Amyotrophic lateral sclerosis and chronic inflammatory demyelinating polyneuropathy coexistence in a patient with a C9orf72 variant: case report.

BACKGROUND

The C9orf72 variation has been strongly implicated in the inheritance of familial ALS, frontotemporal dementia (FTD), and combined ALS-FTD cases. Increasing evidence implicates immune changes and inflammation in some ALS patients. Several studies demonstrated that ALS coexists with CIDP or polyneuropathy. Mouse models of C9orf72 loss-of-function mutations exhibit fatal immune dysregulation.

CASE SUMMARY: A 62-year-old Caucasian man developed right foot drop, and 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 clinical improvement. Subsequently, he developed left foot drop. At the clinic presentation, he exhibited dysarthria, tongue fasciculations, weakness in all extremities, muscle atrophy, widespread fasciculations, and upper extremity hyperreflexia, meeting clinical criteria for ALS. Genetic testing identified a pathogenic variant in the C9orf72 gene, confirming a C9orf72 variant, commonly linked to familial ALS. Brain MRI demonstrated the motor band sign. Although EMG/NCS findings were consistent with lower motor neuron disease, he also had signs of demyelinating polyneuropathy based on conduction parameters. Neuromuscular ultrasound showed significant multifocal nerve enlargement typical of immune-mediated neuropathy. CSF studies revealed albuminocytologic dissociation (protein: 112 mg/dL, with normal cell count) and high albumin quotient and index. He fulfilled the 2021 EAN/PNS criteria for possible typical CIDP. He was treated with intravenous immunoglobulin in addition to riluzole with temporary improvement.

CONCLUSION

This is the first case of the co-existence of CIDP and ALS in the setting of a pathogenic C9orf72 variant.