A 59-year-old man was admitted to the Department of Neurology of the Shanghai Eighth People's Hospital in November 2019 due to a 1-month history of repeated falls and urination/defecation disorders. In September 2019, he was diagnosed with lumbar disc protrusion at another hospital owing to progressive bilateral lower-limb numbness and unsteady walking for 1 year and waist pain for 6 months. His serum VitB12 level was normal and he underwent minimally invasive surgery (percutaneous endoscopic interlaminar lumbar discectomy) without improvement at the time. He had a 30-year history of drinking (yellow rice wine, ~250 g/d), and denied a history of nitrous oxide abuse or anesthesia.
A physical examination at our hospital showed that the patient had a clear mind and multiple sites of pallor in the face, sclera, and lips. Muscle tension and strength were normal in the upper bilateral limbs and decreased in the bilateral lower limbs (left, grade III+; right, grade III+ [proximal] to grade II [distal]). Tendon reflexes were present (++) in bilateral upper limbs and absent in bilateral lower limbs. Pinprick sensation was decreased below the T6 level; vibration, motor, and position sensations were decreased in both lower limbs. The Babinski and Chaddock signs were positive on the left side. Blood tests showed: red blood cells (RBCs), 1.93x1012/L (normal range (NR) 4.3-5.8*1012/L); hemoglobin (Hb), 82 g/L (NR 130-175 g/L); hematocrit (HCT), 23.2% (NR 37-50%); mean corpuscular volume (MCV), 114.9 fL (NR 82-100 fL); mean corpuscular hemoglobin (MCH), 42.5 pg (NR 27-34 pg); red blood cell distribution width (RDW), 62.9% (NR 11.9-14.5%); VitB12, 30 pM (NR 138-652 pM); folic acid (FA), 16.11 nM (NR 7.0-46.4 nM); homocysteine (HCY), 118 muM (NR 5-15 nM); and serum copper, 13.56 muM (NR 7.12-21.29 muM). Anti-nuclear antibody (ANA), anti-cardiolipin antibody (ACA), anti-neutrophil cytoplasmic antibody (ANCA), rheumatoid factor (RF), syphilis, HIV, and tumor markers were negative. Lumbar puncture and cerebrospinal fluid (CSF) examination yielded normal results; autoantibody and oligoclonal bands were negative.
Electromyography showed reduced conduction velocity of multiple sensory and motor nerves in both lower limbs; no evoked potentials were induced, and P40 of the left tibial nerve was not induced. Thoracic vertebral magnetic resonance image (MRI) showed long T2 signals in both dorsal and lateral columns at T5-T6, i.e., the "small character" sign (Figure 1A and B). Cervical vertebral MRI showed C3-C4 intervertebral disc protrusion and C4-5, C5-6, and C6-7 intervertebral disc bulging.
The patient was diagnosed with SCD, megaloblastic anemia, and cervical and L5-S1 lumbar intervertebral disc protrusion. The patient gradually stopped drinking after hospitalization and received daily intramuscular injections of mecobalamine (1 mg; Eisai Pharmaceutical Co., Ltd, China) and oral folic acid (FA; Tianjin Lisheng Pharmaceutical Co., Ltd, China), VitB12 (Eisai Pharmaceutical Co., Ltd, China), and VitB6 (CR Double-Crane Pharmaceutical Co., Ltd, China). Following treatment, the symptoms improved and all biochemical examination results returned to normal. Intramuscular mecobalamine was administered every other day for 4 weeks and was gradually replaced with oral mecobalamine. The patient could walk with assistance and urinate/defecate normally.
However, the patient was re-admitted to our department 1 month later due to worsening lower-limb weakness for 1 week. Re-examination showed VitB12 >1000 pM and positive serum anti-intrinsic factor antibody. Gastroscopy and biopsy showed type A chronic atrophic gastritis (Figures 2 and 3). Intramuscular mecobalamine (1 mg/injection, one injection every other day) was administered for 4 weeks. The lower-limb weakness improved. Pre-discharge examinations showed that deep sensations in the lower limbs had improved since the first hospitalization. Muscle strength also improved (left, grade III+; right, grade IV- [proximal] to III [distal]). Tendon reflexes were positive in both lower limbs, and urination/defecation was normal.
In 2020, the patient was repeatedly admitted to our department for worsening of lower-limb weakness, during which VitB12 treatment was continued, and VitB12 levels were maintained normal. In March 2020, the patient was treated in another hospital for bilateral upper-limb weakness, cough, and difficulty in chewing for 3 days. However, his symptoms did not improve after intramuscular mecobalamine, citicoline sodium infusion, and oral VitB and FA.
After 4 days, he was admitted to our department. Before disease onset, he had diarrhea, which improved after 2 days of oral berberine. Physical examination showed that the patient had a clear mind, but a tender neck, feebleness, hoarseness during speaking, and difficulty in chewing, coughing, shrugging, and raising his head. The lifting of the soft palate was bilaterally poor, and the uvula was in the middle. Both upper-limb muscle tension and strength were reduced (proximal, grade IV-; distal, grade III), and tendon reflexes were positive. Lower-limb muscle tension and strength were identical to the previous examination. No pathological signs were found. Routine blood tests showed normal results. Stool culture 7 days after onset showed Campylobacter jejuni infection, which was treated with gentamicin. Electromyography 9 days after onset showed increased motor latency and decreased amplitude of the terminal median nerve. Reduced motor-nerve conduction velocity, decreased amplitude, and delayed F wave were seen. Increased motor latency of the terminal ulnar nerve, with normal conduction velocity, was found. Fibrillation potentials were detected in the distal upper limbs. No abnormalities were found after repeated electrical stimulations.
Cranial MRI showed no abnormalities. Cervical and thoracic vertebral MRI showed similar changes in the cervical vertebrae as in the previous examinations, along with T10-11 intervertebral disc bulging, thoracic vertebral degeneration, and partial recovery of the T5-T6 spinal cord lesion (Figure 1C and D). Lumbar puncture 11 days after onset showed: pressure, 150 mmH2O; white blood cells, 1x106/L; and total protein, 488 mg/L. Blood GQ1b and GT1a antibodies were positive, while GM1, GM2, GM3, GT1b, GD1a, and GD1b antibodies were negative. Paraneoplastic antibodies (Hu/Yo/Ri), CSF oligoclones, and AQP4 were negative.
The patient was diagnosed with pharyngeal-cervical-brachial (PCB) Guillain-Barre syndrome (GBS) in SCD. Intravenous gamma-globulin (0.4 g/kg) was administered for 5 days beginning 9 days after onset, and on day 12, the following changes were seen: sudden dyspnea with repeated diarrhea; finger oxygen desaturation index, 93%; heart rate, 110 bpm; decreased consciousness; and moderate coma. Oral tracheal intubation and mechanical ventilation were performed immediately. In addition, 1 g methylprednisolone was injected intravenously for 3 days, and gradually tapered until discontinuation. By day 20, the patient could open his eyes when called, had bilaterally reduced light reflexes, and stable vital signs. Anti-infection and supportive treatments were continued, with little effect. Due to the heavy financial burden, his family voluntarily gave up the treatment, and the patient passed away.