Congenital insensitivity to pain: How should anesthesia be managed?

Özmete Ö, Sener M, Bali Ç, Çaliskan E, Aribogan A. Congenital insensitivity to pain: How should anesthesia be managed? Turk J Pediatr 2017; 59: 87-89. Congenital insensitivity to pain syndrome is a rare, sensorial and autonomic neuropathy characterized by unexplained fever, insensitivity to pain and anhidrosis. Patients may require anesthesia even for minor surgical procedures due to mental retardation and trauma arising from self- mutilating behavior. A child diagnosed with congenital insensitivity to pain syndrome was scheduled for gastric endoscopy under sedation due to suspected ingestion of a household cleaning disinfectant. Deep sedation was achieved, and spontaneous respiration was maintained. We did not encounter any complications. There is limited data regarding the safe anesthesia management in these patients because of the rarity of the disease. Therefore, we think that more clinical experience, case reports and studies are needed to establish the appropriate anesthesia management.

[Pain and analgesia : Mutations of voltage-gated sodium channels]. / Schmerz und Schmerzlosigkeit : Mutationen spannungsabhängiger Natriumkanäle.

Voltage-gated sodium channels (Navs) are crucial for the generation and propagation of action potentials in all excitable cells, and therefore for the function of sensory neurons as well. Preclinical research over the past 20 years identified three Nav-isoforms in sensory neurons, namely Nav1.7, Nav1.8 and Nav1.9. A specific role for the function of nociceptive neurons was postulated for each. Whereas no selective sodium channel inhibitors have been established in the clinic so far, the relevance of all three isoforms regarding the pain sensitivity in humans is currently undergoing a remarkable verification through the translation of preclinical data into clinically manifest pictures. For the last ten years, Nav1.7 has been the main focus of clinical interest, as a large number of hereditary mutants were identified. The so-called "gain-of-function" mutations of Nav1.7 cause the pain syndromes hereditary erythromelalgia and paroxysmal extreme pain disorder. In addition, several Nav1.7 mutants were shown to be associated with small-fiber neuropathies. On the contrary, "loss-of-function" Nav1.7 mutants lead to a congenital insensitivity to pain. Recently, several gain-of-function mutations in Nav1.8 and Nav1.9 have been identified in patients suffering from painful peripheral neuropathies. However, another gain-of-function Nav1.9 mutation is associated with congenital insensitivity to pain. This review offers an overview of published work on painful Nav mutations with clinical relevance, and proposes possible consequences for the therapy of different pain symptoms resulting from these findings.

Multidisciplinary assessment of congenital insensitivity to pain syndrome.

BACKGROUND: Congenital insensitivity to pain and anhidrosis (CIPA) is a rare clinical condition characterized by the absence of normal subjective and objective responses to noxious stimuli in patients with intact central and peripheral nervous systems. CASE PRESENTATIONS: Two patients with CIPA are reported. The first patient was a 13-year-old girl who presented to our hospital with multiple joint destructions secondary to osteomyelitis. The second patient was a 10-year-old boy who presented with multiple hand lesions and right leg osteomyelitis. Our patients were treated with multiple debridements and intravenous antibiotics according to our hospital protocol. CONCLUSION: Early recognition of the disease is important. The treatment for this condition is focused more on the prevention of bone injuries and joint infection, as opposed to a cure. There are no standard techniques or guidelines available to treat this rare disease. Overall, effective CIPA treatment is built around family education and patient training.

[Congenital corneal anesthesia: case reports]. / Anestesia congênita de córnea: relatos de casos.

Case series of nine patients with congenital corneal anesthesia, six of them showed systemic changes in association with the ocular status. Three patients were submitted to electromyography, two showed isolated bilateral ophthalmic ramus alteration. Two patients had initial visual acuity better than 20/60 and six had final best corrected visual acuity better than 20/60 at the last visit. All of them were treated surgically and developed cornea opacities of variable sizes. Treatment of corneal congenital anesthesia must be performed as soon as possible to avoid corneal opacification. Systemic investigation, close follow-up and preparing the family for longterm and multidisciplinary approach are crucial to maintain the ocular health.

Anestesia congênita de córnea: relatos de casos / Congenital corneal anesthesia: case reports

Descrição de nove casos de anestesia congênita de córnea, sendo que desses, seis apresentavam alterações sistêmicas associadas ao quadro ocular. Três pacientes realizaram eletroneuromiografia, um sem alteração ao exame e dois com alteração isolada do ramo oftálmico do nervo trigêmeo bilateralmente. Dois pacientes tinham acuidade visual inicial melhor que 20/60 no início da avaliação e seis tinham acuidade visual final melhor que 20/60 na última visita. Todos foram submetidos a algum tipo de tratamento cirúrgico e evoluíram com opacidades corneana de tamanho variável. O tratamento dos pacientes com anestesia congênita de córnea deve ser realizado o mais precoce possível e de forma rigorosa a fim de evitar danos à transparência corneana. Investigação sistêmica, acompanhamento de perto e preparação familiar para tratamento a longo prazo e multidisciplinar são necessários para preservar a saúde ocular.

Case series of nine patients with congenital corneal anesthesia, six of them showed systemic changes in association with the ocular status. Three patients were submitted to electromyography, two showed isolated bilateral ophthalmic ramus alteration. Two patients had initial visual acuity better than 20/60 and six had final best corrected visual acuity better than 20/60 at the last visit. All of them were treated surgically and developed cornea opacities of variable sizes. Treatment of corneal congenital anesthesia must be performed as soon as possible to avoid corneal opacification. Systemic investigation, close follow-up and preparing the family for longterm and multidisciplinary approach are crucial to maintain the ocular health.

[Congenital insensitivity to pain: difficulty of management]. / L'insensibilité congénitale à la douleur : difficultés de prise en charge.

INTRODUCTION: Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare disorder, most often of genetic origin. CASE REPORT: The authors present the case of two siblings, 10 and 13 years old, both followed-up since the age of 2 for CIPA diagnosed after discovering insensitivity to pain during iterative falls, burns, and of severe oro-digital self-mutilating behavior. Sural nerve biopsy and an electromyogram confirmed the diagnosis. DISCUSSION: CIPA with anhidrosis is a very rare disease. It is characterized by unexplained fever episodes, anhidrosis, pain insensitivity, self-mutilating behavior, and sometimes mental retardation. Complications of this insensitivity (non-treated fractures, burns, and oro-digital mutilation) may be lethal. Treatment remains preventive. The patient must observe a very strict hygiene. Prevention for maxillofacial involvement consists in breaking the cycle of oral self-mutilation.

Complicações osteoarticulares da analgesia congênita / Osteoarticular complications of congenital analgesia

Os autores apresentam dois irmãos com diagnóstico de analgesia congênita, com suas características clínicas e evolução. Essa doença é rara, apresenta alta morbidade e gera complicações osteoarticulares de difícil solução. O objetivo dos autores foi ressaltar a importância do diagnóstico tanto para o tratamento de suas afecções secundárias, quanto para seu aspecto jurídico.

The authors present two brothers with congenital pain insensitivity, with their clinical characteristics and evolution. This disease is rare, has high morbidity and originates complex osteoarticular complications. The aim of the authors was to emphasize the value of the diagnosis for a better treatment and to avoid legal problems to the parents.

Insensibilidad congénita al dolor: abordaje rehabilitador / Congenital insensitivity to pain: rehabilitation approach

La insensibilidad congénita al dolor es una rara enfermedad hereditaria muy heterogénea clínicamente. Se caracteriza por una ausencia de sensibilidad al dolor y asocia un gran número de complicaciones ortopédicas. Actualmente se desconoce un tratamiento etiológico, por lo que el tratamiento sintomático es la base del abordaje. Se presenta el caso de un varón de 14 años con anestesia algésica congénita remitido al Servicio de Rehabilitación para el tratamiento de las complicaciones ortopédicas secundarias. El paciente es tratado en cada ocasión según las características específicas de las mismas. La educación del paciente y la prevención de accidentes constituyen dos pilares básicos en el tratamiento, cuyo propósito es garantizar una mejor calidad de vida y un mayor grado de autonomía. El objetivo del trabajo es exponer un tipo de patología poco frecuente, muy incapacitante, con un interesante abordaje rehabilitador debido a las manifestaciones clínicas que lleva asociadas

Congenital insensitivity to pain is a rare and very clinically heterogeneous hereditary disease. It is characterized by absence of sensitivity to pain and is associated to a large number of orthopedic complications. At present, no etiological treatment is known so that these patients are provided symptomatic treatment. We present the case of an 14-year-old boy with congenital insensibility to pain referred to the Rehabilitation Department for treatment of secondary orthopedic complications. The patient is treated on every occasion according to the specific characteristics of the complications he presents. Education of the patient and prevention of accidents constitute two basic elements in the treatments whose purpose is to assure better quality of life and greater degree of autonomy. This work aims to explain a very incapacitating and uncommon type of disease with an interesting rehabilitation approach due to the clinical manifestations associated to it

Spinal anesthesia in a patient with congenital insensitivity to pain with anhidrosis.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare, hereditary, autonomic recessive disorder. The inability to perceive pain results from loss of nociceptive afferents, while anhidrosis is caused by loss of innervation to the sweat glands. Insensitivity to pain and mental retardation lead to self-inflicted injuries, corneal lacerations, painless bony fractures, joint deformities with consequent chronic osteomyelitis, and septic arthritis. There are only a few reports on the anesthetic management for patients with CIPA. We describe the anesthetic management of a young woman with CIPA receiving bilateral arthrodesis of the ankle.

[Clinical and genetic aspects of congenital insensitivity to pain with anhidrosis].

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease, which is characterized by recurrent episodes of fever, anhidrosis, self mutilation, absence of reaction to noxious stimuli, prolonged healing times and mental retardation. The absence of pain sensation combined with mental retardation predisposes the children to recurrent wound infections and deep ulcers that heal at a slower pace than seen in healthy people. The anomalous pain is due to the absence of dorsal root ganglia that are responsible for pain sensation and absence of afferent neurons activated by tissue damaging stimuli. Nerve Growth Factor (NGF) is a growth factor that supports the survival of nociceptive sensory and autonomic sympathetic neurons. Neurotrophin Tyrosine Receptor (NTRK1) encodes a receptor tyrosine kinase that is activated in response to NGF. NTRK1 mutations have been found in mice that presented with clinical signs similar to CIPA, subsequently CIPA patients have been examined for these mutations as well. Currently, 37 different mutations at the NTRK1 are known which cause CIPA. The above syndrome is so rare that until the year 2000 only 84 cases have been reported, not including 28 known cases of CIPA patients from Israeli Bedouins. Since no cure is available, prenatal screening, as conducted in our institution, is the only available preventive option to avoid the birth of an affected child.

Congenital insensitivity to pain: report of two cases.

Congenital indifference or insensitivity to pain (CIP) is a rare syndrome. It mimics a number of other syndromes categorized under peripheral sensory neuropathies, often making early diagnosis difficult. Two cases from the middle east are presented, highlighting possible diagnostic, and management difficulties.

The dental problems and management of a patient suffering from congenital insensitivity to pain.

Congenital insensitivity to pain is a rare condition usually manifested in childhood by a history of unrecognized trauma, indifference to painful stimuli or self-mutilation. This paper describes the management of a 13-month-old male who had severely lacerated his tongue by habitually chewing it, using soft polyvinyl mouthguards retained with a minimal amount of denture fixative.

Orthopedic aspects of congenital insensitivity to pain.

In an 11-year-old girl with congenital insensitivity to pain, diagnosis depended on three diagnostic features: pain sensation absent from birth; entire body affected; all other sensory modalities and deep tendon reflexes present. The cause of this disease is unknown. Other diseases to be considered when insensitivity to pain is present are diabetes, lues, and syringomyelia. Less common neurologic diseases are congenital sensory neuropathy with or without anhidrosis, familial dysautonomia (Riley-Day syndrome), and sensory radicular neuropathy. The three orthopedic manifestations of congenital insensitivity to pain are recurrent fractures, neuropathic (Charcot's) joints, and osteomyelitis. Management is based on proper appreciation of the disease. Prevention of complications is important. Treatment of fractures and osteomyelitis is straightforward. However, the treatment of neuropathic joints demands caution and is done best nonsurgically.

Congenital corneal anesthesia.

A 6-year-old boy with a visual acuity of 6/30 (20/100) in each eye had a diffuse corneal epithelial disruption that was most severe in the interpalpebral area. Corneal anesthesia was demonstrated with the Cochet-Bonnet aesthesiometer. Artificial tears, lubricant ointments, and taping of the eyelids were unsuccessful in ameliorating the problem. The use of therapeutic soft contact lenses provided visual acuity of R.E.: 6/12 (20/40), and L.E.: 6/6 (20/20), and arrested the epithelial breakdown. The contact lenses were discontinued after one year, and the corneal epithelium remained intact. Once the cycle of recurrent epithelial breakdown in congenital corneal anesthesia is interrupted for a prolonged period of time, one can expect a continued remission when therapeutic measures are discontinued. With early recognition and treatment of this disorder, corneal scarring can be avoided.