing on pain control and neurologic status. Existing literature on cordotomy was critically reviewed. RESULTS: There was satisfactory pain relief with preservation of motor function in all 5 cases. Temperature sensation was preserved in all but 1 patient, who lost it after the previous ipsilateral percutaneous cordotomy (PCC). No procedural complications were experienced. We found that the neurophysiology monitoring lesion was guided anterior compared with what would have been lesioned on an anatomic basis. CONCLUSIONS: Open thoracic cordotomy is a safe and effective procedure for intractable cancer-related pain. Technical advancements significantly reduced mortality and major morbidity of PCC. Our series suggests that neurophysiology monitoring alters the location of the lesion and may help better targeting of pain fibers within the spinothalamic tract and preserve other long tracts. The safety profile of open cordotomy with neurophysiology compares favorably with the PCC.

Injury of the Spinothalamic Tract Following Whiplash Injury: A Diffusion Tensor Tractography Study.

OBJECTIVES: Using diffusion tensor tractography (DTT), we demonstrated the spinothalamic tract (STT) injury in patients with central pain following whiplash injury. Our primary hypothesis is that fractional anisotropy (FA) and tract volume (TV) of the STT in injured people differ from non-injured people. Our secondary hypothesis is that the direction of the collision results in a different type of injury. METHODS: Nineteen central pain patients following whiplash injury and 19 normal control subjects were recruited. The STT was reconstructed by the DTT, the FA and TV of the STT were measured. In addition, different characteristics of the STT injury according to the collision direction were investigated. RESULTS: The FA value did not differ significantly between the patient and control groups (p > 0.05). However, the significantly lower value of the TV was observed in patient group than the control group (p < 0.05). The onset of central pain was significantly delayed (13.5 days) in patients who were involved in a frontal collision, compared to patients with rear-end collision (0.6 days) (p < 0.05). In contrast, the Visual Analogue Scale was higher in the patients with rear-end collision (p < 0.05). CONCLUSIONS: We found the STT injury mild traumatic brain injury (TBI) who suffered central pain after whiplash injury, using DTT. In addition, we demonstrated different characteristics of the STT injury according to the collision direction. We believe that injury of the STT would be usefully detected by DTT following whiplash injury.

Diagnostic sensitivity of traumatic axonal injury of the spinothalamic tract in patients with mild traumatic brain injury.

ABSTRACT: Diffusion tensor tractography (DTT) can detect traumatic axonal injury (TAI) in patients whose conventional brain magnetic resonance imaging results are negative. This study investigated the diagnostic sensitivity of TAI of the spinothalamic tract (STT) in patients with a mild traumatic brain injury (TBI) suffering from central pain symptoms, using DTT.Thirty-five patients with central pain following mild TBI and 30 healthy control subjects were recruited for this study. After DTT-based reconstruction of the STT, we analyzed the STT in terms of configuration (narrowing and/or tearing) and the DTT parameters (fractional anisotropy and tract volume).Thirty-three (94.3%) patients had at least 1 DTT parameter value at 1 standard deviation below the control group value, and 20 (57.1%) patients had values at 2 standard deviations, below the control group value. All 35 patients showed STT abnormalities (tearing, narrowing, or both) on DTT.A high diagnostic sensitivity of TAI of the STT in patients with mild TBI was achieved. However, the small number of subjects who visited the university hospital and the limitations of DTT should be considered when generalizing the results of this study.

Microglial deactivation by adeno-associated virus expressing small-hairpin GCH1 has protective effects against neuropathic pain development in a spinothalamic tract-lesion model.

AIMS: Neuropathic pain after spinal cord injury is one of the most difficult clinical problems after the loss of mobility, and pharmacological or neuromodulation therapy showed limited efficacy. In this study, we examine the possibility of pain modulation by a recombinant adeno-associated virus (rAAV) encoding small-hairpin RNA against GCH1 (rAAV-shGCH1) in a spinal cord injury model in which neuropathic pain was induced by a spinothalamic tract (STT) lesion. METHODS: Micro-electric lesioning was used to damage the left STT in rats (n = 32), and either rAAV-shGCH1 (n = 19) or rAAV control (n = 6) was injected into the dorsal horn of the rats at the same time. On postoperative days 3, 7, and 14, we evaluated neuropathic pain using a behavioral test and microglial activation by immunohistochemical staining. RESULTS: A pain modulation effect of shGCH1 was observed from postoperative days 3 to 14. The mechanical withdrawal threshold was 13.0 ± 0.95 in the shGCH1 group, 4.3 ± 1.37 in the control group, and 3.49 ± 0.85 in sham on postoperative day 3 (p < 0.0001) and continued to postoperative day 14 (shGCH1 vs. control: 11.4 ± 1.1 vs. 2.05 ± 0.60, p < 0.001 and shGCH1 vs. sham: 11.4 ± 1.1 vs. 1.43 ± 0.54, p < 0.001). Immunohistochemical staining of the spinal cord dorsal horn showed deactivation of microglia in the shGCH1 group without any change of delayed pattern of astrocyte activation as in STT model. CONCLUSIONS: Neuropathic pain after spinal cord injury can be modulated bilaterally by deactivating microglial activation after a unilateral injection of rAAV-shGCH1 into the dorsal horn of a STT lesion spinal cord pain model. This new attempt would be another therapeutic approach for NP after SCI, which once happens; there is no clear curative options still now.

Identifying Discomplete Spinal Lesions: New Evidence from Pain-Autonomic Interaction in Spinal Cord Injury.

The clinical evaluation of spinal afferents is an important diagnostic and prognostic marker for neurological and functional recovery after spinal cord injury (SCI). Particularly important regarding neuropathic pain following SCI is the function of the spinothalamic tract (STT) conveying nociceptive and temperature information. Here, we investigated the added value of neurophysiological methods revealing discomplete STT lesions; that is, residual axonal sparing in clinically complete STT lesions. Specifically, clinical pinprick testing and thermal thresholds were compared with objective contact heat-evoked potentials (CHEPs) and a novel measure of pain-autonomic interaction employing heat-induced sympathetic skin responses (SSR). The test stimuli (i.e., contact heat, pinprick) were applied below the lesion level in 32 subjects with thoracic SCI while corresponding heat-evoked responses (i.e., CHEPs and SSR) were recorded above the lesion (i.e., scalp and hand, respectively). Readouts of STT function were related to neuropathic pain characteristics. In subjects with abolished pinprick sensation, measures of thermosensation (10%), CHEPs (33%), and SSR (48%) revealed residual STT function. Importantly, SSRs can be used as an objective readout and when abolished, no other proxy indicated residual STT function. No relationship was found between STT function readouts and spontaneous neuropathic pain intensity and extent. However, subjects with clinically preserved STT function presented more often with allodynia (54%) than subjects with discomplete (13%) or complete STT lesions (18%). In individuals with absent pinprick sensation, discomplete STT lesions can be revealed employing pain-autonomic measures. The improved sensitivity to discerning STT lesion completeness might support the investigation of its association with neuropathic pain following SCI.

Cervical Cordotomy in Terminal Cancer: Pain Relieving in Oncological Treatment

Cordotomy consists in the discontinuation of the lateral spinothalamic tract (LST) in the anterolateral quadrant of the spinal cord, which aims to reduce the transference of nociceptive information in the dorsal horn of the gray matter of the spinal cord to the somatosensory cortex. The main indication is for patients with terminal cancer that have a low life expectancy. It improves the quality of life by relieving pain. The results are promising and the pain relief rate varies between 69 and 100%. Generally speaking, the complications are mostly temporary and not remarkable.

Anatomical location of the spinothalamic tract in the subcortical white matter in the human brain: A diffusion tensor imaging study.

INTRODUCTION: We investigated the anatomical location of the spinothalamic tract and its thalamocortical pathway (STT) in the subcortical white matter in normal subjects, using diffusion tensor tractography (DTT). MATERIALS AND METHODS: The STT was reconstructed using FMRIB software in 40 normal subjects. The most probable locations of the STT were defined as the location on an axial slice of the centrum semiovale (CS), corona radiata (CR), and posterior limb of the internal capsule (PL). RESULTS: The STT was located at an average of 62.66% in the anterior to posterior direction along a horizontal line that passed between the anterior and posterior ends of the brain, and an average of 36.29% lateral from the midline in the CS. In the CR, the STT was located at an average of 79.60% in the anterior to posterior direction along the aforementioned horizontal line, and an average of 36.36% lateral from the midline. In the PL, the STT was located at an average of 83.58% in the anterior to posterior direction along a horizontal line that passed the middle point at the genu of the internal capsule and the posterior endpoint of the putamen, and an average of 69.69% lateral from the midline to the lateral end of the putamen. CONCLUSIONS: We found the precise anatomical location of the STT in the subcortical white matter in the human brain using DTT. We believe that the results of this study will be helpful to clinicians in the neuroscience field.

Unusual clinical and topographical midbrain stroke revealed by pure sensory disturbance.

We describe a rare midbrain stroke presenting with predominantly sensory symptoms. A 71-year-old woman was hospitalized due to the recurrence of faciobrachial sensory loss. Magnetic resonance imaging showed an infarct involving the right side of the middle portion of midbrain at the level of the inferior colliculus. In our case we tried to make some clinico-anatomical correlations. The main anatomical structures involved were the medial lemniscal tract, the ventral part of the spinothalamic tract and the trigeminothalamic tract. The location of the stroke would suggest there are overlaps between arterial territories of the midbrain. Clinicians should look for midbrain infarcts in cases of pure sensory stroke.

Cortico-spinal imaging to study pain.

Functional magnetic resonance imaging of the brain has helped to reveal mechanisms of pain perception in health and disease. Recently, imaging approaches have been developed that allow recording neural activity simultaneously in the brain and in the spinal cord. These approaches offer the possibility to examine pain perception in the entire central pain system and in addition, to investigate cortico-spinal interactions during pain processing. Although cortico-spinal imaging is a promising technique, it bears challenges concerning data acquisition and data analysis strategies. In this review, we discuss studies that applied simultaneous imaging of the brain and spinal cord to explore central pain processing. Furthermore, we describe different MR-related acquisition techniques, summarize advantages and disadvantages of approaches that have been implemented so far and present software that has been specifically developed for the analysis of spinal fMRI data to address challenges of spinal data analysis.

Tissue bridges predict neuropathic pain emergence after spinal cord injury.

OBJECTIVE: To assess associations between preserved spinal cord tissue quantified by the width of ventral and dorsal tissue bridges and neuropathic pain development after spinal cord injury. METHODS: This retrospective longitudinal study includes 44 patients (35 men; mean (SD) age, 50.05 (18.88) years) with subacute (ie, 1 month) spinal cord injury (25 patients with neuropathic pain, 19 pain-free patients) and neuroimaging data who had a follow-up clinical assessment at 12 months. Widths of tissue bridges were calculated from midsagittal T2-weighted images and compared across groups. Regression analyses were used to identify relationships between these neuroimaging measures and previously assessed pain intensity and pin-prick score. RESULTS: Pin-prick score of the 25 patients with neuropathic pain increased from 1 to 12 months (Δmean=10.08, 95% CI 2.66 to 17.50, p=0.010), while it stayed similar in pain-free patients (Δmean=2.74, 95% CI -7.36 to 12.84, p=0.576). They also had larger ventral tissue bridges (Δmedian=0.80, 95% CI 0.20 to 1.71, p=0.008) at 1 month when compared with pain-free patients. Conditional inference tree analysis revealed that ventral tissue bridges' width (≤2.1 or >2.1 mm) at 1 month is the strongest predictor for 12 months neuropathic pain intensity (1.90±2.26 and 3.83±1.19, p=0.042) and 12 months pin-prick score (63.84±28.26 and 92.67±19.43, p=0.025). INTERPRETATION: Larger width of ventral tissue bridges-a proxy for spinothalamic tract function-at 1 month post-spinal cord injury is associated with the emergence and maintenance of neuropathic pain and increased pin-prick sensation. Spared ventral tissue bridges could serve as neuroimaging biomarkers of neuropathic pain and might be used for prediction and monitoring of pain outcomes and stratification of patients in interventional trials.

Conduction velocity of the cold spinal pathway in healthy humans.

OBJECTIVES: We aimed to investigate the conduction velocity of the cold spinal pathway in healthy humans. METHODS: Using a cold stimulator consisting of micro-Peltier elements that was able to produce steep cooling ramps up to -300°C/s, we recorded cold-evoked potentials after stimulation of the dorsal midline at C5, T2, T6 and T10 vertebral levels and calculated the conduction velocity of the cold spinal pathway. In all participants, we used laser stimulation to deliver painful heat (Aδ-fibres-mediated) and warm (C-fibres-mediated) stimuli to the same sites in order to compare the conduction velocity of the cold spinal pathway with that of the nociceptive and warm spinal pathways. RESULTS: Cold stimulation evoked large-amplitude vertex potentials from all stimulation sites. The mean conduction velocity of the cold spinal pathway was 12.0 m/s, which did not differ from that of the nociceptive spinal pathway (10.5 m/s). The mean conduction velocity of the warm spinal pathway was 2.0 m/s. DISCUSSION: This study provides previously unreported findings regarding cold spinal pathway conduction velocity in humans that may be useful in the assessment of spinal cord lesions as well as in intraoperative monitoring during spinal surgery. SIGNIFICANCE: This neurophysiological study provides previously unreported findings on cold spinal pathway conduction velocity in healthy humans. Cold-evoked potentials may represent an alternative to laser-evoked potential recording, useful to assess spinothalamic tract in patients with spinal cord lesions and monitor patients during spinal surgery.

Theory of mind network in multiple Sclerosis: A double disconnection mechanism.

The relationship between cognitive and affective theory of mind (ToM), clinical variables, and brain tissue injury is still a subject of debate in multiple sclerosis (MS). By adopting a ToM Networks model, we investigated ToM performance, and brain imaging correlates in relapsing-remitting (RR) and progressive (Pr) MS. 16RR, 19Pr, and 21 healthy controls were assessed with both cognitive (CToM) and affective ToM (AToM) tests and neuropsychological tools and were evaluated with MRI. Cortical thickness, sub-cortical volumetry, and tract-based-spatial-statistics were analyzed. Our results reported a CToM deficit in Pr, correlated with attention. While no relation between gray matter and CToM was observed, a widespread correlation between CToM and normal-appearing white matter was found. In particular, we registered a significant positive correlation between CToM and fractional anisotropy in Superior and Inferior Longitudinal Fasciculus and right thalamic radiation tracts. Moreover, an inverse correlation between CToM and mean diffusivity of the right fronto-occipital fasciculus, bilateral superior longitudinal fasciculus, cortico-spinal, left uncinate, corpus callosum, and forceps minor tracts was also observed. This work highlighted a double disconnection mechanism in Pr MS affecting communication both (1) inside the ToM network and (2) between the ToM network and cognitive execution areas, likely explaining the deficit in cognitive ToM.

A hidden mesencephalic variant of central pain.

BACKGROUND: Central post-stroke pain (CPSP) can arise after lesions anywhere in the central somatosensory pathways, essentially within the spinothalamic system (STS). Although the STS can be selectively injured in the mesencephalon, CPSP has not been described in pure midbrain infarcts. METHODS: Of more than 300 CPSP consecutive cases, we describe five patients who developed definite neuropathic pain following lesions circumscribed to the postero-lateral mesencephalon. RESULTS: The mesencephalic lesion responsible for pain was always haemorrhagic and always involved the spinothalamic tract (STT), as demonstrated by suppressed laser-evoked potentials in every case, with or without preserved lemniscal function. In three cases the midbrain injury could be ascribed to trauma, presumably from the cerebellar tentorium. As a result of the paucity of sensory symptoms, the pain was considered as 'psychogenic' in two of the patients until electrophysiological testing confirmed STT involvement. CONCLUSION: Postero-lateral midbrain lesions should be added to potential causes of CPSP. Because pain and spinothalamic deficits may be the only clinical sign, and because small lateral midbrain lesions may be difficult to trail with MRI, mesencephalic CPSP can be misdiagnosed as malingering or psychogenic pain for years. SIGNIFICANCE: Selective spinothalamic injury caused by small lateral midbrain lesions is a very rare cause of central post-stroke pain that can remain undiagnosed for years. It appears to obey to haemorrhagic, sometimes post-traumatic lesions. Sudden development of contralateral burning pain with isolated spinothalamic deficits may be the only localizing sign, which can be easily objectively detected with electrophysiological testing.

Abdominal pain due to the spinothalamic tract injury in patients with mild traumatic brain injury: a case report.

BACKGROUND: We report on a patient with a mild traumatic brain injury (TBI) who developed abdominal pain due to spinothalamic tract (STT) injuries revealed by diffusion tensor tractography (DTT). CASE PRESENTATION: A 53-year-old female patient suffered head trauma resulting from a backward fall. While bathing at a public bathhouse, she fell backward and struck the occipital area of her head against the floor. After the head trauma, she experienced pain in the abdomen and in both hands and feet. She underwent evaluations including conventional brain MRI, abdominal and pelvic ultrasonography, and stomach and intestine endoscopy. No abnormality was observed in her brain or abdomen. In addition, her abdominal pain had not been relieved by medical management. When she came to our hospital 4 years after the head trauma, her pain characteristics and severity were as follows: intermittent pain without allodynia or hyperalgesia; squeezing and warm creeping-like pain in the abdomen (visual analog scale score: 7); tingling pain in both hands and feet (visual analog scale score: 7). She was prescribed pregabalin and gabapentin, and her abdominal and limb pain was well-controlled at a tolerable level. On DTT 4 years after head trauma, the upper portion of the spinothalamic tracts (STTs) in both hemispheres showed partial tearing. DISCUSSION AND CONCLUSIONS: Injury of the STT was demonstrated by using DTT in a patient who showed abdominal pain that was refractory to medical management following mild TBI. Our results suggest that central pain due to STT injury might be suspected in patients with abdominal pain that is refractory to medical management following TBI.

Stereological study on the numerical plasticity of myelinated fibers and oligodendrocytes in the rat spinal cord with painful diabetic neuropathy.

Painful diabetic neuropathy may associate with nerve morphological plasticity in both peripheral and central nervous system. The aim of this study was to determine numerical changes of myelinated fibers in the spinothalamic tract region and oligodendrocytes in the spinal dorsal horn of rats with painful diabetic neuropathy and the effects of metformin on the above changes. Male Sprague-Dawley rats were randomly allocated into the control group (n = 7), the painful diabetic neuropathy group (n = 6) and the painful diabetic neuropathy treated with metformin group (the PDN + M group, n = 7), respectively. Twenty-eight days after medication, numbers of myelinated fibers in the spinothalamic tract and oligodendrocytes in the spinal dorsal horn were estimated by the optical disector (a stereological technique). Compared to the control group, number of myelinated fibers in the spinothalamic tract increased significantly in the painful diabetic neuropathy and PDN + M group, compared to the painful diabetic neuropathy group, number of myelinated fibers decreased in the PDN + M group (P < 0.05). As the oligodendrocyte in the spinal dorsal horn was considered, its number increased significantly in the painful diabetic neuropathy group compared to the control and the PDN + M group (P < 0.05), there was no significant difference between the control and the PDN + M group (P > 0.05). Our results indicate that painful diabetic neuropathy is associated with a serial of morphometric plasticity in the rat spinal cord including the numerical increase of the myelinated fibers in the spinothalamic tract and the oligodendrocytes in the spinal dorsal horn. The analgesic effect of metformin against painful diabetic neuropathy might be related to its adverse effects on the above morphometric plasticity.

Mechanisms of Below-Level Pain Following Spinal Cord Injury (SCI).

Mechanisms of below-level pain are discoverable as neural adaptations rostral to spinal injury. Accordingly, the strategy of investigations summarized here has been to characterize behavioral and neural responses to below-level stimulation over time following selective lesions of spinal gray and/or white matter. Assessments of human pain and the pain sensitivity of humans and laboratory animals following spinal injury have revealed common disruptions of pain processing. Interruption of the spinothalamic pathway partially deafferents nocireceptive cerebral neurons, rendering them spontaneously active and hypersensitive to remaining inputs. The spontaneous activity among these neurons is disorganized and unlikely to generate pain. However, activation of these neurons by their remaining inputs can result in pain. Also, injury to spinal gray matter results in a cascade of secondary events, including excitotoxicity, with rostral propagation of excitatory influences that contribute to chronic pain. Establishment and maintenance of below-level pain results from combined influences of injured and spared axons in the spinal white matter and injured neurons in spinal gray matter on processing of nociception by hyperexcitable cerebral neurons that are partially deafferented. A model of spinal stenosis suggests that ischemic injury to the core spinal region can generate below-level pain. Additional questions are raised about demyelination, epileptic discharge, autonomic activation, prolonged activity of C nocireceptive neurons, and thalamocortical plasticity in the generation of below-level pain. PERSPECTIVE: An understanding of mechanisms can direct therapeutic approaches to prevent development of below-level pain or arrest it following spinal cord injury. Among the possibilities covered here are surgical and other means of attenuating gray matter excitotoxicity and ascending propagation of excitatory influences from spinal lesions to thalamocortical systems involved in pain encoding and arousal.