G. D'Aleo

Favorable response to intrathecal, but not oral, baclofen of priapism in a patient with spinal cord injury.

Study Design. Case report. Objective. To retrieve data about the utility of intrathecal baclofen for the treatment of otherwise refractory priapism that may occur in patients with spinal spasticity. Summary of Background. Baclofen exerts well-known inhibitory effects on sexual function both in animals and humans. This observation led to the introduction of oral baclofen in the treatment of refractory and recurrent idiopathic priapism. Methods. We report a 41-year-old male patient who sustained a severe traumatic spinal cord injury in a motor vehicle accident. On clinical examination he presented with tetraplegia (motor level C3). Initial cervical magnetic resonance imaging showed a C3 to C4 lesion with a herniated disc and compression of the dural sac. One month later the patient developed priapism episodes. Results. He received oral baclofen with only minimal beneficial effect on priapism. Eight months postinjury the patient underwent a test-trial with intrathecal baclofen bolus, which caused absence of priapism for 10 hours. One month later, an intrathecal pump system was implanted, leading to absence of priapism episodes. Conclusion. In the present case report, reduction of supraspinal control on the spinal cord may have induced an up-regulation of GABAB receptors, which are involved in penile tumescence. The trauma induced also liberation of penile reflexes with episodes of priapism. Normal full blood count and color duplex ultrasonography of the penis excluded a vascular genesis of priapism. This is the first report about the utility of intrathecal baclofen for the successful control of otherwise untreatable priapism in a patient with severe spinal spasticity. Hence, evaluation of intrathecal baclofen should be considered in patients suffering from severe and/or frequent priapism when oral baclofen and/or hormonal therapy are ineffective. The beneficial effect of intrathecal, but not oral baclofen, in our patient suggests a dose-dependent effect.

Sativex in the Management of Multiple Sclerosis-Related Spasticity: Role of the Corticospinal Modulation

Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS). This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement. Nevertheless, since the clinical assessment may not be sensitive enough to detect spasticity changes, other more objective tools should be tested to better define the real drug effect. The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits. To this end, 30 MS patients underwent a complete clinical and neurophysiological examination, including the following electrophysiological parameters: motor threshold, motor evoked potentials amplitude, intracortical excitability, sensory-motor integration, and Hmax/Mmax ratio. The same assessment was applied before and after one month of continuous treatment. Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms. Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability.

Topiramate modulation of R3 nociceptive reflex in multiple sclerosis patients suffering paroxysmal symptoms

Sirs: Painful paroxysmal symptoms (PS) have been linked with multiple sclerosis (MS) ever since the earliest reports of the disease; they include trigeminal neuralgia, painful tonic spasms and dysesthetic or paresthetic symptoms [7, 14]. Topiramate (TPM) is a third generation, well-tolerated antiepileptic drug [13] found to be effective for refractory intercostal neuralgia [1] and trigeminal neuralgia in MS patients [15]. No neurophysiological evaluation of the effects of TPM on PS in MS has been performed. A close relationship has been found between the subjective sensation of pain, the R3 component of the blink reflex and the pain threshold on electrical stimulation of the supraorbital nerve [9–12]. Not all authors accept this reflex as a measure with which to evaluate pain [5]. However, no neurophysiological test regarding pain measurement is at present accepted by all authors. Previously, we studied this reflex in MS patients and found it to be a good tool for evaluating the nociceptive system in this disease without [3] and with [2] antiepileptic drug therapy. In order to reduce these limitations, we evaluated the effects of TPM on the nociceptive system of MS patients suffering PS, by means of the R3 component of the blink reflex associated with the Visual Analogue Scale (VAS) [4]. A study was performed on 13 clinically diagnosed [8] MS patients (Table 1), 5 males, 8 females (mean age 37.2 years), with Expanded Disability Status Scale (EDSS) score [6] between 1.5 and 7.0 (mean 4,2). All were suffering PS with VAS ≥ 6: 4 had trigeminal neuralgia, 5 painful tonic spasms, and 4 dysesthetic-paresthetic symptoms. All were being followed up as outpatients at the MS Ambulatory of Study and Treatment Center for Long-Stay Neurological Patients (of the Chair of Neurophysiopathology, University of Messina). None of the patients were in relapse at the time of the study, nor had they experienced a relapse for at least one month, nor had they been treated with any drugs for at least one month. R3 reflex and the VAS were performed at TPM therapy onset day (before the first administration) and after 12 weeks’ treatment, all at the same hour. TPM was administered twice daily. The initial dose was 50 mg/day. The daily dose was increased by 50 mg each week until the optimal one was achieved (good response: VAS ≤ 3, no severe and persistent, > 24 hours, side effects). Prior to the R3 reflex recording, the patients were informed about the procedure of the test in order to obtain their maximum collaboration. They were asked to lie supine on a bed in a quiet room with their eyes closed and to relax. The room temperature was maintained between 22–24°C. The skin surface was cleaned carefully prior to application of the surface electrodes, which were tightly fixed to the skin with electrolytic gel. The skin temperature was maintained at 32–34°C. The right supraorbital nerve was transcutaneously stimulated by surface electrodes. The cathode was placed over the supraorbital notch on the right; the anode was placed 2 cm higher and rotated laterally at an oblique angle to avoid spread of current to the controlateral supraorbital nerve. Stimulation consisted of a 300 Hz train of rectangular pulses, 20 ms train duration (6 stimuli), 0.1 ms LETTER TO THE EDITORS

Sexual Dysfunction Induced by Intrathecal Baclofen Administration: Is This the Price to Pay for Severe Spasticity Management?

INTRODUCTION Intrathecal administration of baclofen (ITB) is widely recognized as an effective treatment for severe spasticity of both spinal and supraspinal origin with fewer side effects. The lower drug dosages used for spinal intrathecal administration, acting directly on the receptor sites, result in greater therapeutic efficacy with less systemic toxicity than with oral preparations. AIM This study aims to prospectively evaluate the effects of ITB on erectile function in male patients affected by severe spasticity. METHODS Twenty adult male patients, with a 34.85 ± 10.27 mean age, affected by severe spasticity mainly due to spinal cord lesions (10 traumatic, three vascular, six degenerative, and one congenital in origin) and treated with ITB, were enrolled in the study. All participants underwent specific clinical scales to evaluate force, muscle tone, cognition and mood, and specific sexual questionnaires, including an accurate semi-structured interview. MAIN OUTCOME MEASURE The International Index of Erectile Function (IIEF) was used to evaluate sexual function before and after pump implantation. RESULTS A comparative analysis of the neurological scales and psychometric scores at T1 (baseline) and T2 (follow-up) showed statistically significant differences before and after pump implantation. In particular, we noted a significant decrease in the IIEF median scores (from 0.42 ± 0.07 to 0.14 ± 0.02, P value < 0.0001) and a correlation between ITB dosage and IIEF scores (ρ = -0.60; P < 0.05). CONCLUSIONS This study supports previous findings on a possible negative effect of ITB on sexual function, with regard to erection. Patients who are considering ITB for treatment of severe spasticity should be informed about possible but reversible sexual side effects, especially at higher dosage. Future studies with larger samples should be fostered to confirm these findings for a better management of these, often young, patients.

Cardiovascular alterations heralded by intrathecal baclofen bolus

We describe two patients in whom serious bradycardia and arterial hypotension occurred after a small intrathecal baclofen (ITB) test bolus. Both patients suffered from severe spasticity (one due to brain injury, one due to spinal cord injury). Medical history and diagnostic examinations revealed no previous cardiological problems. Ten minutes following a 50 μg ITB bolus, patient 1 developed bradycardia (58 bpm) and incomplete right branch block, lasting for 3 hours. In patient 2, a 20 μg ITB bolus was followed after 5 minutes by severe bradycardia (30 bpm) and hypotension (60/30 mmHg), without loss of consciousness, lasting for 10 minutes. Exaggerated muscle tone was alleviated in both patients after 2 hours by the applied doses. Neither patient underwent implantation of a permanent pump system, both were continued on oral baclofen. Despite numerous unremarkable repeat cardiological exams, both patients suffered fatal cardiac arrest one and two months later, respectively. Our observations suggest that ITB may herald cardiovascular dysfunction in predisposed patients. Careful cardiological examination before ITB treatment, and close monitoring during ITB testing in particular, is advised.

Effects of felbamate on brain polyamine changes following transient cerebral ischemia in the Mongolian gerbil

We sought to determine whether treatment with felbamate was capable to reduce the accumulation of putrescine induced by transient forebrain ischemia in the Mongolian gerbil. Gerbils underwent 10 min ligation of common carotid arteries followed by recirculation. Immediately after the release of the arterial occlusion, felbamate (75 and 150 mg kg−1 i.p.) was administered. Putrescine and polyamine levels were measured in hippocampus and striatum at 1, 8, 24 and 48 h after recirculation. Putrescine levels appeared enhanced already 8 h after the release of the arterial occlusion and kept increasing up to 48 h in the hippocampus and striatum. No significant changes in spermidine levels during recirculation were detected. Conversely, spermine appeared to decrease in the hippocampus while it did not show changes in the striatum. Felbamate significantly reduced the ischemia induced changes in putrescine brain content only at the dose of 150 mg kg−1 i.p.