Most subjects with logopenic primary progressive aphasia (lvPPA) have beta-amyloid (Aβ) deposition on Pittsburgh Compound B PET (PiB-PET), usually affecting prefrontal and temporoparietal cortices, with less occipital involvement.
To assess clinical and imaging features in lvPPA subjects with unusual topographic patterns of Aβ deposition with highest uptake in occipital lobe.
Thirty-three lvPPA subjects with Aβ deposition on PiB-PET were included in this case-control study. Line-plots of regional PiB uptake were created, including frontal, temporal, parietal and occipital regions, for each subject. Subjects in which the line sloped downwards in occipital lobe (lvPPA-low), representing low uptake, were separated from those where the line sloped upwards in occipital lobe (lvPPA-high), representing unusually high occipital uptake compared to other regions. Clinical variables, atrophy on MRI, hypometabolism on F18-fluorodeoxyglucose PET, and presence and distribution of microbleeds and white matter hyperintensities (WMH) were assessed.
Seventeen subjects (52%) were classified as lvPPA-high. Mean occipital PiB uptake in lvPPA-high was higher than all other regions, and higher than all regions in lvPPA-low. The lvPPA-high subjects performed more poorly on cognitive testing, including executive and visuospatial testing, but the two groups did not differ in aphasia severity. Proportion of microbleeds and WMH was higher in lvPPA-high than lvPPA-low. Parietal hypometabolism was greater in lvPPA-high than lvPPA-low.
Unusually high occipital Aβ deposition is associated with widespread cognitive impairment and different imaging findings in lvPPA. These findings help explain clinical heterogeneity in lvPPA, and suggest that Aβ influences severity of overall cognitive impairment but not aphasia.
Based on the amyloid hypothesis, controlling β-amyloid protein (Aβ) accumulation is supposed to suppress downstream pathological events, tau accumulation, neurodegeneration and cognitive decline. However, in recent clinical trials, Aβ removal or reducing Aβ production has shown limited efficacy. Moreover, while active immunisation with Aβ resulted in the clearance of Aβ, it did not prevent tau pathology or neurodegeneration. This prompts the concern that it might be too late to employ Aβ targeting therapies once tau mediated neurodegeneration has occurred. Therefore, it is timely and very important to develop tau directed therapies. The pathomechanisms of tau mediated neurodegeneration are unclear but hyperphosphorylation, oligomerisation, fibrillisation and propagation of tau pathology have been proposed as the likely pathological processes that induce loss of function or gain of toxic function of tau, causing neurodegeneration. Here we review the strategies for tau directed treatments based on recent progress in research on tau and our understanding of the pathomechanisms of tau mediated neurodegeneration.
Significant heterogeneity in clinical features of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) cases with the pathogenic C9orf72 expansion (C9P) have been described. To clarify this issue, we compared a large C9P cohort with carefully matched non-expansion (C9N) cases with a known or highly-suspected underlying TDP-43 proteinopathy.
A retrospective-cohort study using available cross-sectional and longitudinal clinical and neuropsychological data, MRI voxel-based morphometry (VBM) and neuropathological assessment from 64 C9P cases (ALS=31, FTLD=33) and 79 C9N cases (ALS=36, FTLD=43).
C9P cases had an earlier age of onset (p=0.047), and in the subset of deceased patients, an earlier age of death (p=0.014) than C9N. C9P had more rapid progression than C9N: C9P ALS cases had a shortened survival (2.6±0.3 years) compared to C9N ALS (3.8±0.4 years; log-rankλ2=4.183,p=0.041), and C9P FTLD showed a significantly greater annualized rate of decline in letter fluency (4.5±1.3words/year) than C9N FTLD (1.4±0.8words/year, p=0.023). VBM revealed greater atrophy in the right fronto-insular, thalamus, cerebellum and bilateral parietal regions for C9P FTLD relative to C9N FTLD, and regression analysis related verbal fluency scores to atrophy in frontal and parietal regions. Neuropathologic analysis found greater neuronal loss in the mid-frontal cortex in C9P FTLD, and mid-frontal cortex TDP-43 inclusion severity correlated with poor letter fluency performance.
C9P cases may have a shorter survival in ALS and more rapid rate of cognitive decline related to frontal and parietal disease in FTLD. C9orf72 genotyping may provide useful prognostic and diagnostic clinical information for ALS and FTLD patients.
Frontotemporal dementia; Amyotrophic lateral sclerosis; C9orf72; neuropsychological tests; neuroimaging
Glioblastoma multiforme (GBM) is a highly invasive brain tumour that is unvaryingly fatal in humans despite even aggressive therapeutic approaches such as surgical resection followed by chemotherapy and radiotherapy. Unconventional treatment options such as gene therapy provide an intriguing option for curbing glioma related deaths. To date, gene therapy has yielded encouraging results in preclinical animal models as well as promising safety profiles in phase I clinical trials, but has failed to demonstrate significant therapeutic efficacy in phase III clinical trials. The most widely studied antiglioma gene therapy strategies are suicide gene therapy, genetic immunotherapy and oncolytic virotherapy, and we have attributed the challenging transition of these modalities into the clinic to four major roadblocks: (1) anatomical features of the central nervous system, (2) the host immune system, (3) heterogeneity and invasiveness of GBM and (4) limitations in current GBM animal models. In this review, we discuss possible ways to jump these hurdles and develop new gene therapies that may be used alone or in synergy with other modalities to provide a powerful treatment option for patients with GBM.
Mutations in the presenilin (PSEN1, PSEN2) and amyloid precursor protein (APP) genes cause familial Alzheimer’s disease (FAD) in a nearly fully penetrant, autosomal dominant manner, providing a unique opportunity to study presymptomatic individuals who can be predicted to develop Alzheimer’s disease (AD) with essentially 100% certainty. Using tensor-based morphometry (TBM), we examined brain volume differences between presymptomatic and symptomatic FAD mutation carriers and non-carrier (NC) relatives.
Twenty-five mutation carriers and 10 NC relatives underwent brain MRI and clinical assessment. Four mutation carriers had dementia (MUT-Dem), 12 had amnestic mild cognitive impairment (MUT-aMCI) and nine were cognitively normal (MUT-Norm). TBM brain volume maps of MUT-Norm, MUT-aMCI and MUT-Dem subjects were compared to NC subjects.
MUT-Norm subjects exhibited significantly smaller volumes in the thalamus, caudate and putamen. MUT-aMCI subjects had smaller volumes in the thalamus, splenium and pons, but not in the caudate or putamen. MUT-Dem subjects demonstrated smaller volumes in temporal, parietal and left frontal regions. As non-demented carriers approached the expected age of dementia diagnosis, this was associated with larger ventricular and caudate volumes and a trend towards smaller temporal lobe volume.
Cognitively intact FAD mutation carriers had lower thalamic, caudate and putamen volumes, and we found preliminary evidence for increasing caudate size during the predementia stage. These regions may be affected earliest during prodromal stages of FAD, while cortical atrophy may occur in later stages, when carriers show cognitive deficits. Further studies of this population will help us understand the progression of neurobiological changes in AD.
Recent postmortem studies reveal degenerative changes, including Purkinje cell (PC) loss, in most brains from individuals with essential tremor (ET). Heterotopic PCs (HPCs) (ie, PC bodies displaced into the molecular layer) may be found in neurodegenerative diseases with PC loss. HPCs have been observed in ET but no quantitative case control analysis has been performed.
HPCs were counted in 35 ET brains and 32 control brains (including 21 non-diseased controls and 11 diseased controls with progressive supranuclear palsy (PSP)) using a standard 20×25 mm cerebellar cortical section stained with a modified Bielscholwsky method.
The median number of HPCs per section was three times higher in 35 ET cases (median 3, mean±SD 3.8±3.6, range 0–14) versus 32 controls (median 1, mean±SD 1.6±1.7, range 0–5) (p=0.007). The number of HPCs was similarly low in the 21 non-diseased controls and 12 PSP brains (median 1 in each group) (p=0.04 and p=0.01 compared with ET). In ET, the number of HPCs was inversely related to the number of PCs (Spearman's rho −0.36, p=0.038) (ie, cases with more HPCs had fewer PCs).
PC heterotopia, which occurs in cerebellar degenerative disorders, is also a feature of ET. These findings further contribute to our understanding of the postmortem changes in this common neurological disease.
Gait and balance disorders, characterized by freezing of gait and postural instability, represent a major therapeutic challenge in Parkinson’s disease (PD). These symptoms respond poorly to dopaminergic treatments, except in the early phase of the disease. Currently, no other pharmacological treatment is particularly efficient. Furthermore, high frequency stimulation of the subthalamic nucleus or internal globus pallidus is not a therapeutic option and rehabilitation appears to be the most effective approach. Since these gait and balance deficits are resistant to dopaminergic drugs, their occurrence could be related to the development of extra-dopaminergic lesions in PD patients. We provide a comprehensive description of the clinical features of gait and balance disorders in PD. We also highlight the brain networks involved in gait and balance control in animals and humans with a particular focus on the relevant structures in the context of PD, such as the mesencephalic locomotor region. We also review other neuronal systems that may be involved in the physiopathology of gait and balance disorders in PD (noradrenergic and serotoninergic systems, cerebellum and cortex). In addition, we review recent evidence regarding functional neurosurgery for gait disorders in PD and propose new directions for future therapeutic research.
Parkinson’s disease; Gait disorders; Pedunculopontine Nucleus; Acetylcholine; Animal models
Prodromal Huntington disease (prHD) is associated with a myriad of cognitive changes, but the domains that best predict time to clinical diagnosis have not been studied. This is a notable gap because some domains may be more sensitive to cognitive decline, which would inform clinical trials.
The present study sought to characterize cognitive domains underlying a large test battery and for the first time, evaluate their ability to predict to time to diagnosis.
Participants included gene-negative and gene-positive prHD participants who were enrolled in the PREDICT-HD study. The CAG/Age Product (CAP) score was the measure of an individual’s genetic signature. A factor analysis of 18 tests was performed to identify sets of measures or latent factors that elucidated core constructs of tests. Factor scores were then fit to a survival model to evaluate their ability to predict time to diagnosis.
Six factors were identified: 1) speed/inhibition, 2) verbal working memory, 3) motor planning/speed, 4) attention-information integration, 5) sensory-perceptual processing, and 6) verbal learning/memory. Factor scores were sensitive to a worsening of cognitive functioning in prHD, typically more so than performances on individual tests comprising the factors. Only the motor planning/speed and sensory-perceptual processing factors predicted time to diagnosis, after controlling for CAP scores and motor symptoms.
The results suggest that motor planning/speed and sensory-perceptual processing are important markers of disease prognosis. The findings also have implications for using composite indices of cognition in preventive HD trials where they may be more sensitive than individual tests.
prodromal Huntington Disease; time to diagnosis; cognition; survival analysis
The pedunculopontine nucleus (PPN) is a brainstem structure with widespread connections to the basal ganglia. Despite the recent introduction of PPN deep brain stimulation (DBS) for the treatment of gait disorders, little is known about its physiology in humans.
We analyzed the discharge characteristics of single neurons in the PPN region in four patients and PPN local field potentials (LFP) in one patient, recorded during the course of DBS implantation. Two patients had Parkinson’s disease and two had non-sinemet responsive parkinsonism. Cell locations were plotted in the coordinate system of a human brainstem atlas.
Fifty-six units in the PPN region were studied, of which 32 mapped to within PPN boundaries. The mean (+/− SD) discharge rate of neurons in the PPN was 23.2 (+/− 15.6) Hz. Spontaneous neuronal firing rate and burst discharge rate were significantly different between neurons in the region dorsal to PPN and those in the PPN. Responses to passive movement of contralateral and ipsilateral limbs were found. Theta and beta band oscillations were present in the PPN LFP.
PPN discharge characteristics may prove useful in the electrophysiologic identification of PPN during DBS implantation surgery.
Parkinson’s disease; neurophysiology; gait; neurosurgery
To determine how intraoperative microelectrode recordings (MER) and intraoperative lead placement acutely influence tremor, rigidity, and bradykinesia. Secondarily, to evaluate whether the longevity of the MER and lead placement effects were influenced by target location (subthalamic nucleus (STN) or globus pallidus interna (GPi)).
Currently most groups who perform deep brain stimulation (DBS) for Parkinson disease (PD) use MER, as well as macrostimulation (test stimulation), to refine DBS lead position. Following MER and/or test stimulation, however, there may be a resultant “collision/implantation” or “microlesion” effect, thought to result from disruption of cells and/or fibres within the penetrated region. These effects have not been carefully quantified.
47 consecutive patients with PD undergoing unilateral DBS for PD (STN or GPi DBS) were evaluated. Motor function was measured at six time points with a modified motor Unified Parkinson Disease Rating Scale (UPDRS): (1) preoperatively, (2) immediately after MER, (3) immediately after lead implantation/collision, (4) 4 months following surgery—off medications, on DBS (12 h medication washout), (5) 6 months postoperatively—off medication and off DBS (12 h washout) and (6) 6 months—on medication and off DBS (12 h washout).
Significant improvements in motor scores (p<0.05) (tremor, rigidity, bradykinesia) were observed as a result of MER and lead placement. The improvements were similar in magnitude to what was observed at 4 and 6 months post-DBS following programming and medication optimisation. When washed out (medications and DBS) for 12 h, UPDRS motor scores were still improved compared with preoperative testing. There was a larger improvement in STN compared with GPi following MER (p<0.05) and a trend for significance following lead placement (p<0.08) but long term outcome was similar.
This study demonstrated significant acute intraoperative penetration effects resulting from MER and lead placement/collision in PD. Clinicians rating patients in the operating suite should be aware of these effects, and should consider pre- and post-lead placement rating scales prior to activating DBS. The collision/implantation effects were greater intraoperatively with STN compared with GPi, and with greater disease duration there was a larger effect.
Frontotemporal lobar degeneration (FTLD) is most commonly associated with TAR-DNA binding protein (TDP-43) or tau pathology at autopsy, but there are no in vivo biomarkers reliably discriminating between sporadic cases. As disease-modifying treatments emerge, it is critical to accurately identify underlying pathology in living patients so that they can be entered into appropriate etiology-directed clinical trials. Patients with tau inclusions (FTLD-TAU) appear to have relatively greater white matter (WM) disease at autopsy than those patients with TDP-43 (FTLD-TDP). In this paper, we investigate the ability of white matter (WM) imaging to help discriminate between FTLD-TAU and FTLD-TDP during life using diffusion tensor imaging (DTI).
Patients with autopsy-confirmed disease or a genetic mutation consistent with FTLD-TDP or FTLD-TAU underwent multimodal T1 volumetric MRI and diffusion weighted imaging scans. We quantified cortical thickness in GM and fractional anisotropy (FA) in WM. We performed Eigenanatomy, a statistically robust dimensionality reduction algorithm, and used leave-one-out cross-validation to predict underlying pathology. Neuropathological assessment of GM and WM disease burden was performed in the autopsy-cases to confirm our findings of an ante-mortem GM and WM dissociation in the neuroimaging cohort.
ROC curve analyses evaluated classification accuracy in individual patients and revealed 96% sensitivity and 100% specificity for WM analyses. FTLD-TAU had significantly more WM degeneration and inclusion severity at autopsy relative to FTLD-TDP.
These neuroimaging and neuropathological investigations provide converging evidence for greater WM burden associated with FTLD-TAU, and emphasize the role of WM neuroimaging for in vivo discrimination between FTLD-TAU and FTLD-TDP.
To determine the association of self-reported traumatic brain injury (TBI) with loss of consciousness (LOC) with late-life re-injury, dementia diagnosis and mortality.
Ongoing longitudinal population-based prospective cohort study.
Seattle-area integrated health system.
4225 dementia-free individuals age 65 and older were randomly selected and enrolled between 1994 and 2010. Participants were seen every 2 years, with mean (range) follow-up of 7.4 (0–16) years. 606 (14%) participants reported a lifetime history of TBI with LOC at enrolment. 3466 participants provided information regarding lifetime history of TBI and completed at least one follow-up visit.
Main outcome measures
Self-reported TBI with LOC after study entry, incident all-cause dementia and Alzheimer’s disease (AD), and all-cause mortality.
There were 25 567 person-years of follow-up. History of TBI with LOC reported at study enrolment was associated with increased risk for TBI with LOC during follow-up, with adjusted HRs ranging from 2.54 (95% CI 1.42 to 4.52) for those reporting first injury before age 25 to 3.79 (95% CI 1.89 to 7.61) for those with first injury after age 55. History of TBI with LOC was not associated with elevated risk for developing dementia or AD. There was no association between baseline history of TBI with LOC and mortality, though TBI with LOC since the previous study visit (‘recent TBI’) was associated with increased mortality (HR 2.12, 95% CI 1.62 to 2.78).
Individuals aged 65 or older who reported a history of TBI with LOC at any time in their lives were at elevated risk of subsequent re-injury. Recent TBI with LOC sustained in older adulthood was associated with increased risk for mortality. Findings support the need for close clinical monitoring of older adults who sustain a TBI with LOC.
Patients with encephalitis associated with antibodies against N-methyl-D-aspartate-receptor antibody (NMDAR-ab) encephalitis frequently show psychotic symptoms, amnesia, seizures and movement disorders. While brain MRI in NMDAR-ab encephalitis is often normal, abnormalities of cerebral glucose metabolism have been demonstrated by positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in a few usually isolated case reports. However, a common pattern of FDG-PET abnormalities has not been reported.
The authors retrospectively identified six patients with NMDAR-ab encephalitis in two large German centres who underwent at least one whole-body FDG-PET for tumour screening between January 2007 and July 2010. They analysed the pattern of cerebral uptake derived from whole-body PET data for characteristic changes of glucose metabolism compared with controls, and the changes of this pattern during the course of the disease.
Groupwise analysis revealed that patients with NMDAR-ab encephalitis showed relative frontal and temporal glucose hypermetabolism associated with occipital hypometabolism. Cross-sectional analysis of the group demonstrated that the extent of these changes is positively associated with clinical disease severity. Longitudinal analysis of two cases showed normalisation of the pattern of cerebral glucose metabolism with recovery.
A characteristic change in cerebral glucose metabolism during NMDAR-ab encephalitis is an increased frontotemporal-to-occipital gradient. This pattern correlates with disease severity. Similar changes have been observed in psychosis induced by NMDAR antagonists. Thus, this pattern might be a consequence of impaired NMDAR function.
Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to determine the frequency of different genes in a large cohort of patients with CMT and devise guidelines for genetic testing in practice.
The genes known to cause CMT were sequenced in 1607 patients with CMT (425 patients attending an inherited neuropathy clinic and 1182 patients whose DNA was sent to the authors for genetic testing) to determine the proportion of different subtypes in a UK population.
A molecular diagnosis was achieved in 62.6% of patients with CMT attending the inherited neuropathy clinic; in 80.4% of patients with CMT1 (demyelinating CMT) and in 25.2% of those with CMT2 (axonal CMT). Mutations or rearrangements in PMP22, GJB1, MPZ and MFN2 accounted for over 90% of the molecular diagnoses while mutations in all other genes tested were rare.
Four commonly available genes account for over 90% of all CMT molecular diagnoses; a diagnostic algorithm is proposed based on these results for use in clinical practice. Any patient with CMT without a mutation in these four genes or with an unusual phenotype should be considered for referral for an expert opinion to maximize the chance of reaching a molecular diagnosis.
Recent evidence suggests that STN-DBS may have a disease-modifying effect in early PD. A randomized, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable.
Objectives / Methods
Fifteen of thirty early PD patients were randomized to receive STN-DBS implants in an IRB-approved protocol. Operative technique, location of DBS leads, and perioperative adverse events are reported. Active contact used for stimulation in these patients were compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon.
Fourteen of the 15 patients did not sustain any long-term (> 3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior −1.1±1.7mm, lateral 10.7±1.7mm, superior −3.3±2.5mm (AC-PC coordinates). This location is statistically no different (0.77mm, p> 0.05) than the optimal contact used in treatment of 47 advanced PD patients.
The perioperative adverse events in this trial of subjects with early stage PD are comparable to that reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomized, surgical-versus-best-medical-therapy trial for the early treatment of Parkinson’s disease.
Parkinson’s disease; deep brain stimulation; subthalamic nucleus; randomized surgical trial
The objective of this study was to confirm whether an association between handedness and the side of symptom onset exists and to evaluate the impact of this association on specific clinical characteristics of Parkinson’s disease (PD).
1173 PD patients were identified from a clinical database. Patients with asymmetrical onset (n=1015) were divided into those with dominant-side onset and those with non-dominant-side onset, and the clinical characteristics of the two subgroups were compared.
In our PD sample, 86.5% of patients presented asymmetrically. There was a significant association between handedness and the side of the initial symptom; that is, the dominant side was affected first in the majority of both left- and right-handed patients. Compared with patients with non-dominant side onset, more patients with dominant-side onset presented with bradykinesia, while fewer patients presented with gait difficulty. Patients with dominant-side onset were diagnosed and began dopaminergic medication after a longer symptom duration than patients with non-dominant-side onset. The only difference in Unified Parkinson Disease Rating Scale scores between the two groups was in a subscore addressing dominant-hand tasks.
An association exists between the dominant hand and the side of the initial motor symptom in PD. Whether the initial symptom occurs on the dominant or non-dominant side has implications for the reported first symptom, the time to diagnosis and the time to dopaminergic treatment initiation. The side of disease onset does not affect the severity of disease, as measured by the Unified Parkinson Disease Rating Scale.
The hereditary sensory and autonomic neuropathies (HSAN) are rare inherited neuropathies presenting with sensory loss and complications, including ulcers, infections, osteomyelitis and amputations. Usually, sensory symptoms predominate although motor involvement can occur. Autonomic features may be minimal (then hereditary sensory neuropathy, HSN, is preferred). HSAN has been classified into five subtypes depending on clinical presentation.1
Hereditary sensory and autonomic neuropathy II (HSANII or HSNII) is an early onset, autosomal recessive sensory neuropathy with ulcero-mutilating complications due to mutations in the HSN2 isoform of the WNK1 gene.2 Recently, a similar phenotype was described in a Saudi-Arabian family, and a homozygous nonsense mutation found in a new gene, FAM134B (family with sequence similarity 134, member B), encoding a newly identified Golgi protein. The index case in this family was initially thought to have leprosy. Three additional families (out of 75 patients) with similar phenotypes were found to have homozygous loss of function mutations in FAM134B.3
Here, we report the clinical and pathological findings in a further patient with HSNII due to a homozygous mutation in FAM134B.
Anti-Ma2 associated paraneoplastic syndrome usually presents as limbic encephalitis in association with testicular tumours.1, 2 Only four patients have been reported with involvement outside the CNS, two of whom also had limbic or brainstem encephalitis.2, 3 We report a man with anti- Ma2 associated myeloradiculopathy and previous testicular cancer whose neurological syndrome stabilised and anti-Ma2 titres fell following orchidectomy of a microscopically normal testis.
Anti-NMDA receptor (NMDAR) encephalitis is a recently characterised
autoimmune disorder mainly affecting young women. Although the clinical
features of the acute disease are well characterised, cognitive long-term
outcome has not been examined in detail.
The authors investigated cognitive performance in nine patients with
proven anti-NMDAR encephalitis after recovery from the acute disease period
(median 43 months after disease onset, range 23 to 69). Patients underwent a
comprehensive neuropsychological assessment, including memory tasks that
have previously been shown to be sensitive for hippocampal dysfunction.
Substantial persistent cognitive impairments were observed in eight
out of nine patients that mainly consisted of deficits in executive
functions and memory. The severity of these deficits varied
inter-individually. Patients with early immunotherapy performed
significantly better. The most severe deficits were observed with
inefficient or delayed initial treatment.
Our results suggest that cognitive deficits constitute a major
long-term morbidity of anti-NMDAR encephalitis. These deficits relate to the
distribution of NMDARs in the human brain and their functional role in
normal cognition. Good cognitive long-term outcome may depend on early and
Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique inducing prolonged brain excitability changes and promoting cerebral plasticity, is a promising option for neurorehabilitation. Here, we review progress in research on tDCS and language functions and on the potential role of tDCS in the treatment of post-stroke aphasia. Currently available data suggest that tDCS over language-related brain areas can modulate linguistic abilities in healthy individuals and can improve language performance in patients with aphasia. Whether the results obtained in experimental conditions are functionally important for the quality of life of patients and their caregivers remains unclear. Despite the fact that important variables are yet to be determined, tDCS combined with rehabilitation techniques seems a promising therapeutic option for aphasia.
Aphasia; Rehabilitation; Stroke; Electrical Stimulation; Speech Therapy
The contribution of axonal injury to brain damage following aneurysmal subarachnoid hemorrhage (aSAH) is unknown. Neurofilament light chain (NF-L), a component of the axonal cytoskeleton, has been shown to be elevated in the cerebrospinal fluid of patients with many types of axonal injury. We hypothesized that patients with aSAH would have elevated CSF NF-L levels, and sought to explore the clinical correlates of CSF NF-L dynamics.
Serial ventricular cerebrospinal fluid (vCSF) samples were collected from 35 aSAH patients for up to 15 days. vCSF NF-L measurements were determined by enzyme-linked immunosorbent assay. NF-L levels were analyzed in relation to acute clinical status, radiological findings, and 6-month outcomes.
vCSF NF-L concentrations were elevated in all aSAH patients. Patients with early cerebral ischemia (ECI), defined as a CT hypodense lesion visible within the first 3 days, had higher acute vCSF NF-L levels than patients without ECI. These elevated NF-L levels were similar in patients with ECI associated with intracranial hemorrhage and ECI associated with surgical/endovascular complications. vCSF NF-L levels did not differ as a function of acute clinical status, clinical vasospasm, delayed cerebral ischemia, or 6-month Glasgow Outcome Scale.
Elevated vCSF NF-L levels may in part reflect increased injury to axons associated with early cerebral ischemia. However our results suggest that axonal injury following aSAH as reflected by release of NF-L into the CSF may not play a major role in either secondary adverse events or long term clinical outcomes.
cerebral aneurysm; subarachnoid hemorrhage; biomarker; neurofilament; axonal injury
Background and objectives
Parkinson’s disease patients with predominant postural instability and gait difficulties (PIGD) may experience unique cognitive difficulties compared to patients with tremor predominant (TD) symptoms. PIGD patients are also at high risk for falling, and some of the worst fallers seem to react impulsively to their environment. We tested the hypothesis that PIGD patients show poorer control over motor impulses compared to TD patients.
34 PD participants were divided into predominant PIGD (n=17) or TD (n=17) functional subtypes based on their presenting symptoms in their optimally treated motor state. All participants performed a speeded reaction task that quantified motor impulsivity and the proficiency of inhibiting prepotent motor impulses.
The groups showed similar reaction times, but compared to TD patients, PIGD patients made significantly more impulsive motor errors. Notably, when the initial impulsive erroneous response was avoided, PIGD and TD groups were similar in their ability to suppress the incorrect motor impulse from further interfering with the selection of a correct action.
PD patients with PIGD predominant symptoms show greater susceptibility to acting on prepotent motor impulses compared to TD patients. This finding may have direct implications for fall risk and also points to dissociable neurocognitive pathologies in TD and PIGD subtypes. Clinically, the use of specific cognitive instruments to assess the expression and inhibition of motor impulses may help identify PD patients who have difficulty ‘thinking before they leap’ and are at high risk of falling.