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Year : 2018  |  Volume : 11  |  Issue : 3  |  Page : 267-269  

Neurodegeneration with brain iron accumulation for stem-cell therapy: Anesthetic management

1 Department of Anesthesiology, LTMMC and GH, Mumbai, Maharashtra, India
2 Department of Anesthesiology, Dr. RN Cooper Hospital and HBTMC, Mumbai, Maharashtra, India

Date of Web Publication29-Jun-2018

Correspondence Address:
Ruchi A Jain
Department of Anesthesiology, LTMMC and GH, Sion, Mumbai - 400 022, Maharashtra
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Neurodegeneration with brain iron accumulation (Hallervorden-Spatz Disease) is a rare, slowly progressing disorder characterized by progressive extrapyramidal dysfunction resulting in dementia, dystonia, torticollis, ataxia, kyphoscoliosis, and seizures. In chronic cases, muscle contractures, bony changes, temporomandibular joint, and cervical spine immobility may occur. Due to chronic malnutrition, there is increased the tendency for pathological fractures. Any noxious stimulus (anxiety, pain, light plane of anesthesia) intensifies dystonia. Significant speech disturbances, confusion, disorientation, mental retardation, dementia, and visual loss make communication with these patients a problem. Managing anesthesia in such patients is quite challenging as there is difficulty in positioning, intravenous cannulation, and airway management. We present a case report of a 14-year-old male patient with neurodegeneration with brain iron accumulation who was administered anesthesia for the stem-cell therapy.

Keywords: Anesthesia, neurodegeneration with brain iron accumulation, pantothenate kinase-associated neurodegeneration

How to cite this article:
Jain RA, Dalvi N, Karnik H. Neurodegeneration with brain iron accumulation for stem-cell therapy: Anesthetic management. Med J DY Patil Vidyapeeth 2018;11:267-9

How to cite this URL:
Jain RA, Dalvi N, Karnik H. Neurodegeneration with brain iron accumulation for stem-cell therapy: Anesthetic management. Med J DY Patil Vidyapeeth [serial online] 2018 [cited 2021 Aug 2];11:267-9. Available from: https://www.mjdrdypv.org/text.asp?2018/11/3/267/235547

  Introduction Top

Neurodegeneration with brain iron accumulation type 1 (NBIA) or pantothenate kinase-associated neurodegeneration (PKAN) formerly  Hallervorden-Spatz disease More Details is a rare, autosomal recessive, slowly progressing disorder characterized using extrapyramidal dysfunction due to the accumulation of iron in the basal ganglia.[1],[2] There are many challenging difficulties in managing any type anesthesia for these patients. We present a case of a patient with NBIA who was administered sedation for the stem-cell therapy

  Case Report Top

A 14-year-old male patient weighing 23 kg, who was a known case of NBIA, was referred to our institute for stem-cell therapy. Stem-cell therapy is an experimental therapy which involves injecting stem cells which have been extracted from the patient's bone marrow obtained from pelvic bones, into the intrathecal space.

The patient had developed abnormal gait, ataxia, and dystonia at 2 years of age which had progressively worsened, rendering the patient immobile. Retinitis pigmentosa resulted in progressive visual deterioration to only perception of light bilaterally. Dystonia of facial muscles restricted the mouth opening, resulting in a progressive inability to talk or chew. The patient was on nasogastric tube feeds for the past 2 years. He had required multiple hospital admissions for the dystonic crises. He had previously sustained a pathological fracture of the right femur due to trivial trauma. There was no history of convulsions or tremors. The patient was on oral Syndopa 110 mg, trihexyphenidyl 8 mg, Baclofen 25 mg all TDS and clonazepam 8 mg in 5 divided doses. Dystonia was still present in spite of these medications although at a lesser intensity. It worsened in response to any noxious or unpleasant stimulus. There was no family history of adverse events following anesthesia.

The emaciated patient had constant dystonic posturing and generalized hypertonia. Airway examination revealed micrognathia, microstomia, retrognathia, restricted neck movements, and torticollis. Mouth opening was impossible, probably due to temporomandibular joint (TMJ) ankylosis. The thyromental distance was 5 cm. The child responded to verbal commands. The lower limb joints were fixed in hyperextension with contractures at the elbow and wrist joints bilaterally. Kyphoscoliosis and chest asymmetry was present. Respiratory and cardiovascular system examination was normal.

Routine blood investigations were normal. X-ray chest confirmed kyphoscoliosis and osteopenia. Magnetic resonance imaging of the brain showed classic “eye of tiger” sign. A 215–216 insA mutation in the homozygous state in PANK2 gene was found on genetic studies. Sleep electroencephalogram was normal. Visually, evoked potentials showed a unilateral disturbance in visual conduction in the right side pathway.

The patient was given his morning dose of medications through the nasogastric tube. After adequate starvation and consent for anesthesia and SOS tracheostomy, the patient was taken in the operating room at the time of peak effect of his medications. The help of parents was taken in shifting patient carefully on OT table to minimize anxiety and iatrogenic injury. Standard monitoring included an electrocardiogram, pulse oximetry, nasal capnography, and noninvasive blood pressure. A 22-guage intravenous (IV) access was secured. The patient was administered O2 through nasal prongs. The patient was given IV midazolam 0.3 mg, fentanyl 20 μg, propofol 20 mg, and paracetamol 120 mg all in graded doses. Bone marrow was collected from the right anterior superior iliac spine after local infiltration with 2% lignocaine. Duration of the procedure was 40 min. Emergence was accompanied by dystonia. The patient was observed in postanesthesia care unit and given his medications as per schedule.

The processing of the bone marrow to collect stem cells takes about 3 h after which the second part of the procedure was undertaken. The patient was again administered O2, midazolam 0.3 mg, fentanyl 30 μg, and propofol 20 mg. He was given right lateral position. Stem cells (2–3 ml) were injected intrathecally through lumbar puncture in L2–L3 inter space. The duration of the procedure was 45 min. The patient was hemodynamically stable throughout the procedure. SpO2 was maintained at 99% and EtCO2 between 28 and 30 mm Hg. The patient had an uneventful postoperative recovery.

  Discussion Top

PKAN has an onset in childhood, adolescence or rarely in adulthood. Symptoms which usually develop during childhood, may include, choreoathetosis, muscle spasticity, ataxia, confusion, disorientation, seizures, developmental delay, depression, and dementia. Other symptoms include painful muscle spasms, dysphasia, mental retardation, facial grimacing, dysarthria, visual impairment, torticollis, scoliosis, gastroesophageal reflux, and constipation.[2] Patients with early-onset disease have restricted capability to walk, leading to use of a wheelchair by the midteens.[2],[3],[4],[5] With no known effective treatment, life expectancy is variable. Premature death may occur due to malnutrition or aspiration pneumonia. Patients with atypical, late-onset NBIA, are diagnosed as adults.[2] Patients present for a variety of surgeries including feeding tube placement,[6] stereotactic pallidotomy,[7] thalamotomy,[8] intrathecal baclofen pump placement,[9] deep brain stimulation,[10] or for trauma care.[11]

Dystonic posturing is likely to disappear with the induction of anesthesia. Skeletal muscle contractures and bony changes in chronic cases lead to immobility of the TMJ and cervical spine, even under deep general anesthesia and muscle relaxants. The anesthetic management of such a patient is extremely challenging at every step beginning from transporting the patient, getting IV access, securing the airway, and positioning of the patient before and after induction of anesthesia. Anatomic factors make regional anesthesia tough. The airway management is particularly difficult since use of suxamethonium can trigger hyperkalemia and an awake technique provokes dystonia.

A spontaneous breathing technique was chosen since the procedure did not require muscle relaxation. We were prepared for emergency tracheostomy in view of the difficult airway. Our patients mouth opening did not improve after giving propofol; although, other authors have reported no difficulty in securing the airway under anesthesia.[8],[9],[10],[11] There are reports of neuroleptic malignant syndrome (NMS) developing spontaneously in patients with striatonigral degeneration in the absence of antipsychotic drugs.[12],[13] If NMS develops in the perioperative period it may be difficult to differentiate from malignant hyperpyrexia if inhalational agents have been used. Status dystonicus, characterized by severe painful dystonia with hyperpyrexia, dehydration, respiratory insufficiency, and acute renal failure secondary to rhabdomyolysis, may confound the diagnosis.[14] However, nitrous oxide,[6],[8] halothane,[6],[11] sevoflurane,[8],[9],[10],[11] isoflurane,[8],[11] thiopentone,[8] propofol,[7],[8],[10],[11] fentanyl,[8],[9],[11] remifentanil,[10] and dexmedetomidine have been used safely in PKAN.[15] Nondepolarizing muscle relaxants are preferred for intubation to avoid suxamethonium induced hyperkalemia [8],[9],[10] although suxamethonium has been used in an emergency without complications.[8]

  Conclusion Top

Patients with PKAN have many anesthesia concerns with no clearly defined guidelines regarding the conduct of anesthesia. A carefully titrated anesthetic plan, prudently timing the surgery with the peak effect of drugs for dystonia and diligent monitoring can lead to a successful outcome.

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  References Top

Hallervorden J, Spatz H. Eigenartige erkrankung im extrapyramidalen system mit besonderer beteiligung des globus pallidus und der substantia nigra. Zeitschrift f{ü}r die gesamte Neurol und Psychiatr1922;79:254302.  Back to cited text no. 1
Gregory A, Polster BJ, Hayflick SJ. Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J Med Genet 2009;46:73-80.  Back to cited text no. 2
Swaiman KF. Hallervorden-Spatz syndrome. Pediatr Neurol 2001;25:102-8.  Back to cited text no. 3
Kapoor S, Hörtnagel K, Gogia S, Paul R, Malhotra V. Pantothenate kinase associated neurodegeneration (Hallervorden-Spatz Syndrome). Indian J Pediatr 2005;72:261-4.  Back to cited text no. 4
Hinkelbein J, Kalenka A, Alb M. Anesthesia for patients with pantothenate-kinase-associated neurodegeneration (Hallervorden-Spatz disease) - A literature review. Acta Neuropsychiatr 2006;18:168-72.  Back to cited text no. 5
Roy RC, McLain S, Wise A, Shaffner LD. Anesthetic management of a patient with hallervorden-spatz disease. Anesthesiology 1983;58:382-4.  Back to cited text no. 6
Balas I, Kovacs N. Staged bilateral stereotactic pallidothalamotomy for life - Threatening dystonia in a child with Hallervorden – Spatz disease. Mov Disord 2006;21:82-5.  Back to cited text no. 7
Keegan MT, Flick RP, Matsumoto JY, Davis DH, Lanier WL. Anesthetic management for two-stage computer-assisted, stereotactic thalamotomy in a child with hallervorden-spatz disease. J Neurosurg Anesthesiol 2000;12:107-11.  Back to cited text no. 8
Lee C, Chu Y, Chuang C, Chen C, Tsou M, Chan K. Intrathecal baclofen facilitated postanesthetic tracheal extubation in a dystonic patient associated with neurodegeneration of brain iron accumulation (Hallervorden-Spatz disease). Neurosci Med 2011;2:351-4.  Back to cited text no. 9
Koc D, Imer P, Bayri Y, Seker A. Anesthetic management for deep brain stimulation in a patient with pantothenate kinase-associated neurodegeneration. Pediatr Anesth Crit care J 2014;2:122-5.  Back to cited text no. 10
Sinha R, Biyani G, Bhattacharjee S. Anaesthetic management of a child with panthothenate kinase-associated neurodegeneration. Indian J Anaesth 2015;59:43-6.  Back to cited text no. 11
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Itoh M, Nakano E, Ieshima A, Takeshita K. Neuroleptic malignant syndrome in striatonigral degeneration. Pediatr Neurol 1995;13:255-6.  Back to cited text no. 12
Hayashi K, Chihara E, Sawa T, Tanaka Y. Clinical features of neuroleptic malignant syndrome in basal ganglia disease. Spontaneous presentation in a patient with hallervorden-spatz disease in the absence of neuroleptic drugs. Anaesthesia 1993;48:499-502.  Back to cited text no. 13
Mariotti P, Fasano A, Contarino MF, Della Marca G, Piastra M, Genovese O, et al. Management of status dystonicus: Our experience and review of the literature. Mov Disord 2007;22:963-8.  Back to cited text no. 14
Madhusudhana Rao B, Radhakrishnan M. Dexmedetomidine for a patient with hallervorden-spatz syndrome during magnetic resonance imaging: A case report. J Anesth 2013;27:963-4.  Back to cited text no. 15


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