Botulinum toxin type A in cervical dystonia.

Cervical dystonia is a syndrome characterized by anomalous postures and unintentional repetitive movements of the head and the neck. Aim of this study is to show the effectiveness of the combined treatment botulinum toxin-FKT through the use of a recent methodic of investigation, myoton, and of the classical clinical evaluations, such as Tsui and VAS scales. 15 patients (9 females, 6 males) have been selected. During the initial visit and in the following controls, performed every month, patients have been submitted to physiatric examination, clinical evaluation of the dystonia through the Tsui scale, clinical evaluation of the pain through the VAS scale, myometric evaluation. We obtained a statistical reduction of muscular tone values in passive elongation (t0=16,34±1,23) until 4 month (t4 =16,11±1,23), when we performed a second infiltration. After 4 months from the second infiltration (t8=15,99±1,11) value did not present more some statistical correlation and was necessary to perform a new infiltration. Values of elasticity, stiffness, Tsui and VAS scale followed the same course of the tone. Our study demonstrates that combined treatment botulinum toxin-FKT is effective. It emerges that if to the treatment with botulinum toxin follows a suitable FKT treatment, the effect of the drug lasts 4 months and not 3 months as described by the literature. Our study has underlined that using myometric measurement we can consider least changes in muscular tone, elasticity and stiffness; we have a broader view of the spastic muscle, and we can better plan appropriate rehabilitative care for each patient.

Treatment of upper limb spasticity after stroke: one-year safety and efficacy of botulinum toxin type A NT201.

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.

Combined antimuscarinics for treatment of neurogenic overactive bladder.

Antimuscarinic drugs are the first line pharmacotherapy for overactive bladder, but they are not always effective to achieve complete continence. Nevertheless in some patients urodynamic investigations reveal insufficient effects with continuing incontinence events even with dose optimization. The aim of this study is to evaluate the effect of association of Oxybutynin chloride, Trospium chloride and Solifenacin succinate administered orally for a minimum of 12 weeks in subjects with suprasacral spinal cord injury with urge-incontinence, urodynamic–proven neurogenic detrusor overactivity dysfunction and detrusor-external sphincter dyssynergia to improve level of continence, reduce the risks of urologic complications and enhance QOL. This study was a randomized, double blind, controlled, balanced-parallel-groups investigation of orally administed Oxybutynin in addition to Trospium chloride in the first group and Oxybutynin in addition to Solifenacin in the other group. A total of 12 patients with neurogenic detrusor overactivity and clean intermittent catheterization were allocated into two treatment groups: 5 mg tablet of Oxibutinin and 20 mg tablet of Trospium Chloride were administered respectively 3 times a day and 4 times a day in the first group (Group A). 5 mg tablet of Oxibutinin and 10 mg tablet of Solifenacin were administered respective 3 times a day and once daily in the second group (Group B). In both group of patients we found a significant decrease in incontinence episodes, with an improvement of bladder compliance, bladder capacity and volume voided. Side effects were higher in patients of group B, but in generally well tolerated. In conclusion, a combined antimuscarinic treatment might be a right option for patients affected by neurogenic bladder refractory to previous antimuscarinic monotherapy, and might slow down or delay other more invasive treatments.

Associated with intrathecal baclofen treatment and duloxetine in patients with multiple sclerosis.

Baclofen is now used in treatment of patients with severe spasticity secondary to neurological diseases through the direct infusion of the drug into the subarachnoid space with an implanted programmable pump. Among patients whose quality of life improved after the use of intrathecal systems, a very important role belongs to people with multiple sclerosis (MS): a disease that due to a great variety of symptoms and signs, seriously affects the activities of daily living. Among the clinical manifestations of MS are also found mental health problems including depression mood. The drugs most commonly offered, for treatment of depression in patients with MS, are selective serotonin reuptake inhibitors (SSRIs), reuptake inhibitors of serotonin and norepinephrine (SNRIs) and tricyclic antidepressants (TCA). Duloxetine presents a high affinity for transporters reuptake of serotonin and noradrenalin, and exerts its activity on both molecules. In addiction, Duloxetine has demonstrated very effective in treatment of depressive disorders of mood as demonstrated by scientific evidences about the utility of Duloxetine in the modulation of painful physical symptoms associated with depression and in treatment of pain associated with diabetic neuropathy. The purpose of our study is to evaluate the effects of antidepressant therapy with duloxetine, 60 mg/day in 7 patients with multiple sclerosis treated with intrathecal baclofen for spastic modulation of tone. The experience we gained, according to data from several multicenter trials confirmed the efficacy of Baclofen intrathecally administered, especially with regards to modulation of spasticity. Our study also showed, although the limitations of a small sample size still, a good clinical response to combined treatment Baclofen intrathecal/duloxetine 60 mg/day.

Successful extension of assessment and rehabilitation intervention for an adolescent with postcoma multiple disabilities through a learning setup.

Prior to the beginning of this study, the participant (an adolescent with postcoma multiple disabilities) had learned to use a forehead-skin response to access environmental stimuli. These learning data seemed to indicate a minimally conscious state (i.e., awareness of the link between response and stimuli) in spite of 1) a previous diagnosis of postcoma vegetative state; and 2) concomitant electrophysiological measurement showing no evidence of a passive P300 response and of mismatch negativity. The present study was an effort to extend the early learning investigation with two additional responses and related stimuli to broaden learning evidence and ascertain possible choice behavior. Results indicated that the participant learned the new responses and also provided evidence of choice behavior. These data were discussed in terms of the usefulness of the learning paradigm in the assessment and rehabilitation of persons with postcoma multiple disabilities and consciousness disorders.

Bridges between nervous and immune systems: their disconnection and clinical consequences.

Nervous and immune systems are connected by several mutual links, thus constituting a diffuse functional network in the body. In particular, neurohormones, neuropeptides, and cytokines represent the major mediators of the so-called psychoneuroendocrinoimmune axis. In this review, special emphasis is placed on certain pathologies characterized by a disconnection of the existing bridges between nervous and immune systems. For instance, spinal cord injury (SCI) is a clinical condition in which loss of neurons and very poor axon growth represent the main features. The role played by infiltrating and resident immunocompetent cells is still debated in SCI. However, to enhance axon growth in SCI, current therapeutic attempts are based on the stimulation of the immune response within the central nervous system, thus triggering either cell-mediated or humoral immune responsiveness.

Immunohistochemical localisation of tear lipocalin in human nasal mucosa.

Lipocalins are low molecular weight soluble proteins, a sub-class of this family are the odorant binding proteins (OBPs) which are postulated as having an important role in the perireceptor events of olfactory transduction, though their specific physiological function has yet to be defined. From the nasal mucus of normal subjects we recently isolated a 19kDa protein, the amino-acid sequence of which, limited to the first 20 residues, is identical to that of tear lipocalin. In this study we performed an immuno-histochemical investigation on the nasal localisation of this protein, using tissue specimens taken from the inferior (27 samples), middle (7 samples) and superior turbinates (6 samples) in 27 patients undergoing septoplastic surgery. The protein was detected in the sub-epithelial tubulo-acinar glands of the nasal mucosa, particularly in the mucoserous glands, in 74% of the specimens taken from the inferior turbinate, in 71.4% of those from the middle turbinate and in 66.6% of the samples of superior turbinate tissue. The homogeneous distribution of this protein in the nasal mucus could imply that it functions as a general protection agent rather than as an odour carrier or transducer.

Evaluation of hypothalamic-pituitary-adrenocortical hormones and inflammatory cytokines in patients with persistent vegetative state.

Hypothalamic-pituitary-adrenocortical hormones, i.e. prolactin (PRL), human growth hormone (hGH), thyroid stimulating hormone (TSH), and Cortisol and plasma levels of cytokines, i.e. tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and interleukin-6 (IL-6), were assessed in 27 patients with persistent vegetative state (PVS) and in 16 outcome patients. In comparison with normal parameters, plasma levels of TSH were not significantly altered, while elevated basal hGH concentrations in 48.1% of PVS subjects and depressed cortisol levels in all PVS individuals and in patients who emerged from coma (outcome patients), respectively, were observed. In addition, higher TNF-alpha plasma levels in PVS subjects than in outcome patients and in healthy donors were found, while IL-1 beta plasma levels were elevated in both groups of patients in comparison with healthy controls. Of interest, in 55% PVS male patients hyperprolactinemia was observed, whereas in outcome patients more than six months these values were within normal range. In four patients, who emerged from coma in the course of this study, prolactin plasma levels were followed-up and increased basal values progressively fell to normal range within six months.

Impairment of non-specific immunity in patients in persistent vegetative state.

In fourteen patients in persistent vegetative state (PVS) immune responsiveness was investigated. In particular, we studied the relationship between brain lesions following traumatic injury and immune system. In this respect, phagocytosis and killing of Candida albicans by polymorphonuclear cells (PMN) and monocytes were tested. In addition serum levels of Interferon-gamma (IFN-gamma) were evaluated. The patients come out from PVS by 3-4 month were used as control group. Data shown a profound impairement of phagocytosis and killing of monocytes and low serum levels of IFN gamma when compared with normal values. Taken together, these findings suggest that brain lesions, may affect non-specific immune response.

CDP-choline in the treatment of chronic cerebrovasculopathies.

Ninety-two patients affected by chronic cerebrovasculopathy were treated with cytidine diphosphate choline (CDP-choline) 1000 mg/day i.m. or with placebo, in a double-blind study. Two cycles of therapy of 4 weeks each were performed, with an interval of 1 week. There were 46 patients in each group with chronic cerebrovascular diseases, and the two groups were comparable as far as mental deterioration was concerned. The following psychometric tests were administered: Toulouse-Piéron (attention to non-verbal stimuli), Randt Memory test (memory), Sandoz Clinical Assessment of Geriatrics (SCAG, measurement of the behavioral and emotional control). The comparison between the two groups revealed significant improvements in the CDP-choline group compared with the placebo group in some of the attention capabilities (decrease in the number of wrong answers at the Toulouse-Piéron test), of the mnemonic capabilities ('General Information' subtest of Randt Memory test) and behavioral capabilities (SCAG 'affective disturbances' score). No side-effects were detected in the CDP-choline group.

Urodynamic evaluation of 12 ataxic subjects: neurophysiopathologic considerations.

Twelve ataxic subjects (seven with Friedreich's heredo-ataxia and five with a cerebellar vascular or traumatic lesion) were examined by way of urodynamic evaluation. The results explain the role the cerebellum plays in the modulation of the micturition reflex and confirm the importance of bilateral encephalic damage in causing vesico-sphincteral malfunctioning and the important role of the lateral myelon cords in transporting bladder proprioceptive sensitivity.

Psychopathological aspects and emotional behavior in right brain-damaged patients.

We investigated 20 right brain-damaged (RBD) patients and 10 controls with chronic motor deficits for differences in anxiety and depression, measured by psychometric tests, and in aspects of emotional behavior, gauged from videorecordings. We found no group differences in the psychometric scores but, when we correlated these with the behavior scores, we found significant differences in the expression of depression (absent only in RBD patients) and in attitude to illness, ie joking and unconcern (present only in RBD patients). In both groups emotional gesture, facial expression and prosody proved on qualitative analysis to be interrelated, thus demonstrating that emotional behavior has a single cortical-subcortical substrate.