High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo-controlled double-blind study.

UNLABELLED: Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS. The current study, a double blind, placebo-controlled, randomised, stratified, parallel-group clinical trial, was designed to determine whether vitamin E (5000 mg per day) may be efficacious in slowing down disease progression when added to riluzole. METHODS: 160 patients in 6 German centres with either probable or definite ALS (according to the El Escorial Criteria) and a disease duration of less than 5 years, treated with riluzole, were included in this study and were randomly assigned to receive either alpha-tocopherol (5000 mg per day) or placebo for 18 months. The Primary outcome measure was survival, calculating time to death, tracheostomy or permanent assisted ventilation, according to the WFN-Criteria of clinical trials. Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing (BMRC), spasticity scale, ventilatory function and the Sickness Impact Profile (SIP ALS/19). Patients were assessed at entry and every 4 months thereafter during the study period until month 16 and at a final visit at month 18. Vitamin E samples were taken for compliance check and Quality Control of the trial. For Safety, a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 18. Height and weight were recorded at baseline and weight alone at the follow-up visits. A neurological examination as well as vital signs (heart rate and blood pressure), an ECG and VEP's were recorded at each visit. Furthermore, spontaneously reported adverse experiences and serious adverse events were documented and standard laboratory tests including liver function tests performed. For Statistical Analysis, the population to be considered for the primary outcome measure was an "intent-to-treat" (ITT) population which included all randomised patients who had received at least one treatment dose (n = 160 patients). For the secondary outcome measures, a two way analysis of variance was performed on a patient population that included all randomised patients who had at least one assessment after inclusion. RESULTS: Concerning the primary endpoint, no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test. The functional assessments showed a marginal trend in favour of vitamin E, without reaching significance. CONCLUSION: Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. However, administration of this megadose does not seem to have any significant side effects in this patient population.

[Erectile function disorders. Epidemiology, physiology, etiology, diagnosis and therapy]. / Erektile Funktionsstörungen. Epidemiologie, Physiologie, Atiologie, Diagnostik und Therapie.

Erectile dysfunction is a common, age-dependent functional disturbance of men associated to various comorbidities. Interdisciplinary cooperation with neurologists in ca-ses of a suspected neurological aetiology and with psychiatrists in cases with normalorganic diagnostic findings is necessary. Hormone replacement and psychotherapy can cure certain patients. Oral pharmacotherapy is the most effective therapy for erectile dysfunction with the highest patient preference. Oral PDE-5-inhibitors(sildenafil, tadalafil, vardenafil) are superior in effectiveness to centrally acting drugs (apomorphin, yohimbine). Local pharmacotherapy (MUSE, ICI) is a second line therapy in cases of failure or contraindications for oral pharmacotherapy. Vacuum therapy and operative procedures(penile implants) complete the therapeutic options of erectile dysfunction.

[Erectile dysfunction. Epidemiology, physiology, etiology, diagnosis and therapy]. / Erektile Funktionsstörungen. Epidemiologie, Physiologie, Atiologie, Diagnostik und Therapie.

Erectile dysfunction is a common, age-dependent functional disturbance of men associated to various comorbidities. Interdisciplinary cooperation with neurologists in cases of a suspected neurological aetiology and with psychiatrists in cases with normal organic diagnostic findings is necessary. Hormone replacement and psychotherapy can cure certain patients. Oral pharmacotherapy is the most effective therapy for erectile dysfunction with the highest patient preference. Oral PDE-5-inhibitors (sildenafil, tadalafil, vardenafil) are superior in effectiveness to centrally acting drugs (apomorphin, yohimbine). Local pharmacotherapy (MUSE, ICI) is a second line therapy in cases of failure or contraindications for oral pharmacotherapy. Vacuum therapy and operative procedures (penile implants) complete the therapeutic options of erectile dysfunction.

Penile and perianal pudendal nerve somatosensory evoked potentials in the diagnosis of erectile dysfunction.

Neurophysiologic examinations in differential diagnosis of erectile dysfunction comprise electromyogramme of the pelvic floor, pudendal nerve terminal motor latency (PNTML) and evaluation of pudendal somatosensory evoked potentials (SSEP). We focused our interest on comparing diagnostic importance of penile and perianal pudendal nerve SSEP. We examined 20 patients suffering from erectile dysfunction and 20 patients without any manifestation of impotence. The stimulus was administered using penile ring electrodes at the base of the penis (cathode) and distally on the penis shaft (anode), as well as a perianal surface electrode applied at 3 o'clock in lithotomy position and 5 cm laterally on the gluteal skin. The potentials were recorded with intradermal needle electrodes at C(z)-2 cm (different) and F(z) (indifferent). 500 stimuli were averaged for a single tracing. The stimulus strength was set at an average of 3-4 times the stimulus threshold. Cortical latency of P 40 ranged from 39.0 to 45.6 ms (penile) and from 33.6 to 43.2 ms (perianal) in the control group, in the patient group latencies ranged from 38.8 to 51.6 (penile) and 34.0 to 44.8 ms (perianal). In two patients no potential was recordable after perianal stimulation, one patient showed a marked prolongation of the penile response with a normal perianal latency. Penile and perianal latencies of P 40 were significantly prolonged in the patient group compared to the control group (P<0.05). The combination of penile and perianal pudendal SSEP may provide valuable additional information in differential diagnosis of erectile dysfunction, especially allowing to identify different sites of neurogenic lesions. In contrast to perianal pudendal SSEP, penile stimulation may help to discover pathologic changes in the distal course of the pudendal nerve, especially the dorsal nerve of the penis.

Treatment of erectile dysfunction by an external ischiocavernous muscle stimulator.

OBJECTIVE: The aim of the present study was to evaluate the therapeutic potency of an electrotherapy of striated ischiocavernous muscles in patients with erectile dysfunction. PATIENTS AND METHODS: Transcutaneous electrostimulation of striated ischiocavernous muscles by self-adhesive penile or perineal skin electrodes was performed in 48 patients with erectile dysfunction. 6/48 patients (R) responded to intracavernous pharmacotherapy while 42/48 (NR) did not show significant penile rigidity even to intracavernous papaverine/phentolamine/PGE1 triple drug medication. RESULTS: Within the observation time of 3 months, 10/48 patients dropped out. 22/38 patients reported a penile rigidity for sufficient sexual intercourse whereby 3/22 NR required additional intracavernous pharmacotherapy. Penile rigidity could be objectivated by triple drug medicaton in 12/14 NR after ischiocavernous muscle stimulation (EIS) therapy. 5/6 R were treated successfully for premature erection loss. During EIS treatment neither discomfort nor complications could be observed. CONCLUSION: Transcutaneous electrostimulation of ischiocavernous muscles is a new, noninvasive therapy for the improvement of penile rigidity. The clinical results underline the importance of the striated ischiocavernous muscles for penile rigidity.

[Electrophysiologic diagnosis in erectile dysfunction]. / Elektrophysiologische Diagnostik bei der erektilen Dysfunktion.

So far, electrophysiological examinations have rarely been used in the diagnosis of erectile dysfunction (ED) mainly because the methods available only allow somatic neuron pathways to be examined whose relevance for the mainly autonomically controlled crection is evaluated differently. At present, impaired penile nerve supply as the possible cause of ED can only be evaluated through neurophysiological screening of the somatic and autonomic pathways of the pelvic floor, and not just by one simple method. Diagnosing ED should include testing of motoric efferences through electroneurography of the pudendal nerve and electromyography of the external anal sphincter and the urethral sphincter. Sensitive afference is tested with somatosensory evoked potentials of the pudendal nerve. New methods that are available for the examination of autonomic pathways are the penile sympathetic skin response and the EMG of the corpus cavernosum. Together with the other electrophysiological examinations, they allow neurogenic causes to be determined and differentiate not only between central and peripheric lesions, but also between acute and chronic changes. Prognosis can also be estimated. A crucial diagnostic deficit is the fact that it is still not possible to test the parasympathetic system directly.

Eye movement in amyotrophic lateral sclerosis: a longitudinal study.

Eye muscles and the sphincter muscles of the bowel and bladder were formerly thought to be spared in amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder. As frequent subclinical impairment of the anal sphincter muscles in ALS has recently been reported, We suspected an earlier and more frequent, if subclinical, involvement of the oculomotor system than hitherto described. Starting in 1993, we repeatedly studied oculomotor involvement in eight patients with (ALS) using routine orthoptic examination techniques as well as electro-oculographic recordings of ocular movements. Three patients had consistently normal clinical examinations but progressive changes in electro-oculography (EOG). Three patients showed intermittent impairment of eye movements with normal EOG (one patient) or with progressive changes on EOG examination. In two patients, both clinical examination and EOG were progressively pathologic. These findings provide further evidence of early oculomotor involvement, e.g., prior to respiratory failure, in ALS than previously suspected. Since EOG changes seemed to be detectable in all but one patient, EOG changes may allow earlier, subclinical detection of impaired eye movement and thus reveal even an increased frequency of oculomotor impairment in ALS. Due to the heterogeneity of ALS the number of patients examined to settle finally the question of oculomotor involvement in ALS needs to be increased. Newly developed software will allow further interpretation and comparison of more data and, thus, should offer further help in detecting early changes.

[Disorders of eye movement in amyotrophic lateral sclerosis--report of 2 patients]. / Augenbewegunsstörungen bei Amyotropher Lateralsklerose--Bericht über zwei Patienten.

BACKGROUND: Amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder of unknown origin, was thought to spare the extraocular muscles. Extraocular involvement has recently been reported to occur in the late stages of ALS following respiratory insufficiency. CASE REPORT: We report on two patients with ALS who were referred for screening of oculomotor impairment in ALS. Orthoptic examination in a 64-year-old woman with peripheral ALS revealed retraction of the upper eye lids as well as impaired abduction and upgaze in both eyes, developing prior to respiratory insufficiency. A 50-year-old man with bulbar ALS was found to have bilateral impairment of upgaze as well as a negative Bell's phenomenon. Horizontal pursuit was interrupted by compensatory saccades, vertical fixating saccades were slightly hypometric. These oculomotor changes were also seen prior to respiratory insufficiency. CONCLUSION: These findings provide further evidence of early oculomotor involvement in ALS, e.g. prior to respiratory failure and prior than previously suspected. Oculomotor impairment may occur in both the peripheral and the bulbar type of ALS.

Penile sympathic skin response in erectile dysfunction.

Penile sympathic skin response (PSSR) was measured in 20 normal patients and in 46 patients with erectile dysfunction (ED). PSSR could be registered in 80% of normal patients. The latencies were 1,100-1,600 ms. In patients with ED, latencies were 1,240-3,640 ms. A reproducible normal latency of PSSR (< 1,600 ms) indicates a normal sympathic innervation of the penis. Long latencies (> 1,800 ms) indicate neuropathy of unmyelinated nerval fibers. The loss of a reproducible answer however allows no exact diagnostic information. PSSR is a useful diagnostic test for detecting neuropathy of unmyelinated nerval fibers as a possible cause of ED.