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PURPOSE: This study aims to elucidate the incidence of and independent risk factors for spinal cord stimulator implantations for patients who underwent lumbar spine surgery. METHODS: The PERFormance, Effectiveness, and Cost of Treatment (PERFECT) episodes database, which was established for selected diseases and procedures in Finland, includes all patients who underwent lumbar spine surgery for degenerative spine conditions or spinal cord stimulation (SCS) in Finland from 1986 to 2018. The data on age, sex, hospital diagnoses, surgical procedures, and causes of death were imported from the Finnish national registers into the PERFECT database. RESULTS: Between 1986 and 2018, 157,824 patients had their first lumbar spine procedure and for 1769 (1.1%) of them, a subsequent SCS procedure was observed during the follow-up. The cumulative incidence of SCS for persistent or recurrent pain after lumbar disk herniation, spinal stenosis, degenerative disk disease, and spondylolysis and spondylolisthesis surgery at 15 years was 1.2%, 1.0%, 2.7%, and 2.6% respectively. At 15 years, the cumulative incidence of SCS for persistent or recurrent pain after lumbar spine surgery after five or more lumbar spinal operations was 11.9%. CONCLUSION: Repeated surgery was the most prominent significant risk factor for SCS for persistent or recurrent pain after lumbar spine surgery. The risk of SCS for persistent or recurrent pain after lumbar spine surgery increases significantly along with the number of lumbar spine procedures. When considering repeated lumbar spine surgery, careful evaluation of treatment options should take place to ensure good patient outcomes.
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Estimulação da Medula Espinal , Estenose Espinal , Espondilolistese , Humanos , Incidência , Vértebras Lombares/cirurgia , Dor , Fatores de Risco , Estenose Espinal/cirurgia , Espondilolistese/cirurgiaRESUMO
BACKGROUND: Despite national recommendations, disparities in specialised palliative care (SPC) admittance have been reported. The aims of this study were to characterize SPC admittance in patients with pancreatic cancer in relation to region of residence and age. METHOD: The data sources were two nationwide databases: Danish Pancreatic Cancer Database and Danish Palliative Care Database. The study population included patients (18+ years old) diagnosed with pancreatic cancer from 2011 to 2018. We investigated admittance to SPC, and time from diagnosis to referral to SPC and first contact with SPC to death by region of residence and age. RESULTS: In the study period (N = 5851) admittance to SPC increased from 44 to 63%. The time from diagnosis to referral to SPC increased in the study period and overall, the median time was 67 days: three times higher in Southern (92 days) than in North Denmark Region. The median number of days from diagnosis to referral to SPC was lower in patients ≥70 years (59 days) vs patients < 70 years (78 days), with regional differences between the age groups. Region of residence and age were associated with admittance to SPC; highest for patients in North Denmark Region vs Capital Region (OR = 2.03 (95%CI 1.67-2.48)) and for younger patients (< 60 years vs 80+ years) (OR = 2.54 (95%CI 2.05-3.15)). The median survival from admittance to SPC was 35 days: lowest in Southern (30 days) and highest in North Denmark Region (41 days). The median number of days from admittance to SPC to death was higher in patients < 70 years (40 days) vs ≥ 70 years (31 days), with a difference between age groups in the regions of 1-14 days. CONCLUSIONS: From 2011 to 2018 more patients with pancreatic cancer than previously were admitted to SPC, with marked differences between regions of residence and age groups. The persistently short period of time the patients are in SPC raises concern that early integrated palliative care is not fully integrated into the Danish healthcare system for patients with pancreatic cancer, with the risk that the referral comes so late that the patients do not receive the full benefit of the SPC.
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Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias Pancreáticas , Adolescente , Hospitalização , Humanos , Cuidados Paliativos , Neoplasias Pancreáticas/terapia , Encaminhamento e ConsultaRESUMO
OBJECTIVE: Spinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period. MATERIALS AND METHODS: The study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries. RESULTS: Higher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001). CONCLUSIONS: Higher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation.
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Síndrome Pós-Laminectomia , Estimulação da Medula Espinal , Analgésicos Opioides , Síndrome Pós-Laminectomia/tratamento farmacológico , Humanos , Medula Espinal , Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: Few studies have evaluated the impact of risk factors and comorbidity on overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). The aim was to investigate the prognostic importance of Charlson's age-comorbidity index (CACI) and other risk factors on prognosis in a clinical real-world cohort of PDAC patients. METHODS: A total of 1,159 patients with PDAC who had received at least one cycle of adjuvant or palliative chemotherapy were included from the Danish BIOPAC study. We analysed OS according to CACI, tobacco smoking, alcohol intake, performance status (PS), BMI and diabetes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for OS using Cox proportional hazards regression. RESULTS: At the end of follow-up, 994 (86%) patients had died. The median OS was 298 days for all patients (range 3-3010) and shortest in patients with stage IV. No association with short OS was seen for CACI > 2, diabetes, alcohol abuse, tobacco smoking, hypertension, and high BMI. Multivariate analysis showed that stage (IV vs. I: HR = 9.05, 95% CI 5.17-15.84), PS (2 vs. 0: HR = 3.67, 2.92-4.61) and treatment with angiotensin-converting enzyme inhibitors (yes vs. no: HR = 1.31, 1.06-1.61) were independent negative prognostic factors. CONCLUSIONS: We found that CACI, diabetes, tobacco smoking, alcohol abuse, hypertension, and high BMI were not associated with OS in a real-world cohort of patients with PDAC treated with chemotherapy. Only stage and PS were prognostic parameters.
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Carcinoma Ductal Pancreático/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/epidemiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Índice de Massa Corporal , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/fisiopatologia , Comorbidade , Dinamarca/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Estado Funcional , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Obesidade/epidemiologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/fisiopatologia , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Taxa de Sobrevida , Fumar Tabaco/epidemiologiaRESUMO
OBJECTIVES: The aim of the study is to investigate whether benzodiazepine use differs between patients with favorable and unfavorable spinal cord stimulation (SCS) treatment outcome. We hypothesize that the patients with unfavorable SCS outcome would exhibit a higher level of benzodiazepine use. MATERIALS AND METHODS: Using a case-control study setting, we examined benzodiazepine use in SCS patients and in matched population controls as a potential risk factor poor SCS outcome. A total of 373 consecutive SCS patients treated in Kuopio University Hospital between 1997 and 2014 and their 1117 matched population controls were followed until patient death or the end of March 2016. RESULTS: Benzodiazepines were used during the 24-month period before or after SCS implantation by 42.3% of the SCS patients who had the device explanted, 39.5% who had an unsuccessful trial stimulation, 28.0% who still had the device at the end of the follow-up period, and 8.0% of the controls. Diazepam use before SCS increased the odds for explanting of SCS by 2.4-fold (95% Cl: 1.0-5.4). Starting clonazepam use after SCS was associated with a 5.2-fold (95% CI: 1.5-18.9) increase in the odds of unsuccessful trial stimulation. CONCLUSION: The benzodiazepine use in patients with poor SCS outcome illustrates the role of anxiety in SCS outcomes and the need for multidisciplinary treatment of pain.
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Benzodiazepinas/uso terapêutico , Neuralgia , Estimulação da Medula Espinal , Estudos de Casos e Controles , Finlândia , Humanos , Neuralgia/tratamento farmacológico , Medição da Dor , Medula Espinal , Resultado do TratamentoRESUMO
BACKGROUND: Styrene is an important industrial chemical that the general population is exposed to at low levels. Previous research has suggested increased occurrence of leukemia and lymphoma among reinforced plastics workers exposed at high levels of styrene. METHODS: We followed 73,036 workers of 456 small- and medium-sized Danish reinforced plastics companies from 1968 to 2011 and investigated the exposure-response relation between cumulative styrene exposure and incidence of lymphohematopoietic malignancies. We modeled styrene exposure from employment history, survey data, and historical styrene exposure measurements. We retrieved information on lymphohematopoietic malignancies from national cancer and patient registers. RESULTS: We identified 665 cases overall of 21 different lymphohematopoietic malignancies or combinations thereof, each with at least 20 cases, during 1,581,976 person-years of follow-up. Initial analyses suggested higher age, sex, and calendar year-adjusted incidence rate ratios (RRs) for acute myeloid leukemia, Hodgkin lymphoma, and T-cell lymphoma with higher estimates of cumulative styrene exposure. Accounting for time since exposure showed a trend by cumulative styrene exposure (P = 0.01) and a doubled risk (RR = 2.4; 95% CI, 1.2, 4.6) of acute myeloid leukemia following estimated high compared with estimated low cumulative exposure during the prior 15-29 years. We observed no increased risk following exposure during more recent years and less consistent risk patterns for Hodgkin lymphoma and T-cell lymphoma. CONCLUSIONS: This study, to our knowledge the largest epidemiologic study to date of occupational styrene exposure, suggests increased risk of acute myeloid leukemia following high styrene exposure with a latency period of about 15 years.
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Indústrias , Linfoma/induzido quimicamente , Linfoma/epidemiologia , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Plásticos , Estireno/efeitos adversos , Adulto , Idoso , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Sinonasal adenocarcinoma is a rare disease expected to have rare causes and potential for strong risk factors as reflected by the strong association with occupational wood dust exposure. High level styrene exposure is a rare and suspected carcinogen, and this study examines the exposure-response relation between occupational styrene exposure, sinonasal adenocarcinoma and other subtypes. METHODS: We followed 73 092 styrene-exposed workers from 1968 to 2011 and identified sinonasal cancers in the Danish Cancer Registry. We modelled cumulative styrene exposure and estimated incidence rates and age, sex and wood-industry adjusted ORs. RESULTS: During 1 585 772 person-years, we observed nine cases of adenocarcinoma, corresponding to a fivefold non-significantly increased OR for estimates of high versus low cumulative styrene exposure (OR 5.11, 95% CI 0.58 to 45.12). The increased risk was confined to exposure received during the recent 15 years. The other histological subtypes showed no increased risk. CONCLUSION: This study suggests increased risk of sinonasal adenocarcinoma following styrene exposure. The observations are, however, few, confounding from wood dust exposure cannot be ruled out, and additional studies are needed before firm conclusions can be drawn.
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Adenocarcinoma/induzido quimicamente , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Plásticos , Estireno/efeitos adversos , Adenocarcinoma/epidemiologia , Adulto , Dinamarca/epidemiologia , Feminino , Humanos , Indústrias , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Fatores de RiscoRESUMO
Background: Treatment of persistent spinal pain syndrome (PSPS) is challenging. Chronic pain associated with PSPS can lead to an impaired ability to work. Objective: To obtain information on whether receiving a disability pension (DP) affects pain and pain treatments in retiring working-age PSPS patients. Neuropathic pain medication and antidepressant use were considered as an indicator of neuropathic pain. Methods: The study group comprised 129 consecutive PSPS patients with spinal cord stimulation (SCS) devices implanted at Kuopio University Hospital Neurosurgery between January 1, 1996, and December 31, 2014. Purchase data of gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors from January 1995 to March 2016, as well as the data on working ability, were retrieved from national registries. Results: The data showed that 28 of 129 (21.7%) SCS permanent patients had a DP, and 27 had a sufficient follow-up time (two years before and one year after DP). Most patients (61%) used neuropathic pain medications during the follow-up, while 44% used antidepressants. Most patients (70%, n = 19) retired because of dorsopathies. The dose of gabapentinoids started to increase before the DP; after the DP, the doses started to increase again after the decrease but remained at a lower level. Conclusions: Neuropathic pain medication and antidepressant use suggest that pain continues after the DP-that is, pensioners continue to experience inconvenient chronic pain. Resources for patient care are therefore needed after the DP. However, the DP reduces the dose increase of gabapentinoids; the dose is higher immediately before retirement than at the end of the follow-up.
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Dor Crônica , Neuralgia , Estimulação da Medula Espinal , Humanos , Dor Crônica/terapia , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Antidepressivos/uso terapêutico , Pensões , Medula Espinal , Resultado do TratamentoRESUMO
Tick Borne Encephalitis (TBE) is endemic to an increasing number of countries and is a common cause of meningoencephalitis in Europe and Asia making any potential complications of the disease increasingly relevant to clinicians. We present, what is to our knowledge, the second reported case of N-methyl-d-aspartate receptor (NMDAR) encephalitis following Tick Borne Encephalitis (TBE) in a 47-year-old Lithuanian man. The case provides further evidence of TBE being a possible trigger of NMDAR encephalitis and highlights the importance of being aware of symptoms of autoimmune encephalitis in patients with infectious encephalitis.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos , Masculino , Humanos , Pessoa de Meia-Idade , Encefalite Transmitida por Carrapatos/epidemiologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Europa (Continente)/epidemiologia , ÁsiaRESUMO
BACKGROUND: A score to differentiate autoimmune (AE) and viral encephalitis (VE) early upon admission has recently been developed but needed external validation. The objective of this study was to evaluate the performance of the score in a larger and more diagnostically diverse patient cohort. METHODS: We conducted a retrospective nationwide and population-based cohort study including all adults with encephalitis of definite viral (2015-2022) or autoimmune aetiology (2009-2022) in Denmark. Variables included in the score-model were extracted from patient records and individual risk scores were assessed. The performance of the score was assessed by receiver-operating characteristics (ROC) curve analyses and calculation of the area under the curve (AUC). RESULTS: A total of 496 patients with encephalitis [AE n = 90, VE n = 287 and presumed infectious encephalitis (PIE) n = 119] were included in the study. The score was highly accurate in predicting cases of AE reaching an AUC of 0.94 (95% CI 0.92-0.97). Having a score ≥ 3 predicted AE with a PPV of 87% and an NPV of 91%. The risk score was found to perform well across aetiological subgroups and applied to the PIE cohort resulted in an AUC of 0.88 (95% CI 0.84-0.93). CONCLUSION: The excellent performance of the score as reported in the development study was confirmed in this significantly larger and more diverse cohort of patients with encephalitis in Denmark. These results should prompt further prospective testing with wider inclusion criteria.
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Encefalite Viral , Humanos , Dinamarca/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos Retrospectivos , Encefalite Viral/diagnóstico , Encefalite Viral/epidemiologia , Estudos de Coortes , Encefalite/diagnóstico , Encefalite/epidemiologia , Diagnóstico Diferencial , Medição de Risco/métodos , Adulto Jovem , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/diagnóstico , Idoso de 80 Anos ou maisRESUMO
Patient-reported quality-of-life (QoL) and carer impacts are not reported after leucine-rich glioma-inactivated 1-antibody encephalitis (LGI1-Ab-E). From 60 patients, 85% (51 out of 60) showed one abnormal score across QoL assessments and 11 multimodal validated questionnaires. Compared to the premorbid state, QoL significantly deteriorated (p < 0.001) and, at a median of 41 months, fatigue was its most important predictor (p = 0.025). In total, 51% (26 out of 51) of carers reported significant burden. An abbreviated five-item battery explained most variance in QoL. Wide-ranging impacts post-LGI1-Ab-E include decreased QoL and high caregiver strain. We identify a rapid method to capture QoL in routine clinic or clinical trial settings.
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Encefalite , Glioma , Humanos , Leucina , Qualidade de Vida , Peptídeos e Proteínas de Sinalização Intracelular , Autoanticorpos , Fadiga/etiologiaRESUMO
Background: Anti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance. Methods: IgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity. Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method. Results: The median age at onset was 66 years (range: 54-75), disease duration 10 years (range: 15-156 months), and follow-up 25 months (range: 0-83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab. Conclusion: Our findings might indicate that CSF IgLON5-specific IgG4 is frequently produced intrathecally, especially in HLA-DRB1*10:01 carriers. Intrathecally produced IgG4 may be clinically relevant. While many immunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease.
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Autoanticorpos , Imunoglobulina G , Humanos , Feminino , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoanticorpos/líquido cefalorraquidiano , Moléculas de Adesão Celular Neuronais/imunologia , Antígenos HLA/imunologia , Relevância ClínicaRESUMO
The heterogeneity of autoantibody targets in autoimmune encephalitides presents a challenge for understanding cellular and humoral pathophysiology, and the development of new treatment strategies. Thus, current treatment aims at autoantibody removal and immunosuppression, and is primarily based on data generated from other autoimmune neurological diseases and expert consensus. There are many subtypes of autoimmune encephalitides, which now entails both diseases with autoantibodies targeting extracellular antigens and classical paraneoplastic syndromes with autoantibodies targeting intracellular antigens. Here, we review the current knowledge of molecular and cellular effects of autoantibodies associated with autoimmune encephalitis, and evaluate the evidence behind the proposed pathophysiological mechanisms of autoantibodies in autoimmune encephalitis.
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Doenças Autoimunes do Sistema Nervoso , Encefalite , Doença de Hashimoto , Humanos , Autoanticorpos , ConsensoRESUMO
BACKGROUND: To describe the national Danish N-methyl-D-aspartate receptor encephalitis (NMDARE) cohort. METHODS: All NMDAR immunoglobulin G (IgG) positive cases in Denmark from 2009 to 2019 were included. Medical information was assessed retrospectively for clinical phenotype, workup, treatment and outcome. RESULTS: Seventy-seven patients were NMDAR IgG positive in serum/CSF. Fifty-five fulfilled the criteria of NMDARE, 18 did not and 4 had missing data. Incidence was 0.17/100,000 persons per year in 2018, and incidence rates increased since 2009. Of the 55 NMDARE patients (median age 27; 60% female), 9 had post-herpes simplex (HSE) NMDARE and 7 had a tumor (four teratomas). MRI was normal in 51% of patients. Brain FDG PET was performed in 17 patients, and was abnormal in 47% of patients with a normal MRI. First-line therapy was administered to 91%, and 24% required second-line therapy. Maintenance therapy during recovery was given 84% of patients, with no effect on relapse-risk. ICU admission occurred in 29%. Poor outcome (mRS > 2) was reported in 27% and dependent on age and etiology. Patients > 45 years had a poorer outcome (71% vs 8%, p < 0.0001), more frequently post-HSE NMDARE (47% vs 3%, p < 0.0001) and underlying malignancies (18% vs 0%). CONCLUSION: The incidence of NMDARE in Denmark is currently 0.17/100,000 persons per year, and has increased since 2009. NMDARE patients in Denmark display a higher median age, lower female:male ratio, a less frequent tumor association and need for ICU admission. Maintenance therapy did not reduce relapse rate. Poor outcome was seen with higher age, likely related to underlying etiology.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Receptores de N-Metil-D-Aspartato , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , N-Metilaspartato , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
OBJECTIVE: We conducted an open-label cross-over study assessing the global effect of two high-frequency protocols of electric-field navigated repetitive transcranial magnetic stimulation (rTMS) targeted to functional facial motor cortex and comparing their efficacy and tolerability in patients with chronic facial pain. Outcome predictors were also assessed. METHODS: We randomized twenty consecutive patients with chronic facial pain (post-traumatic trigeminal neuropathic pain, n=14; persistent idiopathic facial pain, n=4; secondary trigeminal neuralgia, n=2) to receive two distinct 5-day rTMS interventions (10Hz, 2400 pulses and 20Hz, 3600 pulses) separated by six weeks. The target area was assessed by mapping of lower face representation. The primary endpoint was the change in weekly mean of pain intensity (numeric rating scale, NRS) between the baseline and therapy week (1st week), and follow-up weeks (2nd and 3rd weeks) for each rTMS intervention. Response was defined using a combination scale including the patient's global impression of change and continuance with maintenance treatment. RESULTS: Overall, pain intensity NRS decreased from 7.4 at baseline to 5.9 ten weeks later, after the second rTMS intervention (p=0.009). The repetition of the treatment had a significant effect (F=4.983, p=0.043) indicating that the NRS scores are lower during the second four weeks period. Eight (40%) patients were responders, 4 (20%) exhibited a modest effect, 4 (20%) displayed no effect, and 4 (20%) experienced worsening of pain. High disability and high pain intensity (>7) predicted a better outcome (p=0.043 and p=0.045). Female gender, shorter duration of pain and low Beck Anxiety Inventory scores showed a trend towards a better outcome (p=0.052, 0.060 and 0.055, respectively). CONCLUSIONS: High-frequency rTMS targeted to face M1 alleviates treatment resistant chronic facial pain. Repeated treatment improves the analgesic effect. A protocol with higher frequency (above 10Hz), longer session duration (more than 20 minutes) and higher number of pulses (above 2400 pulses/session) did not improve the outcome. The results support early consideration of rTMS.
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Dor Crônica , Córtex Motor , Neuralgia , Dor Crônica/terapia , Estudos Cross-Over , Dor Facial/terapia , Feminino , Humanos , Manejo da Dor/métodos , Estimulação Magnética Transcraniana/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Spinal cord stimulation (SCS) is an effective treatment for failed back surgery syndrome (FBSS). In patients with FBSS, opioids have often been initiated, even before SCS is trialed. OBJECTIVE: We studied the effect of retirement on opioid use in patients with chronic pain after failed back surgery. STUDY DESIGN: A retrospective study design. SETTING: The study was conducted at Kuopio University Hospital. METHODS: The study group consisted of all 230 patients with SCS trialed or implanted for FBSS at Kuopio University Hospital Neurosurgery from January 1, 1996 through December 31, 2014. All purchases of prescribed opioids and their daily defined doses, as well as data on working ability, were obtained from the Social Insurance Institution. Patients were divided into 3 groups: SCS trial only, SCS implanted permanently, and SCS implanted but later explanted. We analyzed the differences in opioid use among these groups 2 years before and 2 years after the start of their disability pension (DP). RESULTS: During the follow-up period, a total of 60 patients received a DP. One year before DP, the majority of patients used opioids (n = 43, 72%), and throughout the one-year follow-up after retirement, the number of users increased slightly (n = 46, 77%). In the permanently implanted SCS group, the number of strong opioid users decreased after retirement. Most patients used a moderate dose (0.1-10.5 morphine milligram equivalent/d). Retirement appeared to interrupt dose escalation in all groups, but doses increased further as the follow-up continued. LIMITATIONS: No structured questionnaires were used in this study. Also, many underlying factors contributing to chronic pain were missing. CONCLUSIONS: DP did not reduce the use of opioids in patients with FBSS. Opioid doses were lower and dose escalation less steep with continuous SCS therapy.
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Dor Crônica , Síndrome Pós-Laminectomia , Transtornos Relacionados ao Uso de Opioides , Estimulação da Medula Espinal , Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Dor Crônica/etiologia , Síndrome Pós-Laminectomia/tratamento farmacológico , Síndrome Pós-Laminectomia/etiologia , Humanos , Transtornos Relacionados ao Uso de Opioides/etiologia , Pensões , Estudos Retrospectivos , Medula Espinal , Estimulação da Medula Espinal/efeitos adversos , Resultado do TratamentoRESUMO
Autoimmune encephalitis is an important, treatable subtype of acute encephalitis where autoantibodies target intra- or extracellular neural antigens. Despite research advances, diagnosis is often delayed or incorrect, which affects outcome negatively. We summarise clinical features of the most common autoantibody-mediated autoimmune encephalitis subtypes and focus on classification, current diagnostic challenges using commercially available diagnostic assays, in an attempt to increase awareness.
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Encefalite , Doença de Hashimoto , Autoanticorpos , Encefalite/diagnóstico , Encefalite/tratamento farmacológico , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/tratamento farmacológico , HumanosRESUMO
Background and Objectives: The two most common autoimmune encephalitides (AE), N-methyl-D-Aspartate receptor (NMDAR) and Leucine-rich Glioma-Inactivated 1 (LGI1) encephalitis, have been known for more than a decade. Nevertheless, no well-established biomarkers to guide treatment or estimate prognosis exist. Neurofilament light chain (NfL) has become an unspecific screening marker of axonal damage in CNS diseases, and has proven useful as a diagnostic and disease activity marker in neuroinflammatory diseases. Only limited reports on NfL in AE exist. We investigated NfL levels at diagnosis and follow-up in NMDAR and LGI1-AE patients, and evaluated the utility of CSF-NfL as a biomarker in AE. Methods: Patients were included from the National Danish AE cohort (2009-present) and diagnosed based upon autoantibody positivity and diagnostic consensus criteria. CSF-NfL was analyzed by single molecule array technology. Clinical and diagnostic information was retrospectively evaluated and related to NfL levels at baseline and follow-up. NMDAR-AE patients were subdivided into: idiopathic/teratoma associated or secondary NMDAR-AE (post-viral or concomitant with malignancies/demyelinating disease). Results: A total of 74 CSF samples from 53 AE patients (37 NMDAR and 16 LGI1 positive) were included in the study. Longitudinal CSF-NfL levels was measured in 21 patients. Median follow-up time was 23.8 and 43.9 months for NMDAR and LGI1-AE respectively. Major findings of this study are: i) CSF-NfL levels were higher in LGI1-AE than in idiopathic/teratoma associated NMDAR-AE at diagnosis; ii) CSF-NfL levels in NMDAR-AE patients distinguished idiopathic/teratoma cases from cases with other underlying etiologies (post-viral or malignancies/demyelinating diseases) and iii) Elevated CSF-NfL at diagnosis seems to be associated with worse long-term disease outcomes in both NMDAR and LGI1-AE. Discussion: CSF-NfL measurement may be beneficial as a prognostic biomarker in NMDAR and LGI1-AE, and high CSF-NfL could foster search for underlying etiologies in NMDAR-AE. Further studies on larger cohorts, using standardized methods, are warranted.
Assuntos
Encefalite Límbica/líquido cefalorraquidiano , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encefalite Antirreceptor de N-Metil-D-Aspartato/líquido cefalorraquidiano , Encefalite Antirreceptor de N-Metil-D-Aspartato/etiologia , Biomarcadores/líquido cefalorraquidiano , Criança , Doenças Desmielinizantes/complicações , Dinamarca , Encefalite por Herpes Simples/líquido cefalorraquidiano , Feminino , Seguimentos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Leucocitose/etiologia , Encefalite Límbica/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/líquido cefalorraquidiano , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Prognóstico , Teratoma/complicações , Resultado do Tratamento , Adulto JovemRESUMO
Anti-IgLON5 disease is a progressive neurological disorder associated with autoantibodies against a neuronal cell adhesion molecule, IgLON5. In human postmortem brain tissue, the neurodegeneration and accumulation of hyperphosphorylated tau (p-tau) are found. Whether IgLON5 antibodies induce neurodegeneration or neurodegeneration provokes an immune response causing inflammation and antibody formation remains to be elucidated. We investigated the effects of anti-IgLON5 antibodies on human neurons. Human neural stem cells were differentiated for 14-48 days and exposed from Days 9 to 14 (short-term) or Days 13 to 48 (long-term) to either (i) IgG from a patient with confirmed anti-IgLON5 antibodies or (ii) IgG from healthy controls. The electrical activity of neurons was quantified using multielectrode array assays. Cultures were immunostained for ß-tubulin III and p-tau and counterstained with 4',6-Diamidine-2'-phenylindole dihydrochloride (DAPI). To study the impact on synapses, cultures were also immunostained for the synaptic proteins postsynaptic density protein 95 (PSD95) and synaptophysin. A lactate dehydrogenase release assay and nuclei morphology analysis were used to assess cell viability. Cultures exposed to anti-IgLON5 antibodies showed reduced neuronal spike rate and synaptic protein content, and the proportion of neurons with degenerative appearance including p-tau (T205)-positive neurons was higher when compared to cultures exposed to control IgG. In addition, cell death was increased in cultures exposed to anti-IgLON5 IgG for 21 days. In conclusion, pathological anti-IgLON5 antibodies induce neurodegenerative changes and cell death in human neurons. This supports the hypothesis that autoantibodies may induce the neurodegenerative changes found in patients with anti-IgLON5-mediated disease. Furthermore, this study highlights the potential use of stem cell-based in vitro models for investigations of antibody-mediated diseases. As anti-IgLON5 disease is heterogeneous, more studies with different IgLON5 antibody samples tested on human neurons are needed.
Assuntos
Anticorpos/efeitos adversos , Moléculas de Adesão Celular Neuronais/imunologia , Células-Tronco Pluripotentes Induzidas/patologia , Degeneração Neural/etiologia , Neurônios/patologia , Autoanticorpos/metabolismo , Morte Celular , Linhagem Celular , Membrana Celular/metabolismo , Células Cultivadas , Humanos , Células-Tronco Neurais/metabolismo , Neurônios/metabolismoRESUMO
BACKGROUND: Spinal cord stimulation (SCS) is an effective treatment in chronic neuropathic pain, but its efficacy in complex regional pain syndrome (CRPS) needs to be proven. OBJECTIVE: To study the outcome of SCS in CRPS as measured by trial success, explantation rate, complications, and changes in opioid and neuropathic pain medication use over a 4-yr follow-up. METHODS: We retrospectively reviewed all medical records of 35 consecutive CRPS patients who underwent SCS trials at 2 hospitals during January 1998 to December 2016. The purchase data of opioids and neuropathic pain medication during January 1995 to March 2016 were retrieved from national registries. RESULTS: Based on a 1-wk trial, permanent SCS was implanted in 27 (77%) patients. During the median follow-up of 8 yr, 8 (30%) SCS devices were explanted, of which 7 were because of inefficient pain relief. Complications leading to revision occurred in 17 (63%) patients: 8 electrode migrations or stimulation to the wrong area, 1 deep infection, 9 hardware malfunctions, 2 pulse generator discomforts, and 2 SCS replacements. None of the 6 patients using strong opioids discontinued their use during the 2-yr follow-up. The mean opioid dose increased nonsignificantly both in patients with SCS in permanent use (53 ± 150 morphine milligram equivalents morphine milligram equivalent (MME)/day to 120 ± 240 MME/day) and in patients who had SCS explanted (27 ± 72 MME/day to 57 ± 66 MME/day). CONCLUSION: Despite the fact that CRPS patients were not able to discontinue or reduce their strong opioid or neuropathic pain medication use, 70% continued to use their SCS device during a median 8-yr follow-up.