Here, we report the case of a 79-year-old male patient presenting with visual hallucinations, disorientation, difficulty finding words, cognitive decline, and behavioral changes including aggression, as well as burning sensations in both legs and arms, which had gradually evolved over 3 weeks before admission. Upon examination of temporal disorientation, reduced reflex levels of the lower extremities, symmetrical loss of sensation on both feet until below the knees, rigorously increased tone of the upper extremities, predominantly on the right side, and an uncertain gait with small steps, and the patient leaning forward was recorded. The remainder neurologic exam was unremarkable with no headache being reported.
He was under treatment with dupilumab injections every 2 weeks and 6 mg of prednisolone daily for his atopic dermatitis for the past 4 months. Apart from AD, he had undergone two surgeries for his lumbar spinal stenosis and a lumbar disc protrusion during the past year and was also suffering from cervical spinal stenosis, which explained his reduced reflex levels, sensory deficits, burning sensation, and gait impairment. Apart from the rigorously increased tone of his upper limbs, he showed no other signs of parkinsonism, so this was treated as an incidental finding upon examination. He was under treatment with tamsulosin for his prostate adenoma, and atorvastatin for hyperlipidemia and had recently been started on a low dose of pregabalin for his presumed neuropathic pain. His family history was clear for neurologic conditions.
His cognitive decline was objectified using the Montreal Cognitive Assessment (MoCA), which showed a pathological result of 21/30. His EEG showed a mild diffuse bilateral temporal encephalopathy with a focus on the left side. CSF analysis showed a meningitis syndrome with a lymphocytic pleocytosis (up to 48 cells/mul) and elevated protein (up to 261 mg/dl) with no signs of intrathecal antibody production and normal glucose level. A cranial MRI was performed and showed nodular, primarily sulcal, and pial contrast-enhancing formations. These were predominantly located in the right temporoparietal lobe and accompanied by brain edema, in anatomical correlation to the patient's neuropsychiatric symptoms, as well as his difficulties in orientation. Underlying infectious causes were ruled out through negative PCR results in the CSF for bacterial meningitis, tuberculosis, fungal infections, and viral meningitis including herpesviruses 1 to 6. Serology for cryptococcal and aspergillus antigens was negative. Aerobic and anaerobic bacterial cultures and mycobacterial cultures, as well as fungal cultures in the blood and the CSF, showed no growth. Serology for Lyme's disease, HIV, syphilis, hepatitis B, and C was negative. An extensive search for autoantibodies in the CSF inducing meningoencephalitis syndromes, including antibodies against sodium channels (AMPA1/2, NMDA-receptor, NMDA-NR1-receptor), chloride channels (GABA-B-receptor-1), the potassium channel-complex, including anti-CASPR2 and anti-LGI-1 antibodies, anti-amphiphysin-1, anti-GAD, and anti-Ma1/2-autoantibodies, also showed no positive results. Serological vasculitic parameters were unremarkable. A whole-body PET-CT showed no pathological findings largely ruling out a malignancy or granuloma formation outside the central nervous system. The Angiotensin Converting Enzyme (ACE) levels in blood and CSF were within the normal range. Pausing dupilumab and a 3-day-course of 1 g of methylprednisolone intravenously followed by an oral steroid course for 4 weeks led to quick clinical improvement and regression of his radiological findings on follow-up imaging and normalization of his EEG, as well as his CSF findings. His result on the MoCA also improved within <2 months to 24/30. The atopic dermatitis was treated with topical corticoids. Figure 1 shows the dynamics of his CSF parameters before and after initiation of treatment, whereas Figure 2 shows his findings on the MRI during his first hospitalization and on follow-up.
We postulate the diagnosis of a drug-induced neurosarcoid-like reaction caused by dupilumab, based on the typical imaging and CSF findings, as well as the prompt response to the withdrawal of the responsible drug and corticoid treatment. Normal ACE levels do not rule out the diagnosis given their low sensitivity for sarcoidosis.