Human spinal ejaculation generator.

OBJECTIVE: A spinal ejaculation generator (SEG) has been identified in the rat with lumbar galaninergic interneurons playing a pivotal role (Science 2002;297:1566-1569). The aim was to evidence a SEG in humans. METHODS: Spatial distribution of galaninergic neurons was studied in postmortem spinal cord segments of 6 men and compared with that of 6 women for evidencing sexual dimorphism. Based on the identified segmental distribution of galaninergic neurons, the ability for penile vibratory stimulation (PVS) to elicit ejaculation when the concerned spinal segments were injured was studied in 384 patients with clinically complete spinal cord injury (SCI) and consequent anejaculation. Such patients represent a unique model to investigate the role of defined spinal segments in the control of ejaculation. RESULTS: Galaninergic neurons were mostly located between L2 and L5 segments in medial lamina VII, with a maximal density within L4. Three-dimensional 3D reconstruction showed that these neurons were grouped into single columns bilaterally to the central canal. In addition, galaninergic neuron density was found higher in L3 and L4 segments in men as compared to women supporting sexual dimorphism. In the patients' cohort, injury of L3-L5 segments was the sole independent predictor for failure of PVS to induce ejaculation. Although evidence from clinical observations was indirect, there is close correspondence to neuroanatomical data. INTERPRETATION: Organization and sexual dimorphism of human spinal galaninergic neurons were similar to the rat's SEG. Neurohistological data, together with clinical results, corroborate the existence of an SEG in humans in L3-L5 segments. Such a generator could be targeted to treat neurogenic and non-neurogenic ejaculatory disorders. ANN NEUROL 2017;81:35-45.

Impact of the operative delay and the degree of neurologic sequelae on recurrence of excised heterotopic ossification in patients with traumatic brain injury.

The timing of surgery with regard to recurrence risk after neurologic heterotopic ossification (HO) excision is still debated. This study investigated the association between recurrence risk after HO excision in traumatic brain injury (TBI) patients and (1) the operative delay and (2) the degree of neurologic sequelae (Garland status). A case-control study was performed. Patients who developed troublesome HO requiring surgery after TBI with (case, n = 16) or without recurrence (control, n = 64) were retrospectively included. Other matching criteria were sex and age at the time of surgery (± 4 years). The median delay for first HO surgery was 13.7 months (interquartile range: 9.0-37.1) for the case group and 13.2 months (interquartile range: 7.8-30.0) for the control group. No significant link was found between recurrence and operative delay (P = .54), even after inclusion of all matching factors (P = .53), or Garland status (P = .81). The inclusion of Garland status into the model did not change this result (P = .64). After TBI, no link was found between HO operative delay and recurrence. In spite of a common notion of a relationship between initial severity of TBI and HO development, no link was found between HO recurrence risk and the severity of sequelae.

Intracavernous Injections in Spinal Cord Injured Men With Erectile Dysfunction, a Systematic Review and Meta-Analysis.

INTRODUCTION: Despite improvements in the care of patients after spinal cord injury (SCI), permanent impairment of locomotion, sensation, and autonomic function remains a major hurdle. After the acute stage of injury, recovering sexual function is a high priority. AIM: To review the efficacy of intracavernous injections (ICIs) in men with SCI and to identify prognostic factors affecting the efficacy of ICIs in this population. METHODS: Systematic review of the literature was conducted using the PubMed-Medline, Embase, EBSCO, Web of Science, and Cochrane Library databases. The literature search was restricted to articles published in English, French, and Spanish up to November 2014 using the key words alprostadil, papaverine, moxisylite, alpha-blocking agent, phentolamine, intracavernous injection, spinal cord injuries, paraplegia, quadriplegia, and erectile dysfunction. Studies involving patients with SCI and erectile dysfunction treated with ICIs of alprostadil, papaverine, and α-blocking agents, including retrospective and prospective cohorts, population studies, and randomized controlled trials, were included. MAIN OUTCOME MEASURE: Overall response rate to ICI for erectile dysfunction in patients with SCI. RESULTS: Of 283 studies identified, 23 involved 713 patients with SCI. ICIs resulted in successful erections in 88% of patients (n = 713, 95% CI = 83%-92%). Erections were obtained in 93% of patients (n = 101, 95% CI = 83%-99%) with the combination of papaverine and phentolamine, in 91% (n = 274, 95% CI = 78%-97%) with papaverine alone, and in 80% (n = 119, 95% CI = 64%-90%) with alprostadil. Type of injected drug, doses, level of injury (complete or incomplete), extent of injury, age, time since injury, and persistence or transience of erections were evaluated, but statistical analysis could not identify specific factors predictive of a response to ICI. CONCLUSION: ICIs are an effective treatment of erectile dysfunction in men with SCI. No predictive factor for efficacy could be identified. Studies comparing the response to ICI in upper vs lower motor neuron lesions could improve our understanding of ICI failure.

The spinal control of ejaculation revisited: a systematic review and meta-analysis of anejaculation in spinal cord injured patients.

BACKGROUND After spinal cord injury (SCI), most men cannot ejaculate without medical assistance. A major advance in the knowledge of the spinal control of ejaculation has been achieved with the discovery of a spinal generator of ejaculation (SGE) in the rat. The aim of this report was to review studies about ejaculation after SCI in order to revisit the spinal control of ejaculation and especially to assess the existence of an SGE in man. METHODS Studies were identified from Embase, PubMed, EBSCOhost and Cochrane Library. Studies were eligible when they specify the occurrence of antegrade ejaculation as a function of the neurological characterization of SCI. Studies were excluded when ejaculation was elicited by rectal electrical stimulation or when ejaculation could not be discriminated from climax. Meta-analyses were performed to assess the reference ejaculation rates for each procedure used to elicit ejaculation, i.e. masturbation or coïtus, penile vibratory stimulation (PVS) or acetylcholine esterase (AchE) inhibitors prior to masturbation. Subgroup analyses were performed according to the procedure used to elicit ejaculation on (i) the completeness of the SCI and (ii) the upper and lower limits of the SCI. To assess the existence of an SGE, the effect of concurrent lesions of different spinal segments was assessed by means of a stratified bivariate analysis. RESULTS From 523 studies, 45 were selected (n = 3851). Ejaculation occurred in response to masturbation or coïtus, PVS or AchE inhibitors followed by masturbation in, respectively, 11.8% (n = 1161), 47.4% (n = 597) and 54.7% (n = 309) of patients with complete SCI and in, respectively, 33.2% (n = 343), 52.8% (n = 305) and 78.1% (n = 32) of patients with incomplete SCI. Ejaculation, in the case of complete lesion of the sympathetic centres (T12 to L2), of the parasympathetic and somatic centres (S2-S4) or of all spinal ejaculation centres (T12 to S5) occurred in response to PVS in none of the patients (respectively, n = 5, n = 4 and n = 21) and in response to AchE inhibitors followed by masturbation in 4.9% (n = 61), 30.8% (n = 26) and 0% (n = 16) of the patients, respectively. Ejaculation in response to PVS or AchE inhibitors prior to masturbation was rhythmic forceful in 97.9% (n = 48) of the patients with complete lesion strictly above Onuf's nucleus (segments S2-S4). Complete lesion of the S2-S4 segments precluded the occurrence of rhythmic forceful ejaculation (n = 5). Controlling for the number of the injured segments between T12 and L2, the ejaculation rate sharply decreased when the lesion extended to the L3 segment and below. CONCLUSIONS The results reinforce the crucial roles of the spinal sympathetic and parasympathetic centres for emission and the somatic centre for expulsion. The spinal segments between L2 and S2 is more than a pathway to connect the ejaculation centres and likely harbours an SGE in man located in the L3, L4 and L5 segments.

The impact of preoperative hip heterotopic ossification extent on recurrence in patients with head and spinal cord injury: a case control study.

BACKGROUND: The preoperative Heterotopic Ossification (HO) extent is usually one of the main used criteria to predict the recurrence before excision. Brooker et al built a radiologic scale to assess this pre operative extent around the hip. The aim of this study is to investigate the relationship between the recurrence risk after hip HO excision in Traumatic Brain Injury (TBI) and Spinal Cord Injury (SCI) patients and the preoperative extent of HO. METHODOLOGY/PRINCIPAL FINDINGS: A case control study including TBI or SCI patients following surgery for troublesome hip HO with (case, n = 19) or without (control, n = 76) recurrence. Matching criteria were: sex, pathology (SCI or TBI) and age at the time of surgery (+/-4.5 years). For each etiology (TBI and SCI), the residual cognitive and functional status (Garland classification), the preoperative extent (Brooker status), the modified radiological and functional status (GCG-BD classification), HO localization, side, mean age at the CNS damage, mean delay for the first HO surgery, and for the case series, the mean operative delay for recurrence after the first surgical intervention were noted. CONCLUSIONS/SIGNIFICANCE: The median delay for first HO surgery was 38.6 months (range 4.5 to 414.5;) for the case subgroup and 17.6 months (range 5.7 to 339.6) for the control group. No significant link was found between recurrence and operative delay (p = 0.51); the location around the joint (0.07); the Brooker (p = 0.52) or GCG-BD status (p = 0.79). Including all the matching factors, no significant relationship was found between the recurrence HO risk and the preoperative extent of troublesome hip HO using Brooker status (OR = 1.56(95% CI: 0.47-5.19)) or GCG-BD status (OR class 3 versus 2 = 0.67(95% CI: 0.11-4.24) and OR class 4 versus 2 = 0.79(95%CI: 0.09-6.91)). Until the pathophysiology of HO development is understood, it will be difficult to create tools which can predict HO recurrence.