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.

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.

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.

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.

Delayed-onset central poststroke pain due to degeneration of the spinothalamic tract following thalamic hemorrhage: A case report.

RATIONALE: Recent studies have used diffusion tensor tractography (DTT) to demonstrate that central poststroke pain (CPSP) was related to spinothalamic tract (STT) injury in patients with stroke. However, few studies have been reported about delayed-onset CPSP due to degeneration of the STT following a stroke. PATIENT'S CONCERNS: A 57-year-old female patient presented with right hemiparesis after stroke. Two weeks after onset, she did not report any pain. At approximately 6 months after onset, she reported pain in the right arm and leg, and the pain slowly intensified with the passage of time. At 14 months after onset, the characteristics and severity of her pain were assessed to be continuous pain without allodynia or hyperalgesia; tingling and cold-sensational pain in her right whole arm and leg (visual analog scale score: 5). DIAGNOSES: The patient was diagnosed as the right hemiparesis due to spontaneous thalamic hemorrhage. INTERVENTIONS: Clinical assessment and diffusion tensor imaging (DTI) were performed 2 weeks and 14 months after onset. OUTCOMES: She suffered continuous pain in her right whole arm and leg (visual analog scale score: 5). On DTT of the 2-week postonset DTI scans, the configuration of the STT was well-preserved in both hemispheres. However, in contrast to those 2-week postonset results, the 14-month postonset DTT results showed partial tearing and thinning in the left STT. Regardless, both the 2-week and 14-month postonset DTT showed that the left STT passed through the vicinity of the thalamic lesion. LESSONS: Diagnostic importance of performing a DTT-based evaluation of the STT in patients exhibiting delayed-onset CPSP following intracerebral hemorrhage.

Low white-matter integrity between the left thalamus and inferior frontal gyrus in patients with insomnia disorder

Background: Previous studies have reported functional and structural abnormalities in the thalamus and the pars triangularis of the inferior frontal gyrus in patients with insomnia disorder. However, no studies have been conducted on the white-matter tracts between these 2 brain regions. We aimed to compare the white-matter integrity and structure of the left thalamus­pars triangularis tracts between patients with insomnia and controls, and to characterize the relationship between white-matter integrity and clinical features in patients with insomnia. Methods: In total, 22 participants with insomnia disorder and 27 controls underwent overnight polysomnography and brain magnetic resonance imaging, and then completed self-report clinical questionnaires and neurocognitive tests for spatial planning. Structural and diffusion measures such as fractional anisotropy, axial diffusivity, radial diffusivity and trace were analyzed in group comparison and correlation analyses. Results: The insomnia group showed significantly lower fractional anisotropy (F = 8.647, p = 0.02) and axial diffusivity (F = 5.895, p = 0.038) in the left thalamus­pars triangularis tracts than controls. In patients with insomnia, fractional anisotropy in the tracts was correlated with the results of the Stockings of Cambridge test (r = 0.451, p = 0.034), and radial diffusivity was correlated with Epworth Sleepiness Scale score (r = 0.437, p = 0.042). Limitations: Limitations included analyses of limited brain regions and the cross-sectional design. Conclusion: The insomnia group showed decreased integrity in the left thalamus­pars triangularis tracts, and integrity was correlated with cognition and daytime sleepiness. These results may imply that insomnia is characterized by disintegration of the white-matter tract between the left thalamus and inferior frontal gyrus.

Multi-objective particle swarm optimization for postoperative deep brain stimulation targeting of subthalamic nucleus pathways.

OBJECTIVE: The effectiveness of deep brain stimulation (DBS) therapy strongly depends on precise surgical targeting of intracranial leads and on clinical optimization of stimulation settings. Recent advances in surgical targeting, multi-electrode designs, and multi-channel independent current-controlled stimulation are poised to enable finer control in modulating pathways within the brain. However, the large stimulation parameter space enabled by these technologies also poses significant challenges for efficiently identifying the most therapeutic DBS setting for a given patient. Here, we present a computational approach for programming directional DBS leads that is based on a non-convex optimization framework for neural pathway targeting. APPROACH: The algorithm integrates patient-specific pre-operative 7 T MR imaging, post-operative CT scans, and multi-objective particle swarm optimization (MOPSO) methods using dominance based-criteria and incorporating multiple neural pathways simultaneously. The algorithm was evaluated on eight patient-specific models of subthalamic nucleus (STN) DBS to identify electrode configurations and stimulation amplitudes to optimally activate or avoid six clinically relevant pathways: motor territory of STN, non-motor territory of STN, internal capsule, superior cerebellar peduncle, thalamic fasciculus, and hyperdirect pathway. MAIN RESULTS: Across the patient-specific models, single-electrode stimulation showed significant correlations across modeled pathways, particularly for motor and non-motor STN efferents. The MOPSO approach was able to identify multi-electrode configurations that achieved improved targeting of motor STN efferents and hyperdirect pathway afferents than that achieved by any single-electrode monopolar setting at equivalent power levels. SIGNIFICANCE: These results suggest that pathway targeting with patient-specific model-based optimization algorithms can efficiently identify non-trivial electrode configurations for enhancing activation of clinically relevant pathways. However, the results also indicate that inter-pathway correlations can limit selectivity for certain pathways even with directional DBS leads.

Thermal Stimulation Changes Diffusivity of the Spinothalamic Tract.

STUDY DESIGN: An experimental study. OBJECTIVE: This study aimed to investigate task-dependent changes in fractional anisotropy (FA) within the spinal cord during painful stimulation. SUMMARY OF BACKGROUND DATA: Earlier experiments by Mandl et al (2008, 2013) used non-invasive functional diffusion tensor imaging (fDTI) to detect white matter fibers that were active during functional tasks. In two studies, it was observed that FA of involved white matter tracts exhibited repeatable task-related increases. In this study, we attempted to extend the fDTI work in the spinal cord. METHODS: Twenty-three healthy, right-handed men (mean age 22 yrs, standard deviation [SD] = 4) were invited to participate in this study. Diffusion-weighted images were collected over spinal levels C2 to T4 during a painful thermal stimulus applied to the left thenar eminence. In order to investigate task-related activity, FA values within the contralateral (right) spinothalamic tract were analyzed using a generalized estimating equations (GEE) procedure. As a control, we also examined activity in the ipsilateral and contralateral corticospinal tracts, which are not considered to be involved in nociception. RESULTS: Significant task-related decreases in FA were observed in the right spinothalamic tract at vertebral levels C2-C5 (Wald X(1) = 17.754, P < 0.001). There was no change in control regions at levels C7-T2 of the same tract, which are located below the level of input from dermatome C6, Wald X(1) = 0.185, P = 0.667. Results in all other regions assessed, that is, the left spinothalamic tract and bilateral corticospinal tract, were also not significant (P > 0.05). CONCLUSION: The current findings suggest that task-related changes in FA associated with the transmission of pain signals along the spinal cord can be detected using fDTI. We observed decreased FA values in the contralateral (right) spinothalamic tract following painful stimulation, while no such activity was apparent in control regions. LEVEL OF EVIDENCE: 5.

Microstructural mechanisms of analgesia in percutaneous cervical cordotomy revealed by diffusion tensor imaging.

The purpose of this study is to demonstrate the potential of diffusion tensor imaging (DTI) to reveal structural mechanisms underlying spinal ablative procedures, including percutaneous radiofrequency cordotomy (PRFC). PRFC is a surgical procedure that produces analgesia through focal ablation of the lateral spinothalamic tract (STT), thereby interrupting the flow of pain information from the periphery to the brain. To date, studies regarding mechanisms of analgesia after PRFC have been limited to postmortem cadaveric dissection and histology. However, with recent advances in DTI, the opportunity has arisen to study the STT non-invasively in vivo. In this technical note, an individual with successful pain relief following unilateral STT PRFC was examined using DTI, with the contralateral STT serving as an internal control. PRFC substantially reduced rostrocaudal directional DTI signal in the STT from the lesion in the cervical spinal cord through the pons and mesencephalon. Our findings confirm that focal ablation and anterograde degeneration accompany the analgesic effects of PRFC. In vivo imaging of the STT with DTI may contribute to surgical targeting for PRFC procedures, better understanding of the therapeutic and untoward effects of PRFC, and a deeper understanding of spinothalamic contributions to nociception.

O-Arm-Guided Percutaneous Radiofrequency Cordotomy.

BACKGROUND: Pain is often one of the most debilitating symptoms in patients with advanced oncological disease. Patients with localized pain due to malignancy refractory to medical treatment can benefit from selective percutaneous cordotomy that disconnects the ascending pain fibers in the spinothalamic tract. OBJECTIVES: Over the past year, we have been performing percutaneous radiofrequency cordotomy with the use of the O-Arm intraoperative imaging system that allows both 2D fluoroscopy and 3D reconstructed computerized tomography imaging. We present our experience using this technique, focusing on technical nuances and complications. METHODS: A retrospective analysis was conducted of all patients who underwent percutaneous cordotomy between March 2016 and March 2017. RESULTS: Nineteen patients underwent percutaneous cordotomy procedures. Two patients developed intraoperative delirium and were unable to tolerate the procedure. In 16 out of 17 completed procedures, we achieved excellent immediate pain relief (94%). At 1 month after operation, 15 of the 17 (88%) patients were pain free, and at 3 months 5 out of 5 patients available for follow-up were still free of their original pain. Mirror pain developed in 6 of the 17 patients (35%), but was mild in 4 of these cases and controlled with medications. We experienced 1 serious complication (6%) of ipsilateral hemiparesis. CONCLUSION: Percutaneous cordotomy using the O-Arm is safe and effective in the treatment of intractable oncological pain.

Central pain due to spinothalamic tract injury caused by indirect head trauma following a pratfall.

OBJECTIVES: This study reports on patients who showed central pain due to injury of the spinothalamic tract (STT) caused by fall without direct head trauma. DESIGN: Prospective study. PARTICIPANTS: Two patients with mild traumatic brain injury (TBI) resulting from a fall were enrolled. Patient 1 was a 21-year-old female who had suffered a pratfall with no history of direct head trauma. She had begun to feel pain in both upper trunk and lower back and the left leg since ~ 5 days after onset: constant tingling and throbbing sensation with allodynia. Patient 2 was a 39-year-old male who had suffered a pratfall without direct head trauma. He had begun to feel pain in both arms and legs since ~ 4 days after the fall: constant tingling and pricking sensation without allodynia or hyperalgesia. RESULTS: On diffusion tensor tractograhpy (DTT) of patient 1, partial tearing of the right STT was observed at the subcortical white matter. On DTT of patient 2, partial tearing at the subcortical white matter was observed in the right STT and partial narrowing at the subcortical white matter was observed in the left STT. CONCLUSIONS: This study demonstrated injury of the STT in patients who suffered from central pain following a fall. The results suggest that minor indirect head trauma can cause traumatic axonal injury of the brain.

Degeneration of an injured spinothalamic tract in a patient with mild traumatic brain injury.

OBJECTIVES: This study reports on a patient who developed degeneration of an injured spinothalamic tract (STT) detected on diffusion tensor tractography (DTT) following mild traumatic brain injury (TBI). CASE DESCRIPTION: A 56-year-old female had suffered from head trauma resulting from a pedestrian car accident. The patient did not experience loss of consciousness or post-traumatic amnesia and the patient's Glasgow Coma Scale score was 15. She had begun to feel pain in her left hand and foot at ~ 7 days after onset. The characteristics and severity of pain were as follows: constant tingling and pricking sensation without allodynia or hyperalgesia (Visual Analogue Scale score: 3~4). No specific focal lesion was observed on brain and spine MRI and an electromyography study showed no evidence of peripheral nerve injury or radiculopathy. At 6 months after onset, the central pain in the left hand and foot became aggravated, with a Visual Analogue Scale score of 6. RESULTS: On 1-month DTT, partial tearing was observed in both STTs. In contrast, both partially torn STTs had become atrophy on 9-month DTT. CONCLUSIONS: This study recommends further studies conducted on the prognosis (regeneration or degeneration) of injured STTs and on the effect of change of an injured STT on central pain.

CT-guided percutaneous cordotomy for intractable pain in what is more than a disease: lung malignancies.

AIM: Lung cancer is the leading cause of cancer-related mortality worldwide. Pain is a common problem in these patients, yet inadequate or dissatisfactory management is prevalent. MATERIAL AND METHODS: Between 1987 and 2012, 224 patients with intractable pain were treated with computerized tomography (CT)- guided cordotomy. Among them, 210 had intractable pain due to malignancies. The majority of the cases were diagnosed as pulmonary malignancies (108 patients). Sixty-seven were pulmonary carcinoma, 26 mesothelioma and 15 Pancoast tumors. RESULTS: After cordotomy, 98.13% of cancer patients reported initial pain relief. Minimum and maximum preoperative scores of the Karnofsky Performance Scale were 20 and 70, versus postoperative scores of 40 and 90 (p < 0.001). The median preoperative VAS score was 8 (6-9). On the first postoperative day, the score dropped sharply to 0 (0-8) (p < 0.001). In this selected series of 108 percutaneous cordotomy procedures, as well as in the total series of 224 patients, there was no mortality or major morbidity. CONCLUSION: CT-guided percutaneous cordotomy is an effective procedure that should be used in the treatment of cancer-related pain problems. We suggest that cordotomy should be preferred as soon as possible in patients who fail to respond to the classic analgesic therapy.

Painful tonic spasms: an interesting phenomenon in cerebral ischemia.

We report a case of bilateral cerebral ischemia with frequent painful tonic spasms involving face, both upper and sometimes both lower extremities. The spasms subsided after treatment with diazepam.