Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue of the dura mimicking meningioma: a case report and literature review.

MALT lymphoma of the dura is a very rare type of low-grade B-cell lymphoma. Little more than 100 cases have been reported in the literature to date. We report a 43-year-old woman who was referred to hospital because of a series of three tonic-clonic seizures on the day of admission. Neurological examination revealed confusion and aphasia. Magnetic resonance imaging (MRI) showed a contrast-enhanced, broad-based lesion along the dura in the left parieto-occipital area. The suspicion of an en plaque meningioma was raised. The tumour invaded the brain parenchyma with visible extension into the brain sulci. There was a marked brain oedema surrounding the lesion and causing the midline shift 8 mm to the right. After stabilization of neurological condition (intravenous diuretics and steroids), the operation was performed. The diagnosis of dural MALT lymphoma was established. During the pathological examination, it was especially problematic to distinguish MALT lymphoma from follicular lymphoma, but the final diagnosis was MALT lymphoma. Surgical partial removal with additional R-CVP immunochemotherapy (rituximab, cyclophosphamide, vincristine and prednisone) resulted in complete remission. The follow-up period is 1 year. Our presented case of a MALT lymphoma highlights the fact that surgical partial removal with additional immunochemotherapy is an available option in these rare intracranial tumours.

TDP-43 pathology in subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a fatal, slowly progressive brain disorder caused by a mutated measles virus. Both subacute inflammatory and neurodegenerative mechanisms appear to play significant roles in the pathogenesis. TAR DNA-binding protein 43 (TDP-43) inclusions are a common co-pathology in several neurodegenerative disorders with diverse pathogenesis. In the present study, we examined brains of 16 autopsied SSPE patients for the presence of TDP-43 pathology and possible associations with tau pathology. Immunohistochemical staining identified TDP-43 inclusions in 31% of SSPE cases. TDP-43 pathology was widely distributed in the brains, most severely in the atrophied cerebral cortex (temporal and parietal), and most frequently as tangle- and thread-like neuronal cytoplasmic inclusions. It was associated with longer disease duration (>4 years) and tau pathology (all TDP-43-positive cases had tau-positive neurofibrillary tangles). This study demonstrates for the first time an association between TDP-43 pathology and SSPE. The co-occurrence of TDP-43 and tau aggregates and correlation with the disease duration suggest that both pathological proteins are involved in the neurodegenerative process induced by viral inflammation.

Incidence and morphology of secondary TDP-43 proteinopathies: Part 2.

Transactivation (TAR) DNA binding protein 43 kDa (TDP-43) inclusions frequently occur as a comorbid pathology in several neurodegenerative disorders, including Alzheimer's disease, Huntington's disease, Lewy body disease, and progressive supranuclear palsy, and may appear in association with nondegenerative neurological etiology, for example neoplastic, paraneoplastic, traumatic, or infectious. Relationships between various pathological proteins and mechanisms associated with TDP-43-induced neurodegeneration are still not fully understood. Thus, overlap of distinct neuropathological mechanisms frequently leads to greater brain atrophy and a more severe clinical course, suggesting the importance of co-pathologies in ante-mortem diagnosing and treatment. The present review aims to discuss the incidence, morphology, and role of TDP-43 pathology in the context of other dominant, hallmark pathologies, referred to as secondary TDP-43 proteinopathies. The previous part (Part 1) focused on common neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, and Lewy body disease, while the present part (Part 2) discusses TDP-43 pathology in rare neurodegenerative diseases and neurological diseases with nondegenerative etiology.

Recommendations of the Polish Association of Neuropathologists on performing post-mortem examination of the brain and spinal cord.

Neuropathological central nervous system (CNS) post-mortem examination is a highly specialistic element of the autopsy procedure with methodological specificity. Herein we propose updated recommendations for CNS autopsy for pathologists and neuropathologists. The protocol includes the compendium of neuroanatomy with current nomenclature, consecutive steps of gross examination, as well as appropriate sampling algorithms in different clinical and pathological settings. The significance of pathoclinical cooperation in differential diagnosis is exposed. We believe it is essential to create and promote the guidelines to improve the quality of CNS post-mortem examination at the national level.

Influence of SARS-CoV-2 on Adult Human Neurogenesis.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with the onset of neurological and psychiatric symptoms during and after the acute phase of illness. Inflammation and hypoxia induced by SARS-CoV-2 affect brain regions essential for fine motor function, learning, memory, and emotional responses. The mechanisms of these central nervous system symptoms remain largely unknown. While looking for the causes of neurological deficits, we conducted a study on how SARS-CoV-2 affects neurogenesis. In this study, we compared a control group with a group of patients diagnosed with COVID-19. Analysis of the expression of neurogenesis markers showed a decrease in the density of neuronal progenitor cells and newborn neurons in the SARS-CoV-2 group. Analysis of COVID-19 patients revealed increased microglial activation compared with the control group. The unfavorable effect of the inflammatory process in the brain associated with COVID-19 disease increases the concentration of cytokines that negatively affect adult human neurogenesis.

"Neuropatologia Polska". The journal and its topics in the first decade of existence (1963-1972).

In this article authors would like to present the history of the "Neuropatologia Polska" journal (since 1994: "Folia Neuropathologica") in its first decade of existence. It outlines the circumstances surrounding the creation of the journal and shows how it evolved in the first years. The vast material analysed from the consecutive issues of the journal in the years from 1963 to 1972 was subjected to statistical and content analysis. From its first year, the journal has included works of a very high substantive level and a wide range of topics. The authors presented the results of contemporary research in many areas. The "Neuropatologia Polska" journal (later "Folia Neuropathologica") set paths for the development of neuropathology in clinical and experimental aspects. What is very important, it created a platform for international cooperation in many fields, included researchers and scientists from Western countries and foreign academic centres in difficult times. This article was created on the 60th anniversary of creation of "Neuropatologia Polska".

Large haemorrhage within glioblastoma mimicking haemorrhagic stroke and coexistance of meningioma: a case of collision tumours.

Intracranial collision tumours are rare pathologies in which two distinct neoplasms are found in the same location. We present an unusual case of an intracranial collision tumour composed of meningothelial meningioma (CNS WHO G1) and glioblastoma (IDH-wildtype, CNS WHO G4). This collision tumour was found in a 64-year-old man. This patient was hospitalized urgently due to left-sided hemiparesis. The computed tomography (CT) revealed large multilobar intracranial haemorrhage located in the right hemisphere. The history of hypertension and obesity pointed to the misdiagnosis of a typical haemorrhagic stroke. Despite extensive physiotherapy after initial improvement, the magnetic resonance imaging (MRI) showed signs of a marginal contrast enhancement with a suspicion of a brain tumour. Moreover, the meningioma in the same location was suspected. The neuropathological findings confirmed two neoplasms with fragments of the dura mater infiltrated by malignant glioma cells and small nests of meningothelial cells with psammoma bodies. The presented case is extremely rare showing that more malignant tumour may infiltrate a meningioma. Moreover, this case highlights the clinical observation that glioblastoma may mimic a haemorrhagic stroke. In such cases when pharmacological treatment is not effective, suspicions should be raised about a possible underlying brain tumour.

Incidence and morphology of secondary TDP-43 proteinopathies: Part 1.

Transactive response DNA binding protein of 43 kDa (TDP-43) is considered to play an essential role in the pathogenesis of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Growing body of evidence indicate that pathological TDP-43 inclusions frequently occur in the context of other distinctive hallmark pathologies, referred to as secondary TDP-43 proteinopathies. Comorbid TDP-43 pathology is well-documented in several neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, multiple system atrophy, or progressive supranuclear palsy. It may also appear as a consequence of less obvious disease etiologies, i.e. post-traumatic (chronic traumatic encephalopathy), neoplastic (pilocytic astrocytoma), or post-infectious (post-encephalitic parkinsonism). The aim of the present review was to evaluate the incidence, morphology, and role of TDP-43 pathology in the secondary TDP-43 proteinopathies. This article (Part 1) discussed TDP-43 pathology in more common neurodegenerative diseases, including Alzheimer's disease, Lewy body disease, Huntington's disease, multiple system atrophy, corticobasal degeneration, and progressive supranuclear palsy. A follow-up article (Part 2) will describe abnormal TDP-43 changes in rare neurodegenerative diseases or neurological diseases with nondegenerative etiology.

Atypical clinical presentation of glioblastoma mimicking autoimmune meningitis in an adult.

Glioblastoma (GBM) is the most malignant type of glial tumor associated with a very unfavorable prognosis. Typical radiological features of GBM include the presence of a tumor with irregular contrast-enhancing margins and central necrosis surrounded by a wide area of vasogenic edema. Here, we presented an atypical clinical presentation of GBM mimicking autoimmune meningitis. A 69-years-old previously healthy male was admitted to the emergency room due to signs of increasing cognitive impairment, weight loss, changes in behavior, difficulty in walking, and prolonged episodes of nausea over the past month. An magnetic resonance imaging (MRI) brain scan revealed hyperintense changes of the periventricular area surrounding brain ventricles in T2 and FLAIR, and post-contrast leptomeningeal enhancement and thickening of meninges involving cerebellar sulci. An additional MRI scan of the cervical spine showed an in-core contrastenhancing lesion on the C7-Th1 level as well as leptomeningeal thickening and post-contrast-enhancement around the spinal cord. Various laboratory tests and two stereotactic biopsies were performed with no essential to diagnosis clinical findings. A couple of months after first hospital admission, the patient died. Post-mortem examination of the brain revealed numerous foci of abnormal tissue inside the subarachnoid space, lateral ventricles, and cerebral aqueduct. Histological examination showed diffuse malignant astroglial neoplasm, and diagnosis of glioblastoma NOS WHO G IV was established. Even though the appearance of usual GBM is widely recognizable, one must bear in mind the possibility of unusual presentation. The presented case highlights the diagnostic difficulties of diffuse glioblastoma with atypical clinical presentation.

Central nervous system autopsy - a neuropathological procedure based on multidisciplinary pathoclinical cooperation.

INTRODUCTION: Neuropathological brain and spinal cord post mortem examination is a distinct procedure that still plays an important role in modern medicine. In front of increasing amounts of clinical and genetic data, together with important developments in the field of neuroimaging, the Polish Association of Neuropathologists have updated their recommendations regarding central nervous system (CNS) examination. These guidelines are aimed at neuropathologists, pathologists and clinicians. AIM OF THE STUDY: Presentation of the outlined recommendations as their goal is to improve the quality, informativity, and cost effectiveness of CNS post mortem examinations. A comprehensive study of the literature was conducted to provide a clinical background of neuropathological autopsy. There are numerous open questions in neuroscience, and new strategies are required to foster research in CNS diseases. These include the challenge of organizing brain banks tasked with managing and protecting detailed multidisciplinary information about their resources. Complex neuropathological analyses of post mortem series are also important to assess the effectiveness of diagnostics and therapy, identify environmental impact on the development of neurological disorders, and improve public health policy. The recommendations outline the need for collaboration between multiple specialists to establish the proper diagnosis and to broaden knowledge of neurological disorders.

Atypical clinical presentation mimicking stroke in an adult patient caused by a rare diffuse leptomeningeal glioneuronal tumour.

A diffuse leptomeningeal glioneuronal tumours (DLGNT) are very rare tumours of the central nervous system, typically characterized by enhancement of subarachnoid space with cystic lesions, diffuse leptomeningeal infiltration, and no primary mass. We report an atypical clinical presentation of DLGNT. A 48-year-old male was admitted to hospital with symptoms of ischaemic stroke. Magnetic resonance imaging of the head revealed contrast enhancement of the meninges and other parts of the brain. A stereotactic frame biopsy was performed on the patient, which revealed the DLGNT. Diffuse leptomeningeal glioneuronal tumours are mostly seen in individuals less than 18 years old and are characterized by slow growth and low-grade histological appearance. Diffuse leptomeningeal glioneuronal tumours can be aggressive in adults.

Neuropathological Changes in the Brains of Suicide Killers.

BACKGROUND: Homicide combined with subsequent suicide of the perpetrator is a particular form of interpersonal violence and, at the same time, a manifestation of extreme aggression directed against oneself. Despite the relatively well-described individual acts of homicide and suicide, both in terms of psychopathology and law, acts of homicide and subsequent suicide committed by the same person are not well-studied phenomena. The importance of emotional factors, including the influence of mental state deviations (psychopathology), on this phenomenon, is discussed in the literature, but still there is relatively little data with which to attempt neuropathological assessments of the brains of suicide killers. This paper is dedicated to the issue based on the neuropathological studies performed. METHODS: We analyzed a group of murder-suicides using histochemical and immunohistochemical methods. RESULTS: The results of our research indicate the presence of neurodegenerative changes including multiple deposits of ß-amyloid in the form of senile/amyloid plaques and perivascular diffuse plaques. CONCLUSIONS: Neurodegenerative changes found in the analyzed brains of suicide killers may provide an interesting starting point for a number of analyses. The presence of neurodegenerative changes at such a young age in some murderers may suggest preclinical lesions that affect cognitive functions and are associated with depressed moods.

Neuropathological analysis of the brains of fifty-two patients with COVID-19.

Coronavirus disease 2019 (COVID-19) poses a global challenge to healthcare and society in the early 21st century. We report neuropathological changes in 52 patients aged between 22 years and 88 years (median 58 years) who were infected with the CoV-2 coronavirus. Patients died under various circumstances and had various pre-existing diseases. The inclusion criteria for this study were: positive result for the nasopharyngeal swab for SARS-CoV-2 RNA, diagnosis of pneumonia of SARS-CoV-2 or nucleoproteins of SARS-CoV-2 in pulmonary tissue confirmed by immunohistochemical methods (IHC). Samples from all brain structures and lung specimens were taken for histopathological examinations. Brain and pulmonary samples were stained typically with histological and immunohistochemical methods and small tissue fragments were examined with the transmission electron microscope (TEM). The light and electron microscopy examination confirmed the numerous neuropathological changes in the brains of the patients infected with the CoV-2. Many of these changes were caused by pre-existing diseases of patients and/or by necessary treatment. However, vascular lesions and the inflammatory process seem to be characteristic of the CoV-2 infection. In all of the structures of 52 brains of patients, damage of the vessel walls and morphological feature of the damage to the blood-brain barrier were observed. Lymphocytic and microglial infiltrates, both perivascular and diffuse, were also observed. Hence, the brain changes due to COVID-19 infection, could be called COVID-19 cerebral angiopathy with diffuse inflammation.

Clinical presentation of neuroendocrine cancer metastasis to an anterior clinoid process meningioma invading superior orbital fissure. A case report.

Metastasis to a meningioma is an uncommon phenomenon however reported in the literature. Meningiomas are common primary intracranial tumours which most frequently occur to be a recepient of metastases. A 66-year-old female presented with rapid development of visual acuity and visual field loss in the right eye with ipsilateral oculomotor nerve palsy. Magnetic resonance imaging (MRI) showed well-defined tumour intensely enhanced with contrast like a typical skull base meningioma. The neuropathological examination revealed two different morphological fragments of the tumour. In the cell-rich part of the tumour, immunopositivity for CK, chromogranin, and SY were detected. The less cellular portion of the tumour, immunopositivity to epithelial membrane antigen (EMA) and vimentin were detected. To our knowledge, we present the first rare metastasis of neuroendocrine carcinoma to the medial sphenoid meningioma that preceded the clinical symptoms of systemic neuroendocrine carcinoma.

Ultrastructure of mitochondria and damage to small blood vessels in siblings with the same mutation in the NOTCH 3 and coexisting diseases.

We performed ultrastructural studies of mitochondria and evaluated the appearance of small blood vessels of three middle-aged siblings affected by the same mutation in the NOTCH3 gene, causing CADASIL. CADASIL pathognomonic features include granular osmiophilic material (GOM), which we observed. GOMs were located in damaged and thickened basement membranes (BM) of capillaries and arterioles. Our patients were also burdened by type II diabetes (first patient), impaired glucose metabolism (second patient), and hypertension (third patient). The ultrastructure of the capillaries in the first and second patients differed from the third patient. In diabetes/impaired glucose metabolism patients (first and second patients), we observed: pathologies of mitochondria in damaged endothelium and pericytes of capillaries; extremely thickened (BM) with visible remains of vascular cells; well-preserved GOMs anchored in the rebuilt capillary extracellular matrix. We identified degenerated or vestigial small blood vessels of skeletal muscles in the first patient. The capillary damage in the third patient (with hypertension) was milder compared to the diabetes/impaired glucose metabolism patients. We conclude that in patients with a mutation in the NOTCH3 gene, the co-occurrence of diseases such as type II diabetes/impaired glucose metabolism can cause a multiplication the damages to small blood vessels by modifying/masking the pathogenesis of CADASIL.

Elevated serum and urine levels of progranulin (PGRN) as a predictor of microglia activation in the early phase of traumatic brain injury: a further link with the development of neurodegenerative diseases.

Traumatic brain injury (TBI) is a frequent finding during forensic autopsies and neuropathological examinations in medico-legal practices. Despite the unprecedented attention currently focused on TBI pathogenesis, there is a need to improve its diagnostics through the use of novel biomarkers to facilitate detection, treatment, and prognosis. Recently, growth factor progranulin (PGRN) has attracted significant attention because of its neurotrophic and anti-inflammatory activities. The role of PGRN in TBI has not been widely discussed, although PGRN-related neuroinflammatory and neurodegenerative phenomena have been described. The aim of this study was to identify PGRN concentration levels in biofluids and examine PGRN and CD68 protein expression in brain tissue using immunohistochemical staining in individuals with fatal TBI in its early phase. The study was performed using cases (n = 30) of fatal head injury and control cases (n = 30) of sudden death. The serum and urine were collected within ~24 h after death and compared using the ELISA test, where brain specimens were stained with anti-PGRN and anti-CD68 antibodies. In our study, we observed elevated concentration levels of PGRN in the serum and urine of TBI individuals in the early phase of TBI. These changes were accompanied by increased expression of PGRN in the frontal cortex (1st-3rd layers), in which anti-CD68 immunostaining revealed disseminated cortical microglia activation. The possible implementation of performing such assays offers a novel and interesting tool for investigation and research regarding TBI diagnosis and pathogenesis. Furthermore, the above-mentioned surrogate biofluid assays may be useful in clinical prognosis and risk calculation of non-fatal cases of TBI, considering the development of neurodegenerative conditions of TBI individuals.

Encephalomyelitis associated with rheumatoid arthritis: a case report.

Encephalitis/encephalomyelitis in the course of rheumatoid arthritis (RA) remains a matter of debate. We present a case of a patient with encephalomyelitis associated with RA confirmed with post-mortem neuropathological examination. A 68-year-old woman with a long-standing, seropositive history of RA presented progressive disturbances of consciousness. Magnetic resonance imaging (MRI) of the brain and cervical spine revealed an increase of signal intensity on T2-weighted and fluid attenuated inversion recovery (FLAIR) images with corresponding restricted diffusion involving cerebral peduncles, pons, medulla oblongata, and cervical spinal cord and mild contrast-enhancement of the right cerebral peduncle. Extensive radiological and laboratory testing, including autoantibodies to paraneoplastic anti-neuronal and neuronal cell surface antigens, were all negative except for elevated rheumatoid factor. Cerebrospinal fluid (CSF) analysis revealed moderate pleocytosis with mononuclear cell predominance, mildly increased protein level, and negative viral PCRs, bacterial cultures, flow cytometry, and neuronal surface antibodies. Despite intensive treatment with corticosteroids, antibiotics, antiviral drugs, and intravenous immunoglobulin the patient died after 3 months of hospitalization. Post-mortem neuropathological examination revealed numerous, disseminated, heterochronous ischaemic lesions, rarely with haemorrhagic transformation, predominantly in the brainstem, and widespread, diffuse microglia and T-cell infiltrations with neuronal loss and astrogliosis, most severe in the frontal and temporal lobes. Mild, perivascular lymphocyte T infiltrations involved particularly small and medium-sized vessels and were associated with brainstem ischaemic lesions. The neuropathological picture confirmed diagnosis of encephalomyelitis, which together with the clinical course suggested association with RA. Concluding, encepha-lomyelitis due to RA remains a challenging, controversial entity that needs further research and the establishment of effective diagnostic and treatment guidelines.

Pretreatment with a glutamine synthetase inhibitor MSO delays the onset of initial seizures induced by pilocarpine in juvenile rats.

The contribution of glutamatergic transmission to generation of initial convulsive seizures (CS) is debated. We tested whether pretreatment with a glutamine synthetase (GS) inhibitor, methionine sulfoximine (MSO), affects the onset and progression of initial CS by cholinergic stimulus in juvenile rats. Male rats (24 days old, Sprague Dawley) sequentially received i.p. injections of lithium-carbonate, MSO, methyl-scopolamine, and pilocarpine (Pilo). Pilo was given 150 min after MSO. Animals were continuously monitored using the Racine scale, EEG/EMG and intrahippocampal glutamate (Glu) biosensors. GS activity as measured in hippocampal homogenates, was not altered by MSO at 150 min, showed initial, varied inhibition at 165 (15 min post-Pilo), and dropped down to 11% of control at 60 min post-Pilo, whereas GS protein expression remained unaltered throughout. Pilo did neither modulate the effect of MSO on GS activity nor affect GS activity itself, at any time point. MSO reduced from 32% to 4% the number of animals showing CS during the first 12 min post-Pilo, delayed by ~6 min the appearance of electrographic seizures, and tended to decrease EMG power during ~15 min post-Pilo. The results indicate that MSO impairs an aspect of glutamatergic transmission involved in the transition from the first cholinergic stimulus to the onset of seizures. A continuous rise of extracellular Glu lasting 60 min was insignificantly affected by MSO, leaving the nature of the Glu pool(s) involved in altered glutamatergic transmission undefined.

Morphological and ultrastructural changes in Herpes simplex encephalomyelitis: an attempt to determinate the etiological factor.

Herpes simplex encephalomyelitis (HSE) is a rare disease with a high mortality rate. Correct diagnosis is established on the basis of the combination of the clinical and investigative features. Unfortunately, precise diagnosis remains difficult due to several clinical similarities and false negative or inconclusive results of diagnostic tests. Here, we present two cases of HSE together with the morphological and ultrastructural picture. The first case was a 45-year-old man with acute symptoms of encephalitis, and the other one was a 28-year-old woman presenting subacute encephalomyelitis. Both cases had negative serologic and molecular results for Herpes simplex in the blood and cerebrospinal fluid. Brain and spinal cord samples taken from both cases were stained typically with histological and immunohistochemical methods and small tissue fragments were examined with the transmission electron microscope (TEM). Microscopic examination confirmed viral encephalomyelitis in both cases. An electron micrograph showed typical intranuclear viral particles inside of damaged neurons, which together with topography of brain and spinal cord changes suggest HHV-1/HHV-2 in the first case and/or HHV-3 in the other case. Thus, morphological and ultrastructural examinations may be a useful tool to set up correct diagnosis and help to determine the pathogenic factor in patients suspected of viral encephalomyelitis.

POLG gene mutation. Clinico-neuropathological study.

We present a female patient with a mutation of the POLG gene (POLG DNA polymerase gamma, catalytic subunit; *174763) in which the clinical course suggested a mitochondrial disease, a neuropathological examination identified the syndrome more closely, and a genetic test confirmed the disease. Apart from the morphological lesions typical of Alpers-Huttenlocher syndrome, rarely observed symmetrical degenerative changes in the accessory olivary nuclei were found. It was unusual in the clinical course of the disease that pancreatitis was diagnosed before symptoms of liver failure appeared.