Advances in Veterinary Neurology, An Issue of Veterinary Clinics of North America: Small Animal Practice, E-Book (eBook)

Natasha J. Olby (Autor)

eBook Download: PDF | EPUB

2014 | 1. Auflage
100 Seiten
Elsevier Health Sciences (Verlag)
978-0-323-32691-9 (ISBN)

Infos

This issue highlights the advances in neurological treatments for dogs and cats. Articles include: New Treatment Modalities for Brain Tumors in Dogs and Cats, Altered Mental Status in Dogs and Cats: Stupor and Coma, Steroid Use in Veterinary Neurology, Hereditary Ataxia and Paroxysmal Movement Disorders in Dogs and Cats, Paroxysmal Movement Disorders in Dogs and Cats, Cluster Seizures and Status Epilepticus, Aging in the canine and feline brain, Acute Spinal Cord Injury: Tetraparesis and Paraparesis, Meningoencephalitis of Unknown Etiology, and more!

Textauszug

New Treatment Modalities for Brain Tumors in Dogs and Cats

John H. Rossmeisl, DVM, MS [e-mail],     Neurology and Neurosurgery, Department of Small Animal Clinical Sciences, VA-MD Regional College of Veterinary Medicine, Virginia Tech, 215 Duckpond Drive, Mail Code 0442, Blacksburg, VA 24061, USA

Despite advancements in standard therapies, intracranial tumors remain a significant source of morbidity and mortality in veterinary and human medicine. Several newer approaches are gaining more widespread acceptance or are currently being prepared for translation from experimental to routine therapeutic use. Clinical trials in dogs with spontaneous brain tumors have contributed to the development and human translation of several novel therapeutic brain tumor approaches.

Keywords

Canine

Central nervous system

Convection-enhanced delivery

Feline

Glioma

Immunotherapy

Oncology

Radiotherapy

Key points

• Advancements in magnetic resonance (MRI) and functional neuroimaging will continue to improve the clinical management of brain tumors.

• Stereotactic radiosurgery (SRS) is emerging as a viable treatment of many canine and feline brain tumors and can be performed with minimal toxicity using dedicated radiosurgical units or contemporary linear accelerators.

• Convention-enhanced delivery (CED) is a promising therapeutic platform that bypasses the blood-brain barrier (BBB), allowing for direct administration of macromolecular antineoplastic agents to brain tumors.

• CED is used to treat dogs with spontaneous brain tumors but consistent and accurate delivery of drugs remains a challenge to mainstream clinical adoption of this technique.

• Advancements in neuroimmunology and tumor biology have led to the development and clinical translation of several novel immunotherapies with therapeutic potential in canine and human brain tumors.

Introduction

Transformative advances in MRI over the past 3 decades allow for the detailed neuroanatomic characterization and presumptive antemortem diagnosis of many canine and feline brain tumors.1–4 MRI has also served as a fundamental platform for the development of technologies and procedures that have contributed to improvements in the management of brain tumors, including image-guided neuronavigation, functional neuroimaging, surgical and radiotherapeutic planning, and objective therapeutic response assessment.5–9 Despite this progress, definitive antemortem diagnosis of brain tumors in animals remains uncommon, and few data exist in veterinary medicine regarding the influence of treatment on clinical outcomes of animals with brain tumors. Primary brain tumors, in particular the malignant variants, remain a source of significant morbidity and mortality in small animals and humans.10,11

Current Therapeutic Options

The prognosis for dogs with palliatively-treated brain tumors is poor. In one study of dogs with brain tumors definitively diagnosed at necropsy, the reported overall median survival was approximately 2 months after diagnosis via brain imaging.10 Surgical resection and fractionated radiotherapy are currently the principal methods used to treat canine and feline brain tumors, and these therapies are capable of improving both the quality and quantity of life in small animals. However, both surgery and radiotherapy can be associated with treatment-associated morbidity, and local treatment failures after these therapies remain a common cause of death or euthanasia.12–17 Surgical treatment has been best described for forebrain meningiomas, which is the most common primary brain tumor type in both dogs and cats.8,12–15 In dogs with meningiomas, the reported median survival after traditional surgical resection is approximately 7 months.12 In cats, the median survival after surgical resection of forebrain meningiomas is 24 months 13,14 Neurosurgical treatment that incorporates devices that improve intraoperative visualization, such as intracranial endoscopy, or facilitate tumor extirpation have been associated with median survivals ranging from 42 to 70 months.8,15 Transsphenoidal hypophysectomy has been demonstrated to be an effective surgical technique in dogs and cats with nonenlarged to moderately enlarged pituitary adenomas, with a reported 4-year survival rate of 68% in dogs.16 Currently available surgical techniques often preclude safe resection of intraparenchymal tumors that are infiltrating the surrounding brain or intimately associated with critical neuroanatomic structures. There is little information available regarding the efficacy of or indications for surgery in canine and feline brain tumors other than meningiomas and pituitary tumors.

Fractionated radiotherapy is beneficial in the treatment of brain tumors as a sole therapeutic modality or as an adjuvant after surgery.12–18 Studies investigating treatment of a variety of presumptively diagnosed brain tumors in dogs with fractionated radiotherapy reported median survivals that range from approximately 300 to 700 days.17,18 Dogs with meningiomas treated with 3-D conformal radiation therapy had an overall median survival of 577 days, and the median survival increased to nearly 30 months (ie, approximately 900 days) when dogs dying of causes other than meningioma were excluded.19 Systemically administered cytotoxic chemotherapeutics, including those agents capable of penetrating BBB, are largely ineffective as sole agents for the treatment of brain tumors. A recent study failed to demonstrate any difference in survival between dogs with brain tumors treated symptomatically with prednisone and anticonvulsant drugs compared with those that received symptomatic therapy and lomustine.20

There is increasing recognition of the epidemiologic, neuropathologic, molecular, and genetic homologies between canine and human brain tumors, which has driven the use of dogs with spontaneous brain tumors as a translational disease model.21–23 This review introduces contemporary therapeutic advancements for brain tumors and illustrates the role that tumor-bearing dogs have made to progressing the field of translational neuro-oncology. Because an exhaustive survey of brain tumor treatment is beyond the scope of this article, it focuses on SRS, CED, and immunotherapy (IT). These therapies hold great promise for the treatment of brain tumors and are being used clinically in dogs and cats.23–25 Reviews of boron neutron capture therapy, brachytherapy, high-intensity focused ultrasound (HiFU), gene therapy, laser interstitial thermal therapy, proton beam radiotherapy, oncolytic viruses, and pulsed electric fields are available elsewhere.7,26–34

These therapeutic approaches are not mutually exclusive. For example, because many molecularly targeted chemotherapeutics, gene-bearing vectors, and boron delivery agents are high-molecular-weight structures that cannot penetrate the BBB when administered systemically, they require delivery by a method that bypasses or disrupts the BBB, such as CED or HiFU.23,26,30 Distinct advantages are also realized when biologically directed treatments, primarily in the form of target-specific monoclonal antibodies, are conjugated to chemotherapeutics in efforts to sensitize tumors to external beam radiotherapy or radionuclides to allow for more selective tumor irradiation.35,36

Stereotactic radiosurgery

Introduction and History

Stereotactic radiation therapy (SRT) broadly encompasses treatments that involve the delivery of high doses of ionizing radiation to a defined anatomic target in a limited number (typically 1–5) of therapeutic sessions. SRS is a subtype of SRT that consists of the treatment delivered as a single fraction.37 Of the therapies reviewed in this article, only SRT and SRS are currently routinely used in veterinary clinical oncology practice for the treatment of brain tumors.

SRS represents a marriage of stereotactic and radiotherapeutic methods. The origins of the stereotactic method are attributed to Drs Robert Clarke, a surgeon and engineer, and neurosurgeon Victor Horsley, who in 1906 first used a stereotactic frame to lesion the brain of experimental animals.38 It was not until 40 years later that stereotaxis was used in humans by Speigel and colleagues.39 Their stereotactic device was based on the Cartesian coordinate system and modeled after the Clarke-Horsley instrument. Speigel and colleagues launched a revolution in stereotaxy that culminated in numerous apparatus, including those of Leksell,40 Talairach and colleagues,41 Narabayashi,42 Riechert and Mundinger,43 and Todd and Wells,44 providing the foundations for contemporary stereotactic neurosurgery and SRS.

The...

Produkt-Details

• Erscheint lt. Verlag: 12.11.2014
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie
• Themenwelt: Veterinärmedizin ► Kleintier
• ISBN-10: 0-323-32691-9 / 0323326919
• ISBN-13: 978-0-323-32691-9 / 9780323326919