Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Jan 2024
Recurrent de novo SPTLC2 variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific SPTLC1 variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in SPTLC2 c.778G>A [p.Glu260Lys] manifesting with juvenile ALS. ⋯ SPTLC2 is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further.
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J. Neurol. Neurosurg. Psychiatr. · Jan 2024
Intronic FGF14 GAA repeat expansions are a common cause of ataxia syndromes with neuropathy and bilateral vestibulopathy.
Intronic GAA repeat expansions in the fibroblast growth factor 14 gene (FGF14) have recently been identified as a common cause of ataxia with potential phenotypic overlap with RFC1-related cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS). Our objective was to report on the frequency of intronic FGF14 GAA repeat expansions in patients with an unexplained CANVAS-like phenotype. ⋯ GAA-FGF14-related disease is a common cause of cerebellar ataxia with polyneuropathy and/or BVP, and should be included in the differential diagnosis of RFC1 CANVAS and disease spectrum.
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J. Neurol. Neurosurg. Psychiatr. · Jan 2024
Assessing treatment response to oral drugs for multiple sclerosis in real-world setting: a MAGNIMS Study.
The assessment of treatment response is a crucial step for patients with relapsing-remitting multiple sclerosis on disease-modifying therapies (DMTs). We explored whether a scoring system developed within the MAGNIMS (MRI in Multiple Sclerosis) network to evaluate treatment response to injectable drugs can be adopted also to oral DMTs. ⋯ Early relapses and substantial MRI activity in the first year of treatment are associated with worse short-term outcomes in patients treated with some of the oral DMTs.