Title: Necrotizing meningoencephalitis

{{Short description|Dog disease}}
'''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.&lt;ref name=&quot;Barber_2011&quot;&gt;{{cite journal | vauthors = Barber RM, Schatzberg SJ, Corneveaux JJ, Allen AN, Porter BF, Pruzin JJ, Platt SR, Kent M, Huentelman MJ | title = Identification of risk loci for necrotizing meningoencephalitis in Pug dogs | journal = The Journal of Heredity | volume = 102 Suppl 1 | issue = 1 | pages = S40–6 | date = 1 September 2011 | pmid = 21846746 | doi = 10.1093/jhered/esr048 | doi-access = free }}&lt;/ref&gt;&lt;ref name=&quot;Suzuki_2003&quot;&gt;{{cite journal | vauthors = Suzuki M, Uchida K, Morozumi M, Hasegawa T, Yanai T, Nakayama H, Tateyama S | title = A comparative pathological study on canine necrotizing meningoencephalitis and granulomatous meningoencephalomyelitis | journal = The Journal of Veterinary Medical Science | volume = 65 | issue = 11 | pages = 1233–9 | date = November 2003 | pmid = 14665754 | doi = 10.1292/jvms.65.1233 | doi-access = free }}&lt;/ref&gt;&lt;ref name=&quot;Park_2012&quot;&gt;{{cite journal | vauthors = Park ES, Uchida K, Nakayama H | title = Comprehensive immunohistochemical studies on canine necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME) | journal = Veterinary Pathology | volume = 49 | issue = 4 | pages = 682–92 | date = July 2012 | pmid = 22262353 | doi = 10.1177/0300985811429311 | doi-access =  }}&lt;/ref&gt; 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.&lt;ref name=&quot;Cordy_1989&quot;&gt;{{cite journal | vauthors = Cordy DR, Holliday TA | title = A necrotizing meningoencephalitis of pug dogs | journal = Veterinary Pathology | volume = 26 | issue = 3 | pages = 191–4 | date = May 1989 | pmid = 2763409 | doi = 10.1177/030098588902600301 | doi-access =  }}&lt;/ref&gt;&lt;ref name=&quot;Suzuki_2003&quot; /&gt;&lt;ref name=&quot;Greer_2009&quot;&gt;{{cite journal | vauthors = Greer KA, Schatzberg SJ, Porter BF, Jones KA, Famula TR, Murphy KE | title = Heritability and transmission analysis of necrotizing meningoencephalitis in the Pug | journal = Research in Veterinary Science | volume = 86 | issue = 3 | pages = 438–42 | date = June 2009 | pmid = 19014875 | doi = 10.1016/j.rvsc.2008.10.002 }}&lt;/ref&gt; It causes intense necrotizing inflammatory lesions in the [[brain]] stem and [[Cerebellum]].&lt;ref name=&quot;Park_2012&quot; /&gt; The cause is still unclear.&lt;ref name=&quot;Talarico_2010&quot;&gt;{{cite journal |vauthors=Talarico LR, Schatzberg SJ |date=March 2010 |title=Idiopathic granulomatous and necrotising inflammatory disorders of the canine central nervous system: a review and future perspectives |journal=The Journal of Small Animal Practice |volume=51 |issue=3 |pages=138–49 |doi=10.1111/j.1748-5827.2009.00823.x |pmid=19814766|doi-access=free }}&lt;/ref&gt; 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.&lt;ref name=&quot;Suzuki_2003&quot; /&gt; The process is rapidly progressive, culminating in [[status epilepticus]] and ending fatally for the dog.&lt;ref name=&quot;Greer_2009&quot; /&gt;

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 [[Autopsy|necropsy]].&lt;ref name=&quot;Talarico_2010&quot; /&gt;

==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.&lt;ref name=&quot;Talarico_2010&quot; /&gt; 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]].&lt;ref name=&quot;Suzuki_2003&quot; /&gt;&lt;ref name=&quot;Cordy_1989&quot; /&gt;&lt;ref name=&quot;Talarico_2010&quot; /&gt;

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 [[convulsion]]s.&lt;ref name=&quot;Kitagawa_2007&quot;&gt;{{cite journal | vauthors = Kitagawa M, Okada M, Kanayama K, Sato T, Sakai T | title = A canine case of necrotizing meningoencephalitis for long-term observation: clinical and MRI findings | journal = The Journal of Veterinary Medical Science | volume = 69 | issue = 11 | pages = 1195–8 | date = November 2007 | pmid = 18057839 | doi=10.1292/jvms.69.1195| s2cid = 33004172 | doi-access = free }}&lt;/ref&gt;

==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 fluid]] (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.&lt;ref name=&quot;Barber_2011&quot; /&gt;&lt;ref name=&quot;Suzuki_2003&quot; /&gt;&lt;ref name=&quot;Kitagawa_2007&quot; /&gt; Despite clinical examination methods, the specific diagnosis of NME depends on a postmortem, histopathological examination of the brain biopsy tissue or a necropsy.&lt;ref name=&quot;Park_2012&quot; /&gt;

==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.&lt;ref name=&quot;Talarico_2010&quot; /&gt;&lt;ref&gt;{{cite journal | vauthors = Cooper JJ, Schatzberg SJ, Vernau KM, Summers BA, Porter BF, Siso S, Young BD, Levine JM | title = Necrotizing meningoencephalitis in atypical dog breeds: a case series and literature review | journal = Journal of Veterinary Internal Medicine | volume = 28 | issue = 1 | pages = 198–203 | date = 2014 | pmid = 24428322 | pmc = 4895549 | doi = 10.1111/jvim.12233 }}&lt;/ref&gt;  The meninges itself is focally thickened by dense aggregations of lymphocytes, plasma cells and macrophages infiltrating due to the reinforced immune answer (perivascular cuffing).&lt;ref&gt;{{cite journal | vauthors = Higgins RJ, Dickinson PJ, Kube SA, Moore PF, Couto SS, Vernau KM, Sturges BK, Lecouteur RA | title = Necrotizing meningoencephalitis in five Chihuahua dogs | journal = Veterinary Pathology | volume = 45 | issue = 3 | pages = 336–46 | date = May 2008 | pmid = 18487490 | doi = 10.1354/vp.45-3-336 }}&lt;/ref&gt;&lt;ref name=&quot;Kuwamura_2002&quot;&gt;{{cite journal | vauthors = Kuwamura M, Adachi T, Yamate J, Kotani T, Ohashi F, Summers BA | title = Necrotising encephalitis in the Yorkshire terrier: a case report and literature review | journal = The Journal of Small Animal Practice | volume = 43 | issue = 10 | pages = 459–63 | date = October 2002 | pmid = 12400645 | doi = 10.1111/j.1748-5827.2002.tb00014.x | doi-access = free }}&lt;/ref&gt;

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.&lt;ref name=&quot;Barber_2011&quot; /&gt; These lesions are selective with a predilection for the cerebral hemisphere.&lt;ref name=&quot;Cordy_1989&quot; /&gt; 

They can be divided into three phases: 

* Acute - mild inflammatory cell infiltration
* Subacute – intense inflammatory reactions
* Chronic – increase of perivascular cuffing, extensive necrosis &lt;ref name=&quot;Kuwamura_2002&quot; /&gt;

Additionally, temporal lobes with dense mononuclear cells can be observed infiltrating the meninges, and cerebellar herniation through the foramen magnum,&lt;ref name=&quot;Park_2012&quot; /&gt; which leads to neurological symptoms like continuous circling or stroke-like seizures.&lt;ref name=&quot;Talarico_2010&quot; /&gt; Attempts at proving a viral etiology have been unsuccessful.&lt;ref name=&quot;Greer_2009&quot; /&gt;

==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.&lt;ref name=&quot;Kuwamura_2002&quot; /&gt; 

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.&lt;ref name=&quot;Kuwamura_2002&quot; /&gt;

==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.&lt;ref name=&quot;Greer_2009&quot; /&gt;&lt;ref name=&quot;Kitagawa_2007&quot; /&gt;

==References==
{{Reflist|30em}}

[[Category:Dog diseases]]