Successful catheter ablation of a left posterolateral accessory bypass tract and periinterventional management in a patient with MELAS syndrome.

MELAS syndrome is defined as a combination of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes resulting from mutations in mitochondrial DNA. All medical interventions in these patients appear challenging due to a high risk of lactate acidosis or anesthesiological complications. Of note, previous reports suggest that these patients have a higher incidence of Wolff-Parkinson-White (WPW) syndrome. Here, a case of successful catheter ablation of a posteroseptal bypass tract using analgosedation in a patient with MELAS syndrome combined with WPW syndrome is presented.

mTOR inhibitors may benefit kidney transplant recipients with mitochondrial diseases.

Mitochondrial diseases represent a significant clinical challenge. Substantial efforts have been devoted to identifying therapeutic strategies for mitochondrial disorders, but effective interventions have remained elusive. Recently, we reported attenuation of disease in a mouse model of the human mitochondrial disease Leigh syndrome through pharmacological inhibition of the mechanistic target of rapamycin (mTOR). The human mitochondrial disorder MELAS/MIDD (Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like Episodes/Maternally Inherited Diabetes and Deafness) shares many phenotypic characteristics with Leigh syndrome. MELAS/MIDD often leads to organ failure and transplantation and there are currently no effective treatments. To examine the therapeutic potential of mTOR inhibition in human mitochondrial disease, four kidney transplant recipients with MELAS/MIDD were switched from calcineurin inhibitors to mTOR inhibitors for immunosuppression. Primary fibroblast lines were generated from patient dermal biopsies and the impact of rapamycin was studied using cell-based end points. Metabolomic profiles of the four patients were obtained before and after the switch. pS6, a measure of mTOR signaling, was significantly increased in MELAS/MIDD cells compared to controls in the absence of treatment, demonstrating mTOR overactivation. Rapamycin rescued multiple deficits in cultured cells including mitochondrial morphology, mitochondrial membrane potential, and replicative capacity. Clinical measures of health and mitochondrial disease progression were improved in all four patients following the switch to an mTOR inhibitor. Metabolomic analysis was consistent with mitochondrial function improvement in all patients.

Anesthetic considerations for renal transplant surgery in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes syndrome: a case report.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes syndrome is a progressive syndrome with variable involvement of multiple-organ systems. These patients require special consideration for preoperative optimization, intraoperative management, and postoperative care. The medical literature regarding perioperative management of these patients relies heavily on case reports. Here we present a novel experience providing care for a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes syndrome who underwent renal transplantation for focal segmental glomerulosclerosis and end-stage renal disease.

An unusual case of paralytic ileus.

A 26-year-old female patient presented with the clinical picture of an acute ileus. Since childhood the patient has been diagnosed as having a MELAS syndrome, a mitochondriopathy. A subtotal colectomy was performed some years ago because of a similar ileus episode. The further diagnostic work-up revealed an expanded small intestine in abdominal radiography. Laboratory analysis showed increased levels of serum lactate with a consecutive respiratory compensated metabolic acidosis. A conservative treatment regime with nasogastric tube, fluid therapy, parental nutrition via peripheral veins and peristalsis inducing drugs was initiated, but did not resolve ileus symptoms. Under the hypothesis that in MELAS syndrome the ileus-related catabolic state aggravates the ileus symptoms in terms of a circulus vitiosus, we started high-caloric parenteral nutrition by using a central venous catheter. A few hours after this intervention, a clear clinical improvement could be observed. Since this initial presentation, the patient was admitted to our hospital several times with the same ileus symptoms. Each of the episodes was successfully and rapidly treated by this high-caloric parenteral nutrition therapy. The reproducible rapid clinical improvement after starting parenteral nutrition supports the hypothesis that an optimal energy supply is the key therapy not only for cerebral but also for gastrointestinal symptoms in patients with MELAS syndrome.

Anestesia en enfermedades mitocondriales / No disponible

Las enfermedades mitocondriales son un raro grupo de enfermedades que se manifiestan a través de un defecto en la cadena de transporte de electrones o de la fosforilación oxidativa. Se trata de una alteración del ADN nuclear o del mitocondrial que provoca miopatía hipotónica, encefalopatía y aumento del ácido láctico. Para su correcto diagnóstico deben realizarse, entre otras pruebas, una biopsia muscular y una resonancia magnética. El anestesista debe realizar su trabajo en un paciente con miopatía sin diagnosticar y con riesgo de complicaciones cardiorrespiratorias y neurológicas, por ello es importante el conocimiento de las acciones sobre la cadena respiratoria de los agentes anestésicos. Presentamos el desarrollo esquemático de las enfermedades de la cadena respiratoria mitocondrial y su manejo anestésico

Diseases of the mitochondrial respiratory chain are a rare pathologic group that can be manifested through a defect in the transport chain of electrons or by oxidative phosphorylation alteration. It is a disturbance of the nuclear or mitochondrial DNA, causing hypotonic myopathy, encephalopathy and hyperlactacidemya. For its correct diagnosis must be performed muscle biopsy and magnetic resonance. The anaesthetist must do their work in a patient without a correct diagnostic of myopathy, and a high risk of cardiorrespiratory and neurologic complications. That’s why it’s important the knowledge of the actions of de anaesthetic agents by de respiratory chain. We present the schematic development of the mitochondrial respiratory chain diseases and its anaesthetic management

Anesthetic management of a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) during laparotomy.

A 53-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) underwent a gastrectomy. We administered bicarbonated Ringer's solution, which has a physiological concentration of bicarbonate. The level of serum lactate did not increase significantly, and metabolic acidosis did not occur throughout surgery or for 3 h after surgery. Aggressive warming was needed to maintain normothermia, presumably because the mitochondrial respiratory chain, which is responsible for thermogenesis, is impaired in MELAS patients. It is important to maintain normothermia in MELAS patients in order to avoid further mitochondrial metabolic depression.

Resistance to cisatracurium in a patient with MELAS syndrome.

There are conflicting reports on the response of mitochondrial myopathy patients to the neuromuscular blocking drugs, showing either normal response or marked sensitivity. We present a patient with MELAS syndrome who underwent Nissen fundoplication and gastrojejunostomy. Marked resistance to the nondepolarizing muscle relaxant, cisatracurium was observed. The anesthesia management, as well as the various causes of resistance to cisatracurium in this patient are discussed.