Stable Symptom Control Research Articles

Pallidal neurostimulation versus botulinum toxin injections in the treatment of cervical dystonia: protocol of a randomized, sham-controlled trial (StimTox-CD)

BackgroundSelective peripheral denervation via botulinum neurotoxin injections into dystonic muscles is the first-line treatment for cervical dystonia. Pallidal neurostimulation is a potent alternative, but currently restricted to patients failing on neurotoxin therapy. As botulinum neurotoxin is partially effective but often unsatisfactory in a relevant proportion of patients, earlier neurostimulation might be advantageous in providing stable symptom control and preventing disability. This trial intends to demonstrate, that pallidal neurostimulation is superior to neurotoxin injections in best clinical practice for controlling the symptoms of cervical dystonia and that it is safe in patients with a partial therapy response to peripheral denervation. We hypothesize a better outcome in everyday functioning and health-related quality of life of neurostimulated patients.MethodsWe aim to recruit 66 cervical dystonia patients into a double-blind comparison of pallidal neurostimulation versus botulinum neurotoxin type A. Eligible patients need ≥25% motor symptom reduction 4 weeks after a neurotoxin test injection, but are willing to undergo DBS surgery due to unsatisfactory symptom control. All participants will be implanted with a DBS system, and randomized into 2 groups: First group will receive effective neurostimulation and saline injections into dystonic muscles. Second group is treated with regular neurotoxin injections and undergoes a sham-stimulation. Primary outcome is the change in TWSTRS total score between baseline and 6 months of therapy. Secondary outcome parameters are corresponding changes in TWSTRS motor score, Tsui score, CDQ-24 and SF-36. Safety will be assessed by frequency and severity of reported adverse events. Statistical analysis includes intention-to-treat and per protocol populations, analysis based on imputation of missing values and analysis adjusting for differences in baseline TWSTRS. After 6 months of blinded treatment all patients will receive open-label neurostimulation and neurotoxin treatment as needed, and are followed up 48 weeks after randomization.PerspectiveWe will assess if pallidal neurostimulation is a safe and effective alternative to selective peripheral denervation by botulinum toxin injections in cervical dystonia, which may be offered earlier in the course of disease based on patient preference. A positive study outcome would influence future treatment guidelines of cervical dystonia.Trial registrationEudraCT registration number: 2016–001378-13

Surgical resection of vasoactive intestinal peptideoma with hepatic metastasis aids symptom palliation: A case report.

Vasoactive intestinal peptideoma (VIPoma) is a rare pancreatic endocrine tumor associated with a well-defined clinical syndrome characterized by watery diarrhea, hypokalemia and metabolic acidosis. In adults, VIPoma is most commonly found in the pancreas, with 80% of the tumors occurring in the body and tail and 20% occurring in the pancreatic head. VIPomas can represent a significant diagnostic challenge due to their nonspecific clinical presentation, which can result in the misdiagnosis of a VIPoma as another condition, such as laxative overdose or a carcinoid secreting tumor. Surgical clearance of the tumor is the first-line treatment, even in cases with metastasis. The present study describes the case of a patient who presented with chronic watery diarrhea and hypokalemia due to a tumor in the pancreatic head, which was confirmed to contain immunoreactive vasoactive intestinal polypeptide via immunohistochemistry. A hepatic metastasis lesion was diagnosed following computed tomography. Stable control of symptoms was achieved after surgery and drug treatment. The study additionally reviews the clinical, histological, radiological and diagnostic features of the condition, as well as the therapeutic modalities that can be used to treat VIPoma in the pancreatic head with hepatic metastasis.

Maintaining stable symptom control in inflammatory bowel disease: a retrospective analysis of adherence, medication switches and the risk of relapse

SummaryBackground Maintenance therapy with 5-aminosalicylic acid (5-ASA) is a key strategy for preventing relapse in many patients with inflammatory bowel disease (IBD). Factors which disrupt 5–ASA delivery, such as non-adherence and 5-ASA switches, may destabilise symptom control.Aim To investigate the impact of non-adherence and medication switches on stable symptom control in UK patients with IBD.Methods A retrospective cohort study was conducted using a UK dispensing database. Adherence was analysed in randomised matched samples for each of the six leading oral mesalazine formulations, measured by medication possession ratio (MPR); MPR ≥80% was classified as adherent. Relationships among adherence, switch and relapse were analysed over 18 months in patients receiving continuous mesalazine therapy throughout a 6–month baseline period (primary subgroup analysis). Relapses of active ulcerative colitis were identified using a doubling of MPR as a proxy.Results Only 39% of patients in the matched samples (n = 1200) were classed as adherent. No significant differences in adherence were observed among mesalazine formulations. In the primary subgroup analysis (n = 568), non-adherent patients had a significantly greater risk of relapse than adherent patients (RR = 1.44, 95% CI = 1.08–1.94; P = 0.014). Among adherent patients (n = 276), those who switched had a 3.5-fold greater risk of relapse than those who did not switch (95% CI = 1.16–10.62; P = 0.008).Conclusions Both non-adherence and mesalazine switches in adherent patients were associated with significant increases in the risk of relapse, suggesting that disruption of mesalazine maintenance therapy may destabilise symptom control. These findings provide evidence to advocate caution when considering mesalazine switches for stable patients.

Neuroprotective effects of electrical stimulation of the anterior nucleus of the thalamus for hippocampus neurons in intractable epilepsy

Epilepsy and Parkinson’s disease (PD) are common neurological disorders. Both epilepsy and PD are potentially progressive disabling diseases that can be treated with the established therapy of deep brain stimulation (DBS). The difference in therapy is target selection and stimulation parameter modulation. The anterior nucleus of the thalamus (ANT) is chosen for intractable epilepsy and the subthalamic nucleus (STN) is chosen for PD. Long-term stable symptom control of STN–DBS can be seen in PD patients while the positive effect of ANT-DBS can be observed in epilepsy patients. Experimental data and clinical evidence have been reported that indicate the neuroprotective property of STN–DBS could be found in PD patients. Therefore, we hypothesize that the neuroprotective benefits of ANT–DBS may be present in epilepsy patients.

The Impact of Subthalamic Deep Brain Stimulation on Nigral Neuroprotection—Myth or Reality?

In the present review article we summarize available clinical and preclinical evidence, if modulation of the subthalamic nucleus (STN) could be a target for neuroprotection in Parkinson's disease (PD). Chronic deep brain stimulation (DBS) of the STN has emerged as a powerful therapeutic alternative for the treatment of PD, ensuring stable symptom control for up to five years despite the progressive nature PD. Comparative review of literature in PuBMed available up to December 2008. The assessment of neuroprotection has been proven difficult in the clinical situation, as medical or surgical therapeutic options that improve PD symptoms could be erroneously considered to be neuroprotective because of the difficulty of differentiating between symptomatic effects and potential neuromodulative disease-related effects of various treatment options applied in PD. The methodological limitations of clinical trials underline the importance of putative neuroprotective compounds to be tested in clinically driven preclinical studies. Thus, animal models, mimicking progressive nigrostriatal cell death, are indispensable to further advance the important issue of neuroprotection or neuromodulation following DBS. Clear clinical evidence for STN-DBS-related neuroprotection in PD is missing. However, numerous preclinical studies show (and are discussed) that silencing of the STN via lesion or DBS may exert neuromodulative effects on nigral dopamine neurons.

Stability of symptom control after replacement of impulse generators for deep brain stimulation

Impulse generators (IPGs) for deep brain stimulation (DBS) need to be replaced when their internal batteries fail or when technical problems occur. New IPGs are routinely programmed with the previous stimulation parameters. In this study, the authors evaluate the stability of symptom control after such IPG replacements. The authors retrospectively analyzed the outcome of 56 IPG replacements in 42 patients with various movement disorders treated using DBS. Stable symptom control was found in 65% of single-channel IPG replacements and 53% of dual-channel IPG replacements. Worsening of symptoms resulted primarily from changes in stimulation effects requiring reprogramming of stimulation parameters (17% of dual-channel IPG and 25% of single-channel IPG). In 14% of dualchannel IPG replacements, instability resulted from erroneous extension adjustment with change in laterality. A new short circuit of active with previously inactive contacts of the quadripolar stimulation lead resulted in a worsening of symptoms in 4% of replacements. Replacement of the IPG requires careful follow-up of patients with DBS to ensure stable symptom control.

Anti-immunoglobulin E (omalizumab) therapy in allergic asthma.

Several large-scale, double-blind, randomized, placebo-controlled clinical trials of the anti-immunoglobulin E (IgE) monoclonal antibody, rhuMAb-E25 (omalizumab) have demonstrated the benefits of this agent in patients with moderate to severe allergic asthma who remain symptomatic despite treatment with systemic or inhaled corticosteroids. The trials have consistently shown that administration of omalizumab is associated with fewer asthma exacerbations per patient despite significant reductions in corticosteroid dose, stable symptom control despite concomitant reductions in rescue medication use, and improvement in quality of life compared with placebo. In addition, anti-IgE (omalizumab) has been shown to be safe and well tolerated.