• English close
• Frontiers in Neurology close

Background and Purpose: Hypertensive vasculopathy and cerebral amyloid angiopathy are the two most common forms of cerebral small vessel disease. Both forms are associated with the development of primary intracerebral hemorrhage, but the pathophysiological mechanisms underlying spontaneous vessel rupture remain unknown. This work constitutes a systematic review on blood-brain barrier dysfunction in the etiology of spontaneous intracerebral hemorrhage due to cerebral small vessel disease.Methods: We searched Medline (1946-2018) and Embase (1974-2018) for animal and human studies reporting on blood-brain barrier dysfunction associated with intracerebral hemorrhage or cerebral microbleeds.Results: Of 26 eligible studies, 10 were animal studies and 16 were in humans. The authors found indications for blood-brain barrier dysfunction in all four animal studies addressing hypertensive vasculopathy-related intracerebral hemorrhage (n = 32 hypertensive animals included in all four studies combined), and in four of six studies on cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 47). Of the studies in humans, five of six studies in patients with cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 117) and seven out of nine studies examining intracerebral hemorrhage with mixed or unspecified underlying etiology (n = 489) found indications for blood-brain barrier dysfunction. One post-mortem study in hypertensive vasculopathy-related intracerebral hemorrhage (n = 82) found no evidence for blood-brain barrier abnormalities.Conclusions: Signs of blood-brain barrier dysfunction were found in 20 out of 26 studies. Blood-brain barrier integrity deserves further investigation with a view to identification of potential treatment targets for spontaneous intracerebral hemorrhage.

Time series analysis with delay differential equations (DDEs) reveals nonlinear properties of the underlying dynamical system and can serve as a non-linear time-domain classification tool. Here global DDE models were used to analyze short segments of simulated time series from a known dynamical system, the Rössler system, in high noise regimes. In a companion paper, we apply the DDE model developed here to classify short segments of encephalographic (EEG) data recorded from patients with Parkinson's disease and healthy subjects. Nine simulated subjects in each of two distinct classes were generated by varying the bifurcation parameter b and keeping the other two parameters (a and c) of the Rössler system fixed. All choices of b were in the chaotic parameter range. We diluted the simulated data using white noise ranging from 10dB to -30dB signal-to-noise ratios (SNR). Structure selection was supervised by selecting the number of terms, delays, and order of nonlinearity of the model DDE model that best linearly separated the two classes of data. The distances d from the linear dividing hyperplane was then used to assess the classification performance by computing the area A' under the ROC curve. The selected model was tested on untrained data using repeated random sub-sampling validation. DDEs were able to accurately distinguish the two dynamical conditions, and moreover, to quantify the changes in the dynamics. There was a significant correlation between the dynamical bifurcation parameter b of the simulated data and the classification parameter d from our analysis. This correlation still held for new simulated subjects with new dynamical parameters selected from each of the two dynamical regimes. Furthermore, the correlation was robust to added noise, being significant even when the noise was greater than the signal. We conclude that DDE models may be used as a generalizable and reliable classification tool for even small segments of noisy data.

(1)Context: Despite its widespread use, the precise mechanism of action of Deep Brain Stimulation (DBS) therapy remains unknown. The modern urgency to publish more and new data can obscure previously learned lessons by the giants who have preceded us and whose shoulders we now stand upon. Wilder Penfield extensively studied the effects of artificial electrical brain stimulation and his comments on the subject are still very relevant today. In particular, he noted two very different (and seemingly opposite) effects of stimulation within the human brain. In some structures, artificial electrical stimulation has an effect which mimics ablation, while, in other structures, it produces a stimulatory effect on that tissue. (2)Hypothesis:The hypothesis of this paper is fourfold. First, it proposes that some neural circuits are widely synchronized with other neural circuits, while some neural circuits are unsynchronized and operate independently. Second, it proposes that artificial high frequency electrical stimulation of a synchronized neural circuit results in an ablative effect, but artificial high frequency electrical stimulation of an unsynchronized neural circuit results in a stimulatory effect. Third, it suggests a part of the mechanism by which large scale physiologic synchronization of widely distributed independently processed information streams may occur. This may be the neural mechanism underlying Penfield’s centrencephalic system which he emphasized so many years ago. Fourth, it outlines the specific anatomic distribution of this physiologic synchronization, which Penfield has already clearly delineated as the distribution of his centrencephalic system. (3)Evidence:This paper draws on a brief overview of previous theory regarding the mechanism of action of DBS and on historical, as well as widely known modern clinical data regarding the observed effects of stimulation delivered to various targets within the brain. Basic science in

Plectinopathies are orphan diseases caused by PLEC gene mutations. PLEC is encoding the protein plectin, playing a role in linking cytoskeleton components in various tissues. In this study, we describe the clinical case of a 26-year-old patient with an early onset plectinopathy variant “limb-girdle muscle dystrophy type 2Q,” report histopathological and ultrastructural findings in m. vastus lateralis biopsy and a novel homozygous likely pathogenic variant (NM_201378.3:c.58G>T, NP_958780.1:p.Glu20Ter) in isoform 1f of the gene PLEC. The patient had an early childhood onset with retarded physical development, moderate weakness in pelvic girdle muscles, progressive weakening of limb-girdle muscles after the age of 21, pronounced atrophy of axial muscles, and hypertrophy of the gastrocnemius, deltoid, and triceps muscles, intermittent dyspnea, and no skin involvement. Findings included: non-infectious bronchiolitis and atelectasis signs, biopsy revealed myodystrophal pattern without macrophage infiltration, muscle fiber cytoskeleton disorganization resulted from the plectin loss, incomplete reparative rhabdomyogenesis, and moderate endomysial fibrosis. We have determined a novel likely pathogenic variant in PLEC 1f isoform that causes limb-girdle muscle dystrophy type 2Q and described the third case concerning an isolated myodystrophic phenotype of LGMD2Q with the likely pathogenic variant in PLEC 1f isoform. In addition, we have demonstrated the presence of severe lung injury in a patient and his siblings with the same myodystrophic phenotype and discussed the possible role of plectin deficiency in its pathogenesis.

Children and adolescent athletes are at a higher risk for concussion than adults, and also experience longer recovery times and increased associated symptoms. It has also recently been demonstrated that multiple, seemingly mild concussions may result in exacerbated and prolonged neurological deficits. Objective assessments and return-to-play criteria are needed to reduce risk and morbidity associated with concussive events in these populations. Recent research has pushed to study the use of electroencephalography as an objective measure of brain injury. In the present case study, we present a novel approach that examines event-related potentials via a brain network activation (BNA) analysis as a biomarker of concussion and recovery. Specifically, changes in BNA scores, as indexed through this approach, offer a potential indicator of neurological health as the BNA assessment qualitatively and quantitatively indexes the network dynamics associated with brain injury. Objective tools, such as these support accurate and efficient assessment of brain injury and may offer a useful step in categorizing the temporal and spatial changes in brain activity following concussive blows, as well as the functional connectivity of brain networks, associated with concussion.

Intermittent theta burst stimulation (iTBS) is intended primarily to alter corticospinal excitability, creating an attractive opportunity to alter neural output following incomplete spinal cord injury (SCI). This study is the first to assess the effects of iTBS in SCI. Eight individuals with chronic incomplete SCI were studied. Sham or real iTBS was delivered (to each participant) over primary motor and somatosensory cortices in separate sessions. Motor-evoked potential (MEP) recruitment curves were obtained from the flexor carpi radialis muscle before and after iTBS. Results indicate similar responses for iTBS to both motor and somatosensory cortex and reduced MEPs in 56.25% and increased MEPs in 25% of instances. Sham stimulation exceeded real iTBS effects in the remaining 18.25%. It is our opinion that observing short-term neuroplasticity in corticospinal output in chronic SCI is an important advance and should be tested in future studies as an opportunity to improve function in this population. We emphasize the need to re-consider the importance of the direction of MEP change following a single session of iTBS since the relationship between MEP direction and motor function is unknown and multiple sessions of iTBS may yield very different directional results. Furthermore, we highlight the importance of including sham control in the experimental design. The fundamental point from this pilot research is that a single session of iTBS is often capable of creating short-term change in SCI. Future sham-controlled randomized trials may consider repeat iTBS sessions to promote long-term changes in corticospinal excitability.

Bilateral vestibulopathy (BVP) is characterized by its heterogeneous and chronic nature with various clinical presentations and multiple etiologies. This current narrative review reflects on the main insights and developments regarding clinical presentation. In addition, it proposes a new diagnostic algorithm, and describes available and potential future therapeutic modalities.

Objective To evaluate the safety and assess the different symptom improvements found after a combined low frequency primary motor cortex and high frequency prefrontal cortex stimulation using the deep TMS (dTMS) H-coil, as an add-on treatment for Parkinson´s disease (PD). Methods: 45 PD patients underwent 14 dTMS sessions; each consisting of 1Hz stimulation of the primary motor cortex for 15 min, followed by 10Hz stimulation of the prefrontal cortex for 15 min. Clinical assessments were performed, at the START, MIDDLE, and END of therapy as well as at FOLLOW-UP after 30 days, using MDS-UPDRS, TINETTI, UP&GO, SCOPA, HDRS21, BDI and self-applied daily motor assessment scales. Results: Treatment was well tolerated, without serious adverse effects. Treatment induced significant PD symptom improvements at END and at FOLLOW-UP, in all subscales of the UPDRS, gait speed, depressive symptoms, balance, autonomic symptoms and a 73% increase in daily ON time. Conclusions: In the cohort of PD patients treated, dTMS was well tolerated with only minor adverse effects. The dTMS induced significant improvements in motor, postural, and motivational symptoms of PD patients and may potentiate concurrent levodopa treatment. Significance: The present study demonstrates that dTMS may have a much wider spectrum of beneficial effects than previously reported for TMS, including enhancement of levodopa effects, suggesting that future clinical trials with dTMS should include a broader range of symptom measurements.