# A Clinical-Based Diagnostic Approach to Cerebellar Atrophy in Children
## 4 Discussion  
The aim of this study was to create a possible diagnostic workup for pediatric ataxias with cerebellar atrophy, which can guide both the formulation of a clinical suspicion and the interpretation of big genetic data; the proposed algorithm is shown in Figure 3.  
We do not include brain MRI as part of the diagnostic process as it should be the first exam to be performed in a child with a congenital or early onset ataxia [2] in order to discriminate in the first place primary from acquired ataxias (e.g., cerebral tumors, toxins, teratogens, prenatal viral infections...), and, in the case of a primary ataxia, malformations to degenerative diseases. Studies have focused so far on delineating different neuroradiological patterns with CA, while little has been written on the global clinical presentation of the patients. Neuroradiological evaluation is the prerogative and should precede any other investigation. In most patients, it was performed more than once and frequently revealed atrophy  
Figure 3: Proposed diagnostic flowchart for children with cerebellar atrophy. Abbreviations legend: ARSACS: Autosomal Receive Spastic Ataxia of Charlevoix-Saguenay; CDG: Congenital Disorders of Glycoslation; DM I: Diabetes Mellitus type I; NBIA: Neurodegeneration with Brain Iron Accumulation; NCL: Neuronal Ceroid Lipofectamine; PCH: Ponto-Crebellar Hypoplasia; SCA: SpinoCerebellar Ataxias. progression. Consistent with the literature data [2], cerebellar vermis is always atrophic, but the degeneration is global (vermis plus hemispheres) in most kids, without any disease-specific pattern. Children who have a CA superimposed to cerebellar hypoplasia had those disorders in which cerebellar degeneration is known to start at a very early stage of development: PCH and CDG [3; 11]. The hypo-atrophic pattern cannot be missed, as its presence consistently narrows the possible diagnosis to a small group of disorders. A hyperintensity of the cerebellar structure is otherwise less specific; it is generally thought of as a sign of _PLA2G6_ mutations, mitochondrial diseases or, once again, CDG [2; 8]. This is partially confirmed by our study, where more than a half of children with mitochondrial diseases or Neurodegeneration with Brain Iron Accumulation (NBIA) present dentate nuclei and/or cerebellar cortex hyperintensity, but the same sign is also shared by other kind of diseases (e.g., DNA repair disorders, SCA) as found in a previous work [8]. This observation points out that the presence of dentate or cerebellar cortex hyperintensity alone is not sufficient to suggest a specific disease or disease group but, along with other features, it may strengthen the hypothesis of a metabolic disorder. Of note, the only PCH child with cortex and dentate T2-hyperintensity was affected by PCH6, caused by the mutation of a gene implicated in mitochondrial functions (_RARS2_) [12]. The involvement of brainstem structures is common and it is important to recognize the patterns that are disease-specific: beyond PCH, these include the characteristic pontine tigroid hypointensities of ARSACS [6]. Brainstem atrophy is considered rare also in advanced stages2; in our cohort, it is present in 9 out of 52 children. Supratentorial alterations are mostly non-specific, as also found in previous studies [8; 9], although, when associated with other features and consistent with the clinical phenotype, they may aid in the diagnosis (HLD in the case of diffuse hypomyelination, Cockayne syndrome with hypomyelination and calcifications, WM abnormalities and severe atrophy in NCL). Interestingly, of the three patients with mutation in NBIA genes, only one presents a definite basal ganglia anomaly until now. Clinical presentation is often similar in all children with CA. Patients who are sooner brought to the physician attention are mostly affected by diseases with intrinsic malformationsive aspects (e.g., aniridia in Gillespie) or characterized by an early cerebellar dysfunction (e.g., CDG or PCH).