Neuropathological Reports Research Articles

An Audit on the Use of Brain Biopsies for Non-neoplastic Brain Diseases

Introduction: In cases where a brain tumour is suspected, brain biopsies are the gold standard method for confirming the diagnosis. Brain biopsies are not frequently performed in non-neoplastic diseases as they tend to be regarded as an investigation of last resort. The role of brain biopsies, and their impact on subsequent clinical care, in non-neoplastic brain disorders is not well-defined. Methods: This is a retrospective analysis of brain biopsies for non-neoplastic brain diseases performed at a single tertiary neuroscience centre over a ten-year period, from 2008 to 2018. Cases were identified from neuropathology reports. The charts were reviewed where pre-operative clinical information and investigation results were documented and post-biopsy clinical outcome as well as management changes were also recorded. Data analysis was performed using the frequencies tool and Fisher-exact test via SPSS software. Results: Twenty cases were identified from pathology reports. 60% of biopsies (n = 12) were pathologically diagnostic. In those who had clinical management following biopsy recorded, clinical management was altered in 84% (n = 16) of patients. Of those with clinical outcome recorded: 62% (n = 8) had a documented clinical improvement; 15% (n = 2) returning to pre-disease baseline while 46% (n = 6) of patients improved without returning to pre-disease baseline. Complications occurred in 5% of patients (n = 1), a lower respiratory tract infection. Discussion: In comparison with previous papers, the diagnostic yield of biopsies in this study is high. This could be attributable to extensive investigations, particularly neuroimaging resulting in targeted biopsies. Clinical improvements were seen in higher rates compared to previous research and complication rates were low. Conclusion: This study shows that brain biopsies are useful in the investigation of non-neoplastic neurological disease and can have a high diagnostic yield. Clinical outcome was, for the majority, positive with a significant proportion of the patients improving. Complications were rare and did not have an adverse effect on patient outcomes. Our findings support the inclusion of brain biopsies as part of the diagnostic algorithm for non-neoplastic neurological conditions of unknown aetiology.

It’s a no brainer: combat sports should be ground zero for research on concussion

Many combat sports have as their overt goal the incapacitation of the opponent which is often achieved by blows to the head. While head impact in contact sports like football,...

Clinical and neuropathological diversity of tauopathy in MAPT duplication carriers.

Microduplications of the 17q21.31 chromosomal region encompassing the MAPT gene, which encodes the Tau protein, were identified in patients with a progressive disorder initially characterized by severe memory impairment with or without behavioral changes that can clinically mimic Alzheimer disease. The unique neuropathological report showed a primary tauopathy, which could not be unanimously classified in a given known subtype, showing both 4R- and 3R-tau inclusions, mainly within temporal cortical subregions and basal ganglia, without amyloid deposits. Recently, two subjects harboring the same duplication were reported with an atypical extrapyramidal syndrome and gait disorder. To decipher the phenotypic spectrum associated with MAPT duplications, we studied ten carriers from nine families, including two novel unrelated probands, gathering clinical (n = 10), cerebrospinal fluid (n = 6), MRI (n = 8), dopamine transporter scan (n = 4), functional (n = 5), amyloid (n = 3) and Tau-tracer (n = 2) PET imaging data as well as neuropathological examination (n = 4). Ages at onset ranged from 37 to 57years, with prominent episodic memory impairment in 8/10 patients, associated with behavioral changes in four, while two patients showed atypical extrapyramidal syndrome with gait disorder at presentation, including one with associated cognitive deficits. Amyloid imaging was negative but Tau imaging showed significant deposits mainly in both mesiotemporal cortex. Dopaminergic denervation was found in 4/4 patients, including three without extrapyramidal symptoms. Neuropathological examination exclusively showed Tau-immunoreactive lesions. Distribution, aspect and 4R/3R tau aggregates composition suggested a spectrum from predominantly 3R, mainly cortical deposits well correlating with cognitive and behavioral changes, to predominantly 4R deposits, mainly in the basal ganglia and midbrain, in patients with prominent extrapyramidal syndrome. Finally, we performed in vitro seeding experiments in HEK-biosensor cells. Morphological features of aggregates induced by homogenates of three MAPT duplication carriers showed dense/granular ratios graduating between those induced by homogenates of a Pick disease and a progressive supranuclear palsy cases. These results suggest that MAPT duplication causes a primary tauopathy associated with diverse clinical and neuropathological features.

Interpretation of epileptogenic lesions: Its limitations in medico-legal experts’ reports

Focal cortical dysplasia (FCD) is the third leading cause of pharmacoresistant epilepsy diagnosed by epilepsy surgery and is a common malformation of cerebral cortical development. It is marked by abnormalities of cortical lamination, neuronal differentiation, and neuronal maturation. These epileptogenic lesions have proven anatomical and clinical correlations. Only one case of incidental FCD had been described. Incidental findings highlight infrequent lesions that go unnoticed when a person is alive. It can be an important finding for pathologists as well as for the forensic expert. The difficulty of the expertise will be in cases where these incidental lesions are known to cause symptoms that may be the cause of death. We wish to argue if they can be used in a medico-legal procedure. We report two cases demonstrating discrepancies between anatomical and clinical features, which should encourage the medical expert to use caution when interpreting neuropathological reports. La dysplasie corticale focale (DCF) est la troisième cause d’épilepsie pharmacorésistante diagnostiquée par chirurgie de l’épilepsie. Il s’agit d’une malformation courante du développement cortical cérébral. Elle est marquée par des anomalies de la stratification corticale, de la différenciation neuronale et de la maturation neuronale. Ces lésions épileptogènes ont des corrélations anatomiques et cliniques prouvées. Un seul cas de DCF de découverte fortuite à l’imagerie a été décrit dans la littérature. Ces découvertes fortuites mettent en évidence des lésions peu fréquentes qui passent inaperçues lorsqu’une personne est en vie. Or, ces lésions sont une découverte importante pour les pathologistes ainsi que pour l’expert médico-légal. La difficulté de l’expertise se situera dans les cas où ces lésions incidentelles sont connues pour provoquer des symptômes pouvant être la cause du décès. Nous souhaitons discuter s’ils peuvent être utilisés dans une procédure médico-légale. Nous rapportons deux cas démontrant des divergences entre les caractéristiques anatomiques et cliniques, ce qui devrait inciter l’expert médical à faire preuve de prudence dans l’interprétation des rapports neuropathologiques.

Neuropathology of genetically defined malformations of cortical development-A systematic literature review.

AimsMalformations of cortical development (MCD) include a heterogeneous spectrum of clinical, imaging, molecular and histopathological entities. While the understanding of genetic causes of MCD has improved with the availability of next‐generation sequencing modalities, genotype‐histopathological correlations remain limited. This is the first systematic review of molecular and neuropathological findings in patients with MCD to provide a comprehensive overview of the literature.MethodsA systematic review was performed between November 2019 and February 2020. A MEDLINE search was conducted for 132 genes previously linked to MCD in order to identify studies reporting macroscopic and/or microscopic findings in patients with a confirmed genetic cause.ResultsEighty‐one studies were included in this review reporting neuropathological features associated with pathogenic variants in 46 genes (46/132 genes, 34.8%). Four groups emerged, consisting of (1) 13 genes with well‐defined histological‐genotype correlations, (2) 27 genes for which neuropathological reports were limited, (3) 5 genes with conflicting neuropathological features, and (4) 87 genes for which no histological data were available. Lissencephaly and polymicrogyria were reported most frequently. Associated brain malformations were variably present, with abnormalities of the corpus callosum as most common associated feature.ConclusionsNeuropathological data in patients with MCD with a defined genetic cause are available only for a small number of genes. As each genetic cause might lead to unique histopathological features of MCD, standardised thorough neuropathological assessment and reporting should be encouraged. Histological features can help improve the understanding of the pathogenesis of MCD and generate hypotheses with impact on further research directions.

Association of Cognitive Function Trajectories in Centenarians With Postmortem Neuropathology, Physical Health, and Other Risk Factors for Cognitive Decline

Understanding mechanisms associated with prolonged cognitive health in combination with exceptional longevity might lead to approaches to enable successful aging. To investigate trajectories of cognitive functioning in centenarians across domains, and to examine the association of these trajectories with factors underlying cognitive reserve, physical health, and postmortem levels of Alzheimer disease (AD)-associated neuropathology. This cohort study used neuropsychological test data and postmortem neuropathological reports from Dutch centenarians who were drawn from the 100-plus Study between January 2013 and April 2019. Eligible participants self-reported being cognitively healthy, which was confirmed by a proxy. Data analysis was performed between June 2019 and June 2020. Age, sex, APOE ε genotype, factors of cognitive reserve, physical health, and AD-associated neuropathology (ie, amyloid-β, neurofibrillary tangles, and neuritic plaques). In annual visits (until death or until participation was no longer possible), centenarians underwent an extensive neuropsychological test battery, from which an mean z score of global cognition, memory, executive functions, verbal fluency, visuospatial functions, and attention/processing speed was calculated. Linear mixed models with a random intercept and time as independent variable were used to investigate cognitive trajectories, adjusted for sex, age, education, and vision and hearing capacities. In a second step, linear mixed models were used to associate cognitive trajectories with factors underlying cognitive reserve, physical health at baseline, and AD-associated neuropathology. Of the 1023 centenarians approached, 340 were included in the study. We analyzed 330 centenarians for whom cognitive tests were available at baseline (239 [72.4%] women; median [interquartile range] age of 100.5 [100.2-101.7] years), with a mean (SD) follow-up duration of 1.6 (0.8) years. We observed no decline across investigated cognitive domains, with the exception of a slight decline in memory function (β, -0.10 SD per year; 95% CI, -0.14 to -0.05 SD; P < .001). Cognitive performance was associated with factors of physical health (eg, higher Barthel index: β, 0.37 SD per year; 95% CI, 0.24-0.49; P < .001) and cognitive reserve (eg, higher education: β, 0.41 SD per year; 95% CI, 0.29-0.53; P < .001), but none of these factors were associated with the rate of decline. Neuropathological reports were available for 44 participants. While centenarian brains revealed varying loads of postmortem neuropathological hallmarks of AD, this was not associated with cognitive performance or rate of decline. While we observed a slight vulnerability for decline in memory function, centenarians maintained high levels of performance in all other investigated cognitive domains for up to 4 years despite the presence of risk factors of cognitive decline. These findings suggest that mechanisms of resilience may underlie the prolongation of cognitive health until exceptional ages.

Neuropathological consensus criteria for the evaluation of Lewy pathology in post-mortem brains: a multi-centre study

Currently, the neuropathological diagnosis of Lewy body disease (LBD) may be stated according to several staging systems, which include the Braak Lewy body stages (Braak), the consensus criteria by McKeith and colleagues (McKeith), the modified McKeith system by Leverenz and colleagues (Leverenz), and the Unified Staging System by Beach and colleagues (Beach). All of these systems use semi-quantitative scoring (4- or 5-tier scales) of Lewy pathology (LP; i.e., Lewy bodies and Lewy neurites) in defined cortical and subcortical areas. While these systems are widely used, some suffer from low inter-rater reliability and/or an inability to unequivocally classify all cases with LP. To address these limitations, we devised a new system, the LP consensus criteria (LPC), which is based on the McKeith system, but applies a dichotomous approach for the scoring of LP (i.e., “absent” vs. “present”) and includes amygdala-predominant and olfactory-only stages. α-Synuclein-stained slides from brainstem, limbic system, neocortex, and olfactory bulb from a total of 34 cases with LP provided by the Newcastle Brain Tissue Resource (NBTR) and the University of Pennsylvania brain bank (UPBB) were scanned and assessed by 16 raters, who provided diagnostic categories for each case according to Braak, McKeith, Leverenz, Beach, and LPC systems. In addition, using LP scores available from neuropathological reports of LP cases from UPBB (n = 202) and NBTR (n = 134), JT (UPBB) and JA (NBTR) assigned categories according to all staging systems to these cases. McKeith, Leverenz, and LPC systems reached good (Krippendorff’s α ≈ 0.6), while both Braak and Beach systems had lower (Krippendorff’s α ≈ 0.4) inter-rater reliability, respectively. Using the LPC system, all cases could be unequivocally classified by the majority of raters, which was also seen for 97.1% when the Beach system was used. However, a considerable proportion of cases could not be classified when using Leverenz (11.8%), McKeith (26.5%), or Braak (29.4%) systems. The category of neocortical LP according to the LPC system was associated with a 5.9 OR (p < 0.0001) of dementia in the 134 NBTR cases and a 3.14 OR (p = 0.0001) in the 202 UPBB cases. We established that the LPC system has good reproducibility and allows classification of all cases into distinct categories. We expect that it will be reliable and useful in routine diagnostic practice and, therefore, suggest that it should be the standard future approach for the basic post-mortem evaluation of LP.

Detailed neuropathologic report of COVID-19 complicated by large intracerebral hemorrhage and periventricular lesions with macrophagic infiltrates.

Infection with the SARS-CoV-2 virus affects a wide range of systems. Significant involvement of the central nervous system has been described, including ischemic and hemorrhagic strokes. Thus far, neuropathologic reports of patients who passed away from COVID-19 have generally described non-specific findings, such as variable reactive gliosis and meningeal chronic inflammatory infiltrates, as well as the consequences of the infection's systemic complications on the brain, including ischemic infarcts and hypoxic/ischemic encephalopathy. The neuropathological changes in patients with COVID-19 and large hemorrhagic strokes have not been described in detail. We report the case of an elderly male who had a long course of COVID-19 and ultimately passed away from a large intracerebral hemorrhage. In addition to acute hemorrhage, neuropathologic examination demonstrated non-specific reactive changes and chronic periventricular lesions with macrophagic and perivascular lymphocytic infiltrates without evidence of demyelination or presence of SARS-CoV-2 by PCR test. This manuscript expands the spectrum of reported neuropathological changes in patients with COVID-19.

Clinicopathological investigation of the background of cognitive decline in elderly schizophrenia.

We have often observed dementia symptoms or severe neurocognitive decline in the long-term course of schizophrenia. While there are epidemiological reports that patients with schizophrenia are at an increased risk of developing dementia, there are also neuropathological reports that the prevalence of Alzheimer's disease (AD) in schizophrenia is similar to that in normal controls. It is difficult to distinguish, based solely on the clinical symptoms, whether the remarkable dementia symptoms and cognitive decline seen in elderly schizophrenia are due to the course of the disease itself or a concomitant neurocognitive disease. Neuropathological observation is needed for discrimination. We conducted a neuropathological search on three cases of schizophrenia that developed cognitive decline or dementia symptoms after a long illness course of schizophrenia. The clinical symptoms of total disease course were confirmed retrospectively in the medical record. We have evaluated neuropathological diagnosis based on not only Hematoxylin-Eosin and Klüver-Barrera staining specimens but also immunohistochemical stained specimens including tau, β-amyloid, pTDP-43 and α-synuclein protein throughout clinicopathological conference with multiple neuropathologists and psychiatrists. The three cases showed no significant pathological findings or preclinical degenerative findings, and poor findings consistent with symptoms of dementia were noted. Although the biological background of dementia symptoms in elderly schizophrenic patients is still unclear, regarding the brain capacity/cognitive reserve ability, preclinical neurodegeneration changes in combination with certain brain vulnerabilities due to schizophrenia itself are thought to induce dementia syndrome and severe cognitive decline.

Safety and accuracy of frameless electromagnetic-navigated (AXIEMTM)-guided brain lesion biopsies: a large single-unit study.

Brain biopsies are required to establish a definitive histological diagnosis for brain lesions that have been identified on imaging in order to guide further treatment for patients. Various navigation systems are in use but little up to date evidence is available regarding the safety and accuracy of a frameless, electromagnetic technique to target brain lesions. Data was collected retrospectively on all patients that had brain biopsies at our institution from 01/01/2010 to 31/12/2017. Operation notes, neuropathology reports, and clinical notes on electronic patient record were used to determine whether biopsy of adequate identifiable abnormal tissue was achieved, whether a definitive diagnosis was established, any adverse events occurred, and if a repeat biopsy was carried out. Three hundred seventy-one AxiEM (Medtronic, Minneapolis, USA)-guided brain tumor biopsies were performed in this 8-year period. Three hundred forty-nine (94.07%) procedures provided definitive tissue diagnosis, 22 (5.93%) were non diagnostic; in 6 cases (1.62%), repeat biopsy was performed and adverse events which caused clinical compromise were observed in 4 patients (1.08%). The AxiEM is a fast, effective, and safe frameless and pinless neuronavigational system. It offers a high degree of accuracy required for the establishment of a definitive diagnosis, permitting optimal further treatment, and thus improving patient outcomes.

Increasing value of autopsies in patients with brain tumors in the molecular era.

Pediatric brain tumors are associated with high morbidity and mortality, in part due to insufficient understanding of tumor biology. With limited tissue allocation for research from surgical specimens, a key barrier to improving biological understanding, brain tumor autopsies have become an increasingly valuable resource. This study reviews the brain tumor autopsy practice at our institution and describes specific emerging research utilization patterns beyond the clinical autopsy report. We performed a retrospective analysis of brain tumor autopsies at Boston Children's Hospital (BCH) between 2007 and 2017 and reviewed their consents, neuropathology reports and final diagnoses. We reviewed the method of tissue triaging for research consented autopsies (bioregistry, frozen and fresh tissue) and documented their specific uses. Ninety-six deaths at BCH were due to brain tumors; 56 autopsies were performed (58.3%), of which 49 (87.5%) were consented for research. Tumor mapping was performed on all cases and tissue was allocated for DNA- and RNA-based sequencing studies (published and ongoing). Three tissue allocations with a postmortem interval of 8h or less resulted in successful cell lines. Tissue from 14 autopsies was contributed to the National DIPG Registry. Our institutional pediatric brain tumor autopsy clinical experience demonstrates the increased utility and wide utilization of autopsy-derived tissue for multiple types of research. These results support the increased efforts to obtain research consent for brain tumor autopsy and active collection of unfixed autopsy material in the molecular era.

Mycobacterium chimaera encephalitis following cardiac surgery in three adult immunocompetent patients: first detailed neuropathological report

Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.LEARNING OBJECTIVESThis presentation will enable the learner to:1.Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis2.Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management

Neurodegenerative Dementias: Improving Brain Health to Decrease Risk.

Neurodegenerative Dementias: Improving Brain Health to Decrease Risk.

Synaptic plexi of U-fibre layer beneath focal cortical dysplasias: Role in epileptic networks.

The purpose is to demonstrate heterotopic neurones and their synaptic plexi within the U-fibre layer beneath focal cortical dysplasias (FCD). This prospective qualitative neuropathological study included 23 patients, ages from 3 months to 17 years: resections at epileptogenic foci in 10 FCD Ia; 6 FCD IIa,b; 2 FCD IIIa,d; 3 HME; 2 TSC; 8 controls. immunoreactivities for synaptophysin, NeuN, MAP2, SMI32, calretinin, GFAP, vimentin, α-B-crystallin. Bielschowsky silver; LFB; mitochondrial enzyme histochemistry (frozen sections). Subcortical white matter in FCD exhibited neuronal dispersion within U-fibres in FCD I, II and also deep white matter neuronal clusters in FCD II, HME, TSC. Neurones reacted for NeuN, MAP2; few for calretinin. Synaptophysin well demonstrated elaborate U-fibre plexi including axones between U-fibre neurones and projecting to overlying cortex. Deep white matter axones interconnected heterotopia but did not penetrate U-fibres to reach cortex. Mitochondrial enzymatic activity was intense in some neurones, normal in others. Glial α-B-crystallin served as a marker of epileptogenic zones identified electrographically. U-fibre synaptic plexi contribute to excitatory circuitry in the cortex and thus to epileptic networks. Deep white matter neurones form local, less integrated plexi except transmantle dysplasias continuous with cortex. U-fibres may be a barrier to axonal penetration from deep heterotopia. Hypermetabolic neurones suggest repetitive ictogenic depolarizations. Gyral resections should include the U-fibre layer. Neuropathology reports should describe subcortical plexi. Synaptophysin immunoreactivity is a valuable supplement for this purpose. .

Role of the temporal pole in temporal lobe epilepsy seizure networks: an intracranial electrode investigation.

OBJECTIVE A convergence of clinical research suggests that the temporal pole (TP) plays an important and potentially underappreciated role in the genesis and propagation of seizures in temporal lobe epilepsy (TLE). Understanding its role is becoming increasingly important because selective resections for medically intractable TLE spare temporopolar cortex (TPC). The purpose of this study was to characterize the role of the TPC in TLE after using dense electrocorticography (ECoG) recordings in patients undergoing invasive monitoring for medically intractable TLE. METHODS Chronic ECoG recordings were obtained in 10 consecutive patients by using an array customized to provide dense coverage of the TP as part of invasive monitoring to localize the epileptogenic zone. All patients would eventually undergo cortico-amygdalohippocampectomy. A retrospective review of the patient clinical records including ECoG recordings, neuroimaging studies, neuropathology reports, and clinical outcomes was performed. RESULTS In 7 patients (70%), the TP was involved at seizure onset; in 7 patients (70%), there were interictal discharges from the TP; and in 1 case, there was early spread to the TP. Seizure onset in the TP did not necessarily correlate with preoperative neuroimaging abnormalities of the TP. CONCLUSIONS These data demonstrate that TPC commonly plays a crucial role in temporal lobe seizure networks. Seizure onset from the TP would not have been predicted based on available neuroimaging data or interictal discharges. These findings illustrate the importance of thoroughly considering the role of the TP prior to resective surgery for TLE, particularly when selective mesial resection is being considered.

A neuropathological report of familial amyotrophic lateral sclerosis with an R521S FUS/TLS mutation

Background: Neuropathological finding of familial Amyotrophic lateral sclerosis(fALS) with an R521S FUS/TLS mutation was not reported. We report here pedigree report of fALS with the mutation.

Methionine Sulfoxide Reductase-B3 (MsrB3) Protein Associates with Synaptic Vesicles and its Expression Changes in the Hippocampi of Alzheimer's Disease Patients.

Genome-wide association studies (GWAS) identified susceptibility loci associated with decreased hippocampal volume, and found hippocampal subfield-specific effects at MSRB3 (methionine sulfoxide reductase-B3). The MSRB3 locus was also linked to increased risk for late onset Alzheimer's disease (AD). In this study, we uncovered novel sites of MsrB3 expression in CA pyramidal layer and arteriolar walls by using automated immunohistochemistry on hippocampal sections from 23 individuals accompanied by neuropathology reports and clinical dementia rating scores. Controls, cognitively intact subjects with no hippocampal neurofibrillary tangles, exhibited MsrB3 signal as distinct but rare puncta in CA1 pyramidal neuronal somata. In CA3, however, MsrB3-immunoreactivity was strongest in the neuropil of the pyramidal layer. These patterns were replicated in rodent hippocampi where ultrastructural and immunohistofluorescence analysis revealed MsrB3 signal associated with synaptic vesicles and colocalized with mossy fiber terminals. In AD subjects, the number of CA1 pyramidal neurons with frequent, rather than rare, MsrB3-immunoreactive somatic puncta increased in comparison to controls. This change in CA1 phenotype correlated with the occurrence of AD pathological hallmarks. Moreover, the intensity of MsrB3 signal in the neuropil of CA3 pyramidal layer correlated with the signal pattern in neurons of CA1 pyramidal layer that was characteristic of cognitively intact individuals. Finally, MsrB3 signal in the arteriolar walls in the hippocampal white matter decreased in AD patients. This characterization of GWAS-implicated MSRB3 protein expression in human hippocampus suggests that patterns of neuronal and vascular MsrB3 protein expression reflect or underlie pathology associated with AD.

アルコール性脳障害の神経病理 ―一次性アルコール性認知症は存在するか？ 剖検報告―

アルコール性脳障害の神経病理 ―一次性アルコール性認知症は存在するか？ 剖検報告―

CNS findings in chronic fatigue syndrome and a neuropathological case report

Chronic fatigue syndrome (CFS) is characterized as a persistent, debilitating complex disorder of unknown etiology, whereby patients suffer from extreme fatigue, which often presents with symptoms that include chronic pain,...

EP-1115: Stereotactic radiosurgery for brain metastases: neuropathological report of three autopsy cases

EP-1115: Stereotactic radiosurgery for brain metastases: neuropathological report of three autopsy cases