Changes In Brainstem Research Articles

Time for Radical Changes in Brain Stem Nomenclature-Applying the Lessons From Developmental Gene Patterns.

The traditional subdivision of the brain stem into midbrain, pons, and medulla oblongata is based purely on the external appearance of the human brain stem. There is an urgent need to update the names of brain stem structures to be consistent with the discovery of rhomobomeric segmentation based on gene expression. The most important mistakes are the belief that the pons occupies the upper half of the hindbrain, the failure to recognize the isthmus as the first segment of the hindbrain, and the mistaken inclusion of diencephalic structures in the midbrain. The new nomenclature will apply to all mammals. This essay recommends a new brain stem nomenclature based on developmental gene expression, progeny analysis, and fate mapping. In addition, we have made comment on the names given to a number of internal brain stem structures and have offered alternatives where necessary.

Stochastic game of data transmission in the presence of buffers of finite capacity

Current research aimed to investigate informational content of brainstem acoustic evoked potentials (BAEPs) and auditory cognitive event-related potential — mismatch negativity (MMN) in assessment of brain functional status and cognitive functions in patients with ischemic stroke. MMN is a component of auditory event-related potential with peak latency at 100–250 ms, which reflects automatic process of difference detection between stimuli and neurodynamic processes in auditory cortex at pre-attentive stage. Clinical and neurophysiological examination, including registration of BAEPs and MMN was performed for 22 patients (12 — with ischemic stroke in carotid circulation, 10 — without cerebrovascular diseases). According to results obtained using scales of MMSE, FAB, test with 10 words repetition and Schulte tables, patients with IS demonstrated cognitive impairment as compared to control group. During BAEPs examination, functional changes in brainstem were observed (increased latency of wave V and elongation of interpeak intervals III-V on both sides and III–V ipsilaterally) in patients with ischemic stroke. Also they demonstrated increased peak latency and decreased amplitude of MMN. It points at a decline in auditory discrimination accuracy, shortened lifetime of memory traces and deficit in involuntary attention switching and also indicates of cognitive impairment.

Pathophysiological changes in the cerebellum and brain stem in a rabbit model after superior petrosal vein sacrifice.

In certain surgical procedures, sacrificing the superior petrosal vein (SPV) is required. Previous studies have reported transient cerebellar edema, venous infarction, or hemorrhage that might occur after sectioning of the SPV. The present study investigated the pathophysiological changes in cerebellum and brain stem after SPV sacrifice. Rabbits were divided into the operation group where the SPV was sacrificed and the control group where the SPV remained intact. Each group was further subdivided into 4, 8, 12, 24, 48, and 72 h groups which represented the time period from sacrificing of the SPV to killing of the rabbits. The water content (WC), Na+ content, K+ content, and pathophysiological changes in cerebellum and brain stem tissue were measured. In comparison with the control, the WC and Na+ content of cerebellar tissue were increased in the 4, 8, 12, and 24 h operation subgroups (P<0.05), but only increased in the 4-h subgroup of the brain stem tissue (P<0.05). The K+ content of the cerebellar tissue decreased in the 4, 8, 12, and 24 h operation subgroups (P<0.05) but only decreased in the 4-h subgroup of brain stem tissue (P<0.05). Nissl staining and TEM demonstrated that cerebellar edema occurred in the 4, 8, 12, and 24 h operation subgroups but not in the 48- and 72-h subgroups. Brain stem edema occurred in the 4-h operation subgroup. In summary, cerebellum and brain stem edema can be observed at different time points after sacrificing of the SPV in the rabbit model.

Transcriptional profiling and biomarker identification reveal tissue specific effects of expanded ataxin-3 in a spinocerebellar ataxia type 3 mouse model

BackgroundSpinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder caused by expansion of the polyglutamine repeat in the ataxin-3 protein. Expression of mutant ataxin-3 is known to result in transcriptional dysregulation, which can contribute to the cellular toxicity and neurodegeneration. Since the exact causative mechanisms underlying this process have not been fully elucidated, gene expression analyses in brains of transgenic SCA3 mouse models may provide useful insights.MethodsHere we characterised the MJD84.2 SCA3 mouse model expressing the mutant human ataxin-3 gene using a multi-omics approach on brain and blood. Gene expression changes in brainstem, cerebellum, striatum and cortex were used to study pathological changes in brain, while blood gene expression and metabolites/lipids levels were examined as potential biomarkers for disease.ResultsDespite normal motor performance at 17.5 months of age, transcriptional changes in brain tissue of the SCA3 mice were observed. Most transcriptional changes occurred in brainstem and striatum, whilst cerebellum and cortex were only modestly affected. The most significantly altered genes in SCA3 mouse brain were Tmc3, Zfp488, Car2, and Chdh. Based on the transcriptional changes, α-adrenergic and CREB pathways were most consistently altered for combined analysis of the four brain regions. When examining individual brain regions, axon guidance and synaptic transmission pathways were most strongly altered in striatum, whilst brainstem presented with strongest alterations in the pi-3 k cascade and cholesterol biosynthesis pathways. Similar to other neurodegenerative diseases, reduced levels of tryptophan and increased levels of ceramides, di- and triglycerides were observed in SCA3 mouse blood.ConclusionsThe observed transcriptional changes in SCA3 mouse brain reveal parallels with previous reported neuropathology in patients, but also shows brain region specific effects as well as involvement of adrenergic signalling and CREB pathway changes in SCA3. Importantly, the transcriptional changes occur prior to onset of motor- and coordination deficits.

Effects of sildenafil and calcitonin gene-related peptide on brainstem glutamate levels: a pharmacological proton magnetic resonance spectroscopy study at 3.0\xa0T

BackgroundStudies involving human pharmacological migraine models have predominantly focused on the vasoactive effects of headache-inducing drugs, including sildenafil and calcitonin gene-related peptide (CGRP). However, the role of possible glutamate level changes in the brainstem and thalamus is of emerging interest in the field of migraine research bringing forth the need for a novel, validated method to study the biochemical effects in these areas.MethodsWe applied an optimized in vivo human pharmacological proton (1H) magnetic resonance spectroscopy (MRS) protocol (PRESS, repetition time 3000 ms, echo time 37.6–38.3 ms) at 3.0 T in combination with sildenafil and CGRP in a double-blind, placebo-controlled, randomized, double-dummy, three-way cross-over design. Seventeen healthy participants were scanned with the 1H-MRS protocol at baseline and twice (at 40 min and 140 min) after drug administration to investigate the sildenafil- and CGRP-induced glutamate changes in both brainstem and thalamus.ResultsThe glutamate levels increased transiently in the brainstem at 40–70 min after sildenafil administration compared to placebo (5.6%, P = 0.039). We found no sildenafil-induced glutamate changes in the thalamus, and no CGRP-induced glutamate changes in the brainstem or thalamus compared to placebo. Both sildenafil and CGRP induced headache in 53%–62% of participants. We found no interaction in the glutamate levels in the brainstem or thalamus between participants who developed sildenafil and/or CGRP-induced headache as compared to participants who did not.ConclusionsThe transient sildenafil-induced glutamate change in the brainstem possibly reflects increased excitability of the brainstem neurons. CGRP did not induce brainstem or thalamic glutamate changes, suggesting that it rather exerts its headache-inducing effects on the peripheral trigeminal pain pathways.

T86. Correlation of Vagus Somatosensory Evoked Potentials (VSEP) and Heart Rate Variability (HRV)

Introduction Vagus somatosensory evoked potentials (VSEP) were proposed as a means of early and differential diagnosis of Alzheimers disease (AD) with prolonged VSEP latencies reflecting disease-specific changes in the lower brainstem. Heart rate variability (HRV), too is a marker supposed to be influenced by autonomic brainstem nuclei. With the presented study we aimed at testing the hypothesis that prolonged VSEP latencies correlate with changes in HRV parameters in subjects with Mild cognitive impairment (MCI) as a potential state of early AD and healthy controls (HC). Methods In 27 subjects with MCI and 191 HC (age 74 ± 1.4 years), VSEP and HRV were measured according to standard procedures and correlation analyses as well as univariate analyses of variance (ANOVA) to compare VSEP and HRV parameters between the MCI and the HC group were calculated. Results In frontocentral recordings (C4F4), all VSEP latencies correlated negatively with HRV parameters, most strongly P1 with longer latencies coinciding with significantly lower parasympathic tone (respiratory sinus arrhythmia RSA, high frequency power HF). While difference in HRV parameters between the MCI and the HC group did not reach statistical significant difference, there was a significant difference in VSEP parameters with longer P2 latencies in the MCI group. Conclusion Correlation of VSEP latencies with brainstem-regulated HRV is a further hint for VSEP being generated in autonomic brainstem structures. Follow up examination of participants will reveal if subjects who present at baseline with longer VSEP latencies and less HRV will more often develop AD in the future than subjects who do not.

Brainstem Network Disruption in Focal Epilepsy and Sudden Unexplained Death in Epilepsy (SUDEP)

The American Epilepsy Society (AES) annual meeting took place in Washington DC in December 2017. In an expert interview, Susanne Mueller discusses the results of a validation study she presented at the meeting, which investigated brainstem changes in focal epilepsy and sudden unexplained death in epilepsy (SUDEP).1

Human Brainstem Exhibits higher Sensitivity and Specificity than Auditory-Related Cortex to Short-Term Phonetic Discrimination Learning

Phonetic discrimination learning is an active perceptual process that operates under the influence of cognitive control mechanisms by increasing the sensitivity of the auditory system to the trained stimulus attributes. It is assumed that the auditory cortex and the brainstem interact in order to refine how sounds are transcribed into neural codes. Here, we evaluated whether these two computational entities are prone to short-term functional changes, whether there is a chronological difference in malleability, and whether short-term training suffices to alter reciprocal interactions. We performed repeated cortical (i.e., mismatch negativity responses, MMN) and subcortical (i.e., frequency-following response, FFR) EEG measurements in two groups of participants who underwent one hour of phonetic discrimination training or were passively exposed to the same stimulus material. The training group showed a distinctive brainstem energy reduction in the trained frequency-range (i.e., first formant), whereas the passive group did not show any response modulation. Notably, brainstem signal change correlated with the behavioral improvement during training, this result indicating a close relationship between behavior and underlying brainstem physiology. Since we did not reveal group differences in MMN responses, results point to specific short-term brainstem changes that precede functional alterations in the auditory cortex.

0718 7 TESLA IMAGING OF MICROSTRUCTURAL BRAINSTEM CHANGES IN REM SLEEP BEHAVIOR DISORDER

REM-sleep-behavior-disorder (RBD) is characterized by the absence of muscle-atonia during REM-sleep, and represents a prodromal clinical manifestation of evolving Parkinsons’s disease (PD) and other synucleinopathies. Interestingly, RBD is hypothesized to be related to a dysfunction of brainstem-nuclei (Bn) of the arousal/motor networks based on: (i) lesion/connectivity studies in animals, and a few human studies in-vivo; (ii) ex-vivo human staging models of PD progression. Yet, a precise identification of the Bn involved in living humans is still missing, thus limiting our understanding of idiopatic-RBD/prodromal PD. We investigated the presence of microstructural brainstem changes in idiopatic-RBD in humans by high-resolution multi-contrast 7 Tesla MRI and our recently developed stereotaxic probabilistic structural atlas of 11 Bn of the arousal/motor networks, which included two subregions of the substantia nigra (SN) and three raphe nuclei. At 7 Tesla, on 6 patients with idiopathic-RBD (5m/1f, age 70 ± 1) under IRB-approval, we aquired .75mm-isotropic M2PRAGE and multi-echo GRE images. We computed a T1-map from the MP2RAGE. Multi-echo GRE images were coregistered to the T1-map. Regions of interest (ROI) displaying T1 hyperintensity (T1>2500ms) within a brainstem mask were automatically detected. To determine the location of these ROIs with respect to the 11 Bn, we precisely coregistered T1-maps to the Bn atlas space. In 5 out of 6 RBD patients we detected ROIs with T1 hyperintensity (i.e. microstructural changes) in the ventro-caudal part of the right SN-subregion 1 (compatible with SN pars-reticulata) and in a paranigral region (rostro-medial to the caudal part of SN-subregion1). These ROIs colocalized to T2*-weighted hyperintensity and had a volume of .4-1.2mm3. The other 10 Bn displayed normal appearing gray matter. These results provide compelling empirical evidence for the hypothesized role of specific Bn nuclei in the pathogenesis of RBD. Interestingly, the observed contrast (hyperintensities in T1 and T2*-weighted MRI) in the detected ROIs is compatible with the presence of small lacunar infarcts (i.e. parenchymal spaces filled with CSF/interstitial-fluid) in the nigral and peri-nigral region of RBD patients. This original result differs from recent findings of iron accumulation in the SN pars-compacta of idiopatic-RBD patients. NIH-NIBIB: K01-EB019474, P41-RR014075.

Abnormal trajectories in cerebellum and brainstem volumes in carriers of the fragile X premutation

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder typically affecting male premutation carriers with 55–200 CGG trinucleotide repeat expansions in the FMR1 gene after age 50. The aim of this study was to examine whether cerebellar and brainstem changes emerge during development or aging in late life. We retrospectively analyzed magnetic resonance imaging scans from 322 males (age 8–81 years). Volume changes in the cerebellum and brainstem were contrasted with those in the ventricles and whole brain. Compared to the controls, premutation carriers without FXTAS showed significantly accelerated volume decrease in the cerebellum and whole brain, flatter inverted U-shaped trajectory of the brainstem, and larger ventricles. Compared to both older controls and premutation carriers without FXTAS, carriers with FXTAS exhibited significant volume decrease in the cerebellum and whole brain and accelerated volume decrease in the brainstem. We therefore conclude that cerebellar and brainstem volumes were likely affected during both development and progression of neurodegeneration in premutation carriers, suggesting that interventions may need to start early in adulthood to be most effective.

Spectrum of MRI brain findings in subacute sclerosing panencephalitis

Background and objectives: Subacute sclerosing panencephalitis (SSPE) is a progressive catastrophic neurodegenerative disease because of persistent measles viral infection in the brain. This study was designed to determine the spectrum of magnetic resonance imaging (MRI) findings in subacute sclerosing panencephalitis. Design: Case series. Methods: We described the brain MRI findings in 20 pediatric patients with confirmed SSPE with their clinical and electroencephalogram (EEG) correlates. This study was conducted at Aga Khan University Hospital, Karachi, Pakistan between January 2006 and June 2016. Diagnosis of SSPE was on the basis of the clinical signs and symptoms, the characteristic EEG patterns (burst suppression in the early stage and a diffuse, random, slow arrhythmia pattern in the late stage), and high titers of measles antibody in the cerebro-spinal fluid. Results: The mean age at presentation was 7.4 ± 3.3 years. MRI abnormalities included diffuse white matter changes (n = 8), subcortical T2 hyperintesities in both grey and white matter in 1 patient and the brainstem changes in 2 patients. MRI was normal in 8/20 patients. Magnetic resonance spectroscopy (MRS) was performed in 4 patients out of whom 1 patient showed reduced N-acetyl aspartate (NAA) peak with elevated choline peak and inverted doublet lactate peak, 1 showed only reduced NAA, 1 showed isolated choline peak and 1 patient had a normal MRS. Conclusion: MRI brain to date is supportive in understanding the pathology of SSPE. MRI can be normal in patients with SSPE if done early on at the start of the disease.

Impaired auditory processing and altered structure of the endbulb of Held synapse in mice lacking the GluA3 subunit of AMPA receptors

AMPA glutamate receptor complexes with fast kinetics conferred by subunits like GluA3 and GluA4 are essential for temporal precision of synaptic transmission. The specific role of GluA3 in auditory processing and experience related changes in the auditory brainstem remain unknown. We investigated the role of the GluA3 in auditory processing by using wild type (WT) and GluA3 knockout (GluA3-KO) mice. We recorded auditory brainstem responses (ABR) to assess auditory function and used electron microscopy to evaluate the ultrastructure of the auditory nerve synapse on bushy cells (AN-BC synapse). Since labeling for GluA3 subunit increases on auditory nerve synapses within the cochlear nucleus in response to transient sound reduction, we investigated the role of GluA3 in experience-dependent changes in auditory processing. We induced transient sound reduction by plugging one ear and evaluated ABR threshold and peak amplitude recovery for up to 60 days after ear plug removal in WT and GluA3-KO mice. We found that the deletion of GluA3 leads to impaired auditory signaling that is reflected in decreased ABR peak amplitudes, an increased latency of peak 2, early onset hearing loss and reduced numbers and sizes of postsynaptic densities (PSDs) of AN-BC synapses. Additionally, the lack of GluA3 hampers ABR threshold recovery after transient ear plugging. We conclude that GluA3 is required for normal auditory signaling, normal ultrastructure of AN-BC synapses in the cochlear nucleus and normal experience-dependent changes in auditory processing after transient sound reduction.

Transcriptomic Changes in Rat Cortex and Brainstem After Cortical Spreading Depression With or Without Pretreatment With Migraine Prophylactic Drugs.

Our results suggest that early after triggering the CSD, similar consequences are seen at the genetic level with or without prophylactic treatment. Gene expression changes induced by CSD in cortex and brainstem may help to better understand the underlying mechanisms and identify targets for therapeutic approaches.

Aberrant brain stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer's disease.

ObjectiveAmong patients with Alzheimer’s disease (AD), sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD.Materials and methodsIn 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology.ResultsAnalyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group.ConclusionThis study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings.

Changes in Neurocognitive Architecture in Patients with Obstructive Sleep Apnea Treated with Continuous Positive Airway Pressure

BackgroundObstructive sleep apnea (OSA) is a chronic, multisystem disorder that has a bidirectional relationship with several major neurological disorders, including Alzheimer's dementia. Treatment with Continuous Positive Airway Pressure (CPAP) offers some protection from the effects of OSA, although it is still unclear which populations should be targeted, for how long, and what the effects of treatment are on different organ systems. We investigated whether cognitive improvements can be achieved as early as one month into CPAP treatment in patients with OSA. Methods55 patients (mean (SD) age: 47.6 (11.1) years) with newly diagnosed moderate–severe OSA (Oxygen Desaturation Index: 36.6 (25.2) events/hour; Epworth sleepiness score (ESS): 12.8 (4.9)) and 35 matched healthy volunteers were studied. All participants underwent neurocognitive testing, neuroimaging and polysomnography. Patients were randomized into parallel groups: CPAP with best supportive care (BSC), or BSC alone for one month, after which they were re-tested. FindingsOne month of CPAP with BSC resulted in a hypertrophic trend in the right thalamus [mean difference (%): 4.04, 95% CI: 1.47 to 6.61], which was absent in the BSC group [−2.29, 95% CI: −4.34 to −0.24]. Significant improvement was also recorded in ESS, in the CPAP plus BSC group, following treatment [mean difference (%): −27.97, 95% CI: −36.75 to −19.19 vs 2.46, 95% CI: −5.23 to 10.15; P=0.012], correlated to neuroplastic changes in brainstem (r=−0.37; P=0.05), and improvements in delayed logical memory scores [57.20, 95% CI: 42.94 to 71.46 vs 23.41, 95% CI: 17.17 to 29.65; P=0.037]. InterpretationOne month of CPAP treatment can lead to adaptive alterations in the neurocognitive architecture that underlies the reduced sleepiness, and improved verbal episodic memory in patients with OSA. We propose that partial neural recovery occurs during short periods of treatment with CPAP.

Effect of Chronic Alcohol Intake on Auditory System with Changes in Auditory Brainstem Evoked Responses

Effect of Chronic Alcohol Intake on Auditory System with Changes in Auditory Brainstem Evoked Responses

Lack of Significant Brainstem Toxicity is Observed Among Children Following Modern Era Posterior Fossa Tumor Radiation Therapy

Radiation-induced brainstem toxicity after treatment for pediatric posterior fossa (PF) malignancies is incompletely understood, especially in the era of intensity modulated radiation therapy (IMRT). The rates of and predictive factors for brainstem toxicity after photon radiation therapy (RT) for PF tumors were examined. After IRB approval, 40 pediatric patients treated at our institution for non-metastatic infratentorial ependymoma, medulloblastoma, and atypical rhabdoid/teratoid tumor with IMRT were included in this analysis. Dosimetric variables, including maximum dose to the brainstem, dose to 10 and 50% of the brainstem, and the volume of brainstem receiving 40, 45, 50, and 55 Gy were recorded from individual patient dose-volume histogram data. Age at diagnosis, extent of resection, use of chemotherapy, and PTV volumes were also examined for correlation. Acute (onset within 3 months) and late (onset 3 months to 2 years of RT) RT-induced brainstem toxicities (new or worsening brainstem symptoms during or after RT) were scored using CTCAE v4.0. Corresponding changes on posttreatment MRIs were also noted. Patients from ages 9 months to 19 years were treated using IMRT or VMAT postoperatively to the PTV covering the posterior fossa or postoperative bed. Median follow-up time was 4.0 years; median progression-free survival and overall survival were not reached. Acute grade 1-2 brainstem toxicities were noted in 10% of patients (n=4); late grade 1-2 toxicities were seen in 12.5% of patients (n=5). One late grade 3 toxicity was noted (2.5%) in a patient who required repeat surgery for residual disease prior to RT. Nine patients (22.5%) had post-RT brainstem changes on MRI, but without correlative symptoms. Age less than 3 years (P=.048) and subtotal resection (P=.04) predicted for more acute toxicity, but this did not translate to late toxicity. Independent t-tests found only maximum dose to the brainstem above 57.8 Gy to be a significant predictor of late brainstem toxicity (P=.02). Other aforementioned factors did not affect acute or late toxicities. This study provides a unique dosimetric and radiographic analysis of clinically significant brainstem toxicity related to photon-based conformal radiation therapy in the modern treatment-planning era. Current dosimetric guidelines, appear to allow safe delivery of doses 54- 59.4 Gy to the posterior fossa; however, careful attention should be given to maximum brainstem dose, especially in younger patients with subtotal resection to minimize risk of late brainstem toxicity, especially given long-term survival of these patients.

Blast overpressure induced axonal injury changes in rat brainstem and spinal cord.

Introduction:Blast induced neurotrauma has been the signature wound in returning soldiers from the ongoing wars in Iraq and Afghanistan. Of importance is understanding the pathomechansim(s) of blast overpressure (OP) induced axonal injury. Although several recent animal models of blast injury indicate the neuronal and axonal injury in various brain regions, animal studies related to axonal injury in the white matter (WM) tracts of cervical spinal cord are limited.Objective:The purpose of this study was to assess the extent of axonal injury in WM tracts of cervical spinal cord in male Sprague Dawley rats subjected to a single insult of blast OP.Materials and Methods:Sagittal brainstem sections and horizontal cervical spinal cord sections from blast and sham animals were stained by neurofilament light (NF-L) chain and beta amyloid precursor protein immunocytochemistry and observed for axonal injury changes.Results:Observations from this preliminary study demonstrate axonal injury changes in the form of prominent swellings, retraction bulbs, and putative signs of membrane disruptions in the brainstem and cervical spinal cord WM tracts of rats subjected to blast OP.Conclusions:Prominent axonal injury changes following the blast OP exposure in brainstem and cervical spinal WM tracts underscores the need for careful evaluation of blast induced injury changes and associated symptoms. NF-L immunocytochemistry can be considered as an additional tool to assess the blast OP induced axonal injury.

Magnetic resonance imaging correlates of genetically characterized patients with mitochondrial disorders: A study from south India

BackgroundLarge studies analyzing magnetic resonance imaging correlates in different genotypes of mitochondrial disorders are far and few. This study sought to analyze the pattern of magnetic resonance imaging findings in a cohort of genetically characterized patients with mitochondrial disorders. MethodsThe study cohort included 33 patients (age range 18months–50years, M:F — 0.9:1) with definite mitochondrial disorders seen over a period of 8yrs. (2006–2013). Their MR imaging findings were analyzed retrospectively. ResultsThe patients were classified into three groups according to the genotype, Mitochondrial point mutations and deletions (n=21), SURF1 mutations (n=7) and POLG1 (n=5). The major findings included cerebellar atrophy (51.4%), cerebral atrophy (24.2%), signal changes in basal ganglia (45.7%), brainstem (34.2%) & white matter (18.1%) and stroke like lesions (25.7%). Spinal cord imaging showed signal changes in 4/6 patients. Analysis of the special sequences revealed, basal ganglia mineralization (7/22), lactate peak on magnetic resonance spectrometry (10/15), and diffusion restriction (6/22). Follow-up images in six patients showed that the findings are dynamic. Comparison of the magnetic resonance imaging findings in the three groups showed that cerebral atrophy and cerebellar atrophy, cortical signal changes and basal ganglia mineralization were seen mostly in patients with mitochondrial mutation. Brainstem signal changes with or without striatal lesions were characteristically noted in SURF1 group. There was no consistent imaging pattern in POLG1 group. ConclusionMagnetic resonance imaging findings in mitochondrial disorders are heterogeneous. Definite differences were noted in the frequency of anatomical involvement in the three groups. Familiarity with the imaging findings in different genotypes of mitochondrial disorders along with careful analysis of the family history, clinical presentation, biochemical findings, histochemical and structural analysis will help the physician for targeted metabolic and genetic testing.

Differential Effects of Systemic versus Intratracheal Lipopolysaccharide (LPS) Administration on Ventilatory Behavior in Spontaneously Breathing Adult C57BL/6 Male Mice

Both intraperitoneal (ip; systemic) and intratracheal (IT) administration of the bacterial endotoxin LPS have been used to elicit neuroinflammation. While both methods are reported to induce time‐dependent changes in expression levels of pro‐inflammatory cytokines in the CNS, their effects on basal ventilatory activity remain to be characterized. Here, we report the ventilatory behavior (recorded using whole body plethysmography) before and after administration of LPS delivered either ip (5 mg/kg) or IT (0.5 mg/kg) in unanesthetized spontaneously breathing adult C57BL/6 male mice. Before LPS, ventilatory activity consisted of a fairly regular pattern of breathing, which included periodic short duration apneic pauses (as previously described in this strain) and occasional sighs. Both ip and IT LPS altered ventilatory activity; however, the effects were not identical. IP LPS (1) robustly increased breathing frequency and progressively decreased tidal volume and (2) reduced or eliminated the incidence of both apneic pauses and sighs. IT LPS (1) increased breathing frequency and progressively decreased tidal volume, but to a lesser extent than ip, (2) produced periods of dysrhythmic breathing, (3) prolonged the durations of the apneic pauses; and (4) increased the incidence of sighs. These findings indicate that while both methods of administration alter ventilatory activity, the resulting ventilatory patterns are markedly different. We suggest that differences in the extent of ip versus IT LPS‐induced neuroinflammatory changes in respiratory‐related brainstem and spinal cord regions mediate, at least in part, these different ventilatory behaviors.