Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical trial. The effects of protirelin tartrate (TRH-T) administration on chronic post-stroke spasticity were studied in a multicentre trial (study on the treatment of chronic post-stroke spasticity--11 centres involved). Patient evaluation included the quantification of muscular strength examined in proximal and distal areas, muscular tone according to the Ashworth scale, reflex intensities (using a 5 graded scale); daily autonomy was also considered according to the Parkside Behaviour Rating Scale (PBRS). Patients were administered 2 mg of TRH-T twice daily by intramuscular route. The most interesting finding emerging from the trial was that TRH-T administration elicited, at the same time, a reduction of spasticity, hypertonia and hyperreflexia together with an increase in muscular strength and improvement of daily activities. The therapeutic profile of TRH-T therefore seems to be based on its unusual capacity of acting simultaneously on deficiency symptoms (hyposthenia, loss of dexterity) and positive symptoms (hypertonia, hyperreflexia), both of which are present in cases of post-stroke spasticity. Electrophysiological findings. By means of coded electrophysiological tests it is possible to explore specific compartments of the motorial and spinal network and consequently obtain activity profiles for each single substance capable of modifying its reactivity. The H/M ratio, reciprocal Ia inhibition and the activities of the Renshaw circuit were not changed following TRH-T administration. Opposite findings were recorded with regard to the F wave according to whether the flector or extensor nucleus was explored; the consequent hypothesis of TRH-T activity at the interneuron level was supported by the inhibition of the short head biceps reflex following administration of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Use of TRH-T for the symptomatic treatment of the pathology of the upper motoneurons and electrophysiologic evaluation of its efficacy]. 212 88

TRH analogues have a longer half-life than does TRH and enhanced neuropharmacological actions. In motorneurone disease (MND), no benefit was reported with MK771 and DN1417. Focal, transient, and slight improvements in weakness and spasticity were described with CG3509. A controlled trial with a single intravenous dose of RX 77368 showed improvements in dysarthria, tongue movements, respiration, swallowing, and spasticity lasting up to 72 hours. Changes in muscle force were of no functional significance. There was an acute 25-30% increase in mean corrected fiber density and in mean macro-EMG parameters in biceps, but no change in amplitude or area of single macro-EMG motor units followed during the 2-hour infusions. An acute, direct or indirect, central effect of RX77368 on recruitment order or on activation threshold of pathological motor units is suggested. In a subacute open trial with repeated intravenous infusions of RX77368 (median 2 weeks), improvement in bulbar function in 8 of 12 responders, cramps (5 of 9), and spasticity (5 of 8) were maintained for medians of 18, 14, and 7 days, respectively. Side effects were prominent with doses above 0.2 mg/kg. Disease progression has not been halted with any analogue, but whether it may be usefully slowed down with RX77368 is worth investigating.
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PMID:Use of TRH analogues in motorneurone disease. 249 83

Is characterized by several various signs. One of these, spasticity, involves a velocity dependent increase in muscle stiffness during stretch and by hyperactive tendon jerks. When intense, spasticity impedes residual strength in antagonistic muscles and interferes with attempts to move, especially if complicated by clonus and/or spasms. Assessment of spasticity is multifactorial and implies clinical as well as instrumental methods. The pathophysiological mechanisms responsive for the hyperexcitability of the myotatic reflex can be studied by methods of clinical neurophysiology. It appears that there are various factors involved at the spinal level, involving reduction in both pre- and post-synaptic inhibitions. Although spasticity is not responsible for the major part of the disability imposed by upper motor neurone syndrome, it should be reduced. The therapeutic methods are medical, surgical or from physical medicine. In many cases, the results have been validated by blind studies. As paresis is the most disabling effect, it would be worthwhile to develop drugs able to reduce spasticity and increase muscle strength at the same time. Recent trials suggest than TRH-T may be effective in this regard.
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PMID:[Pyramidal syndrome: its physiopathology and treatment]. 269 2

Nine patients (7 with amyotrophic lateral sclerosis, 1 with progressive spinal amyotrophy and 1 with chronic anterior poliomyelitis) were treated by sequential intravenous administration of 240 mg of TRH over one hour every two weeks. Results were assessed by an analytical evaluation of muscle strength before and 24 h after each infusion and by objective and subjective evaluation of spasticity. Significant improvement, as shown by statistical analysis, was noted in muscle strength in the 9 patients by 5 infusions over a 4-week period and a sub-group of 5 patients treated by 8 infusions over 10 weeks. Continued use of this therapy is justified by the need to determine its long-term effects and the psychological improvement noted in some patients after an even transient improvement in motor performance. However this treatment is obviously not curative.
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PMID:[Treatment of amyotrophic lateral sclerosis with thyrotropin releasing hormone]. 308

Twenty five patients with motor neuron disease completed a double blind randomised cross over trial of RX77368, a stabilised TRH analogue, iv over 2 hours against saline. Temporary improvement in bulbar symptoms including speech, respiratory parameters, tongue movements and swallowing were seen. Fasciculations increased and spasticity decreased. Change in muscle force with drug was different from placebo but both increase and decrease in force were seen and did not result in detectable changes in function. Side effects were clinically significant in 50% of the patients and cleared within 12 hours. Prolonged rise of thyroxine and an increase in plasma levels of prolactin, thyroid stimulating hormone and growth hormone were seen and followed characteristic patterns.
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PMID:Controlled acute trial of a thyrotrophin releasing hormone analogue (RX77368) in motor neuron disease. 311 76

Sixteen patients with motor neuron disease received RX77368, a TRH analogue, IV, repeatedly over 1-12 weeks (median 2 weeks). Slight to moderate improvement in bulbar function, particularly speech, was reproduced or persisted with repeated infusions in 8 of 12 responders over a median of 18 days (range 14-90) during the period of study. Cramps (5/9) and spasticity (5/8) improved for a median of 14 days (range 7-35) and 7 days (range 2-14) respectively. The highest benefit/side effect ratio was seen with 0.2 mg/kg (0.15 mg/kg in those with severe bulbar palsy) every 3-4 days. Long term studies with this analogue in MND are indicated.
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PMID:Subacute administration of a TRH analogue (RX77368) in motorneuron disease: an open study. 314 18

Effects of high-dose TRH on the vibratory inhibition of soleus H-reflex have been studied in 9 patients with amyotrophic lateral sclerosis. In 6 of the 9, TRH induced a significant increase in vibratory inhibition. This suggests that the TRH-induced reduction of spasticity might be due to an increase in presynaptic inhibition acting on Ia fibres.
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PMID:[Spinal mechanism of the antispastic action of TRH in patients with amyotrophic lateral sclerosis]. 314 85

The clinical and biochemical features of myxoedematous and neurological cretinism were studied in an endemic goitre area in Algeria (goitre prevalence 51.3%; endemic cretinism 1.1%; mean urinary iodine level 127.6 nmol/l). When comparing the data collected in six different villages of the area, significant negative correlations were found between the decrease in urinary iodide and iodide/thiocyanate ratio (I/SCN) and the increase in prevalences of visible goitres, endemic cretinism and transient neonatal hypothyroidism. The cretins were divided on clinical signs into two groups: myxoedematous (MC) and neurological (NC) cretinism. Differences were noted in the neurological signs and the type of deafness encountered in both types. Although some overlap did exist, proximal spasticity and rigidity were characteristic of NC. The hormonal profiles of the two groups, including TRH tests, were clearly different. The two groups were similar with regard to the percentage of palpable thyroids, the absence of antimicrosomal and anti-thyroglobulin antibodies, seropositive viral antibodies and thiocyanate concentrations in serum and urine. Thus it is unlikely that these factors have any significant aetiological role in NC. The data collected in the general population in this area and those obtained in the mothers of the myxoedematous and neurological cretins support the hypothesis that the neurological signs are the result of hypothyroxinaemia in the mothers and the fetus at different periods of pregnancy. They could be aggravated by neonatal hypothyroidism, which may be transient in NC and permanent in MC.
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PMID:Comparative study of neurological and myxoedematous cretinism associated with severe iodine deficiency. 319 4

Very high intravenous doses (2-19 mg/min) of thyrotropin-releasing hormone (TRH, L-pyroglutamyl-L-histidyl-L-prolinamide) given to 12 patients with amyotrophic lateral sclerosis (ALS) produced a moderate to marked improvement of functions caused by deficiency of lower motor neurons (weakness) and upper motor neurons (spasticity). The improvement was sustained throughout the infusion and for about 1 h thereafter; sometimes a slight improvement was evident 20 h after infusion. At a given dose benefits and side-effects were more evident in men than in women. Whether TRH is replacing an ALS-associated deficiency or is simply a symptomatic treatment is unknown. The results of this study raise the possibility of a treatment for ALS, and may provide new insight into its pathogenesis. The potential response to TRH of spasticity and/or lower motor neuron involvement of other causes is proposed.
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PMID:Effect on weakness and spasticity in amyotrophic lateral sclerosis of thyrotropin-releasing hormone. 613 61

F responses were recorded in 6 cases with SSP and in 22 normal controls. The present study confirmed that frequency, number of phases, F/M amplitude ratio and duration were significantly increased and CV of onset latencies was significantly reduced in cases with SSP. After intravenous injection of TRH (2 mg), all the parameters were altered toward normal sides. It was suggested that the hyperexcitability of motor neuron pool in SSP was stabilized by effects of TRH on injured pyramidal tracts and consequently abnormalities of F responses were improved. The Effect of TRH to correct the abnormal F responses in SSP might be consistent with effects of TRH to reduce spasticity in amyotrophic lateral sclerosis described previously.
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PMID:Abnormalities of F response in cases with spastic spinal paralysis and effects of TRH-T on them. 944 87


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