Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · May 2020
ReviewAnatomy and function of the fornix in the context of its potential as a therapeutic target.
The fornix is a white matter bundle located in the mesial aspect of the cerebral hemispheres, which connects various nodes of a limbic circuitry and is believed to play a key role in cognition and episodic memory recall. As the most prevalent cause of dementia, Alzheimer's disease (AD) dramatically impairs the quality of life of patients and imposes a significant societal burden on the healthcare system. As an established treatment for movement disorders, deep brain stimulation (DBS) is currently being investigated in preclinical and clinical studies for treatment of memory impairment in AD by modulating fornix activity. ⋯ Each pathway's target and origin structures are presented, followed by a discussion of their oscillatory dynamics and functional connectivity. Overall, neuromodulation of each pathway of the fornix is discussed in the context of evidence-based forniceal DBS strategies. It is not yet known whether driving fornix activity can enhance cognition-optimal target and stimulation parameters to rescue memory deficits have yet to be determined.
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J. Neurol. Neurosurg. Psychiatr. · May 2020
ReviewConcussion and long-term cognitive impairment among professional or elite sport-persons: a systematic review.
Understanding whether concussion in sport is associated with worsening cognitive function in later life will likely have immediate repercussion on sports concussion prevention and management policy and sporting rules and regulations. This systematic review aims to summarise the evidence on the association between concussion sustained by professional/elite athletes and long-term cognitive impairment. ⋯ High-quality, appropriately designed and powered epidemiological studies are urgently needed to assess the association between sustaining a sport-related concussion and cognitive impairment later in life. Particular emphasis should be put on the clinical translational value of findings.
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J. Neurol. Neurosurg. Psychiatr. · May 2020
Randomized Controlled TrialEffect of fingolimod on MRI outcomes in patients with paediatric-onset multiple sclerosis: results from the phase 3 PARADIGMS study.
PARADIGMS demonstrated superior efficacy and comparable safety of fingolimod versus interferon β-1a (IFN β-1a) in paediatric-onset multiple sclerosis (PoMS). This study aimed to report all predefined MRI outcomes from this study. ⋯ Fingolimod significantly reduced MRI activity and ARBA for up to 2 years versus IFN β-1a in PoMS.
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J. Neurol. Neurosurg. Psychiatr. · May 2020
ReviewVisual hallucinations in neurological and ophthalmological disease: pathophysiology and management.
Visual hallucinations are common in older people and are especially associated with ophthalmological and neurological disorders, including dementia and Parkinson's disease. Uncertainties remain whether there is a single underlying mechanism for visual hallucinations or they have different disease-dependent causes. However, irrespective of mechanism, visual hallucinations are difficult to treat. ⋯ A broad treatment perspective is needed, including carer support. Despite their frequency and clinical significance, there is a paucity of randomised, placebo-controlled clinical trial evidence where the primary outcome is an improvement in visual hallucinations. Key areas for future research include the development of valid and reliable assessment tools for use in mechanistic studies and clinical trials, transdiagnostic studies of shared and distinct mechanisms and when and how to treat visual hallucinations.
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J. Neurol. Neurosurg. Psychiatr. · May 2020
Comparative StudyDifferent CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion.
The hexanucleotide repeat expansion in the C9orf72 gene is the most common mutation associated with amyotrophic lateral sclerosis (C9-ALS) and frontotemporal dementia (C9-FTD). Until now, it is unknown which factors define whether C9orf72 mutation carriers develop ALS or FTD. Our aim was to identify protein biomarker candidates in the cerebrospinal fluid (CSF) which differentiate between C9-ALS and C9-FTD and might be indicative for the outcome of the mutation. ⋯ This study presents a deep proteomic CSF analysis of C9-ALS versus C9-FTD patients. As a proof of concept, we observed higher NEFM and CHIT1 CSF levels in C9-ALS. In addition, we also show clear upregulation of UCHL1 in C9-ALS and downregulation of NPTXR in C9-FTD. Significant differences in UCHL1 CSF levels may explain diverging ubiquitination and autophagy processes and NPTXR levels might reflect different synapses organisation processes.