We present a case of concurrent ALS and CIDP, highlighting diagnostic challenge and questioning whether they are distinct entities or part of a broader disease spectrum. This is the first reported case of immune-mediated polyneuropathy in an ALS patient with the C9orf72 mutation.

A 62-year-old Caucasian male developed right foot drop that initially was attributed to fibular nerve injury; he underwent fibular nerve release without significant improvement. At the same time, he developed progressive weakness and numbness in his bilateral hands. MRI revealed cervical canal stenosis and neuroforaminal narrowing that prompted neurosurgical decompression, without significant clinical improvement. Then, he developed left foot drop four months before the clinic presentation. On presentation to the neurology clinic, two years after symptom onset, he exhibited dysarthria, tongue fasciculations, weakness (1/5-4/5) in all extremities, muscle atrophy, widespread fasciculations, and upper extremity hyperreflexia, meeting clinical criteria for ALS. Brain MRI demonstrated motor band sign, which further supports the diagnosis of ALS. Although EMG/NCS findings were consistent with lower motor neuron disease, he also had signs of demyelinating neuropathy based on conduction parameters.  Neuromuscular ultrasound showed significant diffuse nerve enlargement typical for inflammatory neuropathy, but not for ALS.  CSF studies revealed albumino-cytologic dissociation (protein of 112 mg/dL) and high albumin quotient and index. He fulfilled CIDP criteria. Genetic testing confirmed a C9orf72 mutation, commonly linked to familial ALS. He was started on intravenous Immunoglobulin with temporary improvement.

This is the first case of the co-existence of CIDP and ALS in the setting of C9orf72 mutation.  Further research is needed to determine if there is a causal link between neurodegeneration and autoimmunity, especially in the setting of C9orf72 mutation.