Michael D. Craggs

Disability, atrophy and cortical reorganization following spinal cord injury

The impact of traumatic spinal cord injury on structural integrity, cortical reorganization and ensuing disability is variable and may depend on a dynamic interaction between the severity of local damage and the capacity of the brain for plastic reorganization. We investigated trauma-induced anatomical changes in the spinal cord and brain, and explored their relationship to functional changes in sensorimotor cortex. Structural changes were assessed using cross-sectional cord area, voxel-based morphometry and voxel-based cortical thickness of T1-weighted images in 10 subjects with cervical spinal cord injury and 16 controls. Cortical activation in response to right-sided (i) handgrip; and (ii) median and tibial nerve stimulation were assessed using functional magnetic resonance imaging. Regression analyses explored associations between cord area, grey and white matter volume, cortical activations and thickness, and disability. Subjects with spinal cord injury had impaired upper and lower limb function bilaterally, a 30% reduced cord area, smaller white matter volume in the pyramids and left cerebellar peduncle, and smaller grey matter volume and cortical thinning in the leg area of the primary motor and sensory cortex compared with controls. Functional magnetic resonance imaging revealed increased activation in the left primary motor cortex leg area during handgrip and the left primary sensory cortex face area during median nerve stimulation in subjects with spinal cord injury compared with controls, but no increased activation following tibial nerve stimulation. A smaller cervical cord area was associated with impaired upper limb function and increased activations with handgrip and median nerve stimulation, but reduced activations with tibial nerve stimulation. Increased sensory deficits were associated with increased activations in the left primary sensory cortex face area due to median nerve stimulation. In conclusion, spinal cord injury leads to cord atrophy, cortical atrophy of primary motor and sensory cortex, and cortical reorganization of the sensorimotor system. The degree of cortical reorganization is predicted by spinal atrophy and is associated with significant disability.

Electrical stimulation for the treatment of bladder dysfunction: current status and future possibilities

Abstract Electrical stimulation of peripheral nerves can be used to cause muscle contraction, to activate reflexes, and to modulate some functions of the central nervous system (neuromodulation). If applied to the spinal cord or nerves controlling the lower urinary tract, electrical stimulation can produce bladder or sphincter contraction, produce micturition, and can be applied as a medical treatment in cases of incontinence and urinary retention. This article first reviews the history of electrical stimulation applied for treatment of bladder dysfunction and then focuses on the implantable Finetech-Brindley stimulator to produce bladder emptying, and on external and implantable neuromodulation systems for treatment of incontinence. We conclude by summarizing some recent research efforts including: (a) combined sacral posterior and anterior sacral root stimulator implant (SPARSI), (b) selective stimulation of nerve fibers for selective detrusor activation by sacral ventral root stimulation, (c) microstimulation of the spinal cord, and (d) a newly proposed closed-loop bladder neuroprosthesis to treat incontinence caused by bladder overactivity. [Neurol Res 2002; 24: 413-430]

Neuromodulation of the lower urinary tract

For many years it has been known that peripheral electrical stimulation of the pudendal nerves through the skin or by implant can have a beneficial effect in the treatment of problems of the lower urinary tract, especially urinary incontinence caused by sphincter weakness or bladder overactivity (Thon et al. 1991; Fall & Madersbacher, 1994). This type of therapy seems to depend on a physiological process, commonly known as neuromodulation, in which the influence of activity in one neural pathway modulates the pre-existing activity in another through synaptic interaction. Little is known about the actual mechanisms underlying the success of this treatment in man, but some animal studies suggest a neurophysiological basis for neuromodulation (Fall & Lindstrom, 199 1). Many of the modulatory reflex mechanisms controlling normal continence are inhibitory in nature and have been shown to occur throughout the central and peripheral nervous systems involving a variety of neurotransmitter pathways (de Groat, 1997). It is probably aberrations in some of these pathways, for example, underactive inhibition at the brainstem level from more rostra1 cerebral structures or loss of descending inhibitory pathways to the sacral segmental reflexes, that causes bladder and sphincter dysfunction in the first place. Such dysfunction usually leads to incontinence. This paper focuses on those spinal and peripheral modulatory mechanisms that appear to be implicated in the pathophysiology of voiding dysfunction. It describes how applied neuromodulation of some specific peripheral pathways can help to overcome the incontinence resulting from these dysfunctions, especially bladder overactivity. It will also describe how neurostimulation is being used to investigate reflex pathways of the lower urinary tract in people both with and without bladder problems and the relevance of these studies in helping us to understand the aetiology of voiding dysfunction and the. physiological basis for its control by neuromodulation in man.

Corticomotor representation to a human forearm muscle changes following cervical spinal cord injury.

Functional imaging studies, using blood oxygen level‐dependent signals, have demonstrated cortical reorganization of forearm muscle maps towards the denervated leg area following spinal cord injury (SCI). The extent of cortical reorganization was predicted by spinal atrophy. We therefore expected to see a similar shift in the motor output of corticospinal projections of the forearm towards more denervated lower body parts in volunteers with cervical injury. Therefore, we used magnetic resonance imaging‐navigated transcranial magnetic stimulation (TMS) to non‐invasively measure changes in cortical map reorganization of a forearm muscle in the primary motor cortex (M1) following human SCI. We recruited volunteers with chronic cervical injuries resulting in bilateral upper and lower motor impairment and severe cervical atrophy and healthy control participants. All participants underwent a T1‐weighted anatomical scan prior to the TMS experiment. The motor thresholds of the extensor digitorum communis muscle (EDC) were defined, and its cortical muscle representation was mapped. The centre of gravity (CoG), the cortical silent period (CSP) and active motor thresholds (AMTs) were measured. Regression analysis was used to investigate relationships between trauma‐related anatomical changes and TMS parameters. SCI participants had increased AMTs (Pu2003=u20030.01) and increased CSP duration (Pu2003=u20030.01). The CoG of the EDC motor‐evoked potential map was located more posteriorly towards the anatomical hand representation of M1 in SCI participants than in controls (Pu2003=u20030.03). Crucially, cord atrophy was negatively associated with AMT and CSP duration (r2u2003≥u20030.26, Pu2003<u20030.05). In conclusion, greater spinal cord atrophy predicts changes at the cortical level that lead to reduced excitability and increased inhibition. Therefore, cortical forearm motor representations may reorganize towards the intrinsic hand motor representation to maximize output to muscles of the impaired forearm following SCI.

Effects of spinal cord injury on semen parameters.

Abstract Objective/Background: Neurogenic reproductive dysfunction in men with spinal cord injury (SCI) is common and the result of a combination of impotence, ejaculatory failure, and abnormal semen characteristics. It is well established that the semen quality of men with SCI is poor and that changes are seen as early as 2 weeks after injury. The distinguishing characters of poor quality are abnormal sperm motility and viability. In the majority of the men with SCI, the sperm count is not abnormal. We elaborate on the effects of the SCI on semen parameters that may contribute to poor motility and poor viability. Methods: Review. Design: PubMed and MEDLINE databases were searched using the following key words: spinal cord injuries, fertility, sexual dysfunction, and spermatogenesis. All literature was reviewed by the team of authors according to the various stages of sperm development and transport in the male reproductive cycle. Findings: The cause of asthenozoospermia appears to be multifactorial. Conclusion: Current literature does not support the preeminence of a single factor relating to neurogenic reproductive dysfunction in men with SCI. After SCI, there is ample evidence of disturbance of sperm production, maturation and storage, and transport due to an abnormal neuroendocrine milieu. Semen quality seems to be primarily affected by changes to the seminal plasma constituents, type of bladder management, and the neurogenic impairment to the ejaculatory function. Further focused and structured studies are required.

A Putative Non-Cholinergic Mechanism in Urinary Bladders of New But Not Old World Primates

The effects of atropine on bladder contractions evoked by sacral ventral root stimulation were investigated in two species of New World monkey (marmoset and cebus) and in paraplegic man. The findings were then compared to those previously obtained for the cat and two species of Old World monkey (rhesus and baboon). The results show the marmoset and cebus to represent a transitional stage between the complete sensitivity of the bladders of Old World monkeys to atropine and the relative insensitivity of the cat bladder. The bladder response is shown to comprise two components, an atropine sensitive component which is slow in onset and an atropine resistant component which is easily fatigued. The experiments in paraplegic people confirm that the parasympathetic innervation of the bladder of man is, like that of Old World monkeys, exclusively cholinergic. A behavioural interpretation is tentatively offered to explain the two types of innervation.

Lower urinary tract dysfunction in ambulatory patients with incomplete spinal cord injury.

PURPOSEnWe evaluated urinary tract dysfunction in individuals with spinal injury who remained able to ambulate. We observed changes with time in urological management.nnnMATERIALS AND METHODSnAll patients attending outpatient clinics with traumatic, incomplete (American Spinal Injury Association grades D and E) spinal cord injury during a 2-year period were identified. All patients had their hospital notes reviewed retrospectively and salient urological data extracted.nnnRESULTSnA total of 43 men and 21 women were identified during this period. Mean age was 46 years (range 18 to 70). Mean followup was 7 years (range 1 to 18). At the time of inpatient discharge 40 of the 64 patients (62.5%) could void spontaneously, 20 required CSIC and 4 had a suprapubic catheter. In 19 of these 40 patients (47.5%) who had been initially assessed as having a bladder that was safe to void spontaneously the condition deteriorated, such that CSIC was required. Conversely 5 of 20 patients (25%) who initially required CSIC improved, such that it became redundant. At last followup 68.7% of the patients had abnormal urodynamics and 24 of the 64 (37.5%) required a change in urological management despite no appreciably detectable neurological change.nnnCONCLUSIONSnDespite relatively near total neurological recovery patients with incomplete SCI have neuropathic bladder unless proved otherwise. Salient deterioration in bladder dysfunction is not uncommon. Regular urological monitoring and appropriate treatment changes are required in the long term.

Interface pressure and cutaneous hemoglobin and oxygenation changes under ischial tuberosities during sacral nerve root stimulation in spinal cord injury

Noninvasive functional magnetic stimulation (FMS) of the sacral nerve roots can activate gluteal muscles. We propose the use of sacral anterior root stimulator (SARS) implants to prevent ischial pressure ulcers in the spinal cord injury (SCI) population. In this study, we (1) investigated the acute effects of sacral FMS on ischial pressure, skin blood content, and oxygenation changes in people with SCI and demonstrated the utility of FMS as an assessment tool, and (2) showed that similar effects are possible with electrical stimulation via a SARS implant. Results indicated that sacral nerve root stimulation, either by FMS or implanted electrical stimulation, induced sufficient gluteus maximus contraction to significantly change subjects ischial pressures and cutaneous hemoglobin and oxygenation during sitting. In addition to these beneficial acute effects, chronic stimulation via a SARS implant may build gluteal muscle bulk and prevent or reduce pressure ulcers in the SCI population.

Seminal Oligouridinosis: Low Uridine Secretion as a Biomarker for Infertility in Spinal Neurotrauma

BACKGROUNDnCompromised sexual health is a major rehabilitative barrier for men with lower-spinal cord injury (SCI). Although studies have revealed decreased sperm motility, the quantitative biochemical changes that underlie the infertility mechanism remain poorly understood.nnnMETHODSnWe employed a nontargeted approach combining 800 MHz hydrogen nuclear magnetic resonance ((1)H NMR) spectroscopy and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) with pattern recognition methods to analyze seminal fluid metabolite profiles in 10 men with and 8 without SCI above thoracic vertebra 10 (T10).nnnRESULTSnThe metabolic phenotype for SCI could be predicted from the (1)H NMR data. The median concentration of uridine in fertile controls was 1.55 mmol/L (range 1.0-5.0 mmol/L), but was undetectable by both NMR and MS in all but 2 individuals from the SCI group, one who later fathered a child without assisted fertility techniques.nnnCONCLUSIONSnWe hypothesize that uridine is likely to be an essential precursor to metabolites required for capacitation and is a potential marker for the prognosis of post-SCI functional fertility recovery. We derived the term seminal oligouridinosis to describe this newly identified condition.

Pelvic somato-visceral reflexes after spinal cord injury: measures of functional loss and partial preservation

For people with spinal cord injuries, the impact of bladder, bowel and sexual problems on quality of life and lost opportunities can be devastating. Supra-sacral spinal lesions can cause incontinence by interrupting those pathways that normally coordinate the function of the bladder, bowel and sphincters. From a scientific perspective, neural control of the pelvic organs is one of the most intriguing in the body, involving both somatic and autonomic pathways participating in an exquisitely fine integration of lumbo-sacral reflexes. This chapter aims to review briefly those aspects of neural control of the pelvic organs that are amenable to neurophysiological examination in man. More specifically, it will focus in greater detail on the interactions of somatic and autonomic lumbo-sacral pathways responsible for coordinating the bladder and sphincters. Where appropriate, it will make comparisons with those controlling the bowel. It will describe how measurement of pelvic floor and sphincter reflexes can be used to assess the modulatory effects of sacral autonomic pathways on sacral somatic reflexes and vice versa including the so-called guarding reflex and vesical inhibitory reflexes. Aberrant activity following spinal cord injury (SCI), such as bladder hyperreflexia and sphincter dyssynergia, will be discussed in relation to these reflexes. The effects of volitional modulation of pelvic floor reflexes in people with both complete and incomplete lesions will be described. Finally, the chapter will address the possible utility of neurophysiological measures for complementing the established neurological classification and the assessment of somatic sensory-motor impairment in SCI.