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Objective To assess the prognostic profile, clinical outcome, treatment-associated morbidity, and treatment burden of elderly patients with glioblastoma (GBM) undergoing microsurgical tumor resection as part of contemporary treatment algorithms. Methods We retrospectively identified patients with GBM ≥65 years of age who were treated by resection at 2 neuro-oncology centers. Survival was assessed by Kaplan-Meier analyses; log-rank tests identified prognostic factors. Results The study population included 160 patients (mean age, 73.1 ± 5.1 years), and the median contrast-enhancing tumor volume was 31.0 cm3. Biomarker analyses revealed O(6)-methylguanine-DNA methyltransferase–promoter methylation in 62.7% and wild-type isocitrate dehydrogenase in 97.5% of tumors. The median extent of resection (EOR) was 92.3%, surgical complications were noted in 10.0% of patients, and the median postoperative hospitalization period was 8 days. Most patients (60.0%) received adjuvant radio-/chemotherapy. The overall treatment-associated morbidity was 30.6%. The median progression-free and overall survival were 5.4 months (95% confidence interval [CI], 4.6–6.4 months) and 10.0 months (95% CI, 7.9–11.7 months). The strongest predictors for favorable outcome were patient age ≤73.0 years (P = 0.0083), preoperative Karnofsky Performance Status Scale score ≥80% (P = 0.0179), postoperative modified Rankin Scale score ≤1 (P Conclusions Clinical outcome for elderly patients with GBM remains limited. Nonetheless, the observed treatment-associated morbidity and treatment burden were moderate in the patients, and patient age and performance status remained the strongest predictors for survival. The risks and benefits of tumor resection in the age of biomarker-adjusted treatment concepts require further prospective evaluation.

BACKGROUND Oligodendrogliomas are rare, slow-growing brain tumors with a survival prognosis of >10 years. Although adjuvant radio-chemotherapy has been shown to prolong survival, aggressive treatment comes at the cost of increased toxicity. Systematic data on the optimal timing of adjuvant treatment in oligodendroglioma are lacking. MATERIAL AND METHODS Patients treated for a newly diagnosed IDH-mutated, 1p/19q-codeleted oligodendroglioma (WHO grades II/III) in 2000 - 2018 at the Medical University of Vienna or the Kepler University Hospital Linz (Austria) were included in this retrospective study. Adjuvant treatment was defined as radiotherapy (RT), chemotherapy (CHT) or radio-chemotherapy (R-CHT) within 6 months after resection in the absence of progression. “Wait and see” was defined as regular follow up with magnetic resonance imaging and treatment at progression. RESULTS 185 patients were identified, comprising 123/185 (66.5%) WHO grade II and 62/185 (33.5%) WHO grade III oligodendrogliomas. Median age at diagnosis was 42 years (range: 20–82). Gross total resection (GTR) could be achieved in 77/178 (42.3%) evaluable patients. Adjuvant treatment was applied in 63/185 (38.2%) patients, of whom 43/63 (68.3%) underwent R-CHT, 9/63 (14.3%) CHT only and 11/63 (17.5%) RT only. 43/52 (82.7%) received temozolomide-based treatment, 1/52 (1.9%) procarbazine, lomustine and vincristine (PCV), 1/52 dacarbazine/fotemustine and in 7/52 (13.5%) patients, no data on used regimens was available. Adjuvant treatment was more frequently applied in WHO grade 3 tumors (p CONCLUSION The application of adjuvant therapy was associated with favorable PFS in patients who underwent resection of newly diagnosed oligodendroglioma in this retrospective study. Prospective clinical trials should investigate the risks and benefits of adjuvant treatment versus initial observation in patients with oligodendroglioma.

Background Parkinson's disease (PD) is a neurodegenerative disorder characterized by the presence of inclusions known as Lewy bodies in some brain regions. Lewy bodies consist of α-synuclein and many other proteins including chaperones. Objective To learn more about the role of chaperone complexes in PD and a related disorder, i.e., dementia with Lewy bodies (DLB), in this work we analyzed the expression of HSP90 and its two quite recently identified co-chaperones, SGT1 and CHP-1, in selected brain regions from patients suffering from these diseases. Methods To fulfill the aim of our study we used human material and applied immunohistochemistry, Western blot analysis and real time/quantitative PCR (RT-qPCR). Results We have found that HSP90 mRNA level is higher in the temporal cortex of PD and in frontal cortex of DLB brains, even though level of protein does not change significantly. The mRNA level of SGT1 is higher in the frontal and temporal cortex of PD and in substantia nigra of DLB brains while no significant changes in the level of protein were noticed. Similarly, the mRNA level of CHP-1 was found to be higher in the frontal and temporal cortex of PD and in all examined regions i.e. substantia nigra, frontal and temporal cortex of DLB brains. In the case of CHP-1 the protein level was found to be higher in frontal cortex of PD and in all examined areas of DLB patients. Conclusions Our data indicate that the level of HSP90, SGT1 and CHP-1 is upregulated in the majority of cases of PD and DLB, which suggests that the examined proteins might be involved in these pathologies.

Background Glioblastoma multiforme (GBM) is usually characterized by diffuse, infiltrative growth and local tumor progression. Extensive leptomeningeal metastases are rarely observed. It is unclear which GBMs are prone to this specific growth pattern and progression, and standardized salvage treatment protocols are unavailable. Case Description In a 45-year-old man without focal neurologic deficit, a right temporal GBM, IDH-wildtype (biomarkers MGMT promoter methylation negative, Ki-67 proliferation rate 70%) was diagnosed. Gross tumor resection followed by concomitant and adjuvant radiotherapy and chemotherapy with temozolomide was performed. Routine follow-up imaging 8 months later showed a right parietal meningeal tumor. Resection confirmed a distant GBM, and next-generation sequencing revealed high tumor mutational burden, high-frequency microsatellite instability, and a pharmacologically targetable KIT mutation. Complete neuraxis imaging revealed multiple contrast-enhancing tumors in the craniocervical junction and levels C7, Th8-Th11, and S1. The craniocervical tumors and the cervical spine from C1-C2 were irradiated as palliative care, and second-line combined chemotherapy and antiangiogenic therapy with irinotecan and bevacizumab was initiated, which was later changed to an immune-checkpoint blockade with pembrolizumab in combination with bevacizumab owing to tumor progression. Tumor growth was slowed, but the patient eventually developed a progressive paraparesis. Subsequent KIT-targeting tyrosine kinase inhibitor therapy with imatinib was administered for a short time. The patient died 13.8 months after initial diagnosis. Conclusions High-risk genetic profiles for GBMs prone to develop extensive leptomeningeal metastases need to be identified. Guidelines on preemptive, complete neuraxis imaging in certain patients with GBM as well as treatment guidelines need to be developed.

Introduction Adult brainstem gliomas (BSGs) are rare central nervous system tumours characterized by a highly heterogeneous clinical course. Median survival times range from 11 to 84 months. Beyond surgery, no treatment standard has been established. We investigated clinical and radiological data to assess prognostic features providing support for treatment decisions. Methods 34 BSG patients treated between 2000 and 2019 and aged ≥ 18 years at the time of diagnosis were retrospectively identified from the databases of the two largest Austrian Neuro-Oncology centres. Clinical data including baseline characteristics, clinical disease course, applied therapies, the outcome as well as neuroradiological and neuropathological findings were gathered and analysed. The tumour apparent diffusion coefficient (ADC), volumetry of contrast-enhancing and non-contrast-enhancing lesions were determined on magnetic resonance imaging scans performed at diagnosis. Results The median age at diagnosis was 38.5 years (range 18–71 years). Tumour progression occurred in 26/34 (76.5%) patients after a median follow up time of 19 months (range 0.9–236.2). Median overall survival (OS) and progression-free survival (PFS) was 24.1 months (range 0.9–236.2; 95% CI 18.1–30.1) and 14.5 months (range 0.7–178.5; 95% CI 5.1–23.9), respectively. Low-performance status, high body mass index (BMI) at diagnosis and WHO grading were associated with shorter PFS and OS at univariate analysis (p p = 0.018). Conclusion ECOG, BMI, WHO grade and ADC values were associated with the survival prognosis of BSG patients and should be included in the prognostic assessment.

Mitochondriopathies represent a wide spectrum of miscellaneous disorders with multisystem involvement, which are caused by various genetic changes. The establishment of the diagnosis of mitochondriopathy is often challenging. Recently, several mutations of the VARS2 gene encoding the mitochondrial valyl-tRNA synthetase were associated with early onset encephalomyopathies or encephalocardiomyopathies with major clinical features such as hypotonia, developmental delay, brain MRI changes, epilepsy, hypertrophic cardiomyopathy, and plasma lactate elevation. However, the correlation between genotype and phenotype still remains unclear. In this paper we present a male Caucasian patient with a recurrent c.1168G>A (p.Ala390Thr) and a new missense biallelic variant c.2758T>C (p.Tyr920His) in the VARS2 gene which were detected by whole exome sequencing (WES). VARS2 protein was reduced in the patient's muscle. A resulting defect of oxidative phosphorylation (OXPHOS) was proven by enzymatic assay, western blotting and immunohistochemistry from a homogenate of skeletal muscle tissue. Clinical signs of our patient included hyperlactatemia, hypertrophic cardiomyopathy (HCM) and pulmonary hypertension, which led to early death at the age of 47 days without any other known accompanying signs. The finding of novel variants in the VARS2 gene expands the spectrum of known mutations and phenotype presentation. Based on our findings we recommend to consider possible mitochondriopathy and to include the analysis of the VARS2 gene in the genetic diagnostic algorithm in cases with early manifesting and rapidly progressing HCM with hyperlactatemia.

Sex-specific differences have been increasingly recognized in many human diseases including brain cancer, namely glioblastoma. Primary CNS lymphoma (PCNSL) is an exceedingly rare type of brain cancer that tends to have a higher incidence and worse outcomes in male patients. Yet, relatively little is known about the reasons that contribute to these observed sex-specific differences. Using a population-representative cohort of patients with PCNSL with dense magnetic resonance (MR) imaging and digital pathology annotation (n = 74), we performed sex-specific cluster and survival analyses to explore possible associations. We found three prognostically relevant clusters for females and two for males, characterized by differences in (i) patient demographics, (ii) tumor-associated immune response, and (iii) MR imaging phenotypes. Upon a multivariable analysis, an enhanced FoxP3+ lymphocyte-driven immune response was associated with a shorter overall survival particularly in female patients (HR 1.65, p = 0.035), while an increased extent of contrast enhancement emerged as an adverse predictor of outcomes in male patients (HR 1.05, p &lt, 0.01). In conclusion, we found divergent prognostic constellations between female and male patients with PCNSL that suggest differential roles of tumor-associated immune response and MR imaging phenotypes. Our results further underline the importance of continued sex-specific analyses in the field of brain cancer.

Background Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counselling.Methods In this retrospective, multicentre, longitudinal, cohort study, patients who had epilepsy surgery between Jan 1, 2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18 European countries of the European Epilepsy Brain Bank consortium were assessed. We included patients of all ages with histopathology available after epilepsy surgery. Histopathological diagnoses and a minimal dataset of clinical variables were collected from existing local databases and patient records. The primary outcomes were freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2, and 5 years after surgery. Proportions of individuals who were Engel class 1 and drug-free were reported for the 11 main categories of histopathological diagnosis. We analysed the association between histopathology, duration of epilepsy, and age at surgery, and the primary outcomes using random effects multivariable logistic regression to control for confounding.Findings 9147 patients were included, of whom seizure outcomes were available for 8191 (89.5%) participants at 2 years, and for 5577 (61.0%) at 5 years. The diagnoses of low-grade epilepsy associated neuroepithelial tumour (LEAT), vascular malformation, and hippocampal sclerosis had the best seizure outcome at 2 years after surgery, with 77.5% (1027 of 1325) of patients free from disabling seizures for LEAT, 74.0% (328 of 443) for vascular malformation, and 71.5% (2108 of 2948) for hippocampal sderosis. The worst seizure outcomes at 2 years were seen for patients with focal cortical dysplasia type I or mild malformation of cortical development (50.0%, 213 of 426 free from disabling seizures), those with malformation of cortical development-other (52.3%, 212 of 405 free from disabling seizures), and for those with no histopathological lesion (53.5%, 396 of 740 free from disabling seizures). The proportion of patients being both Engel class 1 and drug-free was 0-14% at 1 year and increased to 14-51% at 5 years. Children were more often drug-free; temporal lobe surgeries had the best seizure outcomes; and a longer duration of epilepsy was associated with reduced chance of favourable seizure outcomes and drug freedom. This effect of duration was evident for all lesions, except for hippocampal sclerosis.Interpretation Histopathological diagnosis, age at surgery, and duration of epilepsy are important prognostic factors for outcomes of epilepsy surgery. In every patient with refractory focal epilepsy presumed to be lesional, evaluation for surgery should be considered. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

BACKGROUND: Case reports have portrayed spinal cord atypical teratoid/rhabdoid tumor (spATRT) as an aggressive form of ATRT. We conducted a retrospective European survey to collect data on clinical characteristics, molecular biology, treatment, and outcome of children with intramedullary spATRT. METHODS: Scrutinizing a French national series and the European Rhabdoid Registry database, we identified 13 patients (median age 32 months; metastatic disease at diagnosis, n = 6). Systemic postoperative chemotherapy was administered to all patients; three received intrathecal therapy and six were irradiated (craniospinal, n = 3; local, n = 3). RESULTS: Median observation time was 8 (range, 1-93) months. Progression-free and overall survival rates at 1 and (2 years) were 35.2% ± 13.9% (26.4% ± 12.9%) and 38.5% ± 13.5% (23.1% ± 11.7%). Four patients (ATRT-SHH, n = 2; ATRT-MYC, n = 1; DNA methylation subgroup not available, n = 1) achieved complete remission (CR); two of them are alive in CR 69 and 72 months from diagnosis. One patient relapsed after CR and is alive with progressive disease (PD) and one died of the disease. Three patients (ATRT-MYC, n = 2; subgroup not available, n = 1) died after 7 to 22 months due to PD after having achieved a partial remission (n = 1) or stabilization (n = 2). Five patients (ATRT-MYC, n = 2; subgroup not available, n = 3) developed early PD and died. One patient (ATRT-MYC) died of intracerebral hemorrhage prior to response evaluation. CONCLUSIONS: Long-term survival is achievable in selected patients with spATRT using aggressive multimodality treatment. Larger case series and detailed molecular analyses are needed to understand differences between spATRT and their inracranial counterparts and the group of extradural malignant rhabdoid tumors.

Background: Primary CNS lymphoma is a highly aggressive and rare type of extranodal non-Hodgkin lymphoma. Although, new therapeutic approaches have led to improved survival, the management of the disease poses a challenge, practice patterns vary across institutions and countries, and remain ill-defined for vulnerable patient subgroups. Material and Methods: Using information from the Austrian Brain Tumor Registry we followed a population-based cohort of 189 patients newly diagnosed from 2005 to 2010 through various lines of treatment until death or last follow-up (12-31-2016). Prognostic factors and treatment-related data were integrated in a comprehensive survival analysis including conditional survival estimates. Results: We find variable patterns of first-line treatment with increasing use of rituximab and high-dose methotrexate (HDMTX)-based poly-chemotherapy after 2007, paralleled by an increase in median overall survival restricted to patients aged below 70 years. In the entire cohort, 5-year overall survival was 24.4% while 5-year conditional survival increased with every year postdiagnosis. Conclusion: In conclusion, we show that the use of poly-chemotherapy and immunotherapy has disseminated to community practice to a fair extent and survival has increased over time at least in younger patients. Annually increasing conditional survival rates provide clinicians with an adequate and encouraging prognostic measure.

Progressive supranuclear palsy (PSP) and cortico-basal degeneration (CBD) are thought to represent a disease spectrum. The clinical presentation depends on the localization and distribution of the pathological lesions, i.e., PSP affects the hindbrain structures, whereas CBD affects the forebrain.

Choroid plexus tumors are intraventricular; papillary neoplasms are derived from choroid plexus epithelium: choroid plexus papilloma (WHO grade I), atypical choroid plexus papilloma (WHO grade II), and choroid plexus carcinoma (WHO grade III).

Therapy-associated neuropathologic changes include radiation necrosis and fibrosis, therapy-induced leukoencephalopathies, vasculopathies, and secondary neoplasms.

Tumors affecting the sellar region include pituitary adenoma, pituitary carcinoma as well as craniopharyngioma, other tumors (e.g., gangliocytoma, spindle cell oncocytoma of the adenohypophysis, pituicytomas), and cystic lesions.

Demyelination is characterized by destruction of normal myelin with an elative preservation of axons. Demyelinating diseases encompass among others multiple sclerosis (MS), neuromyelitis optica (Devic disease), acute disseminated encephalomyelitis (ADEM), and acute hemorrhagic leukoencephalopathy (AHL).

Multiple system atrophy (MSA) is a rare disorder including, based on clinical presentation, a predominantly parkinsonism subtype (MSA-P) (80% of cases) and a predominantly cerebellar subtype (MSA-C).

Alzheimer’s disease (AD) is the most frequent neurodegenerative disease. It is clinically characterized by progressive dementia with increasing loss of memory, intellectual dysfunction, disturbances in speech, apraxia, agnosia, agitation, and restlessness. Early-onset AD (before age 65) versus late-onset AD might be distinguished.

Meningiomas are usually benign tumors arising from meningeal or arachnoithelial cells. They occur frequently and make up 40–45% of tumors seen in the daily clinical practice. According to biologic behavior, meningioma (with various histologic subtypes) (WHO grade I), atypical meningioma (WHO grade II), and anaplastic meningioma (WHO grade III) are distinguished.

Brain edema or brain swelling is defined as an increase in brain volume due to a localized or diffuse abnormal accumulation of water and sodium within the brain parenchyma. Vasogenic edema, cytotoxic edema, hydrocephalic or interstitial edema, and osmotic edema are distinguished based on pathogenetic mechanisms. Edema manifests as a general or focal brain swelling with consecutive effacement of sulci and compression of ventricles and/or basal cisterns.

Oligodendroglioma (WHO grade II) is a diffusely infiltrating, slow-growing glioma with IDH1 or IDH2 mutation and co-deletion of chromosomal arms 1p and 19q. It affects adults (mean age: 40–45 years) and involves the cortex and white matter of the cerebral hemispheres (frontal lobe in 50–65% of all cases).

Vascular dementia (VaD) is defined as a neurocognitive disorder, which is explained by numerous vascular causes in the general absence of other pathologies. It includes multi-infarct dementia, small vessel disease (SVD), strategic infarct dementia, hypoperfusion dementia, hemorrhagic dementia, and mixed dementia.

A stroke is clinically characterized by an abrupt onset of focal neurological signs lasting more than 24 h while in transient ischemic attack (TIA) the focal signs last less than 24 h. Two types of stroke are distinguished: ischemic stroke (due to an occlusion of a blood vessel with focal tissue ischemia and infarction), and hemorrhagic stroke (due to a rupture of a blood vessel with extravasation of blood and subsequent tissue damage). Clinical signs depend on the anatomical region involved.

The therapeutic response can be defined as complete remission/response (CR), partial remission/response (PR), stable disease, or progressive disease.

Neuropathology is the medical discipline concerned with the study of diseases affecting the central and peripheral nervous system as well as muscle. Its aim is to describe the structural, biochemical, molecular, and functional changes in the various cells which make up the nervous system. Using morphologic, immunologic, and molecular biological techniques, neuropathology tries to explain the signs and symptoms of patients. Delivering a clear-cut diagnosis provides the rational basis for patient care and therapy. Specimens for analysis are obtained through autopsy (brain, spinal cord, meninges), open brain surgery, biopsy (stereotactic or navigated biopsy, muscle and nerve biopsy), and lumbar puncture. The procedures for removal, fixation, and cutting of the brain and spinal cord, fixation and processing of tissue are crucial in the analysis pipeline. Staining techniques for tissue received in the neuropathology laboratory include classical stains (Hematoxylin and Eosin (H&E)), special stains (Periodic acid-Schiff (PAS)), diastase-sensitive PAS or PAS with diastase digestion, Alcian blue), and special stains for connective tissue. Special neuro-stains include cresyl violet (Nissl stain), Luxol fast blue (LFB), phosphotungstic acid hematoxylin (PTAH), modified Bielschowsky, and Gallyas stain. The principles of immunohistochemistry are described and supplemented by short characterization of markers for neurons, synapses, astroglia, oligodendroglia, myelin, microglia, neurodegeneration, tumors, vessels, hematopoietic and lymphatic cells, proliferation markers in tumors, and markers for infectious agents. Immunohistochemical panels for the diagnostic setting are provided. Other techniques used in neuropathology comprise electron microscopy, fluorescence microscopy, enzyme histochemistry, and in situ hybridization (ISH). Molecular biology techniques as used in neuropathology include blot techniques (Western blot to visualize proteins, Northern blot to visualize RNA, Southern blot to visualize DNA, Dot blot), molecular imaging with imaging a mutation after sequencing and imaging a deletion, duplication with RT-PCR as well as microarray techniques. Other imaging techniques, developed during the last decades, include Confocal Laser Scanning Microscopy, Multiphoton Confocal Fluorescence Microscopy, Atomic Force Microscopy (AFM), and many others.

Pituitary adenoma is a neoplastic proliferation of anterior pituitary hormone-producing cells. The tumors are typically benign, but can be aggressive and invasive into adjacent structures. Based on its hormonal activity, pituitary adenoma is characterized as somatotroph, lactotroph, thyrotroph, corticotroph, gonadotroph adenoma, null cell, plurihormonal, and double adenoma. In addition, atypical pituitary adenoma, pituitary carcinoma, pituitary blastoma, and pituitary hyperplasia are considered.

Desmoplastic astrocytoma/ganglioglioma (DIA/DIG) is a benign glioneuronal tumor composed of a prominent desmoplastic stroma with a neuroepithelial population restricted either to neoplastic astrocytes—desmoplastic infantile astrocytoma (DIA)—or to astrocytes together with a variable mature neuronal component—desmoplastic infantile ganglioglioma (DIG)—sometimes with aggregates of poorly differentiated cells. This rare tumor affects young patients (infants: 1–24 months; non-infantile cases: 5–25 years).

Pilocytic astrocytoma (PA) is an astrocytoma classically characterized by a biphasic pattern with variable proportions of compacted bipolar cells with Rosenthal fibers and loose-textured multipolar cells with microcysts and occasional granular bodies. Children are affected during the first two decades of life.

The classification of embryonal tumors still remains in flow and will change based on the acquisition of new molecular insight. Currently, major tumor categories include medulloblastoma, embryonal tumor with multilayered rosettes (ETMR), C19MC-altered, embryonal tumor with multilayered rosettes, NOS (not otherwise specified), other CNS embryonal tumors (medulloepithelioma, CNS neuroblastoma, CNS ganglioneuroblastoma, CNS embryonal tumor (NOS)), atypical teratoid/rhabdoid tumor (AT/RT), and CNS embryonal tumor with rhabdoid features.

Acute demyelinating encephalomyelitis (ADEM) is clinically characterized by fever, headache, impaired conscious level, meningism, seizures, and progressive neurological signs.

Tumors affecting the peripheral nervous system include schwannoma, neurofibroma, perineurioma, malignant peripheral nerve sheath tumor (MPNST), neurofibromatosis type I, neurofibromatosis type II, and schwannomatosis.

Lewy body disease (LBD) is a chronic progressive neuropsychiatric disorder characterized by parkinsonism with or without dementia. Dementia might be the predominant symptom while parkinsonian symptoms occur later during the course of the disease. Several types of LBD are distinguished, i.e., brain stem type (= Parkinson’s disease), traditional type, diffuse type = diffuse Lewy body disease (frequent form and rare form), and cerebral type. Staging of the lesions and regions involves results in four stages.

Pineocytoma (WHO grade I), pineal parenchymal tumor of intermediate differentiation (WHO grades II and III), pineoblastoma (WHO grade IV), and papillary tumor of the pineal region are tumors affecting the pineal region. These tumors are rare and can affect persons of all ages.

Germ cell tumors affecting the nervous system include germinoma, yolk sac tumor, embryonal carcinoma, choriocarcinoma, teratoma, and mixed germ cell tumors.

Various types of hemorrhages are distinguished including subcutaneous, subgaleal, epidural, subdural, subarachnoid, intracerebral, intramedullary, choroid plexus, and germinal matrix hemorrhage. Clinical characterization of hematomas is based on time elapsed after the causing event: hyperacute, acute (6 h to 3 days), early subacute, late subacute, and chronic.

An aneurysm is a localized pathological dilatation of a blood vessel (or of the cardiac wall) involving all layers. Various types of aneurysm exist (saccular (berry), fusiform, inflammatory/infective “mycotic” (septic), dissecting, dolichoectasia, and false aneurysms).

Vasculitis is an inflammation of blood vessel walls due to infectious or non-infectious reasons. The size of the vessel serves for disease classification (e.g., large vessel vasculitis, medium vessel vasculitis, small vessel vasculitis). The morphological changes of the involved vessels might be variable. The pathogenesis of non-infectious vasculitis might be autoimmune, associated with an immunologic reaction directed at elastin, associated with human leukocyte antigen (HLA)-B∗51 (Behcet’s disease), associated with immune and inflammatory response, antineutrophil cytoplasmic antibody-associated vasculitides. Germ line mutations lead to adenosine deaminase 2 deficiency.

Other angiopathies include sporadic and familial angiopathies. Sporadic angiopathies include among others cerebral amyloid (congophilic) angiopathy, fibromuscular dysplasia, Moyamoya angiopathy, Binswanger disease, and Fahr disease. Familial angiopathies are CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), CARASIL (cerebral recessive dominant arteriopathy with subcortical infarcts and leukoencephalopathy), CARASAL (cathepsin A-related arteriopathy with strokes and leukoencephalopathy), hereditary vascular retinopathy, HERNS (hereditary endotheliopathy with retinopathy, nephropathy, and stroke), and COL4A1 mutations (combined small vessel and large arterial disease).

Neuromyelitis optica (NMO) or Devic disease is characterized by optic neuritis (ON) and transverse myelitis. In optic neuritis (ON), visual function is more severely affected than in MS or single isolated idiopathic ON. Attacks may recur. ON may not respond to corticosteroid treatment. Myelitis is characterized by severe paraparesis or tetraparesis and sensory-level and/or sphincter disturbances. Neuromyelitis optica spectrum disorder (NMOSD) is associated with serum antibodies against aquaporin 4 (AQP4).

The use of street drugs like cannabis, opiates, cocaine, amphetamine, and methamphetamine are serious medical and economic problems in the Western countries.

Hypoxia is due to decreased oxygen delivery to the brain which leads to cell injury. Ischemia is characterized by a decreased blood flow and accumulation of toxic cellular metabolites. Various forms of hypoxia are distinguished: hypoxic hypoxia (blood oxygen tension below 40 mmHg), anemic hypoxia (oxygen-carrying hemoglobin falls to half its normal concentration), histotoxic hypoxia (caused by toxic substances), ischemic/stagnant hypoxia (cardiac arrest encephalopathy, transient global ischemia), and non-perfused brain (respirator brain, permanent global ischemia).

“Mesenchymal, non-meningothelial tumors” affecting the nervous system correspond to soft tissue tumors as encountered in other organs. Soft tissue tumors are a heterogeneous group of tumors classified along the line of differentiation according to the adult tissue they resemble. Benign and malignant tumors or sarcomas are encountered.

Diffuse astrocytoma is a diffusely infiltrating astrocytoma with a mutation in either the IDH1 or IDH2 gene. Gemistocytic astrocytoma is a variant of IDH-mutant diffuse astrocytoma characterized by the presence of a conspicuous (though variable) proportion of gemistocytic neoplastic astrocytes (gemistocytes).

Central neurocytoma is an uncommon intraventricular neoplasm composed of uniform round cells with a neural immunophenotype and low proliferation index while extraventricular neurocytoma is a tumor composed of small uniform cells that demonstrate neuronal differentiation but are not IDH-mutant, and that presents throughout the CNS, without apparent association with the ventricular system.

Arteriosclerosis is a hardening or “sclerosis” of the arteries characterized by thickening of the arterial wall and subsequent loss of elasticity. Cerebral imaging demonstrates secondary signs of arteriosclerosis. Plaque morphology consists of thickening of intima, fatty core, subintimal hemorrhage, and rupture of fibrous cap.

Huntington disease (HD) is an autosomal dominant disorder with full penetrance and rare de novo mutations. Early changes include mild motor decline with clumsiness and slowed gait, progressive changes include dystonia and chorea, parkinsonian symptoms, slow and stiff gait, dysphagia, tremor, and depression and suicidal ideation. In the late stages, rigidity, severe bradykinesia, dysphagia, inability to swallow, seizures, and inability to walk or speak predominate.

Parkinson disease (PD) is clinically characterized by tremor, bradykinesia, rigidity, postural instability, and gait disturbance. Non-motor features of PD include pain and sensory phenomena, anxiety and depression, autonomic dysfunction, cognitive impairment, dementia, and psychosis and hallucinations.

Dysembryoplastic neuroepithelial tumor (DNT) is a benign glioneural neoplasm typically located in the temporal lobe of children or young adults with early-onset epilepsy; predominantly with a cortical location and a multinodular architecture, and with a histological hallmark of a specific glioneuronal element characterized by columns made up of bundles of axons oriented perpendicularly to the cortical surface. It affects young patients. DNT has a predilection for the temporal lobe (50% of cases).