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Symptomatic Therapy (symptomatic + therapy)
Selected AbstractsBotulinum neurotoxin type A injections reduce spasticity in mild to moderate hereditary spastic paraplegia, Report of 19 casesMOVEMENT DISORDERS, Issue 2 2008Martin J. Hecht MD Abstract Hereditary spastic paraplegia (HSP) is characterized by lower extremity spasticity. Symptomatic therapy generally includes physical therapy and oral antispastic agents, in selected cases intrathecal baclofen. Because of the positive results in other treatments of spasticity, the use of botulinum neurotoxin type A (BoNT-A) might also be considered for patients with HSP. We report the effect of BoNT-A injections in 19 unselected patients with HSP treated by the members of the German Spasticity Education Group. In 17 patients, the modified Ashworth scale had improved by one point. In one patient, it improved by three points. Most of the patients reported reduction of spasticity. BoNT-A injections were continued in 11 of 19 patients (57.9%). All of the patients with continued injections had a good or very good global subjective improvement. Patients with less pronounced spasticity and patients with accompanying physical therapy tended to exhibit a better effect. Only four patients reported adverse effects which were increased weakness in three patients and pain in one patient. BoNT-A injections appear to reduce spasticity effectively and safely, especially in patients with mild to moderate spasticity. The preliminary results of our case series should encourage larger studies of BoNT-A injections in HSP. © 2007 Movement Disorder Society [source] The symptomatic treatment of multiple system atrophyEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2002C. Colosimo Multiple system atrophy (MSA) is a neurodegenerative disease of undetermined aetiology that occurs sporadically and manifests itself as a combination of parkinsonian, autonomic, cerebellar and pyramidal signs. Despite the lack of any effective therapy to reverse this condition, some of the symptoms may be, at least temporarily, improved with adequate symptomatic therapies. Medical treatment is largely aimed at mitigating the parkinsonian and autonomic features. The therapeutic results of levodopa therapy in cases of MSA are difficult to interpret because of their variability. Nevertheless, the statement that patients with MSA are non or poorly levodopa-responsive is misleading. Clinical and pathologically proven series document about 40,60% levodopa efficacy in patients with MSA presenting with predominant parkinsonian features. Unfortunately, other antiparkinsonian compounds (dopamine agonists, amantadine) are not more effective than levodopa. Orthostatic hypotension (OH) can be suspected from the patient's history and subsequently documented in the clinic by measuring lying and standing blood pressure. The diagnosis ideally should be confirmed in the laboratory with additional tests to determine the cause and evaluate the functional deficit, so as to aid treatment. A variety of pharmacological agents with different mechanisms of action have been used in MSA to reduce OH when this is symptomatic. OH can also be alleviated by avoiding aggravating factors, such as the effects of food, micturition, exposure to a warm environment and physiological diurnal changes and by using other non-pharmacological strategies. The treatment of the very common genito-urinary symptoms (incontinence, retention, impotence) should also be considered in order to improve the quality of life of these patients. [source] Parkinson's disease: 10 years of progress, 1997,2007,,MOVEMENT DISORDERS, Issue S1 2010Stanley Fahn MD Abstract Many people with Parkinson's disease (PD) and their family members ask their physicians "What is happening in research on Parkinson's disease? Is there anything new?" As the initial speaker at the symposium organized by the Parkinson's Disease Foundation in celebration of its 50th anniversary, I sought to address these questions, focusing on research published between the years 1997 and 2007. I cataloged the advances I considered most important in the field, recognizing my viewpoint is a subjective one and most likely differs from similar listings that others would put together. Space limitation allows me to discuss only a tiny fraction of the remarkable new findings that have been discovered during this 10-year span. Nevertheless, I expect the readers of this summation of advances in the field to be as impressed as I am on the wealth, breadth, and excitement stirring in the field of PD research. Included in this overview are highlights in both laboratory science and clinical science of PD research. In the former category are advances in knowledge on the genetics of PD; potential etiologic and pathogenic causes, especially the better understanding of endogenous factors within dopaminergic neurons; pathologic changes including deposition of alpha-synuclein aggregates; and the consequences of altered alpha-synuclein on the degradation of proteins by both the ubiquitin-proteasomal pathway and the lysosome. Clinical science has also been very active and impressively productive with important clinical advances. In this category are new information on the epidemiology of PD, including awareness of additional factors (besides smoking) that might slow the onset and worsening of PD, such as caffeine and urate; neuroimaging with positron emission tomography and single photon emission tomography; keener awareness of nonmotor features of PD and their impact on quality of life for the persons with PD and their family; recognition of behavioral complications of medications utilized to treat PD, such as impulse control problems; appreciation of the natural history of PD with the increasing impairments as the disease relentlessly worsens over time; the many controlled clinical trials attempting to slow the progression of the disease and to provide new symptomatic therapies; and surgical approaches to alleviate symptoms and progression, including cellular and gene therapy as well as deep brain stimulation. © 2010 Movement Disorder Society [source] Gene therapy for lysosomal storage diseases: the lessons and promise of animal modelsTHE JOURNAL OF GENE MEDICINE, Issue 5 2004N. Matthew Ellinwood Abstract There are more than 40 different forms of inherited lysosomal storage diseases (LSDs) known to occur in humans and the aggregate incidence has been estimated to approach 1 in 7000 live births. Most LSDs are associated with high morbidity and mortality and represent a significant burden on patients, their families, and health care providers. Except for symptomatic therapies, many LSDs remain untreatable, and gene therapy is among the only viable treatment options potentially available. Therapies for some LSDs do exist, or are under evaluation, including heterologous bone marrow transplantation (BMT), enzyme replacement therapy (ERT), and substrate reduction therapy (SRT), but these treatment options are associated with significant concerns, including high morbidity and mortality (BMT), limited positive outcomes (BMT), incomplete response to therapy (BMT, ERT, and SRT), life-long therapy (ERT, SRT), and cost (BMT, ERT, SRT). Gene therapy represents a potential alternative therapy, albeit a therapy with its own attendant concerns. Animal models of LSDs play a critical role in evaluating the efficacy and safety of therapy for many of these conditions. Naturally occurring animal homologs of LSDs have been described in the mouse, rat, dog, cat, guinea pig, emu, quail, goat, cattle, sheep, and pig. In this review we discuss those animal models that have been used in gene therapy experiments and those with promise for future evaluations. Copyright © 2004 John Wiley & Sons, Ltd. [source] EFNS guideline on the treatment of cerebral venous and sinus thrombosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2006K. Einhäupl Cerebral venous and sinus thrombosis (CVST) is a rather rare disease which accounts for <1% of all strokes. Diagnosis is still frequently overlooked or delayed due to the wide spectrum of clinical symptoms and the often subacute or lingering onset. Current therapeutic measures which are used in clinical practice include the use of anticoagulants such as dose-adjusted intravenous heparin or body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH), the use of thrombolysis, and symptomatic therapy including control of seizures and elevated intracranial pressure. We searched MEDLINE (National Library of Medicine), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Library to review the strength of evidence to support these interventions and the preparation of recommendations on the therapy of CVST based on the best available evidence. Review articles and book chapters were also included. Recommendations were reached by consensus. Where there was a lack of evidence, but consensus was clear we stated our opinion as good practice points. Patients with CVST without contraindications for anticoagulation should be treated either with body weight-adjusted subcutaneous LMWH or dose-adjusted intravenous heparin (good practice point). Concomitant intracranial haemorrhage related to CVST is not a contraindication for heparin therapy. The optimal duration of oral anticoagulation after the acute phase is unclear. Oral anticoagulation may be given for 3 months if CVST was secondary to a transient risk factor, for 6,12 months in patients with idiopathic CVST and in those with ,mild' hereditary thrombophilia. Indefinite anticoagulation (AC) should be considered in patients with two or more episodes of CVST and in those with one episode of CVST and ,severe' hereditary thrombophilia (good practice point). There is insufficient evidence to support the use of either systemic or local thrombolysis in patients with CVST. If patients deteriorate despite adequate anticoagulation and other causes of deterioration have been ruled out, thrombolysis may be a therapeutic option in selected cases, possibly in those without intracranial haemorrhage (good practice point). There are no controlled data about the risks and benefits of certain therapeutic measures to reduce an elevated intracranial pressure (with brain displacement) in patients with severe CVST. Antioedema treatment (including hyperventilation, osmotic diuretics and craniectomy) should be used as life saving interventions (good practice point). [source] Neurophysiological and neurochemical basis of modern pruritus treatmentEXPERIMENTAL DERMATOLOGY, Issue 3 2008Sonja Ständer Abstract:, Chronic pruritus of any origin is a frequent discomfort in daily medical practice, and its therapy is challenging. Frequently, the underlying origin may not be identified and symptomatic therapy is necessary. Conventional treatment modalities such as antihistamines often lack efficacy, and hence new therapeutic strategies are necessary. The neuronal mechanisms underlying chronic pruritus have been partly identified during the past years and offer new therapeutic strategies. For example, mast cell degranulation, activation of neuroreceptors on sensory nerve fibres and neurogenic inflammation have been identified to be involved in induction and chronification of the symptom. Accordingly, controlling neuroreceptors such as cannabinoid receptors by agonists or antagonists showed high antipruritic efficacy. Pruritus is transmitted to the central nervous system by specialized nerve fibres and sensory receptors. It has been demonstrated that pruritus and pain have their own neuronal pathways with broad interactions. Accordingly, classical analgesics for neuropathic pain (gabapentin, antidepressants) also exhibit antipruritic efficacy upon clinical use. In summary, these recent developments show that highlighting the basis of pruritus offers modern neurophysiological and neurochemical therapeutic models and the possibility to treat patients with refractory itching of different origin. [source] Brief Communications: An Analysis of Migraine Triggers in a Clinic-Based PopulationHEADACHE, Issue 8 2010Diane Andress-Rothrock MS Background., Many migraineurs report attack "triggers," but relatively few published data exist regarding the relative prevalences of individual triggers, variations related to gender, duration of migraine or migraine subtype, or the existence of any regional variations in the prevalences and distributions of triggers. Objective., We sought to determine the prevalence and types of migraine triggers in our clinic population, to determine what influence gender, migraine subtype, or duration of migraine might have on the prevalences and types of triggers reported and to compare our findings with data derived from surveys we previously had conducted involving 2 clinic-based populations and 1 general population sample from other regions of the USA. Methods., We evaluated 200 consecutive new migraine patients referred to our clinic. All patients specifically were queried as to whether they had noted any of 7 specific factors to serve consistently as migraine attack triggers and additionally were surveyed as to whether they might have "other" triggers not listed on the intake questionnaire. Among the other data collected and analyzed were age, gender, age at time of migraine onset, and migraine subtype (ie, episodic vs chronic). Actively cycling females who reported menses as a trigger were questioned as to whether their menstrual migraine (MM) attacks differed from their non-menstrual migraines and, if so, how they differed. Results., One hundred and eighty-two patients (91%) reported at least 1 migraine trigger, and 165 (82.5%) reported multiple triggers. The most common trigger reported (59%) was "emotional stress," followed by "too much or little sleep" (53.5%), "odors" (46.5%), and "missing meals" (39%). Females or subjects of either gender with chronic migraine were no more likely than males or subjects with episodic migraine to report triggers or multiple triggers. Similarly, longer exposure to migraine did not correlate with a higher likelihood of reporting a trigger or multiple triggers. Fifty-three (62%) of 85 actively cycling females reported menses as a trigger, and of the 51 with menstrually related migraine, 34 (67%) reported their MM to be more severe, more refractory to symptomatic therapy or of longer duration than their non-menstrual attacks; 13 (24.5%) of the 53 women with apparent MM reported their MM to be at least occasionally manifested as status migrainosus. The prevalence and type of triggers reported by this predominantly white female population were similar to those reported by clinic-based populations in San Diego, California and Mobile, Alabama, and in a population-based sample of Hispanics in San Diego County. Conclusions., A large majority of migraineurs report migraine attack triggers, and the triggers most commonly reported include emotional stress, a disrupted sleep pattern, and various odors. These findings do not appear to vary according to geographic region or race/ethnicity. Among the triggers, MM appears inclined to provoke headache that is more severe, less amenable to treatment, or longer in duration than headaches that occur at other times during the cycle. (Headache 2010;50:1366-1370) [source] Hereditary angioedema: an update on available therapeutic optionsJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 9 2010Marcus Maurer Summary There is no cure for hereditary angioedema (HAE). Therapeutic approaches consist of symptomatic therapy for acute attacks, short-term prophylaxis before surgery, and long-term prophylaxis for those with frequent and severe attacks. In Germany, C1-INH concentrate and icatibant are licensed for acute therapy. C1-INH concentrate, which is obtained from human plasma, is administered intravenously to restore the deficient C1-INH activity. This therapy, which has been available for decades, is effective and well-tolerated. Batch documentation is required by German law. The synthetic decapeptide icatibant is administered subcutaneously. It competes with bradykinin, the responsible inducer of edema formation, for binding to the bradykinin B2 receptor. Icatibant is also effective and well-tolerated, even on repeated administration. An additional human C1-inhibitor, a recombinant human C1-inhibitor and the recombinant inhibitor of kallikrein ecallantide are currently under development. There are no licensed treatment options available in Germany for long- and short-term prophylaxis. Androgen derivatives are established in long-term prophylaxis. However, they are associated with many adverse effects, some of which are severe. Many drug interactions also limit their use. They are contraindicated in pregnancy, lactation, for children and in cases of prostate cancer. Antifibrinolytics have fewer adverse effects but are also less effective than androgens. They are contraindicated in thromboembolic disease and impaired vision. If androgen therapy has too negative an effect on quality of life, it may be worth reducing the dose or discontinuing therapy entirely and treating attacks with acute therapy. [source] Anti-ischemic effects of inotropic agents in experimental right ventricular infarctionACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2009M. HEIN Background: Right ventricular (RV) function is an important determinant of survival after myocardial infarction. The efficacy of reperfusion therapy might be increased by the cardioprotective action of inotropic agents, which are used for symptomatic therapy in situations with compromised hemodynamics. Therefore, we used a porcine model of RV ischemia and reperfusion (IR) injury to study the influence of milrinone, levosimendan and dobutamine on the extent and degree of myocardial injury. Methods: IR injury was induced by temporary ligation of the distal right coronary artery for 90 min, followed by 120 min of reperfusion. Treatment was initiated 30 min after coronary artery occlusion. A bolus of milrinone (n=12; 50 ,g/kg) and levosimendan (n=10; 24 ,g/kg) was applied in different groups, followed by continuous infusion of the drugs at 0.5 and 0.2 ,g/kg/min, respectively. The effects on myocardial injury and inflammation were compared with a control (n=12) and a dobutamine group (n=10), where treatment was started with an infusion of 5 ,g/kg/min. Results: Milrinone and levosimendan reduced the resulting infarct size with respect to the area at risk (41.7±10.2%, 45.7±8.1%) when compared with the control group (58.3±6.1%). In contrast, dobutamine had no effect (55.8±7.7%). All drugs reduced the number of neutrophils infiltrating into the different myocardial regions and the circulating levels of interleukin-6. Increased levels of tumor necrosis factor , during reperfusion were only abated by milrinone and levosimendan. Conclusions: Cardioprotective properties of milrinone and levosimendan were demonstrated for the first time in a clinically relevant model of RV infarction. [source] No osteonecrosis in jaws of young patients with osteogenesis imperfecta treated with bisphosphonatesJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2008Barbro Malmgren Background:, Recent reports of osteonecrosis of the jaw (ONJ) after dental surgery in patients treated with second- and third-generation nitrogen-containing bisphosphonates instigated this retrospective study. As treatment with bisphosphonates in patients with osteogenesis imperfecta (OI) has become an important symptomatic therapy, especially for severe forms of the disease, we found it important to investigate whether healing after surgical exposure of jaw bone was influenced by the bisphosponate treatment in our group of children, adolescents and young adults with OI. Subjects and methods:, Disodiumpamidronate was given as monthly intravenous infusion to 64 patients with OI aged 3 months to 20.9 years at the start of treatment (mean 8.1, median 7.7). During 0.5,12.5 years of treatment (mean 4.5, median 4.0), a total individual dose of 140,4020 mg/m2 disodiumpamidronate was given (mean 1623 and median 1460). Ten patients continued with oral alendronate and two with zoledronic acid therapy. In 22 of these patients, 38 dental surgery procedures were performed at the age of 3.4,31.9 years (mean 12.2, median 12.3) after 0.03,7.9 years of treatment (mean 3.6, median 3.4). Results:, Despite long-term intravenous monthly disodiumpamidronate treatment, none of the 64 patients had any clinical signs of ONJ. Conclusions:, The risk of ONJ in these patients must be considered so low that the patients with indications for treatment should be treated and get the chance to experience the well-documented beneficial effect for children with severe OI. [source] Clinical measures of progression in Parkinson's disease,MOVEMENT DISORDERS, Issue S2 2009Werner Poewe MD Abstract Despite all recent advances in symptomatic therapy Parkinson's disease (PD) continues to be a relentlessly progressive neurodegenerative disorder. Therefore therapies that will slow or hold disease progression are a major medical unmet need in PD. Clinical measures of disease progression that have been used in disease modification trials so far have focused on indices of progression of cardinal motor features like bradykinesia, rigidity, and tremor as captured by the UPDRS and the emerging need for effective dopaminergic symptomatic therapy. Progression of global disability in PD, however, is driven by additional factors beyond progressive nigrostriatal denervation leading to increasing severity of cardinal motor features. Progressive pathology in extranigral sites in the brain or peripheral autonomic nervous system contribute to poorly levodopa responsive motor symptoms like postural instability, freezing and falls or nonmotor symptoms. In addition treatment-induced motor complications also impact on PD disability. Although it is widely accepted that clinical progression of PD is multidimensional and in addition includes effects of aging, there is no consensus how to best implement more clinically meaningful endpoints for disease progression trials that would reflect these complex interactions impacting on the evolution of global disability in PD. There is an urgent need for biomarkers for disease progression that would faithfully reflect advancing neurodegeneration and resulted clinical disability in PD and that could be used in shorter term clinical trials testing putative disease modifying agents. © 2009 Movement Disorder Society [source] A "cure" for Parkinson's disease: Can neuroprotection be proven with current trial designs?MOVEMENT DISORDERS, Issue 5 2004Carl E. Clarke BSc Abstract Current medical and surgical therapies for Parkinson's disease provide symptomatic control of motor impairments rather than slowing or halting the progression of the disease. Previous clinical trials examining drugs such as dopamine agonists and selegiline for neuroprotective effects used "surrogate" outcomes, including clinical measures (rating scales, time to require levodopa), neuroimaging techniques (,-CIT single photon emission computed tomography; fluorodopa positron emission tomography), and mortality tracking. These studies failed to provide conclusive results because of design faults such as failing to control for symptomatic effects, small sample size, and not accounting for the possible effects of drugs on radionuclide tracer handling. Lessons must be learned from these failed neuroprotection trials. This review summarises the problems with previous neuroprotection studies and makes recommendations for future trial design. It is concluded that the primary outcome of explanatory trials should continue to be clinical measures such as the Unified Parkinson's Disease Rating Scale (UPDRS). It should be assumed that all agents have a symptomatic effect, which necessitates evaluation after a prolonged drug washout period. To achieve the evaluation after a prolonged drug washout period more effectively, trials must be performed in early disease and over a short period (6,12 months) so that symptomatic therapy is not required. To achieve adequate statistical power, these trials will need to include thousands of patients. Radionuclide imaging can only be used in such trials after considerable methodological work has been performed to establish its validity and reliability. To be affordable, such large explanatory trials need more streamlined designs with fewer hospital visits, fewer outcome measures, and rationalised safety monitoring. The clinical effectiveness of promising compounds from explanatory trials will need to be established in large long-term pragmatic trials using outcome measures such as quality of life, cost-effectiveness, and mortality. Such pragmatic trials could be continuations of the explanatory trials: after the primary outcome of the explanatory study (e.g., UPDRS) has been reported in an interim analysis, the trial could be continued for a further 5 to 10 years to report on quality of life and health economics outcomes. © 2004 Movement Disorder Society [source] | ||||||||||||||||||||||