1. AnswerB. Giant axonal neuropathy.2. DiscussionThe T2-weighted MRI (Fig. 1 of Images in Neuroscience: Question) shows hyperintensity of the dentate nuclei, dorsal brainstem tracts and cerebellar white-matter as well as diffuse white-matter hyperintensity with involvement of the globi pallidi and the posterior limb of internal capsules. There is relative sparing of the callosum and U-fibers. By this patient’s age (6 years), myelination is usually complete, with the exception of the ventricular trigones. These MRI findings are typical of giant axonal neuropathy (GAN).[1]van der Knaap M.S. Valk J. Magnetic resonance of myelination and myelin disorders.Third ed. Springer, Berlin Heidelberg New York2005Crossref Google Scholar Diffusion weighted imaging shows facilitated diffusion in the white matter tracts while magnetic resonance spectroscopy (MRS) shows reduction in N-acetyl aspartate. Increased diffusion would suggest increased mobility of water molecules in the brain,2Alkan A. Sigirci A. Kutlu R. et al.Giant axonal neuropathy: diffusion weighted imaging features of the brain.J Child Neurol. 2006; 21: 912-915Crossref PubMed Scopus (6) Google Scholar, 3Demir E. Bomont P. Erdem S. et al.Giant axonal neuropathy: clinical and genetic study in six cases.J Neurol Neurosurg Psychiatry. 2005; 76: 825-832Crossref PubMed Scopus (41) Google Scholar which, when considered with the MRS finding, would suggest neuronal loss, demyelination and glial proliferation in these patients.Light microscopy of the sural nerve biopsy specimen shows the nerve bundles displayed in transverse and longitudinal planes. The characteristic giant axons are scattered between the nerve fibers, and associated with features of Wallerian degeneration (Mason trichrome, ×200). The curly hair of the patient is also seen (Fig. 2 of Images in Neuroscience: Question).GAN is a rare autosomal recessive disorder affecting both the central and peripheral nervous systems. It is caused by mutation of the GAN gene on chromosome 16q24.1 encoding the protein gigaxonin. Gigaxonin is known to enhance microtubule stability by binding directly to microtubule-associated protein 1B light chain. It has a crucial role in the crosstalk between the intermediate filaments and the membrane network.[4]Bruno C. Bertini E. Federico A. et al.Clinical and molecular findings in patients with giant axonal neuropathy (GAN).Neurology. 2004; 62: 13-16Crossref PubMed Scopus (51) Google Scholar The mutation results in a generalized disorganization of intermediate filament networks. The hallmark of the disease is the presence of giant axonal swellings, which are densely packed with aberrant neurofilaments leading to axonal neuropathy. The accumulation of neurofilaments is again responsible for the various cranial MRI findings. Keratin intermediate filaments are also altered, leading to the characteristic kinky hair. 1. AnswerB. Giant axonal neuropathy. B. Giant axonal neuropathy. 2. DiscussionThe T2-weighted MRI (Fig. 1 of Images in Neuroscience: Question) shows hyperintensity of the dentate nuclei, dorsal brainstem tracts and cerebellar white-matter as well as diffuse white-matter hyperintensity with involvement of the globi pallidi and the posterior limb of internal capsules. There is relative sparing of the callosum and U-fibers. By this patient’s age (6 years), myelination is usually complete, with the exception of the ventricular trigones. These MRI findings are typical of giant axonal neuropathy (GAN).[1]van der Knaap M.S. Valk J. Magnetic resonance of myelination and myelin disorders.Third ed. Springer, Berlin Heidelberg New York2005Crossref Google Scholar Diffusion weighted imaging shows facilitated diffusion in the white matter tracts while magnetic resonance spectroscopy (MRS) shows reduction in N-acetyl aspartate. Increased diffusion would suggest increased mobility of water molecules in the brain,2Alkan A. Sigirci A. Kutlu R. et al.Giant axonal neuropathy: diffusion weighted imaging features of the brain.J Child Neurol. 2006; 21: 912-915Crossref PubMed Scopus (6) Google Scholar, 3Demir E. Bomont P. Erdem S. et al.Giant axonal neuropathy: clinical and genetic study in six cases.J Neurol Neurosurg Psychiatry. 2005; 76: 825-832Crossref PubMed Scopus (41) Google Scholar which, when considered with the MRS finding, would suggest neuronal loss, demyelination and glial proliferation in these patients.Light microscopy of the sural nerve biopsy specimen shows the nerve bundles displayed in transverse and longitudinal planes. The characteristic giant axons are scattered between the nerve fibers, and associated with features of Wallerian degeneration (Mason trichrome, ×200). The curly hair of the patient is also seen (Fig. 2 of Images in Neuroscience: Question).GAN is a rare autosomal recessive disorder affecting both the central and peripheral nervous systems. It is caused by mutation of the GAN gene on chromosome 16q24.1 encoding the protein gigaxonin. Gigaxonin is known to enhance microtubule stability by binding directly to microtubule-associated protein 1B light chain. It has a crucial role in the crosstalk between the intermediate filaments and the membrane network.[4]Bruno C. Bertini E. Federico A. et al.Clinical and molecular findings in patients with giant axonal neuropathy (GAN).Neurology. 2004; 62: 13-16Crossref PubMed Scopus (51) Google Scholar The mutation results in a generalized disorganization of intermediate filament networks. The hallmark of the disease is the presence of giant axonal swellings, which are densely packed with aberrant neurofilaments leading to axonal neuropathy. The accumulation of neurofilaments is again responsible for the various cranial MRI findings. Keratin intermediate filaments are also altered, leading to the characteristic kinky hair. The T2-weighted MRI (Fig. 1 of Images in Neuroscience: Question) shows hyperintensity of the dentate nuclei, dorsal brainstem tracts and cerebellar white-matter as well as diffuse white-matter hyperintensity with involvement of the globi pallidi and the posterior limb of internal capsules. There is relative sparing of the callosum and U-fibers. By this patient’s age (6 years), myelination is usually complete, with the exception of the ventricular trigones. These MRI findings are typical of giant axonal neuropathy (GAN).[1]van der Knaap M.S. Valk J. Magnetic resonance of myelination and myelin disorders.Third ed. Springer, Berlin Heidelberg New York2005Crossref Google Scholar Diffusion weighted imaging shows facilitated diffusion in the white matter tracts while magnetic resonance spectroscopy (MRS) shows reduction in N-acetyl aspartate. Increased diffusion would suggest increased mobility of water molecules in the brain,2Alkan A. Sigirci A. Kutlu R. et al.Giant axonal neuropathy: diffusion weighted imaging features of the brain.J Child Neurol. 2006; 21: 912-915Crossref PubMed Scopus (6) Google Scholar, 3Demir E. Bomont P. Erdem S. et al.Giant axonal neuropathy: clinical and genetic study in six cases.J Neurol Neurosurg Psychiatry. 2005; 76: 825-832Crossref PubMed Scopus (41) Google Scholar which, when considered with the MRS finding, would suggest neuronal loss, demyelination and glial proliferation in these patients. Light microscopy of the sural nerve biopsy specimen shows the nerve bundles displayed in transverse and longitudinal planes. The characteristic giant axons are scattered between the nerve fibers, and associated with features of Wallerian degeneration (Mason trichrome, ×200). The curly hair of the patient is also seen (Fig. 2 of Images in Neuroscience: Question). GAN is a rare autosomal recessive disorder affecting both the central and peripheral nervous systems. It is caused by mutation of the GAN gene on chromosome 16q24.1 encoding the protein gigaxonin. Gigaxonin is known to enhance microtubule stability by binding directly to microtubule-associated protein 1B light chain. It has a crucial role in the crosstalk between the intermediate filaments and the membrane network.[4]Bruno C. Bertini E. Federico A. et al.Clinical and molecular findings in patients with giant axonal neuropathy (GAN).Neurology. 2004; 62: 13-16Crossref PubMed Scopus (51) Google Scholar The mutation results in a generalized disorganization of intermediate filament networks. The hallmark of the disease is the presence of giant axonal swellings, which are densely packed with aberrant neurofilaments leading to axonal neuropathy. The accumulation of neurofilaments is again responsible for the various cranial MRI findings. Keratin intermediate filaments are also altered, leading to the characteristic kinky hair.