Necrotizing meningoencephalitis

Last updated

Necrotizing meningoencephalitis (NME) is a fatal inflammatory central nervous system (CNS) disorder in dogs, where an extensive cerebral necrosis is associated with a multifocal, non-suppurative meningoencephalitis of the neuro cortex. [1] [2] [3] It was originally identified and recorded in the 1960s in pure breed pugs, with which this disease is nowadays mostly associated with, occurring essentially in small breed dogs ranging from six months to seven years of age. [4] [2] [5] It causes intense necrotizing inflammatory lesions in the brain stem and Cerebellum. [3] The cause is still unclear. [6] The pathogen that triggers the disease and contributes to its development has not yet been identified. It is presumed to have a multifactorial, heritable, autoimmune etiology. [2] The process is rapidly progressive, culminating in status epilepticus and ending fatally for the dog. [5]

Contents

Although the pattern of inflammation is similar to other neuropathological conditions, resembling CNS inflammatory diseases which produces lesions alike to those that occur in NME, a definitive diagnosis can be made solely based on by histopathological examination through a necropsy. [6]

Signs and symptoms

First signs of this immune dysregulation can show through lethargy and the reluctance to walk. Behavioral changes and an abnormal mentation might occur. [6] After a short amount of time vestibulo-cerebellar symptoms will rapidly progress, leaving the animal in a state of depressed consciousness having seizures, amaurosis and ataxia. [2] [4] [6]

Despite seizures being a promoting factor of necrosis in primary inflammation diseases, it's not proven that the necrosis is extending to the white matter due to these convulsions. [7]

Diagnostics

An antemortem diagnosis is often intricate considering the similarities of general neuro diagnostic profiles. To achieve a presumptive diagnosis on the live animal a multimodal approach is needed. Including the magnetic resonance imaging (MRI), computer tomography (CT), cerebrospinal liquid (CFS) analysis and immunological test. Since only the CNS is affected by the pathology, there won't be any characteristic changes in organ systems other than the nervous system. [1] [2] [7] Despite clinical examination methods, the specific diagnosis of NME depends on a postmortem, histopathological examination of the brain biopsy tissue or a necropsy. [3]

Histopathological features

When examining the transversal sections, the non-suppurative (lymphoplasmacytic and histiocytic) inflammation of both the meninges and encephalitis have characteristic histopathologic changes of necrotizing nature in the corona radiata (white matter), the thalamus and the cerebrocortical area. [6] [8] The meninges itself is focally thickened by dense aggregations of lymphocytes, plasma cells and macrophages infiltrating due to the reinforced immune answer (perivascular cuffing). [9] [10]

Several multifocal encephalic lesions in corona radiata are erasing the border in the cerebral hemispheres between white and grey matter, exposing an asymmetrical ventricular enlargement. [1] These lesions are selective with a predilection for the cerebral hemisphere. [4]

They can be divided into three phases:

Additionally, temporal lobes with dense mononuclear cells can be observed infiltrating the meninges, and cerebellar herniation through the foramen magnum, [3] which leads to neurological symptoms like continuous circling or stroke-like seizures. [6] Attempts at proving a viral etiology have been unsuccessful. [5]

Treatment

In several studies the animals were given immunosuppressive drugs, such as cytarabine, prednisolone and dexamethasone on the behalf that the cause of NME is autoimmune related. Corticosteroids inhibit T-and B-Cells and slow down the production of cytokines, which restrain the immune system from attacking its own cells but also enfeeble its natural protection – the immune answer. [10]

However, since the etiopathogenesis is still not totally understood, the inflammatory reactions are only partly reacting to the corticosteroids, such as the malacic or granulomatous changes. [10]

Prognosis

Even after several years of research, the complete pathogenesis of this disease is still not understood. Immunosuppressive and anticonvulsant drugs have extended the lives of several dogs for up to 7 months after the outbreak of the symptoms, although a complete recovery is not yet possible.

The disease remains fatal, making euthanasia an invariable necessity. [5] [7]

Related Research Articles

<span class="mw-page-title-main">Necrosis</span> Unprogrammed cell death caused by external cell injury

Necrosis is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who is often regarded as one of the founders of modern pathology. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated digestion of cell components. In contrast, apoptosis is a naturally occurring programmed and targeted cause of cellular death. While apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental and can be fatal.

<span class="mw-page-title-main">Canine distemper</span> Viral disease affecting some mammals

Canine distemper virus (CDV) is a viral disease that affects a wide variety of mammal families, including domestic and wild species of dogs, coyotes, foxes, pandas, wolves, ferrets, skunks, raccoons, and felines, as well as pinnipeds, some primates, and a variety of other species. CDV does not affect humans.

<span class="mw-page-title-main">Granuloma</span> Aggregation of macrophages in response to chronic inflammation

A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious organisms including bacteria and fungi, as well as other materials such as foreign objects, keratin, and suture fragments.

Hairy leukoplakia is a white patch on the side of the tongue with a corrugated or hairy appearance. It is caused by Epstein-Barr virus (EBV) and occurs usually in persons who are immunocompromised, especially those with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS). The white lesion, which cannot be scraped off, is benign and does not require any treatment, although its appearance may have diagnostic and prognostic implications for the underlying condition.

<span class="mw-page-title-main">Canine parvovirus</span> Contagious virus mainly affecting dogs

Canine parvovirus is a contagious virus mainly affecting dogs. CPV is highly contagious and is spread from dog to dog by direct or indirect contact with their feces. Vaccines can prevent this infection, but mortality can reach 91% in untreated cases. Treatment often involves veterinary hospitalization. Canine parvovirus often infects other mammals including foxes, wolves, cats, and skunks. Felines (cats) are also susceptible to panleukopenia, a different strain of parvovirus.

<span class="mw-page-title-main">Scleritis</span> Medical condition

Scleritis is a serious inflammatory disease that affects the white outer coating of the eye, known as the sclera. The disease is often contracted through association with other diseases of the body, such as granulomatosis with polyangiitis or rheumatoid arthritis. There are three types of scleritis: diffuse scleritis, nodular scleritis, and necrotizing scleritis. Scleritis may be the first symptom of onset of connective tissue disease.

<span class="mw-page-title-main">Pyoderma gangrenosum</span> Medical condition

Pyoderma gangrenosum is a rare, inflammatory skin disease where painful pustules or nodules become ulcers that progressively grow. Pyoderma gangrenosum is not infectious.

<span class="mw-page-title-main">Meningoencephalitis</span> Medical condition

Meningoencephalitis, also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain tissue.

Granulomatous meningoencephalitis (GME) is an inflammatory disease of the central nervous system (CNS) of dogs and, rarely, cats. It is a form of meningoencephalitis. GME is likely second only to encephalitis caused by canine distemper virus as the most common cause of inflammatory disease of the canine CNS. The disease is more common in female dogs of young and middle age. It has a rapid onset. The lesions of GME exist mainly in the white matter of the cerebrum, brainstem, cerebellum, and spinal cord. The cause is only known to be noninfectious and is considered at this time to be idiopathic. Because lesions resemble those seen in allergic meningoencephalitis, GME is thought to have an immune-mediated cause, but it is also thought that the disease may be based on an abnormal response to an infectious agent. One study searched for viral DNA from canine herpesvirus, canine adenovirus, and canine parvovirus in brain tissue from dogs with GME, necrotizing meningoencephalitis, and necrotizing leukoencephalitis, but failed to find any.

<span class="mw-page-title-main">Progressive outer retinal necrosis</span> Medical condition

Progressive outer retinal necrosis (PORN) syndrome is a form of chorioretinitis, an infection in the retina, the back of the eye. The disease is most commonly caused by the varicella zoster virus and is found almost exclusively in patients with HIV/AIDS. Progressive outer retinal necrosis is the second most common opportunistic retinal infection in North America among people with AIDS. The reason this disease process is considered opportunistic is precisely because it only presents in patients with AIDS, a disease that attacks and weakens the immune system, making space for other infections, like Varicella zoster virus (VZV) and Herpes simplex virus (HSV), to attack the body.

<i>Balamuthia mandrillaris</i> Species of pathogenic Amoebozoa

Balamuthia mandrillaris is a free-living amoeba that causes the rare but deadly neurological condition granulomatous amoebic encephalitis (GAE). B. mandrillaris is a soil-dwelling amoeba and was first discovered in 1986 in the brain of a mandrill that died in the San Diego Wild Animal Park.

<span class="mw-page-title-main">Granulomatous amoebic encephalitis</span> Rare and usually fatal brain infection by certain amoebae

Granulomatous amoebic encephalitis (GAE) is a rare, usually fatal, subacute-to-chronic central nervous system disease caused by certain species of free-living amoebae of the genera Acanthamoeba, Balamuthia and Sappinia. The term is most commonly used with Acanthamoeba. In more modern references, the term "balamuthia amoebic encephalitis" (BAE) is commonly used when Balamuthia mandrillaris is the cause.

<span class="mw-page-title-main">Chronic superficial keratitis</span>

Chronic superficial keratitis (CSK), also known as pannus or Uberreiter's disease, is an inflammatory condition of the cornea in dogs, particularly seen in the German Shepherd. Both eyes are usually affected. The corneas gradually become pigmented and infiltrated by blood vessels, and the dog may eventually become blind.

<span class="mw-page-title-main">Cat-scratch disease</span> Human disease

Cat-scratch disease (CSD) or felinosis is an infectious disease that most often results from a scratch or bite of a cat. Symptoms typically include a non-painful bump or blister at the site of injury and painful and swollen lymph nodes. People may feel tired, have a headache, or a fever. Symptoms typically begin within 3–14 days following infection.

Citrobacter koseri, formerly known as Citrobacter diversus, is a Gram-negative non-spore forming, rod-shaped bacterium. It is a facultative anaerobe capable of aerobic respiration. It is motile via peritrichous flagella. It is a member of the family of Enterobacteriaceae. The members of this family are part of the normal flora and commonly found in the digestive tracts of humans and animals. C. koseri may act as an opportunistic pathogen in individuals who are immunocompromised.

<span class="mw-page-title-main">Sebaceous adenitis</span> Skin disease

Sebaceous adenitis in an uncommon skin disease found in some breeds of dog, and more rarely in cats, rabbits and horses. characterised by an inflammatory response against the dog's sebaceous glands, which can lead to the destruction of the gland. It was first described in veterinary literature in the 1980s.

<span class="mw-page-title-main">Mastocytoma in dogs</span> Mastocytoma in dogs is a neoplasm

Mastocytoma in dogs is a neoplasm (neoplasia) originating from mast cells in the domestic dog, which occurs mainly in the skin and subcutis. Mastocytoma are not only extremely common in dogs, but also tend to be much more malignant in them than in other animal species. The average survival time for malignant tumors is only four months, whereas for benign tumors it is over two years.

References

  1. 1 2 3 Barber RM, Schatzberg SJ, Corneveaux JJ, Allen AN, Porter BF, Pruzin JJ, Platt SR, Kent M, Huentelman MJ (1 September 2011). "Identification of risk loci for necrotizing meningoencephalitis in Pug dogs". The Journal of Heredity. 102 Suppl 1 (1): S40–6. doi: 10.1093/jhered/esr048 . PMID   21846746.
  2. 1 2 3 4 5 Suzuki M, Uchida K, Morozumi M, Hasegawa T, Yanai T, Nakayama H, Tateyama S (November 2003). "A comparative pathological study on canine necrotizing meningoencephalitis and granulomatous meningoencephalomyelitis". The Journal of Veterinary Medical Science. 65 (11): 1233–9. doi: 10.1292/jvms.65.1233 . PMID   14665754.
  3. 1 2 3 4 Park ES, Uchida K, Nakayama H (July 2012). "Comprehensive immunohistochemical studies on canine necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME)". Veterinary Pathology. 49 (4): 682–92. doi:10.1177/0300985811429311. PMID   22262353.
  4. 1 2 3 Cordy DR, Holliday TA (May 1989). "A necrotizing meningoencephalitis of pug dogs". Veterinary Pathology. 26 (3): 191–4. doi:10.1177/030098588902600301. PMID   2763409.
  5. 1 2 3 4 Greer KA, Schatzberg SJ, Porter BF, Jones KA, Famula TR, Murphy KE (June 2009). "Heritability and transmission analysis of necrotizing meningoencephalitis in the Pug". Research in Veterinary Science. 86 (3): 438–42. doi:10.1016/j.rvsc.2008.10.002. PMID   19014875.
  6. 1 2 3 4 5 6 Talarico LR, Schatzberg SJ (March 2010). "Idiopathic granulomatous and necrotising inflammatory disorders of the canine central nervous system: a review and future perspectives". The Journal of Small Animal Practice. 51 (3): 138–49. doi: 10.1111/j.1748-5827.2009.00823.x . PMID   19814766.
  7. 1 2 3 Kitagawa M, Okada M, Kanayama K, Sato T, Sakai T (November 2007). "A canine case of necrotizing meningoencephalitis for long-term observation: clinical and MRI findings" (PDF). The Journal of Veterinary Medical Science. 69 (11): 1195–8. doi: 10.1292/jvms.69.1195 . PMID   18057839. S2CID   33004172.
  8. ↑ Cooper JJ, Schatzberg SJ, Vernau KM, Summers BA, Porter BF, Siso S, Young BD, Levine JM (2014). "Necrotizing meningoencephalitis in atypical dog breeds: a case series and literature review". Journal of Veterinary Internal Medicine. 28 (1): 198–203. doi:10.1111/jvim.12233. PMC   4895549 . PMID   24428322.
  9. ↑ Higgins RJ, Dickinson PJ, Kube SA, Moore PF, Couto SS, Vernau KM, Sturges BK, Lecouteur RA (May 2008). "Necrotizing meningoencephalitis in five Chihuahua dogs". Veterinary Pathology. 45 (3): 336–46. doi:10.1354/vp.45-3-336. PMID   18487490.
  10. 1 2 3 4 Kuwamura M, Adachi T, Yamate J, Kotani T, Ohashi F, Summers BA (October 2002). "Necrotising encephalitis in the Yorkshire terrier: a case report and literature review". The Journal of Small Animal Practice. 43 (10): 459–63. doi: 10.1111/j.1748-5827.2002.tb00014.x . PMID   12400645.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.