Title: Multifactorial Lower Extremity Weakness in a Patient with NeurosarcoidosisAuthors: Helena H Kwon, MPH1; Kevin Batti, MD2; Brian Le, MD21Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 104612Department of Physical Medicine and Rehabilitation, Montefiore Einstein, 111 East 210th Street, Bronx, NY 10467Corresponding author email: hojeong.kwon98@gmail.comConsent: The patient provided informed consent for the publication of this anonymous case report.Conflict of Interest: The authors declare that there are no conflicts of interest.Author Contribution: Helena H Kwon contributed to conceptualization, formal analysis, the original draft preparation, and manuscript review and editing. Dr. Kevin Batti contributed to conceptualization, provided resources, supervised the project, and participated in manuscript review and editing. Dr. Brian Le provided supervision, contributed to validation of the case details, and participated in manuscript review and editing.Key Clinical Message : This case illustrates the interplay between disease progression, treatment-related adverse effects, and comorbid conditions in neurosarcoidosis. Rehabilitation plays a critical role in optimizing functional outcomes for patients with neurosarcoidosis. Even when initiated beyond the acute phase, a structured and individualized rehabilitation program can yield meaningful improvements in mobility and independence.Introduction : Neurosarcoidosis is a rare manifestation of systemic sarcoidosis, occurring in approximately 5–10% of patients, and can affect the brain, spinal cord, or peripheral nerves.1 Its presentation is heterogeneous, ranging from cranial neuropathies and encephalopathy to myelopathy and longitudinally extensive transverse myelitis (LETM). LETM is an uncommon but potentially debilitating complication that may mimic or coexist with other spinal pathologies.1 Diagnosis remains challenging due to the lack of definitive biomarkers and the frequent absence of histologic confirmation. Clinicians often rely on a combination of imaging findings, cerebrospinal fluid analysis, systemic biopsy results, and exclusion of alternative etiologies.2 Treatment typically involves corticosteroids and second-line immunosuppressive therapies, although treatment response is variable and long-term use may be complicated by toxicity and side effects.1, 2Case History/Examination : A 63-year-old male with a history of systemic sarcoidosis diagnosed in 2007 presented with progressive bilateral lower extremity weakness. His sarcoidosis was complicated by LETM extending from T6 to T12 (Figure 1). His medical history was also significant for cervical myelopathy, degenerative disc disease, deep vein thrombosis, osteoarthritis, hypertension, benign prostatic hyperplasia, and chronic venous insufficiency. He had previously undergone anterior cervical discectomy and fusion at C3–C6 for spinal stenosis (Figure 1). The patient reported recent worsening of lower extremity weakness and gait instability. On neurologic examination, upper extremity strength was intact. Lower extremity strength was reduced, particularly in hip flexors (3/5 right, 4/5 left), knee extensors (4+/5 bilaterally), and mild distal weakness including ankle dorsiflexors (4/5 right, 4−/5 left) and plantarflexors (4/5 right, 4−/5 left). Reflexes were decreased (1+ quadriceps bilaterally). His gait was crouched, and he required a rollator for ambulation.Differential Diagnosis, Investigations, and Treatment: Given the progression of weakness in a patient with known LETM, the differential diagnosis included neurosarcoidosis myelitis, baclofen-induced muscle weakness, and complications from chronic immunosuppression. Investigations included serial spinal imaging, review of immunosuppressive therapy response, and medication reconciliation focused on spasticity agents.The patient’s immunosuppressive treatment history included methotrexate, hydroxychloroquine, mycophenolate mofetil, and rituximab, with current therapy consisting of prednisone (5 mg daily) and infliximab infusions (480 mg in sodium chloride 0.9 % 250 mL). He also received intrathecal baclofen (104 mcg/24 hours) and oral baclofen 10 mg nightly for spasticity. Pain was managed with acetaminophen and NSAIDs. Given the recent worsening of lower extremity weakness, oral baclofen taper was initiated while maintaining spasticity control through the intrathecal pump at a minimal dosage. Referrals to physical therapy and orthotic evaluation were also placed.Conclusion and Results (Outcome and Follow-up): This patient’s worsening mobility was attributed to a multifactorial process involving chronic neurosarcoidosis, treatment-related adverse effects, and underlying spinal pathology. After adjusting his baclofen regimen and initiating targeted rehabilitation interventions, his functional strength and gait gradually improved. He remained independent in most ADLs, with walking as his primary limitation. Ongoing follow-up focused on monitoring spasticity, optimizing immunosuppression, and reinforcing long-term rehabilitation strategies to preserve mobility and quality of life.Discussion : Neurosarcoidosis presents a significant therapeutic challenge due to its heterogeneous presentation, variable progression, and limitations of available treatment. Long-term steroids and second-line immunosuppressive agents are commonly used as medical therapies in neurosarcoidosis, but their effectiveness is often limited by adverse effects, poor tolerability, and a lack of robust clinical evidence, as reflected in this patient’s history of multiple discontinued treatments. Symptom-targeted therapies, such as baclofen for spasticity, warrant particular attention as frequent reassessment of both efficacy and tolerability is essential for optimal dosing. While baclofen can effectively reduce spasticity, its dose-dependent side effects including hypotonia and muscle weakness may exacerbate functional impairment, especially when administered via both intrathecal and oral routes.3 In this patient, the multimodal regimen of baclofen likely contributed to his recent decline in mobility. The trade-off between spasticity reduction and preservation of functional strength should be evaluated in the context of the patient’s ability to perform key ADLs including transfers, ambulation, and stair navigation. Clinicians should employ targeted questioning such as inquiring about difficulty rising from a chair or changes in gait, alongside structured functional assessments for optimal dosing.Physical and occupational therapy are also integral components in the management of chronic neurosarcoidosis, especially when neurological deficits persist despite medical treatment. Physical therapy should be individualized to target specific functional impairments. Key interventions include gait and balance training, muscle strengthening, and evaluation for appropriate assistive devices or orthoses. These approaches are critical for enhancing mobility, reducing fall risk, and promoting patient independence. Complementing this, occupational therapy focuses on improving coordination, implementing adaptive strategies for ADLs, and recommending home modifications to maintain autonomy. Previous studies have demonstrated that patients with neurosarcoidosis can achieve rapid improvements in functional independence when managed with comprehensive acute inpatient rehabilitation alongside systemic therapy.4 Additionally, recent case report suggests that intensive rehabilitation initiated beyond the acute phase may still result in meaningful functional gains, provided that the underlying disease is adequately controlled medically.5 The role of supportive intervention such as physical and occupational therapy is critical but often underemphasized. These modalities can help address mobility limitations, prevent secondary complications, and enhance quality of life, especially when neurologic deficits are unlikely to fully reverse with medical therapy alone.References :1. Burns TM. Neurosarcoidosis. Arch Neurol. 2003; 60:1166-8.2. Tana C, Wegener S, Borys E, Pambuccian S, Tchernev G, Tana M, et al. Challenges in the diagnosis and treatment of neurosarcoidosis. Ann Med. 2015; 47:576-91.3. Brandenburg JE, Rabatin AE, Driscoll SW. Spasticity Interventions: Decision-Making and Management. Pediatr Clin North Am. 2023; 70:483-500.4. Nicolosi C, Carrera EJ, Heronemus M, Shivers J, Niehaus W. Neurosarcoidosis in acute inpatient rehabilitation: a case study. Spinal Cord Ser Cases. 2020; 6:99.5. Takeshima S, Furuya T, Yamamoto M, Noma M, Kawate N. Planning and effectiveness of intensive rehabilitation as a treatment for a patient with neurosarcoidosis: A case report. Medicine (Baltimore). 2023; 102:e34519.