Steroid-Responsive Limbic Encephalitis

Watanabe, Yasuhiro; Shimizu, Y; Ooi, Shinji; Tanaka, Keiko; Ishii, Takashi; Nakashima, Kenichiro

doi:10.2169/internalmedicine.42.428

Cited by 15 publications

(6 citation statements)

References 14 publications

(3 reference statements)

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“…In our case, disease progression despite steroid treatment [6,7] required a more aggressive immunotherapy with immunoglobulin [8] and azathioprine, which apparently are good alternative treatment options in NPLE without sufficient response to steroid treatment. Under this medication, there was a partial neuropsychological improvement and a decline of the VGKC-Ab levels.…”

Section: Sirsmentioning

confidence: 76%

Successive affection of bilateral temporomesial structures in a case of non-paraneoplastic limbic encephalitis demonstrated by serial MRI and FDG-PET

et al. 2009

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Sirs,Non-paraneoplastic limbic encephalitis (NPLE) often results in an unfavorable clinical course with progressive neuropsychological deficits and epileptic seizures despite treatment [1][2][3]. Magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET) and antibodies against voltage-gated potassium channels (VGKC-Ab) are helpful in monitoring the course of the disease [3][4][5]. We present a follow-up of a NPLE patient over a 3-year period with successive affection of bilateral temporomesial structures.A 67-year-old man with no relevant medical history presented with recurrent episodes of visual hallucinations, memory impairment, disorientation and myoclonic jerks. Neurological examination was unremarkable; however neuropsychological testing revealed severe verbal (shortterm) memory, speech fluency and visual recognition deficits. EEG showed an intermittent theta-focus as well as intermittent right temporal ictal rhythmic activity. On MRI hyperintensity and diffuse swelling of the right hippocampus on T2-and diffusion-weighted (DWI) images was found. FDG-PET revealed right temporomesial hypermetabolism and bilateral hypometabolism in the temporal lobes (Fig. 2a). There were no signs of tumor in the wholebody PET examination. CSF (including virological analysis) was normal except for elevated VGKC-Ab levels ([9085 pM, controls \100 pM). Thyroid function and autoantibodies tests were negative. The diagnosis of NPLE was made and methylprednisolone (MP; 4000 mg i.v. over 5 days) as well as gabapentin treatment was initiated. Figure 1 shows the course of the disease, examination results and therapeutic management.Three months later, the patient presented with a deterioration of symptoms. MRI showed an atrophy of the right hippocampus, with mild residual T2-hyperintensity. FDG-PET showed left temporal hypermetabolism and a right temporomesial ''cold'' lesion (Fig. 2b). VGKC-Ab were still elevated ([8067 pM). Treatment with MP (5000 mg i.v. over 5 days) was started again. Six months later he was re-admitted with progressive memory impairment, confirmed by neuropsychological examination. Now on MRI, left hippocampal edema was found and FDG-PET demonstrated severe hypometabolism in both temporomesial regions. After 2 months of stable condition, there was once again neuropsychological deterioration. There were no significant changes on MRI compared to the previous examinations and the FDG-PET showed left temporomesial hypometabolism. IV immunoglobulin therapy (150 g over 3 days) was applied. Two and 4 months later MRI and FDG-PET findings remained unchanged. VGCK-Ab levels were almost normal. Memory impairment had temporarily deteriorated before improving again, this time under immunosuppressive treatment with azathioprine (100 mg/ d). At the last two visits (after 2 and 3.5 years) the patient was seizure-free under gabapentin and showed an improvement of his cognitive functions under azathioprine treatment. MRI showed left hippocampal atrophy and FDG-PET hypometabolism in both temporomes...

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Section: Sirsmentioning

confidence: 76%

Successive affection of bilateral temporomesial structures in a case of non-paraneoplastic limbic encephalitis demonstrated by serial MRI and FDG-PET

et al. 2009

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“…Hu, CV2/CRMP5 and Ma2) indicates a paraneoplastic origin and limited response to treatment (Honnorat et al, 1996;Alamowitch et al, 1997;, the detection of antibodies to cell surface antigens such as voltage-gated potassium channels (VGKCs) suggests a lesser risk for an underlying cancer and better response to immunosuppression (Pozo-Rosich et al, 2003;Vincent et al, 2004). However, in at least 20% of patients with subacute limbic encephalitis, initial diagnostic tests are negative (Bien et al, 2000;Gultekin et al, 2000;Watanabe et al, 2003). Because the CSF of these patients often shows abnormalities similar to those found in immune-mediated disorders, and because some patients improve with immunotherapy, we postulated the presence of immune mechanisms that are missed by conventional studies.…”

Section: Introductionmentioning

confidence: 99%

Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates

Ances¹,

Vitaliani²,

Taylor³

et al. 2005

Brain

432

333

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We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [(18)F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment.

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“…La présence d'anti-VGKC ne doit cependant pas être considérée comme un marqueur discriminant entre formes paranéoplasiques et idiopathiques [20]. Par contre, ils ont été décrits comme associés à une bonne réponse à l'immunothérapie, notamment aux corticostéroïdes en bolus intraveineux puis à doses dégressives [21,25]. Certains auteurs, considèrent même les anti-VGKC comme un marqueur de bonne réponse thérapeutique [20], à l'inverse des anti-Hu qui sont considérés comme des marqueurs de non-réponse [26].…”

Section: Discussionunclassified

Une encéphalite limbique non paranéoplasique révélée par une amnésie antérograde

Lang

Sellal

2008

La Presse Médicale

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Steroid-Responsive Limbic Encephalitis

Cited by 15 publications

References 14 publications

Successive affection of bilateral temporomesial structures in a case of non-paraneoplastic limbic encephalitis demonstrated by serial MRI and FDG-PET

Successive affection of bilateral temporomesial structures in a case of non-paraneoplastic limbic encephalitis demonstrated by serial MRI and FDG-PET

Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates

Une encéphalite limbique non paranéoplasique révélée par une amnésie antérograde

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