Abstract
A 68-years-old Hispanic man, complained of night sweats, low grade fewer, unexplained weight loss, and memory problems over 3 months. Abdominal tomography showed multiple intra-abdominal adenopathy and biopsy confirmed classic Hodgkin's lymphoma. He commenced treatment with chemotherapy. Three months later, he had acute onset of inattention, auditory hallucinations and alterations of anterograde memory. The patient developed psychomotor agitation, unresponsive to a combination of neuroleptics and benzodiazepines. Brain MRI showed a small established cerebellar infarction. Electroencephalogram was normal. Tests for toxic metabolic encephalopathy were negative. One oligoclonal IgG bands was found in the Cerebrospinal fluid (CSF), which was not observed in corresponding serum, but cell count and protein were normal. Extensive testing for infectious encephalitis was unremarkable. CSF testing for commercially available neural and non-neural autoantibodies was negative. The patient fulfilled the Gultekin diagnostic criteria for paraneoplastic limbic encephalitis and methylprednisolone IV 1g/d for 5 days was given. He recovered rapidly, with progressive improvement in memory and psychomotor agitation. After treatment commenced, results for antibodies to mGluR5 in CSF taken prior to treatment were returned as positive. mGluR5 is found on post-synaptic terminals of neurons and microglia and is expressed primarily in the hippocampus and amygdala. This case highlights the difficulties in diagnosing this type of encephalitis: the CSF did not show pleocytosis, the MRI showed only chronic change and the electroencephalogram was normal. The dramatic recovery after methylprednisolone help to better characterized the clinical spectrum of auto-immune encephalitis. Diagnosing anti mGlutR5 encephalitis may lead to potentially highly effective treatment option and may anticipate the diagnostic of a cancer. A high index of suspicion is needed to avoid missed diagnosis. In patients with unexplained encephalitis, testing for antibodies to mGluR5 in CSF and serum should be considered. When there is a reasonable index of suspicion of auto-immune encephalitis, treatment should not be delayed for the antibody results.
Highlights
Glutamate is the major excitatory neurotransmitter in the central nervous system and glutamatergic neurotransmission is involved in most aspects of normal brain function
The close link between the autoimmune response and Hodgkin’s lymphoma or other malignancies may contribute to its under-recognition, as neuropsychiatric changes may be attributed to treatment or psychological factors [2, 3, 5,6,7]
Anti-mGluR5 encephalitis can occur without tumor: in the eleven previously reported cases of encephalitis with mGluR5 [2], the association with tumors occurred in six patients: five had Hodgkin’s lymphoma and one had small cell lung cancer
Summary
Glutamate is the major excitatory neurotransmitter in the central nervous system and glutamatergic neurotransmission is involved in most aspects of normal brain function. The metabotropic glutamate receptors belong to a family of G protein-coupled receptors that have been divided into three groups based on their sequence homology, putative signal transduction mechanisms, and pharmacologic properties [3, 4]. MGluR1 and mGluR5 constitute Group I metabotropic glutamate receptors. The antibodies cause a decrease of mGluR5 cluster density at both synaptic and extrasynaptic locations [2], the exact mechanism by which the antibodies alter the receptor density is unknown. Their location may explain the typical behavioral and memory problems in this mGluR5 antibody— associated encephalitis. Clinical correlates of mGluR5 antibodies have been reported in only 11 patients [2]
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