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The diagnosis of FAHN may be suspected when characteristic neurologic findings are accompanied by supportive findings on brain MRI. FA2H is the only gene in which pathogenic variants are known to FAHN.
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The depressant effect of 5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiodiazole (DS103-282) on the polysynaptic excitation of interneurones in the cat spinal cord appears to be related to a postsynaptic reduction in the effectiveness of excitatory transmitters than to interference with their presynaptic release.
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A 43-year-old woman presented with clinical and electrophysiologic features of stiff person syndrome (SPS), without abdominal or lumbar paraspinal muscle involvement. Investigations revealed metastatic adenocarcinoma of the lung with positive anti-Ri antibodies. Her clinical condition improved with diazepam, baclofen, tizanidine, and palliative chemotherapy. Screening for an underlying malignancy and anti-Ri antibodies should be considered in patients with SPS when clinical presentation is atypical.
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To investigate the effects of antispastic drugs baclofen and tizanidine on reflexes and volitional tasks.
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The 54 studies included in this systematic review of treatments for upper limb spasticity after stroke measured multiple outcomes using a variety of instruments. Fifty-one studies focused on treatment with a BTX formulation. BTX appeared to be an effective and well-tolerated focal treatment for reducing tonicity in patients with upper limb spasticity after stroke, supporting current guideline recommendations.
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Recent electrophysiological studies in patients with cranial dystonia (CD) have demonstrated evidence for hyperactivity of brainstem interneurons. Tizanidine (Tz), a centrally acting skeletal muscle relaxant, is thought to act by antagonizing the activity of excitatory interneurons which mediate hypertonic processes (e.g. spasticity). Theoretically this agent may be effective in patients with CD. Ten patients were enrolled in an open-label study with a single-blind placebo wash-in. Eight patients tolerated doses of between 28-36 mg per day. For the most part tizanidine was ineffective for the symptoms of CD. This failure suggests that the reported brainstem interneuronal disturbances may not be altered by Tz. Further studies using concomitant electrophysiological assessment would be necessary to assess this possibility. Alternatively, these disturbances may not be a principle cause of the dystonic movements. The finding of similar changes in other basal ganglia diseases lacking CD (e.g. Parkinson's disease) favours this latter explanation.
Group 1 showed increased CROM, increased mean NRS pain reduction, and decreased incidence of combined tension-type headache compared with group N during the follow-up. Younger patients in group 1 required a shorter treatment cycle and experienced a longer symptom-free period.
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A simple, sensitive and rapid high-performance liquid chromatography/positive ion electrospray tandem mass spectrometry (MS/MS) method was developed and validated for the assay of tizanidine in human plasma. Following liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reversed-phase column and analyzed by MS/MS in the selected reaction monitoring mode. The assay exhibited a linear dynamic range of 50-5000 pg/mL for tizanidine in human plasma. The lower limit of quantification was 50 pg/mL with a relative standard deviation of less than 13%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.5 min for each sample made it possible to analyze more than 300 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies.
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We searched for randomized or quasi-randomized controlled trials.
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Randomised controlled trials (RCTs) of anti-spasticity agents were identified using MEDLINE, EMBASE, bibliographies of relevant articles, personal communication, manual searches of relevant journals and information from drug companies.
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This study assessed bioequivalence between a single, intact, 6-mg capsule of tizanidine and the capsule contents sprinkled in applesauce in fasted healthy subjects.
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To report a case in which significant hypotension occurred after initiation of tizanidine in a patient using the antihypertensive agent lisinopril.
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Double-blind, placebo-controlled, crossover, before-after trial, pilot study.
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To assess the effectiveness and safety of Baclofen, Dantrolene, Tizanidine and any other drugs for the treatment of long term spasticity in SCI patients as well as the effectiveness and safety of different routes of administration of Baclofen.
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An analysis of hospital stay between both groups showed a significant difference during the implantation year. The average number of hospital days per patient in the year in the treated group was 31.5 days and in the match group was 18.7 days. Significant cost differences between both groups in the year that started with pump implantation and the following year can be attributed mostly to the costs of implantation of the pump and related hospitalisation days. The total costs of patient selection, testing, implanting the pump and follow-up amounted to $US28,473 for the first year. Savings must be taken into consideration as well. The savings of direct costs were due to withdrawal of oral medication (estimated annual total of between $US1950 and $US2800 per patient). Indirect savings on employment and nursing home costs, amounted annually to $US1047 and $US5814, respectively. Scenarios make it possible to consider policy consequences. The case of 'extending' the indications for this treatment to a larger population has been calculated and visualised.
Some macrolide and quinolone antibiotics (MQABs) are associated with QT prolongation and life-threatening torsade de pointes (TdP) arrhythmia. MQAB may also inhibit cytochrome P450 isoenzymes and thereby cause pharmacokinetic drug interactions (DDIs). There is limited data on the frequency and management of such risks in clinical practice. We aimed to quantify co-administration of MQAB with interacting drugs and associated adverse drug reactions.
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Postoperative pain was assessed using the NRS. Total analgesic consumption was determined. Return to normal daily activity was evaluated using a five-point daily activity score after the first postoperative week, and health-related quality of life was evaluated using the short form-36 one month after surgery.
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Microinjection of tizanidine into the substantia nigra pars reticulata or entopeduncular nucleus reduces muscle tone in genetically spastic rats. The effect of tizanidine is related to alpha 2-adrenergic mechanism since yohimbine, an alpha 2-adrenergic antagonist, and not prazosin, an alpha 1-adrenergic antagonist, attenuates the muscle relaxation produced by the drug. These results signify basal ganglia output stations as possible sites whereby tizanidine acting via alpha 2-adrenergic mechanism exerts its muscle relaxant action.
Forty patients scheduled to undergo epidural anesthesia in elective surgery were randomly allocated into two groups. The control group received placebo 60 minutes before arrival in the operating room, and the tizanidine group received 3 mg of oral tizanidine as premedication 60 minutes before arrival in the operating room. Every patient was measured heart rate and blood pressure before receiving placebo or premedication and after arrival in the operating room. After an epidural catheter was indwelled, the patients were questioned about the infiltrating pain of local anesthetic, and the degree was assessed by means of visual analog scale score (VAS score, 0 to approximately 100 mm).
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Seven days after CCI and intrathecal catheter surgeries had been performed in Sprague-Dawley rats, baseline neuropathic pain tests including cold-floor ambulation and paw pinch were performed. Either the dimethyl sulfoxide vehicle (seven rats) or one of the antagonists--5, 23, or 46 microg yohimbine (22 rats); 5, 25, 50, or 100 microg prazosin (25 rats); or 5, 45, or 90 microg WB4101 (11 rats)--were intrathecally administered to the animals, followed in 30 minutes by 50 microg intrathecally administered tizanidine. The neuropathic pain tests were repeated 30 minutes later. The resulting profile showed a descending order of antagonist efficacy for yohimbine, prazosin, and WB4101 for the cold-floor ambulation test and for the paw-pinch test of the affected paw. As expected given tizanidine's lack of analgesic effect on the contralateral, normal paw, there were no effects of antagonists on contralateral paw responses. The results of the paw-pinch test on the affected side were compared with binding data cited in the existing literature for the three different alpha2-adrenergic receptor subtypes (alpha2A, alpha2B, and alpha2C) with yohimbine, prazosin, and WB4101. The antagonist response profile for the paw-pinch test of the affected paw most closely approximated the alpha2B receptor binding profile.
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A cost analysis was conducted as part of a prospective, multicentre, multidisciplinary, randomised and placebo-controlled clinical trial. The study covered the period from December 1991 to September 1995. The data on medical consumption and costs were collected over a 3-year period from different sources: administrative databases of health insurance companies, hospital registries and a patient survey. These data were structured by means of a flowchart analysis of the medical decision-making by specialists and general practitioners (GPs). They included data on in- and outpatient care, home care and care in nursing homes. The cost analysis was conducted using data from 18 patients included in the trial and from 15 so-called 'match' patients. The latter group are patients with comparable diseases leading to spasticity and living in comparable circumstances. Next to absolute costs (direct and indirect) of care and treatment for the 2 groups of patients, cost differences between the 2 groups were considered (differential cost analysis).
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Tizanidine HCl is a centrally acting α-2 adrenergic agonist muscle relaxant with a slightly bitter taste having short half-life of 2.5 h. In the present study effect of co-processed excipient bases in formulation of orodispersible tizanidine HCl tablets by direct compression method was investigated. Co-processed excipient of microcrystalline cellulose with SSL-hydroxypropylcellulose was prepared using spray drier in 1:1, 1:2 and 1:3 ratio. Formulated tablets were evaluated for hardness, friability, in vitro disintegration time and in vitro drug release. Formulation F-3 prepared by addition of co-processed excipient base in ratio of 1:3 showed minimum disintegration time of 9.15±0.04 s and higher amount of drug release of 93.75% at the end of 15 min. Granules obtained by spray drying technique were found to be more spherical which improved its flow property and was supported by scanning electron microscope studies. Thermal studies indicated change in amorphous state, compatibility of drug in formulation was confirmed by fourier transform infrared studies. Analyses of drug release data indicated formulation followed first order kinetics. Inclusion of co-processed excipient base in formulation of orodispersible tablets enhanced disintegration significantly.
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Pharmacological manipulation of the excitatory amino acid receptors is likely to be of benefit in important and common diseases of the nervous system. Only a few of the currently available drugs that modify excitatory neurotransmission, such as remacemide, lamotrigine, and tizanidine, have an acceptable therapeutic index. The identification of numerous receptor subtypes, topographic variabilities of distribution, and multiple modulatory sites will provide a true challenge to the neuropharmacologist.
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The piloerection observed after the replacement of fluvoxamine with milnacipran in this patient appears to have been due to an increase in the alpha(1)-adrenoceptor occupancy by endogenous norepinephrine induced by milnacipran.
Non-antiepileptic drugs have been used in trigeminal neuralgia management since the 1970s.
There was a statistically significant difference between the electron, scanning and light microscopic observations and morphometric analysis of SAH + Tizanidine administration group and SAH group, and no statistically significant difference between SAH + Tizanidine administration group and control group.
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The effects of intrathecal (i.th.) injections of antispastic drugs were studied on spontaneous activity in the electromyogram (EMG) in genetically spastic rats and on spinal reflex transmission in anaesthetized normal rats. Baclofen, 0.2-2 nmol, and midazolam, 10-80 nmol, suppressed tonic activity in the EMG recorded from the gastrocnemius muscle in mutant rats, whereas tizanidine, 1-100 nmol, enhanced it. The action of baclofen was antagonized by i.th. co-administration of delta-aminovalerate but not by bicuculline, that of midazolam by systemic pretreatment with Ro 15-1788. The effect of i.th. tizanidine was antagonized by co-administration of prazosin but not by yohimbine. Baclofen, 2 nmol, exerted suppressant effects on Hoffman (H)-reflexes and spinal flexor reflexes in normal animals, midazolam, 80 nmol, only on flexor reflexes. Tizanidine, 100 nmol, failed to suppress H-reflexes and flexor reflexes. The present results demonstrate a myorelaxant effect of i.th. injections of baclofen and midazolam but not of i.th. tizanidine.
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Post hoc analysis of an enriched-design clinical trial of THC:CBD oromucosal spray versus placebo, using records of patients under previous and current ineffective antispasticity therapies. Subgroups were patients with at least 1 failed therapy attempt with either baclofen or tizanidine (Group 1) or at least 2 failed therapy attempts with both baclofen and tizanidine (Group 2).
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Clinical diagnosis of PLP1-related disorders depends on typical neurologic findings, X-linked inheritance pattern, and, usually, the finding of diffusely abnormal myelin on MRI.
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Effects of drugs affecting the central nervous system on the spinal reflexes and the descending modulations of the reflexes were simultaneously evaluated in rats. Mono- and polysynaptic reflexes were, respectively, increased and decreased by conditioning stimulation of the nucleus raphe in the medulla, with a deflection in resting dorsal root potential being evoked by the stimulation. Baclofen exclusively depressed the segmental responses without affecting the descending modulatory systems. On the other hand, KW-6629 (7-chloro-N,N,3-trimethylbenzo[b]furan-2-carboxamide) significantly depressed the descending modulations without affecting the segmental responses which were sensitive to baclofen. Diazepam and suriclone reduced the descending influence without affecting the ventral root reflexes. Tolperisone and chlorphenesin carbamate as well as tizanidine depressed not only the segmental reflexes but also the descending modulations. Thus, sites of drug actions were estimated.