Brainstem intraparenchymal schwannoma : A case report and literature review

Publisher Copyright: ©2021 Published by Scientific Scholar on behalf of Surgical Neurology InternationalBackground: Intracranial intraparenchymal schwannomas (IS) are rare tumors that have mainly been described in case reports. Here, we report on a case of a brainstem IS and included a comprehensive literature review. Case Description: A 74-year-old man presented with progressive gait disturbances. CT- and MRI-imaging revealed a contrast-enhancing mass accompanied by a cyst in the dorsolateral pons. Hemangioblastoma was suspected and surgery was advised. During surgery, gross total resection of a non-invasive tumor was performed. Postoperative recovery was uneventful. Based on histopathological examination, the intraparenchymal brainstem tumor was diagnosed as schwannoma. Conclusion: Our extensive review illustrates that ISs are benign tumors that most often present in relatively young patients. Malignant cases have been described but form an extremely rare entity. Preoperative diagnosis based on radiological features is difficult but should be considered when peritumoral edema, calcifications, and cysts are noted. In benign cases, gross total resection of the lesion is curative. To adequately select this treatment and adjust the surgical strategy accordingly, it is important to include IS in the preoperative differential diagnosis when the abovementioned radiological features are present.Peer reviewe

NON-INVASIVE VASCULAR VERY-HIGH RESOLUTION ULTRASOUND TO QUANTIFY ARTERY INTIMA LAYER THICKNESS : VALIDATION OF THE FOUR-LINE PATTERN

Preliminary findings suggest that very-high resolution ultrasound (VHRU, 55 MHz) could differentiate arterial intima layer thickness (IT) non-invasively in vivo. We aimed to validate ultrasound-derived IT measurements and describe a four-line pattern consistent with intimal thickening. VHRU was applied to temporal arteries of 37 patients with suspected giant cell arteritis without inflammation on histology. Anatomically matched ultrasound-derived measurements of arterial layer thickness with the leading-edge method was compared to histology. Intimal thickening (IT >0.06 mm on histology) was identified as a four-line pattern in VHRU with a sensitivity of 96.3% and a specificity of 100%. Histologic and VHRU IT measurement agreement was excellent (mean difference 0.007 mm; 95% limits of agreement, -0.043 to 0.057) and intra-class coefficient (ICC) 0.923 (95% confidence interval [CI], 0.833-0.964). Intra- and inter-observer agreements for VHRU IT were high: ICC 0.946 (95% CI, 0.877-0.976) and 0.872 (95% CI, 0.773-0.943). VHRU utilizing the leading-to-leading edge method allows accurate and reliable measurements of arterial IT in patients with IT >0.06 mm. Measurements of IT will provide the opportunity to explore early subclinical structural intimal changes in the arterial wall increasing with age. (C) 2019 World Federation for Ultrasound in Medicine & Biology. All rights reserved.Peer reviewe

Loss of mtDNA activates astrocytes and leads to spongiotic encephalopathy

Mitochondrial dysfunction manifests as different neurological diseases, but the mechanisms underlying the clinical variability remain poorly understood. To clarify whether different brain cells have differential sensitivity to mitochondrial dysfunction, we induced mitochondrial DNA (mtDNA) depletion in either neurons or astrocytes of mice, by inactivating Twinkle (TwKO), the replicative mtDNA helicase. Here we show that astrocytes, the most abundant cerebral cell type, are chronically activated upon mtDNA loss, leading to early-onset spongiotic degeneration of brain parenchyma, microgliosis and secondary neurodegeneration. Neuronal mtDNA loss does not, however, cause symptoms until 8 months of age. Findings in astrocyte-TwKO mimic neuropathology of Alpers syndrome, infantile-onset mitochondrial spongiotic encephalopathy caused by mtDNA maintenance defects. Our evidence indicates that (1) astrocytes are dependent on mtDNA integrity; (2) mitochondrial metabolism contributes to their activation; (3) chronic astrocyte activation has devastating consequences, underlying spongiotic encephalopathy; and that (4) astrocytes are a potential target for interventions.Peer reviewe

Progressive Stroke-Like Symptoms in a Patient with Sporadic Creutzfeldt-Jakob Disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in which accumulation of a pathogenic isoform of prion protein (PrPSc) induces neuronal damage with distinct pathologic features. The prognosis of sCJD is devastating: rapid clinical decline is followed by death generally within months after onset of symptoms. The classic clinical manifestations of sCJD are rapidly progressing dementia, myoclonus, and ataxia. However, the spectrum of clinical features can vary considerably. We describe a definite, neuropathologically verified sCJD in a 67-year-old woman who initially presented with progressive stroke-like symptoms: left-sided hemiparesis and ataxia within a few days. The initial brain magnetic resonance imaging (MRI) showed bilateral cortical hyperintensity on diffusion-weighted sequences (DWI) resembling multiple ischemic lesions. Despite anticoagulation with low-molecular-weight heparin, the patient deteriorated rapidly, became dysphagic and bedridden with myoclonic jerks on her left side extremities correlating with intermittent high-amplitude epileptiform discharges on electroencephalography (EEG). Basal ganglia hyperintense signal changes in addition to cortical ribboning were seen in DWI images of a follow-up MRI. Repeated EEG recordings showed an evolution to periodic sharp wave complexes. Protein 14-3-3 was positive in her cerebrospinal fluid specimen, in addition to an abnormally high total tau level. In the terminal stage the patient was in an akinetic, mutistic state with deteriorating consciousness. She died 19 days after admission to the hospital. Neuropathologic investigation corroborated the clinical diagnosis of sCJD with spongiform degeneration and immunohistochemical demonstration of the deposition of pathologic PrPSc

Magnetoencephalographic Abnormalities in Creutzfeldt-Jakob Disease: A Case Report

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disease with no effective therapy available. We recorded spontaneous magnetoencephalography and auditory evoked fields (AEFs) from a male patient with a rapidly progressive memory disorder, ataxia and myoclonus. Post-mortem examination confirmed sporadic CJD. Sources of the abnormal slow wave activity were localized with a beamformer software. Sources of sharp transients and AEFs were modeled with equivalent current dipoles. The estimated sources of spontaneous activity abnormalities were more dominant in the left hemisphere, in line with left-dominant abnormalities in diffusion-weighted MRI. Sources of AEFs were found in both temporal lobes. Magnetoencephalography measurements on CJD patients are feasible, and provide efficient means for localizing abnormal cortical activity in CJD

Immune activation enhances epithelial nerve growth in provoked vestibulodynia

BACKGROUND: Provoked vestibulodynia manifests as allodynia of the vulvar vestibular mucosa. The exact mechanisms that result in altered pain sensation are unknown. Recently, we demonstrated the presence of secondary lymphoid tissue, which is the vestibule-associated lymphoid tissue in the vestibular mucosa, and showed that this tissue becomes activated in provoked vestibulodynia. OBJECTIVE: The purpose of this study was to examine whether expression of intraepithelial nerve fibers and nerve growth factor are related to immune activation in provoked vestibulodynia. STUDY DESIGN: Vestibular mucosal specimens were obtained from 27 patients with severe provoked vestibulodynia that was treated by vestibulectomy and from 15 control subjects. We used antibodies against the protein gene product 9.5, the neuron specific neurofilament, and nerve growth factor for immunohistochemistry to detect intraepithelial nerve fibers and nerve growth factor expressing immune cells in the vestibular mucosa. For intraepithelial nerve fibers, we determined their linear density (fiber counts per millimeter of the outer epithelial surface, protein gene product 9.5) or presence (neuron specific neurofilament). Nerve growth factor was analyzed by counting the staining-positive immune cells. Antibodies against CD20 (B lymphocytes) and CD3 (T lymphocytes) were used to identify and locate mucosal areas with increased density of lymphocytes and the presence of germinal centers (ie, signs of immune activation). B-cell activation index was used to describe the overall intensity of B-cell infiltration. RESULTS: We found more protein gene product 9.5-positive intraepithelial fibers in vestibulodynia than in the control samples (6.3/mm [range, 0.0-15.8] vs 2.0/mm [range, 0.0-12.0]; P = .006). Neuron specific neurofilament -positive intraepithelial fibers were found in 17 of 27 vestibulodynia cases (63.0%) and in none of the control cases. Protein gene product 9.5-positive intraepithelial fibers were more common in samples with more pronounced immune activation. The density of these fibers was higher in samples with than without germinal centers (6.1/mm [range, 4.3-15.8] vs 3.0/mm [range, 0.0-13.4]; P = .020). A positive correlation between the fiber density and B-cell activation index score of the sample was found (Spearman's Rho, 0.400; P = .004; R-2 = 0.128). No significant difference, however, was found in the density or presence of nerve fibers between samples with high and low T-cell densities. We identified areas of minor and major vestibular glands in 16 of the patient samples and in 1 control sample. Protein gene product 9.5-positive nerve fibers were found more often in glandular epithelium surrounded by B-cell infiltration than in glands without B cells (P = .013). Also, the presence of neuron specific neurofilament-positive fibers in glandular epithelium was associated with B-cell infiltrates (P = .053). Nerve growth factor-positive immune cells were more common in mucosal areas with than without B-cell infiltration and intraepithelial nerve fibers. CONCLUSION: Excessive epithelial nerve growth in provoked vestibulodynia is associated with increased B-cell infiltration and the presence of germinal centers. This supports the fundamental role of immune activation in provoked vestibulodynia.Peer reviewe

Hippocampal Sclerosis in the Oldest Old : A Finnish Population-Based Study

Background: There are only few population-based studies that have systemically investigated the prevalence of hippocampal sclerosis (HS) in the very old. The frequency of unilateral versus bilateral HS has been rarely studied. Objective: We investigated the prevalence and laterality of HS and its association with other neurodegenerative and vascular pathologies in a population-based sample of very elderly. Furthermore, the concomitant presence of immunoreactivity for TDP-43, p62, and HPtau was studied. Methods: The population-based Vantaa 85(+) study includes all inhabitants of the city of Vantaa, who were > 85 years in 1991 (n = 601). Neuropathological assessment was possible in 302 subjects. Severity of neuronal loss of CA sectors and subiculum was determined bilaterally by HE-staining. Immunohistochemistry performed using antibodies for TDP-43, p62, and HPtau. Results: Neuronal loss and pathological changes in the hippocampus sector CA1 and subiculum were observed in 47 of the 302 individuals (16%), and 51% of these changes were bilateral. HS without comorbid neurodegenerative pathology was found in 1/47 subjects with HS (2%). Dementia (p <0.001) and TDP-43 immunopositivity of the granular cell layer of the dentate fascia (p <0.001) were strongly associated with HS. The CERAD score, immunopositivity for HPtau and p62 in the granular cell layer of the fascia dentate were also associated. Conclusion: HS is prevalent (16%) in the oldest old population, but HS without any comorbid neurodegenerative pathology is rare. The high frequency of unilateral HS (49%) implied that bilateral sampling of hippocampi should be routine practice in neuropathological examination.Peer reviewe

Pahanlaatuisuusaste ei yksin riitä - molekyylitutkimukset tarkentavat glioomien diagnostiikkaa

Vertaisarvioitu. Teema : aivokasvaimet. English summary.Glioomat ovat primaareista aivokasvaimista yleisimpiä. Glioomien diagnostiikka perustuu kasvainten histologisiin piirteisiin ja molekulaarisiin muutoksiin. Vuonna 2016 päivitetty WHO:n aivokasvainluokitus tuo geneettiset muutokset osaksi kasvainten diagnoosia. Integroitu diagnoosi sisältää kasvaimen histologisen tyypin, pahanlaatuisuusasteen ja molekulaariset muutokset. Glioomien tärkeimmät molekyylimuutokset ovat IDH (isositraattidehydrogenaasi) -geenin mutaatio ja 1p/19q-kodeleetio. Astrosytoomissa IDH-mutaatio erottaa suotuisan ennusteen kasvaimet omaksi ryhmäkseen. IDH-mutatoitumaton glioblastooma on glioomista tavallisin ja pahanlaatuisin. Paremman ennusteen oligodendroglioomassa on samanaikaisesti IDH-mutaatio ja 1p/19q-kodeleetio. H3 K27M -mutatoitunut keskiviivan gliooma on uusi aggressiivinen glioomatyyppi. Molekyylimuutoksiin perustuva luokittelu parantaa glioomien diagnostiikan tarkkuutta ja luo pohjan niiden tulokselliselle hoidolle.Peer reviewe

Genetic and Epigenetic Characterization of Growth Hormone-Secreting Pituitary Tumors

Somatic driver mechanisms of pituitary adenoma pathogenesis have remained incompletely characterized; apart from mutations in the stimulatory G alpha protein (G alpha(s) encoded by GNAS) causing activated cAMP synthesis, pathogenic variants are rarely found in growth hormone-secreting pituitary tumors (somatotropinomas). The purpose of the current work was to clarify how genetic and epigenetic alterations contribute to the development of somatotropinomas by conducting an integrated copy number alteration, whole-genome and bisulfite sequencing, and transcriptome analysis of 21 tumors. Somatic mutation burden was low, but somatotropinomas formed two subtypes associated with distinct aneuploidy rates and unique transcription profiles. Tumors with recurrent chromosome aneuploidy (CA) were GNAS mutation negative (Gsp(-)). The chromosome stable (CS) -group contained Gsp(+) somatotropinomas and two totally aneuploidy-free Gsp(-) tumors. Genes related to the mitotic G(1)-S-checkpoint transition were differentially expressed in CA- and CS-tumors, indicating difference in mitotic progression. Also, pituitary tumor transforming gene 1 (PTTG1), a regulator of sister chromatid segregation, showed abundant expression in CA-tumors. Moreover, somatotropinomas displayed distinct Gsp genotypespecific methylation profiles and expression quantitative methylation (eQTM) analysis revealed that inhibitory G alpha (G alpha(i)) signaling is activated in Gsp(+) tumors. These findings suggest that aneuploidy through modulated driver pathways may be a causative mechanism for tumorigenesis in Gsp(-) somatotropinomas, whereas Gsp(+) tumors with constitutively activated cAMP synthesis seem to be characterized by DNA methylation activated G alpha(i) signaling.Peer reviewe

A Novel Loss-of-Function GRN Mutation p.(Tyr229*) : Clinical and Neuropathological Features

Mutations in the progranulin (GRN) gene represent about 5-10% of frontotemporal lobar degeneration (FTLD). We describe a proband with a novel GRN mutation c.687T>A, p.(Tyr229*), presenting with dyspraxia, dysgraphia, and dysphasia at the age of 60 and a very severe FTLD neuropathological phenotype with TDP43 inclusions. The nephew of the proband had signs of dementia and personality changes at the age of 60 and showed similar but milder FTLD pathology. Three other family members had had early-onset dementia. Gene expression studies showed decreased GRN gene expression in mutation carriers' blood samples. In conclusion, we describe a novel GRN, p.(Tyr229*) mutation, resulting in haploinsufficiency of GRN and a severe neuropathologic FTLD phenotype.Peer reviewe