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2.
Int J Immunopathol Pharmacol ; 25(1 Suppl): 57S-62S, 2012.
Article in English | MEDLINE | ID: mdl-22652163

ABSTRACT

A new preparation of botulinum toxin type A called NT 201, free from complexing proteins, potentially with low antigenicity has been used in the therapy of spasticity in stroke patients. This was an open-label study reported the safety and the efficacy of one-year treatment with NT 201 evaluating the therapeutic effect on functional disability and on quality of life in upper limb spasticity after stroke. Patients received a botulinum toxin therapy in the upper injected intramuscularly. After inoculation, patients were submitted to a motor rehabilitation program for upper limb injected three times/week. Re-treatment was permitted at 12 weeks after the prior treatment. Safety assessment included evaluation of adverse events and efficacy was measured by Modified Ashworth Scale for spasticity (MAS), Spasm Frequency Score (SFS) for the daily spasms, and Disability Assessment Scale (DAS) for disability. Of 35 consecutive patients (13 women and 12 men) screened for study eligibility, 20 (6 women and 14 men) patients (mean age 63,4±7,03) were included in this study and were submitted to NT 201 therapy for one year. At the baseline, botulinum toxin dose in the upper limb ranged from 160 to 450U, whereas total dose in the last treatment administrated was reduced respect the first injections ranging from 120 to 350U. All the enrolled patients completed the year-long study and reported an improvement of clinical picture. MAS, was statistically (px003C;0,001) reduced in all muscles at T1 (mean score ±SD: 2.65±0.67) and T2 (mean score±SD: 2.55±0.60) in comparison to the baseline T0 (mean score±SD: 3.9 ±0.78). Significant reduction (px003C;0,001) from baseline T0 (mean score ±SD: 3.25±0.78) was also noted in SFS at T1 (mean score ±SD: 1.55±0.51) and T2 (mean score±SD :1.30±0.47). The DAS score showed a reduction of the T1score (mean score ±SD: 1.70±0.47) and T2 score (mean score ±SD: 1,40 ±0,50) respect to baseline T0 score (mean score ±SD: 2,65 ±0,48) statistically significant (p≤003C;0,001). No adverse effects were observed in these patients. NT 201 appeared to be an efficacious and well-tolerated long-term treatment option for patients with upper limb spasticity after stroke, obtaining a substantial improvement in functional disability, muscle hypertone, and daily spasms.


Subject(s)
Botulinum Toxins, Type A/therapeutic use , Muscle Spasticity/drug therapy , Stroke/drug therapy , Aged , Botulinum Toxins, Type A/adverse effects , Female , Humans , Male , Middle Aged , Muscle Spasticity/cerebrospinal fluid , Muscle Spasticity/physiopathology , Muscle Spasticity/psychology , Quality of Life , Stroke/physiopathology , Stroke/psychology , Upper Extremity
3.
J Neurosurg ; 92(2): 347-9, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10659025

ABSTRACT

Intrathecal baclofen administered by means of an implantable pump is being increasingly used for successful treatment of spasticity. Meningitis following intrathecally administered baclofen is a rare but serious complication that is difficult to treat without removal of the pump. Because success rates with intravenously administered antibiotic drugs for the treatment of meningitis have been low, intrathecal administration of antibiotic agents is often required to eradicate the pathogen. The authors report the case of a patient in whom Staphylococcus epidermidis meningitis developed after insertion of an intrathecal baclofen pump. The patient was successfully treated by intrathecal coadministration of vancomycin and baclofen.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Baclofen/administration & dosage , Infusion Pumps, Implantable , Meningitis/drug therapy , Motor Neuron Disease/drug therapy , Muscle Spasticity/drug therapy , Prosthesis-Related Infections/drug therapy , Staphylococcal Infections/drug therapy , Staphylococcus epidermidis , Vancomycin/administration & dosage , Adult , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacokinetics , Baclofen/adverse effects , Baclofen/pharmacokinetics , Dose-Response Relationship, Drug , Drug Therapy, Combination , Humans , Injections, Spinal , Male , Meningitis/cerebrospinal fluid , Motor Neuron Disease/cerebrospinal fluid , Muscle Spasticity/cerebrospinal fluid , Prosthesis-Related Infections/cerebrospinal fluid , Staphylococcal Infections/cerebrospinal fluid , Staphylococcus epidermidis/drug effects , Vancomycin/adverse effects , Vancomycin/pharmacokinetics
4.
Neurosurgery ; 33(2): 226-30; discussion 230, 1993 Aug.
Article in English | MEDLINE | ID: mdl-7690122

ABSTRACT

Chronic intrathecal drug infusion for the treatment of neurological diseases, such as spasticity and chronic pain, has become an accepted method of therapy in recent years. Concurrent pharmacokinetic studies have shown that the cisternal cerebrospinal fluid (CSF) drug level is considerably lower than the lumbar CSF level during continuous infusion into the lumbar subarachnoid space. One factor that makes analysis of this decline in drug level difficult to quantify is that it is only feasible to sample CSF at the two extremes of the spinal subarachnoid space. Using a radionuclide technique, we have examined the distribution along the spinal canal of a hydrophilic compound, indium-111 diethylenetriamine pentaacetic acid, that was delivered over 72 hours into the lumbar subarachnoid space in five patients with implanted drug pumps. Over a 20-cm distance of the thoracic cord, radionuclide counts decreased gradually so that the indium-111 diethylenetriamine pentaacetic acid concentration surrounding the cord at the T2 vertebral level was 43% of that at the T12 level in four patients. Therefore, it appears that even with a hydrophilic compound, which minimizes spinal cord capillary losses, there is still a considerable reduction of CSF drug concentration along the spinal canal. The clinical implication of this gradual decline in drug level is that for intrathecal infusion of relatively hydrophilic compounds there may not be any advantage in placing the catheter tip at more rostral locations, such as at the midthoracic or cervical cord.


Subject(s)
Baclofen/pharmacokinetics , Hydromorphone/pharmacokinetics , Infusion Pumps, Implantable , Injections, Spinal/instrumentation , Morphine/pharmacokinetics , Muscle Spasticity/drug therapy , Pain, Intractable/drug therapy , Spinal Cord/metabolism , Analgesia, Epidural/instrumentation , Baclofen/administration & dosage , Endometrial Neoplasms/physiopathology , Female , Humans , Hydromorphone/administration & dosage , Male , Morphine/administration & dosage , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/drug therapy , Muscle Spasticity/cerebrospinal fluid , Pain, Intractable/cerebrospinal fluid , Prostatic Neoplasms/physiopathology , Reflex Sympathetic Dystrophy/cerebrospinal fluid , Reflex Sympathetic Dystrophy/drug therapy , Spinal Cord/drug effects , Spinal Cord Injuries/cerebrospinal fluid , Spinal Cord Injuries/drug therapy
5.
Ann Neurol ; 23 Suppl: S121-6, 1988.
Article in English | MEDLINE | ID: mdl-2894801

ABSTRACT

We report clinical and laboratory investigations of 47 native-born Jamaican patients with endemic tropical spastic paraparesis and of 1 patient with tropical ataxic neuropathy. Mean age at onset was 40 years, with a female-male preponderance (2.7:1). Neurological features of endemic tropical spastic paraparesis are predominantly those of a spastic paraparesis with variable degrees of proprioceptive and/or superficial sensory impairment. Using enzyme-linked immunoabsorbent assay (ELISA), IgG antibodies to human T-lymphotropic virus type I (HTLV-I) were present in 82% of sera and 77% of cerebrospinal fluids. On Western blot analysis, IgG antibodies detected the p19 and p24 gag-encoded core proteins in both serum and cerebrospinal fluid. Titers were tenfold higher by ELISA in serum than in cerebrospinal fluid, and some oligoclonal bands present in fluid were not seen in serum. Serum-cerebrospinal fluid albumin ratios were normal, and IgG indexes indicated intrathecal IgG synthesis. Histopathological changes showed a chronic inflammatory reaction with mononuclear cell infiltration, perivascular cuffing, and demyelination that was predominant in the lateral columns. In 1 patient, a retrovirus morphologically similar to HTLV-I on electron microscopy was isolated from spinal fluid. Our investigations show that endemic tropical spastic paraparesis in Jamaica is a retrovirus-associated myelopathy and that HTLV-I or an antigenically similar retrovirus is the causal agent.


Subject(s)
Deltaretrovirus Infections/complications , Paraplegia/etiology , Tropical Medicine , Adolescent , Adult , Aged , Antibodies, Anti-Idiotypic/analysis , Antibodies, Viral/analysis , Deltaretrovirus/isolation & purification , Deltaretrovirus Antibodies , Female , Humans , Immunoglobulin G/immunology , Jamaica , Male , Middle Aged , Muscle Spasticity/cerebrospinal fluid , Muscle Spasticity/etiology , Muscle Spasticity/immunology , Paraplegia/cerebrospinal fluid , Paraplegia/immunology
6.
Ann Neurol ; 23 Suppl: S127-32, 1988.
Article in English | MEDLINE | ID: mdl-2894802

ABSTRACT

A high-incidence focus of tropical spastic paraparesis (TSP) occurs on the South Pacific coast of Colombia. Of 55 patients studied, 52 (94.5%) had IgG antibodies to the human T-cell lymphotropic virus type I (HTLV-I) in serum and/or cerebrospinal fluid. Control groups did not show similar high positivity. Our results suggest that HTLV-I or other antigenically related retroviruses may be the cause of TSP in Colombia. Similar clinical, laboratory, and epidemiological findings have been reported in widely remote geographical regions of the world, with very similar clinical pictures of TSP in all high-incidence regions. The demonstration of IgG antibodies in serum and cerebrospinal fluid of patients with TSP in the Caribbean and Seychelles Islands, southern Japan, and the Ivory Coast indicate that the HTLV-I retrovirus could be the cause of this "tropical" myeloneuropathy.


Subject(s)
Antibodies, Viral/analysis , Paraplegia/epidemiology , Tropical Medicine , Adolescent , Adult , Antibodies, Anti-Idiotypic/analysis , Antibodies, Anti-Idiotypic/cerebrospinal fluid , Antibodies, Viral/chemical synthesis , Colombia , Deltaretrovirus Antibodies , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G/immunology , Immunoglobulins/analysis , Immunoglobulins/cerebrospinal fluid , Isoelectric Focusing , Male , Muscle Spasticity/cerebrospinal fluid , Muscle Spasticity/epidemiology , Muscle Spasticity/immunology , Oligoclonal Bands , Paraplegia/cerebrospinal fluid , Paraplegia/immunology
7.
Ann Neurol ; 23 Suppl: S151-5, 1988.
Article in English | MEDLINE | ID: mdl-2894807

ABSTRACT

Three of 6 patients with spastic paraparesis in Lima, Peru, were found to have antibodies to human T-lymphotropic virus type I (HTLV-I). Blood and cerebrospinal fluid antibodies were confirmed by Western blot analysis. Multilobulated lymphocytes in blood and cerebrospinal fluid of the index case stained with monoclonal antibodies for T-helper cells and for T10, an activation marker. Blood mononuclear cells from patients with HTLV-I-associated myelopathy showed spontaneous proliferation in culture, evidence of interleukin-2 receptors, and decreased natural killer cell activity.


Subject(s)
Deltaretrovirus Infections , Paraplegia/etiology , Adult , Aged , Antibodies, Viral/analysis , Antibodies, Viral/cerebrospinal fluid , Blood Cells/pathology , Cell Division , Deltaretrovirus Antibodies , Deltaretrovirus Infections/cerebrospinal fluid , Deltaretrovirus Infections/immunology , Deltaretrovirus Infections/pathology , Female , Humans , Leukocytes, Mononuclear/pathology , Male , Middle Aged , Muscle Spasticity/cerebrospinal fluid , Muscle Spasticity/etiology , Muscle Spasticity/immunology , Muscle Spasticity/pathology , Myelitis/etiology , Paraplegia/cerebrospinal fluid , Paraplegia/immunology , Paraplegia/pathology , Peru , T-Lymphocytes/classification
8.
Arch Psychiatr Nervenkr (1970) ; 231(6): 503-8, 1982.
Article in English | MEDLINE | ID: mdl-6127989

ABSTRACT

Using a specific radioimmunoassay we have measured somatostatin-like immunoreactivity (SLIR) of CSF in patients with brain atrophy, spinal spasticity, seizures, brain tumors and inflammatory disorders. Patients with marked brain atrophy had significantly decreased somatostatin levels in CSF. In patients with spinal spasticity significantly higher levels were observed. Seizure patients had reduced levels but the difference was not significant. In patients with inflammatory disorders and malignant brain tumors SLIR levels were significantly elevated but not in patients with benign brain tumors. A possible pathophysiologic meaning of SLIR in spasticity and seizures is discussed. The altered levels in brain atrophy, tumors and inflammatory disorders are probably indirect signs of altered somatostatin turnover or increased somatostatin leakage from damaged CNS.


Subject(s)
Central Nervous System Diseases/cerebrospinal fluid , Peptides/cerebrospinal fluid , Somatostatin/cerebrospinal fluid , Adolescent , Adult , Aged , Atrophy , Brain/pathology , Brain Diseases/cerebrospinal fluid , Brain Neoplasms/cerebrospinal fluid , Child , Epilepsy/cerebrospinal fluid , Female , Humans , Male , Meningoencephalitis/cerebrospinal fluid , Middle Aged , Muscle Spasticity/cerebrospinal fluid , Myelitis/cerebrospinal fluid , Spinal Cord Diseases/cerebrospinal fluid
9.
Acta Neurol Scand ; 55(2): 158-62, 1977 Feb.
Article in English | MEDLINE | ID: mdl-842287

ABSTRACT

Increased concentration of CSF homocarnosine has recently been found in a family with spastic paraplegia. CSF homocarnosine was therefore determined in 13 patients from other families with familial spastic paraplegia. Also examined were seven patients from families where the constellation of symptoms and signs was more complex, but also comprised spastic paraplegia, and five patients with non-familial spastic paraplegia. No changes were found in homocarnosine level. In one patient with spastic familial paraplegia clear elevation of threonine in the CSF was found. The affected brother showed no such abnormality. CSF homocarnosine elevation is thus no common denominator in familial spastic paraplegia.


Subject(s)
Amino Acids/cerebrospinal fluid , Carnosine/cerebrospinal fluid , Dipeptides/cerebrospinal fluid , Muscle Spasticity/genetics , Paraplegia/genetics , Adult , Aged , Carnosine/analogs & derivatives , Female , Genes, Dominant , Genes, Recessive , Humans , Male , Muscle Spasticity/cerebrospinal fluid , Paraplegia/cerebrospinal fluid
10.
Am J Vet Res ; 36(2): 227-8, 1975 Feb.
Article in English | MEDLINE | ID: mdl-1111389

ABSTRACT

Homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined in the cerebrospinal fluid (CSF) of 28 normal calves and 29 spastic calves. Concentrations of HVA were significantly (P less than 0.01) lower in spastic calves, whereas differences in 5-HIAA concentrations were not found between normal and spastic calves. These findings indicate that a lower dopaminergic metabolism takes place in the central nervous system (CNS) of spastic calves.


Subject(s)
Cattle Diseases/cerebrospinal fluid , Homovanillic Acid/cerebrospinal fluid , Hydroxyindoleacetic Acid/cerebrospinal fluid , Muscle Spasticity/veterinary , Phenylacetates/cerebrospinal fluid , Animals , Cattle , Muscle Spasticity/cerebrospinal fluid
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