Dataset Information

Pathologically confirmed autoimmune encephalitis in suspected Creutzfeldt-Jakob disease.

ABSTRACT:

Objective

To determine the clinical features and presence in CSF of antineuronal antibodies in patients with pathologically proven autoimmune encephalitis derived from a cohort of patients with suspected Creutzfeldt-Jakob disease (CJD).

Methods

The Dutch Surveillance Centre for Prion Diseases performed 384 autopsies on patients with suspected CJD over a 14-year period (1998-2011). Clinical information was collected from treating physicians. Antineuronal antibodies were tested in CSF obtained postmortem by immunohistochemistry on fresh frozen rat brain sections, by Luminex assay for the presence of well-characterized onconeural antibodies, and by cell-based assays for antibodies against NMDAR, GABABR1/2, GABAAR GLUR1/2, LGI1, Caspr2, and DPPX.

Results

In 203 patients, a diagnosis of definite CJD was made, while in 181 a variety of other conditions were diagnosed, mainly neurodegenerative. In 22 of these 181, the neuropathologist diagnosed autoimmune encephalitis. One patient was excluded because of lack of clinical information. Inflammatory infiltrates were predominantly perivascular and consisted mainly of T cells. The predominant locations were basal ganglia and thalamus (90%) and temporal lobes and hippocampus (81%). In 6 patients (29%), antineuronal antibodies were detected in postmortem CSF, directed against Hu, NMDAR, GABABR1/2, Caspr2, and an unidentified synaptic antigen in 2. The most frequent symptoms were dementia (90%), gait disturbance (86%), cerebellar signs (67%), and neuropsychiatric symptoms (67%). Immunopathologic and clinical findings did not differ between autoantibody-negative patients and patients with antineuronal antibodies.

Conclusions

It is important to consider immune-mediated disorders in the differential diagnosis of rapidly progressive neurologic deficits.

SUBMITTER: Maat P

PROVIDER: S-EPMC4645173 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Publications

Pathologically confirmed autoimmune encephalitis in suspected Creutzfeldt-Jakob disease.

Maat Peter P de Beukelaar Janet W JW Jansen Casper C Schuur Maaike M van Duijn Cornelia M CM van Coevorden Marleen H MH de Graaff Esther E Titulaer Maarten M Rozemuller Annemieke J AJ Sillevis Smitt Peter P

Neurology(R) neuroimmunology & neuroinflammation 20151112 6

<h4>Objective</h4>To determine the clinical features and presence in CSF of antineuronal antibodies in patients with pathologically proven autoimmune encephalitis derived from a cohort of patients with suspected Creutzfeldt-Jakob disease (CJD).<h4>Methods</h4>The Dutch Surveillance Centre for Prion Diseases performed 384 autopsies on patients with suspected CJD over a 14-year period (1998-2011). Clinical information was collected from treating physicians. Antineuronal antibodies were tested in C ...[more]

PMID: 26601117

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Project description:Creutzfeldt-Jakob disease (CJD) and autoimmune encephalitis with antibodies against neuronal surface antigens (NSA-abs) may present with similar clinical features. Establishing the correct diagnosis has practical implications in the management of care for these patients.To determine the frequency of NSA-abs in the cerebrospinal fluid of patients with suspected CJD and in patients with pathologically confirmed (ie, definite) CJD.A mixed prospective (suspected) and retrospective (definite) CJD cohort study was conducted in a reference center for detection of NSA-abs. The population included 346 patients with suspected CJD and 49 patients with definite CJD.Analysis of NSA-abs in cerebrospinal fluid with brain immunohistochemistry optimized for cell-surface antigens was performed. Positive cases in the suspected CJD group were further studied for antigen specificity using cell-based assays. All definite CJD cases were comprehensively tested for NSA-abs, with cell-based assays used for leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), N-methyl-d-aspartate (NMDA), and glycine (GlY) receptors.Neuronal surface antigens were detected in 6 of 346 patients (1.7%) with rapid neurologic deterioration suggestive of CJD. None of these 6 patients fulfilled the diagnostic criteria for probable or possible CJD. The target antigens included CASPR2, LGI1, NMDAR, aquaporin 4, Tr (DNER [?/notch-like epidermal growth factor-related receptor]), and an unknown protein. Four of the patients developed rapidly progressive dementia, and the other 2 patients had cerebellar ataxia or seizures that were initially considered to be myoclonus without cognitive decline. The patient with Tr-abs had a positive 14-3-3 test result. Small cell lung carcinoma was diagnosed in the patient with antibodies against an unknown antigen. All patients improved or stabilized after appropriate treatment. None of the 49 patients with definite CJD had NSA-abs.A low, but clinically relevant, number of patients with suspected CJD had potentially treatable disorders associated with NSA-abs. In contrast, none of 49 patients with definite CJD had NSA-abs, including NMDAR-abs, GlyR-abs, LGI1-abs, or CASPR2-abs. These findings suggest that cerebrospinal fluid NSA-abs analysis should be included in the diagnostic workup of patients with rapidly progressive central nervous system syndromes, particularly when they do not fulfill the diagnostic criteria of probable or possible CJD.

Project description:ImportanceDetection of prion proteins in cerebrospinal fluid (CSF) using real-time quaking-induced conversion (RT-QuIC) assays has transformed the diagnostic approach to sporadic Creutzfeldt-Jakob disease (CJD), facilitating earlier and more complete recognition of affected patients. It is unclear how expanded recognition of affected patients may affect the diagnostic and prognostic relevance of clinical features and diagnostic tests historically associated with CJD.ObjectiveTo evaluate clinical features and diagnostic testing in patients presenting with CJD and determine the associations of these features with prognosis.Design, setting, and participantsThis cohort study incorporated data from electronic medical records of patients with CJD treated at Mayo Clinic Enterprise tertiary care centers in Rochester, Minnesota; Jacksonville, Florida; and Scottsdale, Arizona. Participants included patients with definite or probable CJD assessed from 2014 to 2021. Data were analyzed October 2021 to January 2022.ExposuresDominant presentation, clinical features, and diagnostic tests associated with CJD.Main outcomes and measuresThe outcomes of interest were the sensitivity and prognostic value of clinical features and accessible diagnostic tests at presentation with possible CJD.ResultsA total of 115 patients were identified, including 40 patients (35%) with definite CJD. Mean (SD) age at symptom onset was 64.8 (9.4) years, and 68 patients were women (59%). The sensitivity of clinical markers (myoclonus) and tests historically considered in patients with suspected CJD was poor (eg, stereotyped electroencephalography anomalies: 17 of 105 patients [16%]; elevated CSF protein 14-3-3 levels: 54 of 90 patients [60%]). By comparison, biomarkers with good diagnostic sensitivity at presentation included RT-QuIC (66 of 71 patients [93%]), CSF total tau (T-tau) level greater than 1149 pg/mL (81 of 92 patients [88%]), and characteristic signal anomalies on magnetic resonance imaging (88 of 115 patients [77%]). Multivariable linear regression confirmed shorter survival in patients with myoclonus (difference, -125.9 [95% CI, -236.3 to -15.5] days; P = .03), visual or cerebellar signs (difference, -180.2 [95% CI, -282.2 to -78.2] days; P < .001), elevated CSF protein 14-3-3 levels (difference, -193 [95% CI, -304.9 to -82.9] days; P < .001), and elevated T-tau level (difference for every 1000 pg/mL elevation, -9.1 [95% CI, -17.7 to -1.0] days; P = .04).Conclusions and relevanceThese findings suggest that CSF RT-QuIC, elevated CSF T-tau level, and stereotyped magnetic resonance imaging anomalies were associated with the diagnosis of CJD, while other clinical findings (eg, myoclonus), stereotyped electroencephalography anomalies, and CSF protein 14-3-3 levels offered less diagnostic value. Visual or cerebellar features, myoclonus, and CSF 14-3-3 and T-tau levels may be associated with disease duration, justifying continued inclusion in the evaluation of patients suspected to have CJD.

Dataset Information

Pathologically confirmed autoimmune encephalitis in suspected Creutzfeldt-Jakob disease.

Objective

Methods

Results

Conclusions

Publications

Pathologically confirmed autoimmune encephalitis in suspected Creutzfeldt-Jakob disease.

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