Comparison of fixed cell-based assay to radioimmunoprecipitation assay for acetylcholine receptor antibody detection in myasthenia gravis.

OBJECTIVE: To compare specificity and sensitivity of a commercially available fixed cell-based assay (F-CBA) to radioimmunoprecipitation assay (RIPA) for acetylcholine receptor antibody (anti-AChR) detection in myasthenia gravis (MG). METHODS: In this retrospective diagnostic cohort study we reviewed the clinical information of suspected MG patients evaluated at the London Health Sciences Centre MG clinic who had anti-AChR RIPA and then F-CBA performed, in order to classify them as MG or non-MG. Classification of each patient as anti-AChR F-CBA-negative/positive, RIPA-negative/positive, and MG/non-MG permitted specificity and sensitivity calculations for each assay. RESULTS: Six-hundred-eighteen patients were included in study analysis. The median patient age at time of sample collection was 45.8 years (range: 7.5-87.5 years) and 312/618 (50.5%) were female. Of 618 patients, 395 (63.9%) were classified as MG. Specificity of both F-CBA and RIPA was excellent (99.6% vs. 100%, P > 0.99). One F-CBA-positive patient was classified as non-MG, although in retrospect ocular MG with functional overlay was challenging to exclude. Sensitivity of F-CBA was significantly higher than RIPA (76.7% vs. 72.7%, P = 0.002). Overall, 20/97 (21%) otherwise seronegative MG (SNMG) patients after RIPA evaluation had anti-AChR detected by F-CBA. CONCLUSIONS: In our study anti-AChR F-CBA and RIPA both had excellent specificity, while F-CBA had 4% higher sensitivity for MG and detected anti-AChR in 21% of SNMG patients. Our findings indicate that F-CBA is a viable alternative to RIPA for anti-AChR detection. Prospective studies comparing F-CBA, RIPA and L-CBA are needed to determine optimal anti-AChR testing algorithms in MG.

Neural Antibody Testing for Autoimmune Encephalitis: A Canadian Single-Centre Experience.

Neural antibodies have emerged as useful biomarkers in suspected autoimmune encephalitis. We reviewed results of neural antibody testing (anti-N-methyl D-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein (LGI1), contactin-associated protein-like 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid type B receptor (GABA(B)R), dipeptidyl-peptidase-like protein-6 (DPPX), IgLON family member 5 (IgLON5) and glutamic acid decarboxylase-65 (GAD65)) using cell-based assays (CBAs) and tissue indirect immunofluorescence (TIIF) at our centre. Our findings suggest increased clinical sensitivity of CBA compared to TIIF. However, this may come at some expense to clinical specificity, as evidenced by possible false-positive results when weak serum positivity by CBA was observed for certain antibodies (i.e. anti-NMDAR, CASPR2). In such cases, correlation with serum TIIF, as well as CSF CBA and TIIF, aids in identifying true-positive results.

Classically Described, Paradoxically Underrecognized: A Case of Proximal Weakness, Hyporeflexia/Areflexia, and Dysautonomia.

ABSTRACT: We present a case of chronic, progressive proximal weakness with dysautonomia and hyporeflexia/areflexia ultimately diagnosed with Lambert-Eaton myasthenic syndrome. An approach to neuroanatomical localization is discussed leading to the appropriate selection of electrodiagnostic studies. The electrophysiologic triad of Lambert-Eaton myasthenic syndrome is demonstrated with diffusely reduced motor amplitudes, decrement with low-frequency repetitive nerve stimulation, and increment of motor amplitudes after maximum voluntary contraction. Subsequent serologic testing for P/Q-type voltage-gated calcium channel antibodies are markedly elevated. We highlight the clinical features and pitfalls of examining a patient with Lambert-Eaton myasthenic syndrome when suspecting this challenging diagnosis. The neurophysiological underpinning of the electrodiagnostic results is explained, and the diagnostic utility of single-fiber electromyography is briefly discussed.