Relapsing polychondritis Is a rare disorder that is characterised by recurrent and progressive inflammation of cartilaginous structures. Nervous system involvement in relapsing polychondritis has been described. We describe two cases of relapsing polychondritis with subacute dementia.
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Relapsing polychondritis (RP) is a rare disorder that is characterised by recurrent and progressive inflammation of cartilaginous structures.1 Nervous system involvement in RP has been described.1–5 We describe two cases of RP with subacute dementia to raise awareness of the existence of this rare but potentially treatable cause of dementia.
A 51-year-old lawyer was diagnosed with RP when he presented with bilateral ear swelling. He was treated with 10 mg/day of oral prednisone during this attack, with a brief taper. He continued to have flare-ups during the next several years and was treated with a short duration of prednisone ranging from 10 to 40 mg/day. Episodes of iritis and scleritis were treated with steroid eye drops. One year after the diagnosis of RP, he started to experience gradual-onset coordination problems, difficulty presenting verbal arguments, distractibility and emotional lability. He developed insomnia and nocturnal myoclonic jerks. Neuropsychological evaluation showed perseveration, prominent attention and concentration deficits. Brain MRI showed extensive periventricular and deep white matter high-signal abnormalities. There was reduced metabolic activity in bilateral temporal cortices and parietal lobes on PET scan. Electroencephalogram was normal. Cerebrospinal fluid (CSF) contained 89 mg/dL of protein, 52 mg/dL glucose, 39 white blood cells (WBCs) (65% lymphocytes) and 2 red blood cells (RBCs). CSF tau/amyloid levels and ratio were considered to be consistent with Alzheimer’s disease. CSF IgG index and synthesis rate were elevated. CSF 14–3–3 protein, borrelia PCR, cryptococcal antigen, paraneoplastic titres, serum HIV serology, VDRL, heavy metal screen, p- and c-ANCA, and RPR were negative. HSV 1/2 IgG antibody was mildly elevated; IgM was negative. Serum WBCs, sedimentation rate and C-reactive protein (CRP) were normal during the course of his progressive dementia. Cerebral angiogram was normal. Given the lack of a diagnosis after non-invasive investigations, brain biopsy of the right frontal cortex was performed 5 months after the onset of neurological symptoms. Biopsy showed findings of non-specific inflammation without evidence of vasculitis (see supplementary fig 1). A diagnosis of meningoencephalitis secondary to RP was made. Prednisone was increased to 80 mg/day without clinical improvement. Cyclophosphamide was added at 150 mg/day 6 months after onset of neurological symptoms. He continued to decline, with increased confusion, speech latency, word-finding difficulty and increased myoclonus. He died 5 months after brain biopsy. Autopsy confirmed diagnosis of non-specific meningoencephalitis involving the meninges, cortical and deep brain parenchyma. There was no evidence of vasculitis. Microglial nodules suggestive of viral encephalitis and protease-resistant prion protein were absent (see supplementary fig 1).
A 68-year-old college instructor presented with myalgias, headache, fever and bilateral ear swelling, and was diagnosed with RP. He was started on a low dosage of prednisone, which was discontinued due to side effects. Two months later, he developed a hoarse voice and vertigo, recurrence of ear swelling and was started on dapsone. Around the same time, he started exhibiting comprehension problems, emotional lability and visuospatial problems. During the course of his illness, he had flare-ups of ear swelling. He also developed conjunctival involvement and lost 30 pounds. Over a course of 8 months, he gradually continued to decline cognitively to a degree where he was unable to perform day-to-day activities independently. He also had two discrete episodes of worsening confusion and language problems lasting several hours. Neuropsychological testing showed impairment in verbal and visual memory, executive dysfunction, visuospatial impairment and mild anomia. CSF contained 49 mg/dl protein, 4 WBCs (44% lymphocytes), 124 RBCs and 39 mg/dl glucose. CSF fungal, viral and bacterial cultures, cryptococcal antigen, VDRL, angiotensin-converting enzyme, stain and culture for acid-fast bacilli were negative. Serum lyme titres, VDRL, paraneoplastic markers, anti-ss-DNA, anti-ds-DNA, anti-ENA, anti-SSA, anti-SSB antibodies, HIV serology, treponemal antibody, serological markers for Sjorgen’s disease, SLE and Wegener’s were negative. Sedimentation rates ranged from 9–15 mm/h and CRP was 0.2 mg/l. Brain MRI at the onset of his symptoms was normal. MRI at 5 months after symptom onset showed oedema and high T2 signal in the right medial temporal lobe, and a small area of enhancement in the left caudate with contrast administration. Repeat brain MRI 1 month later (6 months after onset of neurological symptoms) showed resolution of temporal lobe oedema and caudate enhancement, increased T2 signal in both caudate heads and the right medial temporal lobe with atrophy (see supplementary fig 2). Electroencephalogram showed bilateral low amplitude with beta frequency. He was diagnosed with CNS involvement of RP without brain biopsy and started on 80 mg of prednisone 11 months after the onset of neurological symptoms, with no further deterioration over a 12-month follow-up.
Both patients meet diagnostic criteria for RP.1 CNS involvement has been attributed either to vasculitis or meningoencephalitis.1–3 Only a few case reports describe histopathological findings in CNS involvement in RP.2,3 (See supplementary table 1 for all case reports.)
Dementia and limbic encephalitis have been reported.3–5 Imaging findings of non-specific white matter changes, preferential involvement of the medial temporal lobes and brain atrophy have been reported.3–5 Cerebrospinal fluid may show inflammatory changes.2–5
The pathophysiology of CNS involvement in RP is not well understood. Diagnosis and treatment are not well established. Diagnosis may be delayed when patients present with CNS symptoms while on immunosuppressants for systemic disease and opportunistic infections are in the differential. To rule out steroid contraindications, a CSF examination to exclude bacterial, fungal or TB meningitis, and brain MRI to rule out ring-enhancing lesions should be adequate. Empirical treatment for herpes encephalitis can be initiated early while awaiting PCR diagnosis. Brain biopsy and cerebral angiogram seem to provide minimal diagnostic information in most cases. Steroids or cytotoxic agents have been used for treatment, whereas response to treatment is not consistent and relapses in medication use have been reported.2,3 Greater awareness of the existence of a polychondritis-associated encephalitis may spare patients the morbidity of brain biopsy, and may also lead to prompt and aggressive immunosuppressant therapy, which may reduce morbidity and mortality.
Relapsing polychondritis (RP) is a rare disorder that is characterised by recurrent and progressive inflammation of cartilaginous structures.
RP can rarely cause dementia.
Diagnosis of dementia due to RP is challenging,. Brain biopsy is of questionable utility and usually shows non-specific inflammation,.
Treatment is with immunosupression.
This article has been adapted with permission from Erten-Lyons D, Oken B, Woltjer RL, Quinn J. Relapsing polychondritis: an uncommon cause of dementia. J Neurol Neurosurg Psychiatry 2008;79:609–10.
Competing interests: None.