Schistosomal myeloradiculopathy due to Schistosoma mansoni: Report on 17 cases from an endemic area.

BACKGROUND: After malaria, schistosomiasis is the second most prevalent tropical disease. The prevalence of oviposition in CNS of infected persons varies from 0.3 to 30%. The conus medullaris is a primary site of schistosomiasis, either granulomatous or acute necrotizing myelitis.
OBJECTIVE: To report the clinical, radiological, and laboratory results of spinal cord schistosomiasis (SCS) and to design proper therapeutic regimens.
MATERIALS AND METHODS: Seventeen patients (13 males and four females) with SCS were enrolled between 1994 and 2009 at Mansoura University Hospitals. Their median age at diagnosis was 19 years (13-30 years). Independent neurological, radiological, and laboratory assessments were performed for both groups, excluding pathological confirmation that was done earlier in eight patients (Group 1). In the group 2 (nine patients), indirect hemagglutination (IHA) test for bilharziasis in blood and cerebrospinal fluid (CSF) was performed. Higher positive titer in CSF than serum indicated SCS plus induction of antibilharzial and corticosteroid protocols for 12 months with a three-year follow-up.
RESULTS: Rate of neurological symptoms of granulomatous intramedullary cord lesion was assessed independently in 16 cases and acute paraparesis in one case. All patients in group 2 had positive IHA against Schistosoma mansoni with median CSF and serum ranges 1/640 and 1/320, respectively. Seven patients (41.18%) had complete recovery, eight patients (47.06%) showed partial recovery, and no response was reported in two patients (11.76%) (P = 0.005). There was no recorded mortality in the current registry.
CONCLUSIONS: Rapid diagnosis of SCS with early medical therapies for 12 months is a crucial tool to complete recovery.

Introduction

Spinal cord schistosomiasis (SCS) lesion, especially Schistosoma mansoni, is considered as a primary cause of spinal cord parasitic invasion in Egypt. The worldwide prevalence of central nervous system oviposition has a wide variability (0.3-30%),[12] while in endemic areas, the SCS is a frequent cause of nontraumatic myelopathies (6%).[3]

In 1970, El-Banhawy[4] mentioned 9 spinal cord bilharzial cases that were verified histopathologically additionally, they discussed briefly the clinical presentation and management. Afterward, a few cases with bilharzial spinal cord lesions from Egypt, South Africa, and Brazil were reported.[5]

SCS commonly assaults the lower thoracic/upper lumbar regions. It is clinically characterized by cauda and lower cord neurologic symptoms as well as special radiological, serologic, and pathological findings.[6] According to diverse studies, there are no clear guidelines for proper medical therapies, and their duration as antibilharzial and corticosteroids, or superiority to surgery.[711] Nevertheless, there is a concept for all parasitic diseases including SCS that early treatment will provide superior prognosis and diminish the high morbidity and mortality frequencies.[912]

This prospective long-term study aims to design proper therapeutic regimens and to find out the characteristic clinical, radiological, and laboratory findings of 17 patients with schistosomal radiculomyelopathy.

Materials and Methods

This prospective study, a collaborative effort by the neurosurgery and neurology departments, Mansoura University, Egypt, was conducted between January 1994 and December 2009. A total of 17 patients were enrolled with a highly suspicious history of SCS. They were divided into two groups: Group 1 included 8 patients who had histopathological confirmation based on good spinal cord lesion biopsy and received medical therapy for 12 months and 3-year follow-up; Group 2 included 9 patients who received the same therapies but after cerebrospinal fluid (CSF) and serological tests confirmation. Indirect hemagglutination (IHA) (Schistosomiasis Fumouze, France) in both serum and CSF against S. mansoni is used as a diagnostic test for active parasitic infection with titer ≥1/160.

After a detailed history, routine laboratory tests were done; the investigations included complete blood count, blood urea, serum creatinine, fasting blood sugar, serum potassium, serum sodium, serum calcium, serum phosphorous, liver function tests, ESR, microscopic stool examination for schistosomal eggs, and biochemistry and cytomorphologic examination of the CSF that was obtained through lumbar puncture.

In addition, all patients had initial MRI of the dorsolumbar region (T1-, T2-, and FLAIR-weighted images) and after one year of therapy. All patients were scheduled for 3-year follow-up.

The therapeutic regimen that was applied in the current study included Praziquantel for four therapeutic points over one year. The prescribed dose was 40 mg/kg/day in 3 divided doses. The same dose was repeated for 3 consecutive days. It was ingested with the same previous regimen every 4 months for at least one year. The prednisone was used in initial dose 40 mg/day and tapering over few weeks.

For the current study, we classified response to treatment as follows: (1) Full recovery, if patient has complete improvement; (2) Partial recovery, if the patient indicated minor neurological deficits; and (3) No recovery, if patient has no improvement whatsoever or severe permanent motor or sensory loss. The current study received Institutional Review Board approval.

Statistical analysis

The demographic, clinical, and technical data were collected using a data collection form and entered into a computerized database before statistical analysis. Continuous variables were compared using analysis of variance for repeated measures. P value less than 0.05 was considered statistically significant. All data were expressed as mean ± standard deviation or patient's number (n) and percentage (%) as appropriate.

Results

The 17 patients enrolled in this study were divided into two groups: Group 1 included eight patients (seven males and one female) and Group 2 included nine patients (six males and three females). The mean age for all patients was 20.29 ± 5.8 years. The median age was 19 years (13-30) with male to female ratio of 3.25 : 1.

The common clinical presentations were progressive motor and sensory symptoms with sphincter disorders in the granulomatous type resembling a cauda equine syndrome (16 cases). Acute weakness of both lower limbs with sensory changes and retention of urine in the acute necrotizing type resembling acute areflexic flaccid paraplegia was reported in one case.

Bladder dysfunction was a constant finding in all patients (100%). Paraesthesia, low back pain, or radicular pain in the lower limbs was the most frequent early sensory manifestations (88.2%).

Of 17 patients, 9 patients (52.9%) yielded obvious S. mansoni eggs in their stool; however, IHA against S. mansoni antibodies was positive in CSF and serum of all patients in group 2. The titer was more elevated in the CSF (median titer, 1/640) than the serum (median titer, 1/320) as well as CSF protein raised in all patients (median, 70 mg/dl).

MRI scans with gadolinium enhancement were correlated with the clinical findings in both groups [Figure 1]. Of 17 (5.9%) patients, one showed minimal enhancement with myelitic form [Figure 2], while 16 patients revealed enhanced spinal cord enlargement at conus [Figures 1 and 3]. With treatment 7 patients ((41.2%) made full recovery, 8 patients (47.1%_ had partial recovery and 2 patients (11.8%) failed to make any recovery.

Figure 1

(a) Sagittal T1-weighted MRI image with gadolinium enhancement that shows diffuse conus swelling and irregular enhancement. (b) Contrast axial T1WI shows diffuse conus swelling with hypointense signal, (c) Pathology specimen with multiple bilharzial ova with terminal spine that characterized S. mansoni

Figure 2

Magnetic resonance imaging studies in a Schistosomal myelitis of the conus medullaris. Sagittal T1WI with gadolinium illustrated mild swelling of the conus with scattered granular tissues enhancement

Figure 3

Magnetic resonance imaging studies in a bilharzial granuloma of the conus medullaris. (a) Sagittal T2WI shows diffuse conus enlargement and T2 hyperintense signal (b) Sagittal T2WI of the same patient who underwent treatment for six months with reduction of the conus swelling

Discussion

SCS is a rare disease even in endemic areas. The first case of SCS in Egypt was reported in 1968.[45] The assumed mechanism that explains predilection of lesions to lower spinal cord in current study is the existence of valve-free venous plexus (Batson system) that anatomizes the intraabdominal and spinal veins. This shunt becomes more active and patent in cases with increased intraabdominal pressure which permits the S. mansoni eggs to migrate through these plexus to the spinal cord.[1314]

The hypothesis that mentioned elimination of eggs directly inside the vessels due to the anomalous migration of adult worms is supported by the occasional finding of adult worms and eggs in a row inside vertebral vessels.[15]

The severity of symptoms and extension of the lesions could be relied on the degree of parasitic infestation load and the host's immunologic response. In addition, the interval between infection and onset of the spinal cord manifestations varies from several days up to 6 years.[9]

Spinal cord granuloma was confirmed radiologically in 16 of 17 patients and histopathologically in 7 patients who were enrolled early in this study. In one case, devastating myelitis was diagnosed radiologically and histopathologically [Figure 2]. The onset of symptoms in this patient was acute which suggests myelitis, while the course in the remaining cases was a chronic and progressive form.

The granulomatous or myelitic pathological forms could induce spinal cord damage by mass effect, anterior spinal artery occlusion, or extensive immune reaction due to high antigenic structure of S. mansoni ova, what is called delayed hypersensitivity reactions.[61618]

Besides the pelvic anatomy differences, the male predominance in the current study (3.25 : 1) could be explained by the greater exposure of men to schistosomal infestation because the agriculture is a man job in Egypt.[12]

In the current study, the myelitic form (1 patient) presented acutely and showed no recovery while in granulomatous forms (16 cases), 7 patients showed total recovery, 8 had partial recovery, and 1 showed no recovery. The majority of patients who showed poor recovery had higher titer of IHA test and poor drugs compliance.

In most published series, the myelitic form outcome is very poor compared with the granulomatous form. This study is in harmony with other high-powered studies despite severe motor and sensory symptoms in the current series.[121920]

According to the present study and others, there is a reliable predictor of CNS involvement, if the patient has higher CSF IHA antibodies against S. mansoni titer (1/640) than serum level (1/320). This statement made huge changes in our protocol of SCS diagnosis in the last 6 years. We instituted high CSF-IHA titer as surrogate to pathological confirmation as a noninvasive and reliable laboratory test. There is no outcome differences among both groups.[10]

The sensitivity of single smear is 50% only; so, repeated stool examinations for S. mansoni eggs were performed in all patients of the current study. They revealed positive results in 9 cases (52.9%), which is consistent with results (60%) of Paz et al.[1020]

Although fecal smear is a good positive finding, it does not exclude SCS diagnosis. For this reason, the rectal biopsy is recommended in cases with negative stool examinations; but unfortunately, this procedure was not done in our series because it is an invasive technique and culturally harmful.[12]

Beyond doubt, the definite diagnosis of SCS necessitates proper histopathological examination of the spinal cord biopsy that was done in Group 1 in the current study. In the main, a high-quality MRI that is more sensitive than specific in SCS and reliable surrogate CSF laboratory tests makes the biopsy of the spinal cord a reserve tool for confusing cases because it is an invasive technique.

The therapeutic regimen in the current study for all patients was Praziquantel drug in four therapeutic points over one year. The dose was 40 mg/kg in 3 divided doses every day for 3 consecutive days. The drug was ingested by the same previous regimen every 4 months for at least one year. The prednisone (no less than 2 months) was used in initial dose 40 mg/day and tapering over few weeks. The regimen was designed for heavy infested and neurologically involved patients.

Praziquantel is a broad-spectrum antibilharzial drug against adult worms, so it prevented further deposition of ova and new granulomata formation. The simultaneous use of corticosteroids was aimed to dampen the immune response and reduce proinflammatory cytokines around intramedullary granuloma.[1921]

In the current series, 3 of 4 patients who discontinued steroids early (less than 60 days) developed recurrence of the myelopathy symptoms. In addition, we observed in a few cases a clinical improvement with the maintenance of steroid therapy for a longer therapeutic period.

Reexposure to S. mansoni was not documented. This could be justified by motor disability that prevented them from work and the firm instructions given to the patients to avoid the source of infection during the drug therapy duration.

Based on current results, SCS is a probable diagnosis in a young patient, from endemic area, with symptoms of lower cord lesion and supported by MRI findings in addition to higher titer of CSF IHA test.

In conclusion, although SCS can be managed both medically and surgically, medical regimens are the most wise options in clear cut cases with no role for surgery, except in confusing cases and for biopsy that can be considered for avoiding the side effects of surgery and the problems posed by comorbidity.

Limitation

We accept that our study is underpowered and limited by the small sample size. We tried to highlight the significance of early diagnosis and management of SCS. Therefore, further adequately powered, multicenter trials are recommended.