A 46-year-old woman presented with 14 months of profound progressive asymmetric quadriparesis, sensory loss, and burning paresthesias. Within 6 months she required the use of a wheelchair and Hoyer lift.  Other symptoms included lancinating pain, myoclonic jerks, tremor, insomnia, changes to voice, dysphasia, hypertension, and distal extremity edema.  Examination was notable for 0/5 strength in the toes and ankles, and 2/5 strength in the wrists, hips and knees. Shoulder abduction and elbow flexion/extension were antigravity.  Cold sensation was reduced to the knees and forearms. The patient was areflexic with fasciculations of the eyelid, chin, and upper extremities.  Her symptoms resembled monophasic CIDP, but the severity of her presentation raised suspicion for a CIDP variant.

Spinal accessory nerve conduction suggested demyelination due to a prolonged distal motor latency (8.28ms) and low amplitude CMAP (2.5mV). The remainder of motor and sensory nerves were not able to be evoked. EMG showed widespread upper/lower extremity denervation and chronic reinnervation, with less involvement of the trapezius. MRI showed diffuse enhancement of the trigeminal nerve and cauda equina. Lumbar puncture confirmed albuminocytologic dissociation.  A serum demyelinating neuropathy panel yielded IgM vs Histone H3.  Cerebrospinal fluid and serum yielded antibodies to contactin-1, confirming an IgG4-mediated CIDP variant. The patient was treated with IV methylprednisolone weekly and a cycle of rituximab; she has shown slow, steady improvement in both sensory and motor function.

It is important to consider IgG4 pathology in cases of CIDP which are severe and characterized by atypical symptoms, such as asymmetry and lack of response to IVIG. More work is needed to understand the optimal diagnostic paradigm when IgG4-mediated disease is suspected. Early identification of IgG4 syndromes is essential to guide selection of appropriate therapy since these syndromes are typically most responsive to B-cell inhibition.