Multiple Cranial Nerve Enhancement: A New MR Imaging Finding in Metachromatic Leukodystrophy

Abstract

Metachromatic leukodystrophy (MLD) is a set of several disorders caused by deficient lysosomal activity. This deficiency results in accumulation of a metachromatic lipid material, galactosylceramide sulfatide, leading to the breakdown of the myelin sheath in both central and peripheral nervous systems, initially sparing the subcortical "U" fibers.1,2 Several MR imaging features of MLD have been described, but to the best of our knowledge, cranial nerve involvement demonstrated by MR imaging was never mentioned in this setting. An undernourished 2-year-old girl was hospitalized as a result of uncontrollable vomiting and retarded neuropsychomotor development. Deep tendon reflexes were abolished in the 4 limbs, and the plantar reflex showed bilateral extension response. The routine laboratory tests, cranial nerve examination, and funduscopy were unremarkable. Electroneuromyography showed signs of predominantly sensory peripheral neuropathy in the lower limbs, with a demyelinating pattern that involved all 4 of the limbs, and an ultrastructural examination of the sural nerve was carried out, which showed abnormalities consistent with MLD. The disease was confirmed by a severe decrease of arylsulfatase A activity in leukocytes (1.0 nmol/h/mg of protein; reference range, 5-20 nmol/h/mg).The baseline MR imaging scan showed bilateral and symmetrical involvement of the posterior periventricular white matter and splenium of the corpus callosum, sparing the U fibers. Gadolinium (Gd)-enhanced T1-weighted images showed bilateral and symmetrical abnormal enhancement of several cranial nerves, including the optic, oculomotor, trigeminal, abducens, facial, and vestibulocochlear nerves. The follow-up scan (Fig 1) demonstrated diffuse and symmetrical demyelination in the periventricular white matter and centrum semiovale, with numerous hypointense linear structures in a radiating ("tigroid") pattern, with involvement of the internal capsules, corticospinal tracts, cerebral peduncles, and cerebellar white matter. There was no evidence of leptomeningeal or parenchymal enhancement. There was no evidence of nerve hypertrophy. There was a considerable worsening of the neurologic deficits characterized by spastic tetraplegia without any contact with the environment.Cranial nerve Gd enhancement can be seen in a variety of entities, including neoplastic, infectious, demyelinating, and idiopathic diseases.3-5 Among leukodystrophies, cranial nerve involvement has been documented in infantile Krabbe disease. 6,7 Proposed mechanisms for the abnormal nerve root enhancement have included altered vascular permeability with breakdown of the blood-nerve barrier as a result of perivascular inflammation or infiltration 8 and enhancement in areas of active myelin breakdown. 6 We presume that multiple cranial nerve enhancement in MLD is secondary to the accumulation of the metachromatic lipid material and to the disruption of the myelin sheath, similar to the process that affects peripheral nerves. A future investigation with a larger series is requi...

Multiple Cranial Nerve Enhancement: Uncommon Imaging Finding in Early Infantile Krabbe's Disease

“…Bernal and Lenn 12 have suggested that abnormal cranial nerve enhancement may be secondary to myelin breakdown and a low‐grade inflammation similar to that seen in peripheral nerves. Multiple cranial nerve enhancement is also described in metachromatic leukodystrophy and proposed mechanisms have included altered vascular permeability with breakdown of blood‐nerve barrier as a result of perivascular inflammation 14 . Similar mechanisms have been proposed for spinal cord and nerve root involvement in early infantile Krabbe's disease.…”

“…Multiple cranial nerve enhancement is also described in metachromatic leukodystrophy and proposed mechanisms have included altered vascular permeability with breakdown of blood-nerve barrier as a result of perivascular inflammation. 14 There have been more than 60 described mutations in the galactosylceramidase gene, 6 which may contribute to the variable spectrum of imaging findings in early infantile Krabbe's disease. Routine noncontrast MR imaging techniques including spectroscopy are used to evaluate most leukodystrophies, except for cases with suspected adrenoleukodystrophy or adrenomyeloneuropathy.…”

Isolated Cranial Nerve Enhancement in Metachromatic Leukodystrophy

“…Cranial nerve enhancement has recently been described in metachromatic leukodystrophy, but in conjunction with cortical white matter involvement [8]. It has also been demonstrated, with cortical white matter abnormalities, in Krabbe’s disease [9].…”

“…It has also been demonstrated, with cortical white matter abnormalities, in Krabbe’s disease [9]. It has been proposed that cranial nerve enhancement may be due to disruption of the myelin sheath and accumulation of the metachromatic lipid material, affecting the cranial nerves in a manner similar to the peripheral nerves [7,8]. Isolated peripheral nerve enhancement on MRI early in the course of the disease has been seen in Krabbe’s [10] and striking peripheral nerve enhancement is also known to occur in MLD [11,12].…”

Sixth Cranial Nerve Involvement in Early Onset Krabbe Disease

“…Brain magnetic resonance imaging showed a confluent pattern of T2 signal hyperintensity involving both centrum semiovale, the posterior limb of the internal capsules, the bulbar pyramids, and the dentate nuclei (►Fig. Among leukodystrophies, multiple cranial nerve enhancement may be found on early onset Krabbe disease and metachromatic leukodystrophy [1][2][3][4][5] ; the mechanism responsible for this finding is still unclear, but it is probably related to demyelination and low-grade inflammation similar to that seen in peripheral nerves. 2,3 The finding of multiple cranial nerve enhancement, including CN VI involvement, adds specificity in the diagnosis of these entities, prompting an appropriate laboratory differential, and, in selected cases, referral for stem cell transplantation.…”