Phase 2 trial of sustained-release fampridine in chronic spinal cord injury.

STUDY DESIGN: Double-blind, randomized, placebo-controlled, parallel-group clinical trial. OBJECTIVE: Assess safety and efficacy of sustained-release fampridine in subjects with chronic spinal cord injury. SETTING: A total of 11 academic rehabilitation research centers in the United States. METHODS: A total of 91 subjects with motor-incomplete spinal cord injury (SCI), randomized to three arms: fampridine, sustained release, 25 mg b.i.d. (Group I), 40 mg b.i.d. (Group II), and placebo (Group III) for 8 weeks. OUTCOME MEASURES: Patient diary questionnaire, Ashworth score, American Spinal Cord Injury Association International Standards, International Index of Erectile Function, bladder and bowel management questionnaires, and Clinician and Subject Global Impressions (Clinician Global Impression of change, Subject Global Impression (SGI)). Safety was evaluated from adverse events, physical examinations, vital signs, electrocardiograms, and laboratory tests. RESULTS: In total, 78% of the subjects completed the study. More (13/30) discontinued from Group II than Group I (4/30) and Group III (3/31). The most frequent adverse events across groups were hypertonia, generalized spasm, insomnia, dizziness, asthenia, pain, constipation, and headache. One subject in Group II experienced a seizure. SGI changed significantly in favor of Group I (P=0.02). Subgroup analysis of subjects with baseline Ashworth scores >1 showed significant improvement in spasticity in Group I versus III (P=0.02). CONCLUSIONS: Group I showed significant improvement in SGI, and potential benefit on spasticity. The drug was well tolerated. Group II showed more adverse events and discontinuations.

Effects of level and degree of spinal cord injury on male orgasm.

DESIGN: Controlled, laboratory-based analysis. OBJECTIVE: To determine the impact of spinal cord injuries (SCIs) on the ability to achieve male orgasm. SETTING: US academic medical center. METHODS: A laboratory-based analysis of the ability of 45 men with SCIs and 16 able-bodied control subjects to achieve orgasm coupled with a detailed neurologic examination, history and physical examination, and administration of the International Index of Erectile Function. RESULTS: Men with SCIs were less likely than controls to achieve orgasm. Mean latency to orgasm, blood pressure and heart rates at orgasm were not significantly different between controls and SCI subjects. Men with incomplete SCIs were more likely to achieve orgasm than those with complete SCIs. A disconnect was noted between the presence of orgasm and the presence of ejaculation. Men with complete lower motor neuron dysfunction affecting their sacral segments were less likely to achieve orgasm than men with any other patterns of SCI. CONCLUSION: These results document the ability of men with complete SCIs to achieve orgasm. Characteristics of orgasm in men with SCIs as compared to able-bodied subjects are similar. Although orgasm and ejaculation are more likely to occur together, a number of men with SCIs achieve orgasm without ejaculation. Further research should explore the possibility of retraining ejaculatory and orgasmic responses in men with SCIs.

High-dose methylprednisolone may cause myopathy in acute spinal cord injury patients.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Although Bracken et al have demonstrated a significant neuroprotective effect of high-dose intravenous (i.v.) methylprednisolone (MP) within 8 h post spinal cord injury (SCI), this practice has recently been challenged. We hypothesized it is possible that acute corticosteroid myopathy (ACM) may occur secondary to the MP. This pilot study was performed to test this hypothesis. SETTING: University of Miami School of Medicine/Jackson Memorial Hospital, Miami VA Medical Center, FL, USA. METHODS: Subjects included five nonpenetrating traumatic SCI patients, who received 24 h MP according to National Acute Spinal Cord Injury Studies (NASCIS) protocol, and three traumatic patients who suffered SCI and did not receive MP. Muscle biopsies and electromyography (EMG) were performed to determine if myopathic changes existed in these patients. RESULTS: Muscle biopsies from the SCI patients who received 24 h of MP showed muscle damage consistent with ACM in four out of five cases. EMG studies demonstrated myopathic changes in the MP-treated patients. In the three patients who had SCI but did not receive MP, muscle biopsies were normal and EMGs did not reveal evidence of myopathy. CONCLUSION: Our data suggest that MP in the dose recommended by the NASCIS may cause ACM. If this is true, part of the improvement of neurological recovery showed in NASCIS may be only a recording of the natural recovery of ACM, instead of any protection that MP offers to the injured spinal cord.

Sexual response in women with spinal cord injury: neurologic pathways and recommendations for the use of electrical stimulation.

BACKGROUND: Determination of the exact level and degree of a woman's spinal cord injury (SCI) has allowed researchers to document the aspects of sexual response that are altered with specific patterns of SCI. Based on these findings, recommendations can be made regarding the development and testing of electrical stimulation systems designed to facilitate sexual responses in women with SCI. DESIGN: Literature review. FINDINGS: Studies of the arousal stages of response indicate that psychogenic vaginal lubrication is maintained with pinprick sensation in T11-T12 dermatomes, and that reflex lubrication occurs in women with upper motor neuron injuries affecting the sacral segments. Studies of the orgasmic stage support the hypothesis that orgasm is a reflex response of the autonomic nervous system that appears to depend on an intact sacral arc. CONCLUSIONS: Laboratory studies of arousal and orgasm among women with different types of SCI, and comparisons with able-bodied controls, provide valuable information regarding female sexual neurophysiology. Electrical stimulation can be used to improve sexual response, as well as bladder and bowel function. Interventions that interfere with the sacral reflex arc, such as sacral rhizotomy, can impair the ability to achieve orgasm. To develop alternative treatment protocols, further investigation of sexual response and orgasm is recommended.

Sexual arousal and orgasm in women: effects of spinal cord injury.

Sexual disorders are common in women; however, the neurological basis of female sexual response has not been adequately investigated. This information is necessary to characterize the impact of various neurological disorders on sexual arousal in women and to develop appropriate management strategies for sexual dysfunction. To assess the spinal mediation of sexually stimulated genital vasocongestion in women, we conducted two laboratory-based, controlled analyses: (1) of women's genital, subjective, and autonomic responses to audiovisual erotic and audiovisual erotic combined with manual genital stimulation; and (2) of women's ability to achieve orgasm. Subjects included 68 premenopausal women with spinal cord injuries (SCIs) and 21 able-bodied, age-matched controls. Results indicated that preservation of sensory function in the T11-L2 dermatomes is associated with psychogenically mediated genital vasocongestion. Less than 50% of women with SCIs were able to achieve orgasm, compared with 100% of able-bodied women (p = 0.001). Only 17% of women with complete lower motor neuron dysfunction affecting the S2-S5 spinal segments were able to achieve orgasm, compared with 59% of women with other levels and degrees of SCIs (p = 0.048). Time to orgasm was significantly increased in women with SCIs compared with able-bodied controls (p = 0.049). Independent raters were unable to differentiate between subjective descriptions of orgasm from SCI women compared with controls. This information should be used when counseling women with spinal dysfunction about their sexual potential.

Neurogenic female sexual dysfunction: a review.

The effect of various spinal lesions on female sexual response has recently been investigated in detail. Studies of women with neurologic disabilities and studies of animal models have provided substantial information regarding the spinal control of sexual responses. In this report, the authors explore findings regarding the neurologic pathways underlying the spinal control of sexual arousal and orgasm. Information available about the effects of multiple sclerosis and various cerebral disorders on female sexual function will also be reviewed, with special attention to areas where further research is needed. Lastly, the current status and techniques available to improve the sexual functioning of women with neurologic disabilities affecting the central nervous system will be reviewed.

Sexual function in women with neurologic disorders.

Significant gaps remain in our understanding of the impact of most neurologic disorders, including brain dysfunction and MS. Recent methodology used to assess women with SCIs may be used as a model with which to study these other disorders. The availability of oral agents to treat sexual dysfunction in men should also stimulate research using these agents to treat sexual dysfunction in women.

Sildenafil effects on sexual and cardiovascular responses in women with spinal cord injury.

OBJECTIVES: Sexual dysfunction is common in women with spinal cord injuries (SCIs) and other neurologic conditions. Sildenafil has previously been shown to be safe and effective in the treatment of erectile dysfunction due to SCI. This study is the first to evaluate the sexual and cardiovascular effects of sildenafil in women with SCIs in a controlled, laboratory setting. METHODS: Nineteen premenopausal women with SCIs were randomly assigned to receive either sildenafil (50 mg) or placebo in a double-blind, crossover design study. Physiologic and subjective measures of sexual response, heart rate, and blood pressure were recorded during baseline and sexual stimulation conditions. Adverse events were also recorded. RESULTS: Significant increases in subjective arousal (SA) were observed with both drug (P <0.01) and sexual stimulation conditions (P <0.001), and a borderline significant (P <0.07) effect of drug administration on vaginal pulse amplitude (VPA) was noted. Maximal responses occurred when sildenafil was combined with visual and manual sexual stimulation. Cardiovascular data showed modest increases in heart rate (+/-5 bpm) and mild decreases in blood pressure (+/-4 mm Hg) across all stimulation conditions, consistent with the peripheral vasodilatory mechanism of the drug. Sildenafil was well tolerated with no evidence of significant adverse events. CONCLUSIONS: Findings suggest that sildenafil may partially reverse the sexual dysfunction commonly associated with SCI in women. Consistent with previous findings in men, the sexual effects of the drug were most evident under conditions of optimal stimulation. Mild, clinically insignificant cardiovascular effects were also noted. Further large-scale studies of sildenafil's effects in women with neurogenic sexual dysfunction are strongly indicated.

Recovery of upper-extremity strength in complete and incomplete tetraplegia: a multicenter study.

OBJECTIVE: To examine upper-extremity motor recovery of subjects with tetraplegia with both complete and incomplete injuries, to predict which patients and at what time they would recover a motor level. DESIGN: Prospective, multicenter clinical study of upper-extremity motor recovery in subjects with acute traumatic spinal cord injury. SETTING: Three regional spinal cord injury centers. SUBJECTS: One hundred sixty-seven individuals with acute traumatic tetraplegia (144 males [86%], and 23 females [14%]) between the ages of 15 and 75 years (mean age, 35.5 yrs). METHODS: Subjects were examined and classified using sequential manual muscle tests performed on admission, 72 hours, 1, 2, and 3 weeks, and 1, 2, 3, 6, 12, 18, and 24 months postinjury. C5 biceps, C6 extensor carpi radialis, C7 triceps, and C8 flexor digitorum profundus were evaluated using a 0-5 scale. Analyses of the right motor levels used a series of logistic regression models, and for multiple measurements on each subject, models were estimated using generalized estimating equations. RESULTS: The analysis for recovery of the biceps for the C4 group showed 70% of complete compared with 90% of incomplete injuries recovered (p < .001); of the extensor carpi radialis in the C5 group, 75% complete and 90% incomplete recovered (p < .002); and of the triceps in the C6 group, 85% of complete and 90% of incomplete injuries recovered (p < .16). CONCLUSION: Predicting future potential for upper-extremity motor recovery and for independence in self-care in groups of patients at a specific motor level is possible within the first week of injury.

Report of the international consensus development conference on female sexual dysfunction: definitions and classifications.

PURPOSE: Female sexual dysfunction is highly prevalent but not well defined or understood. We evaluated and revised existing definitions and classifications of female sexual dysfunction. MATERIALS AND METHODS: An interdisciplinary consensus conference panel consisting of 19 experts in female sexual dysfunction selected from 5 countries was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease. A modified Delphi method was used to develop consensus definitions and classifications, and build on the existing framework of the International Classification of Diseases-10 and DSM-IV: Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, which were limited to consideration of psychiatric disorders. RESULTS: Classifications were expanded to include psychogenic and organic causes of desire, arousal, orgasm and sexual pain disorders. An essential element of the new diagnostic system is the "personal distress" criterion. In particular, new definitions of sexual arousal and hypoactive sexual desire disorders were developed, and a new category of noncoital sexual pain disorder was added. In addition, a new subtyping system for clinical diagnosis was devised. Guidelines for clinical end points and outcomes were proposed, and important research goals and priorities were identified. CONCLUSIONS: We recommend use of the new female sexual dysfunction diagnostic and classification system based on physiological as well as psychological pathophysiologies, and a personal distress criterion for most diagnostic categories.

Sexual response in women with spinal cord injuries: implications for our understanding of the able bodied.

This study assesses the impact of psychogenic and reflex sexual arousal on women with complete and incomplete spinal cord injuries (SCIs) and explores the effects of SCI on orgasm in women. Thirty women with SCIs and 10 able-bodied women participated in the study. Three individual experiments were conducted over a 3-day period, assessing (a) the impact of SCI on psychogenic sexual arousal, (b) the impact of SCI on orgasm; and (c) the impact of SCI on reflex sexual arousal. Results support the hypothesis that women with complete SCIs and upper motor neuron injuries affecting the sacral spinal segments and women with incomplete upper motor neuron SCIs had the capacity for reflex lubrication. Women with SCIs were significantly less likely than able-bodied women to achieve orgasm. However, there was not a significant difference among women with different SCIs to achieve orgasm.

Sexual satisfaction and sexual drive in spinal cord injured women.

Levels of sexual satisfaction and sexual drive in women with spinal cord injuries were examined. Eighty-four spinal cord injured (SCI) women and thirty-seven able-bodied (AB) control subjects completed the Derogatis Sexual Functioning Inventory which measured current level of sexual functioning in 10 areas: information, experience, drive, attitude, psychological symptoms, affect, gender role definition, fantasy, body image, and sexual satisfaction. When compared with AB women, SCI women had significantly lower levels of sexual satisfaction and sexual drive and significantly higher levels of psychological symptoms and negative affect. Among SCI women, sexual satisfaction decreased significantly with age. Among AB women, sexual satisfaction increased significantly with age. Married SCI women were no longer less sexually satisfied than AB women. Results support conclusions from previous self-report studies in which significant decreases in sexual satisfaction and drive were reported for SCI women. Implications for continued research on the psychological and physiological aspects of sexuality and sexual functioning in SCI women are discussed.

Sexual functioning in the spinal cord injured.

This article reviews current knowledge about the impact of SCI on male and female sexual responses including erectile function, lubrication ejaculation and orgasm. The ability to achieve erection, lubrication and ejaculation can be described based upon the degree and type of neurologic injury affecting the sacral spinal segments. The ability of SCI individuals to achieve orgasm has not been found to be based upon the type of degree of neurologic injury. The implications of these findings to increase our understanding of human sexual neurophysiology is also discussed.

Physiologic parameters associated with sexual arousal in women with incomplete spinal cord injuries.

OBJECTIVE: To compare the physiologic sexual responses of women with incomplete spinal cord injuries (SCIs) with and without preservation of the ability to perceive T11-L2 pinprick sensation. DESIGN: Controlled laboratory-based analysis of responses to varying combinations of audiovisual erotic stimulation, manual genital stimulation, and performance of a distracting task coupled with manual genital stimulation. SETTING: The sexual physiology laboratory at our freestanding rehabilitation hospital. PARTICIPANTS: A volunteer sample of 17 women with incomplete SCIs. INTERVENTIONS: Two 78-minute protocols using 6-minute baselines alternating with 12-minute testing conditions. One protocol was designed to study the effects of psychogenic and psychogenic combined with manual sexual stimulation, while the other was designed to examine the effects of genital sexual stimulation performed in conjunction with a distracting task. DEPENDENT VARIABLES: Vaginal pulse amplitude, subjective arousal, heart rate, respiratory rate, and blood pressure. RESULTS: Subjective arousal increased in both groups of subjects with isolated audiovisual erotic stimulation; however, only those subjects with the ability to perceive T11-L2 pinprick sensation had concomitant increases in vaginal pulse amplitude. In contrast, when manual genital stimulation was added to the audiovisual erotic stimulation, both groups of subjects developed increases in vaginal pulse amplitude, whereas only those subjects with the ability to perceive T11-L2 demonstrated a further increase in their level of subjective arousal. Performance of manual genital stimulation in conjunction with a distracting task resulted in significantly increased vaginal pulse amplitude and arousal level only in those subjects with preservation of the ability to perceive T11-L2 pinprick sensation. With the changeover to masturbation, neither group of subjects developed significant increases in vaginal pulse amplitude. During masturbation, both groups of subjects had increases in their level of sexual arousal; however, only those subjects with T11-L2 pinprick preservation had a significant increase. CONCLUSIONS: Women with preservation of the ability to perceive T11-L2 pinprick sensation tended to maintain the ability for psychogenic genital vasocongestion. Psychogenic protocol results showed that all subjects appeared to develop reflex genital vasocongestion when manual stimulation was added to audiovisual erotic stimulation. Manual genital stimulation in conjunction with the performance of a distracting task only resulted in increased vaginal pulse amplitudes in those subjects with preservation of T11-L2 pinprick sensation. We believe that this was due to increased subjective sexual arousal and that the reason all subjects did not develop increased genital vasocongestion under these conditions was due to poor hand function. Further research examining women with lower levels of SCI is necessary to understand the neurophysiology of female sexual response after SCI.

Physiological parameters associated with the performance of a distracting task and genital self-stimulation in women with complete spinal cord injuries.

OBJECTIVE: To compare the physiological sexual responses of women with complete spinal cord injuries (SCI) with those of able-bodied women. DESIGN: Controlled laboratory-based analysis of responses to a distracting task coupled with manual genital stimulation versus masturbation. SETTING: The sexual physiology laboratory at our free-standing rehabilitation hospital. PARTICIPANTS: A volunteer sample of 10 women with complete SCI along with 10 able-bodied women, matched for age and educational status. INTERVENTIONS: A 78-minute protocol using 6-minute baselines alternating with 12-minute testing conditions. DEPENDENT-VARIABLES: Vaginal pulse amplitude, subjective arousal, heart rate, respiratory rate, and blood pressure. RESULTS: Subjective sexual arousal increased in able-bodied women with manual genital stimulation in conjunction with performance of a distracting task and was further augmented by removal of the distracting task and continuing with masturbation. In contrast, complete SCI subjects did not demonstrate increased subjective arousal with performance of the distracting task in conjunction with manual genital stimulation; however, they did evidence significant increases in arousal when the distracting task was eliminated. CONCLUSIONS: Genital responses tended to parallel subjective responses in able-bodied women; however, women with SCI revealed nonsignificant changes in genital responses throughout the treatment protocol. It is hypothesized that the genital and subjective responses of able-bodied subjects reflect the additive components of reflex and then psychogenic sexual arousal. Furthermore, the lack of responsivity in the SCI subjects was thought to be related to compromised upper extremity function in the majority of our subjects. Further work is necessary to validate these hypotheses.

Orgasm in women with spinal cord injuries: a laboratory-based assessment.

OBJECTIVE: To understand the characteristics and physiological sexual responses of women with spinal cord injuries (SCI) during orgasm. DESIGN: Controlled laboratory-based analysis of women's physiological and subjective responses during a single session in which they attempted to perform stimulation to orgasm. SETTING: The sexual physiology laboratory at our free-standing rehabilitation hospital. PARTICIPANTS: A volunteer sample of 25 women with SCI and 10 able-bodied control subjects, matched for age. INTERVENTION: A 75-minute protocol designed to obtain information on the physiological events accompanying orgasm. DEPENDENT VARIABLES: Included vaginal pulse amplitude, heart rate, respiration rate, blood pressure, subjective arousal and subscores on the Derogatis Sexual Functioning Inventory (DSFI). RESULTS: Data were analyzed both within and across neurological groups: complete SCI, incomplete SCI, and able-bodied controls. All able-bodied subjects achieved orgasm whereas 52% of SCI subjects achieved orgasm. Degree and type of SCI did not significantly relate to subjects' ability to achieve orgasm. Subjects with no lower extremity function took significantly longer than able-bodied subjects to achieve orgasm. Differences between baseline and orgasm readings are described for each of the major physiological measures. Results of DSFI revealed that able-bodied subjects acknowledged greater sexual satisfaction than SCI subjects. Subjects who achieved orgasm scored higher on sexual information and sex drive. CONCLUSION: Results support previous self-report studies, in that a large percentage of SCI women achieved orgasm regardless of pattern or degree of neurological injury. No consistent characteristics were identified that would allow prediction of which women with SCI would be able to experience orgasm. However, subjects who achieved orgasms had a higher sex drive and greater sexual knowledge. Implications for sex therapy treatment programs with spinal cord injured women are discussed.