**3.8 Friedreich's ataxia**

Since the identification of the FRDA gene and the GAA trinucleotide expansion that causes FRDA, phenotypic variants of this ataxia have been regularly reported in individuals with pathogenic mutations [44, 46]. Some of these variations do not correspond to how this sickness is usually described. Atypical phenotypes include movement abnormalities, pyramidal signals, preserved reflexes, late-onset and verylate-onset ataxia, minor GAA expansions, and ataxia [47, 48].


### **Table 1.**

*The most prevalent kinds of autosomal recessive cerebellar ataxias with genetic definition.*

Friedreich's ataxia is largely an ataxia of the efferent and sensory nerves where neuropathological investigations and more recent neuroimaging studies have both verified the existence of a cerebellar component (**Figure 2**) [44, 46, 49]. Nevertheless, antioxidants like coenzyme Q10 and its derivatives, such as idebenone, have been employed, despite the lack of agreement on a cure. Although it is ineffective for neurological disorders, idebenone has demonstrated notable advantages for hypertrophic cardiomyopathy [50, 51]. Deferiprone and epigenetic treatment for Friedreich's ataxia have both recently undergone testing, as have other novel medications [52, 53].

### **3.9 Ataxia telangiectasia**

More than 200 potentially harmful mutations affecting virtually all of the ataxia telangiectasia-mutated (ATM) gene's coding exons have been identified since the ATM gene was initially characterized [54]. In addition to the typical phenotype with cerebellar ataxia and oculocutaneous telangiectasia, many instances of ataxia telangiectasia with milder phenotypes have been documented (**Figure 3**). These phenotypes involve later diagnosis, lower progression of the disease, longer life expectancy, an affinity for movement disorders such as dystonia, myoclonus, and chorea instead of cerebellar ataxia, an absence of ocular telangiectasia, decreased levels of chromosomal instability and cellular radiosensitivity, as well as the absence of ocular telangiectasia [45, 54]. Actually, ataxia telangiectasia is a multisystem disorder with a range of neurological and systemic symptoms. A more appropriate name for this condition has been suggested: as ATM syndrome.

### **3.10 Spinocerebellar ataxia**

Spinocerebellar ataxias (SCAs) are a sizable and intricate collection of diverse autosomal dominant degenerative illnesses that affect several parts of the

### **Figure 2.**

*Sagittal image of a T2-weighted MRI of the spinal cord of patient presenting Friedreich's ataxia with cervical spinal cord atrophy [23].*

### **Figure 3.** *A patient with ataxia telangiectasia with conjunctival telangiectasia [23].*

neurological system, including the cerebellum and its efferent and afferent connections [25, 26, 28–30, 34, 55–57]. **Table 2** lists the most common SCA subtypes along with the genetic locations, mutations, and proteins linked to each condition from SCA type 1 through SCA type 40. The most prevalent form of SCA is type 3, while types 1, 2, 6, and 7 have significantly different prevalence depending on the racial makeup of the population [25–30, 34, 57]. The genetic etiology of illness is still unknown in roughly 40–50% of ARCAs, despite great progress in the discovery of ARCA genes [58–64]. With the exception of ataxia brought on by a vitamin E shortage and a set of ataxias linked to a coenzyme Q10 deficiency, there is no known therapy for these ataxias [26, 29, 30, 58, 63].


*Ataxia in Multiple Sclerosis: From Current Understanding to Therapy DOI: http://dx.doi.org/10.5772/intechopen.112013*


### **Table 2.**

*Genetic characteristics of spinocerebellar ataxias.*

Other SCAs cover a wide range of clinical symptoms. As opposed to the normal phenotype, which comprises of cerebellar ataxia and epilepsy, the major phenotype seen in the latter is pure cerebellar [29, 30]. It is worth mentioning that several additional SCAs with novel loci and gene mutations have been described more recently and SCA patients have a relatively high number of mutations, however, many patients (30–40%) still lack a genetic or molecular diagnosis [34, 57].

### **3.11 Secondary ataxias**

Secondary or acquired ataxias include ataxias arising from exogenous or endogenous nongenetic origins, including those naturally caused toxins, paraneoplastic, immune-mediated agents, and infections, as well as focal injury to the cerebellum [26, 65, 66]. In MS, inflammation attacks and damages nerve fibers and myelin, a protective tissue around the nerves of the brain and spinal cord. Eventually, nerve cells that control body movements by sending and receiving electrical signals are damaged, which leads to abnormalities in body movement. In patients with MS, three types of ataxias are cerebellar, sensory (proprioceptive ataxia), and vestibular ataxia. Cerebellar ataxia is a syndrome that encompasses gait ataxia, nystagmus, dysarthria, tremor, and cognitive dysfunction, among others [67]. It is caused by damage to the cerebellum, leading to disruptions in the actions of different nerves that control muscle and movements on one or both sides of the body. Vestibular ataxia causes loss of balance, vertigo, dizziness, nausea, and vomiting, among others. Some people with MS develop vestibular ataxia slowly, so they just have a loss of balance or equilibrium, not other severe symptoms. Vestibular ataxia is caused by damage to the vestibular system (i.e., inner ear structures and fluid-filled ear canals that control the sense of balance) and it might also be caused by lesions in the brainstem, or if MS pathology affects nerves that connect tiny organs in the inner ear that control balance. In this setting, neuroimaging studies are of great importance in determining focal lesions in the cerebellum and its connections as well as other affected parts of the brain [67].
