B M Soni

Delayed diaphragm recovery in 12 patients after high cervical spinal cord injury. A retrospective review of the diaphragm status of 107 patients ventilated after acute spinal cord injury.

Study Design: The functional outcome of the diaphragm after acute spinal cord injury was reviewed over a 16 year period for 107 patients who had required assisted ventilation in the acute phase. Objectives: To quantify the incidence of recovery of diaphragm function which occurred beyond the period of acute oedema; to produce a time-related profile of this as a guide to clinicians considering phrenic nerve pacing; and to assess the value of phrenic nerve testing in predicting recovery. Setting: The Southport Regional Spinal Injuries Centre, Southport, England. Methods: Bilateral phrenic nerve and diaphragm integrity was assessed clinically, by spirometry, and by fluoroscopy without and with phrenic nerve stimulation. Results: Thirty-one per cent of all the ventilated patients (33 cases), with a level of injury between C1 and C4 (Scale A in ASIA Impairment Scale), had diaphragmatic paralysis at the time of respiratory failure. The subsequent diaphragm recovery which appeared in seven of these patients, between 40 and 393 days (mean 143), permitted weaning from ventilatory support at 93 to 430 days (mean 246) after the acute injury, with a vital capacity of over 15 ml kg−1 at that stage. The diaphragm recovery in a further five patients, whose vital capacity remained below 10 ml kg−1 and who could not be fully weaned, occurred significantly later, between 84 and 569 days (mean 290), P=0.053. Negative phrenic nerve tests were followed by weaning at a later interval in several cases. By contrast, one patient with an early positive phrenic stimulation test and subsequent diaphragm activity could not be weaned from the ventilator. Conclusion: Twenty-one per cent of the patients with initial diaphragm paralysis were ultimately able to breathe independently after 4 and 14 months, whilst a further 15% had some diaphragm recovery. Phrenic nerve testing should be repeated at 3 monthly intervals for the first year after high tetraplegia.

Pathophysiology of autonomic dysreflexia: long-term treatment with terazosin in adult and paediatric spinal cord injury patients manifesting recurrent dysreflexic episodes.

Introduction: Spinal cord injury (SCI) results in disruption of synaptic influences on the sympathetic preganglionic neurones. Remodelling of spinal cord circuits takes place in spinal neurones caudal to cord injury. There is an increased vascular alpha-adrenoceptor responsiveness, and peripheral afferent (bladder) stimulation in SCI subjects induces a marked noradrenaline spillover below the level of spinal lesion. These neurophysiological changes possibly contribute to the development of autonomic dysreflexia, a condition of sympathetic hyper-excitability that develops after cervical, or upper dorsal cord injury with resultant paroxysmal rise in arterial pressure, and provide the scientific basis for the use of terazosin, a once-a-day, selective alpha-one adrenergic blocking drug. Objectives: The use of terazosin, a long-acting, alpha 1-selective blocking agent was investigated in SCI patients who developed recurrent symptoms of autonomic dysreflexia, eg headache, sweating flushing of the face together with an increase in the arterial pressure. Design: An open, prospective study of the efficacy of terazosin in controlling recurrent autonomic dysreflexia in traumatic tetraplegic/paraplegic patients manifesting clinical features of dysreflexia in the absence of an acute precipitating cause such as a blocked catheter. Setting: The initial assessment and treatment were carried out in the Spinal Injuries Centre. Subsequently, the patients were followed-up in the community. They were monitored by telephonic interviews, follow-up visits by the patients to the hospital, and home-visits by the staff of the spinal unit. Subjects: Eighteen adults with tetraplegia (female: 1; male: 17), three children with ventilator-dependent tetraplegia and three adult male patients with paraplegia who exhibited recurrent features of autonomic dysreflexia in the absence of an acute predisposing factor for dysreflexia eg performance of an invasive procedure such as cystoscopy, digital evacuation of bowels, or acute urinary retention, were enrolled in this study.Intervention: After discussion with the patients and their carers, terazosin was prescribed with a starting dose of 1 mg in an adult and 0.5 mg in a child administered nocte. The patients were observed for (1) drug-induced hypotension; (2) clinical symptoms due to side effects of terazosin; and (3) continued occurrence of dysreflexic symptoms. Step-wise increments of the dose of terazosin (1 mg in case of adults, and 0.5 mg in a child) was carried out at intervals of 3–4 days, if a patient continued to develop dysreflexia but did not manifest any serious side effect. Outcome measures: Complete subsidence of dysreflexic symptoms, or development of an adverse event necessitating termination of the terazosin therapy was the clinical end point. Results: The dysreflexic symptoms subsided completely with the terazosin therapy in all the patients. The twenty-one adult patients required a dose varying from 1–10 mg, whereas the paediatric patients required only 1–2 mg of terazosin. The side effects of postural hypotension and drowsiness were transient, and mild. One tetraplegic patient developed persistent dizziness and therefore, the drug therapy was discontinued. Conclusion: In 21 adult and three paediatric spinal cord injury patients manifesting recurrent episodes of autonomic dysreflexia in the absence of an acute predisposing cause, the use of terazosin, a once-a-day, specific alpha-one blocker resulted in complete subsidence of the dysreflexic symptoms. However, one tetraplegic patient required termination of terazosin therapy because of persistent dizziness.

Urethral cytology in spinal cord injury patients performing intermittent catheterisation

Local reactions of the urethral wall are known to occur by repeated introduction of a catheter in the urethra. Urethritis was found in 2-19% of patients practising intermittent catheterisation. Although the use of catheters of smaller size and the liberal use of lubricants may prevent urethral irritation and trauma, it was postulated that hydrophilic catheters (LoFric, Astra Tech Ltd, Stroud, England) induce significantly less trauma than PVC catheters because of the binding of the water molecules to the catheter surface which consists of polyvinylpyrrolidone and sodium chloride. Although urethritis and urethral stricture may represent one end of the spectrum of repeated urethral trauma, minor degrees of inflammation need to be quantitatively determined while assessing two different catheters for intermittent catheterisation. The degree of urethral inflammation in patients practising intermittent catheterisation was studied by urethral cytology and staining the smear by Papanicolaous method. The number of neutrophil polymorphs and epithelial cells in three random high power fields in the urethral smear was counted and the percentage ratio of polymorphs to epithelial cells was calculated. Group 1 comprised 14 patients practising intermittent catheterisation with a PVC catheter and group 2 comprised 17 patients performing intermittent catheterisation with a LoFric catheter. There was no significant difference between the two groups as regards the age, diagnosis, size of the catheter used for intermittent catheterisation and the number of times that they performed catheterisation during a 24 hour period. Urethral cytology revealed a percentage (mean ratio) ratio of polymorphs to epithelial cells of 66 in group 1 and 0.04 in group 2. (< 0.0005). Urethral cytology also revealed a significantly greater number of bacteria in group 1 as compared to group 2 (p <0.01). In conclusion, use of a LoFric catheter for intermittent catheterisation was associated with significantly lesser degree of urethral inflammatory response when compared to the use of a PVC catheter.

Klippel-Feil syndrome – the risk of cervical spinal cord injury: A case report

BackgroundKlippel-Feil syndrome is defined as congenital fusion of two or more cervical vertebrae and is believed to result from faulty segmentation along the embryos developing axis during weeks 3–8 of gestation. Persons with Klippel-Feil syndrome and cervical stenosis may be at increased risk for spinal cord injury after minor trauma as a result of hypermobility of the various cervical segments. Persons with Klippel-Feil Syndrome often have congenital anomalies of the urinary tract as well.Case presentationA 51-year male developed incomplete tetraplegia in 1997 when he slipped and fell backwards hitting his head on the floor. X-rays of cervical spine showed fusion at two levels: C2 and C3 vertebrae, and C4 and C5 vertebrae. Intravenous urography (IVU) revealed no kidneys in the renal fossa on both sides, but the presence of crossed, fused renal ectopia in the left ilio-lumbar region. This patient had a similar cervical spinal cord injury about 15 years ago, when he developed transient numbness and paresis of the lower limbs following a fall.Discussion and Conclusion1) Persons with Klippel-Feil syndrome should be made aware of the increased risk of sustaining transient neurologic deterioration after minor trauma if there is associated radiographic evidence of spinal stenosis.2) Patients with Klippel-Feil syndrome often have congenital anomalies of the urinary tract. Our patient had crossed, fused, ectopia of kidney.3) When patients with Klippel-Feil syndrome sustain tetraplegia they have increased chances of developing urinary tract calculi. Treatment of kidney stones may pose a challenge because of associated renal anomalies.4) Health professionals caring for cervical spinal cord injury patients with Klippel-Feil syndrome and renal anomalies should place emphasis on prevention of kidney stones. A large fluid intake is recommended for these patients, as a high intake of fluids is still the most powerful and certainly the most economical means of prevention of nephrolithiasis.

Use of Memokath, a second generation urethral stent for relief of urinary retention in male spinal cord injured patients

Memokath (Engineers & Doctors A/S, Hornbaek, Denmark) a second generation urethral stent composed of titanium nickel alloy with shape memory effect was deployed in 10 male spinal cord injured patients with urinary retention. The stent was inserted under sterile conditions via a delivery catheter under fluoroscopic control in seven and with the aid of a flexible cystoscope in three. The proximal end of the stent was positioned at the bladder neck and 50 ml of normal saline at 45 °C was flushed through the stent which resulted in expansion of the distal most four coils of the stent in the proximal bulbar urethra; thus the internal sphincter (bladder neck) and external sphincter zone were kept open by the stent. Urethral stenting helped to achieve complete vesical emptying in all 10 patients. The complications included transient autonomic dysreflexia in two, transient urinary retention due to blood clot in one, and acute urinary tract infection in one patient. With a follow up of 3-7 months, all 10 patients have been aysmptomatic, with residual urine of less than 50 ml. There has been no migration or blocking of the stent. However, these stents require replacement at 12-18 months, but it is a short procedure as the Memokath, when cooled with saline at 4°C, becomes supersoft, enabling its easy and nontraumatic removal. As these stents produce no permanent effect upon the lower urinary tract and their removal is quick, safe and atraumatic, we prefer the second generation nickel titanium alloy stent to transurethral resection of bladder neck, external urethral sphincterotomy or permanent indwelling epithelialising stent, particularly in young spinal cord injured patients who wish to retain their fertility potential.

Effect of intermittent urethral catheterization and oxybutynin bladder instillation on urinary continence status and quality of life in a selected group of spinal cord injury patients with neuropathic bladder dysfunction

Objectives: A comparative assessment of (i) urinary continence status, (ii) quality of life, and (iii) sexuality in spinal cord injury patients prior to, and during intermittent catheterization with adjunctive intravesical oxybutynin therapy (Cystin: manufactured by Leiras Oy, Helsinki, Finland).Setting: A hospital, and community-based study of selected adult, male, spinal cord injury patients registered with the Regional Spinal Injuries Centre, Southport.Patients: Seven patients (mean age: 44.3 years) suffering from neuropathic bladder due to suprasacral spinal cord lesion of traumatic aetiology, and well settled in the community in the north-west of England were the subjects of this study. Before commencing the intermittent catheterization regime, these patients were on penile sheath drainage.Intervention: Intermittent urethral catheterization was performed with sterile, single-use Nelaton catheters 5–6 times a day with intravesical instillation of oxybutynin 5 mg in 30 ml, 1–3 times a day for periods ranging from 14 to 30 months.Outcome measures: Assessment of urinary continence, sexuality, and quality of life was made (i) at the outset before any intervention, (ii) during intermittent catheterization regime, and (iii) when the patients were using the oxybutynin bladder instillation along with intermittent catheterization.Results: Initially all the seven patients were constantly wearing penile sheaths and leg bags. When these patients performed intermittent catheterization 5–6 times in 24 h, they attempted to discard the penile sheath during the day but they were experiencing mild to moderate urine leak between catheterization. They were compelled to wear penile sheaths during night. Subsequently, five patients took oxybutynin by mouth, but developed an unacceptable degree of side-effects necessitating discontinuation of the medication. Following commencement of intravesical oxybutynin therapy, all of them were able to discard the penile sheaths and leg bags during the day as well as during the night. However, on waking-up after a full nights sleep, three patients found dampness of their undergarments 1–2 times per week. None of the patients experienced side-effects attributable either to the intermittent catheterization procedure, or to the intravesical oxybutynin therapy. The number of episodes of urinary infection requiring antibiotic therapy was 0.08/patient/month. All the seven patients noticed a remarkable improvement in the quality of life because they had achieved a high degree of continence. All the seven patients commented on the improved sense of their own sexuality which was attributed to (i) absence of incontinence episodes, (ii) improved self-image, and (iii) not wearing penile sheaths and leg bags.Conclusion: These seven spinal cord injury patients achieved socially acceptable continence with improved quality of life, and enhanced sexuality with the intermittent urethral catheterization regime and intravesical oxybutynin therapy.

The method of bladder drainage in spinal cord injury patients may influence the histological changes in the mucosa of neuropathic bladder – a hypothesis

BackgroundIn spinal cord injury (SCI) patients, no correlation was found between the number of bladder infections per year, the period since injury, the neurologic level of the spinal cord lesion and the histopathology of the urinary bladder mucosa. The use of chronic indwelling urethral and/or suprapubic catheters in SCI patients is often associated with inflammatory and proliferative pathological conditions in neuropathic bladder.Presentation of the hypothesisWe propose a hypothesis that the type of bladder drainage in SCI patients influences the histological changes in the mucosa of neuropathic bladder. This hypothesis implies that SCI patients with long-term indwelling urinary catheters develop certain histological changes in bladder mucosa, which are seen less frequently in SCI patients, who do not use long-term indwelling catheters. The latter group includes patients, who perform regular intermittent catheterisation and those, who wear a penile sheath and empty their bladders satisfactorily by reflex voiding.We hypothesise that the following histological lesions are seen more frequently in the neuropathic bladder of SCI patients with long-term indwelling catheters.(1) Papillary or polypoid cystitis; (2) widespread cystitis glandularis; (3) moderate to severe, acute and chronic inflammatory changes in bladder mucosa; (4) follicular cystitis; (5) squamous metaplasia; and (6) urothelial dysplasiaAs per this hypothesis, it is postulated that the above pathological conditions are seen less often in SCI patients, who achieve complete, low-pressure emptying of the neuropathic bladder by regular intermittent catheterisation, and SCI patients with penile sheath drainage, who empty their bladders satisfactorily by reflex voiding.Testing the hypothesisA large prospective study of bladder biopsies in SCI patients practising different methods of bladder drainage is required to validate this hypothesis that the histological changes in bladder mucosa are related to the method of bladder drainage in SCI patients.Implications of the hypothesisWe propose a hypothesis that the method of bladder drainage in SCI patients influences histological changes in the bladder mucosa. If this hypothesis is validated, methods of bladder drainage such as intermittent catheterisation, which do not require the use of chronic indwelling catheters, should be recommended, in order to minimise adverse histological changes in the mucosa of neuropathic bladder of spinal cord injury patients.

p75 nerve growth factor receptor in the vesical urothelium of patients with neuropathic bladder: an immunohistochemical study.

Introduction: Nerve growth factor (NGF), apart from its role as a growth factor, appears to be involved in neuroimmune interactions and in tissue inflammation. Low-affinity nerve growth factor receptor (p75 NGFR), if demonstrated in the urothelium, could provide the means for (1) NGF-mediated modulation of the urothelial response to inflammation; (2) NGF-mediated autocrine/paracrine regulation of urothelial proliferation; and (3) p75 NGFR-mediated induction of apoptosis. Objectives: To investigate the presence of p75 NGFR in the vesical urothelium of patients with neuropathic bladder by immunohistochemical methods. Setting: A hospital-based study of consecutive, unselected, adult patients of either sex with neuropathic bladder, undergoing procedure on the urinary tract in a Regional Spinal Injuries Centre located in the north-west of England. Intervention: Cold cup biopsies were taken from the trigone of the neuropathic urinary bladder of 26 patients with neuropathic bladder. Immunohistochemical studies were performed using antiNGF-receptor human monoclonal antibody which reacts with the low affinity receptor (p75 NGFR). Results: Both neural and epithelial structures showed positive immunostaining for p75 NGFR. The basal layer of the transitional epithelium showed strongly positive immunostaining for p75 NGFR in all the 26 cases. The luminal layer of transitional epithelium showed varying degree of positive immunostaining in 12 patients. The nerve fibres showed positive immunostaining for p75 NGFR. In many cases, the positively-stained nerve fibres were coursing very close to the basal layer of the urothelium almost entering the urothelium; however, no NGFR-positive intra-epithelial terminals could be seen. The positively-stained single nerve fibres and positively-stained thicker nerve bundles were seen in abundance in the submucosa but they were present in a sparse manner in the muscularis layer. Conclusion: The presence of p75 NGFR was demonstrated in the urothelium of neuropathic bladder of all the 26 patients with neuropathic bladder. This observation may have potential therapeutic implications.

Problems in early diagnosis of bladder cancer in a spinal cord injury patient: Report of a case of simultaneous production of granulocyte colony stimulating factor and parathyroid hormone-related protein by squamous cell carcinoma of urinary bladder

BackgroundTypical symptoms and signs of a clinical condition may be absent in spinal cord injury (SCI) patients.Case presentationA male with paraplegia was passing urine through penile sheath for 35 years, when he developed urinary infections. There was no history of haematuria. Intravenous urography showed bilateral hydronephrosis. The significance of abnormal outline of bladder was not appreciated. As there was large residual urine, he was advised intermittent catheterisation. Serum urea: 3.5 mmol/L; creatinine: 77 umol/L. A year later, serum urea: 36.8 mmol/l; creatinine: 632 umol/l; white cell count: 22.2; neutrophils: 18.88. Ultrasound: bilateral hydronephrosis. Bilateral nephrostomy was performed. Subsequently, blood tests showed: Urea: 14.2 mmol/l; Creatinine: 251 umol/l; Adjusted Calcium: 3.28 mmol/l; Parathyroid hormone: < 0.7 pmol/l (1.1 – 6.9); Parathyroid hormone-related protein (PTHrP): 2.3 pmol/l (0.7 – 1.8). Ultrasound scan of urinary bladder showed mixed echogenicity, which was diagnosed as debris. CT of pelvis was interpreted as vesical abscess. Urine cytology: Transitional cells showing mild atypia. Bladder biopsy: Inflamed mucosa lined by normal urothelial cells.A repeat ultrasound scan demonstrated a tumour arising from right lateral wall; biopsy revealed squamous cell carcinoma. In view of persistently high white cell count and high calcium level, immunohistochemistry for G-CSF and PTHrP was performed. Dense staining of tumour cells for G-CSF and faintly positive staining for C-terminal PTHrP were observed. This patient expired about five months later.ConclusionThis case demonstrates how delay in diagnosis of bladder cancer could occur in a SCI patient due to absence of characteristic symptoms and signs.

A retrospective study of hyponatremia in tetraplegic/paraplegic patients with a review of the literature

The aetiology of hyponatremia in tetraplegic patients is multifactorial and includes not only general factors such as the use of diuretics and the intravenous infusion of hypotonic fluids, but also certain mechanisms which operate in the spinal cord injured: decreased renal water excretion due to both intrarenal and arginine vasopressin dependent mechanisms (resetting of the osmostat), coupled with habitually increased fluid intake, and the ingestion of a low salt diet. Between 1984 and 1993 we treated 28 episodes of hyponatremia in 19 patients (males: 10; females: 9). Fourteen were tetraplegic and five paraplegic (thoracic lesion in four and lumbar lesion in one). Six patients were asymptomatic during seven episodes of hyponatremia which were detected during routine blood tests. Seven patients were suffering from an acute chest infection, three had an acute urinary tract infection, one had an infected ischial pressure sore and a 69 year old paraplegic patient had bronchopneumonia as well as sepsis from a gangrenous pressure sore in the supraanal region. The time interval between the onset of paralysis and occurrence of the first episode of hypnoatremia was less than a month in only four of the patients. The lowest plasma sodium level observed was less than 100mmol/l in two, between 100 and 110mmol/l in four, between 111 and 120mmol/l in eight patients, and between 121 and 128mmol/l in 14 cases. Six patients also had hypokalemia (K+ < 3 mmol/l). Only one patient had an elevated plasma creatinine (201umol/l). Treatment of sepsis and fluid restriction were the mainstay of treatment with only two patients receiving hypertonic saline. All patients with underlying sepsis were treated with antibiotics, usually administered intravenously. The outcome was good in 26 of the 28 episodes.Two patients died: a 68 year old tetraplegic patient with consolidation of the left lung, cystadenocarcinoma of both ovaries and squamous cell carcinoma of the forehead who presented with generalised oedema, with a plasma sodium level of 118 mmol/l, and potassium of 2.4 mmol/l and who was treated with 2N saline + postassium + frusemide; she died 1 day later. The only other death was that of a 78 year old female tetraplegic patient who 2 days after sustaining cervical trauma developed hyponatremia because of intravenous infusion of hypotonic fluids given at another hospital, presumably to correct hypotension. She recovered from hyponatremia with fluid restriction, but 3 days later she succumbed to bronchopneumonia and respiratory insufficiency. No patient developed central pontine myelinolysis. No patient with a severe degree of hyponatremia (sodium < 100 mmol/l) had respiratory involvement requiring ventilatory assistance. In conclusion, hyponatremia is seen in tetraplegic patients often in association with sepsis either in the lungs or in the urinary tract, and is best managed by treament of the predisposing factor(s) along with fluid restriction.