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Linked Comment: E. Epstein. Br J Dermatol 2022; 186:203. Plain language summary available online [ABSTRACT FROM AUTHOR]

Several de novo variants in the KIF1A gene have been reported to cause a complicated form of hereditary spastic paraplegia. Additional symptoms include cognitive impairment and varying degrees of peripheral neuropathy, epilepsy, decreased visual acuity, and ataxia. We describe four patients (ages 10–18 years), focusing on their mobility and gait characteristics. Two patients were not able to walk without assistance and showed a severe abnormal gait pattern, crouch gait. At examination, severe contractures were found. In addition to describing the different phenotypes with specific attention to gait in our cases, we reviewed known KIF1A mutations and summarized their associated phenotypes. We conclude that mobility and cognition are severely affected in children with spastic paraplegia due to de novo KIF1A mutations. Deterioration in mobility is most likely due to progressive spasticity, muscle weakness, and the secondary development of severe contractures, possibly combined with an additional progressive polyneuropathy. Close follow-up and treatment of these patients are warranted. [ABSTRACT FROM AUTHOR]

Objective: The aim of this report is to describe the motor outcome in one year-old children who were born at full-term with perinatal hypoxic-ischemic encephalopathy (HIE). Relationships between motor ability tests and neurological examination at one year, and between these tests and neonatal brain magnetic resonance imaging (MRI) were investigated. Participants and Methods: 32 surviving children, born full-term with perinatal HIE, are included in this report. All children had a neonatal MRI. At one year, motor ability was assessed with the Alberta Infant Motor Scale and the Bayley Scales of Infant Development (2nd version). Neurological examinations included the neurological optimality score (NOS). Results: At one year, 14 children (44%) had normal motor ability, nine (28%) had mildly delayed, and nine had significantly delayed motor ability. The NOS ranged from 14.6-27 points. All children with normal motor ability had (near) optimal NOS, however, not all children with high NOS had normal motor ability. Eleven children (34%) had normal neonatal MRI; at one year, six of them had normal, and five had mildly delayed motor ability. Eight children with normal motor ability showed abnormalities on neonatal MRI. Conclusion: Neonatal brain MRI does not predict motor outcome at one year. Motor ability tests and neurological examinations should be used in a complementary manner to describe outcome after HIE. [ABSTRACT FROM AUTHOR]

The pharmacotherapy of Parkinson's disease mainly consists of treatment with levodopa and/or dopamine receptor agonists, which compensate for the loss of dopamine in the CNS that characterises the disease. Although treatment with levodopa is more effective than that with dopamine receptor agonists, the former frequently causes serious adverse effects, e.g. wearing-off phenomena and dyskinesias. Levodopa (after conversion to dopamine) stimulates dopamine D and D receptors, whereas the presently available dopamine agonists act mainly on D receptors. Therefore, the D receptor might be a potential target for pharmacotherapy in Parkinson's disease. However, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkey model of Parkinson's disease, the partial D agonist SKF-38393 failed to stimulate motor behaviour. Newly developed agents that are full agonists at the D receptor do stimulate motor behaviour of MPTP-lesioned monkeys and act synergistically with D receptor agonists. Nonetheless, several of these compounds lose their efficacy in stimulating motor behaviour upon sustained administration and induce dyskinetic behaviour. Moreover, these compounds are likely to have the potential to induce epileptic seizures. Therefore, the potential value of the newly developed D receptor agonists in the treatment of Parkinson's disease seems limited. [ABSTRACT FROM AUTHOR]