Dorsal Root Ganglion Stimulation Relieves Chronic Neuropathic Pain Along With a Decrease in Cortical γ Power.

BACKGROUND: Stimulation of dorsal root ganglion (DRG) is an ideal neuromodulative intervention, providing pain relief in localized chronic pain conditions because γ-band oscillations reflect the intensity of ongoing chronic pain in patients affected. OBJECTIVE: We aimed to observe the role of cortical γ-band power associated with the relief of chronic neuropathic pain through DRG stimulation (DRGS). MATERIALS AND METHODS: We examined nine patients (two women, mean age 56.8 years; range, 36-77 years) diagnosed with chronic neuropathic pain who underwent DRGS therapy. We used the numeric rating scale (NRS) on the painful limb and simultaneously recorded the electroencephalography to assess the broadband γ power. Assessments were conducted on the first day and on the seventh day after implantation of the DRGS system and then compared and correlated with the results of the NRS. RESULTS: The NRS scores showed a significant decrease from the first day to the seventh day (p = 0.007). The resting-state γ power revealed a significant decrease (p = 0.021) between 30 and 45 Hz, recorded through the central electrode contralateral to the painful limb from the first day (mean [M] = 0.46, SD = 0.25) to the seventh day (M = 0.31, SD = 0.12) after DRGS. There was no significant change in the resting-state γ-band power recorded through the central electrode ipsilateral to the painful limb. However, we found a positive correlation in the γ-band power (rs = 0.628, p = 0.005) with the NRS rating. CONCLUSIONS: A lateralized decrease in broadband γ power may be considered further evidence supporting a reduction in the hyperexcitability of the nociceptive system in response to DRGS therapy. In the future, γ-band power could serve as a biomarker for assessing the efficacy of DRGS during the seven-day test phase preceding the implantation of the DRGS system.

Is it possible to generate an additional pleasant and pain-relieving muscle stimulation when using a low-frequency spinal cord stimulation (SCS) for the treatment of lower back pain? Pilot study: A new technique: "MuscleSCS".

OBJECTIVE: The combined use of spinal cord stimulation (SCS) and muscle stimulation, in the treatment of chronic pain, using the same probe, could improve the clinical results. However, this technique has not been established as yet. It was our hypothesis that it is possible to generate muscle stimulation by using low frequencies with SCS electrodes and use it to additionally treat chronic back pain. METHODS: We generated muscle stimulation in patients with previously implanted SCS electrodes, for the treatment of lower back pain, by using low frequencies (2, 4, 6, and 8 Hz) and different contact combinations of the electrodes. The results were evaluated by using visual inspection (videos), haptic control, surface electromyography (EMG), and sonographic recordings. RESULTS: This pilot study (17 patients, seven females, age 36-87 years, 11 percutaneous paddle leads, and 6 octrodes) was performed at the Neurosurgical Department of the University of Tuebingen. The most preferred frequencies were 6 Hz (45.5% of percutaneous paddle leads) and 8 Hz (50% of octrodes) at contacts 3&4 or 5&6. The preference of frequencies differed significantly among genders (p = 0.023). Simultaneous EMG and ultrasonic recordings demonstrated the generation of muscle potentials and the stimulation of deeper muscle groups. CONCLUSION: In this study, it has been shown that with low-frequency SCS stimulation, pleasant and pain-relieving muscle contractions of the lower and upper back can also be generated. This combined method has been coined by us as "MuscleSCS" technique. Clinical trials are necessary to establish the value of this combined technique and its subtypes.

[Surgical procedures for treatment of spasticity]. / Chirurgische Verfahren zur Therapie von Spastik.

BACKGROUND: The causes of spasticity are various and include cerebral palsy, spinal cord injury, stroke, multiple sclerosis or other congenital or acquired lesions of the central nervous system (CNS). While there is often a partial functional component, spasticity also results in varying degrees of impairment of the quality of life. OBJECTIVE: A review of surgical treatment options for spasticity. MATERIAL AND METHODS: A systematic PubMed review of the literature on epidemiology and treatment options with a focus on neurosurgical interventions for spasticity and developments in the last 20 years as well as inclusion of still valid older landmark papers was carried out. Illustration of indications, technique, follow-up, and possible pitfalls of the different methods for the surgical treatment of spasticity. RESULTS: Depending on the affected region, the number of muscle groups, and the extent of spasticity, focal (selective peripheral neurotomy, nerve transfer), regional (selective dorsal rhizotomy), or generalized (baclofen pump) procedures can be performed. The indications are usually established by an interdisciplinary team. Conservative (physiotherapy, oral medications) and focally invasive (botulinum toxin injections) methods should be performed in advance. In cases of insufficient response to treatment or only short-term relief, surgical methods can be evaluated. These are usually preceded by test phases with, for example, trial injections. CONCLUSION: Surgical methods are a useful adjunct in cases of insufficient response to conservative treatment in children and adults with spasticity.

Early biomarkers predicting outcome in a porcine model of acetaminophen intoxication: A pilot study.

BACKGROUND: Acetaminophen intoxication has become the leading cause of acute liver failure (ALF) in Europe and the USA. OBJECTIVES: To identify early biomarkers in order to predict the development of ALF in a porcine model of acetaminophen intoxication. MATERIAL AND METHODS: Six German Landrace pigs received a single acetaminophen bolus of 1 g/kg body weight via a jejunal catheter. Cytokines and laboratory parameters were analyzed at 8-hour intervals for a total of 40 h. RESULTS: Three of the 6 animals survived the intoxication. The nonsurviving animals had an increase in serum lactate and interleukin (IL)-6, with a simultaneous decrease in prothrombin time (PT) and albumin concentration 8 h after intoxication. In all nonsurviving animals, elevated levels of tumor necrosis factor alpha (TNF-α) at baseline before intoxication and during the course of ALF were observed. The acetaminophen serum concentrations and toxicokinetics did not differ between the nonsurviving and surviving animals. Methemoglobinemia was proportional to the administered doses and acetaminophen blood levels, but methemoglobinemia did not affect survival. CONCLUSIONS: Tumor necrosis factor alpha, IL-6, lactate, prothrombin time, and albumin blood concentration were identified as early predictors of outcome after acetaminophen intoxication. An elevated TNF-α level before acetaminophen exposure was the earliest prognostic marker for a lethal outcome. Therefore, it could serve as a very early indicator of prognosis.

Analysis of Somatosensory Profiles Using Quantitative Sensory Testing During Tonic and BurstDR Stimulation for the Treatment of Chronic Pain.

BACKGROUND: In the presence of neuropathic pain, other sensory qualities, such as touch or pressure, which are a sign of nerve damage, are almost always affected. However, it is unclear to which extent spinal cord stimulation (SCS) influences these simultaneously damaged sensory pathways or possibly contributes to their regeneration. OBJECTIVES: The aim of this study was to investigate the effects and possible differences of tonic and BurstDR (Abbott, Austin, TX) SCS on somatosensory profiles of patients with chronic neuropathic pain, using quantitative sensory testing (QST). STUDY DESIGN: A randomized, single-blinded, single-center study. SETTING: University medical center. METHODS: After a washout phase of 4 hours and having done the basic QST measurement, either tonic or BurstDR stimulation was performed for 30 minutes in a randomized fashion. Then, the second measurement was taken. The third measurement followed after using the remaining stimulation mode for 30 minutes. Mean values of all QST parameters were calculated and compared. We also computed Z-values using standard data. RESULTS: We examined 14 patients (9 women, 5 men, mean age 58.4 years) with previously implanted SCS systems for chronic neuropathic pain, using QST (7 tests, 13 parameters).The QST raw data showed a statistically significant improved vibration sensation (A-Beta) (P = 0.019) and lower mechanical pain threshold (A-Delta) (P = 0,031) when testing BurstDR in comparison to tonic SCS. We found a significant improvement in the vibration sensation and also A-Beta fiber function during BurstDR when we used the Z-value analysis (P = 0.023). With regard to Z-values, BurstDR seemed to be superior regarding the normalization tendency of the A-Delta fiber function in the mechanical pain threshold (P = 0.082), and tonic SCS seemed superior regarding heat detection threshold (C) and cold pain threshold (C and A-Delta) (P = 0.093). LIMITATIONS: The study is limited by its small number of cases. CONCLUSIONS: In this study, it could be shown that, in some QST parameters and tested fiber functions, normalization tendencies were recognizable by using BurstDR or tonic SCS. However, BurstDR SCS seemed to be superior to tonic stimulation in this regard.

Influence of Spinal Cord Stimulation on Insulin Sensitivity in Chronic Pain Patients.

BACKGROUND AND OBJECTIVE: This prospective, sham-controlled, randomized, cross-over study (NCT03637075), was designed to test the hypothesis that spinal cord stimulation (SCS) for the treatment of pain can also improve glucose metabolism and insulin sensitivity when compared to sham stimulation. METHODS: Ten non-diabetic participants (5 females, mean age 48.8 years) who had an SCS system implanted for the treatment of chronic neuropathic pain were studied. Whilst applying a hyperinsulinemic-euglycemic clamp, sham-stimulation and tonic stimulation were performed for 45 min (n=4) or 60 min (n=6) in each case randomly. The insulin sensitivity index and pain levels were determined. A second investigation, BurstDR stimulation was also conducted and the result was compared to that of sham stimulation (cross-over design). RESULTS: The insulin sensitivity improved significantly under the tonic stimulation when compared to the sham stimulation (p=0.037). BurstDR stimulation independently did not lead to a significantly improved insulin sensitivity compared to that after sham stimulation (p=0.16). We also examined the pain during the test and found no significant difference between sham and tonic stimulation (p=0.687). CONCLUSION: The results of this study show that tonic stimulation used for the treatment of pain could also improve glucose metabolism and insulin sensitivity. Further investigations are required to investigate the clinical relevance of the role of glucose metabolism in diabetic chronic pain participants and its underlying mechanisms.

Laser-evoked potentials recover gradually when using dorsal root ganglion stimulation, and this influences nociceptive pathways in neuropathic pain patients.

OBJECTIVE: Dorsal root ganglion stimulation (DRGS) is able to relieve chronic neuropathic pain. There seems evidence that DRGS might achieve this by gradually influencing pain pathways. We used laser-evoked potentials (LEP) to verify our hypothesis that the recovery of the LEP may reflect DRGS-induced changes within the nociceptive system. METHODS: Nine patients (mean age 56.8 years, range 36-77 years, two females) diagnosed with chronic neuropathic pain in the knee or groin were enrolled in the study. We measured each patient's LEP at the painful limb and contralateral control limb on the first, fourth, and seventh day after implantation of the DRGS system. We used the numeric rating scale (NRS) for the simultaneous pain assessment. RESULTS: The LEP amplitude of the N2-P2 complex showed a significant increase on day 7 when compared to day 1 (Z = -2.666, p = 0.008) and to day 4 (Z = -2.547, p = 0.011), respectively. There was no significant difference in the N2-P2 complex amplitude between ON and OFF states during DRGS. The patients' NRS significantly decreased after 1 day (p = 0.007), 4 days (p = 0.007), and 7 days (p = 0.007) when compared to the baseline. CONCLUSIONS: The results show that with DRGS, the LEP recovered gradually within 7 days in neuropathic pain patients. Therefore, reduction of the NRS in patients with chronic neuropathic pain might be due to DRGS-induced processes within the nociceptive system. These processes might indicate neuroplasticity mediated recovery of the LEP.

Effectiveness and Safety of Dorsal Root Ganglion Stimulation for the Treatment of Chronic Pain: A Pooled Analysis.

INTRODUCTION: Since it became available in the mid-2010s, dorsal root ganglion (DRG) stimulation has become part of the armamentarium to treat chronic pain. To date, one randomized controlled trial, and several studies of moderate sample size and various etiologies have been published on this topic. We conducted a pooled analysis to investigate the generalizability of individual studies and to identify differences in outcome between chronic pain etiologic subgroups and/or pain location. MATERIALS AND METHODS: One prospective, randomized comparative trial and six prospective, single-arm, observational studies were identified that met pre-defined acceptance criteria. Pain scores and patient-reported outcome (PRO) measures were weighted by study sample sizes and pooled. Safety data are reported in aggregate form. RESULTS: Our analysis included 217 patients with a permanent implant at 12-month follow-up. Analysis of pooled data showed an overall weighted mean pain score of 3.4, with 63% of patients reporting ≥50% pain relief. Effectiveness sub-analyses in CRPS-I, causalgia, and back pain resulted in a mean reduction in pain intensity of 4.9, 4.6, and 3.9 points, respectively. Our pooled analysis showed a pain score for primary affected region ranging from 1.7 (groin) to 3.0 (buttocks) and responder rates of 80% for foot and groin, 75% for leg, and 70% for back. A substantial improvement in all PROs was observed at 12 months. The most commonly reported procedural or device complications were pain at the IPG pocket site, lead fracture, lead migration, and infection. CONCLUSIONS: DRG stimulation is an effective and safe therapy for various etiologies of chronic pain.

Pain inhibition through transplantation of fetal neuronal progenitors into the injured spinal cord in rats.

Neuropathic pain after spinal cord injury (SCI) is a complex condition that responds poorly to usual treatments. Cell transplantation represents a promising therapy; nevertheless, the ideal cell type in terms of neurogenic potential and effectiveness against pain remains largely controversial. Here, we evaluated the ability of fetal neural stem cells (fNSC) to relieve chronic pain and, secondarily, their effects on motor recovery. Adult Wistar rats with traumatic SCI were treated, 10 days after injury, with intra-spinal injections of culture medium (sham) or fNSCs extracted from telencephalic vesicles (TV group) or the ventral medulla (VM group) of E/14 embryos. Sensory (von Frey filaments and hot plate) and motor (the Basso, Beattie, Bresnahan locomotor rating scale and inclined plane test) assessments were performed during 8 weeks. Thereafter, spinal cords were processed for immunofluorescence and transplanted cells were quantified by stereology. The results showed improvement of thermal hyperalgesia in the TV and VM groups at 4 and 5 weeks after transplantation, respectively. Moreover, mechanical allodynia improved in both the TV and VM groups at 8 weeks. No significant motor recovery was observed in the TV or VM groups compared with sham. Stereological analyses showed that ~70% of TV and VM cells differentiated into NeuN+ neurons, with a high proportion of enkephalinergic and GABAergic cells in the TV group and enkephalinergic and serotoninergic cells in the VM group. Our study suggests that neuronal precursors from TV and VM, once implanted into the injured spinal cord, maturate into different neuronal subtypes, mainly GABAergic, serotoninergic, and enkephalinergic, and all subtypes alleviate pain, despite no significant motor recovery. The study was approved by the Animal Ethics Committee of the Medical School of the University of São Paulo (protocol number 033/14) on March 4, 2016.

Characterization of traumatic spinal cord injury model in relation to neuropathic pain in the rat.

Purpose/aim: Neuropathic pain following spinal cord injury (SCI) has a tremendous impact on patient's quality of life, and frequently is the most limiting aspect of the disease. In view of the severity of this condition and the absence of effective treatments, the establishment of a reliable animal model that reproduces neuropathic pain after injury is crucial for a better understanding of the pathophysiology and for the development of new therapeutic strategies. Thus, the objective of the present study was to standardize the traumatic SCI model in relation to neuropathic pain. MATERIALS AND METHODS: Wistar rats were submitted to SCI of mild intensity (pendulum height 12.5 mm) or moderate intensity (pendulum height 25 mm) using the New York University Impactor equipment. Behavioural assessment was performed during 8 weeks. Thereafter, spinal cords were processed for immunohistochemistry. RESULTS: The animals of the moderate injury group in comparison with mild injury had a greater motor function deficit, worse mechanical allodynia, and latter bladder recovery; moreover, histological analysis revealed more extensive lesions with lower neuronal population. CONCLUSIONS: Our study suggests that moderate SCI causes a progressive and long-lasting painful condition (at least 8 weeks), in addition to motor impairment, and thus represents a reliable animal model for the study of chronic neuropathic pain after SCI.

Neurophysiological Effects of Dorsal Root Ganglion Stimulation (DRGS) in Pain Processing at the Cortical Level.

OBJECTIVES: Dorsal root ganglion stimulation (DRGS) has been used successfully against localized neuropathic pain. Nevertheless, the effects of DRGS on pain processing, particularly at the cortical level, remain largely unknown. In this study, we investigated whether positive responses to DRGS treatment would alter patients' laser-evoked potentials (LEP). METHODS: We prospectively enrolled 12 adult patients with unilateral localized neuropathic pain in the lower limbs or inguinal region and followed them up for six months. LEPs were assessed at baseline, after one month of DRGS, and after six months of DRGS. Clinical assessment included the Numerical Rating Scale (NRS), Brief Pain Inventory (BPI), SF-36, and Beck Depression Inventory (BDI). For each patient, LEP amplitudes and latencies of the N2 and P2 components on the deafferented side were measured and compared to those of the healthy side and correlated with pain intensity, as measured with the NRS. RESULTS: At the one- and six-month follow-ups, N2-P2 amplitudes were significantly greater and NRS scores were significantly lower compared with baseline (all p's < 0.01). There was a negative correlation between LEP amplitudes and NRS scores (rs = -0.31, p < 0.10). CONCLUSIONS: DRGS is able to restore LEPs to normal values in patients with localized neuropathic pain, and LEP alterations are correlated with clinical response in terms of pain intensity.

Dorsal Root Ganglion Stimulation (DRGS) for the Treatment of Chronic Neuropathic Pain: A Single-Center Study with Long-Term Prospective Results in 62 Cases.

BACKGROUND: Dorsal root ganglion stimulation (DRGS) treats discrete, localized areas of neuropathic pain. But there are no long-term results available so far. OBJECTIVES: We studied the long-term outcome of DRGS used in the treatment of chronic neuropathic pain. STUDY DESIGN: A prospective, longitudinal single center investigation. SETTING: Academic medical center in Germany. METHODS: Patients (age >18 years) with chronic neuropathic pain in the hands, back, legs, knees and feet were prospectively examined. After a successful test-trial (duration of 3-14 days, pain decrease > 50%), a permanent generator was implanted. The patients were re-examined after 1 year, 2 years and 3 years. We used the Visual Analogue Scale (VAS), the Pain Disability Index (PDI), the Pain Catastrophizing Scale (PCS), the Brief Pain Inventory (BPI), and, the Beck Depression Inventory (BDI) for our assessments. RESULTS: We included 62 consecutive patients (27 females, 35 males, mean age 56.8 years, with an age range from 28 to 82 years, 62/51 to permanent conversion) during the time period from March 2012 until March 2016. Fifty-one patients had a successful test-trial and a generator was implanted subsequently. Results after 3 years: the VAS dropped from Mdn = 8 to Mdn = 4 (P = 0.0001). The PDI decreased from Mdn = 45 to Mdn = 23 (P = 0.003). The PCS decreased from Mdn = 34 to Mdn = 21 (P = 0.001). The BPI dropped from Mdn = 73 to Mdn = 30 (P = 0.003). The BDI decreased from Mdn = 36 to Mdn = 21 (P = 0.010). Fourteen patients showed complications (27.4%). LIMITATIONS: This study is limited by the small number of patients in the single groups of the different pain locations. CONCLUSION: DRGS may be an effective long-term method of treating discrete, localized areas of chronic neuropathic pain. We would recommend DRGS for the treatment of chronic neuropathic pain in such areas. KEY WORDS: Knee pain, foot pain, hand pain, groin pain, neuromodulation, dorsal root ganglion stimulation, chronic neuropathic pain, paresthesia mapping.

Diagnosis of Lumbar Spinal Stenosis with Functional Myelography.

BACKGROUND AND STUDY AIMS: The diagnosis of a lumbar spinal stenosis demands advanced diagnostic radiologic techniques. In recent decades magnetic resonance imaging (MRI) has replaced myelography, now considered an old-fashioned technique. It was our hypothesis that functional myelography still plays an important role in selected cases. We investigated how our surgical strategy was influenced by the results of MRI, functional myelography, and postmyelography computed tomography (CT) in patients with a lumbar spinal stenosis. METHODS: The sagittal diameters of the lumbar spinal canal were measured from L1 to S1 on patients with lumbar spinal stenosis. MRI, functional myelography, and postmyelography CT were compared in each of the patients. Sensitivity and specificity were calculated in each method. We examined how the surgical strategy was influenced by the results of these different methods. RESULTS: Fifty consecutive patients (21 women and 29 men; mean age: 70 years, [range: 49-86 years]) fulfilled the inclusion criteria. Functional myelography revealed a sensitivity of 0.99, a specificity of 0.79, and a positive predictive value of 0.45. The MRI exhibited a sensitivity of 0.93, a specificity of 0.74, and a positive predictive value of 0.39. Postmyelography CT showed a sensitivity of 0.96, a specificity of 0.75, and a positive predictive value of 0.41. A functional myelography revealed more information than the MRI and resulted in a change in the surgical strategy in 11 of 50 patients (22%) in comparison with the sole results of MRI or a postmyelography CT. CONCLUSIONS: In selected cases with multilevel lumbar spinal stenosis, functional myelography revealed the highest precision in reaching a correct diagnosis. It resulted in a change in the surgical approach in every fifth patient in comparison with the MRI and proved most helpful, especially in elderly patients.

Dorsal Root Ganglion Stimulation Used for the Treatment of Chronic Neuropathic Pain in the Groin: A Single-Center Study With Long-Term Prospective Results in 34 Cases.

OBJECTIVE: Chronic neuropathic pain in the groin is a severe condition and difficult to treat. Dorsal root ganglion stimulation (DRGS) covers discrete painful areas precisely with its stimulation power in comparison to spinal cord stimulation (SCS). It was our hypothesis that DRGS provides a long-term relief of chronic groin pain over a period of more than three years. MATERIALS AND METHODS: Patients (age >18 years) with chronic neuropathic groin pain were prospectively examined. After a successful test-trial (duration of 3-10 days, pain decrease >50%) a permanent generator was implanted. The patients were re-examined after three months, then after one year, two, and three years. We used the Visual Analogue Scale (VAS), the Pain Disability Index (PDI), the Pain Catastrophizing Scale (PCS), the Brief Pain Inventory (BPI), and the Beck Depression Inventory (BDI) for the assessment. RESULTS: We included 34 consecutive patients (13 female, 21 male, mean age 50.4 years, range of age 24-84 years, 30/34 trial to permanent conversion) during the time period from 2012 until 2016. Thirty patients had a successful test-trial and a generator was subsequently implanted. Results after three years: the preoperative VAS dropped from Mdn = 8 to Mdn = 4.5 (p = 0.001). The PDI decreased from Mdn = 48 to Mdn = 23 (p = 0.004). The PCS changed from Mdn = 31 to Mdn = 16 (p = 0.006). The BPI dropped from Mdn = 76 to Mdn = 30 (p = 0.003). The BDI decreased from Mdn = 17 to Mdn = 7 (p = 0.010). Five patients showed complications (16.7%). CONCLUSION: In this study, DRGS proved an efficient long-term method for the treatment of chronic neuropathic groin pain and we strongly recommend its use.

Pathophysiological central nervous system changes in a porcine model of acetaminophen-induced acute liver failure.

BACKGROUND: Critical care management of patients suffering from acute liver failure (ALF) continues to be challenging. Animal models studying the pathophysiological central nervous system alterations during the course of ALF provide an opportunity to improve diagnostic and therapeutic strategies. The aim of this study was to analyse the course of cerebral oxygenation in addition to conventional neuromonitoring during the course of acetaminophen-induced ALF. METHODS: ALF was induced by intrajejunal acetaminophen administration in 20 German landrace pigs. All animals underwent invasive hemodynamic and neuromonitoring and were maintained under standardized intensive care support. Neuromonitoring consisted of continuous intraparenchymatous recording of intracranial pressure and brain partial oxygen pressure. Hemodynamic and ventilation parameters were continuously recorded; laboratory parameters were analysed every eight hours. Mean values were compared using the Wilcoxon test. RESULTS: Acute liver failure occurred in all intoxicated animals after 23±2h, resulting in death due to ALF after further 15±2h. Continuous neuromonitoring was performed in all animals during the whole experiment without observing signs of intracranial haemorrhage. Two hours after manifestation of ALF an increase in brain tissue oxygen (PtiO2) was observed. Brain oxygenation stayed stable until nine hours before death. Intracranial pressure (ICP) remained basically at a plateau level until manifestation of ALF. In the following ten hours a linear and slow increase was observed until five hours before death, followed by a fast and continuous rise in ICP to a final level of 35±1mmHg. Cerebral perfusion pressure (CPP) began to decrease 25h prior to exitus, further decreasing to 18±2mmHg at the end of the experiment. A strong negative linear correlation was found between PtiO2 and ICP (R=0.97). Arterial partial pressure of oxygen (PaO2) below 100mmHg was associated with lower PtiO2 levels. Changes in arterial partial pressure of carbon dioxide (PaC02) did not influence PtiO2 values. Hemoglobin values below 7g/dl were associated with lower PtiO2 values. CONCLUSIONS: The results of our experiments demonstrate that ICP and PtiO2 measurements indicate impending damage well before serious complications occur and their use should be considered in order to protect endangered brain function in the presence of acetaminophen-induced ALF.

Porcine model characterizing various parameters assessing the outcome after acetaminophen intoxication induced acute liver failure.

AIM: To investigate the changes of hemodynamic and laboratory parameters during the course of acute liver failure following acetaminophen overdose. METHODS: Eight pigs underwent a midline laparotomy following jejunal catheter placement for further acetaminophen intoxication and positioning of a portal vein Doppler flow-probe. Acute liver failure was realized by intrajejunal acetaminophen administration in six animals, two animals were sham operated. All animals were invasively monitored and received standardized intensive care support throughout the study. Portal blood flow, hemodynamic and ventilation parameters were continuously recorded. Laboratory parameters were analysed every eight hours. Liver biopsies were sampled every 24 h following intoxication and upon autopsy. RESULTS: Acute liver failure (ALF) occurred after 28 ± 5 h resulted in multiple organ failure and death despite maximal support after further 21 ± 1 h (study end). Portal blood flow (baseline 1100 ± 156 mL/min) increased to a maximum flow of 1873 ± 175 mL/min at manifestation of ALF, which was significantly elevated (P < 0.01). Immediately after peaking, portal flow declined rapidly to 283 ± 135 mL/min at study end. Thrombocyte values (baseline 307 × 103/µL ± 34 × 103/µL) of intoxicated animals declined slowly to values of 145 × 103/µL ± 46 × 103/µL when liver failure occurred. Subsequent appearance of severe thrombocytopenia in liver failure resulted in values of 11 × 103/µL ± 3 × 103/µL preceding fatality within few hours which was significant (P > 0.01). CONCLUSION: Declining portal blood flow and subsequent severe thrombocytopenia after acetaminophen intoxication precede fatality in a porcine acute liver failure model.

High-Resolution Three-Dimensional Computed Tomography for Assessing Complications Related to Intrathecal Drug Delivery.

BACKGROUND: The assessment of the functionality of intrathecal drug delivery (IDD) systems remains difficult and time-consuming. Catheter-related problems are still very common, and sometimes difficult to diagnose. OBJECTIVES: The aim of the present study is to investigate the accuracy of high-resolution three-dimensional computed tomography (CT) in order to detect catheter-related pump dysfunction. STUDY DESIGN: An observational, retrospective investigation. SETTING: Academic medical center in Germany. METHODS: We used high-resolution three dimensional (3D) computed tomography with volume rendering technique (VRT) or fluoroscopy and conventional axial-CT to assess IDD-related complications in 51 patients from our institution who had IDD systems implanted for the treatment of chronic pain or spasticity. RESULTS: Twelve patients (23.5%) presented a total of 22 complications. The main type of complication in our series was catheter-related (50%), followed by pump failure, infection, and inappropriate refilling. Fluoroscopy and conventional CT were used in 12 cases. High-resolution 3D CT VRT scan was used in 35 instances with suspected yet unclear complications. Using 3D-CT (VRT) the sensitivity was 58.93% - 100% (CI 95%) and the specificity 87.54% - 100% (CI 95%).The positive predictive value was 58.93% - 100% (CI 95%) and the negative predictive value: 87.54% - 100% (CI 95%).Fluoroscopy and axial CT as a combined diagnostic tool had a sensitivity of 8.3% - 91.7% (CI 95%) and a specificity of 62.9% - 100% (CI 95%). The positive predictive value was 19.29% - 100% (CI 95%) and the negative predictive value: 44.43% - 96.89% (CI 95%). LIMITATIONS: This study is limited by its observational design and the small number of cases. CONCLUSION: High-resolution 3D CT VRT is a non- invasive method that can identify IDD-related complications with more precision than axial CT and fluoroscopy.

Noninvasive measurement of intracranial pressure via the pulsatility index on transcranial Doppler sonography: Is improvement possible?

PURPOSE: We hypothesized that using hemodynamic variables could improve the prediction of intracranial pressure (ICP) from the middle cerebral artery pulsatility index (PI) measured with transcranial Doppler sonography. METHODS: In this prospective study, 39 patients with traumatic brain injury were routinely examined with transcranial Doppler sonography, and the middle cerebral artery PI was calculated. A multivariate model including hematocrit, mean arterial blood pressure, heart rate, and arterial CO2 pressure (PaCO2 ) was evaluated. RESULTS: Thirty-nine comatose patients (16 women and 23 men; age range 18-73 years; median 44 years) were included, and 234 data pairs (consisting of ICP and corresponding PI values) were analyzed. ICP ranged from -3 mmHg to +52 mmHg, and PI from 0.6 to 2.85. We found a significant but weak correlation between PI and the square root of ICP (R(2) between 0.29 and 0.34, p < 0.0001). A slightly stronger correlation was detected when hemodynamic variables were incorporated (R(2) between 0.37 and 0.43). Of these variables, mean arterial blood pressure had the most significant influence. CONCLUSIONS: In this study, PI was not a sufficiently strong predictor of ICP to be used in clinical practice. Its reliability did not improve even when hemodynamic variables were considered. Therefore, we recommend abandoning the use of PI for the noninvasive measurement of ICP in clinical practice.

MRI-based radiation-free method for navigated percutaneous radiofrequency trigeminal rhizotomy.

UNLABELLED: BACKGROUND/STUDY AIMS: Percutaneous radiofrequency trigeminal rhizotomy (RTR) is a standardized treatment for trigeminal neuralgia, yet it has been associated with serious complications related to the cannulation of the foramen ovale. Some of these complications, such as carotid injury, are potentially lethal. Neuronavigation was recently proposed as a method to increase the procedure's safety. All of the techniques described so far rely on pre- or intraoperative computed tomography scanning. Here we present a simple method based on magnetic resonance imaging (MRI) (radiation free) used to target the foramen ovale under navigation guidance. PATIENTS/MATERIAL AND METHODS: We retrospectively analyzed nine patients who had undergone navigated percutaneous RTR based solely on preoperative MRI and compared them with 35 patients who underwent conventional RTR guided by fluoroscopy. We analyzed immediate and late outcome and categorized the results into pain free, > 70% pain reduction, and persistent pain. We also compared groups in terms of the duration of the procedure and the complication rates. Here we describe the navigation method in detail and review the anatomical landmarks for target definition. RESULTS: The duration of the surgical procedure was similar in both groups (32.1 in the standard technique versus 34.5 minutes with navigation; p = 0.5157). There was no significant difference between groups regarding pain reduction at the immediate (p = 1.0) or late follow-up (p = 0.6284) time points. Furthermore, no serious complications were observed in the navigated group. CONCLUSIONS: We present a simple radiation-free method for neuronavigation-assisted percutaneous RTR. This method proved to be safe and effective, and it is especially recommended for young, inexperienced neurosurgeons.