Anesthetic management of a patient with X-linked adrenoleukodystrophy and related Addison’s disease and Brugada syndrome

Authors: Aslanidis Th^1*, Tsamaslidis G², Gkiauris E², Lazaridou EE⁴

¹MD, PhD, Anesthesiology/ Critical Care-Prehospital emergency medicine
²MD, Anesthesiology
³MD, MSc, Anesthesiology

Anesthesiology Department, Saint Paul (“Agios Pavlos”) General Hospital, Thessaloniki, Greece

*Correspondance: Doridos str 4, PC 54633, Thessaloniki, Greece, e-mail: , Tel.: +306972477166.

 

ABSTRACT

X-linked adrenoleukodystrophy is rarely encountered in the operating room. The clinical presentation is highly variable and creates unique challenges for the anesthesiologist. Case:  We hereby present a successful anesthetic management of patient with X-linked adrenoleukodystrophy and related Addison’s disease and Brugada syndrome for an orthopedic surgery and review the available literature about the topic. Conclusion: The numerous phenotypes of the disease pose unique challenge to the anesthesiologists that must be handled from a multidisciplinary team and on an individual basis.

 

INTRODUCTION

X-linked adrenoleukodystrophy (X-ALD), (ICD – 11: 5C57. 1) is rare progressive peroxisomal disorder characterized by endocrine dysfunction (adrenal failure and sometimes testicular insufficiency), progressive myelopathy, peripheral neuropathy and, variably, progressive leukodystrophy¹. X-linked adrenoleukodystrophy has an estimated birth prevalence of 1 in 17.000 subjects (considering both hemizygous males and heterozygous females), and there is no evidence that this prevalence varies among regions or ethnic groups^1-2. The clinical presentation differs between sexes, the age of onest of the disease is also highly variable and the progression is unpredictable¹. Currently, there is no cure for the prevention and progression of myelopathy. Yet, early diagnosis allows monitoring for the development of cerebral ALD and adrenal failure; thus, allowing timed treatment and supportive care.

Anesthesia for such patients is always challenging due to the diversity of clinical presentation of the disease. We present anesthetic management of a patient with X-ALD and related Addison’s disease and Brugada syndrome for an orthopaedic surgery and we review available literature on the subject.

Case report

A 64-year-old male [body weight (BW)- 82kg, height 180, BMI -25.3 kg/m²], was referred from our orthopedic department for a gamma (γ)-nail fixation for intertrochanteric left femur fracture (type 31A1.2 according to 2018 AO/orthopedic trauma association classification).

Past medical history included X-linked Adrenoleukodystrophy, firsted suspected due to increased hexacosanoic acid C26:0 (5.59 μmol/l), increased C24:0/C22:0 ratio (1.87) and C26:0/C22:0 (0.077) and confirmed by DNA testing which revealed ABCD1 gene (chromosome Xq28) hemizygous variant: c.421G>A (p. Ala541Thr, chromosome location 152991142, exon 1) mutation. Phenotypic presentation of the disease included adrenomyeolopathy (AMN) with progressive spastic paraplegia from the age of 33 years-old and adrenal insufficiency (Addison’s disease). In the course of the disease, Brugada syndrome type 2 was also emerged. Moderate carotid artery stenosis and bening prostatic hyperplasia were also recorded. Bone density scan results T-score was – 1.1. Type I (immediate hypersensitivity) allergy episode to gadoterate meglumine and been recorded in the past. No surgery history amoxicillin/clavulanic acid co-administration has also has been recorded. Finally, past family history did not include any known previous occurrence of the disease (yet one of the offspring of the patient was also diagnosed with X-ALD). Pre-incident drug regiment included: T₄ 50 μg S 1×1 p.os; Hydrocorisone 20 mg , S.2-0-1 p.os; Ακετυλοσαλικυλικό οξύ (ASA) 100 mg S 1×1 p.os; Fludrocortisone 75 μg S. 1×1 p.os; Rosuvastatin/ezetimibe 20/10 mg, S 1×1 p.os; Telmisartan/amlodipine 40/5mg S. 1×2 p.os and Tamsulosin 0.4 mg S 1×1 p.os. Low-Molecular-Weight Heparin (LMWH) prophylaxis and analgesia was added while in clinic.

Preoperative consultation with cardiologist, endocrinologist and neurologist was made for achieving optimum pre-procedure preparation. Baseline (48h preoperative) vitals sings were heart rate (HR) 75 bpm, blood pressure (BP) 142/80 mmHg, SpO₂ 96% on room air. Telmisartan/amlodipine was holded 24h preoperatively, while an infusion of Methylprednisolone 500mg / R/ L 1000ml at 30 ml/h civ started 2 hours before surgery, while ciprofloxacin 400mg iv and amikacin 1gr iv were administered 1hour prior to surgery.

Pre-induction vital signs were HR 101 bpm, BP 169/83 mmHg, SpO₂ 96%.  Preoperatively ondasetron 4mg iv, omeprazole 40 mg was given. Spinal anesthesia was selected as preferred anesthetic technique: Ropivacaine 0.75% 3.8ml (28.5mg) and D₃₅W 0.2ml was administered via 25G Quincke needle at L3-4 interspace. After positioning the patient and assessing level of anesthesia (Th10 dermatome), anxiolysis midazolam 1mg iv was given, and invasive blood pressure monitoring (via left radial artery) and left hemisphere BIS monitoring (BIS® Medtronic, MN, USA) was established. The surgery (duration of 75 min) was uneventfull (Images 1-2); the patient remained in the post anesthesia care unit (PACU) for 35 min after which he was transferred to the ward. Arterial blood gases at PACU were: pH-4.457, PaCO₂-39.7 mmHg, PaO₂-137.2 mmHg (FiO₂-41%), HCO₃^– -27.3mmol/l, Hb (hemoglobin)–9.1 g/dl, Na⁺ -139.2 mmol/l, K⁺-3.3mmol/l, Ca⁺ – 1.1 mmol/l, Anion Gap-11 mmol/l, Glu-95 mg/dl, Lac (lactate)–0.88 mmol/l.  Methylprednisolone infusion stopped 10h post operatively and his previous drug regiment restarted later the same day. The patient was discharged from the hospital 3 days later.

 

 

 

 

DISCUSSION

X-ALD is an inherited neurodegenerative disorder caused by a defect in ABCD1 gene (Xq28 locus), involving mainly the white matter and axons of the central nervous system, the adrenal cortex, and the testis and a frequent but under-recognized cause of primary adrenocortical insufficiency^2,3. Mutations in ABCD1 gene (there are over 1200 described variants) cause the absence or dysfunction of ALD protein (ALDP).ALDP is a peroxisomal transmembrane ATP-binding cassette (ABC) protein that transports very long-chain fatty acids (VLCFA) acyl-CoA esters from the cytosol into the peroxisome. The mutations are characterized by impaired peroxisomal beta-oxidation of VLCFA; (> C22, especially hexacosanoic (C26:0) and lignoceric (C24:0) acid)^1-4. A phenotype/genotype correlation in ALD does not exist. Predicting disease course based on a genetic variant, even within individual families, is not possible. In males, pre-symptomatic adrenoleukodystrophy is common in boys under 3 years of age and very rare in males over 40 years of age. Adrenal insufficiency frequently develops before the onset of neurologic symptoms, but can also be the only expression of the disease. Cerebral ALD can emerge either in childhood, adolescence or adulthood and symptomatology is generally rapidly progressive. Myelopathy is virtually presence in every X-ALD patient that reaches adulthood. The combination of myelopathy and adrenal dysfunction is also referred to as adrenomyeloneuropathy (AMN). Men with myelopathy are at risk to also develop cerebral ALD (20% over a period of 10 years)².

Brugada syndrome (BrS), an inherited autosomal dominant channelopathy disease, caused by genetic changes (e.g. SCN5A gene mutations) in transmembrane ion channels (NaV1.5). There are 3 ECG types of Brugada syndrome^5-6. Recently there have been reports of electrocardiogram (ECG) changes nearly identical to the Brugada syndrome but without the congenital abnormality associated with lethal arrhythmias and normalizes with treatment of the underlying etiology (including adrenal insufficiency), referred as Brugada phenocopy^7-8.

There are several reports of successful anesthetic management of patients, both children and adults, with X-ALD for various procedures. Yet, due to the variety of disease’s presentation, every patient poses unique challenges. Pre-operative sedation is usualle avoided since these patients are prone to respiratory depression^9-10. There is also increased risk of gastro-oesophageal reflux and pulmonary aspiration¹¹. Careful evaluation of the drug regiment is essential: antiseizure agents should be continued till the day of the surgery. Possible adverse effects, such as thrombocytopenia which can be found up to 40% in those who are receiving Lorenzo’s oil, or hepatic enzymes increase should also be assessed¹². The other X-ALD treatment options: lovastatin, hematopoietic stem cell transplantation and gene therapy can also poses extra challenges¹³. Proper corticosteroid (in case of adrenal insufficiency) administration should be initiated pre-operatively. In case of general anesthesia, rapid sequence intubation is preferred due to high aspiration risk. Yet, etomidate should be avoided (adrenal suppression concerns) and propofol should be used cautiously (Commercial propofol is formulated in 10% soybean oil emulsion and does not contain VLCFAs)¹⁴. Succinylcholine use is uncertain due to risk of hyperkalemia and ahould be avoided in case of spinal cord compression or acute demyelinitation. Attention to opioids is also neseccary in case of dementia presence. Regional anesthesia can be difficult (scoliosis) and presence of osteoporosis (hypogonadism) calls for careful intraoperative positioning. In cases like ours (with Brugada Syndrome), neuraxial anesthesia have been successfully performed with lidocaine, mepivacaine, bupivacaine and ropivacaine. Yet, if long-acting agents are used, then ropivacaine or levobupivacaine are to be preferred¹⁴. Postoperative stay at post anesthesia care unit should be longer and close monitoring of the patient is suggested for the first 24h.

CONCLUSION

Though X-ALD is the most frequent peroxisomal disease, encounter of such patients in the operating room is rare. Available literature is limited and provides information that can be evaluated carefully. Thus, it is crucial to keep in mind that the numerous phenotypes of the disease pose unique challenge to the anesthesiologists that must be handled from a multidisciplany team and on an individual basis.

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Addittional materials: No

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Acknowledgements: Not applicable

Authors’ contributions: AT: manuscript preparation, primary case-management, TG: primary case-management, GE: literature review, LEE: literature review. All authors read and approved the final manuscript.

Funding: Not applicable

Availability of supporting data: Not applicable.

Consent for publication: Patient’s consent was obtained

Ethical approval and consent to participate:

No IRB approval required.

Competing interests: The authors declare that they have no competing interests.

Received: May 2024, Accepted: May 2024, Published: July 2024.

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Citation: Aslanidis Th, Tsamaslidis G, Gkiauris E, Lazaridou EE. Anesthetic management of a patient with X-linked adrenoleukodystrophy and related Addison’s disease and Brugada syndrome. Greek e j Perioper Med. 2024;23(b):30-36.

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