Neurofibromatosis type 1 (NFT-1) is an autosomal-dominant disease with an incidence between 1:2500 and 1:3000 and reported prevalence between 1:2000 and 1:5000.1,2 The disorder is caused by a mutation in the neurofibromin gene (17q11.2), and the clinical presentation is dependent on the age of the patient.1 The most common clinical features are pigmentary abnormalities such as café-au-lait spots and iris hamartomas. In addition, mutations in the NF-1 gene result in reduced levels of neurofibromin, which may lead to the development of a wide variety of tumors including those of the central and peripheral nervous systems.3,4 Intraoral manifestations of the disease may be found in 5% of patients and include neurofibromas of the tongue, larynx, arytenoids, and vocal cords.5–9 Large parapharyngeal space tumors have also been reported.10
Initial evaluation and follow-up of children with NFT-1 involves magnetic resonance imaging (MRI), which is usually performed under anesthesia. Because of the possibility of airway involvement, special precautions and specialized airway equipment may be necessary to achieve safe induction and intubation.
We present the case of a 5-month-old child with NFT-1 who developed complete airway obstruction after induction of anesthesia. Factors that could have alerted us to the potential for airway involvement are discussed. Measures that may facilitate safe induction and intubation are also described.
Written informed consent was obtained from the parents of the patient to publish this case report.
A 5-month-old, 4.9-kg boy with multiple café-au-lait spots and a nodule in the region of the left cheek was scheduled for an MRI of the cervical spine, face, orbit, and neck. The patient was born prematurely at 34 weeks of gestation and was admitted to the neonatal intensive care unit for 18 days. He was never intubated but required noninvasive continuous positive airway pressure therapy. His medical history was also significant for laryngeal stridor, recurrent upper respiratory tract infections, persistent nasal congestion, coughing, sleep apnea, poor feeding, and failure to thrive. Medications included Lansoprazole (Takeda Pharmaceuticals, Deerfield, IL), Loratadine (Medique Products, Fort Myers, FL), and Patanase (Alcon Laboratories Inc, Fort Worth, TX) nasal spray. Family history was significant for NFT-1 in his mother and maternal grandfather (left facial fibroma). On physical examination, he had a nodular lesion on his left cheek resulting in facial asymmetry. The patient was crying, coughing, and had visible clear oral secretions and some left ear discharge. There were pulmonary rhonchi on auscultation. Per his mother, this was his baseline status. A 22-gauge peripheral intravenous (IV) line had already been placed in his upper extremity. After preanesthetic evaluation, the decision was made to proceed with total IV anesthesia with spontaneous ventilation.
The patient was taken into the MRI suite where standard American Society of Anesthesiologist monitors were applied. After baseline vital signs were obtained, he was induced with 10 mg propofol, after which he became apneic. Mask ventilation was ineffective, and laryngospasm was suspected. Therefore, continuous positive pressure was applied, and a muscle relaxant was administered. However, there was no improvement in ventilation. The patient was then immediately intubated with a 3.5-mm cuffed endotracheal tube (ETT). However, there was still no improvement in ventilation. Repeat direct laryngoscopy and intubation were performed. However, although the ETT was visualized going through the vocal cords, breath sounds were absent on auscultation. There were copious secretions in the oropharynx, but no visible masses were identified, and suctioning of the ETT produced minimal secretions. Subsequently, inhaled volatile anesthetics and Ventolin (Nepron Pharmaceuticals, Orlando, FL) were administered. This gradually resulted in improved ventilation and oxygenation. His oxygen saturation gradually dropped to 75% after the induction of anesthesia; it then increased to 85% when continuous positive pressure was applied and then to 100% after the administration of albuterol via the ETT. His heart rate and blood pressure remained stable during his hypoxic episode that lasted for approximately 6 minutes. The MRI results revealed a left facial-carotid-base of skull complex plexiform neurofibroma (PN) that had a protruding mass effect on the airway, shifting it from the left to the right (Figure). On the basis of the findings of airway compromise, the decision was made to transport the child to the intensive care unit intubated and sedated until further evaluation could be performed. The child was extubated 2 days later but continued to have problems with airway compression, requiring continuous positive airway pressure at night. It was determined that he was not a candidate for surgical debulking because of the risk of facial and pharyngeal palsy and vascular, cranial, and autonomic nerve injuries. A tracheostomy was recommended for further management and care.
PNs are among the most common and debilitating tumors seen in NFT-1.11 They are benign tumors arising from the peripheral nerve sheath and typically cause local invasion of adjacent soft tissues.12 Approximately 50% of PNs occur in the head, neck, face, and larynx, and 5% to 10% of these may undergo malignant transformation.13,14 PNs may also cause significant pain and disfigurement. Although surgical resection is the mainstay of treatment, the resection of these tumors is usually difficult because they invade local soft tissue, lack a defined capsule, and usually consist of a mesh of interwoven spindle cells, axons, and collagen fibers.14,15
Superficially visible PNs are first noted as subtle nodules in infancy or early childhood, but in many instances progress to exhibit rapid growth.11 Similar to our case, internal PNs in infants and children are usually not known to exist until detected incidentally by imaging studies or diagnosed after the occurrence of obstructive signs and symptoms.16 MRI remains the modality of choice for the evaluation of symptomatic PNs.11 In infants and children, this usually requires general anesthesia. Although NFT-1 may affect all organ systems, airway involvement presents perhaps the biggest challenge to anesthesiologists. In the case of an undiagnosed airway lesion, awareness of the potential for airway involvement and clinical signs of upper airway obstruction may be beneficial in avoiding difficulties during induction and intubation. In addition to the physical symptoms observed (café-au-lait spots and facial swelling), the medical history of our patient was significant for recurrent upper respiratory tract infections, significant laryngeal stridor, persistent nasal congestion, coughing, and sleep apnea. It was reported that these symptoms had been present since birth, and evaluation was ongoing. Although intraoral manifestations of NFT-1 are rare (5%), the described clinical picture may have been an indication of airway involvement. Furthermore, a preanesthesia computed tomography scan or chest x-ray would have provided information about the potential for airway difficulties such as the tracheal deviation described in our case report. Because this was a very young patient (5 months old), a computed tomography scan may have required some form of sedation; therefore, a chest x-ray would have been preferable.
The inability to ventilate after the administration of a muscle relaxant was a classic sign of complete airway obstruction. The lack of ventilation after successful intubation is more difficult to explain. Because there was improvement in ventilation after the administration of inhalation agents and albuterol via the ETT, we are inclined to believe that in addition to upper airway obstruction, the child may have developed severe bronchospasm. The bronchospastic event may have been triggered by a combination of the significant oropharyngeal secretions that were present and a light plane of anesthesia that may have developed while we were trying to establish adequate ventilation. Although our patient had a peripheral IV in place, gradual inhalation induction may have afforded us better control of ventilation. Further avoidance of muscle relaxation may have prevented the loss of pharyngeal muscle tone and subsequent complete airway obstruction. Placement of a laryngeal mask airway or intubation under deep inhalation anesthesia may have been a safer option.
Other authors have described experiences similar to ours. Mersal et al10 described the case of a 15-day-old baby who had to be emergently intubated at birth because of respiratory distress. On physical examination, their patient had café-au-lait spots and a right-sided firm mass involving the neck and lower face. MRI showed extension of the mass into the skull base and parapharyngeal space. The patient required a tracheostomy and gastrostomy because of airway and esophageal obstruction. Crozier6 described the unexpected difficult intubation of a 20-year-old patient with NFT-1. An emergent cricothyroidotomy had to be performed. It was later discovered that the patient had an undiagnosed PN of the tongue. Subsequent questioning revealed a 2-year history of speech disturbance for which she had not sought medical advice. Similar to our case, the medical history and knowledge of the symptoms of speech disturbance may have prompted an alternative approach to induction of anesthesia. Chen et al8 described the case of a 20-month-old child with NFT-1 who presented with cough, stridor, and difficulty feeding and was eventually diagnosed with a laryngeal inlet neurofibroma. Although the authors did not describe their method of anesthesia induction, they were able to visualize the vocal cords by fiberoptic bronchoscopy. However, this may have been because of the relatively small size of the lesion. In addition to the maintenance of spontaneous ventilation, airway adjuncts such as laryngeal mask airways, video laryngoscopes, and fiberoptic bronchoscopes may aid in securing the airway of patients with suspected laryngeal neurofibromas. It may also be safe to have a surgeon on standby in the event that an emergent cricothyroidotomy is necessary.6,7,10
In conclusion, in patients presenting for initial imaging as part of an NFT-1 workup, a high index of suspicion for airway involvement should be maintained if the patient has facial lesions and/or signs of upper airway obstruction. During induction, consideration should be given to the maintenance of spontaneous ventilation and the avoidance of muscle relaxants. Additional airway adjuncts and the ability to perform an emergent cricothyroidotomy may also be beneficial.
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