RESUMO
PURPOSE: Prolonged postoperative neuromuscular respiratory paralysis after administration of a nondepolarizing neuromuscular blocking agent is a serious concern during anesthetic management of patients with Charcot-Marie-Tooth disease (CMTD). Some recent reports have described rocuronium use without respiratory paralysis in CMTD patients when sugammadex was used for its reversal. We report a case in which an induction dose of rocuronium caused a prolonged respiratory paralysis in a patient with undiagnosed type 1A CMTD (CMT1A). CLINICAL FEATURES: A 63-yr-old-male with an American Society of Anesthesiologists Physical Status score of III underwent a left hip arthroplasty under general anesthesia for osteoarthritis. Preoperative pulmonary function testing indicated a restrictive impairment. Anesthesia was induced with fentanyl, remifentanil, propofol, and 0.73 mg·kg-1 of rocuronium. The train-of-four (TOF) count was 0 for the 273-min duration of surgery. After repeated doses of sugammadex failed to recover the TOF count and spontaneous respirations, a total of 1,200 mg (17.3 mg·kg-1) of sugammadex, which was assumed to be a sufficient amount for capturing the residual rocuronium, was administered. Although the patient expressed that he was awake via eye blinking, he could not breathe. Thus, he was placed on mechanical ventilation for 18 hr after surgery. A postoperative neurology consultation revealed a delayed nerve conduction velocity of 20 m·sec-1 and a mutated duplication of the PMP22 gene; a diagnosis of CMT1A was made. CONCLUSIONS: Our case shows that rocuronium can cause a prolonged neuromuscular respiratory paralysis refractory to sugammadex in patients with CMT1A and impaired respiratory function. Our case may also indicate that restrictive pulmonary impairment and low nerve conduction velocity of 20 m·sec-1 are predictive factors that cause prolonged neuromuscular respiratory paralysis refractory to sugammadex in CMT1A.
RéSUMé: OBJECTIF: La paralysie respiratoire neuromusculaire postopératoire prolongée après l'administration d'un bloqueur neuromusculaire non dépolarisant est une préoccupation sérieuse lors de la prise en charge anesthésique des patients atteints de la maladie de Charcot-Marie-Tooth (CMT). Certains comptes rendus récents ont décrit l'utilisation de rocuronium sans paralysie respiratoire chez les patients atteints de CMT lorsque le sugammadex était utilisé pour le neutraliser. Nous rapportons un cas dans lequel une dose d'induction de rocuronium a provoqué une paralysie respiratoire prolongée chez un patient atteint de CMT de type 1A (CMT1A) non diagnostiquée. CARACTéRISTIQUES CLINIQUES: Un homme de 63 ans avec un score de statut physique III selon la classification de l'American Society of Anesthesiologists a bénéficié d'une arthroplastie de la hanche gauche sous anesthésie générale pour son ostéo-arthrite. Les tests préopératoires de la fonction pulmonaire ont indiqué un syndrome restrictif. L'anesthésie a été induite avec du fentanyl, du rémifentanil, du propofol et 0,73 mg·kg-1 de rocuronium. Le décompte du train-de-quatre (TdQ) était de 0 pour toute la durée de la chirurgie, soit 273 minutes. Après l'échec de doses répétées de sugammadex qui n'ont pas réussi à rétablir un TdQ normal ni la respiration spontanée, un total de 1200 mg (17,3 mg·kg-1) de sugammadex (une quantité qu'on a présumé suffisante pour neutraliser le rocuronium résiduel) a été administré. Bien que le patient ait exprimé qu'il était éveillé en clignant des yeux, il ne pouvait pas respirer. Il a donc été placé sous ventilation mécanique pendant 18 heures après l'opération. Une consultation postopératoire en neurologie a révélé une vitesse de conduction nerveuse retardée de 20 m·sec-1 et une duplication mutée du gène PMP22; un diagnostic de CMT1A a été posé. CONCLUSIONS: Notre cas montre que le rocuronium peut provoquer une paralysie respiratoire neuromusculaire prolongée réfractaire au sugammadex chez les patients atteints de CMT1A et d'une altération de la fonction respiratoire. Notre cas pourrait également indiquer qu'un syndrome restrictif pulmonaire et une faible vitesse de conduction nerveuse de 20 m·sec-1 constituent des facteurs prédictifs provoquant une paralysie respiratoire neuromusculaire prolongée réfractaire au sugammadex dans les cas de CMT1A.
Assuntos
Doença de Charcot-Marie-Tooth , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Paralisia Respiratória , Androstanóis/efeitos adversos , Período de Recuperação da Anestesia , Anestesia Geral , Doença de Charcot-Marie-Tooth/induzido quimicamente , Doença de Charcot-Marie-Tooth/complicações , Humanos , Masculino , Bloqueio Neuromuscular/efeitos adversos , Paralisia Respiratória/induzido quimicamente , Rocurônio , SugammadexRESUMO
Vincristine (VCR) is a common chemotherapeutic agent used in the treatment of multiple types of pediatric tumors. VCR's adverse effects are well documented and commonly involve peripheral neuropathy via axonal degeneration. Neuropathic severity is dose-dependent, with sensory deficits occurring with as little as 4 mg cumulative dose. Severe peripheral neuropathy is generally rare, but its effects become additive when given to patients with undiagnosed hereditary peripheral neuropathy such as Charcot-Marie-Tooth. We report a case of an effect of VCR administration given to a patient who developed grade 4 neuropathy and was found to be a carrier of Charcot-Marie-Tooth disease type 4.
Assuntos
Doença de Charcot-Marie-Tooth , Heterozigoto , Neoplasias Mandibulares , Rabdomiossarcoma , Vincristina/efeitos adversos , Doença de Charcot-Marie-Tooth/induzido quimicamente , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Criança , Humanos , Masculino , Neoplasias Mandibulares/diagnóstico , Neoplasias Mandibulares/tratamento farmacológico , Neoplasias Mandibulares/genética , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/genética , Vincristina/administração & dosagemRESUMO
INTRODUCTION: CMT2A2 is associated with mutations in the mitofusin 2 gene, which encodes a protein involved in mitochondrial fusion. Ethambutol is an antimycobacterial agent associated with toxic optic neuropathies. Ethambutol-induced optic neuropathy occurs in patients with mutations in a related fusion gene, OPA1, which is responsible for autosomal dominant optic atrophy. METHODS: We describe a patient with CMT2A2 (MFN2 mutation: T669G, F223L) who developed accelerated weakness, vocal cord paralysis, and optic atrophy after receiving ethambutol. RESULTS: Deterioration began within months of initiating ethambutol therapy. After discontinuation of ethambutol, neurologic deterioration stabilized with subsequent improvement in visual fields. CONCLUSIONS: CMT2A2 is part of a group of genetic disorders which share an association with the process of mitochondrial fusion. This case shows that patients with CMT2A2, and possibly other mitochondrial fusion defects, may be uniquely susceptible to ethambutol-induced neurotoxicity. This has implications regarding the underlying pathophysiology of mitochondrial fusion defects.
Assuntos
Doença de Charcot-Marie-Tooth/induzido quimicamente , Doença de Charcot-Marie-Tooth/genética , Etambutol/efeitos adversos , Fenótipo , Doença de Charcot-Marie-Tooth/diagnóstico , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The development of new animal models is a crucial step in determining the pathological mechanism underlying neurodegenerative diseases and is essential for the development of effective therapies. We have investigated the zebrafish (Danio rerio) as a new model to study CMT2A, a peripheral neuropathy characterized by the selective loss of motor neurons, caused by mutations of mitofusin 2 gene. Using a knock-down approach, we provide evidence that during embryonic development, mitofusin 2 loss of function is responsible of several morphological defects and motility impairment. Immunohistochemical investigations, revealing the presence of severe alterations in both motor neurons and muscles fibres, indicated the central role played by MFN2 in axonal and neuromuscular development. Finally, we demonstrated the ability of human MFN2 to balance the downregulation of endogenous mfn2 in zebrafish, further supporting the conserved function of the MFN2 gene. These results highlight the essential role of mitofusin 2 in the motor axon development and demonstrate the potential of zebrafish as a suitable and complementary platform for dissecting pathogenetic mechanisms of MFN2 mutations in vivo.
Assuntos
Doença de Charcot-Marie-Tooth , Deficiências do Desenvolvimento/etiologia , Regulação para Baixo/efeitos dos fármacos , Doenças Neuromusculares/etiologia , Oligodesoxirribonucleotídeos Antissenso/efeitos adversos , Metaloproteases Semelhantes a Toloide/genética , Proteínas de Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Padronização Corporal/efeitos dos fármacos , Padronização Corporal/genética , Doença de Charcot-Marie-Tooth/induzido quimicamente , Doença de Charcot-Marie-Tooth/complicações , Doença de Charcot-Marie-Tooth/genética , Biologia Computacional , Deficiências do Desenvolvimento/genética , Modelos Animais de Doenças , Regulação para Baixo/genética , Embrião não Mamífero , GTP Fosfo-Hidrolases , Humanos , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Atividade Motora/efeitos dos fármacos , Atividade Motora/genética , Doenças Neuromusculares/genética , RNA Mensageiro/metabolismo , Receptores Colinérgicos/metabolismo , Metaloproteases Semelhantes a Toloide/metabolismo , Tubulina (Proteína)/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismoAssuntos
Antineoplásicos/efeitos adversos , Doença de Charcot-Marie-Tooth/induzido quimicamente , Cisplatino/efeitos adversos , Vincristina/efeitos adversos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Embrionário/tratamento farmacológico , Doença de Charcot-Marie-Tooth/patologia , Humanos , Linfoma/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neoplasias Testiculares/tratamento farmacológicoRESUMO
This article reports on a case of sensorimotor neuropathy in a 55-year-old man that developed after vincristine therapy. Subsequent biopsy of the sural nerve and electromyographic studies revealed the presence of Charcot-Marie-Tooth disease. Only 17 patients who developed severe neuropathy with very low accumulated doses of vincristine have been described in the literature. Pain and lateral ankle instability were treated with a functional orthosis. Orthopedic treatment and the biomechanical basis of foot and ankle problems in patients with vincristine therapy-induced Charcot-Marie-Tooth disease are discussed.
Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Doença de Charcot-Marie-Tooth/induzido quimicamente , Vincristina/efeitos adversos , Doença de Charcot-Marie-Tooth/terapia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A 5 year old boy developed severe weakness after receiving vincristine for treatment of acute lymphoblastic leukaemia. Although weakness improved after the discontinuation of vincristine, other symptoms suggestive of a neuropathy persisted. Neurophysiological and genetic analysis at age 8 years indicated that vincristine had induced symptoms of a hereditary sensory motor neuropathy type 1A, which had previously been asymptomatic; his genetically affected mother was also asymptomatic.
Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Doença de Charcot-Marie-Tooth/induzido quimicamente , Vincristina/efeitos adversos , Doença de Charcot-Marie-Tooth/genética , Pré-Escolar , Seguimentos , Humanos , MasculinoRESUMO
A 16-year-old male suffering from Ewing's sarcoma of the pelvis was treated with vincristine as part of his chemotherapeutic protocol. The boy was never known to suffer from any neurological problems. His father had a mild limp, attributed to prolonged "taxi driving," that was never investigated medically. The first course of treatment, which included 2 mg of vincristine, resulted in clinical improvement. However, at the same time the patient developed severe weakness of both upper and lower limbs, areflexia, and gradually a pes cavus deformity. Nerve conduction studies were suggestive of severe peripheral sensorimotor neuropathy, axonal and demyelinative. A definite diagnosis of Charcot-Marie-Tooth was confirmed by molecular analysis showing the typical duplication of 1.5 megabases at 17 p11.2. This unique manifestation of vincristine neurotoxicity is reported and discussed.