Post-Concussion Syndrome after a Mild Traumatic Brain Injury: A Minefield for Clinical Practice

In this clinical practice review, the controversies and difficulties managing post concussion symptoms following mild traumatic brain injury are discussed. Based on considerable clinical experience in a designated Concussion Clinic, the authors (a neuropsychologist, a psychiatrist, and a neurologist) review relevant literature and issues for clinical practice, particularly with respect to understanding risk factors for and vulnerability to, development of chronic post-concussion symptoms. We contend it is not just the kind of head that matters but also the kind of complications, the kind of outcomes and the kind of management that can influence injury recovery. Given these complexities, a bio-psychosocial conceptualization of chronic post-concussion syndrome is appropriate. Though understanding is still elusive, management should not be biased by physiogenic or psychogenic aetiological theories for management needs to address patient reported outcomes regardless of underpinning aetiology.

Caregiver burden is increased in Parkinson’s disease with mild cognitive impairment (PD-MCI)

Background:There is limited evidence on caregiver outcomes associated with mild cognitive impairment in patients with Parkinson’s disease(PD-MCI)and the coping strategies used by these caregivers.Methods:To investigate this relationship,we examined levels of burden,depression,anxiety,coping strategies and positive aspects of caregiving in the informal caregivers of 96 PD patients.The PD patients were classified using MDS-Task Force Level II criteria as showing either normal cognition(PD-N;n=51),PD-MCI(n=30)or with dementia(PDD;n=15).Results:Mean Zarit Burden Interview(ZBI)score increased significantly between carers of PD-N(M=13.39,SD=12.22)compared to those of PD-MCI patients(M=22.00,SD=10.8),and between carers of PD-MCI and PDD patients(M=29.33,SD=9.59).Moreover,the proportion of carers showing clinically significant levels of burden(ZBI score≥21)also increased as the patients’cognitive status declined(18% for PD-N;60% for PD-MCI;and 80%for PDD)and was mirrored by an increasing amount of time spent providing care by the caregivers.Caregiver ZBI score was independent of patient neuropsychiatric symptoms,motor function,disease duration and time that caregivers spent caregiving.Caregiver use of different coping strategies increased with worsening cognition.However,we found only equivocal evidence that the use of problem-focused,emotion-focused and dysfunctional coping mediated the association between patient cognitive status and caregiver burden,because the inverse models that used caregiver burden as the mediator were also significant.Conclusions:The study highlights the impact of Parkinson’s disease on those providing care when the patient’s cognition is poor,including those with MCI.Caregiver well-being has important implications for caregiver support,nursing home placement and disease course.

Reduced striatal volumes in Parkinson’s disease:a magnetic resonance imaging study

Background:The presence and extent of structural changes in the brain as a consequence of Parkinson’s disease(PD)is still poorly understood.Methods:High-resolution 3-tesla T1-weighted structural magnetic resonance images in sixty-five PD and 27 age-matched healthy control participants were examined.Putamen,caudate,and intracranial volumes were manually traced in the axial plane of 3D reconstructed images.Striatal nuclei volumes were normalized to intracranial volume for statistical comparison.Disease status was assessed using the Unified Parkinson’s Disease Rating Scale and Hoehn and Yahr scale.Cognitive status was assessed using global status tests and detailed neuropsychological testing.Results:Both caudate and putamen volumes were smaller in PD brains compared to controls after adjusting for age and gender.Caudate volumes were reduced by 11%(p=0.001)and putamen volumes by 8.1%(p=0.025).PD striatal volumes were not found to be significantly correlated with cognitive or motor decline.Conclusion:Small,but significant reductions in the volume of both the caudate and putamen occur in PD brains.These reductions are independent of the effects of age and gender,however the relation of these reductions to the functional loss of dopamine,which is characteristic of PD,remains unclear.

α-Synuclein-carrying astrocytic extracellular vesicles in Parkinson pathogenesis and diagnosis

Background The accumulation ofα-synuclein(α-syn),an essential step in PD development and progression,is observed not only in neurons but also in glia,including astrocytes.The mechanisms regulating astrocyticα-syn level and aggregation remain unclear.More recently,it has been demonstrated that a part ofα-syn spreading occurs through extracellular vesicles(EVs),although it is unknown whether this process is involved in astrocytes of PD.It is known,however,that EVs derived from the central nervous system exist in the blood and are extensively explored as biomarkers for PD and other neurodegenerative disorders.Methods Primary astrocytes were transfected with A53Tα-syn plasmid or exposed toα-syn aggregates.The level of astrocyte-derived EVs(AEVs)was assessed by nanoparticle tracking analysis and immunofluorescence.The lysosomal function was evaluated by Cathepsin assays,immunofluorescence for levels of Lamp1 and Lamp2,and LysoTracker Red staining.The Apogee assays were optimized to measure the GLT-1+AEVs in clinical cohorts of 106 PD,47 multiple system atrophy(MSA),and 103 healthy control(HC)to test the potential of plasma AEVs as a biomarker to differentiate PD from other forms of parkinsonism.Results The number of AEVs significantly increased in primary astrocytes withα-syn deposition.The mechanism of increased AEVs was partially attributed to lysosomal dysfunction.The number ofα-syn-carrying AEVs was significantly higher in patients with PD than in HC and MSA.The integrative model combining AEVs with total and aggregatedα-syn exhibited efficient diagnostic power in differentiating PD from HC with an AUC of 0.915,and from MSA with an AUC of 0.877.Conclusions Pathologicalα-syn deposition could increase the astrocytic secretion of EVs,possibly throughα-syninduced lysosomal dysfunction.Theα-syn-containing AEVs in the peripheral blood may be an effective biomarker for clinical diagnosis or differential diagnosis of PD.

Comparison of cognitive and UHDRS measures in monitoring disease progression in Huntington’s disease: a 12-month longitudinal study

Progressive cognitive decline is a feature of Huntington’s disease(HD),an inherited neurodegenerative movement disorder.Comprehensive neuropsychological testing is the‘gold standard’to establish cognitive status but is often impractical in time-constrained clinics.The study evaluated the utility of brief cognitive tests(MMSE and MoCA),UHDRS measures and a comprehensive neuropsychological tests battery in monitoring short-term disease progression in HD.Twenty-two manifest HD patients and 22 matched controls were assessed at baseline and 12-month.A linear mixed-effect model showed that although the HD group had minimal change in overall global cognition after 12 months,they did show a significant decline relative to the control group.The controls exhibited a practice effect in most of the cognitive domain scores over time.Cognitive decline at 12-month in HD was found in the executive function domain but the effect of this on global cognitive score was masked by the improvement in their language domain score.The varying practice effects by cognitive domain with repeated testing indicates the importance of comparing HD patients to control group in research trials and that cognitive progression over 12 months in HD should not be judged by changes in global cognitive score.The three brief cognitive tests effectively described cognition of HD patients on cross-sectional analysis.The UHDRS cognitive component,which focuses on testing executive function and had low variance over time,is a more reliable brief substitute for comprehensive neuropsychological testing than MMSE and MoCA in monitoring cognitive changes in HD patients after 12 months.

Thrombolysis for ischaemic stroke despite direct oral anticoagulation

Intravenous thrombolysis is not recommended in anticoagulated patients receiving direct oral anticoagulants(DOACs)and a recent intake within the last 48hours in US and European guidelines.However,three observational studies now suggest safety of thrombolysis in patients with recent intake of DOACs,and thus support previous experimental data.In this perspective,the current evidence and practical consequences are discussed.