|
Sexual problems
associated with neurological diseases European Federation of Neurological Societies Task Force on Neurosexology*.
Lundberg PO Swash M, Vodusek D B
Correspondence to P O Lundberg Department of Neuroscience: Neurology Tel + 46 18 611 50 26 Fax + 46 18 611 50 27 E-mail: PO.Lundberg@neurologi.uu.se
*The following text is based on Guidelines for Neurologists about Sexual problems associated with neurological diseases (Neurosexology) compiled by the members of the European Federation of Neurological Societies Task Force on Neurosexology published in 2001. The text has been revised, condensed and updated. Members of the task force has in recent years published a number of reviews on the topic of neurosexology (Lundberg 1980, 1992, Lundberg 1997a, 1999, 2001, 2005, 2006, Lundberg et al 2000, Ertekin 1998, Vodusek 1998, Vodusek & Fowler 1999, Ghezzi 1999, Fugl-Meyer et al 1999, Vodusek et al. 2005), Further details on clinical neurosexology can be found in these reviews.
Abstract Sexual disorders, such as loss of sexual desire, erectile dysfunction, decreased lubrication, changes in arousal, disturbances of ejaculation and orgasm are common but often neglected by neurologists. However, they significantly impact on quality of life, and may be early features of a neurological disorder. This review is compiled following a literature search up to including 2005. It includes data on the pathophysiology of sexual function, impaired sexual function in the major neurological disorders, and recommendations for clinical investigation and treatment. The value of the sexual history and neurological examination, which should include the sacral segments, is stressed. Additional testing is not routinely recommended. The majority of neurological patients with sexual dysfunction will respond to treatment. Sexual counseling I san important aspect of management, which should follow the headings of Permission, Limited information, Specific suggestion and Intensive treatment (PLISSIT). For erectile dysfunction oral phosphodiesterase type 5 inhibitors are effective\ in neurological disorders, but should be used with caution in hypertensive patients. Intracavernous injection therapy with vasoactive drugs may be useful when oral agents are ineffective or contra-indicated.
Introduction The normal sexual response is traditionally described as comprising four different phases (Masters & Johnson 1966): Excitement, Plateau, Orgasm and Resolution. According to this model sexual desire is not a phase in itself. Kaplan (1974) suggested a three phase model: Desire, Excitement and Orgasm (Lue et al 2004).
To the neurologist the sexual response involves a series of neurally controlled phenomena occurring in a hormonally defined milieu. The different components; viz, motivation, arousal, genital reactions (erection, lubrication, emission, ejaculation) and orgasm have different neuroanatomical, neurophysiological, neurochemical, and neuropsychological dimensions. Little is known concerning specifically female sexual dimensions. Genital components of sexual function are inevitably the focus of discussion in neurological disorders. Nonetheless, sexual responses have a major psychological dimension, and they are dependent on neuroendocrinological factors. The male erection has to be firm enough for vaginal penetration, and maintained throughout intercourse to bring about ejaculation, which in turn should deliver sperm to the uterine cervix (Basson et al 2004, Goldstein et al 2004, Meston et al 2004).
Basic science Genital innervation is both somatic and autonomic. Somatic sensory afferents deliver information on tactile sexual stimuli to the sacral spinal cord, and can induce local sexual responses (vascular-erectile and glandular). Sensory information projects to suprasacral regions which are also important in sexual awareness and excitation. The erectile response is initiated by parasympathetic efferents travelling through the pelvic plexus and the greater and lesser cavernosal nerves. Blood flow in the penile artery increases. Smooth muscles lining the cavernosal sinuses in the penis relax. Helicine arterioles branching from cavernosal arteries selectively shunt blood flow to the lacunar spaces of the cavernosal bodies which fill with blood; subtunical venules become compressed. Intracorporeal pressure increases and then stabilises at a level approximating systolic blood pressure causing penile tumescence and rigidity. Continued parasympathetic activity maintains this erection (Smith & Bodner 1993). This parasympathetic pathway is, however, not the only proerectile pathway: erections are observed in humans and experimental animals after lesions of sacral cord segments and pelvic nerves, probably througha pathway involving the hypogastric nerves. The role of the hypogastric parasympathetic nerves in human penile ersction is not fully understood.
Continued stimulation eventually induces orgasm with seminal emission, rhythmic phasic contractions of perineal and pelvic floor muscles (ejaculation). Actually emission begins during arousal (Mitsuya et al 1960). Ejaculation requires sympathetic outflow from T11-L2 segments travelling through the hypogastric plexus, and along pelvic and pudendal nerves (Giuliano et al 1995). Animal experiments have shown extensive cross-innervation of the sympathetic nervous system (Kihara & Degroat 1997). Sympathetic activity causes smooth muscle contraction: in seminal vesicles, vas deferens, and prostate – to deliver seminal fluid to posterior urethra; in the bladder neck – to prevent retrograde ejaculation; in the corpora cavernosa – to cause detumescence. The latter "antierectile" activity is probably inhibited during erection through spinal coordination of reflex action. In the periphery the main proerectile transmitter is nitric oxide, which is co-localized with VIP (vasoactive intestinal peptide) and acetylcholine. The main anti-erectile neurotransmitter is probably noradrenaline (Giuliano et al 1995). Although the predominant neural control of the male accessory sexual organs is sympathetic (adrenergic and purinergic), the secretion of seminal fluid is under parasympathetic control (Hoyle et al 1994). Appropriate sensory stimulation leading to erection and orgasm is not necessarily purely genital, and erections caused by stimuli delivered through cranial nerves might also be reflexive, although this is usually subsumed under "psychogenic" (Sachs 1995). Mental imagery is the "real" psychogenic descending activating stimulus of these spinal cord-integrated reflex responses, but very little is known about these evidently important mechanisms.
The pattern of genital activation is probably similar in women, in whom parasympathetic activity causes clitoral erection, engorgement of labia, vaginal lubrication and secretion from a series of glands, the paraurethral gland – often called the female prostate – and Bartholin’s glands (Zaviacic 2000, 2001). Clitoral stimulation, involving pudendal nerve afferents, and vaginal stimulation, especially of the G-spot area, can both result in an orgasmic response. Vaginal stimulation also produces local analgesia, important during childbirth (Komisaruk & Whipple 2000). Orgasmic sympathetic activity results in contractions of uterus and fallopian tubes (Bérard 1989). Somatic motor activation causes rhythmic contractions of pelvic floor muscles sometimes noticed as expulsions from the paraurethral glands through the urethra, called female ejaculation (Whipple 2000).
The spinal cord organisation of the reflex coordination involved in human sexual responses remains to be elucidated. Spinal cord sites concerned with cavernosal smooth muscle control have been localised to preganglionic autonomic nuclei in thoracolumbar and lumbosacral spinal segments in the rat (Marson et al 1993). Genital afferents probably synapse – via interneurons – both with somatic and autonomic motoneurons; those projected to supraspinal structures travel in the anterolateral funiculus. Both thalamic and cortical areas receive sensory input from the genitalia, and sexual feelings may be elicited when such areas are stimulated. In the primary sensory cortex the genitalia are represented in the parasagittal area (Penfield & Jasper 1954). In studies using retrograde labelling in the rat, as revealed by the transneuronal transport of pseudorabies virus, most of the labelling from corpus cavernosum at the level of the brainstem was in the pons and medulla (Marson et al 1993). Descending projections from the brainstem raphe nuclei travel in the lateral funiculus. The nucleus paragigantocellularis contains serotoninergic neurons that projected to the spinal cord and provide tonic inhibition of sexual reflexes in the rat (McKenna et al 1991).
Injection of pseudorabies virus into the corpus cavernosum, revealed hypothalamic neuronal localisation, especially in the paraventricular nucleus, the tuberal region, the medial preoptic area, and the dorsal hypothalamic area (Marson et al 1993). Neurons from the paraventricular nucleus project to the thoracic and lumbosacral nuclei concerned with erection. Hypothalamo-spinal projections are situated in the dorsolateral funiculus (Giuliano et al 1995). The hypothalamus is also directly involved in the control of the gonadotropic pituitary activity and prenatal development of the genital organs, pubertal development, and the menstrual cycle. In the basal hypothalamus there is a region important for sexual desire, which is affected by tissue levels of the sex steroid hormones (testosterone, dihydrotestosterone and estradiol).
Animal experiments have delineated a dopaminergic stimulating and a serotoninergic inhibiting mechanism controlling sexual desire. Androgens are necessary but apparently not essential for normal human sexual desire (Kwan et al 1983). Sexually dimorphic nuclei are localised in the preoptic anterior hypothalamus. The medial preoptic area is important in sexual motivation and performance, and dopamine may regulate penile erection at this level. Stimulation of cortical and subcortical limbic structures– in particular, the hippocampus – can elicit erection in monkeys (Dua & MacLean 1964). Positron emission tomography (PET) studies during normal male sexual activity have shown increased regional blood flow in the ventral tegmentum but not in hypothalamus or limbic cortex (Holstege et al 2003). Important unsolved questions related to diagnostic concepts of erectile dysfunction concern the role of psychogenic and reflex erections, and whether sleep-related erections have identical neural control mechanisms to sexually elicited erections (Tables 1 and 2).
Assessing the patient with sexual dysfunction
General aspects It is essential to define exactly the nature of the abnormality presented, a process that requires careful and empathic enquiry. Always survey the patient´s medical history, particularly concerning psychological and psychiatric disturbances, cardiovascular, endocrine and neurological disorders, local genital disorders, including prior trauma and surgical procedures, the use of prescription drugs, smoking and alcohol habits, and drug abuse. In women a menstrual history should be delineated. How old was the woman at first menstruation? Has menstruation been regular? When was the last menstruation? Are menstruations painful (dysmenorrhoea)? The symptom of galactorrhoea, (and raised blood prolactin levels) suggests hypothalamo-pituitary dysfunction - a cause of sexual dysfunction.
History of sexual dysfunction Seek to understand the patient´s sexual expectations, needs and behaviour and identify sexual problems, and also any misconceptions. Psychological factors are always important, either as an emotional reaction to sexual dysfunction or as a consequence of a socially or physically disabling disease. Try to interview the patient’s partner separately. As always in neurology chronology is very important. Was the onset sudden, rapid or gradual, the course progressive or episodic? Ask about sexual desire. The term Hypoactive Sexual Desire Disorder (HSDD) is sometimes used to define a persistent or recurrent reduction in sexual fantasies, thoughts, desire for sexual activity, alone or with a partner, with inability to respond to sexual cues that would be expected to trigger responsive sexual desire. To be significant, these symptoms be associated with personal distress (Basson et al 2004).
Sensory aspects of sexual function should be elucidated. Present or past disturbances of sensitivity in the region corresponding to the sacral segments are particularly important, as well as pain during sexual arousal or intercourse, and pelvic or superficial dyspareunia. If a man, does the patient have nocturnal erections, morning erections, erections evoked by visual, auditory or psychogenic stimuli and erections evoked or enhanced by genital stimulation? What is the quality of penile tumescence? Is erection sufficient for penetration? Is erection maintained during sexual intercourse? Has priapism or painful nocturnal erection occurred? Women should be asked about erections of the clitoris and vaginal lubrication. Are these female reactions evoked by visual, emotional or direct genital stimulation?
In males, ejaculation should be described. Does the patient have premature or retarded ejaculation, or even absence of ejaculation? Is the ejaculation dribbling, i.e. are there emissions of semen through the urethra without contractions of pelvic floor muscles? Retrograde ejaculation into the bladder with spermatozoa in urine implies an internal urinary sphincteric disorder. Aspermia is lack of emission of semen. Both can be described as dry ejaculation. In women, is there urinary incontinence during sexual intercourse or does forceful ejaculation of fluids from the urethra occur during orgasm (so-called female ejaculation)?
Orgasm can be defined as the sum of all physiological events that occur during the sexual climax and how the individual experiences this, including sexual pleasure. What is the capacity to achieve an orgasm? Does the person – male or female – actually feel the pelvic floor muscle contractions? How is the quality of orgasmic sensations and experiences? An orgasm may be anhedonic, i. e. without pleasurable sensations. Spontaneous orgasms do also occur and orgasms may be painful.
Formal questionnaires can be used to obtain standardised information, e.g., the Brief Male Sexual Function Inventory for Urology (O`Leary et al 1995) and the International Index of Erectile Function (IEEF, 1997), but these are not recommended for assessment of individual patients (Lue 1996).
Examination of the patient with sexual dysfunction
Assess sexual development, height and weight, pigmentation, distribution of body hair and, in women, galactorrhea. Evaluate the external genitalia for any local pathology, including testicular size (normal 15-25 ml), the clitoris and the prostatic gland. Palpate the peripheral pulses (arms, legs, penis), auscultate the heart, and take the blood pressure.
Neurological examination A standard neurological examination, including assessment of the mental state, is important to exclude any underlying neurological disease. Inspect the lower back for naevi, hypertrichosis, and a sacral sinus and the feet for deformity and muscle atrophy. The sacral segments are especially important. The bulbocavernosus muscles can be palpated in the male, and tested for voluntary ("move the penis"), and reflex contraction. Anal sphincter and levator ani tone (pubococcygeus muscle) and their voluntary and reflex contraction can be palpated in both sexes. In addition to standard reflexes the cremasteric reflex (testing the L1 segment), and the bulbocavernosus and external anal reflex (testing the S2-S4/5 segments) should be evaluated. The bulbocavernosus reflex can be elicited by squeezing the glans and assessing contraction of the anal sphincter (in both sexes), or the bulbocavernosus muscle (in males), by palpation. The superficial external anal reflex is an objective response. Touch and pain perception in the perineum, perianal and genital skin, in addition to testing over other dermatomes, is essential. The neurological examination can be extended by neurophysiological tests. Thus, reflex responses can be recorded with greater sensitivity electromyographically; and perineal sensation can be quantified using special devices and algorithms (see below).
Investigation of erectile function Although essential data will be obtained by history, objective evaluation of erection is the "gold standard" to determine its quality. Spontaneous and physiologically induced erection can be studied with a variety of techniques. Spontaneous nocturnal penile tumescence and rigidity can be measured in the sleep laboratory using strain gauges (measuring penile expansion), visual inspection and measuring the buckling force (for assessment of rigidity), with polygraphic confirmation of sleep phases (Karacan and Ilaria 1978, Wasserman et al 1980). Various low-cost screening tests for nocturnal penile expansion have been proposed, but their validity is questionable (Condra et al 1987). Continuous monitoring of nocturnal penile tumescence and rigidity can be obtained by a rigidometer during normal sleeping conditions at home (Kaneko & Bradley 1986), and also during daytime napping (Morales 1994) or in the awake sexually stimulated examinee (Thase et al 1988). A comprehensive discussion of the utility and limitations of the noturnal penile tumescence test has been given by Morales et al (1990).
Investigation of erectile capacity Given that no major vascular problem is present (particularly no significant venous incompetence) an intracorporeal injection of a vasoactive substance (papaverine; combination of papaverine + phentolamine; prostaglandin E1) will lead to an erection, thus strengthening the suspicion of a neurogenic or psychogenic etiology for erectile dysfunction (Mueller & Lue 1988, Haldeman et al 1995). Additional self-stimulation increases this test’s sensitivity (Lue 1990).
Investigation of nervous system function In patients with erectile and ejaculatory dysfunction suspected due to a neurologic disorder neurophysiologic tests are useful (Mauroy et al 2003, Lundberg 2001), including sensory (somatosensory and viscerosensory) and motor (somatic and autonomic), tests (Table 3).
Special devices and algorithms can be used for quantifying genital sensation. Vibratory perception thresholds (biothesiometry/vibrametry) on the penis correlate with electrodiagnostic testing (Padma-Nathan 1988). The vibration perception threshold (VPT) in the penis (glans and shaft) in a neurologically healthy man is similar to that of the feet. In females VPT is best measured on the clitoris, labia majora and perineum (Helström & Lundberg 1992, Hulter et al 1998, Hulter & Lundberg 2005). The vibratory threshold at the clitoris in neurologically healthy women is the same as in the hands. VPT is of particular importance in women with suspected lesions of peripheral sensory nerves in the pelvic floor (Haldeman et al 1995). Tests evaluating small fiber function may be informative, i.e. testing penile (Yarnitsky et al 1996) or vaginal and clitoral warm and cold sensory thresholds (Vardi et al 2000).
Electromyography
(EMG) has been used to demonstrate activation patterns of striated muscles in
the sexual response (Gerstenberg et al 1990) but it is mainly used to
differentiate normal from denervated (reinnervated) muscle. Concentric needle
EMG is the method of choice to diagnose lower motor neuron involvement in the
lower sacral segments (Vodusek & Fowler 2004). Different tests involving
stimulation and recording of somatosensory and motor evoked responses, and
sacral reflexes reflect the function of defined parts of the motor and sensory
nervous system. These tests measure conduction through nervous pathways and are
sensitive to demyelination, but less sensitive to axonal lesions - which
predominate in clinical practice. Tests have been proposed to assess the
lumbosacral sympathetic system (the sympathetic skin responses) and penile
smooth muscle (Vodusek 1998, Vodusek et al 2005). These tests cannot in
themselves define erectile dysfunction as neurogenic (Haldeman et al 1995)
since the relationship of neurophysiologic test abnormalities to sexual
dysfunction itself has proven elusive. However, measurements of dorsal penile
nerve conduction, the bulbocavernosus reflex, and pudendal SEP are valuable in
evaluating patients with suspected neurogenic erectile dysfunction (Haldeman et
al 1995). Unfortunately, tests assessing penile autonomic innervation and
smooth muscle function are unreliable. Cystometry, other urodynamic tests, and
anorectal function tests may strengthen a diagnosis of sacral autonomic
dysfunction. Useful guidelines have been set out by the Therapeutics and
Technology Assessment Subcommittee of the
Laboratory investigation of blood and urine Basic laboratory data (including sedimentation rate, blood cell count, fasting blood sugar, serum lipids, urinanalysis) as well as serum parameters screening for hepatic, kidney and thyroid function rarely add information. Hormone analyses, especially prolactin and testosterone levels have been proposed as screening tests for both sexes. In women with menstrual irregularities or signs of masculinisation, endocrinological opinion may be helpful.
Investigation of vascular function If intracorporeal injection testing of penile tumescence has strengthened a suspicion of vascular etiology in the male patient with erectile dysfunction, further investigations may be contemplated, as a rule performed by urologists. Penile blood pressure can be measured using a simple Doppler method and then related to the arm blood pressure. Vascular competence can be measured by angiography, MRI, colour ultra-sonography and dynamic cavernosography. It has been stressed that the purpose of testing should always be defined: pharmacotesting may be sufficient for the majority of patients, and the invasive tests reserved for those in whom surgery is contemplated (Meuleman & Diemont 1995).
In females there are also a number of vascular tests available. A new technique for quantitative assessment of female sexual arousal using noncontrast dynamic MR imaging has been developed (Maravilla et al 2005). However, the sensitivity of these tests in clinical diagnosis has not been reported.
Sexual dysfunction and neurological disorders
Sexual dysfunction with hypothalamo-pituitary disorders Decreased or absent sexual desire with erectile failure is a cardinal feature in males with hypothalamo-pituitary disorders., and is often the first symptom. However, the diagnosis is made only when other features appear, usually hypothyroidism or visual field defects. As many as 75 % of men with hypothalamo-pituitary disorders report decreased or absent sexual desire at the time of diagnosis. The figures are higher for those with larger tumours extending into the suprasellar region than for those with intrasellar tumours. A highly significant correlation has been found between low serum testosterone levels and a decrease in desire (Lundberg & Wide 1978). Decreased sexual desire is also the first symptom in most men with small pituitary tumours and hyperprolactinaemia (Muhr et al 1985); and these men often have low serum testosterone. In women, amenorrhoea and infertility are usually the presenting problems. In females aged 20-60 years with hypothalamo-pituitary disorders (Hulter & Lundberg 1994) two thirds noticed absent, or decreased sexual desire, especially when the serum prolactin was low. Problems with vaginal lubrication and orgasm are also very common in this group of women.
Although hypothalamo-pituitary disorder has many causes (Lundberg 1980), in a CT/MRI study of 164 impotent males with low serum testosterone values pathology in the hypothalamo-pituitary region was found only in 11 patients (Citron et al 1996). There are many rarer causes, however, including spinocerebellar ataxia (Neuhäuser & Opitz 1975, Berciano et al 1982, Koskinen et al 1995, Seminara et al 2002).
Sexual dysfunction in patients with brain lesions and encephalopathies Sexual impairment is common after a traumatic brain injury. Both decreased and increased sexual desire have been reported. In women endocrine abnormalities are the most sensitive predictors of sexual dysfunction (Hibbard et al 2000). In males both impotence and retarded ejaculation have been reported (Meyer 1955, Kreutzer & Zasler 1989). This may in part be dependent upon post-traumatic anterior pituitary dysfunction (Agha et al 2004). Hypersexuality or altered sexual preference may sometimes follow frontal brain injury (Miller et al 1986) even leading to sex offending (Simpson et al 1999).
Lesions of the frontal and temporal lobe lead more often to sexual problems than lesions of the parieto-occipital part of the brain (De Morsier & Gronek 1972). Bilateral lesions of the anterior temporal regions may result in hypersexuality as in the Klüver-Bucy syndrome (Gerstenbrand & Lücking 1971, Oliveira et al 1989, Hayman et al 1998). Pansexuality, that is sexual drive directed not towards human beings but also towards animals and inanimate objects is sometimes a feature.
Sexual dysfunction and stroke About 75% of stroke patients, especially males, who have been sexually active before their stroke report decreased coital frequency, (Kalliomäki et al 1961, Sjögren et al 1983, Monga et al 1986a, Boldrini et al 1991, Aloni et al 1993, Korpelainen et al 1998). Orgasmic dysfunction is seen in 75% of females and 66% of males after stroke (Sjögren et al 1983). Sexual dysfunction may occur in stroke victims with only mild, or even without disability (Cheung 2002). These problems are usually considered in terms of the stress of stroke as a life event, and may respond to counselling of patient and partner. Cognitive impairment may disturb the sexual relationship, for example, in aphasia (Wiig 1973). Hemi-hypoaesthesia is associated with decreased sexual drive due to loss of erogenous zones. Hypersexuality may follow frontal or temporal infarction (Monga et al 1986b, Donnet et al 1997, Absher et al 2000).
Sexual dysfunction in patients with epilepsy
Interictal phenomena Many men with epilepsy suffer from loss of sexual desire, reduced sexual activity, and/or inhibited sexual arousal (Saunders & Rawson 1970, Dansky et al 1980, Goldner & Morrell 1995). Inability to maintain erection and, more rarely, ejaculatory dysfunction, decreased satisfaction with sexual life, reduced sexual fantasies, reduced sexual dreams and initiatives and reduced orgasmic capacity, have been reported in patients with complex partial epilepsy and mesio-basal temporal lobe spike foci (Taylor 1969, Shukla et al 1979). Morrell et al (1994) noted that sexual dysfunction was more frequent in partial than in generalised epilepsies. Decreased sexual arousability, vaginism and dyspareunia occur (Demerdash et al 1991) and episodic hypersexuality has been reported in a few cases (Blumer 1979). Sexual interest seems to be reduced particularly with right temporal foci compared to left hemisphere disorders. Surgical management of the epilepsy does not appear important (Christianson et al 1995), although life satisfaction and sexuality scores are higher in patients seizure-free compared to those experiencing seizures. Epileptic patients, especially men, have a lower expectation of marriage than the general population, and married women with epilepsy have fewer children than expected (Dansky et al 1980). Epileptic patients describe poorer psychological health than healthy subjects. Antiepileptic drugs, especially the older types (phenytoin, phenobarbital, primidone, carbamazepine and valproate), may lead to hormonal changes (particularly increased oestradiol and decreased free testosterone levels in men), as well as decreased sexual desire and performance in both sexes (Isojärvi et al 1995, Duncan et al 1999, Bauer et al 2004). Menstrual irregularities are common among women with epilepsy (for review, see Lundberg 1997b).
Seizures and sexual phenomena Epilepsy and sexual behaviour may be connected in many ways. Thus, sexual activity may provoke an epileptic attack (perhaps due to hyperventilation), sexual phenomena may be a part of an epileptic seizure, and the epileptic patient may display changes in sexual behaviour (Lundberg 1992). Sexual fantasies as well as genital stimuli (masturbation) or orgasm (Berthier et al 1987, Calleja et al 1988) may perhaps trigger reflex epilepsy. Partial seizures generated from a genital sensory cortical area may result in sensations in the genital organs, e.g, clitoral or vaginal warmth, a pleasant sensation of anal or vaginal constriction or of penetration but also as attacks of actual genital pain. Almost all of the very few described cases have been associated with a parasagittal tumour involving the primary sensory cortex. Motor symptoms such as erection, lubrication, ejaculation or orgasm may also be a part of a seizure. Such genital events may or may not be experienced as sexual. Pelvic sexual movements, as a part of epileptic automatisms, or compulsive masturbation in front of other people may occur during or after a seizure, but these movements are more commonly seen in non-epileptic attacks. Sexual phenomena other than sensory events, occurring as part of an epileptic seizure usually feature in patients with complex partial epilepsy, most often with temporal lobe lesions. Sexual automatisms may also occur with frontal lobe lesions. They are very uncommon in primary generalised epilepsy (with generalised tonic-clonic or absence seizures).
Deviant sexual behaviour, such as exhibitionism, fetishism, frotteurism, sadomasochism, transvestism, and violent sexual or pansexual behaviour, is a rare manifestation of epilepsy. The fact that the behaviour in question may occur episodically and sometimes disappears after treatment favours a causal connection between the behaviour and the epilepsy, or the causative cerebral lesion. In most cases there were partial complex epileptic seizures and lesions in one or both temporal lobes. Sometimes the deviant behaviour correlates with epileptic discharges in the EEG, e.g., in psychomotor status). In addition, paranoid delusions of being violated, abused or seduced are not uncommon in epileptic patients (Lundberg 1992).
Sexual dysfunction in Parkinson's disease and other movement disorders
Decrease in sexual desire is common in Parkinson´s disease, especially in women, resulting in stress to their partners (Brown et al 1990). In addition, patients with Parkinson's disease are often depressed. Erectile dysfunction occurs in half of affected men (Koller et al 1990, Takahashi 1991, Wermuth & Stenager 1995) and nocturnal and morning erections are usually absent. Many affected men have ejaculatory failure, and many women are unable to achieve an orgasm. During sexual arousal tremor is often enhanced, making sexual activity more difficult. In one study, the frequency of sexual dysfunction was similar in patients affected by Parkinson´s disease compared to patients affected by arthritis (Lipe et al 1990). Deep brain stimulation of the subthalamic nucleus has been found to influence sexual well-being in Parkinson´s disease (Castelli et al 2004).
The mechanisms underlying sexual dysfunction in Parkinson’s disease are not well understood. Bladder, and bowel dysfunction is often associated, implying autonomic involvement (Sakakibara et al 2001). There is a high incidence of bladder-detrusor hyperreflexia and of paradoxical contractions of the striated sphincter muscles during defecation (Berger et al 1987, Singer et al 1992). Derangement of cardiovascular regulation may occur (Zesiewicz et al 2003). Treatment with dopaminergic compounds may result in an apparent increase of sexual activity (Uitti et al 1989).
Increased sexual activity is reported in about 10 % of people with Huntington´s disease (HD. However, HD patients may have difficulty in achieving sexual arousal. Paraphilias such as sexual aggression, exhibitionism and pedophilia have been reported (Morris 1995). Disorders of sexual inhibition with pansexuality, occur in Tourette's syndrome (Comings 1994, Lombroso et al 1995). Increased sexual activity is also reported in patients with Wilson's disease (Akil & Brewer 1995). Impotence is almost universal among patients with multiple system atrophy, and may be the presenting symptom (Beck et al 1994, Hodder 1997). Neurophysiological studies, particularly external anal sphincter EMG, showing reinnervation in this muscle, are useful in diagnosis of MSA (Vodusek 2001, Pellegrinetti et al 2003).
Sexual dysfunction in multiple sclerosis
Impaired sexuality is common in multiple sclerosis (MS) in both sexes (McCabe 2004). In a study of 47 women with advanced MS 60% reported decreased sexual desire, 36% decreased lubrication and 40 % diminished orgasmic capacity. Genital sensory dysfunction was experienced by 62% of these women and 77% had weakness of the pelvic floor muscles (Hulter & Lundberg 1995). In other studies reduced sexual drive was reported by 29-86% of female MS patients, reduced sensation by 43-62%, reduced orgasmic capacity by 24-58%, vaginal dryness by 12-40%, and dyspareunia by 6-40% (Ghezzi 1999). Electrodiagnostic data such as cortical evoked potentials of the dorsal nerve of the clitoris (Yang et al 2000) as well as measurement of vibratory thresholds in the clitoris (Hulter & Lundberg 2005) suggest that pudendal somatosensory input is necessary for female orgasmic function, and that this may be disturbed even in early, mild MS. To compensate such a loss more direct stimulation of the anterior vaginal wall is recommended. Sacral segment dysaesthesiae may be so severe that patients may be unable to bear direct genital or non-genital contact (Lundberg 1978). Anorgasmia has been correlated with MRI brain stem and pyramidal abnormalities as well as with total area of lesions on MRI (Barak et al 1996). Zivadinov et al (2003). Correlated sexual dysfunction in MS with T1 lesion load of the pons. Between 34 and 80% men with MS have erectile dysfunction (Vas 1969, Valleroy & Kraft 1984, Kirkeby et al 1988B, Minderhoud et al 1984, Betts et al 1994, Mattson et al 1995, Ghezzi et al 1995, 1999). Ejaculatory dysfunction is also frequent; 34-61% are affected. Orgasmic capacity is similarly reduced (29-64 %), as is sexual desire (37-86%). Genital sensory evoked potentials (SEP) abnormalities are common in men with multiple sclerosis and sexual dysfunction (Yang et al 2001). In general, sexual dysfunction correlates with bladder and bowel sphincter dysfunction, but less closely with motor and sensory dysfunction in the legs (Hulter & Lundberg 1995, Ghezzi et al 1996, Ghezzi 1999, Zivadinov et al 1999), or with disability, clinical course, and disease duration. Depression and cognitive impairment are important.
Sexual dysfunction in amyotrophic lateral sclerosis
In amyotrophic lateral sclerosis the neurones of Onuf's nucleus in the sacral spinal cord innervating the pelvic floor muscles are relatively spared. Sensory and autonomic functions are also unaffected. Thus, urination defecation and sexual functions are normal, and sexual problems arise solely from the paralysis. Erection and ejaculation through psychogenic stimulation or partner stimulation is possible and the experience of orgasm is normal (Jokelainen & Palo 1976). Kaub-Wittemer et al (2003) found that sexuality was an important issue, even among ventilated patients. Decreased libido and impotence may occur in Kennedy´s syndrome (X-linked bulbospinal muscular atrophy) (Ertekin & Sirin 1993, Hokezu et al 1996).
Sexual dysfunction in spinal cord disorders If there is a complete destruction of the genital reflex centre in the sacral part of the conus medullaris, reflex erection and reflex lubrication are usually lost and there is complete paresis of the striated ejaculatory muscles. With spinal cord lesion between the level of the lower thoracic segments and the conus, both cerebral and reflex erection and lubrication may be possible, despite the fact that the patient cannot feel the sexual organs. Loss of sacral sensation does not necessarily imply anorgasmia. Although with a complete lesion of the spinal cord above the conus ejaculatory contractions cannot be felt, autonomic components of the orgasm can be experienced. In spinal cord lesion there is often hyperaesthesia just above or at the segment of the lesion. This may be used as an erogenous zone. A meta-analysis of 24 studies (Lundberg et al 2000) of more than 2,500 men with spinal cord injuries showed that a median of 80% (range 54-95%) reported spontaneous erections. The percentage of SCI men reporting ejaculation without therapeutic assistance was much lower (median 15 %, range 0-52 %). Fewer (26 %) of the patients with complete lower sacral lesions had erectile capacity than those with complete upper cord lesions or incomplete lesions at any level (90-99 %) (Bors & Comarr 1960). In cauda equina lesions of various causation only 15% reported normal sexual function (Podnar et al 2002). The semen of men with spinal cord injuries is characterised by small volume, low sperm count and low spermatic mobility. This is at least partly dependent on insufficient drainage. Ejaculation can be provoked in many paraplegic males through vibratory stimulation or electrostimulation. It has been shown that repeated vibration-induced ejaculations resulted in increased semen volume, a larger number of motile sperms and improved sperm penetration capacity. Insemination with autologous semen obtained in such a way has resulted in pregnancies. Collection of semen very early after the spinal cord injury makes it possible to store semen of good quality for future insemination.
Women with para- or tetraplegia are in a better sexual and reproductive situation than men. Deprived of sensation in the sacral segments they may still reach orgasm through stimulation of other erogenous zones, suprasegmental to the lesion, such as breasts, lips, ears and other areas. Preservation of sensory function in the T11-L2 dermatomes is associated with psychogenically mediated genital vasocongestion (Sipski et al 2001) Deep penetration may provide stimulus enough for orgasm through the sympathetic nervous system or possibly through the vagus nerve. Sexuality, pregnancy, motherhood and quality of life in women with traumatic spinal cord injuries are reviewed by Berard (1989) and Westgren (1999)
Of 224 consecutive male patients referred because of impotence, 17 (31-72 years old) were found to have an unrecognised myelopathy (Brattberg & Lundberg 1991, Lundberg & Brattberg 1992). Morning erections, psychogenic erections and reflex erections were disturbed in most of these men. Disturbances of ejaculation were reported by 10 patients and 7 reported disturbances of the experience of orgasm; in one orgasms were painful. In a study of nearly 2000 patients of both sexes with injuries of the cervical spinal cord without paralysis 85% reported sexual dysfunction (Perese et al 1976). 30% of patients with vitamin B12 deficiency reported sexual dysfunction (Kunze & Leitenmeier 1976).
Spinal cord malformations
The most important malformation giving rise to sexual dysfunction is meningomyelocele. Dependent upon the degree of the malformation there is a more or less pronounced loss of sexual functions. Some boys have no genital sensations at all, some have erections only and some both both erections and emissions. Loss of genital sensations is the major complaint in girls (Dorner 1977, Wabrek et al 1978, Sawyer & Roberts 1999). In Arnold-Chiari malformation loss of sexual desire is very common. Some the men are completely impotent and others have reduced potency. The onset of the sexual complaints nearly always follows the beginning of the neurological disturbances (Caetano de Barros et al 1975).
Sexual dysfunction in disorders of the spinal roots and peripheral mononeuropathies in the sacral region
Knowledge of sexual function in patients with spinal root disordersor sacral mononeuropathies is limited (see Lundberg (1992). Sacral root lesions cause pain at coitus and ejaculation, perhaps leading to Impotence. Bilateral S2-5 root lesions results in dribbling ejaculation, since seminal emission is preserved, but there is weakness of bulbo- and ischiocavernosus muscles. The sacral sensory disorder prevents reflex erection but psychogenic erections are unaffected. Unilateral sacral root lesions causing ipsilateral genital anaesthesia do not usually inhibit sexual activity. Lumbar spinal stenosis may be accompanied by spontaneous erections after walking a short distance (Hopkins et al 1973, Laha 1979), in addition to the classic presenting features. Sitting down relieves all symptoms including the erection over a few minutes. Erections may also appear after kneeling for a few minutes, relieved by sitting with spine flexed. Laminectomy results in complete relief. Mononeuropathies of the pudendal nerve or its branches are common in women (Lundberg 2001) and may cause local pain and dyspareunia.
Sexual dysfunction in polyneuropathies Diabetes mellitus
Impotence in male diabetics is common. In a meta-analysis 1619 patients Neubauer (1971) noted impotence in 39% to 75 % (mean 55 %), a prevalence confirmed by others (Ellenberg 1971, Kolodny et al 1974, Faiburn et al 1982). Jensen (1981) found impotence in 34% of diabetics but in none of a control group of non-diabetics. When the internal urinary sphincter is weak retrograde ejaculation occurs (Greene et al 1963, Ellenberg & Weber 1966, Schirren et al 1973), as noted in about 14% of diabetics. In diabetic males morning erections are absent or rare. Karacan et al (1977, 1978) and Hirshkowitz et al (1990) found that men with diabetic polyneuropathy had fewer sleep-related erections, shorter tumescence time, diminished penile circumference increase and weaker penile rigidity than non-diabetic men.
A correlation between impotence and bladder dysfunction has been noted in diabetic men (Ellenberg 1971, Buvat et al 1985, Ertekin et al 1989), and ikmpotence is also correlated with clinically evident peripheral neuropathy (Ellenberg 1971, Kolodny et al 1974, Jensen 1981, Lehman & Jacobs, 1983). There is little correlation, nonetheless, with neurophysiological abnormalities in peripheral nerve function (Zgur et al 1993), although bulbocavernosus and urethro-anal reflex latencies, and penile (pudendal) evoked potentials are more often abnormal in impotent diabetic males than in potent diabetic males (Bemelmans et al 1994). Neurophysiological testing of pudendal nerve function, however, is not more sensitive in diagnosing neuropathy in impotent diabetics than limb nerve conduction tests (Vodusek et al 1993).
Histological and histochemical studies of the autonomic nervous system have shown reduced norepinephrine content in the corpora cavernosa in insulin-dependent and diet-controlled diabetic men compared with non-diabetic men. Choline acetyltransferase activity and morphological studies of nerve fibers in erectile tissue were normal (Melman et al 1980a, 1980b), although choline accumulation and acetylcholine synthesis and release were significantly reduced in penile tissue from impotent diabetic patients compared to that from impotent non-diabetic patients. Impairment in acetylcholine synthesis correlated with duration of diabetes (Blanco et al 1990). Morphological alterations have been identified in unmyelinated nerve fibres in the penis (Faerman et al 1974). Hyperglycemia, and some glycosylation products, promote inactivation of NO (Brodsky et al 2001) and there seems to be a selective nitrergic neurodegeneration in diabetes (Cellek et al 1999).
Studies of sexual function in women with diabetes mellitus have given conflicting results. In one study 35 % of the diabetic women were reported to have had orgasmic dysfunction in the preceding year as compared to 6 % of controls (Kolodny 1971), but Jensen (1981) found the frequency of sexual dysfunction was 25 % both in insulin-treated diabetic women and in age-matched controls. An important negative impact on sexual life was found in women with type II diabetes (Schreiner-Engel et al 1987); but not in type 1 diabetes (Newman & Bertelsen 1986, Campbell et al 1989). In a structured interview Hulter et al (1998) found that 26 % of 42 women with insulin dependent diabetes had a decreased sexual desire, 22 % had decreased vaginal lubrication (Tyrer et al, 1983) and 10 % had decreased capacity to achieve orgasm. Several women reported more than one dysfunction. Taken together the figure for sexual dysfunction was 40 %. Among age-matched controls without diabetes or any neurological disease only 7 % of women reported any sexual dysfunction. A number of autonomic and sensory symptoms, including higher vibration perception thresholds in the hands and in clitoris, reduced foot perspiration, increased gustatory perspiration, constipation and incontinence correlated with sexual dysfunction (Hulter et al 1998). Women with more diabetic complications have more sexual dysfunction (Enzlin et al 2002). Psychophysiological studies in women with diabetes mellitus revealed less physiological arousal to erotic stimuli (Wincze et al 1993), or no difference compared to controls (Slob et al 1990). Microvascular damage leading to decreased decreased blood flow to the cavernous tissues in both sexes is another possible factor (Ertekin 1998, Enzlin et al 1998).
Other polyneuropathies
Autonomic dysfunction, including sexual dysfunction, is a feature of many peripheral neuropathies (McDougall & McLeod 1996), e.g., vitamin B1 deficiency (Tjandra & Janknet 1997), vitamin B12 deficiency (Kunze & Leitenmaier 1978) and plasma cell dyscrasia (Takatsuki & Sanada 1983). Impotence and ejaculatory problems have been observed in patients with Guillain-Barré syndrome, Charcot-Marie-Tooth syndrome (Bird et al 1994, Crabtree 1997), adrenomyeloneuroleukodystrophy (Sakakibara et al 1998, Garside et al 1999), Refsum's disease (Lundberg, unpublished observation), Friedreich's ataxia, Riley-Day syndrome, HSAN I-IV and especially in primary amyloidotic polyneuropathy (Anderson & Hofer 1974, Obayashi et al 2000). Involvement of the somatic nerves e.g., the pudendal nerves is not important in causing impotence in hereditary motor and sensory neuropathies (Vodusek & Zidar 1987).
Myopathies
In some progressive muscular dystrophies, especially myotonic dystrophy (Marinkovic et al 1990, Mastrogiacomo et al 1994, Olsson et al 1996, Becker dystrophy (Hallen 1971) and autosomal progressive external ophthalmoplegia (Lundberg 1966, Melberg et al 1996) hypogonadism may occur leading to disturbances of erectile function and desire. Impotence and amenorrhoea may also occur in mitochondrial encephalomyopathies such as MERFF and MELAS syndromes (Chen & Huang 1995).
Sexual dysfunction and medications Antidepressant drugs
Decreased desire, impotence and ejaculatory problems are the most frequent sexual effects of non-selective monoamine reuptake inhibitors. Orgasmic dysfunction is more prevalent with selective serotonin reuptake inhibitors (SSRIs) than for non-selective monoamine reuptake inhibitors (Patterson 1993, Montejo-Gonzalez et al 1997, Lundberg & Biriell 1998). Impotence is less frequent with SSRIs than non-selective monoamine reuptake inhibitors. Trazodone is an antidepressant drug that seems prone to cause priapism (Saenz de Tejada et al 1991, Lundberg & Biriell 1998, Lundberg 2000).
Antihypertensive drugs All classes of anti-hypertensive drugs may cause sexual dysfunction (Lundberg & Biriell 1993). Impotence is the best known effect. However, since decrease in libido is also reported, this effect may be partly central. Ejaculatory failure occurs with alpha-adrenoreceptor blocking agents, beta-adrenoreceptor agents and guanidine derivatives. Priapism has been reported with alpha-adrenoreceptor blocking agents such as prazosin.
Other types of drugs Anti-epileptic drugs, dopaminergic drugs, antipsychotic drugs and anxiolytic drugs have been reported to cause sexual dysfunction. Hormonal contraceptives for systemic use are reported to cause a decrease in sexual desire. Antiepileptic drugs often decrease sexual desire and may cause impotence or anorgasmia. Dopaminergic drugs (L-dopa, bromocriptine, selegiline) represent the only group more often associated with increased desire than with decreased desire (Hyyppä et al 1975). Antipsychotic drugs with alpha-adrenoreceptor blocking properties, in particular, chlorpromazine, thioridazine, haloperidol and clozapine, have been reported to cause priapism and also ejaculation failure. These drugs may also cause painful, retrograde or spontaneous ejaculations (Sitsen 1988, Keitner & Selub 1983).
Treatment and counselling strategies for sexual dysfunction in neurological disorders
General treatment principles
Sexual counselling, discussion and communication with the patient and their partner about their sexual life are an important part of the rehabilitation strategy in neurological disorders. Specific suggestions about therapeutic methods and strategies are important (Table 4). In a limited number of cases psychotherapy is indicated, combined with sensate focus exercises. Aloni & Katz (2003) and Fugl-Meyer et al (1999) have described sexual rehabilitation methods in the context of neurological disorders.
Oral treatment in patients with neurogenic impotence Specific phosphodiesterase-5 inhibitors have been developed to treat erectile dysfunction. The oldest of these drugs, sildenafil, has been used for eight years in more than 25 million men. A dosage of 25, 50 or 100 mg can be given orally one hour before desired sexual activity. The drug enhances erection mechanisms if the individual is sexually stimulated. Sildenafil taken at bedtime significantly increases nocturnal erections (Montorsi et al 2000). Sildenafil is an effective treatment for erectile dysfunction in men with diabetes (Price et al 1998, Rendell et al 1999, Boulton et al 2001, Ng et al 2002), multiple sclerosis (Fowler et al 1999), Parkinson´s disease (Zesiewicz et al 2000, Hussain et al 2001, Raffaele et al 2002), spinal cord injury (Derry et al 1998, Guiliano et al 1999, Maytom et al 1999, Schmid et al 2000, Hultling et al 2000, Gans et al 2001, Sanchez Ramos et al 2001, Ethans et al 2003), spina bifida (Palmer et al 1999) and familial amyloidotic polyneuropathy (Obayashi et al 2000). Sildenafil have been used in women with neurological disorders causing lack of sexual arousal, e.g., multiple sclerosis (DasGupta et al 2004) and spinal cord injuries (Sipski et al. 2000) with few side effects. Sildenafil can be used repeatedly. However, it should be used with great care in the cardiac patient and is contraindicated in combination with vasodilator drugs of the nitro-type (Boolell et al 1996, Goldstein et al 1998). It should not be used in patients with retinitis pigmentosa and it should be used cautiously in multiple system atrophy (Hussain et al 2001) (Vodusek, personal observation). The most common adverse events are headache and dyspepsia. Ischemic optic neuropathy (Egan 2000) and third nerve palsy (Donahue & Taylat 1998) have also been associated with sildenafil. A number of cases of cerebrovascular incidents in men taking sildenafil have been reported to the WHO database on Adverse Drugs Reactions: Sildenafil may also provoke epileptic seizures. Two other phosphodiasterase-5 inhibitors have also been used with good results for treatment of impotence in neurological disorders. Thus in men with diabetes mellitus vardenafil (Goldstein et al 2003) and tadalafil have been used (Saenz de Tajada 2002), and also in patients after spinal cord injuries. Vardenafil has been used in doses from 5 mg to 20 mg and tadalafil in doses of 2.5 mg to 20 mg. Tadalafil has a longer half-life and is thus more long-acting (Fazio & Brock 2004).
Treatment with apomorphine sublingually is another therapeutic option for men with erectile dysfunction. The action is through a dopaminergic effect in the hypothalamus (cf. adverse drugs reaction of L-dopa described above). Doses of 2 to 4 mg are given. Erection occurs within 10-25 minutes. Nausea is the most common adverse reaction (Heaton 2000). However, in a randomised study of 130 men with diabetes mellitus, only 22 % had a significant erectile response (Gontero et al 2004).
Intracavernous injection as a treatment for neurogenic impotence
Intracavernous injection (ICI) of vasoactive substances was introduced as the standard treatment for erectile dysfunction 20 years ago. It has mostly been used in men with spinal cord injuries or multiple sclerosis (Beretta et al 1986, Bodner et al 1987, Sidi et al 1987, Kirkeby et al 1988A, Costa et al 1993, Hirsh et al 1994). Intracavernous injection should be taught during medical supervision before self-administrated by the patient or his partner. Originally papaverine was used but this drug has been largely replaced by prostaglandin E1 (alprostadil). In neurogenic impotence rather low doses of PGE 1 are needed, 2.5 µg up to maximum 10 µg. In arteriogenic impotence higher doses are needed. The effect is very rapid and may last for 2-4 hours. Its efficacy in patients with impotence and diabetes mellitus has been proven with a high level of evidence (Heaton et al 2001). Longer lasting erection should be treated as priapism (see below). Haematological malignancies and anticoagulant therapy are contraindications. Local bleeding, pain and fibrosis may develop in the corpora cavernosa leading to loss of effectiveness., are common side effects. Moxisylate, an alpha-blocking agent has been studied in spinal cord injured patients (Costa et al 1993) with good results. However, long term studies are lacking. Prostaglandin E1 can also be administered as a gel intraurethrally (MUSE). This is more practical but less effective than ICI (Padma-Nathan et al 1997, Bodner et al 1999).
Surgical procedures and technical devices
Surgical revascularisation is never indicated in the neurological patients. So are also procedures to treat cavernous insufficiency, i.e., venous leakage. Penile prostheses, implantation of semi-firm or inflatable rods were used between 1970 and 1980 but these techniques have many disadvantages and are now rarely recommended. Penile vacuum devices and penile rings continue to have a role neurological impotence (Heller et al 1992, Rivas & Chancellor 1994, Seckin et al 1996, Denil et al 1996).
Treatment of anejaculation
In cases of anejaculation/anorgasmia vibratory stimulation may be helpful (Brindley 1981). The presence of intact dorsal penile nerves is necessary for the ejaculatory response to penile vibratory stimulation (Wieder et al 2000). If the aim is to retrieve sperm for in vitro fertilisation or intracytoplasmic sperm injection electroejaculation is preferred (Sato 1991), preferably supervised by experienced specialists. A comprehensive description is available in two reviews (Kamischke & Nieschlag 1999, Lundberg et al 2000). Penile vibrations been found to have an considerable antispastic effect in men with spinal cord injuries (Laessoe et al 2004).
Treatment of priapism
Priapism caused by a spinal cord disorder or appearing as an adverse drug reaction usually has a good prognosis with conservative treatment. Painless priapism of less than 6 hours duration should be treated at first by cooling (Bondil et al 1997, Lundberg 2000). If the priapism is painless but has been present for more than 6 but less than 24 hours intracavernous injection of an alpha-adrenergic agonist such as metaraminol is recommended. In painful priapism or when other conservative methods have failed penile puncture should be used. Few cases of this type of priapism need open surgery. When ICI or puncture is performed it is recommended to draw a cavernosal blood sample for blood gas analysis to evaluate cavernosal hypoxia.
Treatment of lack of sexual arousal and anorgasmia in women
Women showing signs of oestrogen insufficiency should be given hormone replacement therapy. Androgens may also be supplemented in women with no risk of pregnancy. Otherwise there is at present no drug treatment with proven effect available. Vibratory stimulation may be helpful in patients with genital sensory disturbances and in those with weakness or movement disorders. The vibrators should preferably be applied against the clitoris. Dildos of various types, also in combination with vibration, are useful for intravaginal stimulation. In women with dysesthetic or painful sensations in the genitalia not alleviated by improving lubrication antiepileptic drugs may be helpful, e.g., gabapentin, and carbamazepine.
Treatment of abnormal sexual desire
Hormone insufficiency, testosterone in men and oestrogens in women, should always be corrected. Testosterone may also be helpful in women, but cannot very often be used in fertile women because of the risk of masculinization. Hyperprolactinaemia should be treated. Dopaminergic drugs may be tried in certain cases with reduced desire. However, there is currently no effective drug for use in women with low sexual desire. For increased sexual desire (a rare disorder) androgen antagonists (cyproterone acetate, medroxyprogesterone acetate) may be effective. In severe cases neuroleptics may be tried.
References
Absher JR, Vogt BA, Clark DG, Flowers DL, Gorman DG, Keyes JW, Wood FB (2000). Hypersexuality and hemiballism due to subthalamic infarction. Neuropsychiatry Neuropsychology and Behavioral Neurology 13:220-229.
Agha
A,
Akil M, Brewer GJ (1995). Psychiatric and behavioral abnormalities in Wilson´s disease. Advances in Neurology 65:171-186.
Aloni
R, Katz S (2003). Sexual difficulties after traumatic brain injury and ways to
deal with it.
Aloni R, Schwartz J, Ring H (1993) Sexual function in male patients after stroke - a follow up study. Sexuality and Disability 11:121-128.
Andersson R, Hofer P-Å (1974) Genitourinary disturbances in familial amd sporadic cases of primary amyloidosis with polyneuropathy. Acta Medica Scandinavica 195:49-58.
Barak Y, Achiron A, Elizur A, Gabbay U, Noy S, Sarova-Pinhas I (1996) Sexual dysfunction in relapsíng-remitting multiple sclerosis: magnetic resonance imaging, clinical, and psychological correlates. Journal of Psychiatry and Neuroscience 21:255-258.
Basson
R, Weijmar Shultz WCM, Binik YM, Brotto LA, Eschenbach DA, Laan E, Redmond G,
Utian WH, Wesselmann U, van Lankveld J, Wyatt G, Wyatt L, Leiblum S, Althof SE.
(2004). Women´s sexual desire and arousal disorders and sexual pain. Chapter 22
in Lue TF, Basson R, Rosen R, Giuliano F, Khoury S, Montorsi F (eds). Sexual
Medicine.
Bauer J, Blumenthal S, Reuber M, Stoffel-Wagner B (2004). Epilepsy syndrome, focus location, and treatment choice affect testicular function in men with epilepsy. Neurology 62:243-246
Beck RO, Betts CD, Fowler CJ (1994). Genitourinary dysfunction in multiple system atrophy. Journal of Urology 151:1336-1341.
Bemelmans BLH, Meuleman EJH, Doesburg WH, Notermans SLH, Debruyne FMJ (1994). Erectile dysfunction in diabetic men: The neurological factor revisted. Journal of Urology 151:884-889.
Bérard EJ (1989). The sexuality of spinal cord injured women) physiology and pathophysiology. A review. Paraplegia 27:99-112.
Berciano J, Amado JA, Freijanes J, Rebollo M, Vaquero A (1982). Familial cerebellar ataxia and hypogonadotropic hypogonadism: evidence for hypothalamic LHRH deficiency. Journal of Neurology Neurosurgery and Psychiatry 45:747-751.
Beretta G, Zanolio A, Fancuillacci F, Cantazaro F (1986). Intracavernous injection of papaverine in paraplegic males. Acta Europaea Fertilitatis 17:283-284.
Berger Y, Blaivas JG, DeLaRocha ER, Salinas JM (1987). Urodynamic findings in Parkinson´s disease. Journal of Urology 138:836-838.
Berthier M, Starkstein S, Leiguarda R (1987). Seizures induced by orgasm. Annals of Neurology 22:394-395.
Betts CD, Jones SJ, Fowler CG, Fowler CJ (1994). Erectile dysfunction in multiple sclerosis. Brain 117:1303-1310.
Bird TD, Lipe HP, Crabtree LD (1994). Impotence associated with Charcot-Marie-Tooth syndrome. European Neurology 34:155-157.
Blanco R., de Tejada IS, Goldstein I, Krane RJ, Wotiz HH, Cohen RA (1990). Dysfunctional penile cholinergic nerves in diabetic impotent men. Journal of Urology 144:278-280.
Blumer D (1979). Hypersexual episodes in the temporal lobe epilepsy. American Journal of Psychiatry 126:83-90.
Bodner D, Lindan R, Leffler E, Kursh E, Resnick M (1987). The application of intracavernous injection of vasoactive medications for erection in men with spinal cord injury. Journal of Urology 138:310-311.
Boldrini P, Basaglia N, Calancq MC (1991). Sexual changes in hemiparetic patients. Archives of Physical Medicine and Rehabilitation 72:202-207.
Boolell M, Gepi-Attee S, Gingell JC, Alien MJ (1996). Sildenafil, a novel effective oral therapy for male erectile dysfunction. British Journal of Urology 78:257-261.
Bondil P, Descottes JL, Salti A, Sabbagh R, Hamza T (1997). Medical treatment of venous priapism apropos of 46 cases: puncture, pharmacologic detumescence or penile cooling? Progres en Urologie 7:433-441.
Bors E, Comarr AE (1960). Neurological disturbances of sexual function with special reference to 529 patients with spinal cord injury. Urological Survey 10:191-222.
Boulton AJM, Selam JL, Sweeney M, Ziegler D. (2001). Sildenalfil for the treatment of erectile dysfunction in men with type II diabetes mellitus. Diabetologia 44:1296-1301.
Brattberg
A, Lundberg PO (1991) Disorders of the spinal cord in males with sexual
dysfunction. Proc 10th World Congr Sexology
Brindley GS (1981). Reflex ejaculation under vibratory stimulation in paraplegic men. Paraplegia 30:550-553.
Brodsky SV, Mirrishow AM, Dharia N, Gross SS, Goligorsky MS (2001). Glucose scavenging of nitric oxide. American Journal of Physiology. Renal Physiology 280:F480-486.
Brown RG, Jahanshahi M, Quinn N, Marsden CD (1990). Sexual function in patients with Parkinson`s disease and their partners. Journal of Neurology Neurosurgery and Psychiatry 53:480-486.
Buvat J, Lemaire A, Buvat-Herbaut M, Guieu JD, Bailleul JP, Fossati P (1985). Comparative investigations in 26 impotent and 26 nonimpotent diabetic patients. Journal of Urology 133:34-38.
Caetano De Barros M, Farias Da Silva W, DeAzevedo Filho HC, Spinell C (1975). Disturbancies of sexual potency in patients with basilar impression and Arnold-Chiari malformation. Journal of Neurology Neurosurgery and Psychiatry 38:598-600.
Calleja J, Carpizo R, Berciano J (1988). Orgasmic epilepsy. Epilepsia 29:635-639.
Castelli L, Perozzo P, Genesia ML, Torre E, Pesare M, Cinquepalmi A, Lanotte M, Bergamasco B (2004). Sexual well being in parkinsonian patients after deep brain stimulation of the subthalamic nucleus. Journal of Neurology Neurosurgery and Psychiatry 75:1260-1264.
Cellek S, Rodrigo J, Lobos E, Fernandez P, Serrano J, Moncada S (1999). Selective nitrergic neurodegeneration in diabetes mellitus - a nitric oxide-dependent phenomenon. British Journal of Pharmacology 128:1804-1812.
Chen CM, Huang CC (1995). Gonadal dysfunction in mitochondrial encephalomyopathies. European Neurology 35:281-286.
Cheung RT (2002). Sexual functioning in chinese stroke patients with mild or no disability. Cerebrovascular Diseases 14:122-128.
Christianson S-Å, Silfvenius H, Säisä J, Nilsson M (1995). Life satisfaction and sexuality in patients operated for epilepsy. Acta Neurologica Scandinavica 92:1-6.
Citron JT, Ettinger B, Rubinoff H, Ettinger VM, Minkoff J, Hom F, Kan P, Alloo R (1996). Prevalence of hypothalamic-pituitary imaging abnormalities in impotent men with secondary hypogonadism. Journal of Urology 155:529-533.
Comings DE (1994). Role of genetic factors in human sexual behavior based on studies of Tourette syndrome and ADHD probands and their relatives. American Journal of Medical Genetics 54:227-241.
Condra M, Fenemore J, Reid K, Philips P, Morales A, Owen J, Surridge D (1987). Screening assessment of penile tumescence and rigidity: Clinical test of snap gauge. Urology 29:254-257.
Costa P, Sarrazin B, Bressole F, Colson M, Bondil F, Saudubray F (1993). Efficiency and side effects of intracavernous injections of moxisylate in impotent patients: a dose findning study versus placebo. Journal of Urology 149:301-305.
Crabtree L (1997). Charcot-Marie-Tooth disease: sex, sexuality and self-esteem. Sexuality and Disability 15:293-311.
Dansky
DasGupta R, Wiseman OJ, Kanabar G, Fowler CJ, Mikol DD (2004). Efficacy of sildenafil in the treatment of female sexual dysfunction due to multiple sclerosis. Journal of Urology 171:1189-1193.
Demerdash A, Shalaan M, Midani A, Kamel F, Bahri M (1991). Sexual behavior of a sample of females with epilepsy. Epilepsia 32:82-85.
De Morsier G, Gronek B (1972). Sur 92 cas de troubles sexual post-traumatiques. Annales Medico-Psychologiques 130, 653-670.
Denil J, Ohl D, Smythe C (1996). Vacuum erection device in spinal cord injured men: Patient and partner satisfaction. Archives of Physical Medicine and Rehabilitation 77:750-753.
Donahue SP, Taylar LJ (1998). Pupil-sparing third nerve palsy associated with seldenafil citrate (Viagra). American Journal of Ophthalmology 126:376-477.
Donnet A, Schmitt A, Poncet M, Graziani N, Grisoli F (1997). [Hallucinations of supernumerary limbs, left hemineglect and hypersexuality in a case of right capsulo-lenticular hematoma]. In French. Pub Med abstract. Revue Neurologique 153:587-590.
Dorner S (1977). Sexual interest and activity in adolescents with spina bifida. Journal of Child Psychology and Psychiatry 18:229-237.
Dua S, MacLean PD (1964) . Localization of penile erection in medial frontal lobe. American Journal of Physiology 207:1425.
Duncan S, Blacklaw J, Beastall GH, Brodie MJ (1999). Antiepileptic drug therapy and sexual function in men with epilepsy. Epilepsia 40:197-204.
Egan R (2000). Sildenafil (Viagra) associated with anterior ischemic optic neuropathy. Archives of Ophtahmology 118:291
Ellenberg M (1971). Impotence in diabetes: the neurological factor. Annals of Internal Medicine 75:213-219.
Ellenberg M, Weber H (1966). Retrograde ejaculation in diabetic neuropathy. Annals of Internal Medicine 65:1237-1246.
Enzlin P, Mathieu C, Vanderschueren D, Demyttenaere K (1998). Diabetes mellitus and female sexuality: a review of 25 year´s research. Diabetes Medicine 15:809-815.
Enzlin P, Mathieu C, Van Den Bruel A, Bosteels J, Vanderschueren D, Demyttenaere K (2002). Sexual dysfunction in women with type 1 diabetes: A controlled study. Diabetes Care 2002;25:672-677.
Ertekin C (1998). Diabetes mellitus and sexual dysfunction. Scandinavian Journal of Sexology 1:3-21.
Ertekin C, Ertekin N, Almis S (1989). Autonomic sympathetic nerve involvement in diabetic impotence. Neurourology and Urodynamics 8:589-598.
Ertekin C, Sirin H (1993). X-linked bulbospinal muscular atrophy (Kennedy´s syndrome): a report of three cases. Acta Neurologica Scandinavica 87:56-61.
Ethans KD, Casey AR, Schyvers OI et al (2003).The effects of sildenafil on the cardiovascular response in men with spinal cord injury at or above the sixth thoracal level. Journal of Spinal Cord Medicine 26:222-226
Faerman
I, Glocer L, Fox D,
Fairburn
CG, Wu FCW., McCulloch DK, Borsey DQ,
Fazio L, Brock G (2004). Erectile dysfunction; management update. Canadian Medical Association Journal 170;1429-1437.
Fowler C, Miller J, Sharief M (1999). Viagra (sildenafil citrate) for the treatment of erectile dysfunction in men with multiple sclerosis. Annals of Neurology 46;497-?
Gans WH, Zaslau S, Wheeler S, Galea G, Vapnek JM (2001) Efficacy and safety of oral sildenafil in men with erectile dysfunction and spinal cord injury. Journal of Spinal Cord Medicine 24:35-40
Gerstenberg TC, Levin RJ, Wagner G (1990). Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocaver-nosus and ischiocavernosus muscles. British Journal of Urology 65:395-402.
Gerstenbrand F, Lücking CH (1971). Hypersexualität im Rahmen der Klüver-Bucy-Symptomatik nach traumatischem apallischem Syndrom. Journal of Neuro-Visceral Relations suppl.X: 524-537.
Ghezzi A (1999). Sexuality and multiple sclerosis. Scandinavian Journal of Sexology 2:125-140.
Ghezzi A, Malvestiti GM, Baldini S, Zaffaroni M, Zibetti A (1995). Erectile impotence in multiple sclerosis patients. Journal of Neurology 242:123-126.
Ghezzi A, Zaffaroni M, Baldini S, Zibetti A (1996). Sexual dysfunction in multiple sclerosis male patients in relation to clinical findings. European Journal of Neurology 53:462-466.
Giuliano
FA, Rampin O, Benoit G, Jardin A (1995). Neural control of penile erection.
Urological Clinics of
Giuliano F, Hultling C, El Masry WS, Smoth MD, Osterloh IN, Orr M, Maytom M (1999). Randomizaed trial of sildenafil for the treatment of erectile dysfunction in spional cord injury. Annals of Neurology 46:15-21.
Goldner GT, Morrell MJ (1995). Nocturnal penile tumescence and rigidity evaluation in men with epilepsy. Epilepsia 37:1211-1214.
Goldstein
I, Giraldi A, Kodigliu A, van Lunsen HW, Marson L, Nappi R, Pfaus J, Salonia A,
Traish AM, Vardi Y (2004) Physiology of female sexual function and
pathophysiology of female sexual dysfunction. Chapter 19 in Lue TF, Basson R,
Rosen R, Giuliano F, Khoury S, Montorsi F (eds). Sexual Medicine.
Goldstein I, Lue TIF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA (1998). Oral Sildenafil in the treatment of erectile dysfunction New England Journal of Medicine 338:1397-404. Goldstein I, Young JM, Fischer J, Bangerter K, Segerson T, Taylor T (2003). Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes. A multicenter double-blind placebo-controlled fixed-dose study. Diabetes Care 26:77-283.
Gontero P,
D´Antonio R, Pretti G, Fontana F, Panella M, Kocjancic E, Allochis G, Frea B.
(2004). Clinical efficacy of apomorphine SL in erectile dysfunction of diabetic
men. International Journal of Impotence Research Online publication
Greene LF, Kelalis PP, Weeks PE (1963). Retrograde ejaculation of semen due to diabetic neuropathy. Fertility and Sterility 14:617-625.
Haldeman S,Lue T, Krane RJ, Shabsigh R, Bradley W (1995). Assessment: Neurological evaluation of male sexual dysfunction. Neurology 45: 2287-2292.
Hallen O (1971). Über Potenz- und Libidostörungen bei der progressiven Muskeldystrophie. Journal of Neuro-Visceral Relations suppl X:573-579.
Hayman LA, Rexer JL, Pavol MA, Strite D, Meyers CA (1998). Klüver-Bucy syndrome after bilateral selective damage of amygdala and its cortical connections. Journal of Neuropsychiatry and Clinical Neuroscience 10:354-358.
Heaton JPW (2000). Apomorphine: an update of clinical trial results. International Journal of Impotence Research 12;Suppl 4:S67-73.
Heaton JP, Lording D, Liu SN, Litonjua AD et al (2001), Intracavernousal alprostadil is effective for the treatment of erectile dysfunction in diabetic men. International Journal of Impotence Research 13:317-321.
Heller L, Keren O, Aloni R, Davidoff G (1992). An open trial of vacuum penile tumescence: constriction therapy for neurological impotence. Paraplegia 30:550-553.
Helström
L, Lundberg
Hibbard MR, Gordon WA, Flanagan S, Haddad L, Labinsky E (2000), Sexual dysfunction after traumatic brain injury. NeuroRehabilitation 15:107-120.
Hirsh I, Smith R, Chancellor M, Bagley D, Carsello J, Stass W (1994). Use of intracavernous injection of prostaglandin E1 for neuropathic erectile dysfunction. Paraplegia 32:661-664.
Hirshkowitz M, Karacan I, Rando KC, Williams RL, Howell JW (1990). Diabetes, erectile dysfunction and sleep-related erections. Sleep 13:53-68.
Hodder J (1997). Shy Drager syndrome. Axone 18:75-79.
Hokezu Y, Yanai S, Nagai M, Nagamatsu K, Yamamoto Y (1996). [A case of Kennedy-Alter-Sung (KAS) syndrome presenting as hypersexuality and elevetad serum CK: usefulness of genetic analysis] Rinsho Shinkeigaku 36:471-474. In japanese. Pub Med abstract.
Holstege G, Georgiadis JR, Paans AMJ, Meiners LC, van der Graaf FHCE, Reinders AAS (2003). Brain activation during human male ejaculation. Journal of Neuroscience 23:9185-9193.
Hoyle
CHV, Lincoln J, Burnstock G (1994). Neural control of pelvic organs. In:
Rushton DN (ed). Handbook of Neuro-Urology.
Hulter BM, Berne C, Lundberg PO (1998). Sexual function in women with insulin dependant diabetes mellitus. Scandinavian Journal of Sexology 1:43-50.
Hulter
BM, Lundberg
Hulter
BM, Lundberg
Hulter BM, Lundberg PO (2005).Genital vibratory perception threshold in women with sexual dysfunction and/or sexual pain disorders. In maniscript-
Hultling C, Giuliano F, Quirk F, Pena B, Mishra A, Smith MD (2000). Quality of life in patients with spinal cord injury receiving Viagra (sildenafil citrate) for the treatment of erectile dysfunction. Spinal Cord 38:363-370.
Hussain IF, Brady CM, Swinn MJ, Mathias CJ, Fowler CJ (2001). Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonsim due to Parkinson´s disease or multiple syctem atrophy with observation on orthostatic hypotension. Journal of Neurology Neurosurgery Psychiatry 712:571-574.
Hyyppä
MT, Falck SC, Rinne
IIEF (1997). The International Index of Erectile Function: a multidimensional scale for assessment of erectile dysfunction. Urology 49:822-830.
Isojärvi JIT, Repo M, Pakarinen AJ, Lukkarinen O, Myllylä VV (1995). Carbamazepine, phenytoin, sex hormones, and sexual function in men with epilepsy. Epilepsia 36:366-370.
Jensen SB (1981). Diabetic sexual dysfunction: A comparative study of 160 insulin treated diabetic men and women and an age-matched control group. Archives of Sexual Behavior 10:493-504.
Jokelainen M, Palo J (1976). Amyotrophic lateral sclerosis and autonomic nervous system. Lancet June 5 :1246.
Kalliomäki
JL, Markkanen TK,
Kamischke A, Nieschlag E (1999). Treatment of retrograde ejaculation and anejaculation. Human Reproduction Update 5:448-474.
Kaneko S, Bradley WE (1986). Evaluation of erectile dysfunction with continuous monitoring of penile rigidity. Journal of Urology 136:1026-1029.
Kaplan
HS (1974). The New Sex Therapy.
Karacan I, Ilaria RL (1978). Nocturnal penile tumescence (NPT): the phenomenon and its role in the diagnosis of impotence. Sexuality and Disability 1:260-271.
Karacan I, Scott FB, Salis PJ, Attia SL, Ware JC. Altinel A, Williams RL (1977). Nocturnal erections, differential diagnosis of impotence and diabetes. Biological Psychiatry 12:373-380.
Karacan I, Salis PJ, Ware JC, Dervent B, Williams RL, Scott FB, Attia SL, Beutler LE (1978). Nocturnal penile tumescence and diagnosis on diabetic impotence. American Journal of Psychiatry 135:191-197.
Kaub-Wittemer D, von Steinbüchel N, Wasner M, Laier-Groeneveld G, Borasio GD (2003). Quality of life and psychosocial issues in ventilated patients with amyotrophic lateral sclerosis and their caregivers. Journal of Pain and Symptomatic Management 26:890-896.
Keitner GI, Selub S (1983). Spontaneous ejaculations and neuroleptics. Journal of Clinical Psychopharmacology 3:34-36.
Kihara K, Degroat WC (1997). Sympathetic efferent pathways projecting bilaterally to the vas deferens in the rat. Anatatomical Records 248:291-299.
Kirkeby H, Petersen T, Poulsen E (1988A). Pharmacologically induced erection in patients with multiple sclerosis. Scandinavian Journal of Urology and Nephrology 22:241-244.
Kirkeby HJ, Poulsen EU, Petersen T, Dørup J (1988B). Erectile dysfunction in multiple sclerosis. Neurology 38:1366-1371.
Koller WC, Vetere-Overfield B, Williamson A, Busenbark K, Nash J, Parrish D (1990). Sexual dysfunction in Parkinson´s disease. Clinical Neuropharmacology 13:461-463.
Kolodny RC (1971). Sexual dysfunction in diabetic females. Diabetes 20:557-559.
Kolodny RC, Kahn CB, Goldstein HH, Barnett DM (1974). Sexual dysfunction in diabetic men. Diabetes 23:306-309.
Komisaruk
BR, Whipple B (2000). How does vaginal stimulation produce pleasure, pain and
analgesia? Chapter 7 in Filligim RB (ed) Sex Gender and Pain. Vol 17 in
Progress in Pain Reseach Management.
Korpelainen JT, Kaulhanen M-L, Kemola H, Malinen U, Myllylä VV (1998). Sexual dysfunction in stroke patients. Acta Neurologica Scandinavica 98:400-405.
Koskinen T, Pihko H, Voutilainen R (1995). Primary hypogonadism in females with infantile onset spinocerebellar ataxia. Neuropediatrics 26:263-266.
Kreutzer
JS,
Kunze K, Leitenmaier K (1976). Vitamin B12 deficiency and subacute combined degeneration of the spinal cord. In Vinken PJ, Bruyn GW (eds) Handbook of Clinical Neurology 28:141-198.
Kwan M, Greenleaf WJ, Mann J, Crapo L, Davidson JM (1983). The nature of androgen action on male sexuality: A combined laboratory-self-report study on hypogonadal men. Journal of Clinical Endocrinology and Metabolism 57:557-562.
Laessoe L, Nielsen JB, Biering-Sorensen F, Sönksen J. (2004). Antispastic effect of penile vibration in men with spinal cord lesions. Archives of Physical Medicine and Rehabilitation 85:919-924.
Laha RK, Dujovny M, Huamg PS (1979). Intermittent erection in spinal canal stenosis. Journal of Urology 121:123-124
Lehman TP, Jacobs JA (1983). Etiology of diabetic impotence. Journal of Urology 129:291-294.
Lipe H, Longstreeeth WT, Bird TD, Linde M (1990). Sexual function in married men with Parkinson´s disease compared to married men with artritis. Neurology 40:1347-1349.
Lombroso PJ, Scahill LD, Chappell PB, Pauls DL, Cohen DJ, Leckman JF (1995). Tourette´s syndrome: A multigenerational, neuropsychiatric disorder. Advances in Neurology 65:305-318.
Lue TF (1990). Impotence. A patient´s goal directed approach to treatment. World Journal of Urology 8:67-74.
Lue TF (1996). Editorial comment. Journal of Urology 156:552.
Lue
TF, Basson R, Rosen R, Giuliano F, Khoury S, Montorsi F (eds) (2004). Sexual
Medicine.
Lundberg PO (1966).Observations on endocrine function in ocular myopathy. Acta Neurologica Scandinavica 42:39-61.
Lundberg PO (1978) Sexual dysfunctionin women with multiple sclerosis. Sexuality ans Disability1:218-222.
Lundberg
Lundberg
Lundberg PO (1994) (ed). Sexologi. Stockholm: Liber.
Lundberg
Lundberg
Lundberg
Lundberg
Lundberg
Lundberg
Lundberg
Lundberg
Lundberg
Lundberg
PO, Brackett LB, Denys P, Chartier-Kastler E, Sønksen J, Vodusek DB (2000).
Neurological disorders: Erectile and ejaculatory dysfunction. In Jardin A,
Wagner G, Khoury S, Giuliano F, Padma-Nathan H, Rosen R. (eds) Erectile
dysfunction.
Lundberg
Lundberg
Maravilla
KR, Cao Y, Hewman JR, Yang C,
Marinkovic Z, Prelevic G, Würzburger M, Nocic S (1990). Gonadal dysfunction in patients with myotonic dystrophy. Experimental Clinical Endocrinology 96:37-44.
Marson L, Platt KB, McKenna KE (1993). Central nervous system innervation of the penis as revealed by the transneuronal transport of pseudorabies virus. Neuroscience 55:263-280.
Masters
WH, Johnson VE (1966). Human Sexual Response.
Mastrogiacomo I, Pagani E, Novelli G, Angelinin C, Gennarelli M, Menegazzo E, Bonanni G, Dallapiccola B (1994). Male hypogonadism in myotonic dystrophy is related to (CTG)n triplet mutation. Journal of Endocrinological Investigation 17:381-383.
Maytom
MC,
Mattson D, Petrie M, Srivastava K, McDermott M (1995). Multiple sclerosis. Sexual dysfunction and its response to medications. Archives of Neurology 52:862-868.
Mauroy B, Demondion X, Drizenko A, Goullet E, Bonnal J-L, Biserte J, Abbou C (2003). The inferior hypogastric plexus (pelvic plexus): its importance in neural preservation techniques. Surgical and Radiological Anatomy 25:6-15.
McCabe MP (2004). Exacerbation of symptoms among people with multiple sclerosis: Impact of sexuality. Archives of Sexual Behavior 33:593-601.
McDougall AJ, McLeod JG (1996). Autonomic neuropathy, I. Clinical features, investigation, pathophysiology, and treatment. Journal of the Neurological Sciences 137:79-88.
McKenna KE, Chung SK, McVary KT (1991). A model for the study of sexual function in anesthetized male and female rats. American Journal of Physiology 261: R1276.
Melberg A, Arnell H, Dahl N, Stålberg E, Raininko R, Oldfors A, Bakall B, Lundberg PO, Holme E (1996). Anticipation of autosomal progressive external ophthalmoplegia with hypogonadism. Muscle and Nerve 19:751-757.
Melman A, Henry DP, Felten DL, O´Connnor B (1980a). Effect of diabetes upon penile sympathetic nerves in impotent patients. Southern Medical Journal 73:307-310.
Melman A, Henry DP, Felten DL, O´Connor B (1980b). Alteration of the penile corpora in patients with erectile impotence. Investigative Urology 17:474-477.
Meston
CM, Hull E, Levin RJ, Sipski M. (2004) Women´s orgasm. Chapter 21 in Lue TF,
Basson R, Rosen R, Giuliano F, Khoury S, Montorsi F (eds). Sexual Medicine.
Editions 21
Meuleman EJ, Diemont WL (1995). Investigation of erectile dysfunction. Diagnostic testing for vascular factors in erectile dysfunction. Urological Clinics of North America 22:803-819.
Meyer JE (1955). Die sexuellen Störungen der Hirnverletzten. Archive für Psychiatatrie Zeitschrift für Nervenheilkunde 193:449-469.
Miller BL, Cummings JL, McIntyre H, Ebers G, Grode M (1986). Hypersexuality or altered sexual preference following brain injury. Journal of Neurology Neurosurgery and Psychiatry 49:867-873.
Minderhoud JM, Leemhuis JG, Kremer J, Labon E, Smits PML (1984). Sexual disturbances arising from multiple sclerosis. Acta Neurologica Scandinavica 70:299-306.
Mitsuya H, Asai J, Suyama K, Ushida T, Hosoe K (1960). Application of X-ray cinematography in urology. 1. Mechanisms of ejaculation. Journal of Urology 83: 86-95.
Monga TN, Monga M, Raina MS, Hardjsudarma M (1986b). Hypersexuality in stroke. Archives of Physical Medicine and Rehabilitation 67:415-417.
Montejo-González AL, Liorca G, Izquierdo JA, Ledesma A, Bousoño M, Calcedo JL, Ciudad J, Daniel 0E, de la Gandara J, Derecho J, Franco M, Gomez MJ, Macias JA, Maartin T, Perez V, Sanchez JM, Sanchez S, Vicens E (1997). SSRI-induced sexual dysfunction: Fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. Journal of Sex and Marital Therapy 23:176-194.
Montorsi F, Maga T, Strambi LF, Salonia A, Berbieri L, Scattonmi V, Guazzoni G, Losa A, Rigatti P, Pizzini G (2000). Sildenafil taken at bedtime significantly increases nocturnal erection: results of a placebo-controlled study. Urology 56:906-911.
Morales A (1994). Impotence. Journal of Urology 151:1235-1238.
Morales A, Condra M, Reid K (1990). The role of nocturnal penile tumescence monitoring in the diagnosis of impotence: a review. Journal of Urology 143:441-446.
Morrell MJ, Sperling MR, Stecker M, Dichter MA (1994). Sexual dysfunction in partial epilepsy: A deficit in physiological arousal. Neurology 44:243-247.
Morris M (1995). Dementia and cognitive changes in Huntington´s disease. Advances in Neurology 65:187-200.
Mueller
SC, Lue TF (1988). Evaluation of vasculogenic impotence. Urological Clinics of
Muhr
C, Hulting A-L, Lundberg
Neubauer M (1971). Die Behandlung von Potenzstörungen beim Diabetiker. Therapiewoche 21:614-620.
Neuhäuser G, Opitz JM (1975). Autosomal recessive syndrome of cerebellar ataxia and hypogonadotropic hypogonadism. Clinical Genetics 7:426.434.
Newman AS, Bertelson AD (1986). Sexual dysfunction in diabetic women. Journal of Behavioral Medicine. 9:261-270.
Ng KK,
Lim HCP, Ng FC, Li MK, Consigliere D, Chia SJ.(2002). The use of sildenafil in
patients with erectile dysfunction in relation to diabetes mellitus - a study
of 1,511 patients.
Obayashi K, Ando Y, Terazaki H, Yamashita S, Nakagawa K, Nakamura M, Yamashita T, Suge M, Ishizaki T, Uchino M, Ando M (2000). Effect of sildenafil citrate (Viagra) on erectile dysfunction in a patient with falilial amyloidotic polyneuropathy ATTR Val30Met. Journal of the Autonomous Nervous System 80:89-92.
Oliveira V, Ferro JM, Foreid JP, Costa T, Levy A (1989). Klüver-Bucy syndrome in systemic lupus eruthematosus. Journal of Neurology 236:55-56.
O`Leary MP, Fowler FJ, Lenderking WR, Barber B, Sagnier PP, Guess HA, Barry MJ (1995). A brief male sexual function inventory for urology. Urology 46:697-706.
Olsson T, Olofsson B-O, Hägg E, Grankvist K, Henriksson A (1996). Adrenocortical and gonadal abnormalities in dystrophia myotonica - a common enzyme defect? European Journal of Internal Medicine 7:29-33.
Padma-Nathan
H (1988). Neurological evaluation of erectile dysfunction. Urological Clinics
of
Padma-Nathan
H, Hellstrom WJ, Kaiser FE, Labasky RF, Lue TF, Nolten WE,
Palmer JS, Kaplan WE, Firlit CF (1999). Erectile dysfunction in spina bifida is treatable. Lancet 354.125-126.
Pellegrinetti A, Moscato G, Siciliano G, Bonuccelli U, Orlando G, P Maritato, Sartucci F (2003). Electrophysiological evaluation of genito-sphincteric dysfunction in multiple systeme atrophy. International Journal of Neurosciences 113:1353-1369.
Patterson WM (1993). Fluoxetine induced sexual dysfunction. Journal of Clinical Psychiatry 54:71.
Penfield
W, Jasper H (1954). Epilepsy and the Functional Anatomy of the Human Brain.
Perese DM, Prezzo JA, Perese EF (1976). Sexual dysfunction caused by injuries of the cervical spinal cord without paralysis. Spine 1:149-154.
Podnar S, C Oblak C, Vodusek DB (2002). Sexual function in men with cauda equina lesions: a clinical and electromyographic study. Journal of Neurolology Neurosurgery and Psychiatry 73: 715-20.
Raffaele R, Vecchio I, Giammusso B, Morgia G, Brunetto MB, Rampello L (2002). Efficacy and safety of fixed-dose oral sildenafil in the treatment of sexual dysfunction in depressed patients with idopathic Parkinson´s disease. European Urology 41:382-386.
Rendell MS, Rajfer J, Wicker PA, Smith MD for the Sildenafil Diabetes Study Group (1999). Sildenafil for treatment of erectile dysfunction in men with duabetes. Journal of American Medical Association 281:421-426.
Rivas D, Chancellor M (1994). Complications associated with the use of vacuum contsriciton devices for erectile dysfunction in the spinal cord injured population. Journal of American Paraplegia Society 17:136-139.
Sachs BD (1995). Placing erection in context: The reflexogenic psychogenic dichotomy reconsidered. Neuroscience and Biobehavioral Review 19:211-224.
Saenz de Tejada I, Anglin G, Knight JR, Emmick J. (2002). Effects of tadalafil on erectile dysfunction in men with diabetes. Diabetes Care 25:2159-2164.
Saenz de Tejada I, Ware JC, Blanco R, Pittard JT, Nadig PW, Azadzoi KM, Krane RJ, Goldstein I (1991). Pathophysiology of prolonged penile erection associated with trazodone use. Journal of Urology 145:60-64.
Sakakibara R, Hatteri T, Fukutake T, Mori M, Yamanishi T, Yasuda K (1998). Micturitional disturbances in a patient with adrenomyelo-neuropathy (AMN). Neurourology and Urodynamics 17:207-212.
Sakakibara R, Shinotoh H, Uchiyama T, Sakuma M, Kashiwado M, Yoshiyama M, Hattori T (2001). Questionnaire-based assessment of pelvic organ dysfunction in Parkinson´s disease. Autonomous Neuroscience 17:76-85.
Sanchez Ramos A, Vidal J, Jáuregui ML, Barrera M, Recia C, Giner M, Toribio L, Salvador S, Sanmartin A, de la Fuente M, Santos JF, de Juan FJ, Moraleda S, Mendez JL, Ramirez L, Casado RM (2001). Efficacy, safety and predictive factors of therapeutic success with sildenafil for erectile dysfunction in patients with different spinal cord injuries. Spinal Cord 39:637-643.
Sato K (1991). Seminal emission by electrical stimulation of the spermatic nerve and epidydimis. Internationl Journal of Andrology 14:461-463.
Saunders M, Rawson M (1970). Sexuality in male epileptics. Joaurnal of the Neurological Sciences 10:577-583.
Sawyer SM, Roberts KV (1999). Sexual and reproductive health in young people with spina bifida. Developmental Medicine and Child Neurology. 41:671-675.
Schirren C, Rehacek M, De Cooman S, Widman H-U (1973). Die retrograde Ejakulation. Andrologie 5:7-14.
Schmid DM, Schur B, Hauri D (2000). Sildenafil in the treatment of sexual dysfunction in spinal cord-injured patients. European Urology 38:184-193.
Schreiner-Engel P, Schiavi RC, Vietorisz D, Smith H (1987). The differential impact of diabetes type on female sexuality. Journal of Psychosomatic Research 31:23-33.
Seckin B, Atmaca I, Ozgok Y, Gokalp A, Harmankaya C (1996). External vacuum device therapy for spinal cord injured males with erectile disorders. International Urology and Nephrology 28:235-240.
Seminara
SB, Acierno JS, Abdulwahid NA,
Shukla
GD,
Sidi A, Cameron J, Dystra D, Reinberg Y, Lange P (1987), Vasoactive intracavernous pharmacotherapy for the treatment of erectile impotence in men with spinal cord injury. Journal of Urology 138:539-542.
Simpson G, Blaszczynski A, Hodgkinson A (1999). Sex offending as a psychosocial sequela of traumatic brain injury. Journal of Head Trauma Rehabilitation 14:567-580.
Singer C, Weiner WJ, Sanchez-Ramos JR (1992). Autonomic dysfunction in men with Parkinson´s disease. European Neurology 32:134-140.
Sipski ML, Alexander CJ, Rosen R (2001). Sexual arousal and orgasm in women: Effects of spinal cord injury. Annals of Neurology 49:35-44.
Sipski ML, Rosen RC, Alexander CJ, Hamer RM (2000). Sildenafil effects on sexual and cardiovascular responses in women with spinal cord injury. Urology 55:812-815
Sitsen
JMA (1988). Prescription drugs and sexual function. In Money J, Musaph H (eds):
Handbook of Sexology.
Sjögren K, Damber J-E, Lilieqvist B (1983). Sexuality after stroke. I. Aspects of sexual function. Scandinavian Journal of Rehabilitation Medicine 15:55-61.
Smith
EM,
Takahashi A (1991). Autonomic nervous system disorders in Parkinson's disease. European Neurology 31:suppl. 1:41-47.
Thase ME, Reynolds CF III, Jennings JR, Frank E, Howell JR, Houck PR, Berman S, Kupfer DJ (1988). Nocturnal penile tumescence is diminished in depressed men. Biological Psychiatry 24:33-46.
The
Therapeutics and Technology Assessment Subcommittee of the
Tjandra BS, Janknet RA (1997). Neurogenic impotence and lower urinary tract symptoms due to vitamin B1 deficiency in chronic alcoholism. Journal of Urology 157:954-955.
Tyrer
G, Steel JM,
Uitti RJ, Tanner CM, Rajput AH, Goetz CG, Klawans HL, Thiessen B (1989). Hypersexuality with antiparkinsonian therapy. Clinical Neuropharmacology 12:375-383.
Valleroy M, Kraft G (1984). Sexual dysfunction in multiple sclerosis. Archives of Physical Medicine and Rehabilitation 65:125-128.
Vardi Y, Sprecher E, Kanter Y, Livne PM, Hemli JA, Yarnitsky D (1996). Polyneuropathy in impotence. International Journal of Impotence Research 8:65-68.
Vardi Y, Gruenwald I, Sprecher E, Gertman I, Yartnisky D (2000). Normative values for female genital sensation. Urology 56:1035-1040.
Vas CJ (1969). Sexual impotence and some autonomic disturbances in men with multiple sclerosis. Acta Neurologica Scandinavica 45:166-182.
Vodusek DB (1998). Neurophysiological tests in erectile dysfunction. Scandinavian Journal of Sexology 1:81-95.
Vodusek DB (2001). Sphincter EMG and differential diagnosis of Multiple system atrophy. Movement Disorders 16: 600-607.
Vodusek DB, Fowler CJ (2004). Pelvic floor
clinical neurophysiology. In: Binnie C, Cooper R, Mauguière F, Osselton J,
Prior P, Tedman B, editors. Clinical neurophysiology. Vol. 1. EMG, nerve
conduction and evoked potentials.
Vodusek DB, Zidar J (1987). Pudendal nerve involvement in patients with hereditary motor and sensory neuropathy. Acta Neurologica Scandinavica 76:457-460.
Vodusek DB, Ravnik-Oblak M, Oblak C (1993). Pudendal versus limb nerves electrophysiologic abnormalities in diabetics with erectile dysfunction. International Journal of Impotence Research 2: 37-42.
Vodusek DB
(Chairman), Amarenco G, Batra A, Benson T, Bharucha AE, Podnar S, Yang CC
(2005). Committee 8: Clinical neurophysiology. In: Abrams P, Cardozo L, Khoury
S, Wein A (eds.) Incontinence, volume 1,
Basics & Evaluation, chapter 12. 3rd International
Consultation on Incontinence,
Wabrek AJ, Wabrek CJ, Burchell RC (1978). The human tragedy of spina bifida. Spinal myelomeningocele. Sexuality and Disability 1:210-217.
Wasserman MD, Pollak CP, Spielman A J, Weitzman ED (1980). Theoretical and technical problems in the measurement of nocturnal penile tumescence for differential diagnosis of impotence. Psychosomatic Medicine 42:575-585.
Wermuth L, Stenager E (1995). Sexual problems in young patients with Parkinson´s disease. Acta Neurologica Scandinavica 91:453-455.
Westgren
N (1999). Women with traumatic spinal cord injury. Doctoral Thesis.
Whipple B (2000). Beyond the G spot. New research on human female sexual anatomy and physiology. Scandinavian Journal of Sexology 3;35-42.
Wieder JA, Brackett NL, Lynne CM, Green JT, Aballa TC (2000). Anesthetic block of the dorsal penile nerve inhibits vibratory-induced ejaculation in men with spinal cord injuries. Urology 55:915-917.
Wiig EH (1973). Counseling the adult aphasic for sexual readjustment. Rehabilitation Counseling Bulletin (Dec)110-119.
Wincze JP, Albert A, Bansal S (1993). Sexual arousal in diabetic females: physiological and self-report measures. Archives of Sexual Behavior 22:587-601.
Yang CC, Bowen JR, Kraft GH, Uchio EM, Kromm BG (2000). Cortical evoked potentions of the dorsal nerve of the clitoris and female sexual dysfunction in multiple sclerosis. Journal of Urology 164:2010-2013.
Yang CC, Bowen JD, Kraft GH, Uchio EM, Kromm BG (2001). Physiologic studies of male sexual dysfunction in multiple sclerosis. Multiple Sclerosis 7:249-254.
Yarnitsky D, Sprecher E, Vardi Y (1996). Penile thermal sensation. Journal of Urology 156:391-393.
Zaviacic M (2000). The Human Female Prostate. Litera Medica, CD
Zaviacic M (2001). The human female prostate and its role in women`s life: Sexology implications. Scandinavian Journal of Sexology 4:199-211.
Zesiewicz TA, Baker MJ, Wahba M, Hauser RA (2003). Autonomic nervous system dysfunction in Parkinson´s disease. Current Treatment Options in Neurology 5:149-160.
Zesiewicz TA, Helal M, Hauser RA (2000). Sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men with Parkinson´s disease Movement Disorders 15.305-308.
Zgur T, Vodusek DB, Krzan M, Vrtovec M, Denislic M, Sibanc B (1993). Autonomic system dysfunction in moderate diabetic polyneuropathy assessed by sympathetic skin response and Valsalva index. Electromyography and Clinical Neurophysiology 33: 433-439.
Zivadinov R, Zorzon M, Bosco A, Bragadin LM, Moretti R, Bonfigli L, Iona LG, Cazzato G (1999). Sexual dysfunction in multiple sclerosis: II. Correlation analysis. Multiple Sclerosis 5:428-431.
Zivadinov R, Zorzon M, Locatelli L, Stival B, Monti F, Nasuelli D, Tommasi MA, Bratina A, Cazzato G (2003). Sexual function in multiple sclerosis: a MRI, neurophysiological and urodynamic study. Journal of the Neurological Sciences 210:73-76.
|