Supportive clinical evidence from sibling studies suggests that early intervention provides multiple opportunities to improve patient outcomes through disease-specific management and early initiation of ERT, if available.1–6
ERT, whether initiated early or later in life, has been shown to improve key clinical parameters, such as endurance and pulmonary measures, which are critical to quality of life, maintenance of ambulation, and activities of daily living.7,8
The new era of management for progressive, complex, genetic conditions, such as mucopolysaccharidosis (MPS) disorders, hinges on the efficient coordination of each patient’s healthcare team by a medical home.1
Geneticists and/or metabolic specialists are typically at the centre and help to coordinate multidisciplinary care and an individualised management plan.2,3
Neurologists play a critical role in multidisciplinary coordinated care. Brain and spinal involvement are often prominent features of the disease, and some manifestations can be addressed with surgical intervention.3–6
Signs and symptoms can vary widely in frequency and disease progression across and within MPS subtypes, making continued neurological assessment a key component to effective management of these patients.3–6
Many MPS disorders have available management guidelines and
speciality-specific consensus recommendations regarding lifelong management of MPS. Guidelines typically recommend the following:3,7
For neurologists managing patients with MPS, an understanding of the exact neurological involvement associated with a patient’s specific MPS subtype can inform management approaches.2
Common neurological features of MPS by subtype are outlined below.
A number of expert reviews are available that present state‐of‐the‐art practices in the assessment and monitoring of brain and spinal abnormalities in patients with MPS.3–5,8 Many MPS disorders also have available management guidelines and neurology‐specific consensus recommendations regarding chronic care.3,7,9
The reviews and guidelines include the following overarching recommendations:
The goals of these neurological assessments in patients with MPS include:4,5,8
As an example, the tables below detail suggested schedules for general and spinal-specific neurological evaluation of patients with Morquio A (MPS IVA), an MPS subtype with predominant spinal abnormalities.
As seen above, neurological examination, as well as brain and spinal imaging, are cornerstones of neurological assessment in patients with MPS.3,5,8
Common brain and spinal MRI findings according to MPS subtype are summarised below.
Initial and continued spinal imaging is critical for patients with MPS, as spinal abnormalities account for a high proportion of neurological manifestations and can lead to paraplegia, quadriparesis, and death.4 In Morquio A and MPS VI especially, spinal abnormalities are some of the most prominent features of neurological disease and frequently require surgical intervention.4–6
Comprehensive risk assessment and stratification for spinal abnormalities in MPS generally consists of:5
Spinal MRI features most commonly associated with MPS include these vertebral/disc abnormalities and craniocervical junction abnormalities:4
Brain imaging by MRI is another key component of initial patient assessment and ongoing monitoring. The majority of MPS subtypes (I, II, III, VII) are associated with MRI abnormalities consistent with progressive and primary neurological etiology.4,8
In patients with MPS disorders with primary neurological progression, the following are the most common MRI features in the brain:4,6
Of note, a unique MRI feature described in patients with MPS disorders with primary neurological progression is the ‘honeycomb‐like’ appearance in the basal ganglia and thalami.4 Additional MRI features have been described in multiple case reports across MPS disorders, although these are much less frequently observed.
Existing MRI scoring systems for both spinal cord and brain disease in MPS are intended to standardise procedures for evaluating and monitoring neuroimaging alterations in patients with MPS so that proper treatment can be offered before irreversible damage occurs. These scoring systems are detailed in the tables below.8
Frequency of assessments and involvement of specific specialists vary across the different MPS types. For patients with MPS diseases associated with primary neurodegenerative and cognitive complications, such as MPS I, II, and III, additional and regular neurobehavioral and psychiatric evaluations are recommended.7,10,11
In addition to speciality-specific assessments that should be done to facilitate positive long-term outcomes for patients with MPS, important steps can be taken by the coordinating physician, typically the geneticist and/or metabolic specialist, related to general health. Their role in educating other healthcare professionals (e.g. dentists, physiotherapists, paediatricians, family doctors) and families about the disease and general management strategies is critical and should include:
Speciality-specific assessments, as well as regular physical examinations and overall health interventions, should follow recommended guidelines, which may vary among MPS subtypes.3
Improvements in the treatment of MPS disorders are contributing to long-term outcomes for patients, necessitating new approaches to lifelong management.
As patients age, some may begin to manage their own healthcare, making physician-guided transition to the adult setting critical.3 Physicians should ensure the following:
The transition from paediatric to adult care and long-term adult care are critical areas to address in care plans for adolescent and adult patients.2 Long-term care considerations are ideally best addressed in a centre with significant MPS experience, and they require careful coordination across specialities.3,13 Long-term issues include but are not limited to the following:
Long-term management of MPS disorders, including ongoing assessments and a site-specific transition strategy from paediatric to adult care, may lead to sustained improvement in quality of life and a better future for your patients.3,6,13
Because clinical manifestations of mucopolysaccharidosis (MPS) disorders are multisystemic, a patient-specific, multidisciplinary approach is required to proactively recognise and manage complications. The involvement of a neurologist in this process is key, as surgical management of spinal complications (e.g. cervical fusion and/or decompression) is often necessary.1
Patients with MPS disorders typically have a number of surgical interventions over their lifetimes. A natural history study assessing a cohort of 325 patients with Morquio A (MPS IVA) found that over 70% of patients had at least one surgical procedure.2
Patients with MPS have a high perisurgical mortality rate due to multiple factors, including upper and lower airway obstruction, cervical spinal instability, respiratory impairment, cardiovascular morbidities, and frequent infections.2-4 For example, surgical complications resulted in an 11% mortality rate in patients with Morquio A (n=27).5
Creating a surgical plan is crucial and involves a multidisciplinary team of specialists who are, ideally, also experienced in treating patients with MPS.3
Neurology-specific procedural care often includes surgical management of spinal complications. The overall goals of spinal surgery in patients with MPS include the following:1
Additional neurology-specific procedural interventions are presented below.
Indications for spinal surgery include the development of pathological reflexes and neurological deficits on neurological examination with instability, or cord compression with signal change on magnetic resonance imaging (even without symptoms).1
Surgical risk assessment and perioperative monitoring are fundamental components of a tailored surgical plan, and they can reduce the risks of negative surgical outcomes and mortality in patients with MPS.1,3,11