The Effect of Various Spinal Neurostimulation Paradigms on the Supraspinal Somatosensory Evoked Response: A Systematic Review.

INTRODUCTION: Spinal neurostimulation is a therapy for otherwise intractable chronic pain. Spinal neurostimulation includes stimulation of the spinal cord (SCS), dorsal root ganglion (DRGS), and dorsal root entry zone (DREZS). New paresthesia-free neurostimulation paradigms may rely on different mechanisms of action from those of conventional tonic neurostimulation. The aim of this systematic review is to assess the existing knowledge on the effect of spinal neurostimulation on somatosensory processing in patients with chronic pain. We therefore reviewed the existing literature on the effect of various spinal neurostimulation paradigms on the supraspinal somatosensory evoked response (SER). MATERIALS AND METHODS: Multiple scientific data bases were searched for studies that assessed the effect of spinal neurostimulation on the supraspinal SER, evoked by painful or nonpainful peripheral stimuli in patients with chronic pain. We found 205 studies, of which 24 were included. Demographic data, study design, and study outcome were extracted. RESULTS: Of the 24 included studies, 23 used electroencephalography to assess the SER; one study used magnetoencephalography. Fifteen studies evaluated tonic SCS; six studies (also) evaluated paresthesia-free paradigms; three studies evaluated the effect of tonic DRGS or DREZS. Sixteen studies used nonpainful stimuli to elicit the SER, 14 observed a decreased SER amplitude. Ten studies used painful stimuli to elicit the SER, yielding mixed results. DISCUSSION: The included studies suggest that both paresthesia-based and paresthesia-free spinal neurostimulation paradigms can decrease (part of) the SER elicited by a nonpainful peripheral stimulus. The observed SER amplitude reduction likely is the effect of various spinal and supraspinal mechanisms of spinal neurostimulation that also contribute to pain relief. CONCLUSIONS: Spinal neurostimulation modulates the processing of a peripherally applied nonpainful stimulus. For painful stimuli, the results are not conclusive. It is not yet clear whether paresthesia-free neurostimulation affects the SER differently from paresthesia-based neurostimulation.

Evaluating Community-Based Intrathecal Baclofen Therapy: Effectiveness, Safety, and Feasibility.

Background: Intrathecal baclofen (ITB) is used for the treatment of intractable spasticity. The burden of traveling for ITB screening and aftercare is problematic for nursing home residents with severe spasticity and seems to result in undertreatment of spasticity. The aim of this study is to evaluate the effectiveness, safety, and feasibility of ITB for nursing home residents treated in their home, describing the selection phase, the initial trial of ITB, and aftercare up to 3 months after implantation of an ITB pump. Methods: This retrospective database study included immobile, adult nursing home residents with severe spasticity, referred to an Ambulatory Care Clinic between 2016 and 2021. When eligible, an ITB trial was performed by ITB experts in the nursing home. If a permanent pump was implanted, dose titration and aftercare were performed on location. Results: A total of 102 patients were referred; 80 underwent an ITB trial on location, and 94% improved significantly on the Modified Ashworth Scale and clonus scale pre-ITB trial versus post-ITB trial, as well as at 3 months post-implantation. There was a low incidence of adverse events, mostly procedure- and drug-related. Conclusions: This study indicates that selection, testing, and aftercare for ITB on location is effective and safe.

Effect of intravenous low-dose S-ketamine on pain in patients with Complex Regional Pain Syndrome: A retrospective cohort study.

OBJECTIVE: The objective of this study was to assess the effectiveness of a low-dose intravenous S-ketamine treatment on refractory pain in patients with Complex Regional Pain Syndrome (CRPS). METHODS: In this retrospective study, patients with CRPS who received intravenous S-ketamine from March 2010 to April 2019 were included. According to our inpatient protocol, S-ketamine dose was increased until pain reduction was achieved or side effects were observed. Maximum dose was 14 mg/h and treatment duration was 7 days. Primary outcome parameters were pain scores (Numeric Rating Scale) at baseline (T0), end of infusion (T1), and approximately 4 weeks postinfusion (T2). Patients were categorized as responder/nonresponder at T1 and T2. Patients were considered a responder in case there was pain score reduction of greater than or equal to 2 points or if treatment was reported as successful. RESULTS: Forty-eight patients were included. Mean disease duration was 5 years (interquartile range [IQR] = 6 years). Median pain score significantly decreased from 8 (IQR = 2) at T0 to 6 (IQR = 4) at T1 (p < 0.001). At T1, 62% of the patients were responders. At T2, 48% of the patients remained a responder. A significant proportion of the responders at T1 turned into nonresponders at T2 (p = 0.03). CONCLUSION: In a group of patients with CRPS with refractory pain, low-dose intravenous S-ketamine treatment resulted in effective pain relief during infusion. Although a significant proportion of initial responders became nonresponders at follow-up, half of the patients were still a responder at ~ 4 weeks postinfusion. Further research is needed to investigate mechanisms responsible for pain relief by S-ketamine infusions and to ascertain possible predictors of response to the treatment.

Restoration of rostral cerebrospinal fluid flow to solve treatment failure caused by obstruction in long-term intrathecal baclofen administration.

Objects: We describe five traumatic spinal cord injury (SCI) patients with an intrathecal baclofen administration (ITB) failure caused by a rostral CSF flow obstruction referred to our expert center between January 2014 and January 2019. We discuss the diagnostic workup, rostral CSF flow obstruction as the cause of the ITB failure and treatment.Methods: When we could not determine the cause of the ITB failure through the patient's history, physical spasticity examination, pump readout, absence of fluid in the pump reservoir during aspiration, or plain radiography, we performed pump catheter access port (computed tomography [CT]) myelography. When CT myelography did not reveal the diagnosis, we used scintigraphy. In an obstruction, we aimed for CSF flow restoration. In three cases, we conducted a laminectomy with microsurgical adhesiolysis. In two of these patients, we could not achieve CSF flow restoration; thus, we placed an intradural catheter bypass. Recently, in three patients, we applied a less invasive technique of percutaneous fenestration of the obstruction.Results: In one case, we performed a successful catheter replacement. In another case using surgical adhesiolysis, spasticity control was complete. In two cases, we could obtain improvement with an additional intradural bypass, followed by a percutaneous fenestration of the obstruction, resulting in further improved CSF flow restoration. In one case, percutaneous fenestration was the first line of treatment. In all cases with percutaneous fenestration, we experienced spasticity control.Conclusion: Preliminary results showed that the restoration of rostral CSF flow might result in an effective ITB treatment in patients with an intrathecal obstruction.

Intrathecal baclofen as emergency treatment alleviates severe intractable autonomic dysreflexia in cervical spinal cord injury.

Context: Episodic attacks of autonomic dysreflexia (AD) are regularly experienced by patients with a spinal cord injury (SCI) on T6 or higher levels. The episodes can result in a pounding headache, flushing, blurred vision, anxiety, a stroke, posturing, hyperthermia, retinal bleeding, seizures, myocardial ischemia, cardiac arrhythmias, and death. The observed associated bradycardia is explained as a baroreceptor reflex response to the high blood pressure. Intrathecal baclofen (ITB) has been used to treat chronic AD. This case highlights the occurrence of intractable AD after removal of the ITB delivery system because of a pump pocket infection. We describe the benefit of ITB as an emergency treatment for intractable AD.Findings: A 53-year-old male suffered from spasticity and AD after a C5 ASI B SCI in 2002 was successfully treated with ITB for 14 years. He developed Staphylococcus aureus and Pseudomonas aeruginosa cellulitis at the orifice of his suprapubic catheter, which caused an abscess in the pump pocket. To prevent a withdrawal syndrome, the medication was reduced in three steps of 25%, and the pump was explanted. Postoperatively, he experienced severe AD and was treated with clonazepam, clonidine, and urapidil. The next day, the severely fluctuating blood pressure and pulse rate were no longer controllable with the medication. At L2-3, a temporary external intrathecal catheter for reinitiating ITB was inserted. With this treatment, the AD and the spasticity symptoms could be controlled.Conclusion/Clinical Relevance: The case demonstrated that refractory AD could be managed with ITB in an emergency.

Isotopic Scintigraphy in Intrathecal Drug Delivery Failure: A Single-Institution Case Series.

BACKGROUND: The aim of this study was to assess the feasibility and diagnostic accuracy of an optimized 111 Indium-diethylenetriamine-penta-acetic-acid single-photon-emission computed tomography (CT) (111 In-DTPA SPECT-CT) examination in patients with suspected intrathecal drug delivery (ITDD) failure. MATERIALS AND METHODS: Retrospective analysis of routinely collected observational data from a case series of patients in the setting of the academic Center for Pain Medicine, Departments of Radiology and Nuclear Medicine and Neurosurgery. Twenty-seven patients participated between January 2014 and January 2019. Thirty-six optimized examinations including standardized pump flow rate with additional SPECT-CT imaging and a stepwise standardized analysis were performed. A 10 mL mixture of medication and 20 MBq 111In-DTPA was injected into the pump reservoir. Planar and SPECT-CT images were acquired at 24, 48, and 72 hours (h) after injection and at 96 hours and/or seven days, if needed. All images were reassessed by the first two authors using an optimized procedure. RESULTS AND CONCLUSIONS: Twenty-two abnormalities were identified in 21 examinations, with these abnormalities consisting of leakage (n = 7), spinal catheter obstruction (n = 7), and cerebrospinal fluid flow obstruction (n = 8). Interventions (n = 19) confirmed the cause of ITDD failure. A false-positive finding at follow-up (n = 1) and a false-negative finding (n = 1) were encountered. Sensitivity was 95% (20/21) and the specificity 93% (14/15). A significant difference (p < 0.001) was found between the accuracy of the conventical and the optimized analysis. The optimized 111 In-DTPA SPECT-CT examination is a powerful diagnostic tool for detecting the cause of ITDD failure.

Catheter Access Port (Computed Tomography) Myelography in Intrathecal Drug Delivery Troubleshooting: A Case Series of 70 Procedures.

OBJECTIVES: Intrathecal drug delivery is used for the treatment of intractable spasticity, dystonia, and pain. When the symptomatology fails to respond to therapy, the cause could be failure of the medication infusion. The purpose of this study is to assess pump catheter access port (CAP)-myelography and CAP-CT-myelography as advanced imaging methods in treatment failure. MATERIALS AND METHODS: We analyzed observational routinely collected data of 70 CAP procedures with 2D/3D reconstructions and additional imaging of 53 adult patients where the cause of treatment was unclear between November 2013 and November 2018. CAP-myelography and CAP-CT myelography were performed with postprocessing 2D/3D reconstructions. When myelography could not be obtained or when the result did not reveal the cause of the treatment failure, additional procedures, such as noncontrast CT, MRI, lumbar puncture CT, and 111Indium-DTPA SPECT-CT, were performed. RESULTS: CAP fluid aspiration prior to contrast medium injection was not possible (N = 17). In one case, contrast was injected into the pump pocket unintentionally (N = 1). Of 70 procedures, 24% were unaspiratable. The remaining CAP myelography examinations (N = 52) had limited value for the diagnosis. CAP-CT myelography (N = 50) was normal (N = 31). The abnormal results (N = 19) were dorsal dural leak (N = 5), subdural catheter position (N = 2), limited rostral flow of contrast material (N = 4), limited and abnormal contrast distribution (N = 3), obstruction of rostral flow (N = 2), a leak at the pump-catheter connection (N = 1), and a sheared catheter localized in the pump pocket (N = 2). Limited contrast distributions were found to be false positive findings (N = 2). Four normal CT-CAP myelographic procedures were false negatives, as the reference tests revealed a cause of intrathecal drug delivery (ITDD) failure. The CAP-CT procedures resulted in a sensitivity of 81% (17/21) and a specificity of 93% (27/29). CONCLUSIONS: CAP-CT myelography with 2D/3D reconstructions is an essential step in the diagnostic algorithm for cases involving ITDD failure.

Efficiency and Safety of Aftercare With Intrathecal Baclofen on Location.

OBJECTIVES: Patients with intractable spasticity treated with intrathecal baclofen (ITB) need regular evaluation and aftercare in an outpatient clinic or pain clinic setting. Logistically, this can be challenging. A solution could be to perform treatment at the patient's home setting. In the Netherlands, a project of the Dutch Healthcare Authority was initiated to deliver ambulatory ITB-related services via a home-based Ambulant Care Clinic. This aftercare is performed by nurse practitioners (NP) with support from a medical specialist. The scope of the study was to investigate the efficiency and safety of ITB-care for patients with severe disabling spasticity in their home setting. MATERIALS AND METHODS: A retrospective analysis of prospectively collected data. Patients with congenital or acquired spasticity were treated with ITB (1st April 2011 to January 1st 2016) using an implanted programmable pump system were referred to the home-based Ambulant Care Clinic by various neuromodulation centers in the Netherlands. All study parameters were a part of the standard intake and follow-up documentation. RESULTS: Of the 900 patients treated with ITB in the Netherlands, 239 were referred to the home-based Ambulant Care Clinic and included in this study. Mean age was 45.5 (range 7-82) years; 52% lived at home; the average satisfaction score was 9 (scale 0-10); and 0.29% had (serious) adverse events (60% of clinical manifestations were prevented by remote double-check control). Certifications for patient safety and quality standards were obtained. CONCLUSIONS: The concept of ITB aftercare on location demonstrated efficacy and safety in the described setting. For troubleshooting, close collaboration with a neuromodulation center is necessary and can be arranged in chain-based care.

Plain radiography in patients treated with intrathecal drug delivery using an implantable pump device.

OBJECTIVES: Intrathecal drug administration using an implanted pump system is well established in intractable spasticity and pain. However, despite continuous advancements in manufacturing technology, adverse events related to the pump and catheter still occur. Most of them, such as migration, damage, disconnection and occlusion, are related to the spinal catheter. The aim of this overview is to update radiologists on how plain radiography of the implanted delivery system for intrathecal drug administration should be interpreted and to increase awareness for the need of urgent and timely multidisciplinary troubleshooting. METHODS: Plain radiographic images of patients treated with intrathecal drug administration using an implantable drug delivery system were analysed in a multidisciplinary setting at our (university) referral centre for complications in intrathecal drug administration. RESULTS: Examples of catheter-related adverse events are described and a proposal is made for stepwise interpretation of standard plain radiographic images. CONCLUSIONS: Plain radiological images are the mainstay for the diagnosis of catheter-related adverse events in intrathecal drug delivery. Radiologists play an important role in an early diagnosis. An awareness of abnormal radiological findings seems important to avoid a life-threatening withdrawal syndrome. TEACHING POINTS: • Untimely cessation of intrathecal drug delivery can lead to a life-threatening withdrawal syndrome. • Initially mild symptoms can lead to an exacerbation of a withdrawal syndrome. • Most intrathecal catheter-related problems are visible on plain radiography. • Common causes of catheter problems are migration, lacerations, occlusion and disconnection. • Knowledge on implanted intrathecal catheters is crucial for interpretation of plain radiography.

Helicopter emergency medical services (HEMS): impact on on-scene times.

BACKGROUND: This study compared prehospital on-scene times (OSTs) for patients treated by nurse-staffed emergency medical services (EMS) with OST for patients treated by a combination of EMS and physician-staffed helicopter emergency medical services (HEMS). A secondary aim was to investigate the relationship between length of OST and mortality. METHODS: All trauma patients treated in the priority 1 emergency room of a Level I trauma center between January 2002 and 2004 were included in the study. To determine OST and outcome, hospital and prehospital data were entered into the trauma registry. OSTs for EMS and combined EMS/HEMS-treated patients were compared using linear regression analysis. Logistic regression analysis was used to compare mortality rates. RESULTS: The number of trauma patients included for analysis was 1,457. Of these, 1,197 received EMS assistance only, whereas 260 patients received additional care by an HEMS physician. HEMS patients had longer mean OSTs (35.4 vs. 24.6 minutes; p < 0.001) and higher Injury Severity Scores (24 vs. 9; p < 0.001). After correction for patient and trauma characteristics, like the Revised Trauma Score, age, Injury Severity Scores, daytime/night-time, and mechanism of trauma, the difference in OSTs between the groups was 9 minutes (p < 0.001). Logistic regression analyses showed a higher uncorrected chance of dying with increasing OST by 10 minutes (OR, 1.2; p < 0.001). This apparent effect of OST on mortality was explained by patient and trauma characteristics (adjusted OR, 1.0; p = 0.89). CONCLUSIONS: Combined EMS/HEMS assistance at an injury scene is associated with longer OST. When corrected for severity of injury and patient characteristics, no influence of longer OST on mortality could be demonstrated.

Physician-staffed HEMS dispatch in the Netherlands: Adequate deployment or minimal utilization?

INTRODUCTION: In the Netherlands, a physician-staffed helicopter emergency medical system (HEMS), called the Helicopter Mobile Medical Team (HMMT), provides prehospital care for severely injured patients in addition to ambulance services. This HMMT has proven to increase chances of survival and reduce morbidity. HMMT dispatch is performed following certain dispatch criteria. The goal of this study was to analyze actual dispatch rates and assess the protocol adherence of the emergency dispatchers in Rotterdam regarding HMMT dispatch. METHODS: All high priority ambulance runs between April 1 and July 1, 2003, were prospectively documented and cross-referenced to dispatch criteria. It was determined whether the emergency call warranted either immediate dispatch of the HMMT or a secondary dispatch after arrival of the first ambulance. When dispatch actually occurred, this was also documented. RESULTS: In The Studied Period A Total Of 5765 A1 Ambulance Runs During Daylight Were Documented. Of These, 1148 Runs Met Primary Dispatch Criteria And 38 Runs Met Secondary Dispatch Criteria. Actual Hmmt Dispatch Occured In 162/1186 (14%) Cases. CONCLUSIONS: HEMS dispatch rates and dispatch criteria adherence are low (14%). Better protocol adherence by emergency dispatchers could lead to a sevenfold increase of HMMT dispatches. The reasons for suboptimal protocol adherence remain unclear and persist, despite proven value of the HMMT in reducing patient mortality and morbidity.

Comparison of current injury scales for survival chance estimation: an evaluation comparing the predictive performance of the ISS, NISS, and AP scores in a Dutch local trauma registration.

BACKGROUND: Prediction of survival chances for trauma patients is a basic requirement for evaluation of trauma care. The current methods are the Trauma and Injury Severity Score (TRISS) and A Severity Characterization of Trauma (ASCOT). Scales for scoring injury severity are part of these methods. This study compared three injury scales, the Injury Severity Score (ISS), the New ISS (NISS), and the Anatomic Profile (AP), in three otherwise identical predictive models. METHODS: Records of the Rotterdam Trauma Center were analyzed using logistic regression. The variables used in the models were age (as a linear variable), the corrected Revised Trauma Score (RTS), a denominator for blunt or penetrating trauma, and one of the three injury scales. The original TRISS and ASCOT models also were evaluated. The resulting models were compared in terms of their discriminative power, as indicated by the receiver-operator characteristic (ROC), and calibration (Hosmer-Lemeshow [HL]) for the entire range of injury severity. RESULTS: For this study, 1,102 patients, with an average ISS of 15, met the inclusion criteria. The TRISS and ASCOT models, using original coefficients, showed excellent discriminative power (ROC, 0.94 and 0.96, respectively), but insufficient fits (HL, p = 0.001 and p = 0.03, respectively). The three fitted models also had excellent discriminative abilities (ROC, 0.95, 0.97, and 0.96, respectively). The custom ISS model was unable to fit the entire range of survival chances sufficiently (p = 0.01). Models using the NISS and AP scales provided adequate fits to the actual survival chances of the population (HL, 0.32 and 0.12, respectively). CONCLUSIONS: The AP and NISS scores particularly both managed to outperform the ISS score in correctly predicting survival chances among a Dutch trauma population. Trauma registries stratifying injuries by the ISS score should evaluate the use of the NISS and AP scores.