We present the case of a 66-year-old Chinese male patient with no previous relevant history or family history of neurological disease. He initially noticed numbness of the feet and weakness of the legs. Two months later, the numbness spread to his thigh root, followed by weakness and numbness of his hands. Subsequently, he presented with gait ataxia and distal limb numbness. Therefore, he went to a local hospital for help. He showed mild facial bilateral paralysis. As his symptoms worsened, it was difficult for him to walk without assistance. Clinical examination showed that muscle weakness and sensory disturbance were observed in the distal parts of all limbs. In a manual muscle strength test, his upper limb muscle strength was grade 4 and lower limb muscle strength was grade 3. Deep tendon reflexes had disappeared in all limbs and no muscle atrophy was observed. No other abnormalities were found in the patient’s cranial nerves or autonomic nervous system. A head computerized tomography (CT)-scan was normal. He then underwent a lumbar puncture, which revealed albuminocytological dissociation, with protein concentration of 2.78 g/L and 2 cells /μl. Electromyography showed that sensory nerve conduction was prolonged in the upper and lower limbs, while motor nerve conduction and F-wave latency was prolonged in the upper limbs and disappeared in the lower limbs. Lumbar spine magnetic resonance imaging (MRI) showed mild herniated disc at lumbar segments 4 and 5 (L4–L5) and lumbar segment 5 and sacral segment 1 (L5–S1). Cervical spine MRI showed mild herniated disc at cervical segment 3–6 (C3–C6). The thorax–abdomen–pelvis CT scan detected no malignancy. A biochemical examination revealed no abnormal findings, with the exception of low hemoglobin (124 g/L), low albumin (30.4 g/L), high cholesterol (7.13 mmol/L), and high D-Dimer (1.48 mg/l). The results of screening tests for human immunodeficiency virus, syphilis reaction, antineutrophil cytoplasmic antibody (ANCA), antinuclear antibody (ANA), common cancer markers, and lead level were negative. The patient’s levels of creatine kinase and vitamins B1, B12, and E were normal. Other normal or negative antibody tests included myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP4), antibodies associated with paraneoplastic neurological syndromes (PNS), and antiganglioside complex antibody profiles. He was suspected as CIDP and treated with intravenous immunoglobulin (0.4 g/kg/day for five consecutive days) and prednisone tablets 40 mg daily. The symptoms got worse after 1 month of therapy. The patient was then admitted to our hospital. He complained that sensory symptoms of numbness were more prominent than his motor weakness. Physical examination revealed bilateral periphery facial paralysis, decreased temperature of the limb extremities, reduced pinprick and vibration sense, absent reflexes of both the upper and lower extremities, and an unsteady gait. Muscle strength was grade 3 in the upper and lower limbs. Nerve conduction studies showed motor and sensory demyelinating neuropathy in the upper and lower limbs. Deep venous thrombosis was found in the right lower extremities by ultrasonography. Whole body positron emission tomography (PET)-CT scan showed diffuse low-density nodules in the liver without high glucose metabolism, which probably indicated benign lesions, bilateral renal cysts, and spinal degeneration. Enhanced MRI of the liver showed diffuse intrahepatic lesions, which were considered bile duct hamartomas in the liver. The patient was diagnosed as definite CIDP, referring to the diagnostic criteria of European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) []. The patient’s lack of response to intravenous immunoglobulins prompted us to consider autoantibodies targeting node of Ranvier proteins. Therefore, the serum sample was tested for auto antibodies against Ranvier proteins, including NF155, NF186, CNTN1, CNTN2, and Caspr1 []. Finally, the antibody test was positive for anti-Caspr1 antibodies (1:1000). We made the diagnosis of CIDP associated with anti-Caspr1 antibody. Then the patient received high-dose methylprednisolone, followed by standard plasma exchange and rituximab therapy. The patient’s sensory and motor manifestations were significantly improved at 1 year follow-up.