The spinocerebellar ataxias comprise a large and heterogeneous group of autosomal dominant ataxias. There are at least 28 subtypes identified. They lead to degeneration of the cerebellum and its tracts, but also of the brainstem, basal ganglia, cortex, and peripheral nervous system [7]. Although multiple studies have described various MRI findings in SCAs, no specific pattern of atrophy or sign is pathognomonic of a particular sporadic ataxia [8–10]. MRI findings correlate poorly with disease severity, with some asymptomatic carriers showing mild atrophy while mildly symptomatic patients may have normal imaging results [9]. Image processing methods have, however, produced interesting results that increased our understanding of the progression of some of the SCAs and their clinical correlations.

Friedreich’s ataxia is the most common autosomal recessive ataxia and is characterized by ataxia, head titubation, distal amyotrophy, and areflexia, Babinski sign, decreased joint position sense and vibratory sensation, cardiac involvement, and diabetes [54]. In most cases it is caused by a homozygous GAA intronic expansion at the frataxin gene (9q13) [54]. Prior to genetic testing becoming widely available, MRI findings provided initial clues to the clinical diagnosis of FRDA due to the major atrophy observed in the cervical spinal cord and a relatively normal cerebellum [55]. However, especially in patients with late-onset FRDA, cerebellar atrophy is not uncommon (Fig. 14.6) [56, 57]. A volumetric study measuring the cross-sectional area of the SCP found a 60 % reduction in the area in FRDA compared to controls. More importantly, SCP cross-sectional area inversely correlated with the Friedreich’s Ataxia Rating Scale scores and disease duration, and directly correlated with the age of onset [58].

Although GM atrophy has been concordant in most studies using different neuroimaging techniques (dorsal medulla, cerebellar hemispheres, the rostral vermis, dentate nucleus), WM involvement is discrepant [59–61]. França et al. [59] studied cerebral involvement by means of VBM and reported WM loss in the posterior cingulate gyrus, middle frontal gyrus and paracentral lobule, as well as inferomedial portions of cerebellar hemispheres and rostral vermis, while in another VBM study the WM loss was restricted to the posterior fossa [60]. França et al. corroborated their findings of WM changes with single voxel MRS acquired over the superior–posterior region of the right hemisphere at the level of the corpus callosum. They found a significant reduction of NAA/Cr in FRDA compared to controls. Two studies utilizing DTI confirmed the involvement of the WM in FRDA in areas outside the cerebellum and brainstem, though the particular regions identified were different among the studies [62, 63].

Ataxia Telangiectasia is the second most common autosomal recessive ataxia [64]. The onset is usually before age 5, and is characterized by progressive cerebellar ataxia, oculomotor apraxia , teleangiectasia, choreoathetosis, high risk of malignancy, recurrent sinopulmonary infections due to immunoglobulin deficiencies and enhanced sensitivity to ionizing radioactivity [64, 65]. At symptom onset, the MRI may be normal but as disease progresses there is considerable cerebellar atrophy (see Fig. 14.6) [66–68]. Cerebral capillary telangiectasias are best seen on postcontrast T1-weighted images or T2*-weighted gradient-echo images and cases with multiple brain telangiectasias in the brain and brainstem have been identified [69, 70]. There are few neuroimaging studies in AT. In a study using DWI and apparent diffusion coefficient (ADC) maps, authors calculate trace ADC values in 16 ROIs. ADC values of the cerebellar WM and cortex differentiated patients from controls with 100 % certainty. The cut-off ADC value of 0.699 mm²/s in the middle cerebellar cortex yielded 100 % sensitivity and specificity [71]. Contrary to other cerebellar ataxias that usually show reduced NAA levels on MRS, cases with AT show an increase in cerebellar Cho levels, suggesting an ongoing process of cellular degeneration and membrane breakdown [70].

Fragile-X-associated tremor/ataxia syndrome is caused by a CGG expansion (55–200 repeats; premutation range) of the fragile X mental retardation 1 (FMR1) gene. FXTAS is clinically characterized by action tremor, cerebellar ataxia, cognitive and psychiatric symptoms . The primary MRI findings consist of atrophy of the cerebral hemispheres, brainstem, and cerebellum, along with increased T2 signal intensity in the WM of the MCP and the WM surrounding the dentate nuclei (see Fig. 14.2) [72]. Other findings include increased T2 or FLAIR signal in periventricular and deep WM regions of the cerebral hemispheres and corpus callosum [72]. A VBM study compared three groups: symptomatic premutation carriers (PFX+), asymptomatic premutation carriers (PFX−) and controls [73]. When compared to healthy controls, PFX+ had significant GM reduction in mostly the frontal lobes, but also temporal, parietal, and occipital lobes, cerebellum, and thalamus. The bilateral posterior superior/middle temporal gyri also showed increased GM in the PFX+ group. A comparison of PFX+ and PFX− showed GM reductions in the cerebellum, dorsomedial prefrontal cortex, and precuneus in the PFX+ group. Other findings included significant neuroimaging and clinical correlations such as: GM loss in the left amygdala and increased levels of obsessive–compulsiveness and depression; decreased GM in the left inferior frontal cortex and anterior cingulate cortex and poor working memory performance; clinical severity and a reduction of vermal GM [73]. Female patients with FXTAS present a similar pattern of cerebral and cerebellar involvement, though to a lesser degree [74]. Significant WM compromise is also present in FXTAS. Patients with FXTAS showed decreased FA in several WM tracts, mostly the MCP, SCP, cerebral peduncle, fornix, and stria terminalis. Axial and radial diffusivities were increased in the MCP of asymptomatic premutation carriers [75].

Prefrontal cortex impairment seems to be responsible for the cognitive dysfunction in FXTAS. Functional MRI (fMRI) performed during a verbal working memory task in symptomatic and asymptomatic carriers exhibited reduced activation in the right ventral inferior frontal cortex and left premotor/dorsal inferior frontal cortex when compared to controls. Symptomatic carriers showed decreased activation of the right premotor/dorsal inferior frontal cortex. There was also a negative correlation between the right ventral inferior frontal cortex activity and the levels of FMR1 mRNA after excluding the effect of disease severity [76].

Autosomal Recessive Spastic Ataxia of Charlevoix–Saguenay is a neurodegenerative disease that encompasses early onset spasticity, cerebellar ataxia, distal amyotrophy, peripheral neuropathy, skeletal deformities, and retinal hypermyelination [65]. It is caused by mutations in the SACS gene. MRI shows early atrophy of the superior vermis and progressive atrophy of the cerebellar hemispheres and the spinal cord (see Fig. 14.6) [66]. A linear hypointensity on T2-weighted images and FLAIR may be present in the pons [66, 77]. This area has been shown to be the pontocerebellar fibers, using diffusion tensor color encoded MRI maps, whereas the pyramidal tracts were thin and not in their usual location [78]. Recently, hypointense lesions in the MCP were described in T2-weighted and FLAIR images [79].

In ataxia with oculomotor apraxia (AOA)-1 and AOA-2, cerebellar atrophy occurs early in the course of the disease and is present in the vast majority of patients [66, 80]. There are very few reports of MRI in ataxia with isolated vitamin E deficiency (AVED) [66] (see Fig. 14.6).

Multisystem Atrophy is a neurodegenerative disease clinically characterized by a variable combination of autonomic, cerebellar, parkinsonian, and pyramidal signs [81]. The distinctive neuropathological feature is glial cytoplasmic inclusions in oligodendroglial cells [1]. Clinically, MSA is usually divided in two subtypes: one with a predominant parkinsonism (MSA-P) and another with predominant cerebellar findings (MSA-C). Routine MRI is the most important diagnostic test in MSA and the introduction of different sequences and imaging analyses have improved the diagnosis and may lead to potential surrogate biomarkers [81]. Most imaging studies of MSA typically focus on differentiating the various atypical parkinsonisms from idiopathic PD [82–88]. Since this is beyond the scope of this chapter, we will concentrate on MSA-C.

The most common MRI findings are a hyperintense rim at the lateral edge of the dorsolateral putamen and the “hot cross bun” sign (see Fig. 14.3) [1, 89]. However, the latter has been described in other ataxias, including SCA2, SCA3, SCA7, and SCA8 [90, 91]. Significant infratentorial atrophy is also noted.

Studies comparing MSA-P to MSA-C have demonstrated a similar pattern of cerebral compromise, however, with a differential degree of atrophy within the involved areas [92–95]. A VBM and voxel-based relaxometry study comparing MSA-C and MSA-P showed differences only in the infratentorial ROIs, which were more severe in MSA-C than in MSA-P [92]. Conversely, comparing to controls, Wang et al. [94] found an increase in ADC values in the MCP and cerebellum; a reduction in FA in the pyramidal tract, MCP, and WM of the cerebellum in both MSA-C and MSA-P. This confirmed a previous study that found increased ADC values at the MCP and pons in MSA-C [96]. In addition, isotropic diffusion-weighted image (DWI) values were decreased in the cerebellar cortex and deep cerebellar nuclei in MSA-C and increased in the basal ganglia in MSA-P [94]. Pellecchia et al. [93] used DWI images and measured the diffusion Trace(D) brain maps. They demonstrated that in MSA-P Trace(D) values were significantly increased in the putamen, while in MSA-C Trace(D) values were significantly higher in the cerebellar WM and MCP.