A sham-controlled, randomized trial of spinal cord stimulation for the treatment of pain in chronic pancreatitis.

BACKGROUND: Spinal cord stimulation (SCS) has emerged as a treatment option for patients with chronic pancreatitis (CP) who experience pain that does not respond to standard interventions. However, there is a lack of sham-controlled trials to support its efficacy. METHODS: This randomized, double-blinded, sham-controlled, cross-over trial enrolled 16 CP patients with insufficient pain relief from standard therapies. Patients underwent high-frequency (1000 Hz) paraesthesia-free SCS or sham for two 10-day stimulation periods, separated by a 3-day washout period. The primary outcome was daily pain intensity registered in a pain diary based on a numeric rating scale (NRS). Secondary outcomes included various questionnaires. Quantitative sensory testing was used to probe the pain system before and after interventions. RESULTS: The average daily pain score on the NRS at baseline was 5.2 ± 1.9. After SCS, the pain score was 4.2 ± 2.1 compared to 4.3 ± 2.1 in the sham group (mean difference -0.1, 95% CI [-1.4 to 1.1]; P = 0.81). Similarly, no differences were observed between groups for the maximal daily pain score, secondary outcomes or quantitative sensory testing parameters. During an open-label, non-sham-controlled and non-blinded extension of the study, the average daily NRS was 5.2 ± 1.7 at baseline, 3.2 ± 1.8 at 3 months, 2.9 ± 1.9 at 6 months and 3.4 ± 2.2 at 12 months of follow-up (P = 0.001). CONCLUSION: In this first sham-controlled trial of SCS in painful CP, we did not find evidence of short-term pain relief with paraesthesia-free high-frequency (1000 Hz) stimulation. However, evaluation of the long-term effect by larger sham-controlled trials with long-term follow-up is warranted. SIGNIFICANCE STATEMENT: In this first sham-controlled trial to apply high-frequency (1000 Hz) spinal cord stimulation in patients with visceral pain due to chronic pancreatitis, we did not find evidence for clinically relevant pain relief. Taken together with potential procedure-related complications, adverse effects and costs associated with spinal cord stimulation, our findings question its use for management of visceral pain.

Use of an Antibacterial Envelope in Spinal Cord Stimulation Reduces the Rate and Severity of Iatrogenic Infections.

OBJECTIVE: To examine if the use of an antibacterial envelope (TYRX) decreases the rate of postoperative infection in chronic pain patients undergoing treatment with spinal cord stimulation (SCS) involving device implantation. METHODS: Single-center retrospective cohort study comparing postoperative infections rates in non-TYRX recipients from 2018 to 2020 with recipients of a TYRX antibacterial envelope from 2020 to 2021. Infection was registered if a patient received any form of antibiotic treatment after hospital discharge within a follow-up period of 100 days. RESULTS: A total of 198 patients were included: 100 in the TYRX group and 98 in the non-TYRX group. There were no significant differences between the 2 groups regarding age, body mass index (BMI), smoking, diabetes, and use of immunosuppression. The overall infection rate was 5.6%. The infection rate was 4% in the TYRX group and 7.1% in the non-TYRX group (P = 0.6). However, the 4 cases of postoperative infection in the TYRX group could be effectively managed with oral antibiotics alone, whereas 6 out of the 7 patients in the non-TYRX group required intravenous antibiotics. Moreover, device explantation was necessary in 3 of these patients suggesting the event of more severe infections in the non-TYRX group (P = 0.014). CONCLUSIONS: The TYRX antibacterial envelope displayed infection rates reducing capabilities, along with a clear tendency to reduce revision surgeries and system removals due to infections.

Examining the Duration of Carryover Effect in Patients With Chronic Pain Treated With Spinal Cord Stimulation (EChO Study): An Open, Interventional, Investigator-Initiated, International Multicenter Study.

OBJECTIVES: Spinal cord stimulation (SCS) is a surgical treatment for severe, chronic, neuropathic pain. It is based on one to two lead(s) implanted in the epidural space, stimulating the dorsal column. It has long been assumed that when deactivating SCS, there is a variable interval before the patient perceives the return of the pain, a phenomenon often termed echo or carryover effect. Although the carryover effect has been problematized as a source of error in crossover studies, no experimental investigation of the effect has been published. This open, prospective, international multicenter study aimed to systematically document, quantify, and investigate the carryover effect in SCS. MATERIALS AND METHODS: Eligible patients with a beneficial effect from their SCS treatment were instructed to deactivate their SCS device in a home setting and to reactivate it when their pain returned. The primary outcome was duration of carryover time defined as the time interval from deactivation to reactivation. Central clinical parameters (age, sex, indication for SCS, SCS treatment details, pain score) were registered and correlated with carryover time using nonparametric tests (Mann-Whitney/Kruskal-Wallis) for categorical data and linear regression for continuous data. RESULTS: In total, 158 patients were included in the analyses. A median carryover time of five hours was found (interquartile range 2.5;21 hours). Back pain as primary indication for SCS, high-frequency stimulation, and higher pain score at the time of deactivation were correlated with longer carryover time. CONCLUSIONS: This study confirms the existence of the carryover effect and indicates a remarkably high degree of interindividual variation. The results suggest that the magnitude of carryover may be correlated to the nature of the pain condition and possibly stimulation paradigms. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03386058.

Treatment of patients with chronic malignant pain with intrathecal morphine.

Chronic malignant pain is a common and feared condition. Especially, since many patients do not achieve proper pain relief from conventional peroral medication regimes and possible unacceptable side effects of high dosing. As argued in this review, in these patients, continuous intrathecal infusion of pain medicine by a programmable subcutaneously placed pump enables good pain relief, less systemic side effects, and better life quality. Intrathecal pain treatment should therefore be considered in patients with a proper performance score and suitable estimated life expectancy.

The TRH test provides valuable information in the diagnosis of central hypothyroidism in patients with known pituitary disease and low T4 levels.

Objective: To evaluate the value of the thyrotropin-releasing hormone (TRH) test in the diagnosis of central hypothyroidism (CH) in patients with pituitary disease. Methods: Systematic evaluation of 359 TRH tests in patients with pituitary disease including measurements of thyroxine (T4), TBG-corrected T4 (T4corr), baseline TSH (TSH0) and relative or absolute TSH increase (TSHfold, TSHabsolute). Results: Patients diagnosed with CH (n=39) show comparable TSH0 (p-value 0.824) but lower T4corr (p-value <0.001) and lower TSH increase (p-value <0.001) compared to patients without CH. In 54% (42 of 78 cases) of patients with low T4corr, the CH diagnosis was rejected based on a high TSHfold. In these cases, a spontaneous increase and mean normalization in T4corr (from 62 to 73 nmol/L, p-value <0.001) was observed during the follow-up period (7.6 ± 5.0 years). Three of the 42 patients (7%) were started on replacement therapy due to spontaneous deterioration of thyroid function after 2.8 years. Patients diagnosed with CH reported significantly more symptoms of hypothyroidism (p-value 0.005), although, symptoms were reported in most patients with pituitary disease. The TRH test did not provide clinical relevant information in patients with normal T4 or patients awaiting pituitary surgery (78%, 281 of 359). There were only mild and reversible adverse effects related to the TRH test except for possibly one case (0.3%) experiencing a pituitary apoplexy. Conclusion: The TRH test could be reserved to patients with pituitary disease, low T4 levels without convincing signs of CH. Approximately 50% of patients with a slightly decreased T4 were considered to have normal pituitary thyroid function based on the TRH test results.

The prevalence of acromegaly is higher than previously reported: Changes over a three-decade period.

OBJECTIVE: To study time-related changes in the prevalence and patient characteristics of acromegaly, as well as to assess the impact of changes in treatment on disease control. METHODS: A total of 107 patients with acromegaly were identified by healthcare registries and subsequently validated by patient chart review over a three-decade period (1992-2021). A systematic literature review focusing on the incidence and prevalence of acromegaly was performed identifying 31 studies. RESULTS: The prevalence of acromegaly significantly increased throughout the study period (R2 = 0.94, p < .001) and was 122 cases/106 persons in 2021 whereas the annual incidence remained constant at 4.6 cases/106 persons. The age at the first sign of acromegaly and the age at diagnosis significantly increased during the study period, whereas growth hormone and insulin-like growth factor I decreased. Incidentalomas constituted 32% of all cases diagnosed with acromegaly in the last decade. Primary surgery was used in 93% of all cases, and repeated surgery decreased from 24% to 10% during the three decades. The use of first-generation somatostatin analogues (21%-48%) and second-line medical treatment (4%-20%) increased with a concomitant improvement of biochemical disease control (58%-91%). CONCLUSION: The prevalence of acromegaly is higher than previously reported and the clinical presentation has shifted towards a milder phenotype. Modern treatment of acromegaly enables individualized treatment and disease control in the majority of patients.

Congenital hydrocephalus in a trisomy 9p gained child: a case report.

BACKGROUND: Hydrocephalus caused by excessive liquor production due to choroid plexus hyperplasia is a rare condition that may necessitate unusual treatment paradigms. It can be seen in trisomy 9p where coexisting congenital heart disease additionally may complicate the therapeutic approach as illustrated in the current case report. CASE PRESENTATION: At 20 months of age, a Caucasian girl with trisomy 9 and family history of an older brother and twin sister having the same syndrome displayed sign of congenital hydrocephalus due to increasing head circumference. Magnetic resonance imaging revealed enlarged lateral ventricles and a prominent choroid plexus, and the girl was treated with a ventriculoperitoneal shunt, which 2 days later had to be replaced with a ventriculoatrial shunt as cerebrospinal fluid formation greatly exceeded the ability of the patient's abdominal absorptive capability. At 16 years of age, the patient was diagnosed with cardiomyopathy and diminished ejection fraction. Some months later, she was admitted to the neurosurgical ward showing signs of shunt dysfunction due to a colloid cyst in the third ventricle. Cystic drainage through endoscopic puncture only helped temporarily. Revision of the shunt system showed occlusion of the ventricular drain, and replacement was merely temporary alleviating. Intracerebral pressure was significantly increased at around 30 mmHg, prompting externalization of the drain, and measurements revealed high cerebrospinal fluid production of 60-100 ml liquor per hour. Thus, endoscopic choroid plexus coagulation was performed bilaterally leading to an immediate decrease of daily cerebrospinal fluid formation to 20-30 ml liquor per hour, and these values where stabilized by pharmaceutical treatment with acetazolamide 100 mg/kg/day and furosemide 1 mg/kg/day. Subsequently a ventriculoperitoneal shunt was placed. Follow-up after 1 and 2 months displayed no signs of hydrocephalus or ascites. CONCLUSIONS: High cerebrospinal fluid volume load and coexisting heart disease in children with trisomy 9p may call for endoscopic choroid plexus coagulation and pharmacological therapy to diminish the daily cerebrospinal fluid production to volumes that allow proper ventriculoperitoneal shunting.

Comparison of Spinal Cord Stimulation Outcomes Between Preoperative Opioid Users and Nonusers: A Cohort Study of 467 Patients.

OBJECTIVES: Spinal cord stimulation (SCS) is a surgical treatment modality reserved for a subset of patients with neuropathic pain in which conventional pharmacologic treatment has proven insufficient. Previous studies have suggested a possible negative relationship between opioid use at referral and subsequent success of SCS therapy. The aim of this cohort study was to investigate whether preoperative opioid use was associated with inferior SCS outcomes. MATERIALS AND METHODS: Data were obtained from the Danish Neurizon Neuromodulation Database and comprised preoperative registrations of analgesic use, postoperative Patients' Global Impression of Change (PGIC) ratings, pre- and postoperative pain intensity scores (Numeric Rating Scale), and detailed surgical data. Patients were dichotomized according to preoperative opioid use (users vs nonusers) with subsequent assessment of the latest PGIC rating, reduction in pain intensity, and current treatment status (implanted/explanted). In addition, daily preoperative opioid dosages were quantified in oral morphine equivalents (OME) and correlated to the treatment outcomes. RESULTS: A total of 467 patients were included; 296 consumed opioids before SCS implantation (median 80 OME/d). Preoperative opioid use was not associated with the latest PGIC rating, reduction in pain intensity (30% or 50%), or risk of undergoing explantation (median follow-up = 3.0 years). Likewise, preoperative median OME per day of opioid users was not correlated with any of the defined outcomes. CONCLUSIONS: Preoperative opioid usage did not predict the outcome of SCS therapy in a large cohort of patients permanently implanted with an SCS system. The results do not support withholding otherwise well-indicated SCS therapy in patients with chronic neuropathic pain conditions based merely on preoperative opioid usage.

[Recognition, classification and treatment of trigeminal neuropathy].

Trigeminal neuropathy (TNO) manifests with unilateral or bilateral facio-oral sensory disturbances accompanied by pain and trigeminal nerve dysfunction. Although TNO may be posttraumatic or idiopathic, a thorough history and examination including magnetic resonance imaging is needed to exclude the multitude of secondary TNO causes. TNO-related pain necessitates multimodal treatment which in severe cases may encompass neurosurgical neuromodulation.

Complications and Effects of Dorsal Root Ganglion Stimulation in the Treatment of Chronic Neuropathic Pain: A Nationwide Cohort Study in Denmark.

OBJECTIVES: Dorsal root ganglion (DRG) stimulation is a novel treatment of chronic neuropathic pain and has been shown to be efficacious across several case reports and randomized trials. However, long-term follow-up is limited, as are reports of complication rates. This study presents efficacy and complications for patients treated with DRG stimulation. MATERIALS AND METHODS: We performed an observational, multicenter cohort study of all patients in Denmark implanted with FDA-approved DRG stimulation systems to treat chronic, neuropathic pain between 2014 and 2018. Follow-up period was one to three years. RESULTS: Forty-three patients underwent trial DRG stimulation; 33 were subsequently fully implanted. Pain location: 58% lower extremity; 21% upper extremity; 21% thoracic/abdominal. At the end of the observation period, 58% of fully implanted patients were still implanted; 42% had fully functional systems. In these patients, average Numerical Rating Scale (NRS)-score of pain was reduced from 6.8 to 3.5 (p = 0.00049) and worst NRS-score was reduced from 8.6 to 6.0 (p = 0.0039) at 12 months follow-up. Pain Catastrophizing Score was reduced from 32 to 15 (p = 0.0039). Thirteen patients experienced complications related to defect leads (39% of implanted systems). In four patients (12%), lead removal left fragments in the root canal due to lead fracture, and three patients suffered permanent nerve damage during attempts to replace broken leads. CONCLUSIONS: This study suggests a significant, clinically relevant effect of DRG stimulation on neuropathic pain, but also demonstrates substantial problems with maintenance and revision of currently available systems. Consequently, treatment with equipment marketed specifically for DRG stimulation is currently paused in Denmark.

Pain Catastrophizing Does Not Predict Spinal Cord Stimulation Outcomes: A Cohort Study of 259 Patients With Long-Term Follow-Up.

OBJECTIVE: Spinal cord stimulation (SCS) is an important treatment modality used to treat chronic neuropathic pain. However, reported success rates of 26%-70% entail an increased focus on patient selection. An area of core interest is psychological evaluation, often using scales such as the Pain Catastrophizing Scale (PCS). The aim of this study was to assess the relation between baseline PCS scores obtained before implantation and SCS outcomes defined as (1) Rating on Patients' Global Impression of Change scale (PGIC), (2) Pain relief on the Numeric Rating Scale (NRS), (3) Cessation of pain medication, and (4) Risk of permanent explantation. MATERIALS AND METHODS: Using records from the Neurizon Neuromodulation Database, we performed a multicenter open cohort study of 259 permanently implanted SCS patients. Follow-up ranged from six months to nine years (median = three years). For each of the defined SCS outcomes, patients were grouped according to their latest follow-up registration. Subsequently, we used a one-way ANOVA and exact t-tests to compare mean baseline PCS scores between groups. RESULTS: No difference in mean baseline PCS scores was found between PGIC groups. Baseline PCS scores was not associated with the probability of obtaining 30% or 50% pain relief on latest registration. Baseline PCS scores of patients able to cease all usage of tricyclic antidepressants, antiepileptics, or opioids during SCS treatment did not differ from baseline scores of continuous users. We found no association between baseline PCS scores and risk of permanent explantation. CONCLUSION: This study did not demonstrate any associations between baseline PCS scores and SCS outcomes.

[Screening for intracranial aneurysms].

This review states the reasons for considering screening for intracranial aneurysms in Denmark: if patients have two first-degree relatives with intracranial aneurysms, are 30-70 years old, do not have competing disorders, which could significantly shorten life expectancy, and subsequently in patients with autosomal dominant kidney disease and a family history of subarachnoid haemorrhage. MR angiography should be the imaging study of choice, unless contraindicated. Generally, the ethical consequences ought to be considered before carrying out screening.

[Cerebral manifestations of influenza A (H1N1)v]. / Cerebrale manifestationer ved influenza A (H1N1)v.

We describe two patients with cerebral manifestations of influenza A (H1N1)v. A 13-year-old boy developed severe cerebral oedema and increased intracranial pressure despite medical treatment and external drainage of cerebrospinal fluid. He was treated with bifrontal decompressive craniectomy with good result. A 25-year-old man with a previous kidney transplant developed encephalopathy and convulsions. Magnetic resonance imaging showed encephalitis. The patient fully recovered. The cases demonstrate that influenza A (H1N1)v can cause seriously and potentially life-threatening neurological complications.