• Infantile Neuroaxonal Dystrophy: Case Report with MRI Findings and Review of Literature
Infantile Neuroaxonal Dystrophy
A 2 year old female child, from Saudi Arabia presented with complaints of regression of developmental milestones initially motor and then cognitive. She was unable to hold her head properly. She also could not walk properly with loss of speech articulation. The parents were consanguineous. Recognition of family members by the patient was occasional. Patient smile was occasional with poor interaction. Patient head size was normal with no dysmorphism or neurocutaneous markers. On examination patient eyes did not follow light with fundus examination revealing bilateral optic nerve atrophy. Generalized hypotonia was present with paucity of spontaneous movements.
MRI brain revealed diffuse cerebellar atrophy with T2W/FLAIR cerebellar cortex hyperintensity (Figure 1). Bilateral symmetrical T2W/FLAIR hyperintensity was seen in globus pallidus (Figure 2) and bilateral deep parieto-occipital periventricular white matter (Figure 3). Thin vertically oriented splenium of corpus callosum and apparent clavum hypertrophy were also seen in sagittal T2W images (Figure 4). The ADC maps revealed high signal intensity and increased ADC values in the cerebellar parenchyma (ADC value in cerebellar parenchyma was 1.2-1.5 x 10 -3 mm2/s) and normal signal intensity and ADC values in dentate nuclei (ADC value in dentate nuclei was 0.96 -1.0 x 10 -3 mm2/s) compared with values in normal regions of brain .ADC values in affected deep periventricular cerebral white matter was mildly elevated (1.2-1.3 x 10 -3 mm2/s) as compared to normal fronto-parietal white matter (0.8 x 0.9 x 10 -3mm2/s). EEG showed delta activity with superimposed beta activity which was suggestive of diffuse cerebral dysfunction. VEP showed absent P2 waves suggestive of visual pathway dysfunction with poor visual acuity. NCV was normal. Tandem Mass Spectrometry and urine Gas chromatography-Mass Spectrometry for inborn error of metabolism were negative. Ultrasound abdomen revealed no significant abnormality with normal size of liver and spleen. 2-D echo findings were normal. Diagnosis was finally confirmed with molecular genetic testing and the finding of PLA2G6 mutation.
[1, 3]Neurodegeneration with Brain Iron Accumulation (NBIA) represent a class of neurodegenerative diseases characterize by progressive motor symptoms, extrapyramidal movement disorder, intellectual deterioration, and radiologically discernible brain iron accumulation. The major childhood NBIA syndromes include pantothenate kinase associated neurodegeneration (PKAN), fatty acid hydroxylase associated neurodegeneration (FAHN), mitochondrial membrane protein associated neurodegeneration (MPAN), betapropellar protein associated neurodegeneration (BPAN) and phospholipase A2 associated neurodegeneration (PLAN) . PLA2G6 gene mutations account for approximately 20% of childhood onset NBIA. PLAN is a continuum of three distinct, yet overlapping phenotypes: classical infantile onset neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (NAD) of childhood onset and PLA2G6 related dystonia-pakinsonism with onset in childhood. Infantile onset INAD is the most common of PLA2G6 – associated neurodegeneration (PLAN). Infantile neuroaxonal dystrophy (INAD) is an extremely rare, autosomal recessive inherited degenerative disorder of the nervous system characterized by abnormalities of nerve endings (axon terminals) within the brain and spinal cord (central nervous system) and outside the central nervous system (peripheral nerves and terminals). INAD is typified by developmental arrest, then regression of language and motor skills. INAD is characterized mainly by a pyramidal syndrome with spastic tetraplegia, axial hypotonia, bulbar dysfunction, contractures, spinal deformities, dystonia, cerebellar dysfunction and optic nerve atrophy with visual impairment. A progressive peripheral neuropathy leads to hyporeflexia. Ataxia/dysmetria may also be seen. Atypical childhood onset NAD may present with progressive spasticity, ataxia, and dystonia, along with optic atrophy, peripheral neuropathy, and cognitive impairment. [1-9] Histopathologically, the most characteristic microscopic features in INAD are cerebellar atrophy with gliosis, widespread axonal spheroid formation, and abnormal myelin patterns. Swollen, dystrophic axons are present in both the central nervous system and the peripheral nervous system. [1, 2, 4, 5, 7, 8, 9]Significant cerebellar atrophy, mainly involving inferior part of the vermis and hyperintensity of the cerebellar cortex on T2W/FLAIR images are the most characteristic MR findings observed in INAD patients. The absence of the signal hyperintensity of the cerebellar cortex however does not rule out the diagnosis of INAD. [1-9] The spectrum of MR abnormalities observed in INAD patients is however extremely wide. Cerebral cortical atrophy, hyperintensity of posterior periventricular cerebral white matter, thinning of the optic chiasm, elongated vertically oriented splenium and signal hyperintensity in the dentate nuclei consistent with pathologic data can also be seen. Iron deposition with bilateral symmetrical T2W
Considering the wide spectrum of clinical features, mutations in PLA2G6 gene and MR findings in INAD mentioned above; diffuse cerebellar atrophy on MRI is the most consistent and characteristic feature of INAD with variable DWI and other findings. Presence of cerebellar atrophy therefore should arouse suspicion of INAD because it has not been described in any other neurodegenerative disease with the same age onset.