Diagnostic overshadowing in primary progressive multiple sclerosis with coexisting tethered cord syndrome and long-standing urological dysfunction: a case report and literature review

Abstract

Background

Primary progressive multiple sclerosis (PPMS) may be diagnostically challenging when coexisting structural spinal abnormalities produce overlapping neurological and urinary manifestations. Tethered cord syndrome (TCS) and PPMS can both present with progressive myelopathy and lower urinary tract symptoms, increasing the risk of diagnostic overshadowing.

Case presentation

A 42-year-old woman with a history of sacrococcygeal meningocele and prior surgical resection presented with a 20-year history of urinary dysfunction and a 2-year history of progressive ascending sensory symptoms and mild paraparesis. Her symptoms had initially been attributed to her structural and surgical history. However, neurological examination, brain and whole-spine MRI, and CSF analysis demonstrated characteristic demyelinating lesions and positive oligoclonal bands. She fulfilled the 2024 McDonald criteria for PPMS. Because ocrelizumab was unavailable locally, rituximab was initiated as an off-label alternative.

Conclusion

This case highlights the importance of considering a concurrent neuroinflammatory disorder in patients with pre-existing structural spinal pathology and chronic urinary dysfunction. Careful integration of clinical, radiological, and CSF findings is essential to avoid diagnostic delay in complex dual-pathology presentations.

Introduction

Primary progressive multiple sclerosis (PPMS) is a progressive inflammatory demyelinating disease of the central nervous system characterized by steady neurological worsening from onset rather than discrete relapses [1, 2]. The 2024 revisions of the McDonald criteria provide a unified diagnostic framework for multiple sclerosis across relapsing and progressive phenotypes, emphasizing the integration of clinical progression, MRI, and CSF findings in establishing the diagnosis [3].

Tethered cord syndrome (TCS), in contrast, is a structural spinal dysraphism caused by abnormal fixation of the spinal cord, most often related to a low-lying conus, thickened filum terminale, lipoma, or other dysraphic lesions [4, 5]. In adults, TCS may present with slowly progressive sensorimotor deficits, pain, and urinary dysfunction, which can closely overlap with manifestations of demyelinating myelopathy [4, 6].

Because both PPMS and TCS may produce chronic gait disturbance, pyramidal signs, sensory loss, and bladder dysfunction, a pre-existing structural or urological history may contribute to diagnostic overshadowing and delay recognition of a concurrent demyelinating disorder [7, 8]. This overlap makes combined presentations clinically challenging and diagnostically important.

Case presentation

Patient history and clinical presentation

A 42-year-old woman with no relevant family history of neurological disease presented with a long-standing history of progressive urinary and sensory symptoms. Her past surgical history was notable for three cesarean deliveries, the most recent of which, performed 18 years earlier, was complicated by a bladder wall injury. This led to the development of a bladder diverticulum and recurrent urinary tract infections. She also had a history of sacrococcygeal meningocele, which had been identified at the age of 14.

as a sacrococcygeal swelling and surgically resected at the age of 19, with an uneventful postoperative course. Her urinary symptoms had started approximately 20 years earlier with loss of bladder sensation and urinary overflow incontinence. Two years before presentation, she developed progressive paresthesia in the right foot, which gradually ascended over one year to involve the anterior aspect of the knee. One year before presentation, similar sensory symptoms appeared in the left foot and persisted up to the ankle (Fig. 1).

Fig. 1.

Clinical timeline of neurological and urological events

Neurological examination

On examination, the patient was alert, cooperative, and fully oriented. There were no cortical signs, cranial nerve deficits, or cerebellar abnormalities. The optic nerve examination was clinically normal. Muscle tone was normal in all four extremities, and no spasticity or clonus was documented. Motor examination revealed full proximal strength (5/5) bilaterally in the upper limbs. Distal strength in the forearm and hand was mildly reduced on the right (4+/5) and normal on the left (5/5). In the lower limbs, both proximal and distal muscle groups showed full strength (5/5) bilaterally. Deep tendon reflexes were globally brisk (+ 3) in all four extremities. The plantar reflex yielded no response (neutral) bilaterally, and Hoffmann and Lhermitte signs were absent. Sensory examination demonstrated a bilateral loss of sensation (anesthesia) in the L5–S1 dermatomal distributions.

Investigations

Brain and whole-spine magnetic resonance imaging demonstrated a tethered spinal cord along with multiple T2-hyperintense lesions; these spinal lesions were located at the cervical (C3–C4 vertebral segment) and lumbar (L3–L4 vertebral segment) levels. In the brain, imaging revealed a lesion in the corpus callosum, bilateral white-matter abnormalities, and bilateral parietal lobe atrophy (Figs. 2 and 3). Cerebrospinal fluid analysis was positive for oligoclonal bands. Due to the unavailability of urodynamic testing, bladder assessment relied on clinical presentation and ultrasonography. Post-void ultrasonography showed a residual volume of approximately 35% of the total bladder capacity, compatible with a flaccid neurogenic bladder. Advanced MRI biomarkers, such as the central vein sign, paramagnetic rim lesions, and kappa-free light chains, were not available in our setting.

Fig. 2.

Brain MRI. A Axial FLAIR image showing subcortical white matter hyperintense lesions. B Sagittal T2-weighted image showing a hyperintense lesion in the corpus callosum with associated parietal lobe atrophy

Fig. 3.

Spinal MRI. A Sagittal T2-weighted cervical spine image showing a hyperintense lesion at the C3–C4 level. B Sagittal T2-weighted lumbar spine image showing an elongated tethered spinal cord with a long hyperintense lesion. C Axial T2-weighted lumbar spine image at the L3–L4 level showing a hyperintense intramedullary lesion

Diagnosis and management

The patient fulfilled the 2024 McDonald criteria for primary progressive multiple sclerosis, based on more than one year of progressive neurological disability, characteristic brain and spinal cord lesions, and positive cerebrospinal fluid oligoclonal bands. The neurological progression was objectively documented over the two years preceding presentation, beginning with right foot paresthesia and later involving the contralateral lower limb. Alternative diagnoses were considered, but the available clinical, radiological, and CSF findings strongly supported PPMS. The coexistence of a tethered spinal cord and chronic urinary dysfunction created a diagnostic challenge because of overlapping structural and demyelinating manifestations. Neurosurgical untethering was not pursued, as the tethering had been present for more than five years and the neurological deficits were considered more likely to be driven predominantly by the demyelinating process. Because ocrelizumab was not available locally, rituximab was initiated as an alternative anti-CD20 therapy. Given the clinical diagnosis of a flaccid bladder, urinary symptoms were managed with the Credé maneuver. Additionally, the urology team had initiated duloxetine 30 mg, which subsequently led to a documented improvement in her urinary symptoms.

At 4 months of follow-up after rituximab initiation, the patient remained clinically stable without new neurological deficits or worsening urinary symptoms. Repeat MRI had not yet been performed at the time of reporting.

Discussion

Clinical differentiation between PPMS and adult tethered cord syndrome

The coexistence of primary progressive multiple sclerosis (PPMS) and adult tethered cord syndrome (TCS) creates a challenging diagnostic scenario because both conditions may present with progressive myelopathy and lower urinary tract symptoms [8]. However, the phenotype of bladder dysfunction often differs. In PPMS, bladder involvement generally reflects a suprasacral neurogenic process and may manifest as urgency, storage dysfunction, or detrusor-sphincter dyssynergia [2]. In contrast, adult TCS more commonly produces a sacral or lower motor neuron bladder phenotype, characterized by loss of bladder sensation, overflow incontinence, and incomplete emptying [5]. In this patient, the 20-year history of absent urinary urge and overflow incontinence, together with persistent post-void residual urine, was more consistent with a chronic structural sacral voiding disorder than with PPMS alone. At the same time, these urinary symptoms did not explain the later appearance of multifocal brain and spinal cord lesions [6, 7].

Pyramidal and sensory findings

The neurological examination also suggested more than one process. Adult TCS may cause focal or asymmetric lower-limb deficits and sacral sensory disturbance, whereas PPMS more often produces a diffuse corticospinal pattern with globally brisk reflexes and gradually progressive sensory-motor impairment. In this patient, globally brisk reflexes together with distal weakness and progressive spread of sensory symptoms supported a central demyelinating process superimposed on the pre-existing structural anomaly. The absence of overt spasticity, clonus, or a positive Babinski sign does not exclude concurrent PPMS, particularly in a predominantly sensory presentation and in the setting of coexisting structural spinal pathology.

Diagnostic significance of the 2024 McDonald criteria

The 2024 revisions of the McDonald criteria were pivotal in establishing the diagnosis of PPMS in this case [3]. PPMS requires objective neurological progression over at least one year, together with supportive MRI and CSF evidence. In our patient, more than one year of progressive neurological worsening was documented, beginning with right foot paresthesia and later involving the contralateral lower limb over the following year, in addition to characteristic MRI lesions and cerebrospinal fluid oligoclonal bands. Although advanced biomarkers such as the central vein sign, paramagnetic rim lesions, and kappa free light chains were not available in our setting, the diagnosis remained supportable through the core clinical, MRI, and CSF criteria. Thus, the challenge in this case was not whether PPMS criteria could be fulfilled, but how to avoid attributing all neurological and urinary manifestations to the known spinal dysraphism.

Imaging interpretation and differential diagnosis

Adult tethered cord should not be regarded as a childhood-only disorder. Reviews and adult series describe a broad spectrum, including pain, subtle sensorimotor deficits, and urinary dysfunction, and these features may remain compensated for years before clinical recognition [4, 5]. At the same time, inflammatory demyelinating disorders such as MOG antibody-associated disease and AQP4-positive NMOSD can mimic MS clinically and radiologically, which is why careful MRI interpretation and CSF analysis remain essential [9, 10]. In this case, the combination of a corpus callosum lesion, bilateral white-matter abnormalities, multifocal spinal cord lesions at cervical and lumbar levels, and CSF-restricted oligoclonal bands strongly favored PPMS over a purely mechanical explanation related to cord tethering. The structural tethering explained part of the urinary history, but not the full neuroimaging burden.

Therapeutic considerations

Ocrelizumab remains the evidence-based standard for PPMS, having shown benefit over placebo in the ORATORIO trial [11]. Nevertheless, access limitations often shape real-world treatment choices. Observational data suggest that rituximab may achieve comparable effectiveness to ocrelizumab in PPMS, and recent low-resource recommendations support off-label rituximab as a pragmatic option, albeit with conditional recommendations and low certainty of evidence [12–15]. In this context, the use of rituximab in our patient was a reasonable local alternative rather than a substitute of equal regulatory status. The neurosurgical question was also considered: untethering was not pursued because the tethering had been longstanding, the likelihood of meaningful neurological benefit was judged limited, and the progressive demyelinating disease was considered the predominant driver of the current deficits.

What the literature adds

Recent reports help place this case in context. Adult TCS may remain clinically silent for years before becoming symptomatic, and recent reports by Hashimoto, Ohmae, and Hyuga show that adult tethering disorders related to filum terminale lipoma or split cord malformation can present with progressive lower-limb dysfunction and bladder symptoms [16–18]. In contrast, Jamil et al. described progressive MS presenting predominantly with obstructive uropathy and acute kidney injury, illustrating how a demyelinating disorder may initially appear to be a primary urological disease [19]. Our Table 1 is therefore most useful when interpreted as a phenotypic comparison rather than a list of identical cases: adult TCS cases are characterized by structural tethering with sacral/lower-limb symptoms, whereas progressive MS is supported by dissemination of lesions in typical CNS locations and by CSF evidence of intrathecal inflammation (Table 1).

Table 1.

Comparison of Recent Literature on Adult-Onset TCS and Progressive MS Presentations

Study (Year)	Primary Diagnosis	Clinical Presentation	Key Urological/Neurological Findings
Jamil et al. (2025) [19]	Progressive MS	67 M; Obstructive uropathy and Acute Kidney Injury (AKI).	Severe neurogenic bladder dysfunction masked by AKI; 3-year history of limb weakness.
Hashimoto et al. (2024) [16]	Adult TCS (Filum terminale lipoma)	Adult; Lower limb weakness and bladder dysfunction.	Mechanical cord stretching is causing progressive motor and sphincter deficits.
Ohmae et al. (2025) [17]	SCM Type II with TCS	54 F; Gradually progressive paraparesis and bladder dysfunction.	Low-lying conus (S3) due to spinal lipoma with fibrous tethering structures.
Hyuga et al. (2025) [18]	Adult TCS (Spinal lipoma)	33 M; Nocturnal enuresis and daytime urinary incontinence.	Residual urine > 500 mL; sudden urological deterioration after years of stability.

Limitations

This case has several limitations. Urodynamic testing was unavailable, so the bladder phenotype could not be objectively characterized. In addition, advanced MRI biomarkers were not available in our setting, and follow-up after rituximab initiation was short. Formal disability metrics, including EDSS, 25-FWT, 9-HPT, and cognitive testing, were not routinely documented in this sensory-predominant presentation and could not be reconstructed retrospectively; clinical follow-up was therefore based on serial neurological assessment. These limitations constrain bladder physiology phenotyping and long-term treatment-response assessment, although they do not weaken the diagnosis of PPMS established through the available clinical, MRI, and CSF data.

Conclusion

This case illustrates how a long-standing structural spinal abnormality and a progressive demyelinating disease can coexist and obscure one another clinically. Chronic urinary dysfunction and progressive myelopathy should not automatically be attributed to a single lesion or prior surgical history. A careful synthesis of neurological examination, MRI, and CSF findings is essential to avoid delayed recognition of PPMS in patients with tethered cord or other pre-existing spinal pathology.

Abbreviations

PPMS

Primary Progressive Multiple Sclerosis

MS

Multiple Sclerosis

TCS

Tethered Cord Syndrome

MRI

Magnetic Resonance Imaging

CSF

Cerebrospinal Fluid

OCBs

Oligoclonal Bands

MOGAD

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

NMOSD

Neuromyelitis Optica Spectrum Disorder

CNS

Central Nervous System

Authors’ contributions

T.A. and H.A. wrote the main manuscript text, R.A. prepared Figs. 1 and 2, and G.A.Conceptualization. All authors reviewed the manuscript.

Funding

No funding was received for this research.

Data availability

The clinical data and imaging that support the findings of this case are not publicly available due to patient confidentiality. De-identified imaging and the pathology report are available from the corresponding author upon reasonable request and subject to institutional approval.

Declarations

Ethics approval and consent to participate

Ethical approval was waived by the Institutional Review Board of the University of Hama because this manuscript reports a single de-identified case and did not involve experimental intervention beyond routine clinical care. The work was conducted in accordance with the Declaration of Helsinki. Written informed consent to participate was obtained from the patient.

Consent for publication

Written informed consent for publication of clinical details and accompanying images was obtained from the patient.

Competing interests

The authors declare no competing interests.