Search

SARS-CoV-2 virus was first identified in 2019 in Wuhan (China) and is responsible for the ongoing COVID-19 pandemic. Although the virus causes mild, transient symptoms of an upper respiratory tract infection in most cases, it can also lead to severe pneumonia, respiratory failure and/or death. Approximately 85% of patients experience central and peripheral neurological symptoms. In the acute phase of the disease, ischaemic strokes, intracranial haemorrhages, meningitis and encephalitis, acute demyelinating diseases and acute inflammatory polyneuropathies may occur. However, mild neurological symptoms that can persist for months and significantly affect daily functioning are much more common. These include headache and dizziness, olfactory and gustatory dysfunction, mild cognitive disturbances, as well as depressive, anxiety, and sleep disorders. Some of them are encompassed by popular terms “post-covid syndrome” and “brain fog.” The pathogenesis of neurological complications of SARS-CoV-2 infection is still not fully understood; overproduction of cytokines induced by viral infection may be of great importance. There is no causal treatment, while symptomatic treatment is of limited effectiveness. Primary prevention in the form of SARS-CoV-2 vaccinations is of great importance. In the following review, we would like to present the current knowledge on epidemiology, pathology, pathogenesis and treatment of neurological complications after SARS-CoV-2 infection. Further multi-centre, large-scale clinical studies are necessary to identify the exact pathogenetic mechanisms.

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.

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.

Introduction Migraine is considered not only as a separate clinical entity but also as a symptom of various brain disorders, including cerebral small vessel diseases. Since cerebral small vessel diseases are usually general angiopathies, evaluation of biopsy material other than brain tissue may help in their diagnosis in vivo. In patients with migraine, brain magnetic resonance imaging (MRI) often shows hyperintense changes in the cerebral white matter. Such changes may indicate the symptomatic nature of migraine and coexisting structural or biochemical vascular abnormalities. Material and methods To verify the hypothesis of the symptomatic nature of migraine in patients with abnormal brain neuroimaging, we performed an ultrastructural examination of skin and skeletal muscle vessels in biopsy material from 40 patients with clinically diagnosed migraine and hyperintense white matter lesions on MRI. Results In 80% of the examined patients, ultrastructural examination showed various pathological changes in the microvessels including abnormalities characteristic of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and elastin disorders, as well as less specific changes such as thickening of the basal lamina, narrowing of the vessel lumen, degeneration of the vessel wall cells, endothelial activation, oncosis-like changes, and the presence of various types of deposits in the vessel wall. In 20% of the examined cases, ultrastructural examination of the vessels was normal. Conclusions Patients with migraine and hyperintense cerebral white matter changes on MRI have an increased risk of concomitant microangiopathy. In this group of patients, skin-muscle biopsy allows the identification of cases with coexisting vessel abnormalities.

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.

Background Since the new World Health Organization (WHO) classification of nervous system tumors (2016, revised, 4th edition) has been released, gliomas are classified depending on molecular and genetic markers in connection with histopathology, instead of histopathology itself as it was in the previous classification. Over the last years, epigenetic analysis has taken on increased importance in the diagnosis and treatment of different cancers. Multiple studies confirmed that deoxyribonucleic acid (DNA) methylation and hydroxymethylation play an important role in the regulation of gene expression during carcinogenesis. Methods In this review, we aim to present the current state of knowledge on DNA hydroxymethylation in human high-grade gliomas (WHO grades III and IV). Results The correlation between DNA hydroxymethylation and survival in glioblastoma multiforme (GBM) patients was evaluated by different studies. The majority of them showed that the expression of 5-hydroxymethylcytosine (5-hmC) and ten-eleven translocation (TET) enzymes were significantly reduced, sometimes almost undetectable in high-grade gliomas in comparison with the normal brain. A decreased level of 5-hmC was associated with poor survival in patients, but high expression of the TET3 enzyme was related to a better prognosis for GBM patients. This points to the relevance of DNA hydroxymethylation in molecular diagnostics of human gliomas, including survival estimation or differentiating patients in terms of response to the treatment. Conclusion Future studies may shed some more light on this epigenetic mechanism involved in the pathogenesis of human high-grade gliomas and help develop new targeted therapies.

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.

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.

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.

Introduction Adult neurogenesis includes proliferation and differentiation of progenitor cells as well as their migration and maturation. In the adult human brain, two neurogenic regions, the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ) of lateral ventricles, have been identified. In the dentate gyrus, three types of transcriptionally active cells and in the subventricular zone, four types of transcriptionally active cells, including GFAP-positive neural stem cells (NSCs), have been differentiated. Material and methods The aim of the study was to identify and compare density of neurogenic cells between two study groups of patients (7 men, 7 women, mean age 70 ± 6.03) with ischemic stroke and with hemorrhage (6 men, 2 women, mean age 64.75 ± 12.23) and the control group of patients (6 men, 2 women, mean age 64 ± 10.95) free of neuropathologic changes who died suddenly within less than 10 min. Results In both groups, in the hippocampal dentate gyrus and in the subventricular zone of lateral ventricles, the presence of single GFAP-positive neural stem cells and the transcriptionally active cells labelled with phosphorylated histone H3Ser-10 (p-Histone H3Ser-10)/neural progenitor cells (NPCs), was observed. The quantitative analysis of cells with p-Histone H3Ser-10 expression in the hippocampal DG revealed significant differences between the hemorrhage and control groups (p = 0.001, test t). However, in the SVZ, it showed a statistically significant decrease in the density of transcriptionally active cells in the group of patients with ischemic stroke (p = 0.001, test t). A distinct decrease in the density of transcriptionally active cells, proportional to the length of the patients' hospitalization, was observed. Conclusions Hypoxia belongs to pathomechanic factors responsible for ischemic stroke, which can induce neurogenesis. However, hypoxia along with ischemia and other factors implicated in ischemic stroke, such as the patient's age or duration of ischemia can have a decisive influence on the decrease in the density of transcriptionally active cells in this pathologic process.

Writers’ cramp is a movement disorder with dystonic co-contraction of fingers and hand during writing and is part of the clinical spectrum of focal dystonias. Previous studies showed reduced striatal dopamine receptor D2 (DRD2) availability in dystonia. The expression of D2 receptors is modulated by a DRD2/ANKK1-Taq1A polymorphism (rs1800497). This study addresses the question of whether the DRD2/ANKK1-Taq1A polymorphism is a risk factor for writer’s cramp. We determined the DRD2/ANKK1-Taq1A polymorphism 34 patients with writer’s cramp compared to 67 age matched controls. 35.3% of the patients and 31.3% of our controls were assigned to the A1 genotype status (p = .7). Therefore DRD2/ANKK1-Taq1A gene is not a significant risk factor in the evolution of writer’s cramp.

Intramedullary arteriovenous malformations (AVMs) in the cervical region are a rare clinical condition. They represent a therapeutic challenge, as the lesions may cause serious functional disorders due to their location within or immediately adjacent to the critical ascending and descending sensorimotor pathways. In this case report, we present a patient with a cervical intramedullary AVM that was treated with endovascular therapy. Our experience suggests that endovascular treatment is an effective and safe method for treating AVMs located in the cervical region of the spinal cord. More studies are needed to establish appropriate treatment protocols depending on the clinical course, the anatomy of the lesion, and the region in which it is found.

Aims : An assessment of the acoustic startle response (ASR) and prepulse inhibition (PPI) of ASR in laboratory animals is used to model human anxiety and psychotic states, respectively. The aim of the study was to evaluate ASR and PPI in alcohol-naive male and female Warsaw alcohol high-preferring (WHP) and Warsaw alcohol low-preferring (WLP) rats. Methods : ASR and PPI were assessed in two separate experiments by using the SR-LAB apparatus (San Diego Instruments, San Diego, CA, USA). In the ASR session, animals ( n = 13–16 rats per group) were exposed to startling stimuli of different intensities (72, 84, 98, 112 and 124 dB) in a random order. In the PPI session, prepulse stimuli (78, 81, 84 and 90 dB) preceded a pulse startling stimulus (120 dB) in a random order. The background white noise was set at 70 dB. PPI was calculated according to the formula: [(startle amplitude in pulse alone trials—startle amplitude in prepulse-and-pulse trials)/startle amplitude in pulse alone trials] × 100%. Results : The WHP males exhibited higher startle amplitudes in response to 112 dB stimuli when compared with their WLP counterparts. The WHP females showed higher startle reactivity to 112 and 124 dB stimuli when compared with the WLP females. There were no differences between the WHPs and WLPs in PPI of ASR. Conclusion : The results of the present study suggest that exaggerated startle responses can be a physiological/behavioral marker of a propensity to abuse alcohol.

Spinal and bulbar muscular atrophy (SBMA, Kennedy's disease) is an X-linked recessive disease affecting lower motor neurons. In the present case report, we describe morphological changes in a muscle biopsy obtained from a 62-year-old patient with gynecomastia and with the following neurological symptoms: dysphagia, dysarthria, wasting and fasciculation of the tongue, proximal weakness, fasciculations in the limb muscles, and an absence of all tendon reflexes. Neurogenic alternations were predominantly observed using light and electron microscopy. The angulated atrophic muscle fibers formed bundles. The numerous nuclei were pyknotic or pale, some of them were also ubiquitin positive; they were grouped inside so-called "nuclear sacks". At the ultrastructural level, atrophic muscle fibers revealed disruption and loss of sarcomeres, duplication of Z-line, and rod-like structures. The nuclei, often with irregular shapes, revealed varying degrees of chromatin condensation, from dispersed to highly condensed, like pyknotic nuclei. Occasionally electron-dense inclusions in the nuclei were found. Some myogenic features like hypertrophic muscle fibers and proliferation of connective tissue were also visible. The neurogenic and myogenic pathological changes suggested SBMA, which was confirmed with genetic analysis (trinucleotide CAG (glutamie)-repeat expansion in the androgen-receptor gene).

Anxiety, depression, and alcohol use disorders often go together. The aim of the present study was to evaluate anxiety- and depressive-like traits in selectively bred Warsaw alcohol high-preferring (WHP) and Warsaw alcohol low-preferring (WLP) rats. Alcohol-naïve WHP rats were more active in the open field test as compared to alcohol-naïve WLP rats. WHP rats made more central entries and spent more time in the central sector of the open field, i.e. presented less "neophobia", as compared to WLP subjects. The latter difference remained significant after controlling for the difference in locomotor activity as the anti-thigmotaxis ratio was also higher in WHP subjects. WHPs presented less freezing (i.e. less conditioned fear) than WLPs in the fear conditioning test. The difference in conditioned fear could not be explained by different pain sensitivity as the lines did not differ in pain threshold assessed in the flinch-jump test. WHPs were slightly less immobile in the Porsolt forced swim test as compared to WLPs. In conclusion, the present results suggest that alcohol high-preferring WHP rats show less anxiety- and depressive-like behavior than their low-preferring WLP counterparts.

Individuals prone to drug self-administration may be vulnerable not only to a single drug reinforcer but to a variety of drug reinforcers. It has been shown that two thirds of alcoholics regularly use drugs other than ethanol (alcohol). Up to 30% of alcohol-dependent patients report concurrent misuse of cocaine. The aim of the present study was to investigate intravenous cocaine self-administration in selectively bred, alcohol-preferring WHP (Warsaw high-preferring) and non-preferring WLP (Warsaw low-preferring) rats. It was hypothesized that WHPs could be more prone to cocaine self-administration in comparison to WLPs. Rats from both lines were allowed to nose-poke for cocaine infusions (0.33 mg/kg/infusion) under the FR-1, FR-2, and FR-3 schedule of reinforcement. Dose–response curves were assessed with increasing doses of cocaine (0.03, 0.1, 0.33, 1.0 mg/kg/infusion). The WHP and WLP rats did not differ in cocaine self-administration. Both groups quickly acquired nose-poke responding for cocaine, presented a similar response profile when the schedule of reinforcement was increased from FR-1 to FR-3, and similar sensitivity to cocaine in the dose–response test. The present results may indicate that the selective breeding of alcohol-preferring WHP and alcohol non-preferring WLP rats did not lead to differences in cocaine's rewarding effects as assessed in the self-administration procedure.