Reversible central neurogenic hyperventilation in an awake patient with multiple sclerosis

Abstract

Sirs: Central neurogenic hyperventilation (CNH) is a rare respiratory condition characterized by sustained hyperventilation. We present the first report of CNH successfully treated in an awake patient in multiple sclerosis (MS). A 43-year-old woman was admitted because of sudden gait disturbance, dysarthria and worsening of visual acuity. She had suffered from left and right optic neuritis 6 months and 18 months before admission, respectively. Steroid treatment partially improved her visual acuity. On admission she was fully awake. Her respiratory pattern was sustained, rapid (24 breaths/min), regular, deep, and unchanged during sleep but voluntarily changeable. Restricted left eye movement in all directions, horizontal gaze nystagmus in both eyes and ataxic speech was observed. Deep tendon reflexes were increased in four limbs without pathological reflexes. Arterial blood gas (ABG) values were PaO2 95.9 mm Hg, PaCO2 28.2 mm Hg, and pH 7.486. The patient’s hyperventilation was not psychogenic, because hyperpnea and respiratory alkalosis had been continued during sleep, after receiving intravenous 10 mg midazolam, and after breathing into a paper bag for 5 min. Chest X-ray, pulmonary function test and blood sample analysis revealed no abnormalities. Lactate concentrations in serum and cerebrospinal fluid (CSF) were within reference intervals. CSF analysis revealed cell count 11/mm3 without malignant cell, protein concentrations 0.35 g/L, pH 7.661. Multiple oligoclonal bands were detected in CSF but not in serum. The brain MRI showed many lesions spreading throughout the pons and midbrain (Fig.1A, B) and small number of supratentorial lesions (Fig.1C). The spinal cord was intact. We excluded other differential diagnosis and diagnosed the patient’s illness as MS, according to McDonald criteria [1]. After treatment with high-dose intravenous methylprednisolone, some of her symptoms improved but visual acuity and hyperventilation did not. Although there is not much evidence that plasma exchange is effective for an acute attack in MS [2], plasma exchange was reported to be effective for severe optic neuritis [3], or neuromyelitis optica (Davic’s disease) [4]. To prevent complete blindness, we performed plasma exchange six times. After these therapies, her visual acuity and hyperventilation gradually improved. After 52 days from admission, respiratory rate normalized to 16 breaths per minute and ABG values were PaO2 95.5 mm Hg, PaCO2 38.8 mm Hg, and pH 7.403. Lesions previously detected on brain MRI were markedly decreased (Fig.1D–F). CNH is defined as sustained hyperventilation persisting during sleep, normal or increased arterial oxygen tension, decreased arterial carbon dioxide tension, and respiratory alkalosis in the absence of cardiac disease, pulmonary disease, and respiration-stimulating drugs [5]. Our patient’s hyperventilation met the definitive criterion for CNH. CNH is usually seen in deeply comatose patients and rarely in conscious patients [5]. To the best of our knowledge, 27 cases in conscious patients have been reported. All reported cases were associated with brainstem tumor [6, 8–12], except a case after bilateral medial thalamic infarction [7]. The pathophysiological mechanisms that lead to CNH are still unknown. From the fact that CNH are frequently associated with brainstem tumors, both structural and chemical factors have been considered. One hypothesis is that a destructive lesion in the medial pons would interrupt descending inhibitory impulses to the medullary respiratory centers and produce CNH. The alternate hypothesis is local lactate production could stimulate medullary chemoreceptors and cause CNH. However, these two hypotheses did not account for all cases with CNH. Recently, a third hypothesis was reported. From a study using rats or cats, chemical stimulation of lateral parabrachial neurons in the pons increased respiratory rate, tidal volume or both [13]. Tarulli et al. reported that tumorous infiltration in these neurons caused CNH [6]. The current lesions are diffusely distributed in pons including parabrachial neurons; therefore, the mechanism of CNH in this case can be explained by all three explanations. Respiratory complications are relatively uncommon in MS [14] and CNH has not been reported. LETTER TO THE EDITORS