such as numbness tend to be unrecognized. Diagnosis is often delayed and can be difficult if the patient fails to disclose inhalation activity. A detailed medical history and laboratory evidence of decrease serum levels of vitamin B₁₂ are necessary for accurate diagnosis. Here we describe a case of N₂O abuser who presented the mixed manifestations of myelopathy and polyneuropathy. He fully recovered after treatment with vitamin B₁₂ injection and N₂O abstinence.

A 19-year-old man presented to the neurosurgery depart- ment with a 1-month history of progressive 4-limb numbness and gait imbalance. He reported a kicking-related injury to the left foot while climbing stairs about 1 month previously, after which he developed left foot pain, bilateral lower limb numbness, and an unstable gait. Conservative treatments with nonsteroidal anti-inflammatory drugs proved to be ineffec- tive. The regions of numbness expanded to include the upper limbs and eventually his entire body (complete numbness from shoulders to his toes). When the condition progressed to include general weakness, the individual visited the outpatient department (OPD) of our hospital for help.

The individual had no known medical history, was on a normal diet, had a 3-year cigarette smoking history, and indicated no use of alcohol or illicit drugs. He reported no constipation or urinary incontinence. Our initial examination indicated the following: height, 184 cm; weight, 125 kg; temperature, 36.8?C; blood pressure, 128/93 mm Hg; pulse, 90 beats/min; and respiratory rate, 22 breaths/min. He was fully conscious, with normal mentality and speech; eyeballs were conjugated and freely movable without nystagmus. Cranial nerve function was intact, except for mild bilateral facial paresis. Muscle strength was generally reduced to grade 4 on the Medical Research Council scale, and muscle tone was reduced; anal tone, however, was normal. There was no muscle fasciculation, but the brachioradialis and knee jerk tendon reflexes were absent bilaterally. Plantar responses were negative on both sides. The finger-nose-finger test was normal. No tremor was observed, but pseudoathetosis of the fingers was found when the upper limbs were outstretched with the eyes closed. The patient exhibited an equivocal Lhermitte sign and a positive Romberg sign, and he walked with a wide-based, ataxic steppage gait. The sensory tests showed diminished superficial sensation below a segmental

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level around his cervical-thoracic junction. Also, symmetric decreased pinprick and temperature sensations over all his distal extremities (glove-and-stocking pattern) was noted; the sensory decrease was greater distally than proximally.

Most of the laboratory tests were within the reference range, except for the presence of megaloblastic red blood cells. The complete blood cell count indicated hemoglobin,

15.7 g/dL (reference range, 14-18 g/dL); hematocrit, 47.1% (reference range, 42%-52%); and mean corpuscular volume,

96.5 fL (reference range, 80-94 fL). A peripheral blood smear showed anisocytosis and 2% metamyelocyte. The serum vitamin B₁₂ concentration was 156 pg/nL (reference range, 246-900 pg/nL), and red cell folate concentration was

9.5 nmol/L (reference range, 5-30 nmol/L). Serologic tests for syphilis, Epstein-Barr virus, cytomegalovirus, and human immunodeficiency virus antibodies were negative. thyroid function and autoimmune screen were within normal limits; intrinsic factor antibodies were absent. Results of the Cerebrospinal Fluid studies were normal, with no evidence of albuminocytological dissociation (protein: 23 mg/dL, glucose: 60 mg/dL).

Initial cervical spine magnetic resonance examination (Fig. 1) was done under the suspicion of spinal cord lesion. It revealed increased signals in posterior and anterior columns bilaterally on T₂-weighted images in cervical cord. At this point, the patient was admitted to the neurosurgery unit for further evaluation.

Table 1 shows the results of motor nerve conduction velocity (NCV), which revealed prolonged distal latency in bilateral median nerves, reduced NCV in bilateral ulnar and

left tibial nerves, poor response in bilateral peroneal and right tibial nerves, and prolonged F latency in all of the excitable nerves. The H reflexes of tibial and median nerves were markedly prolonged on both sides. Sensory NCV revealed no response in the right sural nerve and markedly reduced sensory nerve action potential in the left sural nerve. Needle electromyography showed no spontaneous activity during rest in the left anterior tibialis, gastrocnemius, vastus medialis, right abductor pollicis brevis, flexor digiti minimi, brachioradialis, left lower cervical paraspinal, and left lower lumbar paraspinal muscles. We did find, however, a decrease in the number of motor unit potentials during voluntary contractions in these 6 muscles. After reviewing the NCV and electromyography findings, we concluded that the patient had a demyelination-predominated polyneuropathy.

Table 1 Motor nerve conduction in a patient with a history of N₂O abuse

Fig. 1 Magnetic resonance findings in a 19-year-old man with a 4-month history of N₂O abuse who presented with gait imbalance, limb weakness, and numbness from the nipples to the toes. A, T₂-weighted (4000/120) sagittal image showing increased signal intensity (arrowhead) in the cervical spinal cord. B, T₂-weighted (4000/120) axial image showing abnormal signal involvement in the posterior and anterior spinal cord columns.

Table 2 shows all the data of evoked potentials (EP). Basically, all visual EPs, brainstem auditory EPs (BAEPs), and median nerve somatosensory EPs (SEPs) were in the reference range, with a trend toward the upper limit. However, the markedly prolonged cortical potential (P37) in the bilateral tibial nerve SEP implied a delayed, prolonged conduction in posterior column of spinal cord.

After further inquiry, the patient was admitted to the recreational use of N₂O inhalant over a period of 2 months up until the time that his ascending paresthesia became worse. During this period, he inhaled approximately 500 to 600 cartridges from N₂O-filled balloons during 5- to 6-hour sessions, 4 to 5 times per week. The final diagnosis was N₂O- induced polyneuropathy and myelopathy.

One week after hospital admission, the patient began a course of vitamin B₁₂ injections: 1000 ug/day for 5 days, followed by 1000 ug/week for 2 months. The numbness decreased within 1 week, but a mild sensory ataxic gait remained. After 2 months of N₂O abstinence, the patient recovered fully without any neurologic sequela.

Complaints of “numbness” are common in either emergen- cy department or OPD. However, evaluation of such sensory problems can be quite complicated, particularly because the subjective symptom can result from either a disease process located in the central or Peripheral nervous systems. To evaluate a patient with the chief complaint of numbness, the first thing is to localize the problem by history and examination. Recognition of the temporal features of patient’s symptoms and the distribution of the numb area are essential. This case presented a subacute course of symmetrical numbness, which had the mixed characters of sensory level below cervical-thoracic junction and glove-stocking pattern. The initial anatomical diagnosis included cervical cord lesion and polyneuropathy. On the other hand, the pseudoathetosis, Romberg sign, and the ataxic gait were derived from a proprioceptive disturbance, which could result from a dorsal

Table 2 Multimodal EPs of a patient with a history of N₂O abuse

cord lesion. Therefore, a cervical magnetic resonance imaging (MRI) (Fig. 1) was performed first. The signs of areflexia and absent plantar response indicated that the lesion of Lower motor neuron caused his motor deficit. The MRI (Fig. 1) revealed pathological changes in posterior and anterior columns, but the lateral column was spared. This answered the question: “Why is it that this patient with myelopathy had no upper motor neuron signs?” The corticospinal tract in lateral column was not involved in the pathological process.

Magnetic resonance imaging studies of N₂O abusers are rare. So far, there have only been case reports of abnormal findings at both the cervical and thoracic spinal levels [2,3], the cervical level alone [4], or the thoracic level alone [5]. Hyperintense signals in T₂-weighted images may be identified in the posterior spinal cord alone, or in both the posterior and lateral spinal cord. To our knowledge, there have been rarely reported MRI studies in those cases involving the anterior column. The typical changes of spinal cord in subacute combined degeneration caused by vitamin B₁₂ deficiency begin in the posterior column and spread into the lateral column. However, the lesions are not limited to specific systems of fibers within the posterior and lateral funiculi, but also can be scatted irregularly through the white matter [6], so that the involvement of the anterior column in subacute combined degeneration is noted [7].

In our patient, vitamin B₁₂ deficiency was presumed to have caused the clinical symptoms. A key interaction occurs between vitamin B₁₂ and folate during the synthesis of methionine from homocysteine by the enzyme methionine synthase. The activity of vitamin B₁₂ in this process can be inhibited by N₂O. This can result in decreased synthesis of methionine and S-adenosyl methionine, which, in turn, can lead to nervous system demyelination, provoking polyneuro- pathy and spinal cord degeneration [8-10].

An earlier study by Heyer et al [11] reported a 25-year-old student who abused N₂O and developed signs of a sensorimotor polyneuropathy and myelopathy. The patient’s sensory EPs revealed prolonged latency of scalp EPs after tibial nerve stimulation within normal median nerve values, which is similar to that of our patient. The prolonged cortical potential latencies were due to spinal cord demyelination [11]. Both audiometry and BAEP studies were normal in the patient of Heyer et al [11], and our patient had normal BAEP, too. However, abnormal BAEPs have been reported in patients with vitamin B₁₂ deficiency [1,8,9].

The incidence of N₂O-induced neurotoxicity is under- estimated and should be recognized as an important cause of subacute combined degeneration. Although the patient in this report presented initially to the OPD of our hospital, the potential for encountering similar cases of acute numbness in emergency departments is not insignificant, given the relatively high incidence of N₂O abuse, particularly among adolescents [12]. This case report offers insights into the recognition and diagnosis of N₂O-related toxicity. Neuroi- mages and electrophysiological studies provide important clues clinically, but a complete patient history is critical for

the diagnosis of N₂O-induced polyneuropathy and myelop- athy. In a case characterized by megaloblastic red blood cells and symmetric neurologic deficits, an inquiry regarding the history of N₂O exposure is necessary.

Chih-kang Hsu MD Yue-quen Chen MD Vei-zen Lung MD

Division of Neurosurgery, Department of Surgery Armed Forces Tao-Yuan General Hospital

Taoyaun, Taiwan National Defense Medical Center, Taipei

Sheng-Chuan His MD Division of General surgery, Department of Surgery Armed Forces Tao-Yuan General Hospital

Taoyaun, Taiwan National Defense Medical Center, Taipei

Huan-Chu Lo MD Department of Radiology, Tri-Service General Hospital National Defense Medical Center, Taipei

Hann-Yeh Shyu MD Section of Neurology, Department of Internal Medicine Armed Forces Tao-Yuan General Hospital

Taoyaun, Taiwan Institute of Biology and Anatomy

National Defense Medical Center, Taipei,Taiwan E-mail address: [email protected]

doi:10.1016/j.ajem.2011.05.001

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