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We investigated the intrathecally administrated unbilical cord mesenchymal stem cells (UC-MSCs) by lumbar puncture and assessed the technical difficulties and effects in various neurological conditions. One hundred patients underwent subarachnoid placement of UC-MSCs between December 2006 and May 2010 in the Affiliated Hospital of Medicine. Technical difficulties in patients in the form of localization of subarachnoid space, number of attempts, and post-procedural complications were evaluated. Functional evaluation was done using Hauser Ambulation Index (HAI) by the stem cell transplant team on a regular basis. All patients were followed-up for more than 1 yr after the treatment. Clinical symptoms, related biochemical index and photographic examinations were observed regularly. We encountered technical difficulties in 31 patients (31%) in the form of general anesthesia supplementation and difficulty localizing the lumbar space. Side effects (headache, low-grade fever, low back pain and lower limb pain) were observed in 22 (22%) patients, which were treated with symptomatic therapy within 48 h. One year after the treatment, functional indices improved in 47 patients (47%): 12 patients with spinal cord injury, 11 patients with cerebral palsy, 9 patients with post-traumatic brain syndrome, 9 patients with post-brain infarction syndrome, 3 patients with spinocerebellar ataxias, and 3 patients with motor neuron disease. In conclusion,intrathecal administration of UC-MSCs is a safe and effective way to treat neurological disorders. Our encouraging results of intrathecal administration of UC-MSCs indicate the potential of restoration of lost tissue and improvement of function in patients with profound neurological defects and inefficient conventional cure. These data support expanded double-blind, placebo-controlled studies for this treatment modality.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Injections, Spinal , Male , Mesenchymal Stem Cells , Middle Aged , Nervous System Diseases/therapy , Stem Cells , Umbilical Cord/cytology , Young AdultABSTRACT
Objective To investigate the clinical effect of lumbar catheter drainage combined with intrathecal injection on patients with cerebrospinal fluid leakage and intracranial infection.Methods A retrospective study was conducted.One hundred and fifty-two cases with cerebrospinal fluid leakage and intracranial infection were selected as our subjects who were hospitalized in the First Hospital of Yuncheng from 2006 to 2014.The patients were divided into lumbar puncture + intrathecal group (A),lumbar (group B) and lumbar intrathecal large pool + group (group C) based on post-processing methods.A experimental data were recorded and compared in terms of the total efficiency of treatment,the therapeutically effective time,bacterial clearance and security differences.Results After treatment,the levels of white blood cells,protein,glucose and intracranial pressure were changed compared with that of before treatment in three group(P ＜ 0.01),but there was no significant difference among the three groups(P ＞ 0.05).The therapy periods in group A,group B and group C were (12.80 ± 2.25) d,(12.64 ± 2.00) d and (9.44 ± 1.50) d respectively and the difference was significant(F =25.94,P ＜ 0.05).Compared with Group C,the therapy periods in group A and B were significant different(t =2.769,2.854;P ＜ 0.05),but there was no significant difference between group A and B (t =0.119,P =0.908).The cases with success.effect was 45 (89.1％) in group A,53 (94.6％) in group B,46 (95.8％) in group C,and there was no significant difference among three groups (P ＞ 0.05).In terms of bacterial clearance rate,33 cases(68.75％) was in group A,35 cases(72.91％) in group C and 23 cases (41.07％) in group B and the effective rate in group A or C were higher than that in group B (x2 =9.478,10.63 ; P ＜ 0.05).Conclusion The methods of lumbar catheter drainage combinedwith intrathecal injection is proved with a high clinical value of therapy,effective treatment can effectively shorten the time and improve the overall treatment effect.
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Objective To analyze the clinical manifestation,auxiliary examination,treatment,prognosis of 16 cases who experienced inadvertent injection of intrathecal microcontent vincristine,and and they were followed up for 5 years.Methods To collect detailed medical record material for 5 years of 16 pediatric blood oncology patients who appeared with nervous system damage symptoms caused by inadvertent administration of microcontent vincristine intrathecally,combined with subsequent visits at the clinic,or through telephone and letters followed-up.Results Clinical manifestations of lumbosacral radicular dysfunction were found in all 16 cases,among them 2 cases also had cervicothoracic radicular damage symptoms.The first sign was weakness in lower limbs,subsequently,walking difficulty.Cerebrospinal fluid protein was higher than normal in 3 cases.Magnetic resonance imagine of the brain and spinal cord revealed demyelination in the white matter of 2 cases.Electromyographic revealed neurogenic damage and showed complete or partial denervation changes in 11 cases that received this examination.After the treatment consisted of medication use to improve nerve nutrition metabolism and promote nervous function recovery,combined with positive rehabilitation therapy,13 cases had improvement from level Ⅰ to Ⅲ in myodynamia.Of 9 cases with neurogenic bladder,4 cases were back to normal,3 cases were improved to different extent.Till Oct.2012,6 cases lived in remission,9 cases including 6 cases of recurrence died of the primary disease or complication in the treatment process,and 1 case died of penicillin anaphylactic shock almost 1 year after chemotherapy.Conclusions Inadvertent intrathecal injection of microcontent vincristine can cause lumbosacral radicular dysfunction.Trace amounts of vincristine intrathecally cumulative can also cause serious damage to the nervous system.The early application of horrmone and nerve nutrition drugs combined with positive rehabilitation therapy have surely curative effect to alleviate the neuropathy for inadvertent administration of microcontent vincristine intrathecally.
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<b>Introduction</b>: Few studies have examined neuropathological changes such as the degenerative necrosis and demyelination of spinal nerve cells accompanying intrathecal administration of opioids (ITO) to relieve refractory cancer pain. Previous studies have produced conflicting results as to whether or not ITO causes nerve tissue damage. The current study neuropathologically investigated autopsy specimens from patients who received ITO. <b>Methods</b>: Subjects were 7 patients who received continuous intrathecal analgesia and who were later autopsied (4 males, 3 females). Six patients were administered morphine and bupivacaine while 1 patient was administered fentanyl and bupivacaine. The duration of administration ranged from 6-345 days. <b>Results</b>: Two patients who received long-term administration of morphine were found to have severe necrotic degeneration and gliosis of spinal neurons and demyelination in the dorsal horn and dorsal roots. However, neuropathological changes were not noted in Patient 4, who was briefly administered morphine, or in the patient who was administered fentanyl. <b>Conclusion</b>: The total dose of morphine used for ITO and the duration of its administration were suggested to be related to the extent of nerve tissue damage. Thus, nerve tissue damage due to ITO might be primarily associated with morphine.
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In general, intrathecal opioid administration is considered for intractable cancer pain management. We would like to report a case of carcinomatous meningitis that was successfully treated by using an intrathecal catheter with subcutaneous port. A female in her fifties with carcinomatous meningitis secondary to invasive ductal breast cancer was suffering multiple neurological symptoms including headache. Intrathecal catheterization with subcutaneous port was considered as an alternative to Ommaya reservoir placement to continue intrathecal antineoplastic treatment. The port was used for collection of CSF, antineoplastic drug administration and opioid delivery. Neoplastic cells in the CSF disappeared within one month and the headache and other neurological symptoms improved. The patient died five months post diagnosis (four months after initiation treatment via intrathecal catheter) without recurrence of significant headache, before developing coma seven days prior to death. This case suggests an intrathecal catheter with subcutaneous port may be used effectively for both symptom management and the administration of antineoplastic drugs. However, further study is necessary.
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BACKGROUND: Neuropathic pain can be induced by nerve injury or inflammation. An N-methyl-D-Aspartate (NMDA) antagonist (MK-801), and a sodium channel blocker (lidocaine) have been found to reduce mechanical allodynia. This study was conducted to determine whether intrathecal lidocaine or MK-801 had an antiallodynic effect on established mechanical allodynia in two well-characterized neuropathic pain rat models. METHODS: Male Sprague Dawley rats (n = 107) were anesthetized, and the left L5 and L6 spinal nerves were ligated (SNL group) or Freund complete adjuvant (FCA) was administrated to the same spinal nerves (FCA group) in order to cause neuropathic pain. A catheter was then implanted into the lumbar intrathecal space. After obtaining the baseline scores, time-effect curves of each drug were established for the antiallodynic effects of lidocaine (30g, 100g and 300g) and MK-801 (1g, 3g, 10g and 30g). The allodynic thresholds for the left hind paw withdrawal to von Frey hairs were assessed and converted to %MPE, and the ED50 value was then calculated using the %MPE. The antiallodynic effects of the two groups were then compared by analyzing the dose-response curves and the ED50 values. RESULTS: Both intrathecal lidocaine and MK-801 resulted in a dose dependent antiallodynic effect. ED50 values and the analysis of dose response curves showed that intrathecal lidocaine provided more effective antiallodynia in the SNL group, whereas intrathecal MK-801 resulted in a greater antiallodynic effect in the FCA group. CONCLUSIONS: In the SNL group, lidocaine had a better effect in reducing allodynic pain, whereas in the FCA group, MK-801 showed a greater antiallodynic effect.
Subject(s)
Animals , Humans , Male , Rats , Catheters , Dizocilpine Maleate , Hair , Hyperalgesia , Inflammation , Lidocaine , Models, Animal , N-Methylaspartate , Neuralgia , Rats, Sprague-Dawley , Sodium Channels , Spinal NervesABSTRACT
BACKGOUND: Cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) antagonists reduce the mechanical allodynia in neuropathic pain models. In this study our aim was to compare the antiallodynic effects between intrathecal cholinesterase inhibitors and NMDA antagonists on two well-characterized neuropathic pain rat models. METHODS: Male Sprague Dawley rats were anesthetized and either had the left L5 and L6 spinal nerves ligated (SNL group) or Freund complete adjuvant (FCA) administrated to the sciatic nerve (FCA group) in order to cause neuropathic pain. A catheter was implanted into the intrathecal space for drug administration. After obtaining baseline values, edrophonium (3-100microgram), neostigmine (0.3-10microgram), AP-5 (0.3-3microgram) and MK-801 (1-30microgram) were administered intrathecally to each group. The allodynic left hind paw withdrawal thresholds to von Frey hairs were assessed and converted to % MPE. Antiallodynic effects on the two groups were compared by analyzing dose-response curves and ED 50 values. Motor weakness was also checked. RESULTS: Intrathecal edrophonium, neostigmine, AP-5 and MK-801 had a dose-dependent antiallodynic effect on the two neuropathic pain models. Comparing the antiallodynic effect dose response curves, intrathecal cholinesterase inhibitors had lower ED 50 with steep slopes in the SNL model, whereas intrathecal NMDA antagonists had lower ED 50 in the FCA model, but there were no statistically significant differences between the two models. CONCLUSIONS: Intrathecal cholinesterase inhibitors and NMDA antagonists have relatively better antiallodynic effects on the SNL and FCA neuropathic pain rat models, respectively.
Subject(s)
Animals , Humans , Male , Rats , Catheters , Cholinesterase Inhibitors , Cholinesterases , Dizocilpine Maleate , Edrophonium , Hair , Hyperalgesia , Models, Animal , N-Methylaspartate , Neostigmine , Neuralgia , Rats, Sprague-Dawley , Sciatic Nerve , Spinal NervesABSTRACT
Intrathecal clonidine injection induces analgesia without significant respiratory depression, but decreases blood pressure and causes sedation. Injection of spinal cholinesterase inhibitor alone increases blood pressure in animals, and enhances clonidine induced analgesia. To evaluate the effect of pretreated pyridostigmine on the change of blood pressure and heart rate, clonidine was injected intrathecally in cats. We divided fifteen cats into three groups and administered saline(0.5 cc) to group 1, pyridostigmine(0.5 cc, 2.5 mg) to group 2, pyridostigmine(0.5 cc, 2.5 mg) and glycopyrrolate(0.5 cc, 0.1 mg) to group 3 before 20 minute of clonidine injection and measured mean arterial pressure, heart rate, P CO2 and central venous pressure. The results were as follows: 1)After clonidine injection, all mean arterial pressure values were significantly reduced in group 1, but in group 3, 20, 30 and 40 minutes values were significantly reduced, and 10, 40 minutes values after clonidine injection were not reduced significantly in group 2 compared to group 1. 2)After clonidine injection, heart rates were significantly reduced in all groups, but there was no significant difference between group 1, group 2 and group 3. 3)There was no significant difference of central venous pressure in any groups. 4)There was no significant difference for reversal of pyridostigmines effect by glycopyrrolate. Based on these results, these data suggest that pyridostigmine pretreatment counteracts clonidine induced hypotension, but further study of spinal az adrenergic-cholinergic combination for pain therapy is needed before clinical application.
Subject(s)
Animals , Cats , Analgesia , Arterial Pressure , Blood Pressure , Central Venous Pressure , Cholinesterases , Clonidine , Glycopyrrolate , Heart Rate , Heart , Hypotension , Pyridostigmine Bromide , Respiratory InsufficiencyABSTRACT
The present study was performed to elucidate the changes of regional cerebral blood flow(rCBF) and the effect of nifedipine, a calcium antagonist, on rCBF in acute subarachnoid hemorrhage(SAH) in cats. Another Purpose of this study was to document the effective dose and route of administration of nifedipine for maintaining rCBF in acute SAH. Subarachnoid hemorrhage was induced by intrathecal injection of autologous blood in 12 cats and rCBF was measured on the territories of both PCA, MCA, ACA, every 30 minutes for three hours using hydrogen clearance method. Sham operation was done in 5 cats. To study the effectiveness of nifedipine, nifedipine was administered after the induction of SAH in three different methods in 20 cats:intravenous injection in the amount of 0.1mg/kg in 7 cats, intravenous injection in the amount of 0.5mg/kg in 7 cats, and intrathecal adminstration of 10(-3)M, 1 ml, in 6 cats. The results were as follows; 1) Cerebral blood flows before the subarachnoid hemorrhage were 40.3+/-4.4ml/min/100g, 41.9+/-9.4ml/min/100g, 39.0+/-5.7ml/min/100g on the territories of right PCA, MCA, ACA and 41.5+/-7.4ml/min/100g, 42.5+/-9.6ml/min/100g, 41.3+/-9.9ml/min/100g on the territories of left PCA, MCA, ACA respectively. There was no significant difference between the territories. 2) After the subarachnoid hemorrhage, the cerebral blood flow was reduced immediately by 23.4-35.8% of control values and remained low for 3 hours in all six territories. 3) The rCBF in the group of intravenous injection of nifedipine in the amount of 0.1mg/kg was not significantly reduced immediately after SAH(p>0.05), but reduced after 3 hours(p0.01), but those in ACA territories were reduced to 60.4% and 61.7% of control values respectively. 6) Blood pressure was elevated from 135.4+/-20.2mmHg to 148.3+/-22.9mmHg at 30 minutes and then dropped to control level in SAH group. Groups of intrathecal administration of 10(-3)M and intravenous injection of 0.1mg/kg showed no significant change but group of intravenous injection of 0.5mg/kg showed significant drop of blood pressure. Intracranial pressure was elevated after SAH but returned to control value in 30 minutes. Intracranial pressure in the intrathecal injection group was markedly elevated and remained high for 3 hours. In conclusion, the rCBF was reduced immediately and remained low for 3 hours after SAH. Intravenous injection of nifedipine in the amount of 0.1ml/kg effective on increasing the reduced cereral blood flow. Intravenous injection of nifedipine in the concentration of 0.5mg/kg was less effective and showed significant hypotension. The effect of intrathecal administration of nifedipine was varied according to the location.