Vestibular evoked myogenic potentials in Bell’s palsy

The aim of the present study was to evaluate vestibular nerve involvement in patients with Bell’s palsy with ocular and cervical vestibular evoked myogenic potentials (oVEMP and cVEMP). Ten patients who were diagnosed with Bell’s palsy and ten healthy controls were included. All patients underwent VEMP recordings within 6 days after their initial presentation. Patients with Bell’s palsy had greater oVEMP asymmetry ratio comparing to healthy controls (?38.4 ± 28.7 % vs ?1.3 ± 19.3 %, p = 0.005). As well N10 latencies of the oVEMP response were prolonged comparing to healthy controls (11.575 vs 9.72 ms). There was no difference in cVEMP asymmetry ratio or latencies between groups. We found no correlation between House–Brackmann grading scale and oVEMP asymmetry ratio (r = 0.003, p = 0.994). There are three possible explanations for increased oVEMP amplitudes on the affected side: (1) oVEMP response on the ipsilateral eye could be contaminated by facial nerve activity (blink reflex); (2) the amplitude of N10-P33 could be affected through the stapedial reflex; and (3) increased oVEMP amplitude could be the consequence of the vestibular nerve dysfunction itself, with prolonged latencies of the N10 oVEMP further supporting this explanation. The results of this study indicate possible involvement of the superior branch of the vestibular nerve in patients with Bell’s palsy.     

Mechanisms of unilateral STN-DBS in patients with Parkinson’s disease

Bilateral symptoms and signs of Parkinson’s disease (PD) are often improved by unilateral subthalamic nucleus deep brain stimulation (STN-DBS). However, the mechanism for such bilateral effects is unknown. This study was intended to examine effects of unilateral STN-DBS using positron emission computed tomography (PET) and to elucidate mechanisms for bilateral improvement achieved by unilateral stimulation. We conducted ¹⁸F-fluorodeoxyglucose (¹⁸FDG) and ¹⁸F-fluorodopa (¹⁸F-DOPA ) PET scans in PD patients whose bilateral limb symptoms and axial symptoms were improved by unilateral DBS. Two scans were performed in each PET study: when DBS was on and off. We compared those images using statistic parametric mapping (SPM) 99. The significant clinical improvement obtained by unilateral DBS was shown as improvements in bilateral motor limb, axial, and gait subscores of the Unified PD Rating Scale (UPDRS). Moreover, ¹⁸FDG PET revealed significant metabolic increases in the ipsilateral ventrolateral thalamic areas and metabolic decrease at the contralateral globus pallidus interna (GPi). In contrast, ¹⁸F-DOPA PET showed no significant differences between DBS on and off. Ipsilateral thalamic activation might induce ipsilateral motor cortical activation, which explains the improvement of contralateral limb symptoms. Furthermore, deactivation of the contralateral GPi might disinhibit the thalamus and contralateral motor cortex, which explains reduction of ipsilateral limb symptoms. These results suggest the mechanisms for bilateral improvement achieved by unilateral DBS.     

Ocular and cervical vestibular-evoked myogenic potentials to bone conducted vibration in Ménière’s disease during quiescence vs during acute attacks

ObjectiveTwo indicators of otolithic function were used to measure dynamic otolith function in the same patients both during an acute attack of Ménière’s disease (MD) and in the quiescent period between attacks.MethodsThe early negative component (n10) of the ocular vestibular-evoked myogenic potential (the oVEMP) to brief 500 Hz bone conducted vibration (BCV) stimulation of the forehead, in the midline at the hairline (Fz) was recorded by surface EMG electrodes just beneath both eyes while the patient looked up. It has been proposed that the n10 component of the oVEMP to 500 Hz Fz BCV indicates utricular function. It has been proposed that the early positive component (p13) of the cervical vestibular-evoked myogenic potential (the cVEMP) recorded by surface electrodes on both tensed SCM neck muscles to 500 Hz Fz BCV indicates saccular function.ResultsSixteen healthy control subjects tested on two occasions showed no detectable change in the symmetry of oVEMPs or cVEMPs to 500 Hz Fz BCV. In response to 500 Hz Fz BCV 15 early MD patients tested at both attack and quiescent phases showed a dissociation: there was a significant increase in contralesional of n10 of the oVEMP during the attack compared to quiescence but a significant decrease in the ipsilesional p13 of the cVEMP during the attack compared to quiescence.ConclusionsDuring an MD attack, dynamic utricular function in the affected ear as measured by the n10 of the oVEMP to 500 Hz Fz BCV is enhanced, whereas dynamic saccular function in the affected ear as measured by the p13 of the cVEMP to 500 Hz Fz BCV is not similarly affected.SignificanceThe MD attack appears to affect different otolithic regions differentially.     

Habituation of auditory event-related potentials in patients with Behcet’s disease

Abstract Behcets disease is a progressive and/or relapsing-remitting multisystem inflammatory disorder. Involvement of the central nervous system occurs in 10%–29% of cases with Behcets disease. The aim of the present study was to assess the effect of repetitive auditory stimulations on event-related potentials (ERP) in patients with Behcets without neurologic manifestations. The study was performed in 14 patients with Behcets disease and 14 healthy volunteers. ERPs were recorded from Fz, Cz and Pz. The auditory ERPs test was continued until 20 artefact-free rare tones were averaged, which was accepted as one trial block. After six blocks were obtained in a sequential manner, the test was completed. According to the results of the present study, P300 latency changed in different manners over trial blocks in the two groups. P300 latency values showed a progressive increase in the controls; however this was not determined in the Behcets group. Thus, habituation was not observed in the patient group. Because of the lack of habituation related to P300 latency, it may be thought that there is an insidious pathologic process in Behcets disease without neurologic manifestation.     

The role of event-related potentials in cognitive decline in Alzheimer’s disease

ObjectivesEarly diagnosis and monitoring of disease progression have become vital in clinical practice as disease modifying treatments for Alzheimer’s disease (AD) become available. This one-year prospective study aimed to clarify the usefulness of event-related potentials (ERPs) in cognitive decline and elucidate their cognitive significance in AD.MethodsUsing the Cognitive Abilities Screening Instrument (CASI) and ERPs, probable AD patients, mild cognitive impairment (MCI) patients, and normal controls were recruited.ResultsThe AD and MCI patients had significantly decreased cognitive function and manifested a delay of P300 latency. The P300 latencies demonstrated significantly more prolongation than their baseline values in probable AD and MCI patients, although their CASI scores showed no statistically significant decline. Whereas N100, P200, and N200 components did not reach statistical differences between groups either in the baseline or follow-up assessments and did not show significant change on follow-up.ConclusionThe combination of neuropsychological tests and P300 measurements proved useful in improving reliability and increasing sensitivity to early cognitive decline or disease progression in AD patients.SignificanceThe P300 latency may reflect cognitive decline more sensitively than neuropsychological tests in the longitudinal follow-up of AD patients.     

Degeneration of nigrostriatal dopaminergic neurons in an experimental model of the early clinical stage of Parkinson’s disease

The basis of the pathogenesis of Parkinson’s disease (PD) is progressive degeneration of dopaminergic neurons in the nigrostriatal system of the brain. The most important treatment of PD is using of drugs that delay neuronal death. The aim of the present study was to adapt our model of the early clinical stage of PD in mice [1] for its use as a test system for trials of potential neuroprotectors. Our data show that degeneration of the bodies of dopaminergic neurons in the substantia nigra starts 3 h after the last injection of 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) whereas the number of dopaminergic axons in the striatum is significantly decreased by this time point. Degradation of axons and neuronal bodies continues for the next 3 h. This period of time appears to be more appropriate for testing of neuroprotectors because later the number of neuronal bodies in the substantia nigra and axons in the striatum do not change. For the development of the test system, it is important to evaluate the functional state of surviving neurons. We found that 3 h after the last MPTP injection, the dopamine (DA) content in the substantia nigra decreased to 25% of the control level and 24 h later the DA content increased again and was 70% of the control value. The tyrosine hydroxylase content in neuronal bodies was similar to the control during the entire period of the study. In the striatum, the DA level decreased to 90% 3 h after the last MPTP injection and remained unchanged by the end of the study; however, the content of tyrosine hydroxylase decreased gradually by 12 h after the injection. Our data probably show the compensatory activation of tyrosine hydroxylase in both the substantia nigra and striatum. Thus, in a mouse model of the early clinical stage of PD we revealed that degeneration of nigrostriatal dopaminergic neurons ends 14 h after the start of the action of the specific neurotoxin. This was accompanied by activation of compensatory processes, which enhance DA-ergic neurotransmission.     

Variations in the neuropathology of familial Alzheimer’s disease

Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes cause autosomal dominant familial Alzheimer’s disease (AD). PSEN1 and PSEN2 are essential components of the γ-secretase complex, which cleaves APP to affect Aβ processing. Disruptions in Aβ processing have been hypothesised to be the major cause of AD (the amyloid cascade hypothesis). These genetic cases exhibit all the classic hallmark pathologies of AD including neuritic plaques, neurofibrillary tangles (NFT), tissue atrophy, neuronal loss and inflammation, often in significantly enhanced quantities. In particular, these cases have average greater hippocampal atrophy and NFT, more significant cortical Aβ42 plaque deposition and more substantial inflammation. Enhanced cerebral Aβ40 angiopathy is a feature of many cases, but particularly those with APP mutations where it can be the dominant pathology. Additional frontotemporal neuronal loss in association with increased tau pathology appears unique to PSEN mutations, with mutations in exons 8 and 9 having enlarged cotton wool plaques throughout their cortex. The mechanisms driving these pathological differences in AD are discussed.     

Sequestration of iron by Lewy bodies in Parkinson’s disease

Central to the oxidative stress hypothesis of Parkinson’s disease (PD) pathogenesis is the ability of iron to generate hydroxyl radicals via the Fenton reaction, and the consistent demonstration of iron elevation in the pars compacta region of the substantia nigra. However, uncertainty exists as to whether the excess iron exists in a state suitable for redox chemistry. Here, using a method we developed that detects redox-active iron in situ, we were able to demonstrate strong labeling of Lewy bodies in substantia nigra pars compacta neurons in PD. In contrast, cortical Lewy bodies in cases of Lewy body variant of Alzheimer’s disease were unstained. While the presence of elevated iron in PD substantiates the oxidative stress hypothesis, one must remember that these are viable neurons, indicating that Lewy bodies may act to sequester iron in PD brains in a protective, rather than degenerative, mechanism. The absence of redox-active iron in neocortical Lewy bodies highlights a fundamental difference between cortical and brain stem Lewy bodies. Received: 9 February 2000 / Revised: 31 March 2000 / Accepted: 2 April 2000     

Role of exosomes in the pathogenesis of inflammation in Parkinson’s disease

Inflammatory responses,including glial cell activation and peripheral immune cell infiltration,are involved in the pathogenesis of Parkinson’s disease(PD).These inflammatory responses appear to be closely related to the release of extracellular vesicles,such as exosomes.However,the relationships among different forms of glial cell activation,synuclein dysregulation,mitochondrial dysfunction,and exosomes are complicated.This review discusses the multiple roles played by exosomes in PD-associated inflammation and concludes that exosomes can transport toxicα-synuclein oligomers to immature neurons and into the extracellular environment,inducing the oligomerization ofα-synuclein in normal neurons.Misfoldedα-synuclein causes microglia and astrocytes to activate and secrete exosomes.Glial cell-derived exosomes participate in communications between glial cells and neurons,triggering anti-stress and anti-inflammatory responses,in addition to axon growth.The production and release of mitochondrial vesicles and exosomes establish a new mechanism for linking mitochondrial dysfunction to systemic inflammation associated with PD.Given the relevance of exosomes as mediators of neuron-glia communication in neuroinflammation and neuropathogenesis,new targeted treatment strategies are currently being developed that use these types of extracellular vesicles as drug carriers.Exosome-mediated inflammation may be a promising target for intervention in PD patients.     

Degeneration of the centré median-parafascicular complex in Parkinson's disease

Two major noncortical inputs to the striatum originate from the substantia nigra and the thalamic centré median-parafascicular complex. Although it is established that in Parkinson's disease there is degeneration of the nigral dopaminergic neurons, there has been little analysis of the glutamatergic centré median-parafascicular complex. We therefore evaluated these and neighboring thalamic nuclei (for specificity of any changes) in 9 Parkinson's disease patients and 8 age-matched controls. Degeneration in the substantia nigra and centré median-parafascicular complex was estimated by using quantitative neuronal counts. On average, 70% of the pigmented nigral neurons degenerated and there was 30% to 40% neuronal loss in the centré median-parafascicular complex in Parkinson's disease. Thalamic degeneration was marked in neuronal subpopulations (50% loss of parvalbumin-positive neurons in the parafascicular, and 70% loss of non-parvalbumin-positive neurons in the centré median nuclei). In contrast, adjacent thalamic nuclei did not degenerate, which supports a selective neurodegeneration of the centré median-parafascicular complex. Our results show that the thalamic centré median-parafascicular complex is an additional nondopaminergic site of neurodegeneration in Parkinson's disease. Because this thalamic region provides important sensorimotor feedback to the striatum, degeneration of this region is likely to exacerbate the clinical signs and symptoms of Parkinson's disease.     

Can verapamil be effective in controlling vertigo and headache attacks in vestibular migraine accompanied with Meniere’s disease? A preliminary study

Journal of Neurology -     

Altered functional connectivity of the amygdala in Crohn’s disease

Brain Imaging and Behavior - Crohn’s disease (CD), a chronic inflammatory bowel disease, involved in brain structural and functional changes, including the amygdala. Amygdala is a key...     

High-resolution ultrasound changes of the vagus nerve in idiopathic Parkinson’s disease (IPD): a possible additional index of disease

Neurological Sciences - Histopathological studies revealed degeneration of the dorsal motor nucleus of the vagus nerve (VN) early in the course of idiopathic Parkinson’s disease (IPD)....     

Auditory event-related potentials in subcortical vascular cognitive impairment and in Alzheimer’s disease

Summary. Background: Few studies exist on ERPs and patients with subcortical vascular cognitive impairment (SVCI). This latter is a quite homogeneous subtype of vascular dementia whose cognitive profile is quite different from that of Alzheimer disease (AD). Aims: The present study aims at comparing the ERPs profile both in patients with SVCI and in patients with AD. Subjects and methods: ERPs and psychometric tests were collected from 39 healthy elderly controls, 51 patients with SVCI and 43 patients with AD. Subjects mentally count high pitched target tones that were randomly intermixed with low pitched frequent tones. We measured ERPs latencies (N1, P2, N2 and P3), and interpeak latencies (N1–P3, N1–P2, N1–N2). Results: Grand averaged potentials in SVCI showed a significant increase of P3 latency. AD patients showed a prolongation of N1, P2, N2, P3 latencies. As far as interpeak latencies are concerned, SVCI patients showed a significant prolongation of N1–P3, AD patients had a significant increase of N1–N2, and N1–P3 intervals. When all patients were considered as a single group, correlation of neuropsychological tests scores showed a significant negative relationship between P300 latency and, respectively, Mini Mental Status Examination, auditive and visual span forward. In both groups, ERPs latency sensitivity, was low, whilst specificity values were quite high. Conclusions: Our finding suggest that these two dementing diseases have different electrophysiologic features that may be related to their specific underlying pathogenetic mechanism; in particular, we hypothesise that, differently from AD, P300 latency prolongation characterizes the early stage of SVCI. So, this ERPs approach could be helpful to detect early alterations of the attentional/working-memory functions in patients with subcortical ischaemic vascular disease.     

Possible roles ofl-phosphoserine in the pathogenesis of Alzheimer’s disease

l-Phosphoserine is a membrane metabolite that is elevated in Alzheimer’s disease brain. This compound has close structural similarity tol-glutamate. Electrophysiological studies indicate thatl-phosphoserine has an acute inhibitory effect, but a delayed excitatory action. A hypothesis is developed based on pharmacological and electrophysiological studies that suggest that the inhibition may be mediated through presynaptic inhibition ofl-glutamate release or perhaps antagonism of postsynaptic kainic acid receptors. The mechanism of the delayed excitation may lie in the tendency ofl-phosphoserine to mimic the action ofl-2-amino-4-phosphonobutyric acid, a blocker of chloride- and calcium-sensitivel-glutamate transport.l-Phosphoserine has also been found to be a competitive antagonist at theN-methyl-d-aspartate recognition site and an antagonist of metabotropic receptor-mediated hydrolysis of inositol phospholipids. Because of these actions, there are several potentially important implications for the elevation ofl-phosphoserine in Alzheimer’s disease, including production memory impairment through presynaptic inhibition ofl-glutamate release or blockade of postsynapticN-methyl-d-aspartate receptors and/or blockade of certainl-glutamate transport sites resulting in increasedl-glutamate levels in the synaptic cleft.     

Short-chain fatty acids in the context of Parkinson’s disease

Research on neurodegenerative diseases such as Alzheimer’s disease,Parkinson′s disease(PD),Huntington’s disease or amyotrophic lateral sclerosis is becoming increasingly important in our society.Due to the ageing of the population,the prevalence of these diseases continue to rise worldwide,and causal cures are not yet available(Erkkinen et al.,2018).This Perspective focusses on PD,a movement disorder of the central nervous system with an estimated prevalence between 65 and 1250/100,000 in Europe,affecting about 1 percent of the population older than 60 years.The clinical symptoms include motor symptoms like bradykinesia,tremor or rigidity which are associated with loss of dopaminergic neurons in the substantia nigra and their innervating axonal fibers to the striatum.Additional non-motor symptoms may consist in depression,hyposmia,cognitive decline or constipation due to impaired motility of the gastrointestinal tract.     

Blood-brain barrier integrity in the pathogenesis of Alzheimer’s disease

The blood–brain barrier (BBB) tightly controls the molecular exchange between the brain parenchyma and blood. Accumulated evidence from transgenic animal Alzheimer’s disease (AD) models and human AD patients have demonstrated that BBB dysfunction is a major player in AD pathology. In this review, we discuss the role of the BBB in maintaining brain integrity and how this is mediated by crosstalk between BBB-associated cells within the neurovascular unit (NVU). We then discuss the role of the NVU, in particular its endothelial cell, pericyte, and glial cell constituents, in AD pathogenesis. The effect of substances released by the neuroendocrine system in modulating BBB function and AD pathogenesis is also discussed. We perform a systematic review of currently available AD treatments specifically targeting pericytes and BBB glial cells. In summary, this review provides a comprehensive overview of BBB dysfunction in AD and a new perspective on the development of therapeutics for AD.