Alexander disease

Abstract

Signal abnormalities or atrophy of the medulla or spinal cord on MRI are sufficient to warrant DNA analysis for Alexander disease. Ventricular garlands constitute a new sign of the disease. Unusual phenotypes of Alexander disease are found among patients with late onset and protracted disease course.

Late onset Alexander’s disease presenting as cerebellar ataxia associated with a novel mutation in the GFAP gene

“…In accordance with previous reports of AOAD, clinical progression in our patient was relatively slow compared with that seen in childhood onset of AD [1,[4][5][6]. In summary, sequencing of the GFAP gene should be considered in cases of late onset cerebellar ataxia, in particular in the presence of MRI findings compatible with AD.…”

“…The present case report highlights the importance of MR imaging in the differential diagnosis of adult onset leukodystrophies. Although our patient met only three out five MRI criteria for AD [7], the severe atrophy of the medulla oblongata along with signal abnormalities in the hilus of the dentate nucleus were suggestive of AOAD [5,6,8]. However, the symmetrical signal abnormalities of the globus pallidus on T2-weighted images are only rarely seen in AOAD [5,6,8].…”

“…Nearly all AD mutations involve amino acid substitutions, and a dominant toxic or gain-of-function effect for mutant GFAP protein was hypothesized [2,3]. While AD in infants and children typically presents with psychomotor retardation, seizures, ataxia and progressive spasticity leading to death within a few years [1,2], clinical phenotypes with AOAD vary considerably and the clinical course is more protracted [4][5][6]. MRI criteria have been proposed for the diagnosis of AD [7].…”

“…MRI criteria have been proposed for the diagnosis of AD [7]. However, more recent case series of patients with AOAD involving individuals with atypical clinical and MRI features not fully meeting the above diagnostic criteria, suggest that the spectrum of clinical phenotypes of AOAD may be broader than previously expected [4][5][6]8].…”

Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter

“…A first clinical trial, where human neural stem cells were transplanted in the frontal white matter of patients with PMD, showed no adverse effects and indications of myelination on MRI in the transplanted regions (Gupta et al, 2012). Remarkably, most transplantation studies have so far focused on the brain, while many leukodystrophies also show spinal cord involvement, such as Alexander disease (Liu et al, 2016; van der Knaap et al, 2006), PMD (Koeppen & Robitaille, 2002), MLD (Toldo, Carollo, Battistella, & Laverda, 2005) and Krabbe disease (Wang, Melberg, Weis, Mansson, & Raininko, 2007). In rodent models of spinal cord injury, glial transplantations in the spinal cord resulted in decreased pathology and functional recovery (Haidet‐Phillips et al, 2014; Li et al, 2015; Nicaise, Mitrecic, Falnikar, & Lepore, 2015).…”