Multibehavioral Phenotyping in Early-Life-Stage Zebrafish for Identifying Disruptors of Nonassociative Learning.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare, autosomal dominant white matter disorder that presents with cognitive decline, parkinsonism, pyramidal signs, and gait disturbance. Early diagnosis is often challenging due to its heterogeneous clinical presentation. A 34-year-old woman presented with right-sided weakness and gait disturbance. Six months later, she developed dysarthria and dysphagia. Neurological examination showed mild weakness (Medical Research Council grade 4) in the right upper and lower extremities and hyperreflexia in both legs. Sensory examination was normal, and cognition was relatively preserved. Brain magnetic resonance imaging (MRI) revealed multiple bilateral T2 hyperintense lesions involving the periventricular, juxtacortical, and deep white matter, with diffusion restriction on diffusion-weighted imaging without splenial involvement or calcification (). Cerebrospinal fluid analysis showed normal cell count and protein level, with negative oligoclonal bands. Serum aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies were negative. Based on the 2017 McDonald criteria, she was initially diagnosed with relapsing-remitting multiple sclerosis (MS). Dissemination in space was fulfilled by the presence of periventricular and juxtacortical lesions, while dissemination in time was based on two clinical attacks occurring six months apart (right-sided weakness followed by dysarthria and dysphagia). The patient was treated with intravenous methylprednisolone followed by teriflunomide. Despite sequential treatment with dimethyl fumarate, cladribine, and rituximab, her symptoms progressively worsened. Behavioral and personality changes emerged, including emotional lability, perseveration, and impaired emotional control. At 14 months, follow-up brain MRI demonstrated progressive bilateral frontal-predominant white matter lesions, corpus callosum thinning, and persistent diffusion restriction (). The Mini-Mental State Examination score declined from 25/30 at 26 months to 23/30 at 34 months despite 16 years of education. She became bedridden within 3 years after onset.