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Recent Progress and Diagnostic Innovations in Veterinary Neuropathology: In Dedication...
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Recent Progress and Diagnostic Innovations in Veterinary Neuropathology: In Dedication to Professor Martí Pumarola on the Occasion of His Retirement

A special issue of Animals (ISSN 2076-2615). This special issue belongs to the section "Veterinary Clinical Studies".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 7754

Special Issue Editors

Dr. Roberto José-López

E-Mail Website
Guest Editor
Neurology and Neurosurgery Service, Hamilton Specialist Referrals – IVC Evidensia, Halifax Road, Cressex Business Park, High Wycombe HP12 3SD, UK
Interests: glioma; neuro-oncology; neurosurgery; onco-immunology; One Health; translational medicine; veterinary neurology
Dr. Jéssica Molín

E-Mail Website
Guest Editor
Department of Animal Science, Universitat de Lleida, 25198 Lleida, Spain
Interests: comparative neuropathology; neuromuscular diseases; neuro-oncology; veterinary neuropathology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Veterinary neuropathology is essential in the diagnosis and understanding of diseases that affect the nervous system of animals. The field has expanded greatly over recent decades and a Special Issue focusing on its recent progress and diagnostic innovations will be published in Animals in honor of Professor Martí Pumarola on his retirement.

Professor Martí Pumarola is one of the pioneering pathologists that recently developed veterinary neuropathology into the increasingly established discipline of veterinary medicine it has become. He has published hundreds of papers on veterinary neuropathology and taught thousands of veterinary students during his years at the Universitat Autònoma de Barcelona, inspiring many to specialize in this field. He is an outstanding teacher, and his courses attract veterinary neurology and pathology residents from around the world and have become a cornerstone in their specialty training. In light of his attached disciples, we dedicate this Special Issue to Professor Pumarola to show recognition of and gratitude for his great contribution to veterinary neurology and neuropathology.

The definitive diagnosis of most diseases in veterinary neurology requires a neuropathologic analysis of tissue, and advances in research and novel techniques have provided great insight into these diseases by elucidating their etiopathogenesis, facilitating improved characterization and classification, and identifying therapeutic targets. This enhanced understanding of diseases of the nervous system in domestic animals also feeds into comparative neuropathology and sets the foundation for translational research and one health medicine.

For this Special Issue, we are pleased to invite you to submit original research articles and reviews focusing on recent advances in veterinary neuropathology diagnostics, new and emerging diseases, the further characterization and classification of diseases of the nervous system of domestic animals and their molecular pathology and biology, the assessment of biomarkers in the clinical setting and for translational research, and the development and application of software in digital pathology. Case series or case reports on unique clinical presentations or novel diagnostic techniques will also be considered.

We look forward to receiving your contributions.

Dr. Roberto José-López
Dr. Jéssica Molín
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Animals is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

 

Keywords

  • companion animals
  • comparative neuropathology
  • degenerative disease
  • digital pathology
  • histopathology
  • immune-mediated
  • immunohistochemistry
  • large animals
  • molecular neuropathology
  • neuromuscular
  • neoplasia
  • nervous system

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Published Papers (6 papers)

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14 pages, 3734 KiB  
Article
Applying the Techniques of Materials Science towards an Understanding of the Process of Canine Intervertebral Disc Degeneration
by Viviana Rojas, Ravin Jugdaohsingh, Andrew Rayment, Andrew Brown, Joseph Fenn, James Crowley, Vedran Lovric, Jonathan Powell and Paul Freeman
Animals 2024, 14(18), 2665; https://doi.org/10.3390/ani14182665 - 13 Sep 2024
Viewed by 535
Abstract
Intervertebral disc degeneration in dogs occurs in an accelerated way and involves calcification, which is associated with disc herniation or extrusion. The degenerative process is complex and involves the transformation of collagen fibres, loss of proteoglycans and notochord cells and a reduction in [...] Read more.
Intervertebral disc degeneration in dogs occurs in an accelerated way and involves calcification, which is associated with disc herniation or extrusion. The degenerative process is complex and involves the transformation of collagen fibres, loss of proteoglycans and notochord cells and a reduction in water content; however, how these processes are linked to future disc extrusion remains unknown. We have employed techniques including Fourier Transform Infra-red Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Uniaxial Compression Loading and Atomic Force Microscopy (AFM) in an attempt to gain a greater understanding of the degenerative process and its consequences on the physical properties of the disc. FTIR verified by TEM demonstrated that calcium phosphate exists in an amorphous state within the disc and that the formation of crystalline particles of hydroxyapatite occurs prior to disc extrusion. AFM identified crystalline agglomerates consistent with hydroxyapatite as well as individual collagen fibres. SEM enabled the identification of regions rich in calcium, phosphorous and oxygen and allowed the visualization of the topographical landscape of the disc. Compression testing generated stress/strain curves which will facilitate investigation into disc stiffness. Ongoing work is aimed at identifying potential areas of intervention in the degenerative process as well as further characterizing the role of calcification in disc extrusion. Full article
(This article belongs to the Special Issue Recent Progress and Diagnostic Innovations in Veterinary Neuropathology: In Dedication to Professor Martí Pumarola on the Occasion of His Retirement)
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14 pages, 4699 KiB  
Article
Pathologic Changes in and Immunophenotyping of Polymyositis in the Dutch Kooiker Dog
by Vanessa Alf, Yvet Opmeer, G. Diane Shelton, Guy C. M. Grinwis, Kaspar Matiasek, Marco Rosati and Paul J. J. Mandigers
Animals 2024, 14(17), 2519; https://doi.org/10.3390/ani14172519 - 29 Aug 2024
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Abstract
Earlier, we described a breed-specific inflammatory myopathy in Dutch Kooiker dogs (Het Nederlandse Kooikerhondje), one of the nine Dutch breeds. The disease commonly manifests itself with clinical signs of difficulty walking, muscle weakness, exercise intolerance, and/or dysphagia. In nearly all dogs’ creatine kinase [...] Read more.
Earlier, we described a breed-specific inflammatory myopathy in Dutch Kooiker dogs (Het Nederlandse Kooikerhondje), one of the nine Dutch breeds. The disease commonly manifests itself with clinical signs of difficulty walking, muscle weakness, exercise intolerance, and/or dysphagia. In nearly all dogs’ creatine kinase (CK) activity was elevated. Histopathology reveals the infiltration of inflammatory cells within the skeletal muscles. The objective of this study was to further investigate and characterize the histopathological changes in muscle tissue and immunophenotype the inflammatory infiltrates. FFPE fixed-muscle biopsies from 39 purebred Kooiker dogs were included and evaluated histopathologically according to a tailored classification scheme for skeletal muscle inflammation. As in other breed-related inflammatory myopathies, multifocal, mixed, and predominantly mononuclear cell infiltration was present, with an initial invasion of viable muscle fibres and the surrounding stroma leading to inflammation, necrosis, and tissue damage. Immunophenotyping primarily revealed lymphohistiocytic infiltrates, with CD3+ T-cells being the predominant inflammatory cell type, accompanied by CD8+ cytotoxic T-cells. The concurrent expression of MHC-II class molecules on myofibres suggests their involvement in initiating and maintaining inflammation. Additionally, CD20+ B-cells were identified, though in lower numbers compared to T-cells, and IBA-1-positive macrophages were frequently seen. These findings suggest a breed-specific subtype of polymyositis in Kooiker dogs, akin to other breeds. This study sheds light on the immune response activation, combining adaptive and innate mechanisms, contributing to our understanding of polymyositis in this breed. Full article
(This article belongs to the Special Issue Recent Progress and Diagnostic Innovations in Veterinary Neuropathology: In Dedication to Professor Martí Pumarola on the Occasion of His Retirement)
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13 pages, 4403 KiB  
Article
Immunohistochemical Expression of PTEN in Canine Gliomas
by Jéssica Molín, Roberto José-López, Gustavo A. Ramírez and Martí Pumarola
Animals 2024, 14(14), 2115; https://doi.org/10.3390/ani14142115 - 20 Jul 2024
Viewed by 699
Abstract
Phosphatase and tensin homolog (PTEN) is a critical tumor suppressor gene with a vital role in regulating cell proliferation, migration, and survival. The loss of PTEN function, either by genetic alterations or decreased protein expression, is frequent in human gliomas and has been [...] Read more.
Phosphatase and tensin homolog (PTEN) is a critical tumor suppressor gene with a vital role in regulating cell proliferation, migration, and survival. The loss of PTEN function, either by genetic alterations or decreased protein expression, is frequent in human gliomas and has been correlated with tumor progression, grade, therapeutic resistance, and decreased overall survival in patients with glioma. While different genetic mutations in PTEN gene have been occasionally reported in canine gliomas, no alterations in protein expression have been reported. This study investigates the immunohistochemical expression of PTEN in canine gliomas to evaluate possible alterations, as those reported in human gliomas. Immunohistochemical PTEN expression and pattern distribution were analyzed in 37 spontaneous canine gliomas. Among gliomas, 52.6% cases showed high PTEN expression and 48.6% displayed reduced (13.5%) or highly reduced (35.1%) immunopositivity. Most oligodendrogliomas showed high expression (73.7%), while the majority of astrocytomas (69.2%) showed a reduced or highly reduced expression. A reduced PTEN expression was mostly associated with a heterogeneous loss of PTEN immunopositivity. These observations are in line with those reported in human gliomas and provide a rationale for future studies regarding abnormalities in PTEN expression and PI3K/Akt/mTor pathway in canine gliomas, to evaluate its prognostic and therapeutic implications. Full article
(This article belongs to the Special Issue Recent Progress and Diagnostic Innovations in Veterinary Neuropathology: In Dedication to Professor Martí Pumarola on the Occasion of His Retirement)
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12 pages, 3826 KiB  
Article
Variants in CLCN1 and PDE4C Associated with Muscle Hypertrophy, Dysphagia, and Gait Abnormalities in Young French Bulldogs
by G. Diane Shelton, James R. Mickelson, Steven G. Friedenberg, Jonah N. Cullen, Karina Graham, Missy C. Carpentier, Ling T. Guo and Katie M. Minor
Animals 2024, 14(5), 722; https://doi.org/10.3390/ani14050722 - 25 Feb 2024
Viewed by 1824
Abstract
(1) Background: Muscle hypertrophy, swallowing disorders, and gait abnormalities are clinical signs common to many muscle diseases, including muscular dystrophies, non-dystrophic myotonias, genetic myopathies associated with deficiency of myostatin, and acquired inflammatory myopathies. Here, we investigated underlying causes of this triad of clinical [...] Read more.
(1) Background: Muscle hypertrophy, swallowing disorders, and gait abnormalities are clinical signs common to many muscle diseases, including muscular dystrophies, non-dystrophic myotonias, genetic myopathies associated with deficiency of myostatin, and acquired inflammatory myopathies. Here, we investigated underlying causes of this triad of clinical signs in four young French bulldogs via muscle histopathology coupled with whole genome and Sanger sequencing. (2) Methods: Dogs were evaluated by veterinary clinical internists and neurologists, and biopsies were obtained for histopathological diagnosis. DNA was submitted for whole genome sequencing, followed by bioinformatics evaluation and confirmation of variants via Sanger sequencing in two cases. (3) Results: Two novel variants were identified. The first, found in two related French bulldogs, was a homozygous variant in the chloride channel gene CLCN1 known to cause non-dystrophic congenital myotonia, and the second, found in an unrelated French bulldog, was a heterozygous variant in the cAMP phosphodiesterase gene PDE4C, which is the major phosphodiesterase expressed in skeletal muscle and may play a role in decreasing muscle atrophy. An underlying molecular basis in one other case has not yet been identified. (4) Conclusions: Here, we identified two novel variants, one in the CLCN1 and one in the PDE4C gene, associated with clinical signs of muscle hypertrophy, dysphagia, and gait abnormalities, and we suggested other bases of these phenotypes in French bulldogs that are yet to be discovered. Identification of genes and deleterious variants associated with these clinical signs may assist breeders in improving the overall health of this very popular breed and may lead to the identification of new therapies to reverse muscle atrophy in people and animals with neuromuscular diseases. Full article
(This article belongs to the Special Issue Recent Progress and Diagnostic Innovations in Veterinary Neuropathology: In Dedication to Professor Martí Pumarola on the Occasion of His Retirement)
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17 pages, 4499 KiB  
Article
Primary Feline Tauopathy: Clinical, Morphological, Immunohistochemical, and Genetic Studies
by Laura Vidal-Palencia, Cristina Font, Agustín Rebollada-Merino, Gabriel Santpere, Pol Andrés-Benito, Isidro Ferrer and Martí Pumarola
Animals 2023, 13(18), 2985; https://doi.org/10.3390/ani13182985 - 21 Sep 2023
Cited by 1 | Viewed by 1712
Abstract
Tauopathies are a group of neurodegenerative diseases characterized by the pathological aggregation of hyperphosphorylated tau in neurons and glia. Primary tauopathies are not uncommon in humans but exceptional in other species. We evaluate the clinical, neuropathological, and genetic alterations related to tau pathology [...] Read more.
Tauopathies are a group of neurodegenerative diseases characterized by the pathological aggregation of hyperphosphorylated tau in neurons and glia. Primary tauopathies are not uncommon in humans but exceptional in other species. We evaluate the clinical, neuropathological, and genetic alterations related to tau pathology in 16 cats aged from 1 to 21 years with different clinical backgrounds. Interestingly, a 10-year-old female cat presented a six-year progressive history of mental status and gait abnormalities. The imaging study revealed generalized cortical atrophy. Due to the poor prognosis, the cat was euthanatized at the age of ten. Neuropathological lesions were characterized by massive neuronal loss with marked spongiosis and associated moderate reactive gliosis in the parietal cortex, being less severe in other areas of the cerebral cortex, and the loss of Purkinje cells of the cerebellum. Immunohistochemical methods revealed a 4R-tauopathy with granular pre-tangles in neurons and coiled bodies in oligodendrocytes. Deposits were recognized with several phospho-site antibodies (4Rtau, tau5, AT8, PFH, tau-P Thr181, tau-P-Ser 262, tau-P Ser 422) and associated with increased granular expression of active tau kinases (p38-P Thr180/Tyr182 and SAPK/JNK-P Thr138/Thr185). The genetic study revealed well-preserved coding regions of MAPT. No similar alterations related to tau pathology were found in the other 15 cats processed in parallel. To our knowledge, this is the first case reporting a primary 4R-tauopathy with severe cerebral and Purkinje cell degeneration in an adult cat with neurological signs starting at a young age. Full article
(This article belongs to the Special Issue Recent Progress and Diagnostic Innovations in Veterinary Neuropathology: In Dedication to Professor Martí Pumarola on the Occasion of His Retirement)
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7 pages, 1819 KiB  
Case Report
Suspected Primary Intracranial Melanoma with Widespread Distant Metastases in a Cat
by Jonathan Deacon, Samuel Beck, Francesca Pitorri and Catherine Stalin
Animals 2023, 13(24), 3751; https://doi.org/10.3390/ani13243751 - 5 Dec 2023
Viewed by 1033
Abstract
An 8-year-old female Domestic Shorthair presented with signs of intracranial disease. Magnetic resonance imaging (MRI) of the head showed an extra-axial space-occupying mass within the cranial vault with a similar intensity lesion within the overlying temporalis muscle. Postmortem examination found masses within the [...] Read more.
An 8-year-old female Domestic Shorthair presented with signs of intracranial disease. Magnetic resonance imaging (MRI) of the head showed an extra-axial space-occupying mass within the cranial vault with a similar intensity lesion within the overlying temporalis muscle. Postmortem examination found masses within the head, lung, liver, spleen, and kidney consistent with malignant melanoma. Intracranial melanoma is rarely reported in cats and is typically only seen as a metastatic lesion associated with an ocular mass. Melanomas can be readily recognised on MRI as they are one of the few lesions which are hyperintense on T1-weighted images. Full article
(This article belongs to the Special Issue Recent Progress and Diagnostic Innovations in Veterinary Neuropathology: In Dedication to Professor Martí Pumarola on the Occasion of His Retirement)
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