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Several studies have shown that, in spite of the fact that motor symptoms manifest late in the course of Alzheimer's disease (AD), neuropathological progression in the motor cortex parallels that in other brain areas generally considered more specific targets of the neurodegenerative process. It has been suggested that motor cortex excitability is enhanced in AD from the early stages, and that this is related to disease's severity and progression. To investigate the neurophysiological hallmarks of motor cortex functionality in early AD we combined transcranial magnetic stimulation (TMS) with electroencephalography (EEG). We demonstrated that in mild AD the sensorimotor system is hyperexcitable, despite the lack of clinically evident motor manifestations. This phenomenon causes a stronger response to stimulation in a specific time window, possibly due to locally acting reinforcing circuits, while network activity and connectivity is reduced. These changes could be interpreted as a compensatory mechanism allowing for the preservation of sensorimotor programming and execution over a long period of time, regardless of the disease's progression. Hum Brain Mapp 37:2083-2096, 2016. © 2016 Wiley Periodicals, Inc.

Obstructive sleep apnea (OSA) is linked to an increased mortality rate. However, the severity of individual obstruction events is rarely considered quantitatively in clinical practice. We hypothesized that OSA with especially severe obstruction events would predispose a patient to greater health risks than OSA with a similar apnea-hypopnea index (AHI), but lower severity of individual events. This hypothesis was tested in a follow-up (198.2 ± 24.7 months) of a population of 1068 men referred for ambulatory polygraphic recording due to suspected OSA. The recordings were analysed according to the guidelines of the American Academy of Sleep Medicine. Furthermore, a novel obstruction severity parameter was determined; this was defined as the product of duration of the individual obstruction event and area of the related desaturation event. Patients treated with continuous positive airway pressure (CPAP) were omitted. We identified 125 deceased patients from our original population and for 113 of these a matching alive patient with similar AHI, age, body mass index (BMI), smoking habits and follow-up time could be found. The deceased patients with severe OSA (based on conventional AHI) showed higher obstruction severity values than their AHI-matched alive controls. Based on the multivariate logistic regression analysis, obstruction severity was the only parameter which was related statistically significantly to mortality in the severe OSA category. Furthermore, 59% of all deceased patients and 83% of those who had severe OSA displayed higher obstruction severity than the AHI-matched alive counterparts. To conclude, the obstruction severity parameter provided valuable prognostic information supplementing AHI. The obstruction severity parameter might improve recognition of the patients with the highest risk.

Unverricht-Lundborg disease is the most common form of progressive myoclonus epilepsies. In addition to generalized seizures, it is characterized by myoclonus, which usually is the most disabling feature of the disease. Classically, the myoclonus has been attributed to increased excitability of the primary motor cortex. However, inhibitory cortical phenomena have also been described along with anatomical alterations. We aimed to characterize the relationship between the excitability and anatomy of the motor cortex and their association with the severity of the clinical symptoms. Seventy genetically verified patients were compared with forty healthy controls. The symptoms were evaluated with the Unified Myoclonus Rating Scale. Navigated transcranial magnetic stimulation was applied to characterize the excitability of the primary motor cortex by determining the motor thresholds and cortical silent periods. In addition, the induced cortical electric fields were estimated using individual scalp-to-cortex distances measured from MRIs. A cortical thickness analysis was performed to elucidate possible disease-related anatomical alterations. The motor thresholds, cortical electric fields, and silent periods were significantly increased in the patients (P < 0.01). The silent periods correlated with the myoclonus scores (r = 0.48 to r = 0.49, P < 0.001). The scalp-to-cortex distance increased significantly with disease duration (r = 0.56, P < 0.001) and correlated inversely with cortical thickness. The results may reflect the refractory nature of the myoclonus and indicate a possible reactive cortical inhibitory mechanism to the underlying disease process. This is the largest clinical series on Unverricht-Lundborg disease and the first study describing parallel pathophysiological and structural alterations associated with the severity of the symptoms.

Background: The clinical benefits of intensive stroke rehabilitation vary individually. We used multimodal functional imaging to assess the relationship of clinical gain and imaging changes in patients with chronic stroke whose voluntary motor control improved after constraint-induced movement therapy (CIMT). Methods: Eleven patients (37.6 ± 36.8 months from stroke) were studied by functional MRI (fMRI), transcranial magnetic stimulation (TMS), and behavioral assessment of hand motor control (Wolf Motor Function Test) before and after 2 weeks of CIMT. Individual and group-level changes in imaging and behavioral parameters were investigated. Results: Increase in fMRI activation in the sensorimotor areas was greater amongst those subjects who had poor hand motor behavior before therapy and/or whose motor behavior improved notably because of therapy than amongst subjects with relatively good motor behavior already before therapy. The magnitude of CIMT-induced changes in task-related fMRI activation differed between lesioned and non-lesioned hemispheres, and the fMRI laterality index was different for paretic and non-paretic hand tasks. The corticospinal conduction time in TMS was significantly decreased after CIM therapy. Conclusions: Alterations in sensorimotor cortical activations (fMRI) and corticospinal conductivity (TMS) were observed after intensive rehabilitation in patients with chronic stroke. Activation and functional changes in fMRI and TMS correlated significantly with the degree of clinical improvement in hand motor behavior. The present data advance the understanding of the functional underpinnings of motor recovery, which may be obtained even years after the stroke.

Patients with Unverricht-Lundborg disease, also referred to as progressive myoclonus epilepsy type 1, exhibit widespread motor symptoms and signs in addition to epileptic seizures, which suggest abnormal excitability of the primary motor pathways. To explore the plasticity of the sensory-motor cortex, we employed a modern neurophysiological method, the paired associative stimulation protocol, which resembles the concept of long-term potentiation of experimental studies. Seven patients with genetically verified Unverricht-Lundborg disease and 13 healthy control subjects were enrolled in the study to characterize cortical sensory-motor plasticity. In the study protocol, peripheral electric median nerve stimulation preceded navigated transcranial magnetic stimulation targeted to the representation area of thenar musculature on the contralateral primary motor cortex. The protocol consisted of 132 transcranial magnetic stimulation trials at 0.2 Hz, preceded by peripheral sensory stimulation at 25 ms. Motor-evoked potential amplitudes were analyzed at baseline and after the paired associative stimulation protocol at an intensity of 130% of the individual motor threshold. The patients with Unverricht-Lundborg disease exhibited an average decrease of 15% in motor-evoked potential amplitudes 30 minutes after paired associative stimulation, whereas in the control subjects, a significant increase (101%) was observed (P < .05), as expected. The results indicate a lack of normal cortical plasticity in Unverricht-Lundborg disease, which stresses the role of abnormal motor cortical functions or sensorimotor integration as possible pathophysiological contributors to the motor symptoms. The impaired cortical plasticity may be associated with the previously reported structural and physiological abnormalities of the primary motor cortex.

Summary Purpose: The outcome of surgery in patients with temporal lobe epilepsy (TLE) and normal high-resolution magnetic resonance imaging (MRI) has been significantly worse than in patients with unilateral hippocampal damage upon MRI. The purpose of this study was to determine the long-term outcomes of consecutive true MRI-negative TLE patients who all underwent standardized preoperative evaluation with intracranial electroencephalography (EEG) electrodes. Methods: In this study we present all adult MRI-negative TLE surgery candidates evaluated between January 1990 and December 2006 at Kuopio Epilepsy Center in Kuopio University Hospital, which provides a national center for epilepsy surgery in Finland. During this period altogether 146 TLE surgery candidates were evaluated with intracranial electrodes, of whom 64 patients with normal high-resolution MRI were included in this study. Results: Among the 38 patients who finally underwent surgery, at the latest follow-up (mean 5.8 years), 15 (40%) were free of disabling seizures (Engel class I) and 6 (16%) were seizure-free (Engel class IA). Twenty-one (55%) of 38 patients had poor outcomes (Engel class III–IV). Outcomes did not change compared to 12-month follow-up. Histopathologic examination failed to reveal any focal pathology in 68% of our MR-negative cases. Only patients with noncongruent positron emission tomography (PET) results had worse outcomes (p = 0.044). Discussion: Our results suggest that epilepsy surgery outcomes in MRI-negative TLE patients are comparable with extratemporal epilepsy surgery in general. Seizure outcomes in the long-term also remain stable. Modern imaging techniques could further improve the postsurgical seizure-free rate. However, these patients usually require chronic intracranial EEG evaluation to define epileptogenic areas.

Summary Purpose: Appropriate treatment of generalized convulsive refractory status epilepticus (RSE) requires general anesthesia in the intensive care unit (ICU) with continuous electroencephalography (cEEG) monitoring. During out of office hours and weekends, cEEG monitoring is not always available. The Bispectral Index (BIS) monitor can be used to assess the hypnotic component of general anesthesia. We conducted a study to evaluate the feasibility of using the BIS monitoring to assess the burst suppression (BS) pattern during propofol anesthesia in RSE. Methods: Ten adult patients with RSE admitted to the ICU were monitored simultaneously with cEEG and BIS monitoring. We compared the BIS and suppression ratio (SR) values with the EEG burst suppression pattern when the depth of anesthesia was titrated to the BS level monitoring by cEEG. Results: We found an excellent correlation between the cEEG burst rate per minute and the BIS (r2 = −0.9; p

Human temporal lobe epilepsy (TLE) is associated with cellular alterations (eg, hilar cell death, neurogenesis, and granule cell dispersion) in the dentate gyrus but their underlying molecular mechanism are not known. We previously demonstrated increased expression of cystatin C, a protease inhibitor linked to both neurodegeneration and neurogenesis, during epileptogenesis in the rat hippocampus. Here, we investigated cystatin C expression in the dentate gyrus in chronic epilepsy and its association with neuronal loss and neurogenesis. In both rats with epilepsy and human patients with TLE, cystatin C expression was increased in glial cells in the molecular layer of the dentate gyrus, being most prominent in cases with granule cell dispersion. In patients with TLE, high cystatin C expression associated with greater numbers of polysialylated neural cell adhesion molecule-positive newborn cells in the molecular layer, although the overall number was decreased, indicating that the newborn cells migrate to abnormal locations in the epileptic dentate gyrus. These data thus demonstrate that cystatin C expression is altered during the chronic phase of epilepsy and suggest that cystatin C plays a role in network reorganization in the epileptic dentate gyrus, especially in granule cell dispersion and guidance of migrating newborn granule cells.

Summary: The effect of short-term discontinuation of antiepileptic drugs (AEDs) on spectral analysis of EEG background activity (spectral EEG) was studied in patients undergoing preoperative evaluation for epilepsy surgery. We also wished to clarify whether AED discontinuation would provide lateralizing evidence in spectral EEGs of patients with temporal lobe epilepsy (TLE). Spectral EEGs were performed in 15 patients receiving their regular medication regimen and again after a 1-week period during AED withdrawal. A subgroup of 9 patients who had previously undergone temporal lobectomies (TLE group) was studied separately. In this group, we evaluated the effect of preceding seizures on spectral EEG derived from temporal neocortical areas. In all patients, spectral EEG changes were detected even after a short-term AED withdrawal. The total amount of absolute delta activity was reduced and occipital peak frequency and relative alpha activity were increased as compared with baseline values. In TLE patients with habitual seizures occurring

To evaluate the role of different EEG methods with respect to postoperative clinical follow-up, 32 non-lesionary epilepsy patients who had undergone temporal lobectomy were studied preoperatively and at 2-week, 3-month, and 1-year postoperative follow-up. Routine, sleep, and sphenoidal EEG recordings as well as intraoperative electrocorticography (ECoG) were made for all patients. At 1-year follow-up, the EEGs with sphenoidal electrodes and with sleep deprivation procedure provided important prognostic information; the appearance of seizures was associated with the presence of interictal epileptiform abnormalities in EEG. In the postresection ECoG, however, epileptiform abnormalities were not associated with clinical outcome or with postoperative epileptiform EEG at 1 year. Routine EEG reliably reflects clinical outcome after temporal lobectomy; with sphenoidal electrodes as well as with sleep deprivation procedure, the diagnostic yield can be further improved.

Summary: We studied auditory event-related potentials (ERPs) in 11 surgically treated patients with intractable temporal lobe epilepsy (TLE) pre- and postoperatively. ERPs through sphenoidal electrodes (Sp1-T3, Sp2-T4) provided clinically relevant and correctly lateralizing electrophysiologic evidence of temporal lobe dysfunction in 9 of 11 patients, confirmed by EEGs, electrocorticograms, neuroradiologic, and neuropsychological results, and clinical follow-up. Lateralizing asymmetries were noted in P300 amplitude, but latencies were prolonged bilaterally. Sphenoidal ERPs might serve as a new functional indicator of temporal lobe dysfunction in patients evaluated for epilepsy surgery.

Summary: Visual and brainstem auditory evoked potentials (VEP and BAEP, respectively) and quantitative EEG were studied in 16 patients with Baltic progressive myoclonus epilepsy (PME). The study demonstrated significantly delayed VEP latencies but normal amplitudes in Baltic PME. BAEPs showed slight but significant prolongation in central conduction time. Quantitative EEG revealed diminution of beta and alpha activity and accentuation of theta and delta activity. The slowing in VEP latencies is suggested to be due to impaired synaptic transmission and to reflect dopaminergic dysfunction in Baltic PME. We conclude that there is a multimodal disturbance in sensory projections to cortical areas in Baltic PME. The results give further evidence that nondemyelinating disorders—but with synaptic transmission defects—can produce changes in evoked potentials. The changes in epileptic brain are not confined to hyperexcitable epileptic neurons, but more widespread electrophysiological phenomena are produced. RESUME Les potentiels evoques visuels (VEP), les potentiels evoques auditifs du tronc cerebral (BAEP) et l'EEG quantitatif ont eteetudies chez 16 patients ayant une epilepsie myoclonies progressive (PME) type Baltique. Cette etude a mis en evidence des latences augmentees significativement mais des amplitudes normales pour les VEP dans la PME baltique. Les BAEP montraient un allongement leger mais significatif du temps de conduction central. L'EEG quantitatif montrait une diminution des activites beta et alpha et une accentuation des activites theta et delta. L'augmentation des latencies des VEP serait due a un trouble de la transmission synaptique et refleterait une dysfonction dopaminergique dans la PME baltique. Les auteurs concluent qu'il y a un dysfonctionnement plurimodal des projections sensorielles vers les aires corticales. Ces resultats confirment que des desordres non-demyelinisants mais s'accompagnant d'un defaut de la transmission synaptique peuvent modifier les potentiels evoques. Les changements dans le cerveau epileptique ne se limitent pas aux neurones epileptiques hyperexcitables mais peuvent produire des phenomenes electrophysiologiques plus diffus. RESUMEN En 16 pacientes con epilepsia mioclonica progresiva tipo Baltico, se han estudiado los potenciales evocados visuales (VEP) y auditivos de tronco cerebral (BAEP) y tambien se ha cuantifi-cado el EEG. El estudio ha demostrado una lentificacion significativa de las latencias de los VEP pero con amplitudes normales en los casos de epilepsia mioclonica Baltica. Los potenciales BAEPs mostraron una leve pero significativa prolongacion del tiempo de conduccion central. El EEG cuantitativo revelo una disminucion de la actividad'beta y alfa y una acentuacion de las actividades zeta y delta. La lentificacion de las latencias de los VEP se interpreta como debida a una alteracion de la transmision sinaptica y podria ser debida a una disfuncion dopaminergica en los casos de epilepsia mioclonica Baltica. Se concluye que existe un trastorno multimodal en las proyecciones sensitivas hacia las areas corticales en los casos de epilepsia mioclonica Baltica. Estos resultados anaden mas evidencia al concepto de que defectos de la transmision sinaptica no debidos a procesos no-desmielinizantes pueden producir cambios en los potenciales evocados. Los cambios en el cerebro epileptico no se limitan a las neuronas epilepticas hiperexcitables, sino que se producen fenomenos electrofisiologicos mas dispersos. ZUSAMMENFASSUNG Visuelle (VEP) und akustische evozierte Hirnstamm Potentiale (BAEP) und quantitative EEG-Untersuchungen wurden bei 16 Patienten mit baltischer progressiver Myoklonus Epilepsie durchgefuhrt. Die Untersuchung zeigte signifikant verzogerte VEP-Latenzen, aber normale Amplituden bei der baltischen PME. Die BAEPs zeigten eine geringe aber signifikante Verlan-gerung der zentralen Leitungszeit. Die quantitative EEG-Untersuchung zeigte eine Verminderung von Beta-und Alpha-Akti-vitat und eine Zunahme von Theta- und Delta-Aktivitat. Die Verlangsamung der VEP-Latenzen wird einer beeintrachtigten synaptischen Ubertragung zugeschrieben und ist Ausdruck einer dopaminergischen Dysfunktion bei der baltischen PME. Wir folgern, das eine multimodale Storung der sensorischen Projektion zu kortikalen Arealen bei der baltischen PME vorhanden ist. Die Ergebnisse zeigen weiterhin, das nicht demyelinisierende Storungen mit Defekten der synaptischen Ubertragung Veranderungen der evozierten Potentiale hervorrufen konnen. Die Veran-derungen im epileptischen Gehirn sind nicht auf die hyperexzitablen epileptischen Neurone beschrankt sondern es werden ausgedehntere elektrophysiologische Phanomene hervorgerufen.

Summary: The effects of -γ-vinyl GABA (GVG) and carbamazepine (CBZ) monotherapy on somatosensory (SEP) and visual (VEP) evoked potentials and spectral quantitative EEG (QEEG) were studied in 17 patients with complex partial seizures using a cross-over double-blind study design. CBZ was associated with statistically significant prolongation of SEP latencies. When the drug was switched to GVG, shortening of the peak latencies was observed. Prolonged pattern-VEP peaks were observed both during CBZ and GVG monotherapies. A similar but more subtle tendency of the peaks was observed in P100 latencies. Spectral EEG revealed a slowing of the occipital rhythm with CBZ. No QEEG changes related to GVG were found. The use of multimodal evoked potentials and QEEG should be considered in studying the effects of new antiepileptic drugs (AEDs). Key Words: An-tiepileptic drugs–γ-Vinyl GABA–Carbamazepine– Electroencephalography–Evoked potentials–Spectral EEG. RESUME Les effets du Gamma-vinyl-GABA (GVG) et de la carbamazepine (CBZ) sur les potentiels evoques somesthesiques (PES) et visuels (PEV) ainsi que sur l'EEG quantife par analyse spec-trale ont eteetudies chez 17 patients presentant des crises partielles complexes dans une protocole croise en double aveugle. La CBZ a ete associee a un allongement significatif des latences des PES. Lorsque la CBZ etait remplaces par le GVG, une di minution des latences du pic etait observed. Un retard au pic des PEV par damiers a ete observe sous monotherapie par CBZ et par GVG. Une tendance similaire, mais moins prononcee, a ete constatee dans l'eude des latences P100. L'EEG spectral a mis en evidence un ralentissement du rythme occipital sous CBZ; il n'a pas ete constate de modification de l'EEG quantife sous GVG. Les potentiels evoques multimodalitaires et l'EEG quantifie devraient etre utilises dans l'evaluation des nouveaux medicaments anti-epileptiques. RESUMEN En 17 enfermos con ataques parciales complejos y utilizando un estudio cruzado doble ciego, se nan valorado los efectos del Gamma-vini] GABA (GVG) y de la Carbamazepina (CBZ) como monoterapias, sobre los potenciales evocados somatosensoriales (SEP) y visuales (VEP) y sobre el estudio espectral cuantitativo del EEG (QEEG). Se observo que la CBZ mostraba una prolon-gacion estadisticamente significativa de las latencias de los SEP. Cuando la medicacion se cambio a GVG se observo un acor-tamiento de los picos de las latencias. El patron de alargamiento de los picos de los VEP se observo tanto durante la monoterapia con CBZ como con la GVG. Una tendencia similar pero mis sutil de los picos se observd en las latencias P100. El EEG espectral revelo una lentificacion de los ritmos occipitales con CBZ. No se encontraron cambios del QEEG relacionables al tratamiento con GVG. La utilizacion de potenciales evocados multimodales y el QEEG deberia ser considerada en el estudio de los efectos de las drogas antiepilepticas.

Summary: Twenty ambulatory outpatients with generalized tonic-clonic seizures with primary generalized discharges and photoconvulsive reponse on electroencephalogram (EEG) and 11 ambulatory outpatients with partial complex seizures with or without secondary generalization were studied with pattern-reversal light-emitting diode (LED) stimulator visual evoked potential (VEPs) and short-latency median nerve cortical somatosensory evoked potentials (SEPs). The patients with primary generalized epilepsy had significantly prolonged latencies of VEP components P2 and N3 and SEP component P22. The patients with partial epilepsy had significantly prolonged latency of VEP component N3. It is concluded that both functional and structural factors may cause a slowing of central impulse conduction. RESUME Chez 20 sujets consultants ayant des crises generalisees tonico-cloniques, et sur l'EEG des decharges generalisees primaires et une reponse photoconvulsive, et chez 11 sujets consultants ayant des crises partielles complexes avec ou sans generalisation secondaire ont eteetudies les PEV obtenus avec une stimulation LED par damier reversible et les PES a courte latence (par stimulation du nerf median). Les patients ayant une epilepsie generalisee primaire avaient une latence significativement allongee des composants P2 et N3 du PEV et P22 du PES. Les patients ayant une epilepsie partielle avaient une latence significativement allongee avec les composants N3 du PEV. II est conclu que des facteurs fonctionnels et structurels peuvent provoquer un ral-entissement de la conduction cerebrale. RESUMEN Mediante la utilizacion de un estimulador LED de patron-inverso, se han estudiado los VETs y los SETs de corta latencia del nervio mediano a la corteza en 20 pacientes ambulatorios que padecian ataques tonico-clonicos generalizados con descargas generalizadas primarias y respuestas fotoconvulsivas en el EEG y en 11 pacientes ambulatorios con ataques parciales complejos con o sin generalizacion secundaria. Los pacientes con epilepsia generalizada primaria tenian latencias significativamente prolongadas de los componentes E2 y N3 de los VET y del componente T22 de los SET. Los pacientes con epilepsia parcial demostraron una latencia significativamente prolongada del componente N3 de los VET. Se concluye que factores funcionales y tambien estructurales pueden ser causa de una lentificacion de la conduccion de impulsos centrales. ZUSAMMENFASSUNG Bei 20 ambulanten Patienten mit generalisierten tonischklonischen Anfallen bei primar generalisierten Entladungen und fotokonvulsiver Antwort im EEG und bei 11 ambulanten Patienten mit komplexen Partialanfallen mit oder ohne sekundare Generalisation wurden die VEP mit Hilfe des Muster-Umkehr LED-Stimulators und die fruhen corticalen SEP nach Stimulation des N. medianus untersucht. Die Patienten mit primar generalisierter Epilepsie zeigten signifikant verlangerte Latenzen der VEP-Komponenten P2 und N3 und der SEP Komponente P 22. Die Patienten mit Partialepilepsie hatten signifikant verlangerte Latenzen der VEP Komponente N3. Es ist zu folgern, das sowohl funktionelle wie strukturelle Faktoren eine Verlangsamung der zentralen Erregungsleitung bewirken konnen.