Saturday 6 August 2011

Mucopolysaccharidosis MRI Brain

A ~7 yo boy with mental retardation.
On clinical examination – Macrocephaly.

MRI Brain axial T2 images show enlarged peri vascular spaces in Centrum semi ovale. Metopic beaking in frontal region despite of macrocrania. 
Diffuse cerebral cortical atrophy.
Cord compression at CV junction on sagittal T2 images due to short posterior arch of C1.
Radiograph of dorso lumbar spine lateral view show beaking of L1 with exaggerated anterior curvature at dorso lumbar junction.
Usg abdomen revealed no hepato spleenomegaly.

Imaging wise diagnosis : Mucopolysaccharidosis (MPS) or its variant is possible.

Mucopolysaccharidoses (MPS)

Inherited disorder of metabolism characterized by enzyme deficiency and inability to break down Glycosaminoglycan (GAG), failure to break down result in accumulation of toxic intracellular substrates.

GAG accumulates in brain and is toxic to neurons leading to neuronal loss result in dilated VR spaces. CNS spared in MPS 4 (Morquio)

In CT / MRI Brain imaging wise best diagnostic clue Perivascular spaces (PVS), also known as Virchow-Robin spaces (VRS), dilated by accumulated GAG common in white matter, corpus callosum (CC), peritrigonal white matter (WM), can occur in other lobes. Dilated VR spaces gives Cribriform appearance to the White matter.
Size varies usually less than 5 mm and number vary from few to too many to count. Shape varies from round, oval, spindle are often parallel to veins. 

Other important associated findings are Metopic beaking despite macrocrania. 
May see aditional patchy WM signal abnormality around VR Spaces. 
In spine, at CV junction cord compression seen in majority of MPS due to C2 meningeal hypertrophy and Short C1 posterior arch. May see atlantoaxial subluxation secondary to Progressive odontoid dysplasia.
In rest of the spine screening, may see Upper lumbar gibbus in MPS 1H (Hurler) with Inferior beaking and MPS 4 (Morquio) with Middle beaking of vertebra. 

GAG also accumulates in most other organs/ligaments
In liver and spleen leading to Hepatosplenomegaly.
Umbilical hernia.
Skeletal dysostosis multiplex, joint contractures
Arterial wall (mid-aortic stenosis) and cardiac valve thickening
Coarse facies (formerly called "gargoylism")
Submucosal deposition in pharynx lead to small, abnormal shape trachea with abnormal configuration vocal cords may lead to Upper airway obstruction and intubation difficult.
Dermal melanocytosis (mongolian-like spots) are extensive, blue skin pigmentation differs from typical mongolian spots in persistence or progression.

Velocardiofacial syndrome (microdeletion Chr 22):
Dilated VR spaces and plaques, typically frontal predominance.
Deviated carotid arteries in pharynx a clue.
Macrocephaly with dilated VRS:
Lacks typical beaked metopic suture and foramen magnum compression
Hypomelanosis of Ito:
Periventricular signal change (brighter and more persistent than MPS) with large VRS
May also have hemimegalencephaly
Typical whorled skin lesions
Lack "beaked" metopic suture present in MPS
Normal VR spaces:
Vary in number and prominence, common with increasing age.

Clinical presentation
Age: MPS IH presents in infancy.
Gender: MPS 2 (Hunter) is X-linked: Male
Prevalence of specific MPS disorders varies with country.

Typical coarse facies (mild in MPS 3,6,7)
Macroglossia, bushy eyebrows, flat nasal bridge.
Prototype MPS 1H, appear normal at birth.
Corneal clouding (except MPS 2): Proteoglycans in keratocytes
Mental retardation (significant except MPS 2b, 4, 1HS)
Joint contractures, dysostosis multiplex, short stubby fingers, carpal tunnel syndrome
Loses walking skills: Spinal claudication / myelopathy at Cl-2 and vascular claudication from mid-aortic stenosis
Recurrent upper respiratory infection, nasal discharge, ear infections, sleep apnea, sensorineural deafness.
Middle ear effusions.

BMT or IV recombinant human enzyme (e.g., MPS 1H: Murine embryonic stem cell models under evaluation for gene therapy.

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