Neurosarcoidosis with Recurrent Cranial Neuropathies as Primary Presentation: A Case Report

Abstract

Introduction

Sarcoidosis is defined as an immune-mediated disorder characterised by granulomatous inflammation of affected organs. Neurosarcoidosis is demographically reported in 5%–10% of all patients with primary sarcoidosis. A similar genetic mechanism for inflammation compared to active systemic tuberculosis suggests that identical inflammatory pathways are acting in both tuberculosis and sarcoidosis.

Case Report

We, hereby, report a case of recurrent cranial nerve neuropathy, which was falsely diagnosed as tuberculosis, and the diagnosis of neurosarcoidosis was masked for more than a year.

Conclusion

Any case with recurrent cranial nerve involvement, bilateral lymphadenopathy with multi-system involvement and a history of steroid-dependent resolution of symptoms must be primarily evaluated for sarcoidosis with histological evidence.

Introduction

Sarcoidosis is defined as an immune-mediated disorder characterised by granulomatous inflammation of affected organs. ¹ The collective group of granulomas disrupts the normal tissue integrity and causes focal or multiple organ dysfunction, which is a characteristic feature of sarcoidosis. ² Common organs affected include the lungs (90%), followed by eyes (10%–30%), liver (20%–30%), lymph nodes (15%–20%) and skin (15%). According to consensus, Neurosarcoidosis was demographically found in 5%–10% of all patients with sarcoidosis.^{1, 3} Due to genetic similarities in inflammatory responses to sarcoidosis and tuberculosis, there is a bias of misdiagnosis of tuberculosis in cases of sarcoidosis. ⁴

We, hereby, report a case of recurrent cranial nerve neuropathy, which was falsely diagnosed as tuberculosis and was responding to steroids given alongside ATT, and the diagnosis of neurosarcoidosis was masked for more than a year.

Case Presentation

A 57-year-old female, homemaker by occupation, diabetic, hypertensive for the past 10–15 years, presented to us with complaints of dysphagia for 9 months, recurrent facial weakness (left side followed by right) for the past 30 days & weakness of both upper limbs for the past 10 days. Patient was asymptomatic 1.5 years back when in Nov 2021, she developed a fever, once every 2–3 days for 15 days with mild-to-moderate severity and evening rise of temperature (Documents unavailable). Then, she had two episodes of vomiting after which she was taken to a nearby hospital. To rule out COVID-19 due to the prevalent epidemic at the time, her CT Thorax was done. It was suggestive of small patches of subpleural consolidation in the Antero-basal segment, and an impression of Pulmonary Koch’s was given. However, the doctor did not prescribe any ATT and asked to get all investigations repeated after 1 month and was given symptomatic management. She was healthy for the next 1 month when, in December 2021, she developed an acute onset of difficulty in swallowing, with more difficulty swallowing liquids than solids and had nasal regurgitation of fluids along with dysphonia. Her laryngoscopy showed left vocal cord palsy, UGI Endoscopy was not significant & MRI Brain was suggestive of Chronic ischemic small vessel changes in bilateral deep cerebral white matter. Her CSF Study was done, which showed Glucose 163 mg/dL (Corresponding RBS - 178 mg/dL), M-Protein - 155, Cells - 26 cells (96% LMN, 4% PMN). She continued having oral feeds all through. Based on her previous CT Thorax and CSF profile, she was referred to the Pulmonology department, IMS & Sum Hospital for an anti-tubercular regimen and was started on ATT and low-dose tapering steroids in January 2022. She was symptomatically better, improved completely & was stable for the next 5 months. In June 2022, she developed a complaint of acute onset weakness and tingling sensation in both hands and feet for the past 4 months, with weakness while gripping objects, associated with pain in the neck and discomfort in her neck and upper back in the form of numbness. She had consulted a local physician for the same and was put on symptomatic medications for the same, with partial improvement in symptoms. In Sept 2022, she woke up one morning to find her mouth deviated to the right and an inability to close her left eye. It was acute in onset and non-progressive. She was taken to a nearby clinic, labelled as left-sided Bell’s palsy and was put on symptomatic medications. Twenty days later, as her left-sided facial weakness was improving, she developed deviation of her angle of mouth to the left and an inability to close the right eyelid. She was then referred by the clinic to us. She was admitted for further evaluation, keeping in mind a history of old bulbar palsy and recurrent bilateral facial nerve palsy.

On examination, she had bilateral palmar fascia thickening Figure 1. Her left-sided gag reflex was diminished, and she had bilateral (right > left) LMN facial palsy. Her hand grip was bilaterally weak and the distal hand muscles were also bilaterally weak. Her motor examination showed spasticity in all four limbs with mild quadriparesis and hyper-reflexia, with both her plantar reflexes being equivocal. Her Chest X-ray showed bilateral hilar lymphadenopathy. Her ESR was 60, Hb 11.1, CRP 1.72, Ca- 8.68, ALP – 111 and her ANA Profile was negative. Her ACE Levels were sent, which was 82. Her repeat HRCT Thorax Figure 2 showed multiple mediastinal & bilateral Hilar lymphadenopathy along with ill-defined ground glass opacities in the bilateral lower lobes. Her ultrasound of both parotids showed enlargement with multiple superficial and deep lymphadenopathy without necrosis Figure 3. Thereafter, an EBUS was performed, and a lymph node biopsy from the Subcarinal Lymph node was taken, which showed granulomatous non-caseating non-necrotic lymphadenitis with calcification Figure 4. Her MRI Cervical Spine showed a hyperintense intramedullary lesion at C4/5 level Figure 5.

Figure 1.

Bilateral Palmer Fascia Thickening.

Figure 2.

HRCT Thorax s/o Pre-tracheal, Subcarinal, AP Angle and Bilateral Hilar Lymphadenopathy.

Figure 3.

USG Bilateral Parotids Showing Deep and Superficial Parotid Lymph Node Enlargement.

Figure 4.

LN Biopsy from Subcarinal LN Was Taken: Showed Epithelioid Cell Granulomas Along with Multinucleated Histiocytic Giant Cells in a Reactive Lymphoid Background. Calcification Was Noted. No Necrosis/Malignant Cells Were Seen. Special Stain for AFB was Negative.

Figure 5.

MRI Cervical Spine s/o Focal Demyelinating T2-weighted Hyperintense Lesion at C4/5 Level with Post-contrast Enhancement.

She was then started on an induction dose of steroids (60 mg prednisolone) for 6 weeks, followed by a maintenance dose of steroids (40 mg Prednisolone) for the next 6 months. After monitoring her for effectiveness after 6 months, she was bridged with Azathioprine as long-term immunosuppressant and after 2 years of regular follow-ups, currently the patient is maintaining well with almost complete resolution of old symptoms and no new neurological symptoms or deficits since treatment.

Discussion

Initial presentation mimicking cranial neuropathies with complete resolution and later on having progressive quadriparesis with sensory symptoms suggested of a descending cervical lesion, probably demyelinating. ATT was started primarily based on radiological findings mimicking tuberculosis, though no other clinical features supported it. However, the protocol of low-dose steroids for neurotuberculosis unwaveringly improved the symptoms of sarcoidosis, and the patient & clinician were under a false impression of anti-tubercular treatment as the reason for improvement.

Discrete, coalescing, well-formed, coalescent, sometimes necrotising epithelioid granulomas with scattered lymphocytes are pathologic hallmarks of the disease. ⁵ Myelitis from sarcoidosis is relatively common in 75% of Neurosarcoidosis cases. ⁶ Cranial nerve neuropathies are among the most commonly reported manifestations of Neurosarcoidosis. Multiple, concurrent, or serial cranial neuropathies should raise suspicion for Neurosarcoidosis. ⁴ Hence, referring to multiple literatures and knowledge regarding neurosarcoidosis, similar genetic mechanisms for inflammation compared to active systemic tuberculosis suggest that identical inflammatory pathways are acting in both tuberculosis and sarcoidosis. ⁷ Spinal cord involvement is observed in about 27% of neurosarcoidosis patients, and Cranial nerve involvement is seen in 50%–75% of cases. ⁸ Lin J et al. ⁹ described a man diagnosed with tuberculous meningitis who deteriorated neurologically after treatments, later on diagnosed as neurosarcoidosis. Many other literature described the overlapping presentations and confusion regarding diagnosing tuberculosis and sarcoidosis.^10–13

Conclusion

Based on long clinical history, laboratory investigations, radiological investigations and histological evidence, the 2018 Neurosarcoidosis Consortium Consensus diagnostic criteria suggest it is a case of Definite Neurosarcoidosis. Hence, any case with recurrent cranial nerve involvement, bilateral lymphadenopathy with multi-system involvement, with a history of steroid-dependent resolution of symptoms must be primarily evaluated for sarcoidosis with histological evidence. At 6-month follow-up, our patient has completely resolved her symptoms with no recurrence.