Sirs: Several patients with pathologically proven amyotrophic lateral sclerosis (ALS) have been reported to run a benign course without need for a mechanical ventilator [5, 6, 9]. We observed autonomous breathing in a case of long-surviving ALS, and the effects of the metabolic control system on respiration were revealed. The patient in this report is a housewife with no family history of neuromuscular disease or consanguineous pedigree. She noticed difficulty in speech at age 53 years, followed by gradual muscular weakness in her upper and lower extremities. She was diagnosed as ALS based on the clinical and EMG findings. At age 56, her developing dyspnea led to a tracheostomy and mechanical ventilation control. Three months later, she was transferred to our hospital. At that time, she was alert and had no sensory deficits. Though her ocular movements were normal, there was both moderate weakness of her facial muscles together with marked tongue atrophy with fasciculation. Muscular atrophy and motor weakness were remarkable in the upper limbs and moderate in the lower limbs. Muscle stretch reflex was hyperactive in facial muscles, jaw jerk and lower extremities, but there was areflexia in the upper extremities. There was foot clonus but no Babinski’s reflex. In spite of being under mechanical ventilation when admitted to our hospital, spontaneous breathing with SpO2 of 97–98 % has been observed during these past three years since admission. Now, she is 60 years old and in a state of tetraplegia with marked facial muscle weakness. PTR and ATR are still hyperactive. She is alert, very intelligent, and communication is maintained via a computer-assisted communication system. Neuroimaging studies show normal finding. Her respiration states are minute volume of 3–4 l and PO2 92.7 Torr/PCO2 43.5 Torr without mechanical ventilator, but she cannot voluntarily control her breathing (Fig. 1A). Her attempt to hold her breath causes decreasing amplitude of her breathing while maintainig respiration rhythm, and her intention to hold her breathing merely increases the amplitude. Laughing causes irregular respiration rhythm and increases amplitude (Fig. 1B), and her cough reflex from tracheal stimulation is positive (Fig. 1C). She cannot speak via a tracheostomy tube equipped with a speech bulb. The hypercapnic response was measured by a modification of Read’s method [10], which was performed after obtaining the informed consent of the patient and her family. She rebreathed 5 % CO2 in oxygen from a 7 l anesthesia bag. The results revealed an augmentation of ventilation in response to the progressive increase of PtCO2 up to 55 Torr (Fig. 2). Breathing is controlled separately by the autonomic and voluntary pathways [1]. A discrete lesion in the central nervous system may cause a selective paralysis of one type of respiration, but spare the other. The respiratory findings in the present case are a loss of voluntary respiration but preservation of autonomous rhythm, metabolic control and evidence of activation in response to emotional stimuli. These findings have been reported in patients with lesions in the ventral pons [2, 3, 4, 8] and bilateral pyramidal tracts [7]. The reverse condition of an impaired autonomic but preserved volitional system is called central alveolar hypoventilation syndrome or Ondine’s curse [11, 12], which requires mechanical ventilation during sleep. Preservation of autonomous respiration suggests intact medullary respiratory neurons such as the ambiguous and retroambiguous nuclei of the vagus, and respiratory rhythm-generating neurons in the caudal ventral pons [1]. Also, this patient showed normal activity of CO2/H+ sensitive neurons which are located in the solitary nuclei and ventrolateral field of the caudal medulla oblongata [1]. The influence of emotional laughing on the autonomic respiration rhythm suggests the retained pathway of limbic cortex to these respiratory neurons [3, 8]. Descending bulbospinal respiratory pathways, which run in the anterior funiculus [1], and the anterior horn cell originating the phrenic nerve must be preserved to some degree to maintain spontaneous breathing. At the same time, a loss of volitional respiration indicates quite severe degeneration in the corticospinal tract, which is indicated by hyperactive tendon reflex in extremely weakened muscle. This case shows a peculiar symptom of impaired volitional but preserved autonomous respiration. To our knowledge, this is the first report of physiological study in ALS with a benign respiration course. Metabolic stimulation seems to be useful to reinforce the respiratory movement in such patients. LETTER TO THE EDITORS
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Open Access
Jun 30, 2022
Ki-Hwan Ji 
