Editorial Board

Publication date: March 2016
Source:Clinical Neurophysiology, Volume 127, Issue 3





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Correlation of tau pathology in eye movement related brainstem nuclei in cases of progressive supranuclear palsy (PSP) and a proposed role of perineuronal nets

Publication date: March 2016
Source:Clinical Neurophysiology, Volume 127, Issue 3
Author(s): A. Horn, A. Fröschl, J. Feige, S. Röber, H. Kretzschmar
BackgroundProgressive supranuclear palsy (PSP) is characterized by hyperphosphorylated tau protein (HTP) accumulations in different brain regions. A hallmark of clinical symptoms is a vertical gaze palsy, which may be accompanied by horizontal gaze palsy, whereas the VOR is rather preserved until late in the disease. Based on monkey studies functional cell groups of the oculomotor system including transmitters have been identified in the human brainstem (Büttner-Ennever & Horn, 2010).MethodsTo study the spread of the disease through the oculomotor premotor network sections of 8 archival PSP cases with different eye movement deficits were immunostained for HTP. The analysis involved the glutaminergic rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF) and paramedian pontine reticular formation (PPRF), the glycinergic saccadic omnipause neurons (OPN), the cholinergic oculomotor nucleus (nIII) and the vestibular nuclei (VN). Since the RIMLF and nIII contain well-developed perineuronal nets (PN) (Horn et al., 2003), we further stained sections of the PSP cases for the presence of aggrecan (ACAN) and HTP to prove a possible protective role of PNs as suggested from Alzheimer's disease cases (Morawski et al., 2010).ResultsAll PSP-cases showed HTP-staining in neurons and glia of RIMLF, PPRF and OPNs, in late cases in motonuclei as well. Thereby a correlation between eye movement deficits and degeneration of premotor gaze centers and the complete pathways to motoneurons was found, whereas the VN are less affected. The analysis of PNs revealed that ACAN-based PNs were mainly found around HTP-negative neurons, and only few HTP-positive neurons showed weak ACAN staining.ConclusionsThe early and more severe degeneration of premotor centers compared to nIII support a hypothesis that in PSP the pathology progresses along neuronal chains in an anterograde fashion, and it is not confined to specific transmitters. The severe tau pathology in RIMLF and nIII in late PSP cases implies that the presence of PNs may not protect them from degeneration, but on a cellular basis the integrity of PNs is affected by tau-pathology.Support: BMBF (IFB-01EO0901, Brain-Net-01GI0505).



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Investigation of the brainstem blink reflex circuitry in patients with juvenile myoclonic epilepsy

Publication date: March 2016
Source:Clinical Neurophysiology, Volume 127, Issue 3
Author(s): N. Uzun, M. Kandemir, M.E. Kiziltan, A. Gunduz, S.N. Yeni
BackgroundJuvenile myoclonic epilepsy (JME) which is among idiopathic generalized epilepsies presents with myoclonus and/or generalized tonic–clonic seizures during puberty. Electrophysiological studies showed findings at several levels including cortex, thalamus and spinal cord in JME. Given these information, we aimed to analyze electrophysiological findings at the level of brainstem using blink reflex (BR) and blink reflex recovery cycle (BR-RC).MethodsEighteen JME patients and age and sex matched 18 healthy volunteers are included in the study. BR and BR-RC with interstimulus intervals of 200ms and 400ms were recorded over orbicularis oculi on the nondominant side under the same conditions.ResultsJME patients had longer onset latencies (p=0.046) and higher amplitudes (p=0.022) of R2 component of BR. Recovery of responses after double stimulation with interstimulus interval of 400ms was higher in JME patients (p=0.040). Use of valproate did not have an impact on reflex responses.ConclusionOur results support increased excitability of BR pathway in JME without relevant pathological findings regarding BR.



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Somatosensory and auditory startle reflex in patients with stroke and spinal cord injury

Publication date: March 2016
Source:Clinical Neurophysiology, Volume 127, Issue 3
Author(s): M.E. Kiziltan, M. Sohtaoglu, A. Gunduz, M. Bozluolçay, N. Uzun
BackgroundSomatosensory startle reflex (SSSR) was recently studied in healthy subjects. Following corticospinal tract lesions caused by stroke or spinal cord injury (SCI), auditory startle reflex (ASR) has been reported to enhance due to reorganization of circuits rostral and caudal to the lesion. To further understand changes in SSSR and ASR, we investigated both responses in patients with spinal cord injury (SCI) and stroke.MethodsWe examined characteristics of ASR and SSSR in 14 SCI and 40 stroke patients (16 brainstem and 24 cerebral hemispheric infarctions) and 39 age and gender matched healthy subjects. ASR was obtained after eight auditory stimuli and SSSR was elicited after median nerve stimulation at the wrist. Surface electromyographic recordings were obtained from orbicularis oculi (O.oc), sternocleidomastoid (SCM), biceps brachii (BB) and abductor pollicis brevis (APB) muscles.ResultsTotal ASR probabilities at distal muscles were significantly higher in patients with SCI and in stroke patients especially with brainstem infarctions. Similarly SSSR rates were increased in both patient groups compared to controls (for APB p<0.05). SSR latency of O.oc in SCI patients were similar to controls whereas it was markedly prolonged in stroke patients (p<0.05).ConclusionsIn conclusion, we have found that SSR and ASR were enhanced in stroke and SCI and this enhancement was more prominent in distal muscles. Secondly, the properties of ASr and SSSR differed according to the lesion site.



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Startle reaction evoked by kinematic stimuli

Publication date: March 2016
Source:Clinical Neurophysiology, Volume 127, Issue 3
Author(s): J.M. Castellote, M. Kofler, A. Mayr, L. Saltuari
BackgroundKinematic stimuli are used for both assessment and treatment in neurorehabilitation. A patient's voluntary or reflex response may be affected by a startle reaction. We therefore explored whether certain kinematic stimuli are able to elicit a startle reaction.MethodsEleven healthy subjects were suspended in a Lokomat system and were exposed to unexpected passive left knee flexion at 3 velocities (6, 60, 240°/s). Subjects were asked to perform a right wrist extension as soon as they felt their leg move (conditions: 6-React, 60-React, 240-React, respectively). In some 240°/s trials movement onset was preceded by a low-intensity electrical pre-pulse to the left index finger (240-Prep-React). We recorded EMG activity from right orbicularis oculi and sternocleidomastoid muscles to assess startle responses, from left quadriceps muscle to obtain stretch reflexes, and from right wrist extensors to assess reaction time.ResultsStartle responses were present in most 240-Reacttrials, as evidenced by (1) EMG activity in orbicularis oculi and/or sternocleidomastoid, (2) significant reaction time shortening in wrist extensors, and (3) stretch reflex latency shortening in quadriceps, as compared to responses without startle reaction. Only few trials at lower angular velocities resulted in startle responses. In 240-Prep-React trials no startle responses occurred.ConclusionsKinematic stimuli of high angular velocity, used to assess muscle stiffness, may elicit a generalized startle reaction, which in turn may modulate stretch reflex latencies of the muscle tested in a passive movement paradigm.



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Visualization of human brainstem substructures using gray matter nulling 3D-MPRAGE at 7Tesla

Publication date: March 2016
Source:Clinical Neurophysiology, Volume 127, Issue 3
Author(s): B. Daeubler, M. Wyss, M. Bruegger, L. Vionnet, D. Brunner, K. Pruessmann
BackgroundThe human brainstem is one of the most complex neural entities, in both, structural and functional domains. Its plurality of small and densely packed substructures results in demanding settings for in vivo MR visualization. We addressed this issue applying ultra-high field MRI at 7Tesla focusing on enhanced differentiation of brainstem substructures. This approach is an essential prerequisite breaking down the complex brainstem anatomy.MethodsA modified 3D-MPRAGE-sequence in the sagittal and transverse plane was applied in a 7T MR-system. To compensate for B1-inhomogeneities, a highly adiabatic inversion prepulse was implemented. Five healthy volunteers were examined. The resulting images were visually correlated to histological plates and post-mortem MRI images from Duvernoy's Atlas.ResultsWe identified 22 structures (sagittal), clearly assignable to histology data. In the brainstem 12 substructures were manually outlined for all five subjects, also based on histology. Adopting histology nomenclature clearly identifiable structures were labeled.ConclusionsOptimized 3D-MPRAGE-imaging in the gray matter nulling regime at 7Tesla provides enhanced image contrast between substructures in the human brainstem, giving rise to better understanding anatomy and potentially related pathology.



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Optokinetic nystagmus of Chiari Malfromation. The aim of our study is to determine the special characteristics of disorders of the Optokinetic nystagmus in the early stages of Chiari Malformation

Publication date: March 2016
Source:Clinical Neurophysiology, Volume 127, Issue 3
Author(s): D. Demidenko, V. Viktor
BackgroundDiagnosis and treatment of cochleovestibular dysfunction becomes complicated in case of genetically based combination of pathology. The Chiari Malformation (CM) is a congenital development defect and associated with the caudal displacement of cerebellum and brain stem.The aim of this study is to determine the special characteristics of disorders of the Optokinetic nystagmus in the early stages of CM.At the otorhinolaryngology department of North-West State Medical University named after I.I.Mechnikov (Russia, St Petersburg), 54 cases (patients aged 16–69 ) were studied. All patients showed the symptoms of cochleovestibular dysfunction.MethodsThe Optokinetic nystagmus was taken in a dark-room using VNGULMAR system manufactured by the German company "Heinemann Medizintechnik GmBH" running software developed by the French company Synapsys. The fixed speed horizontal and vertical Optokinetic stimulus on screen (20 o/s) was applied with distracted and focused attention of the patients.All the studies were conducted before the calloric test (CT) and after CT. The intensity of Optokinetic nystagmus was assessed as per SSC (speed of slow component) of nystagmus. Later on the relative asymmetry in Optokinetic nystagmus was calculated for each same name pair of horizontal and vertical Optokinetic reactions.ResultsThe studies showed that in order to diagnose CM in the early stages it is important not only to identify the asymmetry in horizontal and vertical Optokinetic nystagmus but to mark the value and the sign of asymmetry as well. The sign of asymmetry is especially important after CT. Patients with the low placement of cerebellar tonsil Optokinetic reactions are more susceptible to CT.ConclusionsTherefore, in the early stages of CM and "in the risk group", i.e. the patients with low placement of cerebellar tonsil, before the neurological symptoms have taken place and we have only vestibular dysfunction, the videonystagmography with quantitative evaluation of Optokinetic reaction becomes a voluble source of important diagnostic information and an indication for MRI studies.



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