Utilizing Cerebral Perfusion Scan and Diffusion-tensor MR Imaging to Evaluate the Effect of Hyperbaric Oxygen Therapy in Carbon Monoxide-induced Delayed Neuropsychiatric Seqeulae- A Case Report and Literature Review.

PURPOSE: Detection of regional cerebral blood flow (rCBF) and/or brain magnetic resonance imaging (MRI) has been used to investigate functional defect of brain caused by carbon monoxide (CO) poisoning. In this report, we attempted to demonstrate the correlation of changes in brain singlephoton emission computed tomography (SPECT) and diffusion-tensor MR image (DTI) with functional improvement of severe delayed neuropsychiatric sequelae (DNS) after CO intoxication during the treatment of hyperbaric oxygen therapy (HBOT). CASE REPORT: The patient had normal activities of daily life after he recovered from acute CO poisoning. One month later, he presented symptoms of declined cognitive functioning, aphasia, apraxia, dysphagia, muscle rigidity, urine and fecal incontinence. After one course of HBOT, these symptoms improved significantly and the patient could regain most of his previous functioning. The patient's improvement was evidenced by increased rCBF in Brodmann areas 7, 8, 11 and 40, as well as higher mean fractional anisotropy (FA) value of DTI. CONCLUSION: Although the efficacy of HBOT in DNS patients is still needed to be evaluated in large clinical study, these data suggest that HBOT may be the choice to improve DNS efficiently and shorten the duration of suffering with favorable outcome.

Effects of glutamate and alpha2-noradrenergic receptor antagonists on the development of neurotoxicity produced by chronic rotenone in rats.

Systemic inhibition of complex I by rotenone in rats represents a model of Parkinson's disease (PD). The aim of this study was to elucidate whether neramexane (NMDA, nicotinic alpha9/alpha10 and 5-HT3 receptor antagonist), idazoxan (alpha2-adrenoceptor antagonist) or 2-methyl-6-(phenyl-ethyl)-pyrimidine (MPEP, metabotropic glutamate receptor 5 antagonist) prevents rotenone-induced parkinsonian-like behaviours and neurochemical changes in rats. Rotenone (2.5 mg/kg i.p. daily) was administered over 60 days together with saline, neramexane (5 mg/kg i.p., b.i.d.), idazoxan (2.5 mg/kg i.p., b.i.d.) or MPEP (2.5 mg/kg i.p., b.i.d.). The same doses of neramexane, idazoxan and MPEP were administered to rats treated with vehicle instead of rotenone. Treatment-related effects on parkinsonian-like behaviours, such as hypokinesia/rigidity and locomotor activity, were evaluated. Moreover, concentrations of dopamine, serotonin and their metabolites were measured in rats from each experimental group. Over the 60-day treatment period, the rotenone+saline treated animals developed hypokinesia, expressed as an increase in the bar and grid descent latencies in the catalepsy test, and a decrease in locomotor activity. Neramexane and idazoxan partially prevented the development of catalepsy in rotenone-treated rats. Co-administration of MPEP with rotenone resulted only in a decrease in descent latency in the grid test on day 60. Chronic rotenone treatment reduced concentrations of dopamine and serotonin in the anterior striatum, which was blocked by co-treatment with neramexane or idazoxan but not with MPEP. Only neramexane treatment blocked the rotenone-induced decrease in dopamine levels in the substantia nigra pars compacta. In conclusion, neramexane and idazoxan counteracted to some extent the development of parkinsonian symptoms and neurochemical alterations in the rotenone model of Parkinson's disease.

Priming with rocuronium or vecuronium prevents remifentanil-mediated muscle rigidity and difficult ventilation.

PURPOSE: The aim of this study was to test our hypothesis that priming with rocuronium would prevent muscle rigidity and difficult ventilation due to remifentanil administration. METHODS: One hundred patients, American Society of Anesthesiologists (ASA) status I or II, were recruited into the study, and randomly allocated to one of four protocols (n = 25 each). Remifentanil was administered at 0.2 microg.kg(-1).min(-1) in group A and at 0.7 microg.kg(-1).min(-1) in groups B, C, and D. Priming with vecuronium (0.02 mg.kg(-1)) or rocuronium (0.06 mg.kg(-1)) was performed at the same time as the infusion of remifentanil in groups C and D, respectively. Anesthesia was induced with 1 mg.kg(-1)propofol 2 min after the start of remifentanil infusion. After the patient had lost consciousness, the anesthesiologist performed mask ventilation, and watched for the presence of muscle rigidity. Ventilation and rigidity were evaluated using a scoring system. RESULTS: Of the 100 patients, 9 were excluded; the number of patients in group A was 24, while groups B and D had 22 patients each, and group C had 23 patients. A lower dose of remifentanil (group A) or priming with vecuronium or rocuronium (groups C, D) significantly reduced the incidence of some difficulty with ventilation (P = 0.0010, P = 0.0053, and P = 0.021, respectively, vs group B). Of the patients in group B, 10 (45.5%) developed some difficulty with ventilation, and ventilation was impossible in 2 of them. On the other hand, 1 (4.1%) of the patients in group A, 2 (8.7%) in group C, and 3 (13.6%) in group D developed some difficulty with ventilation. CONCLUSION: The present study showed that priming with rocuronium or vecuronium reduced the incidence of difficult ventilation by avoiding the muscle rigidity caused by remifentanil.

Effect of bilateral subthalamic nucleus stimulation on levodopa-unresponsive axial symptoms in Parkinson's disease.

BACKGROUND: The levodopa responsiveness of motor, particularly axial symptoms is a good predictor of the effectiveness of subthalamic nucleus (STN) stimulation in patients with Parkinson's disease (PD). However, many Japanese PD patients are intolerant of higher doses of antiparkinsonian drugs and some aspects of their axial symptoms may remain unresponsive to treatment. We retrospectively investigated the effects of bilateral STN stimulation on the axial signs unresponsive to levodopa in Japanese patients with PD. METHODS: We enrolled 29 consecutive patients into this study. Six independent axial symptoms, i.e. falling, freezing, gait, standing, posture, and postural instability, were scored on the Unified Parkinson's Disease Rating Scale (UPDRS), before and 3 months after bilateral STN stimulation and differences were statistically analysed. FINDINGS: Postoperatively, the mean levodopa dosage was decreased by 27%. The preoperative responsiveness to antiparkinsonian drugs with respect to freezing, gait, posture, and postural instability were positively correlated with postoperative off-medication improvement (p < 0.05). For each individual axial symptom, some patients showed an excellent response to STN stimulation, despite preoperative unresponsiveness to levodopa. These selected patients were not always treated with lower doses of antiparkinsonian drugs preoperatively, but they had milder preoperative scores on the UPDRS with respect to daily activities and overall axial function. CONCLUSIONS: The axial symptoms of PD unresponsive to levodopa were ameliorated by bilateral STN stimulation in patients manifesting a milder degree of preoperative axial signs. Our findings suggest that STN stimulation exerted a definite but limited effect on levodopa-unresponsive axial features, pointing to the need to identify different target structures that control axial functions via non-dopaminergic systems.

Nicotinic mechanisms contribute to soman-induced symptoms and lethality.

The symptoms and lethality of intoxication with the acetylcholinesterase inactivator soman are attributed primarily to excessive activation of muscarinic acetylcholine receptors; nicotinic activation is considered of less importance, a notion that may rely on studies that have used nicotinic antagonists at low doses. In this study pretreatment with the centrally acting nicotinic antagonist mecamylamine, 20mg/kg, but not 2mg/kg, prolonged survival in mice exposed to soman, 250 microg/kg (1.5 LD(50)), from 14+/-3 to 135+/-38 min (mean+/-S.E.M.; surviving animals were killed 240 min after soman administration). Pretreatment with the muscarinic blocker scopolamine, 2 or 20mg/kg (but not 0.5mg/kg) prolonged survival significantly (mean for both groups: 91 min), but the animals responded to soman with immobility, irregular respiration, fasciculation, and short episodes of convulsive crawling. These symptoms were absent in animals pretreated with scopolamine plus mecamylamine, both drugs 20mg/kg, a suggestion that they were caused by activation of nicotinic receptors. All animals pretreated with scopolamine and mecamylamine (both drugs 20 mg/kg) survived the full 240 min observation period. Administration of mecamylamine, 5 mg/kg, 5 min after soman exposure to scopolamine-pretreated animals reduced fasciculation and respiratory irregularity and prolonged survival compared to scopolamine alone, but mecamylamine, 20 mg/kg, given 10 min after soman exposure shortened survival (18+/-1 min). These results suggest that nicotinic activation plays an important part in soman-induced symptomatology and lethality but also that nicotinic antagonists given in large doses after soman exposure may have untoward effects.

Prevention of amphotericin B-induced rigors by dantrolene.

Three patients had severe amphotericin B-induced rigors refractory to conventional prophylactic measures. Rigors improved or disappeared when dantrolene sodium was given prophylactically or during an episode. These observations suggest that dantrolene is useful as an alternative or adjuvant agent for severe rigors associated with amphotericin 3 infusion.

Blockade of the metabotropic glutamate receptor subtype 5 (mGluR5) produces antiparkinsonian-like effects in rats.

The aim of the present study was to examine a potential beneficial effect of the blockade of metabotropic glutamate receptor subtype 5 (mGluR5) by the selective non-competitive antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), in models of parkinsonian symptoms in rats. Haloperidol, 0.25, 0.5 and 1mg/kg ip, was used to induce hypolocomotion, catalepsy and muscle rigidity, respectively. The locomotor activity was estimated by an open-field test, the catalepsy -- by a 9-cm cork test. The muscle rigidity was measured as an increased resistance of a hind leg to passive extension and flexion at the ankle joint. Additionally, increases in the electromyographic activity were recorded in the gastrocnemius and tibialis anterior muscles. MPEP (1.0-10mg/kg ip) inhibited the muscle rigidity, electromyographic activity, hypolocomotion and catalepsy induced by haloperidol. MPEP administered alone (5mg/kg ip) did not induce catalepsy, nor did it influence the muscle tone or locomotor activity in rats. The present results suggest that blockade of mGluR5 receptors may be important to amelioration of both parkinsonian akinesia and muscle rigidity.

The pharmacological properties of CS-722, a newly synthesized centrally acting muscle relaxant.

The pharmacological properties of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized, centrally acting muscle relaxant, were studied in rats. The drug CS-722 reduced the radio frequency decerebrate rigidity in a dose-dependent manner (25-100 mg/kg, p.o.); it inhibited the increase in discharges from Ia afferent fibers, gamma-motor activity, which was induced by stimulation of the reticular formation. The compound, however, showed no effect on the basal discharge of Ia afferent fibers. The polysynaptic reflex was depressed by CS-722, with less influence on the monosynaptic reflex in intact and spinal preparations and CS-722 did not prolong thiopental-induced sleeping time. In rats anesthetized with halothane, CS-722 did not affect the electroencephalogram (EEG) arousal response, which was elicited by stimulation of the reticular formation. The results of this study suggest that CS-722 can exert a muscle relaxant action, at a dose range at which depression of the ascending reticular activating system was negligible. The results also suggest that depressions of the gamma-motor system and the polysynaptic reflex may contribute to the muscle relaxant action of CS-722.

A new class of potent centrally acting muscle relaxants: pharmacology of oxazolidinones in rat decerebrate rigidity.

The severity of anaemic decerebrate rigidity was quantitatively determined by measuring the frequency of electromyographic potentials in the rat. Some oxazolidinones markedly reduced the severity of this decerebrate rigidity in a dose-dependent manner, (4S,5R)-4-(2-methylpropyl)-3- [3-(perhydroazepin-1-yl)propyl]-5-phenyl-1,3-oxazolidin-2-on e (MLV-6976) being the most potent. In addition to the oxazolidinones, an aminoalcohol derivative, (1RS,2SR)-5-methyl-1-phenyl-2-(3-piperidinopropylamino )hexan-1-ol (MLV-5860) also reduced the rat decerebrate rigidity. In the oxazolidinone series, the optical isomers with absolute configuration (S) at the 4-position were more potent than the corresponding (4R)-isomers, while there was no significant difference in their LD50 values. Normal rats and mice receiving MLV-6976 at doses which reduced decerebrate rigidity showed no behavioural changes, impairment of motor coordination only appearing at extremely high doses. MLV-6976 and its derivatives did not affect spinal reflex potentials in cats. MLV-6976 reduced the severity of harmaline-induced tremor in mice in a dose-dependent manner, but slightly augmented tremorine-induced tremor. The frequency of the spike discharges induced by iontophoretically applied glutamate was reduced by MLV-6976 in a dose-dependent manner in rat cortical neurones. The amplitude of miniature endplate potentials of the rat diaphragm was decreased by MLV-6976 only at concentrations greater than 0.1 mM. It is concluded that MLV-6976 acts on the brainstem or/and higher levels of the brain rather than on the spinal cord or the peripheral nervous system to reduce the excessive activities of the nervous system.

Riluzole prevents MPTP-induced parkinsonism in the rhesus monkey: a pilot study.

Previous studies have shown that riluzole (2-amino-6-trifluoromethoxy-benzothiazole), a drug which interferes with glutamate neurotransmission, has a neuroprotective action in rodent models of global and focal cerebral ischemia. In this pilot study, the protective and palliative effects of riluzole have been examined using an animal model of Parkinson's disease. Two monkeys were rendered hemiparkinsonian by one intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and motor signs were evaluated using clinical examination and electromyographic recordings. When riluzole (4 mg/kg) was administered before the injection of MPTP, parkinsonian motor symptoms, in particular bradykinesia and rigidity, were absent. When injected daily in one monkey which presented stable motor symptoms, bradykinesia and rigidity were significantly reduce d. Riluzole pretreatment induced a persistent increase in dopamine turnover when compared to MPTP alone. Thus, a possible neuroprotection and a facilitation of dopamine release may explain the behavioural effects reported with riluzole treatment. These preliminary results suggest that riluzole could possess neuroprotective and palliative effects in a primate model of Parkinson's disease.

Atropine reduces raclopride-induced muscle rigidity by acting in the ventral region of the striatum.

Parkinson-like extrapyramidal motor side effects associated with the use of antipsychotic drugs, such as increased muscle rigidity, are thought to result from blockade of striatal dopamine D2 receptors. While anticholinergic medications (muscarinic receptor antagonists) ameliorate extrapyramidal side effects, the mechanisms underlying their effectiveness remain unclear. We investigated the site of action of atropine, a non-selective muscarinic receptor antagonist, in reducing increased muscle rigidity, assessed as increases in tonic electromyographic (EMG) activity, induced by the selective dopamine D2 receptor antagonist, raclopride. Atropine significantly reduced raclopride-induced EMG increases in rat hindlimb muscles, when injected into the ventral striatum, but not the dorsal striatum or the substantia nigra. Atropine's site of action was localised to a small area of muscarinic receptors within the ventral part of the striatum, using quantitative autoradiography. These findings provide new information about the regulation of motor control by muscarinic receptor antagonists and additional evidence about the functional heterogeneity of the striatum.

LY354740, a group II metabotropic glutamate receptor agonist with potential antiparkinsonian properties in rats.

The aim of this study was to examine whether (+)-2-aminobicyclo[3.1.0]-hexane-2,6-dicarboxylate monohydrate (LY354740), a selective agonist of group II metabotropic glutamate receptors, possesses antiparkinsonian properties. Parkinsonian-like muscle rigidity was induced by pretreatment with haloperidol (1 mg/kg i.p.). It was measured as increased resistance developed by the rat's hind leg to passive extension and flexion. LY354740 (5 and 10 mg/kg i.p.) dose-dependently diminished the haloperidol-induced muscle rigidity. The present results suggest that LY354740 counteracts the muscle rigidity in an animal model of parkinsonism.

An in vivo alpha-2 assay reversal of opioid-induced muscular rigidity and neuroleptic-induced ptosis.

A method is described to detect selective alpha-2 adrenergic agonists in vivo. Palpebral ptosis is induced in rats by the neuroleptic agent haloperidol (Hal), or by tetrabenazine (TBZ) methanesulfonate. Twenty minutes later, test compounds are injected, and ptosis is scored. In a separate test, muscular rigidity is induced by the opioid, fentanyl, and subsequently, test compounds are assessed for their ability to reverse muscular rigidity. Results indicate that only alpha-2 agonists reliably reverse neuroleptic-induced and TBZ-induced ptosis, as well as opioid-induced rigidity. An alpha-1 antagonist reversed only rigidity, whereas, alpha-2 antagonists and beta-agonists were generally ineffective in all tests. Therefore, the ability to reverse neuroleptic and TBZ-induced ptosis along with the ability to reverse opioid-induced muscular rigidity is a characteristic unique to alpha-2 agonists.

Prevention of reserpine rigidity by alpha-2 adrenergic antagonists.

Since alpha adrenergic antagonists are known to protect rats from the extrapyramidal effects of reserpine, the purpose of this study was to examine the relative contribution of alpha-2 receptors in modifying the reserpine-induced syndrome. Rats were pretreated with either clonidine, yohimbine, phentolamine, methysergide or SKF-7265. Thirty minutes later they were given reserpine (20 mg/kg) and evaluated using eleven categories of behavioral responses for three hours. Yohimbine, an alpha-2 antagonist, was the most effective agent in protecting against the reserpine effects. Phentolamine and SKF-7265, which block both alpha-1 and alpha-2 receptors, were also effective. Clonidine, an alpha-2 agonist, and methysergide a serotonin antagonist, were not. In all cases the alpha blocking drugs prevented the motor responses but did not alter the autonomic responses induced by reserpine. The results show not only the efficacy of alpha adrenergic antagonists in protecting against reserpine rigidity but more importantly that the blockade of alpha-2 receptors may be the functionally important action. These results are consistent with the view that some descending motor pathways are controlled by an adrenergic mechanism and suggest that alpha-2 receptors are an important component.

Magnesium sulfate for control of muscle rigidity and spasms and avoidance of mechanical ventilation in pediatric tetanus.

OBJECTIVE: To describe the use of intravenous magnesium sulfate for the control of muscle spasms and severe generalized rigidity in a child with moderate to severe tetanus without the need for prolonged deep sedation, mechanical ventilation, or neuromuscular blockade. DESIGN: Case report. SETTING: Pediatric intensive care unit in a tertiary care, university-based children's hospital. INTERVENTIONS: A continuous infusion of magnesium sulfate. MEASUREMENTS AND MAIN RESULTS: We describe a 12-yr-old child with moderate to severe tetanus who was treated with a continuous infusion of magnesium sulfate to control painful muscle spasms and severe generalized rigidity initially refractory to moderate sedation. Muscle spasms and severe generalized rigidity were improved with magnesium sulfate. No adverse effects associated with the use of magnesium sulfate were noted during the monitoring of cardiovascular and respiratory function, reflexes, and serum magnesium concentrations. CONCLUSIONS: An infusion of magnesium sulfate can be utilized to treat muscle spasms and severe generalized rigidity without the need for deep sedation, mechanical ventilation, or neuromuscular blockade. We recommend that magnesium sulfate be considered in the armamentarium of therapeutics utilized to treat muscle spasms and rigidity associated with tetanus, provided the patient's neurologic, cardiovascular, and respiratory status can be closely monitored in the pediatric intensive care unit.

Pretreatment with sedative-hypnotics, but not with nondepolarizing muscle relaxants, attenuates alfentanil-induced muscle rigidity.

STUDY OBJECTIVE: To evaluate and compare the efficacy of various pretreatment agents to attenuate or prevent opioid-induced muscle rigidity using a well-established, previously described clinical protocol. DESIGN: Prospective, controlled, single-blind, partially randomized study. SETTING: Large medical center. PATIENTS: ASA physical status I-III patients undergoing elective surgical procedures of at least 3 hours' duration. INTERVENTIONS: The effect of pretreatment with nondepolarizing muscle relaxants (atracurium 40 micrograms/kg or metocurine 50 micrograms/kg), benzodiazepine agonists (diazepam 5 mg or midazolam 2.5 mg), or thiopental sodium 1 mg/kg on the increased muscle tone produced by alfentanil 175 micrograms/kg was compared with a control group (given no pretreatment). MEASUREMENTS AND MAIN RESULTS: Rigidity was assessed quantitatively by measuring the electromyographic activity of five muscle groups (biceps, intercostals, abdominals, quadriceps, and gastrocnemius). Rigidity also was rated qualitatively by attempts to initiate and maintain mask ventilation, attempts to flex an extremity, and the occurrence of myoclonic movements. Pretreatment with the two nondepolarizing muscle relaxants had no effect on the severe muscle rigidity produced by high-dose alfentanil. Whereas thiopental was only mildly effective, the benzodiazepines midazolam and diazepam significantly attenuated alfentanil rigidity (p < 0.05). CONCLUSION: This study suggests that benzodiazepine pretreatment is frequently, but not always, effective in preventing opioid-induced muscle rigidity.

[Early patient mobilization after apoplectic stroke]. / Ranniaia mobilizatsiia bol'nykh posle apopleksicheskogo udara.

Principles of individualized functional mechanotherapy in the early post-hemorrhagic period are briefly presented. This therapy makes it possible to prevent or to alleviate complications specific for cerebral hemorrhage (rigidity of the muscles in the humoral region, development of contractures of the joints and pathological models of movements, unfavourable influence of the psychic syndrome developing after organic affections of the brain). While giving the therapy it is recommended to take into consideration the pathophysiological conditions present by the beginning of the development of the motor activity. Principal rules for the individualized functional mechanotherapy are formulated.