Hereditary spastic paraplegia (HSP) describes a heterogeneous group of genetic neurodegenerative diseases characterised by progressive spasticity of the lower limbs. The pathogenic mechanism, associated clinical features and imaging abnormalities vary significantly according to the affected gene. Here, we describe the clinical and imaging characteristics of the more common forms of HSP. We discuss how to approach the diagnosis and management of a suspected case of HSP in the era of next generation sequencing, before discussing treatment and the potential of emerging therapeutic options for specific causes of HSP based on their underlying molecular mechanism.

This systematic review and meta-analysis demonstrates that people with constipation are at a higher risk of developing Parkinson's disease compared with those without and that constipation can predate Parkinson's diagnosis by over a decade.

The main presenting features of Wilson disease, many of which mimic common hepatic and neurologic disorders, are discussed. There is a need for specialists in these and related fields to be aware of hints from within and, more importantly, outside their area of expertise that should alert them to consider the diagnosis. Delayed diagnosis and treatment are potentially damaging for the patient. The importance of recognising and promptly investigating Wilson disease at the initial presentation should be understood by all those who assess patients with hepatic or neurologic disorders and/or train others in their specialty.

Wilson’s disease is an autosomal–recessive disorder of copper metabolism caused by mutations in ATP7B and associated with neurological, psychiatric, ophthalmological and hepatic manifestations. Decoppering treatments are used to prevent disease progression and reduce symptoms, but neurological outcomes remain mixed. In this article, we review the current understanding of pathogenesis, biomarkers and treatments for Wilson’s disease from the neurological perspective, with a focus on recent advances. The genetic and molecular mechanisms associated with ATP7B dysfunction have been well characterised, but despite extensive efforts to identify genotype–phenotype correlations, the reason why only some patients develop neurological or psychiatric features remains unclear. We discuss pathological processes through which copper accumulation leads to neurodegeneration, such as mitochondrial dysfunction, the role of brain iron metabolism and the broader concept of selective neuronal vulnerability in Wilson’s disease. Delayed diagnoses continue to be a major problem for patients with neurological presentations. We highlight limitations in our current approach to making a diagnosis and novel diagnostic biomarkers, including the potential for newborn screening programmes. We describe recent progress in developing imaging and wet (fluid) biomarkers for neurological involvement, including findings from quantitative MRI and other neuroimaging studies, and the development of a semiquantitative scoring system for assessing radiological severity. Finally, we cover the use of established and novel chelating agents, paradoxical neurological worsening, and progress developing targeted molecular and gene therapy for Wilson’s disease, before discussing future directions for translational research.

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