Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord. Eighteen patients presenting a severe spastic syndrome were treated with chronic intrathecal infusion of baclofen in the lumbar cerebrospinal fluid. After clinical preselection, 38 patients were implanted with a lumbar access port allowing long-term trials in order to determine the efficacy of baclofen therapy and the effective 12-hour dose. The 18 patients selected for chronic administration were implanted with a programmable pump. The pathology in these cases was: multiple sclerosis (6 cases), posttrauma spastic syndrome (eight cases), and (one case each) cerebral palsy, ischemic cerebral lesion, spinal ischemia, and transverse myelitis. The mean follow-up period was 18 months (range 4 to 43 months). The clinical results were evaluated according to muscular hypertony on Ashworth's scale (changed for occurrence of painful spasms) and functional improvement. Results were better for spastic syndrome secondary to traumatic medullary lesion than for demyelinating disease. Hypertonia was improved in all cases as confirmed by the registration of the Hoffman (H) reflex. Painful muscular spasms disappeared in 14 of the 16 affected patients. Significant functional improvement was noted in nine patients and was considerable in three. The risk of side effects secondary to overdose (such as excessive hypotonia or central depression) and the absence of a specific baclofen antagonist stresses the necessity for accurate determination of the efficient dose. After an initial titration period and adjustment of the therapeutic dose, the individual doses were from 21 to 500 micrograms/24 hrs (mean 160 micrograms/24 hrs). This new conservative method is very effective, perfectly reversible, and safe when administered in conditions favorable to its use.
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PMID:Chronic intrathecal baclofen administration for control of severe spasticity. 230 74

The reflex EMG responses from a tendon tap or an imposed, medium amplitude (30 degrees), stretch at a range of stretch velocities have been recorded from the triceps and biceps muscles of normal human subjects and in both the affected and "unaffected" arms of hemiparetic patients under relaxed conditions. In the hemiparetic arm, exaggerated tendon jerks were, as expected, observed in both muscles. The response of the biceps to elbow extension was also exaggerated compared with normal values and displayed both an additional earlier component and a much reduced velocity threshold. The triceps, in contrast, showed depressed responses to elbow flexion, with a much higher velocity threshold than normal subjects. Furthermore, on the supposedly "unaffected" side of the hemiparetic subjects, the reciprocal pattern was seen, with depression of the biceps response and a raising of its threshold, along with considerably exaggerated responses in the triceps including earlier components not seen in the normal subjects. The increased excitability of the flexor musculature on the spastic side may be paralleled by increases in activity in the segmental pathways responsible for modulation of agonist/antagonist activity in the ipsi and contralateral limb, leading to an inhibition of the ipsilateral extensors and contralateral flexors and excitatory input to the contralateral extensors. Thus the "good" side of hemiparetic patients also receives pathological changes, and studies of the mechanisms of spasticity should avoid the use of the "unaffected" side of hemiparetic subjects as a control for monitoring pathological reflexes.
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PMID:Pathological stretch reflexes on the "good" side of hemiparetic patients. 232 53

The effects of conditioning stimulation of a mixed nerve in the leg, the common peroneal nerve (CPN), on the ipsilateral soleus H-reflex were compared with the effects of stimulating its cutaneous branch, the superficial peroneal nerve (SPN), in two groups of subjects--normals and patients with spinal spasticity subsequent to a clinically complete transection of the spinal cord. Condition-test delays of 20 msec to 2 sec, measured from the end of the 20 msec train (3 pulses at 100 Hz), were investigated. In normal subjects, CPN stimulation at 1.4 X MT profoundly depressed the soleus H-reflex. There was an initial depression (peak 40-90 msec) followed by a slow recovery which was incomplete at condition-test delays of 2 sec. One-half of the subjects showed a late facilitation, or disinhibition, peaking at 170-190 msec. The inhibitory effects were attributed to activation of low threshold, groups I and II, muscle afferents because stimulation of the SPN, at 1.5 X threshold for a compound action potential recorded from the CPN, had only facilitatory effects on the soleus H-reflex. Facilitation occurred at condition-test delays of 30-190 msec. The cutaneous stimulation was presumed to activate the largest, A beta, cutaneous afferents as it elicited a weak paraesthesia on the dorsum of the foot. The results suggested that cutaneous afferents may have contributed to the late facilitation seen with CPN conditioning stimulation. In spinal cord-lesioned subjects, CPN stimulation depressed the soleus H-reflex but the decrease was less and the recovery was faster and more complete than in normals. The magnitude of the initial depression at 20-100 msec varied with the severity of the spasticity, subjects with mild spasticity showing less of a depression. Weak cutaneous conditioning stimulation either had no effect or produced a slight depression of the soleus H-reflex, providing clear evidence that transmission in the pathways mediating the facilitatory effects of cutaneous afferents onto extensor motoneuronal pools is depressed in spinal spasticity. This may shift the balance of activity toward the flexor motoneurones, thus favouring the development of, for example, flexor spasms and flexor hypertonia. Since inhibitory effects from cutaneous stimulation are associated with activation of higher threshold afferents in normal man, the present results may reflect a decrease in the threshold for flexor withdrawal reflexes commonly associated with spasticity of spinal origin.
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PMID:Inhibitory and facilitatory effects from the peroneal nerve onto the soleus H-reflex in normal and spinal man. 244 16

Postoperative pain control can be a major problem after selective dorsal rhizotomy for the treatment of spasticity. We report the use of epidural morphine delivered via a catheter placed at surgery for postoperative analgesia in 28 consecutive patients undergoing this procedure. Pain was well controlled using this technique, and no patients required concomitant parenteral analgesia. There were no instances of respiratory depression, wound infection, or central nervous system depression, and the patients were easily mobilized in the early postoperative period. Epidural morphine is concluded to be a safe and very efficacious method of analgesia after selective dorsal rhizotomy.
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PMID:Use of epidural morphine for control of postoperative pain in selective dorsal rhizotomy for spasticity. 248 50

A yin-yang hypothesis is presented linking noradrenergic activity, thromboxane, melatonin, left hemisphere functioning, and cyclic AMP on the one hand, and dopamine, beta-endorphin, calcium, right hemisphere functioning, and cyclic GMP on the other. It is further suggested that there is a yoking of NA, TXA2, serotonin and melatonin in the left hemisphere, and a similar yoking of DA, BE, calcium and cGMP in the right. Evidence is presented to support the hypothesis that each element (NA, TXA2, etc.) on one side can modulate or balance a corresponding element (DA, BE, etc.) on the other. It is suggested that thromboxane is the key element in noradrenergic overactivity and that not taking this into consideration has confounded much prior research. This theory takes into account information processing models as well as pharmacological data and neurochemical theory on coupling of adenylate cyclase to its hormone receptors. Inhibiting noradrenergic overactivity can be obtained by inhibiting thromboxane and concomitantly activating opiate receptors. This protocol may have clinical utility in treating a wide range of disorders such as: anxiety, depression, schizophrenia, sleeplessness, withdrawal states, enuresis, Gilles de la Tourette syndrome, Parkinsonism, Alzheimers, dementia, anorexia, infant ruminations, essential tremor, spasticity of spinal cord injury, diarrhoea, ulcerative colitis, extrapyramidal symptoms, akathisia, neuroleptic malignant syndrome, attention deficit disorder, hyperhidrosis, and possibly AIDS.
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PMID:Inhibiting noradrenergic overactivity by inhibition of thromboxane and concomitant activation of opiate receptors via dietary means. 254 22

The expanding use of intrathecal baclofen for spasticity has raised a concern about the treatment of overdose in these patients, since no specific baclofen antagonist is available. Since physostigmine has been reported to reverse the respiratory depression and somnolence due to opiates, the drug was tried for the treatment of baclofen overdose. In three cases, intravenous physostigmine (2 mg) completely reversed the respiratory depression and coma caused by boluses of 80 to 800 micrograms of lumbar intrathecal baclofen. Physostigmine, although not a specific antagonist, should provide increased safety for patients receiving intrathecal baclofen.
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PMID:Physostigmine in the treatment of intrathecal baclofen overdose. Report of three cases. 274 50

Homosynaptic depression of H-reflex was studied in 25 healthy persons and 33 patients with hemiplegia. The mean duration of the homosynaptic depression in healthy persons was 5200 ms. After the initial relative facilitation the time course of the homosynaptic depression corresponded to a logarithmic function of the interval between the conditioning and testing stimuli. The homosynaptic depression in patients with hemiplegia decreased depending on the degree of the muscular spasticity.
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PMID:[Homosynaptic depression of the monosynaptic spinal reflex in healthy people and patients, suffering from a cerebral stroke]. 281 45

The literature regarding the intrathecal use of morphine, baclofen, and midazolam to treat spasticity is reviewed. Nine patients with significant spasticity due to different etiologies were treated. Morphine and midazolam decreased spasticity but did not change the patient's functional status. Baclofen improved patient status, but was associated with significant CNS depression in two cases.
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PMID:Intrathecal application of drugs for muscle hypertonia. 304 64

Two types of spinal reflex responses, extensor reflex and ventral root potential, were compared physiologically and pharmacologically in acute and chronic spinal cord transected rats. The recovery curve of the extensor reflex, recorded as evoked electromyogram, in chronic spinal rats was strikingly different from that in acute spinal rats. Namely, shortening of the reflex amplitude suppression period (stimulus interval: 20 msec) and appearance of the supernormal period (30-60 msec) were observed in chronic spinal rats. The recovery curves of ventral root potential (monosynaptic reflex) and M wave were almost the same in both preparations. In the frequency depression curve, the amplitude of the extensor reflex in chronic spinal rats was higher at high frequency stimulation than that in acute spinal rats. 5-Hydroxytryptophan, 5-methoxy-N,N-dimethyltryptamine and quipazine enhanced the extensor reflex in chronic spinal rats with a potency of 200-400, 8 and 4 times stronger than that in acute spinal rats, respectively. These drugs did not show consistent effects on the monosynaptic reflex of ventral root potential in chronic spinal rats. These results strongly suggest that the spinal interneurons where descending serotonergic fibers terminate become supersensitive and functionally modified in chronic spinal rats. It is speculated that the supersensitivity of these interneurons may play an important role in spasticity.
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PMID:Functional change in the rat spinal cord by chronic spinal transection and possible roles of monoamine neurons. 387 2

Cognitive impairments, often unrecognized in multiple sclerosis, include memory loss, new learning problems, denial and depression. Spasticity and incoordination of the oropharyngeal and respiratory muscles create functional problems with speech and swallowing. Genitourinary problems include sexual dysfunction and neurogenic bladder. Specific measures can be used to alleviate these problems.
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PMID:Multiple sclerosis: Part II. Common functional problems and rehabilitation. 406 Dec 42


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