BackgroundHeterozygous GAA expansions in the FGF14 gene have been related to autosomal dominant cerebellar ataxia (SCA27B‐MIM:620174). Whether they represent a common cause of sporadic late‐onset cerebellar ataxia (SLOCA) remains to be established.ObjectivesTo estimate the prevalence, characterize the phenotypic spectrum, identify discriminative features, and model longitudinal progression of SCA27B in a prospective cohort of SLOCA patients.MethodsFGF14 expansions screening combined with longitudinal deep‐phenotyping in a prospective cohort of 118 SLOCA patients (onset >40 years of age, no family history of cerebellar ataxia) without a definite diagnosis.ResultsPrevalence of SCA27B was 12.7% (15/118). Higher age of onset, higher Spinocerebellar Degeneration Functional Score, presence of vertigo, diplopia, nystagmus, orthostatic hypotension absence, and sensorimotor neuropathy were significantly associated with SCA27B. Ataxia progression was ≈0.4 points per year on the Scale for Assessment and Rating of Ataxia.ConclusionsFGF14 expansion is a major cause of SLOCA. Our natural history data will inform future FGF14 clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Summary:Purpose: Hippocampal sclerosis (HS) is the most frequent lesion found in mesial temporal lobe epilepsy (mTLE). MR imaging is considered to be the most sensitive and specific method to detect HS. Despite extensive studies performed on humans and except in a recent study, the morphologic pattern of HS is usually analyzed when the disease has already fully developed, thus not allowing any insight into the mapping of the progressive morphologic changes inducing the development of mTLE. We have recently characterized a model of mTLE that reproduces the unilateral pattern of HS, induced by intrahippocampal injection of low doses of kainate (KA) in mice.Methods: In this study, we monitored the temporal evolution of the development of HS in this model of mTLE by using T,-weighted sequence, T,-relaxation time measurements, and T,-weighted spin-echo technique after injection of gadolinium, from 1 h to 120 days after KA injection.Results: HS induced by intrahippocampal KA injection occurred in two phases. First, we observed a transient hyperintense T,-weighted signal in the cortex above the injected hippocampus, most likely indicative of vasogenic edema partly due to the neurotoxic effect of KA. The concomitant increase in the T, signal in the injected hippocampus and ipsilateral amygdala likely reflects the phase of cytotoxic edema occurring probably in relation to the excitotoxic consequences of both KA and seizure activity. Second, from 15 days on, a persistent unilateral increased T, signal was detected in the hippocampus, which most probably reflects gliosis.Conclusions: Our findings indicate that longitudinal followup would permit a better understanding of the mechanisms underlying the constitution of HS in humans and eventually development of prevention strategies. Key Words: Mesial temporal lobe epilepsy-Kainic acid-MRI-Hippocampal sclerosis-Mice.Mesial temporal lobe epilepsy (mTLE), which is the most frequent of drug-resistant epileptic syndromes, has been precisely characterized in terms of EEG and behavioral symptoms as well as morphologic and functional imaging findings. Typically, mTLE starts several years after an early childhood precipitating event (complicated febrile seizures, encephalitis, head trauma, etc.), with onset of complex partial seizures toward the end of the first decade of life. Seizures may initially respond well to antiepileptic drugs (AEDs), but usually return in adolescence or early adulthood and become refractory to medical treatment. Pathologic analysis of temporal tissues performed since the 1940s, either at autopsy or on surgically excised specimens, has shown that the most com-

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