Urological manifestations of chronic schistosomal myeloradiculopathy
Cristiano M. Gomes, Hospital das Clinicas da Universidade de Sao Paulo, Divisao de Clinica Urologica, Caixa Postal: 11273–9, CEP: 05422–970 Sao Paulo, SP Brazil.
To describe the clinical and urodynamic features of patients with chronic voiding dysfunction secondary to schistosomal myeloradiculopathy (SM), as the clinical involvement of the spinal cord is a well recognized complication of Schistosomiasis mansoni infection.
PATIENTS AND METHODS
We reviewed the records and urodynamic studies of 26 consecutive patients (17 males and nine females, aged 8–58 years) with chronic neurological and urinary symptoms secondary to SM. The voiding function history, radiological and urodynamic findings and therapeutic approaches were reviewed. Patients with and without upper urinary tract complications were compared in terms of age, duration of voiding dysfunction and urodynamic pattern.
The most common urinary symptoms were difficulty in emptying the bladder (17 patients, 65%), urinary incontinence (14, 54%), and urgency and frequency (13, 50%). Laboratory and radiographic evaluation showed urinary tract infection in eight (30%) patients, bilateral hydronephrosis in five (19%) and bladder calculi in five (19%). Urodynamics showed detrusor overactivity with detrusor-external sphincter dyssynergia (DESD) in 14 patients (54%), detrusor arreflexia in six (23%), detrusor overactivity with no dyssynergia in four (15%), and detrusor underactivity in two (8%). Comparing patients with and without upper tract complications showed no differences in age and duration of urinary symptoms, but there was a significant association of detrusor overactivity with DESD and upper urinary tract complications (P = 0.04). Urological management consisted of antibiotics, clean intermittent catheterization, anticholinergic medication and stone removal, as appropriate. Conservative treatment failed in three patients and they required an injection with botulinum-A toxin into the detrusor (two) or ileocystoplasty (one).
Patients with chronic SM behave clinically like those with other causes of spinal cord disease and neurogenic bladder dysfunction requiring lifelong surveillance. The severity of illness in these patients should re-emphasize the need for early recognition and treatment of this condition, to prevent or reverse the neurological deficits.
detrusor-external sphincter dyssynergia
clean intermittent catheterization
Worldwide, ≈ 200 million people are infected with schistosome worms, the parasitic helminthes responsible for the greatest morbidity and mortality . Of the three major species infecting humans, Schistosoma mansoni, S. japonicum and S. haematobium, S. mansoni is the only species found in Brazil and the most frequently reported cause of schistosomal myeloradiculopathy (SM) worldwide [2–4].
Patients are infected by schistosomal cercariae when exposed to infected fresh water. The parasites migrate through the venous system to the mesenteric veins, where they mature into adult worms and start passing eggs. Most eggs are released in the stool, but some become lodged in the intestinal wall and liver. Over a period of many years, immunological responses to the deposited eggs may lead to granuloma formation and fibrosis in the affected organs. Because the eggs are not excreted in urine and there is no egg-laying in vesical and pelvic venules; the urinary tract is not primarily affected by S. mansoni, and only one case of primary vesical involvement by S. mansoni has been reported .
Clinical involvement of the spinal cord is a well-recognized complication of the disease, manifesting from weeks to several years after exposure. Although uncommon, this complication is not rare in endemic areas for schistosomiasis [3,4,7] and several cases have been reported in Europe and the USA [8,9–14]. Neuroschistosomiasis mansoni usually affects the inferior thoracic or lumbosacral region, with the highest segments of the spinal cord and brain usually being preserved . The route of spread is not well defined but the most accepted mechanism is felt to be related to reflux from the visceral pelvic veins to the spinal cord via the Batson's venous plexus that connect intra-abdominal and spinal veins . Once the eggs are deposited in the nervous system, antigenic and immunogenic substances are released, resulting in an inflammatory reaction that varies, according to the status of the host immune system, from an intense granulomatous reaction to very little reaction at all.
SM can take the form of an acute transverse myelitis or granulomatous intrathecal mass lesions in the spinal cord, conus medularis and cauda equina [4,8,7]. The typical manifestations are those of an acute transverse myelitis, with sudden onset of lower extremity neuropathy associated with bladder and bowel dysfunction. The prognosis largely depends on early recognition and treatment [4,15].
Despite adequate treatment, the neurological injury might be permanent. We report our clinical and urodynamic experience with 26 patients with chronic SM evaluated for voiding dysfunction.
PATIENTS AND METHODS
We retrospectively reviewed the records of 26 consecutive patients (nine females and 17 males) with SM evaluated over 36 months. All had chronic neurological and urinary symptoms, and were referred by neurologists from our hospital having had a previously established diagnosis of SM. The criteria used to diagnose SM were those proposed by the Center of Disease Control and Prevention .
All patients had a history of exposure to S. mansoni infection and either lived in an endemic region in Brazil or contracted the disease after visiting an endemic area. The diagnosis of SM was based on symptoms, neurological examination, history of exposure to S. mansoni and stool examination for ova . Spinal CT and/or MRI was used in all patients during the initial investigation, and revealed signs of compression of the spinal cord in only one patient, who had a laminectomy to excise a compressive inflammatory mass. Most patients had either no abnormalities or mild and nonspecific alterations, including an increase in the diameter of the spinal cord, especially the medullary cone, and/or thickening of the cauda equina. All patients had S. mansoni ova in their stool or rectal biopsy at some point during their clinical course, but had been previously treated and were negative at the time of the present evaluation. In addition to the diagnostic criteria proposed by the Center for Disease Control, diagnosis was confirmed with cerebrospinal fluid immunological tests; all but one patient tested positive for S. mansoni on ELISA or immunoblotting of the cerebrospinal fluid.
The urological assessment included the history of voiding function and a focused neuro-urological and physical examination. A structured questionnaire for urological symptoms was used, but not a validated symptom score. All patients were investigated with urine culture, serum creatinine level, urinary tract ultrasonography and cystography.
The urodynamic evaluation consisting of filling cystometry and pressure-flow voiding studies, including electromyographic monitoring in all cases using surface electrodes. All definitions conform to the standardized terminology of the ICS .
We defined upper urinary tract complications as the occurrence of bilateral hydronephrosis and/or VUR. The Mann–Whitney U-test was used to compare patients with and without complications in terms of age and duration of voiding dysfunction. Based on the known significance of detrusor-external sphincter dyssynergia (DESD) and associated elevated bladder pressures as a prognostic indicator of upper urinary tract complications in other patient populations [18,19], we compared patients with this urodynamic pattern with those with other urodynamic abnormalities. Fisher's exact test was used to assess the association of the urodynamic pattern with upper tract complications. Data were analysed using commercially available statistical software, with P < 0.05 considered to indicate significance.
The median (range) age of patients was 32.5 (8–58) years at the time of the urological evaluation, and the median duration of neurological and urinary symptoms was 5 (1–20) years, defined as the time between the start of the clinical symptoms of acute spinal cord schistosomiasis and the referral for urological evaluation.
Patients had varying degrees of motor and/or sensory deficits in the inferior limbs, associated with voiding and bowel dysfunction. The predominant urinary symptoms were difficulty in emptying the bladder (17 patients, 65%), urinary incontinence (14, 54%), urgency and frequency (13, 50%). Retrospective investigation showed that 19 of these patients (73%) had urinary dysfunction during the acute phase of the disease and three claimed that the urological symptoms preceded other clinical manifestations. The serum creatinine level was normal in all patients. Urine analysis and urine culture showed UTI in eight (30%) patients, and radiological investigation showed a normal upper urinary tract in 21 (80%), while five (19%) had bilateral hydronephrosis; evaluation of the lower urinary tract with ultrasonography and cystography was normal in 10 (39%) patients, while 14 (54%) had bladder wall thickening, including 10 with multiple diverticula. Two patients had unilateral VUR and five (19%) presented with bladder calculi.
Urodynamics showed abnormalities in all patients, including detrusor overactivity with DESD in 14 (54%), detrusor arreflexia in six (23%), detrusor overactivity with no dyssynergia in four (15%) and detrusor underactivity in two (8%). Patients with bladder calculi had urodynamics at least 3 months after being rendered stone-free.
There were upper urinary tract complications in five (19%) patients, including three with bilateral hydronephrosis and two with hydronephrosis and VUR. Comparing patients with and without upper tract complications showed no differences in age and duration of urinary symptoms, but there was a significant association of detrusor overactivity with DESD and upper urinary tract complications (Table 1).
Table 1. Association of age, duration of voiding dysfunction and urodynamic pattern with upper urinary tract complications
|Patients, n||21|| 5|| |
|age, years||36.8 (7.0)||29.8 (2.0)||0.18|
|years of voiding dysfunction|| 4.2 (0.5)|| 11.6 (3.9)||0.14|
|Urodynamic pattern, n|
|DESD*|| 9|| 5||0.04|
|No DESD||12|| 0|| |
All patients had been previously treated for schistosomiasis and their neurological deficits were considered permanent. The urological management (Table 2) varied according to the patients’ clinical and urodynamic findings. Eighteen (69%) patients emptied their bladder with clean intermittent catheterization (CIC), 10 of whom also took anticholinergic medication. Seven (28%) patients could void spontaneously by controlling their urge sensation or by suprapubic tapping and Valsalva manoeuvre, with reduced residual urine. Four of these had detrusor overactivity without dyssynergia and received anticholinergic drugs. One patient had DESD but could spontaneously empty the bladder satisfactorily. The other patient had detrusor underactivity and was empirically treated with doxazosin but reported little improvement. Four of the five patients presenting with bladder stones at initial evaluation had open cystolithotomy and one transurethral cystolithotripsy. Conservative treatment with anticholinergics failed in three patients with detrusor overactivity; two were treated by injection with 300 units of botulinum-A toxin into the detrusor at 30 sites, remaining completely continent and satisfied for 6 months, at their last follow-up visit. The other patient had an ileocystoplasty for severe detrusor overactivity and poor bladder compliance with a high detrusor leak point pressure. One patient with detrusor overactivity and dyssynergia refused CIC and had a sphincterotomy.
Table 2. Treatments used in all patients
|CIC|| 7 (27)|
|CIC and anticholinergic||10 (39)|
|Ileocystoplasty|| 1 (4)|
|Anticholinergic and void with Valsalva|| 4 (15)|
|Botulinum-A toxin injection|| 2 (8)|
|α-blockers|| 1 (4)|
|Sphincterotomy|| 1 (4)|
Clinical involvement of the spinal cord is an uncommon but well-recognized complication of S. mansoni infection; it is critical to identify patients with the acute form of the disease. Our previous experience and that of others has shown that SM is a potentially reversible spinal cord insult if appropriate treatment is instituted in the early phase of the disease [4,8,7,15]. That some of these patients might have urological symptoms as their sole clinical manifestation underscores the importance of urologists being able to recognize SM as a potential cause of neurogenic voiding dysfunction [4,13,15]. It is estimated that 40% of patients who had an acute form of the disease may have persistent neurological deficits and voiding dysfunction ; such patients were included in the present study.
Urinary tract imaging was important for detecting lower and upper urinary tract abnormalities. Seven of the present patients presented with serious urological complications, including bladder stones, bilateral hydronephrosis and VUR; and 14 (54%) had bladder wall thickening, including 10 with multiple diverticula.
A urodynamic investigation is essential to dictate and monitor the urological treatment in such patients. Detrusor overactivity with or without sphincter dyssynergia was the most common urodynamic finding in the present patients with chronic spinal SM. As expected, DESD was the urodynamic pattern most frequently associated with urological complications, including the five patients with bilateral hydronephrosis and four of the five with bladder stones. Most of these patients were successfully managed with CIC and anticholinergic drugs. However, in three patients the conservative treatment failed and they required additional therapy. Botulinum-A toxin injected into the detrusor muscle was very effective in two of these patients, while the other required ileocystoplasty.
In conclusion, patients who had an acute form of spinal cord schistosomiasis may have persistent neurological deficits and voiding dysfunction, despite adequate treatment. They behave clinically like patients with other causes of spinal cord disease and neurogenic bladder dysfunction. Detrusor overactivity with DESD is the most common urodynamic pattern in these patients, who may develop urological complications and need lifelong surveillance. The severity of illness in these patients should emphasize the need for early recognition and treatment of this condition, to prevent or reverse the neurological deficits.
CONFLICT OF INTEREST