Common Peroneal Nerve and Tarsal Tunnel Release Surgery in an Adolescent Male with Hunter Syndrome: Illustrative Case.

BACKGROUND: Children with Hunter syndrome have a high prevalence of nerve compression syndromes given the buildup of glycosaminoglycans in the tendon sheaths and soft tissue structures. These are often comorbid with orthopedic conditions given joint and tendon contractures due to the same pathology. While carpal tunnel syndrome and surgical treatment has been well-reported in this population, the literature on lower extremity nerve compression syndromes and their treatment in Hunter syndrome is sparse. OBSERVATIONS: We report the case of a 13-year-old male with a history of Hunter syndrome who presented with toe-walking and tenderness over the peroneal and tarsal tunnel areas. He underwent bilateral common peroneal nerve and tarsal tunnel releases, with findings of severe nerve compression and hypertrophied soft tissue structures demonstrating fibromuscular scarring on pathology. Post-operatively, the patient's family reported subjective improvement in lower extremity mobility and plantar flexion. LESSONS: In this case, peroneal and tarsal nerve compression were diagnosed clinically and treated effectively with surgical release and postoperative ankle casting. Given the wide differential of common comorbid orthopedic conditions in Hunter syndrome and the lack of validated electrodiagnostic normative values in this population, the history and physical examination and consideration of nerve compression syndromes are tantamount for successful workup and treatment of gait abnormalities in the child with Hunter syndrome.

Hidden Bow Hunter's Syndrome Diagnosed Using Dynamic Cerebral Angiography and Successfully Treated with Spinal Surgery: A Case Report and Review of the Literature.

Hidden bow hunter's syndrome (HBHS) is a rare disease in which the vertebral artery (VA) occludes in a neutral position but recanalizes in a particular neck position. We herein report an HBHS case and assess its characteristics through a literature review. A 69-year-old man had repeated posterior-circulation infarcts with right VA occlusion. Cerebral angiography showed that the right VA was recanalized only with neck tilt. Decompression of the VA successfully prevented stroke recurrence. HBHS should be considered in patients with posterior circulation infarction with an occluded VA at its lower vertebral level. Diagnosing this syndrome correctly is important for preventing stroke recurrence.

Flexible Bronchoscopy Combined With Videolaryngoscope For Tracheal Intubation In A Child With Hunter Syndrome: A Case Report.

Hunter syndrome (mucopolysaccharidosis type II) has the highest reported prevalence of difficult tracheal intubation among the seven known types of mucopolysaccharidoses. Despite improved difficult airway guidelines and equipment, conventional approaches may fail in some cases. A 10-year-old child with Hunter syndrome, was scheduled for multiple dental extractions. On the first visit, failed intubation was declared as per Difficult Airway Society guidelines in the surgical day-care suite of our institute and the procedure was postponed. The case was then planned to be handled in the main operating room with additional preparation and input from the paediatric otolaryngologist for possible tracheostomy, paediatric intensive care for postoperative need for ventilation, and difficult airway resource faculty for an unconventional approach-videolaryngoscope combined with fibreoptic bronchoscope-which resulted in safe administration of anaesthesia. This case illustrates the importance of meticulous planning in the management of previously failed airway.

Bow Hunter's syndrome combined with ipsilateral vertebral artery dissection/pseudoaneurysm: case study and literature review.

BACKGROUND: Bow hunter's syndrome (BHS), also known as rotational vertebral artery occlusion syndrome, is rare. Occasionally, it combines with dissection/pseudoaneurysm of the ipsilateral VA. METHODS: We report a case of BHS combined with ipsilateral VA dissection/pseudoaneurysm and review eight similar cases reported in the literature. Their aetiology, clinical and imaging features, treatment, and prognosis were analysed. RESULTS: Nine patients (seven male, two female; average age 22.0 ± 4.5 years) were enrolled. Visual symptoms comprised the most common clinical finding (66.7%, 7/9). Clinical symptoms were not related to neck rotation in seven patients (77.8%). Eight patients (88.9%) had multiple, scattered, new and old infarctions of the posterior circulation revealed on computed tomography/magnetic resonance imaging (CT/MRI) scans. Dissection/pseudoaneurysm was found in the ipsilateral VA - usually subtle and localised in the atlas, axis, and occipital bone - in all nine patients. Seven patients (66.7%) had special causes for the syndrome (i.e. congenital bone dysplasia). Altogether, 87.5% (7/8) experienced recurrence with cerebral infarction after antithrombotic therapy alone. Aetiologically targeted treatment, including surgical decompression or vertebral fixation, was performed in seven patients (77.8%). CONCLUSION: Young patients presenting with cryptogenic stroke in the posterior circulation and localised, subtle dissection/pseudoaneurysm of the ipsilateral VA around the atlanto-axial joint should undergo carotid ultrasonography with a neck rotation test or dynamic CT angiography/MR angiography/digital subtraction angiography, if necessary, to rule out/diagnose BHS.

Thyroid Cartilage Compression Causing Bow Hunter's Syndrome.

OBJECTIVES AND METHODS: We report a unique case of Bow Hunter's syndrome with a dominant aberrantly coursing right vertebral artery (VA), presenting with persistent dizziness and syncope despite previous decompressive surgery at vertebral levels C5-C6. RESULTS: Re-evaluation with computed tomography-scan during provocation of dizziness by neck rotation revealed compression of the right VA at level C6 from against the ipsilateral posterior border and superior cornu of the thyroid cartilage. Laryngoplasty resulted in complete resolution of symptoms. CONCLUSION: This extremely rare cause of Bow's Hunter's syndrome should be considered, especially in refractory cases after neurosurgical decompression, and surgical management is straightforward and successful.

Severe central airway stenosis and tracheomalacia in hunter syndrome.

Hunter Syndrome is a genetic disease characterized by deficiency of Iduronate-2-Sulfatase enzyme activity, resulting in accumulation of glycoaminoglycans in various organs including the central airways. We report a case of severe tracheomalacia and airway stenosis at Hospital Sultanah Aminah, Johor Bahru, Malaysia requiring mechanical ventilation in a middle aged gentleman who was previously undiagnosed of mucopolysaccharidosis. The patient underwent emergency tracheostomy for failed intubation, when he presented with shortness of breath and acute respiratory failure. A contrast-enhanced computed tomography of the neck and thorax revealed that the trachea distal to the tracheostomy tube had collapsed with narrowed right and left main bronchus. These findings were confirmed via direct visualization of the airway through a flexible bronchoscopy. Eventually, a tracheal stenting were performed to maintain the airway patency and assist in weaning off from mechanical ventilation. Further investigations to identify the aetiology of the central airway stenosis revealed elevated urinary glycoaminoglycans and the absence of iduronate-2-Sulfatase activity tested on dried blood spots, thus confirming the diagnosis of Hunter Syndrome. Managing mucopolysacharidosis with central airway obstruction requires multidisciplinary team effort in handling the difficult airway, anaesthesiology risk, potential comorbidities and providing genetic counselling.

Nasal Polyposis in mucopolysaccharidosis type II.

Mucopolysaccharidosis (MPS) type II is a rare multisystem disorder resulting from the accumulation of breakdown products of glycosaminoglycans in the body tissues. Many patients with this disease undergo ENT (ear, nose and throat) surgeries such as adenotonsillectomy and tympanocentesis at a very early age, much before the diagnosis of MPS. Nasal polyposis is a rare occurrence, with only one case of MPS II with polyposis reported in the literature. We present a patient who presented with recurrent nasal polyposis from the age of 2 years. Hale's colloidal iron was used to stain these 'nasal polyps', which revealed that they are, in fact, mucopolysaccharide-laden sinonasal mucosa prolapsing into the nasal cavities. We believe this is the first time that this stain has been used to stain nasal polyps in MPS. In addition to the histopathological peculiarities of these nasal masses, we also discuss the natural history of nasal polyposis in MPS II.

Efficient engraftment of genetically modified cells is necessary to ameliorate central nervous system involvement of murine model of mucopolysaccharidosis type II by hematopoietic stem cell targeted gene therapy.

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease (LSD) caused by a deficiency of the iduronate-2-sulfatase (IDS) that catabolizes glycosaminoglycans (GAGs). Abnormal accumulations of GAGs in somatic cells lead to various manifestations including central nervous system (CNS) disease. Enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are the currently available therapy for MPS II, but both therapies fail to improve CNS manifestations. We previously showed that hematopoietic stem cell targeted gene therapy (HSC-GT) with lethal irradiation improved CNS involvement in a murine model of MPS II which lacks the gene coding for IDS. However, the strong preconditioning, with lethal irradiation, would cause a high rate of morbidity and mortality. Therefore, we tested milder preconditioning procedures with either low dose irradiation or low dose irradiation plus an anti c-kit monoclonal antibody (ACK2) to assess CNS effects in mice with MPS II after HSC-GT. Mice from all the HSC-GT groups displayed super-physiological levels of IDS enzyme activity and robust reduction of abnormally accumulated GAGs to the wild type mice levels in peripheral organs. However, only the mice treated with lethal irradiation showed significant cognitive function improvement as well as IDS elevation and GAG reduction in the brain. These results suggest that an efficient engraftment of genetically modified cells for HSC-GT requires strong preconditioning to ameliorate CNS involvement in cases with MPS II.

Otorhinolaryngological manifestations in 61 patients with mucopolysaccharidosis.

OBJECTIVES: The mucopolysaccharidoses (MPS) are inherited lysosomal storage disorders with multisystemic and highly variable clinical manifestation. ENT symptoms are common and early signs of MPS. The most common ENT diagnoses are chronic/recurrent rhinosinusitis, acute otitis media, otitis media with effusion, hearing loss and airway obstruction. METHODS: A single-centre retrospective chart review of 61 patients (36 M/25F) with different MPS subtypes (MPS I (n = 15), MPS II (n = 10), MPS III (n = 17), MPS IV (n = 15) and MPS VI (n = 4)) was conducted. The age of ENT presentation and frequency of ENT symptoms, surgeries and their distribution among MPS subtypes was studied. The relationship between ENT presentation, first ENT surgery and the age of diagnosis was also evaluated. RESULTS: Median age at the first ENT manifestation was 2.8 years, median age at MPS diagnosis 4.1 years. The great majority of patients (90%) manifested at least one ENT diagnosis; often before the diagnosis of MPS (75%). Chronic/recurrent rhinosinusitis was the most prevalent ENT diagnosis (77%), followed by upper airway obstruction (65%) and hearing loss (53%). Chronic/recurrent rhinosinusitis was the first ENT symptom to appear (median age 2.2 years), followed by otitis media with effusion (3.7 years) and hearing loss (4.5 years). At least one ENT surgery was performed in 57% of patients; in 69% before MPS diagnosis was established. Median age of the first ENT surgery was 4.1 years. ENT symptoms and surgical procedures were earliest present in MPS II. CONCLUSIONS: Our study documents high and early occurrence of various otolaryngologic symptoms in MPS and thus highlights the role of ENT specialist in prompt diagnosis of these rare diseases and their long-term management.

Visual Loss Post Ross Procedure in an Adolescent With Newly Diagnosed Mucopolysaccharidosis Type II.

Perioperative visual loss is a rare but serious complication after cardiac surgery. The etiology is not fully understood, and there is no consensus on the optimal management of this condition. A 15-year-old male patient developed severe visual impairment attributed to nonarteritic anterior ischemic optic neuropathy after a Ross aortic root replacement procedure. A new diagnosis of the lysosomal storage disorder, mucopolysaccharidosis type II (Hunter syndrome), was subsequently made, raising questions about the pathogenesis of this devastating postoperative complication.

Surgical consideration in Hunter syndrome: a case of hydrocephalus and a case of epidural hematoma.

INTRODUCTION: Hunter syndrome (HS) is a rare X-linked lysosomal storage disorder which affects multiple organ systems. Surgical intervention and general anesthesia should be used with caution because of significant airway complications. CASE REPORT: Two HS patients underwent surgery with different prognosis are presented below. In the first case, symptoms of progressive disabilities on motor function, language, intelligence, and development last for 1 year in a 6-year-old boy; magnetic resonance imaging (MRI) showed severe hydrocephalus. Third ventriculostomy was performed in this patient to relieve the hydrocephalus. Unfortunately, this patient died postoperatively due to postsurgical tracheal collapse. In the second case, an 8-year-old girl was referred to our hospital with epidural hematoma because of a falling accident. Trephination surgery was performed under local anesthesia to remove the hematoma. Three days postsurgical, the patient was discharged uneventfully. CONCLUSION: General anesthesia in HS patients was associated with poor prognosis due to respiratory complications. Local anesthesia and less intensified treatment should be recommended.

Oral and craniofacial manifestations in a Hunter syndrome patient with hematopoietic stem cell transplantation: A case report.

We described herein the oral and craniofacial features of a 7-year-old boy, diagnosed in utero with mucopolysaccharidosis II (MPS II), who was treated with hematopoietic stem cell transplantation (HSCT) at 70 days of age. The main oral clinical findings were the following: macroglossia, posterior cross-bite, crowding, pointed cuspid teeth, delayed tooth eruption, retained primary teeth, and enamel hypoplasia. The image examination showed: retention eruption, posterior primary teeth with short roots, absence of some permanent teeth, and stretching of the stylohyoid processes bilaterally. This patient showed the importance of early diagnosis and HSCT therapy in attenuating the clinical and radiographic oral and craniofacial manifestations of the MPS II patient.

Moving target: transient rotational stenosis precipitating jugular bow hunter's syndrome.

A 60-year-old man presented with a 10-month history of of stereotypical spells characterized by vertigo, tinnitus, blurred vision, left hemibody numbness, and occasional syncope, precipitated by turning his head leftwards. Cerebral angiography and CT angiography of the head and neck with provocative maneuvers did not demonstrate vertebral artery narrowing. However, there was narrowing of the left internal jugular vein due to extrinsic compression from the sternocleidomastoid with leftward head rotation in the setting of hypoplasia of the right internal jugular vein. The patient underwent a cervical venogram which confirmed the finding. Manometric evaluation demonstrated a gradient of 29 mm Hg across the stenosis with the head turned leftwards compared with 1 mm Hg in the neutral position. The patient was treated with myectomies of the left sternocleidomastoid, posterior belly of the digastric, stylohyoid and omohyoid and styloid process removal. Following surgery, the patient reported complete resolution of symptoms. Repeat venography demonstrated resolution of the stenosis and pressure gradient.

Thoracolumbar kyphoscoliosis with unilateral subluxation of the spine and postoperative lumbar spondylolisthesis in Hunter syndrome.

Surgical correction for kyphoscoliosis is increasingly being performed for patients with mucopolysaccharidosis (MPS). Reported case series have predominantly included patients with Type I (Hurler) and Type IV (Morquio) MPS. To their knowledge, the authors describe the first case report of surgical management of thoracolumbar kyphoscoliosis in Hunter syndrome (MPS Type II) and the rare occurrence of lumbar spondylolisthesis following surgical stabilization. A 12-year-old boy with Hunter syndrome presented with severe thoracolumbar kyphoscoliosis and no associated symptoms. Spinal radiographs demonstrated kyphosis of 48° (T11-L3) and scoliosis of 22° (T11-L3) with an anteriorly hypoplastic L-1 vertebra. The deformity progressed to kyphosis of 60° and scoliosis of 42° prior to surgical intervention. Spinal CT scans identified left T12-L1 facet subluxation, causing anterior rotatory displacement of the spine proximal to L-1 and bilateral L-5 isthmic spondylolysis with no spondylolisthesis. A combined single-stage anterior and posterior instrumented spinal arthrodesis from T-9 to L-4 was performed. Kyphosis and scoliosis were corrected to 4° and 0°, respectively. Prolonged ventilator support and nasogastric feedings were required for 3 months postoperatively. At 2.5 years following surgery, the patient was asymptomatic, mobilizing independently, and had achieved a solid spinal fusion. However, he had also developed a Grade II spondylolisthesis at L4-5; this was managed nonoperatively in the absence of symptoms or further deterioration of the spondylolisthesis to the 3.5-year postoperative follow-up visit. Satisfactory correction of thoracolumbar kyphoscoliosis in Hunter syndrome can be achieved by combined anterior/posterior instrumented arthrodesis. The risk of developing deformity or instability in motion segments adjacent to an instrumented fusion may be greater in patients with MPS related to the underlying connective tissue disorder.

Characterization of Hip Morphology in Children With Mucopolysaccharidosis Types I and II.

BACKGROUND: The purpose of this study is to describe the natural history of hip morphology in patients with mucopolysaccharidoses (MPS) I and MPS II. METHODOLOGY: This is a retrospective radiographic analysis of 88 hips in 44 children with MPS I and II. Radiographs were examined to determine hip migration, femoral head sphericity, and acetabular dysplasia at different ages throughout childhood. In individual hips, change in morphology and rate of change were analyzed. RESULTS: There was a high rate of hip migration and femoral head dysplasia in both MPS I and MPS II. Progressive migration was seen in three quarters of hips and progressive femoral head deformity in over half of hips. Acetabular dysplasia was variable, ranging from normal to severely dysplastic, but did not change with time. Overall, hips were more dysplastic in MPS I than MPS II. CONCLUSIONS: Hip morphology is variable in MPS I and MPS II ranging from almost normal to severely dysplastic. Some hips do not deteriorate with time and thus surgical intervention may not be necessary in all cases. Deterioration is slow allowing time to plan a holistic approach to treatment. LEVEL OF EVIDENCE: Level IV-case series.

Carotid intima-media thickness is increased in patients with treated mucopolysaccharidosis types I and II, and correlates with arterial stiffness.

BACKGROUND: Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but coronary artery disease (CAD) and cardiovascular complications cause mortality in a high percentage of patients. Non-invasive measures of sub-clinical atherosclerosis, such as carotid intima-media thickness (cIMT) and arterial stiffness, may be useful for prediction of CAD outcomes in MPS patients. OBJECTIVES: The aim of the study was to determine if cIMT and arterial stiffness are abnormal in MPS I and II patients compared to healthy controls. METHODS: MPS patients underwent carotid artery ultrasonography, and electronic wall-tracking software was used to measure cIMT, carotid artery cross-sectional compliance (cCSC), cross-sectional distensibility (cCSD), and incremental elastic modulus (cIEM). Control data from healthy subjects were obtained from a different study that utilized identical testing within the same laboratory. RESULTS: A total of 406 healthy controls and 25 MPS patients (16 MPS I, 9 MPS II) were studied. All MPS patients had or were receiving treatment: 15 patients (6 MPS I, 9 MPS II) were receiving enzyme replacement therapy (ERT), 9 patients (all MPS I) had received hematopoietic stem cell transplant (HSCT), and 1 patient with MPS I had received HSCT and was receiving enzyme replacement therapy (ERT). MPS patients had significantly higher mean (± SD) cIMT (0.56 ± 0.05 mm) compared to controls (0.44 ± 0.04 mm; adjusted p<0.001). MPS patients also had increased stiffness compared to controls, showing significantly lower cCSC (0.14 ± 0.09 mm(2)/mmHg versus 0.16 ± 0.05 mm(2)/mmHg; adjusted p=0.019), and higher cIEM (1362 ± 877 mmHg versus 942 ± 396 mmHg; adjusted p<0.001). cCSD in MPS patients was lower than that of controls (29.7 ± 16.4% versus 32.0 ± 8.2%) but was not statistically significant; p=0.12. Among MPS patients, cCSD showed a significant association with cIMT (p=0.047), while the association between cIEM and cIMT approached significance (p=0.077). No significant differences were observed in cIMT, cCSD, cCSC, and cIEM between MPS I and MPS II patients. CONCLUSIONS: Despite treatment, MPS patients had higher cIMT compared to healthy controls, indicating this marker of sub-clinical atherosclerosis may be a useful predictor of CAD outcomes. The association of arterial stiffness measures with cIMT suggests that mechanical and structural changes may occur in concert among MPS patients. Although yet to be confirmed, increased cIMT and arterial stiffness in MPS I and II patients may be a consequence of inflammatory signaling pathways triggered by heparan or dermatan sulfate-derived oligosaccharides. Prospective, longitudinal studies will need to be performed in order to evaluate the usefulness of these carotid measurements as predictors of adverse CAD outcomes in MPS patients.

A retrospective audit of anesthetic techniques and complications in children with mucopolysaccharidoses.

OBJECTIVES AND AIMS: To document the incidence of difficult airway management and difficult intubation in the era of replacement therapy for Australian children with mucopolysaccharidosis (MPS). BACKGROUND: Medical treatment for MPS has developed significantly since 1980's with a large number of patients now being offered either bone marrow transplant or enzyme replacement. The impact of these therapies on the incidence of difficult airway management has not been adequately documented. Similarly, anesthesia techniques and airway devices have been developed, which are thought to have greatly increased the safety of managing these patients under anesthesia but their role in children with MPS has not been systematically described. METHODS: A retrospective chart review of 17 patients with MPS who had received anesthetics at the Royal Children's Hospital during the time frame January 1998-January 2011. The primary outcome was the incidence of difficult or failed intubation. Secondary outcomes were the relationship between the incidence of difficult intubation and treatment with enzyme replacement therapy (ERT) or bone marrow transplantation. RESULTS: Seventeen patients received 141 anesthetics for 214 procedures. Difficult face mask ventilation occurred in 20 anesthetics (14.2%). Difficult intubation occurred in 40 anesthetics (25%). Failed intubation occurred in two cases (1.6%).The incidence of difficult intubation was 12% in MPS I, 35% MPS II, 86.7% in MPS VI, and 0% in MPS III and IV. CONCLUSIONS: Hematopoietic stem cell transplantation prior to 2 years of age reduces the incidence of difficult mask ventilation and difficult intubation in children with MPS I. ERT was initiated late in the clinical course of MPS II and VI and induced improvements in upper airway patency but did not reduce the incidence of difficult airway management.

The first cardiac transplant experience in a patient with mucopolysaccharidosis.

Hunter syndrome (MPSII) is a rare X-linked lysosomal storage disorder that can affect multiple systems but primarily affects the heart. We report the case of a previously asymptomatic 23-year-old patient who had an attenuated form of MPSII and presented with refractory heart failure that required a heart transplant. The diagnosis was confirmed by detection of an increase in urinary excretion of glycosaminoglycans, a deficiency in enzymatic activity, and molecular analysis. A myocardial biopsy revealed hypertrophic cardiomyocytes, mild fibrosis, and lysosomal storage in interstitial cells. Molecular analysis identified a novel mutation in the iduronate-2-sulfatase gene. Although the clinical outcome was not favorable, we believe that this approach may be valid in end-stage heart failure.