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R Eleopra

Publications and source records attributed to R Eleopra.

At least 19 recordsLinked to original sources

Clinical use of non-A botulinum toxins: botulinum toxin type B.

Botulinum neurotoxin type B (BT, BT-B) has been used as NeuroBloc/MyoBloc since 1999 for treatment of cervical dystonia, hyperhidrosis, spastic conditions, cerebral palsy, hemifacial spasm, bladder dysfunction, spasmodic dysphonia, sialorrhoea, anal fissures, piriformis syndrome, various pain conditions and cosmetic applications. Generally, its therapeutic effects are comparable to BT type A (BT-A). The adverse effect profiles of BT-B and BT-A, however, differ considerably. BT-B has been found to produce more regional as well as systemic anticholinergic adverse effects, such as dryness of mouth, accommodation difficulties, conjunctival irritation, reduced sweating, dysphagia, heartburn, constipation, bladder voiding difficulties and dryness of nasal mucosa. In BT-B the relationship between autonomic and motor effects known from BT-A is substantially shifted towards autonomic effects. BT-B, therefore, should be used carefully in patients with autonomic disorders and in patients with concomitant anticholinergic therapy. If NeuroBloc/MyoBloc is used to treat cervical dystonia patients with antibody-induced failure of BT-A therapy, 86% of those will develop complete secondary therapy failure after five applications. If NeuroBloc/MyoBloc used to treat cervical dystonia patients without prior exposure to BT, 44% of those will develop complete secondary therapy failure after nine applications. NeuroBloc/MyoBloc, therefore, is associated with substantial antigenicity problems originating from a particular low specific biological potency. Systemic anticholinergic adverse effects and high antigenicity limits the clinical use of NeuroBloc/MyoBloc considerably.

Animals↗

Clinical use of non-A botulinum toxins: botulinum toxin type C and botulinum toxin type F.

Botulinum neurotoxin (BoNT) serotype A is commonly used in the treatment of focal dystonia, but some patients are primarily or become secondarily resistant to it. Consequently, other serotypes have to be used when immuno-resistance is proven. In the literature, patients with focal dystonia have been treated with BoNT serotype F with clinical benefit but with short lasting effects. Recently, BoNT serotype C has been used with positive clinical outcome. An update on the clinical use of BoNT serotype F and BoNT serotype C is provided.

Adult↗

Explosive-aggressive behavior related to bilateral subthalamic stimulation.

We describe a patient with Parkinson's Disease who underwent bilateral subthalamic nucleus deep brain stimulation and later presented with episodes of aggressive behavior disorder with disturbed impulse control and an inability to control anger likely related to the deep brain stimulation "switch-on stimulation". We hypothesize that increasing voltage intensity could influence neighboring passing fibers coming from basal limbic system that are involved in the regulation of affect and emotional behavior. We suggest investigating these neuropsychological disturbances considering their influence on quality of life after surgery.

Aggression↗

Recovery cycle of the masseter inhibitory reflex after magnetic stimulation in normal subjects.

OBJECTIVE: To evaluate the differences in the recovery cycle of the masseter inhibitory reflex (MIR) obtained with electrical and magnetic stimulation. METHODS: In 31 healthy subjects we studied the MIR evoked by electrical or magnetic stimulation of the mental territory and the recovery cycle of this reflex with the paired stimuli technique at different interstimulus intervals (ISI), between 100 and 600 ms. RESULTS: Latency and area of the early and late silent periods (SPs) of the MIR were similar after electrical and magnetic stimulation. The recovery cycle of the test late SP was similar with the two kinds of stimulation, except for short ISIs. The main difference between the two kinds of stimulation was in the painful quality of the stimulus: the magnetic stimuli were always below pain threshold. CONCLUSIONS: As with electrical stimulation, it is possible to obtain a MIR with magnetic peripheral stimulation. The magnetic paired stimuli are equally effective in the evaluation of the recovery cycle of the MIR. The results demonstrate that magnetic stimulation is a useful tool in the evaluation of excitability of the trigeminal motoneuronal system, with little discomfort for the patient. They also confirm the unlikelihood of nociceptive afferences involvement.

Adult↗

Neurophysiological study of corticomotor pathways in restless legs syndrome.

OBJECTIVE: To test the variations in cerebral motor excitability in patients with primary restless legs syndrome (RLS) by using electrophysiological techniques. In RLS patients periodic legs movements (PLMs) in sleep and wake have been described and it is hypothesised that PLMs result from a sleep-related disinhibition of descending central motor inhibitory pathways. Moreover, in primary RLS, these modifications are still debated. METHODS: In 15 patients with primary RLS, transcranial magnetic stimulation (TMS) was carried out using several paradigms, particularly paired pulse TMS with short interstimulus intervals (ISI) in abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. RESULTS: Short ISI paired TMS showed a significant decrease in inhibition and increase in facilitation in ADM muscles. This result was even more evident in TA muscles of patients as compared to the controls and these modifications were more evident in the limbs which were more affected by PLM. Moreover, intracortical (corticocortical) inhibition (ICI) and intracortical facilitation (ICF) unchanged their biphasic time course. CONCLUSIONS: In our study the changes in short paired-pulse ICI and ICF revealed the presence of an altered excitability of central motor pathways, with good correlation with asymmetric distribution of symptoms.

Adult↗

The role of gustatory flushing in Frey's syndrome and its treatment with botulinum toxin type A.

After parotid surgery, gustatory sweating and flushing occur more frequently, the former reportedly in 15-100% of cases, while no reliable data are available for the latter. Although botulinum toxin (BoNT) is effective in controlling sweating, little is known about its effect on flushing. In 17 patients suffering from Frey's syndrome after parotid surgery, we studied the gustatory flushing phenomenon as compared to gustatory sweating, analyzing their frequency, area, type of stimulus and response to BoNT administration. Cutaneous blood flow (CBF) was monitored by laser Doppler flowmetry (LDF) on affected and unaffected areas of the cheek in basal conditions and after meals, before and then 1 month after starting the BoNT injections. The Minor test was used to identify the sweating area. Flushing was observed in 7 of 17 patients after masticatory activity, spicy meals or citrus fruits. No clinical data correlated with any presence of flushing. Flushing regressed completely after BoNT administration and CBF reached similar values in the affected and unaffected sites. No adverse effects were observed. BoNT administration proved an effective and safe treatment for gustatory sweating and flushing in patients with Frey's syndrome.

Adult↗

Hyperhidrosis and sympathetic skin response in chronic alcoholic patients.

Palmoplantar hyperhidrosis is frequently observed in patients with a clinical history of chronic abnormal alcoholic intake. It can be related to peripheral or central mechanisms such as abnormal spontaneous activity in peripheral damaged fibres; receptor hypersensitivity; compensatory incremented activity in segmentary anhidrosis; or impairment of central sweat control. With the aim of quantifying this phenomenon and of identifying its possible origin, sympathetic skin response (SSR) analysis was performed in 20 chronic alcoholic patients with clinical diffuse acral hyperhidrosis, compared with 30 normal subjects and 2 patients affected by primary palmoplantar hyperhidrosis (PPH). SSRs were recorded by disc electrodes place on the hands and feet, simultaneously. At the hand level two recording sites were selected: palm-dorsum proximally and ventral-dorsal tip of the third finger distally. Attention was paid to the number of SSR after a single endogenous or exogenous stimulus. The alcoholic patients were divided into two groups, with and without mild polyneuropathy. Both patient groups showed synchronous SSR at recording sites, with the same pattern and the normal delay between upper and lower arms. In the control group one response was generally related to a single stimulus; if more responses were elicited an evident adaptation was shown; in the two groups of patients an increase of the waves was observed in all the recording sites without any adaptation. The SSR profile described in alcoholic patients was observed also in PPH. The pattern of SSR waves in alcoholic patients seems to suggest a possible central origin of this type of hyperhidrosis.

Adolescent↗

Different time courses of recovery after poisoning with botulinum neurotoxin serotypes A and E in humans.

Botulinum toxin serotypes A and E (BoNT/A and /E) cleave the carboxy-terminus of synaptosomal associated protein-25 (SNAP-25) removing nine and 26 residues, respectively. To investigate the effect of these lesions of the same target molecule, 11 volunteers were injected with 3 IU of BoNT/A in the extensor digitorum brevis (EDB) muscle of one foot and with 3 IU of BoNT/E in the contralateral one. In addition, seven volunteers were similarly injected with mixtures of BoNT/A + BoNT/E. Compound muscular action potential (CMAP) was measured at different time intervals and the percentage variation of CMAP (%CMAP) was calculated. Unexpectedly, a much faster recovery of %CMAP after BoNT/E injections was observed. Double poisoned EBD muscles recovered similarly to BoNT/E. So, a larger deletion of the SNAP-25 molecule caused by BoNT/E leads to a faster functional recovery.

Action Potentials↗

On the action of botulinum neurotoxins A and E at cholinergic terminals.

Botulinum neurotoxins type A and E (BoNT/A and /E) are metalloproteases with a unique specificity for SNAP-25 (synaptosomal-associated protein of 25 kDa), an essential protein component of the neuroexocytotic machinery. It was proposed that this specificity is based on the recognition of a nine-residue sequence, termed SNARE motif, which is common to the other two SNARE proteins: VAMP (vesicle-associated membrane protein) and syntaxin, the only known substrates of the other six clostridial neurotoxins. Here we report on recent studies which provide evidence for the involvement of the SNARE motif present in SNAP-25 in its interaction with BoNT/A and /E by following the kinetics of proteolysis of SNAP-25 mutants deleted of SNARE motifs. We show that a single copy of the motif is sufficient for BoNT/A and /E to recognise SNAP-25. While the copy of the motif proximal to the cleavage site is clearly involved in recognition, in its absence, other more distant copies of the motif are able to support proteolysis. We also report on studies of poisoning human neuromuscular junctions with either BoNT/A or BoNT/E and describe the unexpected finding that the time of recovery of function after poisoning is much shorter in the case of type E with respect to type A intoxication. These data are discussed in terms of the different sites of action of the two toxins within SNAP-25.

Animals↗

Botulinum neurotoxin serotype C: a novel effective botulinum toxin therapy in human.

Botulinum neurotoxin (BoNT) serotype A is commonly used in the treatment of focal dystonia. Nevertheless, some patients are or become resistant to this serotype. Consequently, other different serotypes have to be used. A comparison of the neuromuscular blockade induced by BoNT type A and C in the extensor digitorum brevis muscles of voluntary subjects was studied, by evaluating the amplitude variation over the time (until 90 days) of the compound muscular action potential elicited by supramaximal electrical stimulation of the peroneal nerve at the ankle. A very similar effect and temporal profile, was observed for each serotype. On this basis, two patients with idiopathic facial hemispasm and one with blepharospasm were treated with BoNT serotype C with very beneficial long lasting effects.

Adult↗

The variability in the clinical effect induced by botulinum toxin type A: the role of muscle activity in humans.

When botulinum toxin (BT) is administered for the first time at fixed doses, variable clinical responses can be observed in patients with the same form of dystonic disorder. Many factors may contribute to this phenomenon, including the variability rate of absorption of the drug. Animal experimental models (rat diaphragm preparation) have demonstrated an increased absorption of BT in the terminal nerve endings of the muscle under repetitive electrical stimulation, suggesting that "muscle activity" also may play an important role. The aim of our study was to evaluate in humans the role of the muscle activity on the variability of the effect induced by BT type A. Eleven patients with blepharospasm and idiopathic facial hemispasm were studied by using neurophysiologic techniques. In nine patients, both extensor digitorum brevis (EDB) muscles were injected with low (3 IU), fixed doses of type A BT. For the first 24 h after administration of the drug, periodic electrical stimulation of only one EDB was used. The subsequent percentage changes in compound muscle action potential (CMAP) amplitude was calculated at different intervals over a 30-day period. The percentage in the CMAP for the stimulated EDB was compared with that of the contralateral nonstimulated side. We found that the effect of the induced neuromuscular blockade was significantly greater for the stimulated side. In the other two patients, we injected BT in one EDB and the same volume of normal saline solution in the contralateral muscle to assess the stability of the CMAP in untreated muscle over time. We observed that the CMAP was unchanged in the untreated EDB; therefore we concluded that muscle activity plays an important role in the variability of clinical response often seen.

Adult↗

The therapeutic use of botulinum toxin.

Since Alan Scott's research, botulinum toxin (BoNT) has been used in several diseases or conditions characterised by muscular overactivity. BoNT acts on either neuromuscular or autonomic cholinergic junctions. Seven different serotypes are known, with antigenic specificity and different therapeutic profiles. BoNT is made up of a heavy chain, involved in binding and membrane translocation, and a light chain, involved in blocking neuroexcytosis. Each serotype shares a specific acceptor on the presynaptic membrane of a cholinergic junction. The available BoNT preparations differ in toxicity, purity and stability. Injection of the neurotoxin produces several modifications at a neuromuscular junction. Axonal sprouting, muscular fibre atrophy, and new end-plates are the most evident histological events after BoNT treatment. They appear to be reversible in untreated muscles. Diffusion can occur at first by haematogeneous or local BoNT spread. Several factors, such as dose, volume, site of injection, muscle size, and muscular fascia, can influence the amount of diffusion and possible side-effects. After prolonged BoNT treatment patients can become unresponsive. Antibodies directed against BoNT have been observed with ELISA or mouse bioassay. Different serotypes have been used to treat non-responder patients. Novel toxins with lower immunogenicity and prolonged clinical efficacy are required for more effective treatment.

Journal Article↗

Botulinum toxin treatment in the facial muscles of humans: evidence of an action in untreated near muscles by peripheral local diffusion.

In a population of subjects with blepharospasm and facial hemispasm treated for the first time with botulinum toxin type A (BT) in the orbicularis oculi muscle, we performed an electrophysiologic study (compound muscle action potential and motor evoked potential) to assess whether BT effect could be detected in near untreated muscles (orbicularis oris and masseter). There was a significant BT action in nearly untreated muscles with different peripheral innervation that can be explained by local diffusion of the drug.

Action Potentials↗

Cryoglobulinemic neuropathy related to hepatitis C virus infection. Clinical, laboratory and neurophysiological study.

Peripheral neuropathy is frequently reported in mixed cryoglobulinemia. As a close relationship has been established between mixed cryoglobulinemia and hepatitis C virus (HCV), the clinical, neurophysiological, and serologic findings of five patients affected by neuropathy, cryoglobulinemia and HCV infection were investigated. HCV infection was ascertained by the presence in the serum of anti-HCV antibodies detected by enzyme-linked immunosorbent assay(ELISA), and of HCV RNA assessed by polymerase chain reaction (PCR). Initial symptoms included paresthesias and painful dysesthesias in the legs. Later on, the patients developed a mainly asymmetric axonal polyneuropathy or a multifocal neuropathy associated with signs of systemic vasculitis. In this case series we report the short-term prognosis, as well as the response to interferon (IFN) alpha and conventional treatment. The presence of HCV RNA supports the hypothesis that a persistent HCV infection might be involved in the pathogenesis of mixed cryoglobulinemia and cryoglobulinemia-associated disorders.

Adult↗