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Both progressive supranuclear palsy and Parkinson’s disease cause impulsivity and impair executive function. Using a saccadic Go/No-Go paradigm and hierarchical Bayesian models, Zhang et al. show differential decision-making deficits in the two disorders, and that model parameters are better than common behavioural measures for single-patient classification of the diseases.

The ability of HIV-1 to establish latent infection is a key obstacle to its eradication despite the existence of effective antiretroviral drugs. The brain has been postulated as a reservoir for latent infection, but its role in HIV persistence remains unclear. In this review, we discuss the evidence surrounding the role of the central nervous system (CNS) as a viral reservoir and the potential challenges this might present in eradicating HIV. The strategies for eradication of HIV and their application to latent CNS infection are explored. Finally, we outline new developments in drug delivery and new therapeutic modalities designed to target HIV infection in the CNS.

Genetic early-onset parkinsonism presenting from infancy to adolescence (≤21 years old) is a clinically diverse syndrome often combined with other hyperkinetic movement disorders, neurological and imaging abnormalities. The syndrome is genetically heterogeneous, with many causative genes already known. With the increased use of next-generation sequencing in clinical practice, there have been novel and unexpected insights into phenotype-genotype correlations and the discovery of new disease-causing genes. It is now recognized that mutations in a single gene can give rise to a broad phenotypic spectrum and that, conversely different genetic disorders can manifest with a similar phenotype. Accurate phenotypic characterization remains an essential step in interpreting genetic findings in undiagnosed patients. However, in the past decade, there has been a marked expansion in knowledge about the number of both disease-causing genes and phenotypic spectrum of early-onset cases. Detailed knowledge of genetic disorders and their clinical expression is required for rational planning of genetic and molecular testing, as well as correct interpretation of next-generation sequencing results. In this review we examine the relevant literature of genetic parkinsonism with ≤21 years onset, extracting data on associated movement disorders as well as other neurological and imaging features, to delineate syndromic patterns associated with early-onset parkinsonism. Excluding PRKN (parkin) mutations, >90% of the presenting phenotypes have a complex or atypical presentation, with dystonia, abnormal cognition, pyramidal signs, neuropsychiatric disorders, abnormal imaging and abnormal eye movements being the most common features. Furthermore, several imaging features and extraneurological manifestations are relatively specific for certain disorders and are important diagnostic clues. From the currently available literature, the most commonly implicated causes of early-onset parkinsonism have been elucidated but diagnosis is still challenging in many cases. Mutations in ∼70 different genes have been associated with early-onset parkinsonism or may feature parkinsonism as part of their phenotypic spectrum. Most of the cases are caused by recessively inherited mutations, followed by dominant and X-linked mutations, and rarely by mitochondrially inherited mutations. In infantile-onset parkinsonism, the phenotype of hypokinetic-rigid syndrome is most commonly caused by disorders of monoamine synthesis. In childhood and juvenile-onset cases, common genotypes include PRKN, HTT, ATP13A2, ATP1A3, FBX07, PINK1 and PLA2G6 mutations. Moreover, Wilson’s disease and mutations in the manganese transporter are potentially treatable conditions and should always be considered in the differential diagnosis in any patient with early-onset parkinsonism.

Background Management of acute ischaemic stroke is time critical. Reducing time to treatment with thrombolysis is strongly associated with improved outcomes in properly selected patients. However, there are barriers to ensuring timely treatment in the hospital setting. Aim To determine if simple, no‐cost protocol changes could improve time to treatment for acute ischaemic stroke at a busy tertiary hospital. Methods Prospectively collected routine clinical data were compared retrospectively before and after a protocol change designed to mirror the successful model from Helsinki University Central Hospital. Consecutive patients who activated a ‘code stroke’ (presentation consistent with acute stroke, eligible for acute stroke therapy) during working hours were included. Results Prior to the protocol change, 143 patients activated a code stroke, and 30 patients received thrombolysis. Following the protocol change, 134 patients activated a code stroke, and 14 patients received thrombolysis. The median time to administer thrombolysis was reduced from 76 min (interquartile range 54–91) to 33 min (27–44), P < 0.01. The median time to perform diagnostic computed tomography was unchanged between the two groups, 23 (14–54) min versus 22 (9–49) min, P = 0.12. However, this was reduced on subgroup analysis of patients whose arrival was pre‐notified by the ambulance service, 16 (9–22) min versus 8 (4–14) min, P < 0.01. Conclusion Time to treatment in acute stroke was dramatically improved with a simple intervention. This was achieved without a large stroke team or additional funding, making it highly accessible to other health services also seeking to improve their stroke service.

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Background and purpose Tremor in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is underrecognized, and the pathophysiology remains incompletely understood. This study evaluated tremor in CIDP and tested the hypothesis, established in other demyelinating neuropathies, that tremor occurs due to mistimed peripheral inputs affecting central motor processing. Additionally, the tremor stability index (TSI) was calculated with the hypothesis that CIDP‐related tremor is more variable than other tremor disorders. Methods Consecutive patients with typical CIDP were prospectively recruited from neuromuscular clinics. Alternative causes of neuropathy and tremor were excluded. Cross‐sectional clinical assessment and extensive tremor study recordings were undertaken. Pearson correlation coefficient was used to compare nerve conduction studies and tremor characteristics, and t‐test was used for comparisons between groups. Results Twenty‐four patients with CIDP were included. Upper limb postural and action tremor was present in 66% and was mild according to the Essential Tremor Rating Assessment Scale. Tremor did not significantly impact disability. Surface electromyography (EMG) found high‐frequency spectral peaks in deltoid (13.73 ± 0.66 Hz), biceps brachii (11.82 ± 0.91 Hz), and extensor carpi radialis (11.87 ± 0.91 Hz) muscles, with lower peaks in abductor pollicis brevis EMG (6.07 ± 0.45 Hz) and index finger accelerometry (6.53 ± 0.42 Hz). Tremor was unchanged by weight loading but correlated with ulnar nerve F‐wave latency and median nerve sensory amplitude. TSI (2.3 ± 0.1) was significantly higher than essential tremor. Conclusions Postural tremor is a common feature in CIDP. Tremor was unaffected by weight loading, typical of centrally generated tremors, although there was a correlation with peripheral nerve abnormalities. The high beat‐to‐beat variability on TSI and gradation of peak frequencies further suggest a complex pathophysiology. These findings may assist clinicians with the diagnosis of neuropathic tremor.

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