Unusual association of seronegative, nonparaneoplastic limbic encephalitis and relapsing polychondritis in a patient with history of thymectomy for myasthenia: a case study

Abstract

Sirs,Limbic encephalitis (LE) associated with other autoimmune disorders is relatively rare. There is an evidence of LE with relapsing polychondritis [1,2] or Sjogren's syndrome [3], and also with myasthenia gravis [6]. We present a case of LE with an unusual association of different autoimmune conditions.A 73-year-old man developed headache and fever over 2 weeks and a transitory loss of consciousness. His wife reported episodes of confusion over the previous 2 months.He had a medical history of seropositive myasthenia gravis in 1996 requiring artificial ventilation, plasmapheresis, immunotherapy and thymectomy. Removed thymus showed atrophy without histopathological finding of thymoma or thymic hyperplasia. After 2 years, the patient was asymptomatic and decided to stop all treatment and follow up. His medical history also included acute myocarditis in 1972, asthma, gastric ulcer. He was followed up for bladder carcinoma without signs of activity since the operation in 1994 and recent biopsy revealed prostatic microcarcinoma.On admission, he was disoriented in place and person and was confabulating. He had painful erythema of his right auricle, which he had experienced in the past. Neurological examination was unremarkable except for slight gait instability.Laboratory results showed mild inflammatory changes (hyperleucocytosis, higher erythrocyte sedimentation rate 20 mm/h, and raised C reactive protein 20.3 mg/l). Thyroid function was normal. Serum auto-antibodies ANA, ANCA, GBMi and dsDNA were negative; only anti-striatal muscle antibodies were slightly positive. Cerebrospinal fluid analysis showed mild protein-cytological association (hyperproteinorachia 0.657 g/l and 89 mononuclear cells). Serology for HIV, Borrelia, HSV1,2, CMV, EBV, VZV and neurosyphilis was negative. Onconeural antibodies anti-Yo, Hu, Ri, anti-VGKC antibodies, anti-GAD, antiamphiphysin and anti-NMDA receptor antibodies were negative in serum and cerebrospinal fluid.MRI showed FLAIR and T2 hippocampal temporal hyperintensities, vascular white matter lesions and moderate atrophy (Fig. 1). EEG repeatedly showed slow waves in the temporal regions. Whole body PET scan was negative.Progressively, myoclonic jerks, cerebellar signs, aphasia and hallucinations appeared with worsening of cognitive impairment. Bilateral auricle swelling occurred with softening and loss of cartilage contour. Biopsy revealed nonspecific cartilage inflammation without signs of an acute vasculitis (Fig. 2b), compatible with criteria for relapsing chondritis. Parenteral bolus of methylprednisolone 1,500 mg over 3 days led to partial and transitory improvement, therefore a month later bolus of 3,500 mg was repeated followed by permanent treatment with oral methylprednisolone 24 mg daily. Painful swelling extended to elbows and knees, and partial complex seizures with orofacial automatisms developed. A third bolus of 1,500 mg methylprednisolone was administered and four cycles of plasmapheresis were performed with only limited effect, moreover, massive eruptions of herpes...

Relapsing Polychondritis with Encephalitis: A Case Report and Literature Review

“…Although CNS involvement due to vasculitis is rare, RP has been reported to be associated with aseptic meningitis, meningoencephalitis, encephalitis, and ischemic stroke (3). To our knowledge, there have been 18 cases of RP-associated meningoencephalitis and encephalitis demonstrated clinically and on neuroimaging in the English literature (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The clinical features of the previously reported cases and the present case are summarized in Table. Among these cases, the age of onset was between 29 and 73 years (mean, 55 years).…”

“…Although perivascular cuffing around the meningeal and intracerebral vessels was observed with an increased vascular wall thickness, these histological features were not specific for vasculitis (7). Brain autopsies performed in three cases showed neuronal loss and gliosis in the hippocampus with leptomeningeal lymphocytic infiltrates (8), non-specific meningoencephalitis without evidence of vasculitis (12) and non-specific subacute and chronic inflammation of the meninges and both white and grey matter spreading cortically (18). Although vasculitis is assumed to be the cause of CNS involvement in patients with RP (16), the above-mentioned observations do not support this assumption.…”

Perivasculitic Panencephalitis with Relapsing Polychondritis: An Autopsy Case Report and Review of Previous Cases

“…Stewart et al (13) reported extensive cerebral and systemic vasculitis to be the cause of CNS involvement in patient with RP. In contrast, other authors have reported inflammatory changes not specific to vessels in patients presenting with limbic encephalitis or meningoencephalitis associated RP (7,(14)(15)(16)(17). In these autopsy cases, diffuse vasculitis and/or perivascular infiltration were observed, with gliosis in the leptomeninges and brain parenchyma of the limbic area and basal ganglia, etc.…”

The Diagnostic Challenge of Seronegative Autoimmune Encephalitis With Super-Refractory Status Epilepticus

“…The term seronegative autoimmune encephalitis has been used to describe a subgroup of autoimmune encephalitis cases with negative serologic tests for autoantibodies [2][3].…”

“…Seronegative autoimmune encephalitis is a subcategory of autoimmune encephalitis diagnosed when autoimmune antibodies are not detected in cerebrospinal fluid (CSF) or serum [2][3]. The possible reasons for the absence of antibodies, as stated by Najjar et al, include declining serum antibodies and the existence of unidentified antibodies which are yet to be discovered [2].…”