A current view of mitochondria damage and the diversity of lipopigment inclusions in neuronal ceroid lipofuscinose type 2 from rectal biopsy.

Neuronal ceroid lipofuscinoses (NCLs) are a growing group of neurodegenerative storage diseases, in which specific features are sought to facilitate the creation of a universal diagnostic algorithm in the future. In our ultrastructural studies, the group of NCLs was represented by the CLN2 disease caused by a defect in the TPP1 gene encoding the enzyme tripeptidyl-peptidase 1. A 3.5-year-old girl was affected by this disease. Due to diagnostic difficulties, the spectrum of clinical, enzymatic, and genetic tests was extended to include analysis of the ultrastructure of cells from a rectal biopsy. The aim of our research was to search for pathognomonic features of CLN2 and to analyse the mitochondrial damage accompanying the disease. In the examined cells of the rectal mucosa, as expected, filamentous deposits of the curvilinear profile (CVP) type were found, which dominated quantitatively. Mixed deposits of the CVP/fingerprint profile (FPP) type were observed less frequently in the examined cells. A form of inclusions of unknown origin, not described so far in CLN2 disease, were wads of osmophilic material (WOMs). They occurred alone or co-formed mixed deposits. In addition, atypically damaged mitochondria were observed in muscularis mucosae. Their deformed cristae had contact with inclusions that looked like CVPs. Considering the confirmed role of the c subunit of the mitochondrial ATP synthase in the formation of filamentous lipopigment deposits in the group of NCLs, we suggest the possible significance of other mitochondrial proteins, such as mitochondrial contact site and cristae organizing system (MICOS), in the formation of these deposits. The presence of WOMs in the context of searching for ultrastructural pathognomonic features in CLN2 disease also requires further research.

A primary multiple pleomorphic rhabdomyosarcoma of the heart in an adult dog.

BACKGROUND: Heart tumors are rare in dogs. They can be benign or malignant. Clinical signs depend primarily on the location of the tumor and its effect on blood flow. CASE PRESENTATION: An eleven-year-old crossbreed male dog lethargic and anorectic for previous 3 days was presented to the veterinary clinic. The focused ultrasound assessment with sonograms in trauma (FAST) revealed multiple tumors in the heart which were then confirmed in echocardiographic examination performed by a veterinary cardiologist. Due to the poor general condition and grave prognosis, the dog was humanely euthanized. The autopsy revealed numerous intracardiac tumors in all four heart chambers. No proliferative changes were found in other organs either in thoracic or abdominal cavity. Immunohistochemical examination was performed using formalin-fixed, paraffin-embedded tissue from heart masses. The antibodies against myoglobin, desmin, smooth muscle actin, vimentin, CD34, S100, and pan-cytokeratin (AE1/AE3) were used. Microscopically, the tumor was composed of fascicles of spindle-shaped cells with pale eosinophilic cytoplasm with round, oval, and focally elongated nuclei and one or two prominent nucleoli. The tumor cells showed strong diffuse cytoplasmic immunopositivity for myoglobin and vimentin and focal staining for desmin. Immunostainings for smooth muscle actin-SMA, CD34, pan-cytokeratin, S-100 protein were negative. The immunohistochemical staining pattern confirmed rhabdomyosarcoma. CONCLUSIONS: This is the first description of the primary multiple heart rhabdomyosarcoma in a dog.

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.

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.

Integrated Basic Heart and Lung Ultrasound Examination for the Differentiation between Bacterial Pneumonia and Lung Neoplasm in Dogs-A New Diagnostic Algorithm.

The diagnostics of two of the most prevalent lung diseases in dogs, bacterial pneumonia (BP) and lung neoplasm (LN), are challenging as their clinical signs are identical and may also occur in extrapulmonary diseases. This study aims to identify ultrasonographic criteria and develop a lung ultrasound (LUS)-based diagnostic algorithm which could help distinguish between these two conditions. The study is carried out in 66 dyspneic dogs in which a heart disease was excluded using echocardiography. Based on imaging and laboratory diagnostic tests, as well as follow-up, the dogs are classified into LN (35 dogs) and BP (31 dogs) groups. LUS is performed at admission and the presence of seven lung abnormalities (pleural thickening, B-lines, subpleural consolidations, hepatization with or without aeration, nodule sign and mass classified together as a tumor, and free pleural fluid) and classification and regression trees are used to develop an LUS-based diagnostic algorithm. Distribution of all LUS abnormalities except for aerations differs significantly between groups; however, their individual differentiating potential is rather low. Therefore, we combine them in an algorithm which allows for definitive classification of 60 dogs (91%) (32 with LN and 28 with BP) with correct diagnosis of LN and BP in 31 dogs and 27 dogs, respectively.

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.