Brainstem atrophy in focal epilepsy destabilizes brainstem-brain interactions: Preliminary findings.

BACKGROUND: MR Imaging has shown atrophy in brainstem regions that were linked to autonomic dysfunction in epilepsy patients. The brainstem projects to and modulates the activation state of several wide-spread cortical/subcortical regions. The goal was to investigate 1. Impact of brainstem atrophy on gray matter connectivity of cortical/subcortical structures and autonomic control. 2. Impact on the modulation of cortical/subcortical functional connectivity. METHODS: 11 controls and 18 patients with non-lesional focal epilepsy (FE) underwent heart rate variability (HRV) measurements and a 3 T MRI (T1 in all subjects, task-free fMRI in 7 controls/ 12 FE). The brainstem was extracted, and atrophy assessed using deformation-based-morphometry. The age-corrected z-scores of the mean Jacobian determinants were extracted from 71 5x5x5 mm grids placed in brainstem regions associated with autonomic function. Cortical and non-brainstem subcortical gray matter atrophy was assessed with voxel-based-morphometry and mean age corrected z-scores of the modulated gray matter volumes extracted from 380 cortical/subcortical rois. The profile similarity index was used to characterize the impact of brainstem atrophy on gray matter connectivity. The fMRI was preprocessed in SPM12/Conn17 and the BOLD signal extracted from 398 ROIs (16 brainstem). A dynamic task-free analysis approach was used to identify activation states. Connectivity HRV relationship were assessed with Spearman rank correlations. RESULTS: HRV was negatively correlated with reduced brainstem right hippocampus/parahippocampus gray matter connectivity in controls (p \u3c .05, FDR) and reduced brainstem to right parietal cortex, lingual gyrus, left hippocampus/amygdala, parahippocampus, temporal pole, and bilateral anterior thalamus connectivity in FE (p \u3c .05, FDR). Dynamic task-free fMRI analysis identified 22 states. The strength of the functional brainstem/cortical connectivity of state 15 was negatively associated with HRV (r = -0.5, p = .03) and positively with decreased brainstem-cortical (0.49, p = .03) gray matter connectivity. CONCLUSION: The findings of this small pilot study suggest that impaired brainstem-cortex gray matter connectivity in FE negatively affects the brainstem\u27s ability to control cortical activation

Auditory evoked potentials and vestibular evoked myogenic potentials in evaluation of brainstem lesions in multiple sclerosis

OBJECTIVE: The aim of this study was to determine the roles of magnetic resonance imaging (MRI), auditory evoked potentials (AEP) and vestibular evoked myogenic potentials (VEMP) in the evaluation of brainstem involvement in multiple sclerosis (MS). ----- PATIENTS AND METHODS: Altogether 32 patients with the diagnosis of MS participated in the study. The following data was collected from all patients: age, gender, Expanded Disability Status Scale (EDSS) score, brainstem functional system score (BSFS) (part of the EDSS evaluating brainstem symptomatology), and involvement of the brainstem on the brain MRI. AEP and ocular VEMP (oVEMP) and cervical VEMP (cVEMP) were studied in all patients. ----- RESULTS: BSFS, MRI, AEP, oVEMP and cVEMP involvement of the brainstem was evident in 9 (28.1%), 14 (43.8%), 7 (21.9%), 12 (37.5%) and 10 (31.0%) patients, respectively. None of the tests used showed statistically significant advantage in the detection of brainstem lesions. When combining oVEMP and cVEMP 18 (56.3%) patients showed brainstem involvement. This combination showed brainstem involvement in greater percentage than BSFS or AEP, with statistical significance (p=0.035 and p=0.007, respectively). ----- CONCLUSION: VEMP is a reliable method in detection of brainstem involvement in MS. It is comparable with MRI, but superior to clinical examination or AEP

Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity.

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords "subacute sclerosing panencephalitis" and "brainstem" using the National Library of Medicine PubMed database (March 1981-September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment

Brainstem metastases treated with Gamma Knife stereotactic radiosurgery: the Indiana University Health experience

Brainstem metastases offer a unique challenge in cancer treatment, yet stereotactic radiosurgery (SRS) has proven to be an effective modality in treating these tumors. This report discusses the clinical outcomes of patients with brainstem metastases treated at Indiana University with Gamma Knife (GK) radiosurgery from 2008 to 2016. 19 brainstem metastases from 14 patients who had follow-up brain imaging were identified. Median tumor volume was 0.04 cc (range: 0.01-2.0 cc). Median prescribed dose was 17.5 Gy to the 50% isodose line (range: 14-22 Gy). Median survival after GK SRS treatment to brainstem lesion was 17.2 months (range: 2.8-45.6 months). The experience at Indiana University confirms the safety and efficacy of range of GK SRS prescription doses (14-22 Gy) to brainstem metastases

Migraine and motion sickness: what is the link?

The brainstem is a structurally complex region, containing numerous ascending and descending fibres that converge on centres that regulate bodily functions essential to life. Afferent input from the cranial tissues and the special senses is processed, in part, in brainstem nuclei. In addition, brainstem centres modulate the flow of pain messages and other forms of sensory information to higher regions of the brain, and influence the general excitability of these cortical regions. Thus, disruptions in brainstem processing might evoke a complex range of unpleasant symptoms, vegetative changes and neurovascular disturbances and that, together, form attacks of migraine. Migraine is linked with various co-morbid conditions, the most prominent being motion sickness. Symptoms such as nausea, dizziness and headache are common to motion sickness and migraine; moreover, migraine sufferers have a heightened vulnerability to motion sickness. As both maladies involve reflexes that relay in the brainstem, symptoms may share the same neural circuitry. In consequence, subclinical interictal persistence of disturbances in these brainstem pathways could not only increase vulnerability to recurrent attacks of migraine but also increase susceptibility to motion sickness. Mechanisms that mediate symptoms of motion sickness and migraine are explored in this paper. The physiology of motion sickness and migraine is discussed, and neurotransmitters that may be involved in the manifestation of symptoms are reviewed. Recent findings have shed light on the relationship between migraine and motion sickness, and provide insights into the generation of migraine attacks

Differential sensitivity of brainstem vs cortical astrocytes to changes in pH reveals functional regional specialization of astroglia

Astrocytes might function as brain interoceptors capable of detecting different (chemo)sensory modalities and transmitting sensory information to the relevant neural networks controlling vital functions. For example, astrocytes which reside near the ventral surface of the brainstem (central respiratory chemosensitive area) respond to physiological decreases in pH with vigorous elevations in intracellular Ca(2+) and release of ATP. ATP transmits astroglial excitation to the brainstem respiratory network and contributes to adaptive changes in lung ventilation. Here we show that in terms of pH-sensitivity ventral brainstem astrocytes are clearly distinct from astrocytes residing in the cerebral cortex. We monitored vesicular fusion in cultured rat brainstem astrocytes using total internal reflection fluorescence microscopy and found that approximately 35% of them respond to acidification with an increased rate of exocytosis of ATP-containing vesicular compartments. These fusion events require intracellular Ca(2+) signaling and are independent of autocrine ATP actions. In contrast, the rate of vesicular fusion in cultured cortical astrocytes is not affected by changes in pH. Compared to cortical astrocytes, ventral brainstem astrocytes display higher levels of expression of genes encoding proteins associated with ATP vesicular transport and fusion, including vesicle-associated membrane protein-3 and vesicular nucleotide transporter. These results suggest that astrocytes residing in different parts of the rat brain are functionally specialized. In contrast to cortical astrocytes, astrocytes of the brainstem chemosensitive area(s) possess signaling properties which are functionally relevant – they are able to sense changes in pH and respond to acidification with enhanced vesicular release of ATP

Characterizing aging in the human brainstem using quantitative multimodal MRI analysis.

Aging is ubiquitous to the human condition. The MRI correlates of healthy aging have been extensively investigated using a range of modalities, including volumetric MRI, quantitative MRI (qMRI), and diffusion tensor imaging. Despite this, the reported brainstem related changes remain sparse. This is, in part, due to the technical and methodological limitations in quantitatively assessing and statistically analyzing this region. By utilizing a new method of brainstem segmentation, a large cohort of 100 healthy adults were assessed in this study for the effects of aging within the human brainstem in vivo. Using qMRI, tensor-based morphometry (TBM), and voxel-based quantification (VBQ), the volumetric and quantitative changes across healthy adults between 19 and 75 years were characterized. In addition to the increased R2* in substantia nigra corresponding to increasing iron deposition with age, several novel findings were reported in the current study. These include selective volumetric loss of the brachium conjunctivum, with a corresponding decrease in magnetization transfer and increase in proton density (PD), accounting for the previously described “midbrain shrinkage.” Additionally, we found increases in R1 and PD in several pontine and medullary structures. We consider these changes in the context of well-characterized, functional age-related changes, and propose potential biophysical mechanisms. This study provides detailed quantitative analysis of the internal architecture of the brainstem and provides a baseline for further studies of neurodegenerative diseases that are characterized by early, pre-clinical involvement of the brainstem, such as Parkinson’s and Alzheimer’s diseases

Unilateral hyperhidrosis secondary to brainstem meningioma producing mass effect

Unilateral hyperhidrosis of neurological origin has been associated with head trauma, cerebral palsy, spinal cord injury, peripheral neuropathy, lesions of the hypothalamus, and cerebral or brainstem strokes. In this report, we describe a 61-year-old man with isolated sweating on the left side of his entire body. A right-sided brainstem meningioma producing mass effect is suspected as the underlying etiology