Case Presentation: A 52-year-old man with pulmonary sarcoidosis and epilepsy was admitted with paranoia and disorganized behavior. Exam was only notable for agitation. Labs were unremarkable, and he was admitted to psychiatry service. The patient was diagnosed with neurosarcoidosis four years prior after presenting with seizures. MRI at that time showed frontotemporal and leptomeningeal enhancement. CSF had elevated angiotensin-converting enzyme (ACE) and high IgG index. He was started on prednisone and levetiracetam and had no recurrence of seizures. Two months prior to current admission, he was hospitalized for behavioral disturbances and had improved with high-dose steroids, but worsened while on a prednisone taper in a rehabilitation facility. On current admission, MRI demonstrated progressive confluent hyperintensities and leptomeningeal enhancement in the bilateral frontal and anterior temporal lobes, concerning for neurosarcoidosis. CSF showed ACE 8.7 U/L (0-3 IU/L) and high IgG, with negative infectious and autoimmune panels.Chest CT showed bilateral upper-lobe fibrosis and calcified mediastinal lymphadenopathy, consistent with chronic pulmonary sarcoidosis. Infectious workup including HIV, hepatitis, VZV IgM, and interferon gamma release assay were negative.Given radiographic and clinical progression despite steroids, infliximab was initiated for steroid-refractory neurosarcoidosis. Over subsequent weeks, his agitation and disorganization gradually improved.
Discussion: Sarcoidosis most commonly affects the lungs, but neurologic involvement can occur in 5-15% of patients. CNS disease may involve the meninges, brain parenchyma, spinal cord, cranial or peripheral nerves. Presentations are highly variable depending on the location of disease. Frontotemporal involvement, like in our patient, can manifest with personality changes, agitation, paranoia and impaired executive functioning, often mimicking psychiatric disorders.Diagnosis is challenging as there is no single diagnostic test for neurosarcoidosis. A combination of clinical features, imaging, CSF studies, and evidence of systemic sarcoidosis is used to exclude mimics such as CNS infections, autoimmune encephalitis, and lymphoma. MRI commonly reveals leptomeningeal enhancement, white matter lesions, or mass-like granulomas. CSF abnormalities include lymphocytic pleocytosis, elevated protein, increased IgG index, and occasionally elevated ACE levels, though ACE lacks specificity. Identifying sarcoidosis elsewhere, like in the lungs or lymph nodes, helps support the diagnosis.Glucocorticoids are the first-line treatment of neurosarcoidosis. Anti-TNF-α agents, like infliximab, are used to treat steroid-refractory neurosarcoidosis. Prior to initiating infliximab, appropriate screening for TB, hepatitis B and C is essential.This patient’s deterioration during a steroid taper, along with MRI progression and recurrent CSF ACE elevation, strongly suggested active neurosarcoidosis. His subsequent improvement on infliximab reinforces the role of biologic therapy in refractory disease, especially in cases with neuropsychiatric involvement.
Conclusions: Clinicians should suspect neurosarcoidosis in patients with known sarcoidosis who present with psychiatric symptoms, as misattribution to primary psychiatric illness can lead to mistriage and delay appropriate management. When symptoms or imaging progress despite steroids, clinicians should escalate to biologic therapy.