RESUMEN
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.
Asunto(s)
Dolor Crónico , Estimulación de la Médula Espinal , Humanos , Estimulación de la Médula Espinal/métodos , Masculino , Femenino , Persona de Mediana Edad , Dolor Crónico/terapia , Anciano , Adulto , Factores de Tiempo , Estudios Prospectivos , Dimensión del Dolor/métodos , Resultado del Tratamiento , Internacionalidad , Neuralgia/terapiaRESUMEN
BACKGROUND: Patients receiving a brain cancer diagnosis may face cognitive decline and a poor prognosis. In addition, they suffer from a high symptom burden in a complex cancer pathway. The aim of this study was to investigate the early hospital experiences of brain tumour patients during the diagnostic and surgical treatment phase. METHODS: A descriptive longitudinal single-case study design was used, and data were analysed via systematic text condensation. RESULTS: The patients' experiences of being diagnosed with and treated for brain cancer were interpreted in terms of the central theme: a fast transition into an unknown journey. This theme consisted of the following subthemes: emotionally overwhelmed, putting life on hold and an unfamiliar dependency. CONCLUSIONS: Patients diagnosed with brain cancer struggle with overwhelming emotions due to this sudden life-threatening diagnosis, their fear of brain surgery and their progressing dependence. Patients did not voice their feelings, fears or needs, so these may easily be overlooked and unmet. A proactive and continuous care approach throughout the diagnostic phase is needed to support these patients.
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Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/psicología , Neoplasias Encefálicas/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Longitudinales , AdultoRESUMEN
BACKGROUND: Chronic cluster headache (CCH) is a debilitating primary headache disorder. Occipital nerve stimulation (ONS) has shown the potential to reduce attack frequency, but the occipital paresthesia evoked by conventional (tonic) stimulation challenges a blinded comparison of active stimulation and placebo. Burst ONS offers paresthesia-free stimulation, enabling a blinded, placebo-controlled study. Identification of a feasible preoperative test would help select the best candidates for implantation. This study aims to explore ONS as a preventive treatment for CCH, comparing burst stimulation to tonic stimulation and placebo, and possibly identifying a potential preoperative predictor. METHODS: An investigator-initiated, double-blinded, randomized, placebo-controlled trial is conducted, including 40 patients with CCH. Eligible patients complete a trial with the following elements: I) four weeks of baseline observation, II) 12 weeks of transcutaneous electrical nerve stimulation (TENS) of the occipital nerves, III) implantation of a full ONS system followed by 2 week grace period, IV) 12 weeks of blinded trial with 1:1 randomization to either placebo (deactivated ONS system) or burst (paresthesia-free) stimulation, and V) 12 weeks of tonic stimulation. The primary outcomes are the reduction in headache attack frequency with TENS and ONS and treatment safety. Secondary outcomes are treatment efficacy of burst versus tonic ONS, the feasibility of TENS as a predictor for ONS outcome, reduction in headache pain intensity (numeric rating scale), reduction in background headache, the patient's impression of change (PGIC), health-related quality of life (EuroQoL-5D), self-reported sleep quality, and symptoms of anxiety and depression (Hospital Anxiety and Depression Scale, HADS). Data on headache attack characteristics are registered weekly. Data on patient-reported outcomes are assessed after each trial phase. DISCUSSION: The study design allows a comparison between burst ONS and placebo in refractory CCH and enables a comparison of the efficacy of burst and tonic ONS. It will provide information about the effect of burst ONS and explore whether the addition of this stimulation paradigm may improve stimulation protocols. TENS is evaluated as a feasible preoperative screening tool for ONS outcomes by comparing the effect of attack prevention of TENS and tonic ONS. TRIAL REGISTRATION: The study is registered at Clinicaltrials.gov (trial registration number NCT05023460, registration date 07-27-2023).
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Cefalalgia Histamínica , Estimulación Eléctrica Transcutánea del Nervio , Humanos , Estimulación Eléctrica Transcutánea del Nervio/métodos , Cefalalgia Histamínica/terapia , Calidad de Vida , Estudios Prospectivos , Cefalea , Resultado del Tratamiento , Método Doble Ciego , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVES AND BACKGROUND: Chronic cluster headache (CCH) is a rare but severely debilitating primary headache condition. A growing amount of evidence suggests that occipital nerve stimulation (ONS) can offer effective treatment in patients with severe CCH for whom conventional medical therapy does not have a sufficient effect. The paresthesia evoked by conventional (tonic) stimulation can be bothersome and may thus limit therapy. Burst ONS produces paresthesia-free stimulation, but the amount of evidence on the efficacy of burst ONS as a treatment for intractable CCH is scarce. METHODS: In this case series, we report 15 patients with CCH treated with ONS at Aarhus University Hospital, Denmark, from 2013 to 2020. Nine of these received burst stimulation either as primary treatment or as a supplement to tonic stimulation. The results were assessed in terms of the frequency of headache attacks per week and their intensity on the Numeric Rating Scale, as well as the Patient Global Impression of Change (PGIC) with ONS treatment. RESULTS: At a median (range) follow-up of 38 (16-96) months, 12 of the 15 patients (80%) reported a reduction in attack frequency of ≥50% (a reduction from a median of 35 to 1 attack/week, p < 0.001). Seven of these patients were treated with burst ONS. A significant reduction was also seen in maximum pain intensity. Overall, 10 patients stated a clinically important improvement in their headache condition following ONS treatment, rated on the PGIC scale. A total of 16 adverse events (nine of which were in the same patient) were registered. CONCLUSION: Occipital nerve stimulation significantly reduced the number of weekly headache attacks and their intensity. Burst ONS seems to function well alone or as a supplement to conventional tonic ONS as a preventive treatment for CCH; however, larger prospective studies are needed to determine whether the effect can be confirmed and whether the efficacy of the two stimulation paradigms is even.
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Cefalalgia Histamínica , Trastornos de Cefalalgia , Humanos , Cefalalgia Histamínica/terapia , Cefalea , Trastornos de Cefalalgia/terapia , Investigación , Cafeína , ParestesiaRESUMEN
OBJECTIVES: Spinal cord stimulation (SCS) is a treatment for chronic neuropathic pain. It is based on the delivery of electric impulses to the spinal cord, traditionally in a regular square-wave pattern ("tonic" stimulation) and, more recently, in a rhythmic train-of-five "BurstDR" pattern. The safety of active SCS therapy in pregnancy is not established, and recommendations are based on limited casuistic evidence. We present in this study clinical data on a case series of six women treated with burst SCS during pregnancy. In addition, we present the ultrasonographic flow measurements of fetal and uteroplacental blood flow in a pregnant patient. MATERIALS AND METHODS: Patients were included if they had been implanted with a full SCS system at Aarhus University Hospital, Denmark, between 2006 and 2020 and received active burst SCS stimulation during a pregnancy. Telephone interviews were conducted, including details on SCS therapy, medication, pregnancy course and outcome, and health status of the offspring. In one patient, the uteroplacental and fetal blood flow was assessed in gestational week 29 by Doppler flow measurements performed during both ON and OFF phases of the SCS system. RESULTS: Six patients were included with a total of 11 pregnancies. Three pregnancies ended in miscarriages, all in the same patient who had preexisting significant risk factors for miscarriage. Eight resulted in a live-born child with normal birth weight for gestational age; seven were born at term, and one was born late preterm, in gestational week 36. Ultrasonographic Doppler flow, measured in one patient, was normal and did not reveal any immediate changes between burst SCS ON and OFF. Seven children were reported healthy with normal neurodevelopment and one physically healthy but with developmental delays. CONCLUSIONS: The data presented in this study add to the accumulating evidence of the safety of SCS in pregnancy.
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Neuralgia , Estimulación de la Médula Espinal , Embarazo , Niño , Recién Nacido , Humanos , Femenino , Estimulación de la Médula Espinal/métodos , Neuralgia/terapia , Médula Espinal/diagnóstico por imagen , Resultado del TratamientoRESUMEN
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.
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Dolor Crónico , Neuralgia , Trastornos Relacionados con Opioides , Estimulación de la Médula Espinal , Analgésicos Opioides/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Estudios de Cohortes , Humanos , Neuralgia/tratamiento farmacológico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Médula Espinal , Estimulación de la Médula Espinal/métodos , Resultado del TratamientoRESUMEN
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.
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Dolor Crónico , Estimulación de la Médula Espinal , Catastrofización , Dolor Crónico/terapia , Estudios de Cohortes , Estudios de Seguimiento , Humanos , Resultado del TratamientoRESUMEN
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.
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Dolor Crónico , Neuralgia , Estimulación de la Médula Espinal , Dolor Crónico/terapia , Estudios de Cohortes , Dinamarca/epidemiología , Ganglios Espinales , Humanos , Neuralgia/terapiaRESUMEN
Amines synthesized by plants may be considered a dietary source of bioactive compounds, which are of interest due to possible health promoting effects. Developing Sinapis alba sprouts are known to produce 4-hydroxybenzylamine, but the reaction mechanism has not yet been established. We propose here a suggested metabolic pathway for the formation of 4-hydroxybenzylamine in S. alba plants. The catabolic sequence starts with a reaction between l-glutamine (Gln) as ammonia donor and 4-hydroxybenzyl carbocation, the enzymatic catalyzed hydrolysis product from sinalbin (4-hydroxybenzylglucosinolate). The suggested reactions are compared with alternative plant metabolic reactions used in the biosynthesis of biogenic amines.
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Amoníaco/química , Bencilaminas/metabolismo , Aminas Biogénicas/metabolismo , Glucosinolatos/metabolismo , Aminas Biogénicas/química , Colina/análogos & derivados , Colina/química , Colina/metabolismo , Glucosinolatos/química , Glutamina , Hidrólisis , Estructura Molecular , Sinapis/química , Sinapis/metabolismoRESUMEN
BACKGROUND: The high mortality and morbidity after SAH is partly due to DCI, which is traditionally ascribed to development of angiographic vasospasms. This relation has been challenged, and capillary flow disturbances are proposed as another mechanism contributing to brain damage after SAH. OBJECTIVE: To investigate capillary flow changes 4 days following experimental SAH. METHODS: SAH was induced by endovascular perforation of circle of Willis. We used TPM to evaluate blood flow characteristics. Cortical capillary diameters were investigated by both TPM and histology. RESULTS: We found elevated CTH and MTT of blood in SAH mice compared to sham animals. We observed capillaries with stagnant RBCs, and capillaries with increased RBC LD in the SAH group, suggesting severe blood maldistribution among cortical capillaries. Favoring that these capillary flow changes were primary to upstream vasoconstrictions, TPM showed no significant differences in arteriolar diameter between groups, while histological examination showed reduced capillary diameter in SAH group. CONCLUSION: Our study shows profound subacute hypoperfusion and capillary flow disturbances in a mouse SAH model and suggests that these changes are the result of changes in capillary function, rather than upstream vasospasm.
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Capilares , Infarto Cerebral , Circulación Cerebrovascular , Microcirculación , Hemorragia Subaracnoidea , Animales , Capilares/patología , Capilares/fisiopatología , Infarto Cerebral/patología , Infarto Cerebral/fisiopatología , Modelos Animales de Enfermedad , Masculino , Ratones , Hemorragia Subaracnoidea/patología , Hemorragia Subaracnoidea/fisiopatologíaRESUMEN
OBJECTIVES: In spinal cord stimulation (SCS), the electrical stimulation of the spinal cord with an implanted lead evokes a tingling peripheral sensation known as paresthesias. Newer stimulation paradigms allow paresthesia-free treatment, but during the implantation of the lead, paresthesias must cover the painful area to achieve optimal treatment effect. The localization of the evoked paresthesias can be difficult to accurately describe for the patient, and furthermore depends on a complex and only partially predictable set of parameters that includes the anatomical localization and the programming of the electrical field. We aimed to optimize SCS implantation procedures by devising a way to aid the patient in making useful descriptions of the evoked paresthesias, then to visually convey the full set of information-anatomical position of the lead, programming parameters, and evoked paresthesias-directly to the implanting physician. MATERIALS AND METHODS: To aid the patient in making accurate descriptions of the evoked paresthesia, we use an app dedicated to creating pain drawings on a tablet. We used Chromecast and Apple TV to project the information from the pain drawing tablet and the programming device to two monitors placed in the implanter's field of vision, right next to the fluoroscopy monitor. RESULTS: The three monitors combined provide a direct visual representation of the dynamic dataset used during SCS implantation: Position, Programming, and Paresthesias, essentially creating the equivalent of the dashboard of a car. CONCLUSIONS: We present an Implanter's Integrated Information (I3) system; a simple, inexpensive solution for gathering, integrating, and conveying the complex set of information necessary for a successful SCS procedure.
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Electrodos Implantados , Imagenología Tridimensional/métodos , Monitorización Neurofisiológica Intraoperatoria/métodos , Manejo del Dolor/métodos , Parestesia/diagnóstico por imagen , Estimulación de la Médula Espinal/métodos , Integración de Sistemas , Humanos , Imagenología Tridimensional/instrumentación , Monitorización Neurofisiológica Intraoperatoria/instrumentación , Manejo del Dolor/instrumentación , Parestesia/terapia , Estimulación de la Médula Espinal/instrumentaciónRESUMEN
The nutritional quality of rapeseed press cakes (RPCs) in piglet feed is closely linked to its digestibility and the content of glucosinolates. This study investigates the significance of intact glucosinolate (glc) levels and degree of glc transformations on piglets performance. Four different RPCs were made from a low glc (11 µmol/g seed DM) containing B. napus L. seed variety Lioness (RPC-LW, RPC-LXW, RPC-LC, RPC-LCD). RPC made from the variety Excalibur containing the upper level of glc (24 µmol/g seed DM) of double rapeseed and produced at higher and prolonged temperature (RPC-UXW) served as negative control, while soya bean protein concentrate served as positive control. Piglets (8 kg) were fed ad libitum diets balanced for RPC protein content, with RPC inclusion of 84-98 g/kg (day 0-14) and 151-178 g/kg (day 15-50). Glc transformation was reduced from 42% to 24% (7.3-4.2 µmol/g RPC) when the temperature input was lowered in the warm pressing of oil, while the glc loss was less pronounced (17%) when cold pressing was applied. The following feed pelleting process further reduced Glc concentration from 11% to 40% in warm-pressed RPCs and 54 to 85% in cold-pressed RPCs. The RPC products replaced soya bean protein without any negative effects on performance, except for piglets served cold-pressed RPC, which had a reduction in average daily weight gain (ADG) (5%-7%, p < 0.05, Day 15-50). RPC in the feed led to increased liver weight in all piglets (p = 0.026). This may point at long-term effects from feeding with RPC. Intestinal absorption of intact glcs was proven by their detection in urine. In conclusion, warm-pressed RPC can be used as feed for piglet, while the presence of active myrosinase may have a negative effect on performance and cakes should either be included in lower amounts than used in the present study (18%) or include myrosinase inactivation before use.
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Alimentación Animal/análisis , Brassica rapa/química , Dieta/veterinaria , Glucosinolatos/farmacología , Porcinos/crecimiento & desarrollo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Peso Corporal/efectos de los fármacos , Proteínas en la Dieta/química , Proteínas en la Dieta/metabolismo , Glucosinolatos/administración & dosificación , Glucosinolatos/química , Glucosinolatos/metabolismo , Riñón/anatomía & histología , Riñón/efectos de los fármacos , Hígado/anatomía & histología , Hígado/efectos de los fármacos , Masculino , Nitrógeno/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Distribución Aleatoria , Ratas , Glándula Tiroides/anatomía & histología , Glándula Tiroides/efectos de los fármacosRESUMEN
The Göttingen minipig is being used increasingly in biomedical research. The anatomical structure of the porcine peripheral nervous system has been extensively characterized, but no equivalent to the dermatome map, which is so valuable in human neurophysiological research, has been created. We characterized the medullar segmental skin and muscle innervations of the minipig hind body, using neurophysiological methodology. Six adult minipigs underwent unilateral laminectomy from L2 to S3, exposing the nerve roots. The skin of the hind part of the body was divided into 36 predefined fields, based on anatomical landmarks for consistent reproducibility. We recorded the evoked potential in each exposed nerve root L2-S3 for cutaneous stimulation of each skin field, mapping the sensory innervation of the entire hind body. We subsequently recorded the motor response in seven predefined muscles during sequential stimulation of the L2-S3 nerve roots. We obtained a clear sensory evoked potential in the nerve roots during stimulation of the skin fields, allowing us to map the sensory innervation of the minipig hind body. Neurophysiological data from skin stimulation and muscle recordings enabled us to map the sensory innervation of the Göttingen minipig hind body and provide information about muscular innervation. The skin fields were sensory innervated by more than one root. The muscles each had one dominant root with minor contribution from neighboring roots. This is consistent with experimental data from human studies.
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Miembro Posterior/inervación , Región Lumbosacra/inervación , Músculo Esquelético/inervación , Piel/inervación , Animales , Electrofisiología , Potenciales Evocados Somatosensoriales , Femenino , Porcinos , Porcinos EnanosRESUMEN
Parkinson's disease is characterized by a progressive loss of substantia nigra (SN) dopaminergic neurons and the formation of Lewy bodies containing accumulated alpha-synuclein (α-syn). The pathology of Parkinson's disease is associated with neuroinflammatory microglial activation, which may contribute to the ongoing neurodegeneration. This study investigates the in vivo microglial and dopaminergic response to overexpression of α-syn. We used positron emission tomography (PET) and the 18 kDa translocator protein radioligand, [11 C](R)PK11195, to image brain microglial activation and (+)-α-[11 C]dihydrotetrabenazine ([11 C]DTBZ), to measure vesicular monoamine transporter 2 (VMAT2) availability in Göttingen minipigs following injection with recombinant adeno-associated virus (rAAV) vectors expressing either mutant A53T α-syn or green fluorescent protein (GFP) into the SN (4 rAAV-α-syn, 4 rAAV-GFP, 5 non-injected control minipigs). We performed motor symptom assessment and immunohistochemical examination of tyrosine hydroxylase (TH) and transgene expression. Expression of GFP and α-syn was observed at the SN injection site and in the striatum. We observed no motor symptoms or changes in striatal [11 C]DTBZ binding potential in vivo or striatal or SN TH staining in vitro between the groups. The mean [11 C](R)PK11195 total volume of distribution was significantly higher in the basal ganglia and cortical areas of the α-syn group than the control animals. We conclude that mutant α-syn expression in the SN resulted in microglial activation in multiple sub- and cortical regions, while it did not affect TH stains or VMAT2 availability. Our data suggest that microglial activation constitutes an early response to accumulation of α-syn in the absence of dopamine neuron degeneration.
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Neuroglía/metabolismo , Enfermedad de Parkinson/metabolismo , alfa-Sinucleína/genética , Amidas , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Femenino , Células HEK293 , Humanos , Isoquinolinas , Enfermedad de Parkinson/diagnóstico por imagen , Tomografía de Emisión de Positrones , Porcinos , Porcinos Enanos , Tetrabenazina/análogos & derivados , Proteínas de Transporte Vesicular de Monoaminas/metabolismo , alfa-Sinucleína/metabolismoRESUMEN
AIMS AND OBJECTIVES: To identify and describe patients' experiences and care needs throughout the diagnostic phase of an integrated brain cancer pathway. BACKGROUND: A malignant brain tumour is a devastating diagnosis, which may cause psychical symptoms and cognitive deficits. Studies have shown that the shock of the diagnosis, combined with the multiple symptoms, affects patients' ability to understand information and express needs of care and support. Unmet needs have been reported within this group of patients; however, the experiences and care needs of patients going through the diagnostic phase of a standardised integrated brain cancer pathway have not previously been explored. DESIGN: A case study design was used to provide detailed information of the complex needs of patients being diagnosed with a malignant brain tumour. METHODS: Research interviews and direct participant observation of four patients during hospital admission, brain surgery and discharge were conducted in a Danish university hospital. Systematic text condensation was used to analyse the data material. RESULTS: Four major themes were identified: information needs, balancing hope and reality while trying to perceive the unknown reality of brain cancer, not knowing what to expect and participants' perceptions of the relationship with the healthcare providers. The analysis revealed that participants were in risk of having unmet information needs and that contextual factors seemed to cause fragmented care that led to feelings of uncertainty and loss of control. CONCLUSIONS: Brain tumour patients have complex care needs and experience a particular state of vulnerability during the diagnostic phase. Through personal relationships based on trust with skilled healthcare providers, participants experienced an existential recognition and alleviation of emotional distress. RELEVANCE TO CLINICAL PRACTICE: Patients receiving a brain tumour diagnosis experience unmet care needs in several areas during their hospital stay. There is a need for interventions from healthcare providers.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/psicología , Necesidades y Demandas de Servicios de Salud , Examen Neurológico/psicología , Participación del Paciente/psicología , Relaciones Médico-Paciente , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Ventriculostomy/external ventricular drain (EVD) is a common neurosurgical procedure. Various techniques are used to fixate the drain and the objective of this study was, in a retrospective setting, to compare the incidence of complications when using bolt-connected EVD (BC-EVD) versus tunneled EVD (T-EVD). METHODS: All patients subjected to an EVD performed through a new burr hole from 2009 through 2010 at two Depts. of Neurosurgery in Denmark (Odense and Aarhus) were retrospectively identified. Patient files were evaluated for EVD fixation technique (tunneled or bolt-connected EVD) and complications including unintended removal, catheter obstruction, infection, CSF leakage, and mechanical problems. RESULTS: A total of 271 patients with 272 separate EVDs met the inclusion criteria. There was a statistically higher rate of complications leading to reinsertion in the tunneled EVD group (40 %), compared to the bolt-connected EVD group (6.5 %). There was no significant difference in infection rates. CONCLUSIONS: Tunneled EVD has a relatively high frequency of complications leading to reinsertion. The use of Bolt-connected EVD technique can lower this frequency significantly. The number needed to treat is three for preventing a complication requiring reinsertion. Infection rates are low for both types of ventriculostomies. Accordingly, we recommend use of Bolt-connected EVDs in neurosurgical practice.
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Drenaje/métodos , Complicaciones Posoperatorias , Trepanación/métodos , Ventriculostomía/métodos , Adulto , Anciano , Catéteres de Permanencia/efectos adversos , Drenaje/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trepanación/efectos adversos , Ventriculostomía/efectos adversosRESUMEN
OBJECTIVES: The ability to safely place viable intracerebral grafts of human-derived therapeutic stem cells in three-dimensional (3D) space was assessed in a porcine model of human stereotactic surgery using the Intracerebral Microinjection Instrument (IMI) compared to a conventional straight cannula. MATERIALS AND METHODS: Two groups of healthy minipigs received injections of the human stem cell line, NSI-566, into the right hemisphere and cell suspension carrier media into the left hemisphere. Group A received all injections using a straight, 21-gauge stainless steel cannula. Group B received all injections using the IMI, whereby radial distribution of injections was achieved via angular extension of a 196-micron diameter cannula from a single overlying penetration of the guide cannula. Each animal received six 20 µL intracerebral-injections within each hemisphere: three in a radial distribution, covering a 180° arc with each injection separated by a 60° arc distance, within both frontal cortex and basal ganglia. H&E and immunocytochemistry (HuNu and GFAP) were used to identify implanted cells and to assess tissue response. RESULTS: The presence of surviving cells in appropriate brain regions demonstrated that the IMI is capable of accurately delivering viable human-derived stem cells safely in a 3D array at predetermined sites within the pig brain. In addition, qualitative evaluation of the target tissue suggests efficient delivery with decreased surgical trauma. CONCLUSIONS: In contrast to traditional straight cannulas, the IMI enables the delivery of multiple precise cellular injection volumes in accurate 3D arrays. In this porcine large animal model of human neurosurgery, the IMI reduced surgical time and appeared to reduce neural trauma associated with multiple penetrations that would otherwise be required using a conventional straight delivery cannula.
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Lesiones Traumáticas del Encéfalo/cirugía , Células Madre Embrionarias/fisiología , Microinyecciones/métodos , Trasplante de Células Madre/métodos , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/patología , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Modelos Animales de Enfermedad , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Fosfopiruvato Hidratasa/metabolismo , Porcinos , Porcinos EnanosRESUMEN
OBJECTIVE: A comparison of cryoneurolysis or radio frequency (RF) with placebo in patients with facetogenic chronic low back pain (LBP) for patient global impression of change (PGIC), pain intensity, function and quality of life, with 1-year follow-up. DESIGN: Single-centre, single-blinded placebo-controlled randomised controlled trial. SETTING: Single-centre study. PARTICIPANTS: Inclusion from March 2020 to September 2022: consenting adults over 18 years of age, LBP>3 months, average Numeric Rating Scale LBP≥4 average last 14 days and a positive response to a diagnostic medial branch block (>50% pain reduction after 60 min). INTERVENTIONS: 120 patients were block randomised 1:1:1 to cryoneurolysis, RF or placebo of the medial branch nerves. Physical therapy was added after 4 weeks for all groups. MAIN OUTCOME MEASURES: Primary outcome was PGIC 4 weeks after the intervention. Secondary outcomes included pain intensity (Numeric Rating Scale, NRS), quality of life (Short Form 36, EQ-5D-5L), disability (Oswestry Disability Index), depression (Major Depression Inventory) and catastrophising (Pain Catastrophising Scale). Outcomes were measured at 4 weeks, 3, 6 and 12 months. RESULTS: There was no statistically significant difference in PGIC at 4 weeks between cryoneurolysis and placebo (risk ratio (RR) 2; 95% CI 0.75 to 5.33, p=0.17) and RF and placebo (RR 1.6; 95% CI 0.57 to 4.49, p=0.37), except PGIC for cryoneurolysis at 6-month follow-up (RR 5.1; 95% CI 1.20 to 22.03, p=0.03). No statistically significant differences were found in secondary follow-up endpoints. CONCLUSIONS: Denervation of the medial branch nerve by either cryoneurolysis or RF compared with placebo did not demonstrate significant improvement in PGIC, pain intensity, function and quality of life in patients with facetogenic chronic LBP at short-term or long-term follow-up. TRIAL REGISTRATION NUMBER: NCT04786145.
Asunto(s)
Dolor Crónico , Dolor de la Región Lumbar , Dimensión del Dolor , Calidad de Vida , Ablación por Radiofrecuencia , Humanos , Dolor de la Región Lumbar/terapia , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/psicología , Masculino , Femenino , Persona de Mediana Edad , Ablación por Radiofrecuencia/métodos , Ablación por Radiofrecuencia/efectos adversos , Dolor Crónico/terapia , Dolor Crónico/etiología , Dolor Crónico/psicología , Resultado del Tratamiento , Adulto , Método Simple Ciego , Criocirugía/métodos , Anciano , Manejo del Dolor/métodosRESUMEN
OBJECTIVES: Spinal cord stimulation (SCS) is increasingly gaining widespread use as a treatment for chronic pain. A widely used electronic registry could play a pivotal role in improving this complex and cost-intensive treatment. We aimed to construct a comprehensive, universally available data base for SCS. MATERIALS AND METHODS: The design considerations behind a new online data base for SCS are presented; basic structure, technical issues, research applications, and future perspectives are described. RESULTS: The Aarhus Neuromodulation Database covers core SCS treatment parameters, including procedure-related details and complications, and features recording of key success parameters such as pain intensity, work status, and quality of life. It combines easy access to patient information with exhaustive data extraction options, and it can readily be adapted and expanded to suit different needs, including other neuromodulation treatment modalities. CONCLUSIONS: We believe that the data base described in this article offers a powerful and versatile data collection tool suited for both clinicians and researchers in the field. The basic data base structure is immediately available on a no-cost basis, and we invite our colleagues to make use of the data base as part of the efforts to further the field of neuromodulation.