41 y/o F with PMH newly-diagnosed DM who presented with horizontal diplopia x 3 months and ptosis that developed shortly thereafter. She was evaluated by an outpatient neurologist, who diagnosed her with myasthenia gravis. Anti-AchR and MUSK antibodies were negative. She was started on Mestinon and did not respond. Over the next two months, she developed progressive weakness with difficulty breathing and fatigueability in arms>legs, problems with speech and swallowing, as well as difficulty coughing. In July, she visited family in New York, who noticed significant dyspnea, weakness, and bilateral facial droop. When she returned from her trip, she saw her outpatient neurologist, who discontinued Mestinon and referred her to neuro-ophthalmology. In neuro-ophthalmology clinic, she was noted to have bulbar weakness and respiratory distress, and she was referred to the ER.
On admission, she was afebrile with normal blood pressure. Her heart rate was 105, and she was tachypneic but with O2 saturation 99% on room air taking shallow breaths. She was able to count to 20 in a single breath. Her cardiovascular exam was normal.
Cranial nerve exam was significant for conjugate vertical gaze palsy, gaze-evoked horizontal nystagmus, bilateral ptosis, bilateral upper and lower facial weakness, hypophonic voice with absent cough, and weakness with bilateral tongue movement. Motor exam was significant for 2/5 neck flexion and 5/5 strength in her extremities with fatigueable weakness in her arms. Sensory and coordination exams were normal. Reflexes were 3+ throughout with upgoing toes bilaterally.
Admission chemistry showed sodium 133, Cl 93, gap 12, glucose 244, LFTs WNL. CBC showed no leukocytosis, and H/H 16.2/47.1. U/A showed glucosuria, ketonuria, large leukocyte esterase, 12 WBCs, and 20 squamous cells. Beta-hcg was negative.
She was admitted to the neuro floor and had the following workup:
–ESR 46, CRP 7.63
–Blood and urine cultures negative
–Borrelia Burgdorferi negative
–CSF: 2-3 WBCs, 220-250 RBCs without xanthochromia, Protein 39, and glucose 118. Bacterial culture negative. CMV, VZV, HSV, EBV negative. Cytology and flow cytometry negative.
–Negative serum antibody studies: Acetyl receptor binding and striational, ANNA1, ANNA2, ANNA3, Anti-glial nuclear, Anti-collapsin, Anti-Purkinje Cytoplasm 1 and 2 and TR, Anti-Ampiphysin, Anti-P/Q type calcium channel, Anti-N type calcium channel, Anti-ganglionic neuron Ach-R, Anti-Voltage gated K channel, ANCA, Anti-dsDNA, Anti-Tissue Transglutaminase, Anti-Centromere, Anti-Smith, Anti-RNP, Anti-SCL70, Anti-SSB, Anti-JO1, Anti-CCP, Anti-GQ1B
–Positive serum antibody studies: Anti-SSA/RO (IgG titer 91), Anti-Thyroid Peroxidase (titer 75), Anti-glutamic acid decarboxylase (titer 69.8), Anti-thyroglobulin antibody (titer 116.8), Anti-ma2 (Anti-Ta)
–Cortisol, FSH, LH, ACTH, PRL, TSH levels all WNL.
–Negative Tumor Markers: alpha-fetoprotein, CEA, and CA 125 all negative.
–Positive Tumor Markers: Elevated CA GI 19 9 (level = 49)
–MRI brain and C-spine with and without contrast: WNL
–CT C/A/P, MRI pelvis, bilateral breast sonogram, whole body PET: No evidence of malignancy
She developed respiratory failure within a few days of admission, for which she was transferred to the ICU and intubated. Her hospital course has been complicated by PNA. She received IVIG, PLEX x 5, and IV steroids without response, and she is currently being treated with Rituxan with a working diagnosis of Anti-GAD65, Anti-Ma2 antibody mediated autoimmune bulbar encephalitis.
Dalmau J, Graus F, Villarejo A, Posner JB, Blumenthal D, Thiessen B, Saiz A, Meneses P, Rosenfeld MR. Clinical analysis of anti-Ma2-associated encephalitis. Brain. 2004 Aug;127(Pt 8):1831-44.
Article Summary: Increasing experience indicates that anti-Ma2-associated encephalitis differs from classical paraneoplastic limbic or brainstem encephalitis, and therefore may be unrecognized. To facilitate its diagnosis we report a comprehensive clinical analysis of 38 patients with anti-Ma2 encephalitis.