A 22-year old female patient was admitted to another hospital due to weakness of both lower limbs, gait disturbance and urinary incontinence for 2 weeks. She was taking anti-depressant and had habit of inhaling N₂O daily more than 100 ‘happy balloon’s for the past 6 weeks. She was transferred to our hospital 3 weeks after symptom onset. Physical exams showed lower limbs motor grades of 3 (fair), bilateral hypoesthesia of the T4 dermatomes and below, impaired proprioception and vibration, hyperactive knee and ankle jerks, positive Romberg sign and ataxic gait. Pathologic reflexes were absent. Her standing and gait balance was poor, resulting in a Berg balance scale (BBS) of 32 points out of 56.

Serologic tests conducted 2 weeks after onset revealed a mean corpuscular volume (MCV) 95 fL (normal range 81-99 fL); hemoglobin 10.9 g/dl (12-15g/dL); Cbl level 165 pg/ml (200-1000 pg/ml); homocysteine 20.9 umol/L (3.7-13.9 umol/L). She received intramuscular (IM) injection of Cbl in previous hospital. Follow-up serologic tests at admission showed normal range of Cbl (530.4 pg/ml), folic acid and other vitamins. Autoantibodies were negative.

Initial whole spine magnetic resonance imaging (MRI) was taken 2 weeks after initiation of symptoms and showed no spinal cord signal abnormalities. However, follow-up MRI taken 1 week later demonstrated high signal intensities on the dorsal columns of the spinal cord at C2-C5 on T2 weighted images (Fig. 1A, B), suggestive of SCD.

Initial electrodiagnostic studies (EDX) was conducted 3 weeks after symptom onset. Motor nerve conduction studies (NCS) demonstrated prolonged latencies and low amplitudes of the right peroneal and bilateral tibial compound motor unit action potentials (CMAPs). The left peroneal CMAP revealed low amplitude and decreased nerve conduction velocity. Sensory NCS were within normal limits, except low amplitude of the left superficial peroneal sensory nerve action potential (SNAP). The F-waves were prolonged with the bilateral peroneal and tibial nerves stimulation. The H-reflexes were prolonged, bilaterally (Table 1). Needle electromyography (EMG) demonstrated abnormal spontaneous activities (ASA) and reduced motor unit recruitments in the right first dorsal interosseous, gastrocnemius, and tibialis anterior muscles. Initial EDX resulted in demyelinating and axonal PNs, mainly involving the motor nerves.

Additional treatment were administered after admission; daily intramuscular (IM) injections of cobamamide (1 mg) for 12 days and daily oral Cbl supplementation (1.5 mg) for the following 20 days. Her urinary incontinence and sensory symptoms at all dermatome levels resolved 7 weeks after symptom onset. Although she had improvement of motor grade of the both lower extremities improved to grade 4+ (good +) and gait performance (BBS 40), she still had difficulties to keep dynamic standing balance. Follow-up EDX exhibited some improvements: normalization of the H-reflex latencies, amplitude increments of CMAPs of the median nerve (Table 1).

A 33-year old male with a history of N₂O abuse two or three times a week (about 20 ‘happy balloon’s at a time) for 7 months complained gait difficulty and weakness of bilateral lower limbs for 1 months. At the first time, he only complained numbness of trunk and below and ataxic gait. After 3 months, weakness and gait disturbance developed and he admitted another hospital. Serologic test conducted 3 months after symptom onset showed that increased MCV (106 um3) and decreased hemoglobin (10.2 mg/dL) and Cbl level (130 pg/ml). Spine MRI taken 3 months after symptom initiation revealed high signal intensities on the dorsal columns of the spinal cord C2-C6 on T2 weighted images. He was diagnosed with SCD and received mecobalamin IM injection (1mg) for 5days. After treatment, Cbl level (617.3 pg/ml) was normalized and numbness had improved. He admitted to our hospital and took further evaluations since weakness and gait disturbance persisted 5 months from the initial symptom onset.

Physical exams showed motor grades of 2 (Poor) for both ankle and below, bilateral hypoesthesia of the C5 dermatomes and below, impaired proprioception and vibration, hyperactive knee and ankle jerks and positive Romberg sign. His dynamic standing and gait balance was poor (BBS 37).

Serologic examination at admission showed normal levels of hemoglobin, MCV, folic acid and various vitamins including Cbl. The anti-intrinsic factor antibody was negative. Compared to initial MRI, follow-up spine MRI still showed abnormalities of spinal cord C2-C6 (Fig. 1C, D).

EDX were also performed upon admission. Motor NCS revealed prolonged latencies and low amplitudes of the right median and left tibial CMAPs. The right tibial and the bilateral peroneal CMAPs were unobtainable. The superficial peroneal SNAP showed low amplitude on the right side, and was unobtainable on the left side. The F-waves were unobtainable with the bilateral tibial and peroneal nerves stimulation. The bilateral H-reflexes were prolonged (Table 2). On the needle EMG, ASA and polyphasic motor unit potentials with reduced recruitments were noted in the right flexor carpi radialis and first dorsal interosseous muscles and the bilateral tibialis anterior, peroneus longus and gastrocnemius muscles. EDX were suggestive of motor dominant PNs.

Additional treatment including daily IM injections of cobamamide (1 mg) for 13 days and oral Cbl supplement (1.5 mg) and folic acid (3 mg) for the following 32 days were administered. Six months after symptom onset, his gait balance (BBS 46) and motor grades bilateral lower extremities (grade 4, Good) were improved. In spite of clinical improvements, follow-up EDX showed not significant change except for some improvement in the right median CMAPs (Table 2).