Title: Granulomatous meningoencephalitis

{{Short description|Inflammatory disease of the central nervous system of dogs}}

'''Granulomatous meningoencephalitis''' (GME) is an inflammatory disease of the [[central nervous system]] (CNS) of [[dog]]s and, rarely, [[cat]]s. It is a form of [[meningoencephalitis]].  GME is likely second only to [[encephalitis]] caused by ''[[canine distemper|canine distemper virus]]'' as the most common cause of inflammatory disease of the canine CNS.&lt;ref name=JAVMA&gt;{{cite journal |vauthors=Adamo F, O'Brien R |title=Use of cyclosporine to treat granulomatous meningoencephalitis in three dogs |journal=J Am Vet Med Assoc |volume=225 |issue=8 |pages=1211–6, 1196 |year=2004 |pmid=15521442 |doi=10.2460/javma.2004.225.1211}}&lt;/ref&gt;  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 [[telencephalon|cerebrum]], [[brain stem|brainstem]], [[cerebellum]], and [[spinal cord]].&lt;ref&gt;{{cite journal |vauthors=Suzuki M, Uchida K, Morozumi M, Yanai T, Nakayama H, Yamaguchi R, Tateyama S |title=A comparative pathological study on granulomatous meningoencephalomyelitis and central malignant histiocytosis in dogs |journal=J Vet Med Sci |volume=65 |issue=12 |pages=1319–24 |year=2003 |pmid=14709820 |doi=10.1292/jvms.65.1319|doi-access=free }}&lt;/ref&gt;  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 disease|immune-mediated]] cause, but it is also thought that the disease may be based on an abnormal response to an infectious agent.&lt;ref name=Braund&gt;{{cite web|author=Vite, C.H.|year=2005|title=Inflammatory Diseases of the Central Nervous System|work=Braund's Clinical Neurology in Small Animals: Localization, Diagnosis and Treatment|url=http://www.ivis.org/advances/Vite/braund27/chapter_frm.asp?LA=1|accessdate=2007-02-15}}&lt;/ref&gt;  One study searched for viral [[DNA]] from ''[[canine herpesvirus]]'', ''[[infectious canine hepatitis|canine adenovirus]]'', and ''[[canine parvovirus]]'' in brain tissue from dogs with GME, necrotizing meningoencephalitis, and necrotizing leukoencephalitis (see below for the latter two conditions), but failed to find any.&lt;ref&gt;{{cite journal |vauthors=Schatzberg S, Haley N, Barr S, de Lahunta A, Sharp N |title=Polymerase chain reaction screening for DNA viruses in paraffin-embedded brains from dogs with necrotizing meningoencephalitis, necrotizing leukoencephalitis, and granulomatous meningoencephalitis |journal=J Vet Intern Med |volume=19 |issue=4 |pages=553–9 |year=2005 |pmid=16095173 |doi=10.1892/0891-6640(2005)19[553:PCRSFD]2.0.CO;2|doi-access=free }}&lt;/ref&gt;

==Types of GME==
*Disseminated – This is a diffuse disease throughout the CNS.  It was previously known as '''inflammatory reticulosis'''.  There is an accumulation of [[monocyte|mononuclear cell]]s and [[neutrophil granulocyte|neutrophil]]s around the blood vessels (perivascular) of the CNS.  [[Meningitis]] is seen with this form of GME and causes fever and neck pain.&lt;ref name=Merck&gt;{{cite web | title = Idiopathic Inflammatory Diseases | work = The Merck Veterinary Manual | year = 2006 | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/100710.htm | accessdate = 2007-02-15 }}&lt;/ref&gt;  It has an acute progression over a few weeks.  Symptoms include incoordination, [[pathologic nystagmus|nystagmus]], head tilt, seizures, and depression.&lt;ref name=Braund/&gt;
*Focal – The disease presents as a [[granuloma]], which mimics a tumor.  It usually is found in the cerebrum or [[cerebellum|cerebellopontine angle]].&lt;ref name=Ettinger_1995&gt;{{cite book|author1=Ettinger, Stephen J. |author2=Feldman, Edward C. |title=Textbook of Veterinary Internal Medicine|edition=4th|publisher=W.B. Saunders Company|year=1995|isbn=0-7216-6795-3}}&lt;/ref&gt;  Symptoms may be acute or develop slowly over several months and depend on the location of the lesion.&lt;ref name=Merck/&gt;
*Ocular – This is an uncommon form of GME and is characterized by sudden blindness caused by [[optic neuritis]].  The disease is bilateral.  Ocular GME is considered to be an extension of CNS disease.  The blood vessels of the [[posterior segment]] of the eye and anterior [[uvea]] have the same infiltrates of inflammatory cells as the intracranial vessels.  [[Uveitis]], [[retinal detachment]], and [[secondary glaucoma]] may be seen.&lt;ref name=&quot;Gelatt_1999&quot;&gt;{{Cite book |last=Gelatt |first=Kirk N. |title=Veterinary ophthalmology |publisher=Lippincott Williams &amp; Wilkins |year=1999 |isbn=978-0-683-30076-5 |edition=3rd |location=Philadelphia}}&lt;/ref&gt;

==Diagnosis and treatment==
[[Cerebrospinal fluid]] (CSF) analysis shows a large number of [[white blood cell]]s.  Typically small mature [[lymphocyte]]s are the majority of cells seen, with [[monocytes]] and neutrophils making up the rest.&lt;ref&gt;{{cite web | last = Vernau | first = William | title = Cerebrospinal Fluid Analysis in Dogs and Cats | work = Proceedings of the 50° Congresso Nazionale Multisala SCIVAC | year = 2005 | url = http://www.ivis.org/proceedings/scivac/2005/Vernau5_en.pdf?LA=1 | format = PDF | accessdate = 2007-02-18 }}&lt;/ref&gt;  Definitive diagnosis is based on histopathology, either a brain biopsy or post-mortem evaluation (necropsy).  A [[computed tomography|CT scan]] or [[magnetic resonance imaging|MRI]] will show patchy, diffuse, or multifocal lesions.  For a number of years, the basic treatment was some type of [[corticosteroid]] in combination with one or more immunosuppressive drugs, typically [[cytarabine|cytosine arabinoside]] and/or [[ciclosporin|cyclosporine]] or other medications such as [[azathioprine]], [[cyclophosphamide]],&lt;ref name=Ettinger_1995/&gt; or [[procarbazine]], of which were usually added one at a time to the corticosteroid until a successful combination was found.  There is evidence that treatment with [[radiation therapy]] for focal GME provides the longest periods of [[remission (medicine)|remission]].&lt;ref name=JAVMA/&gt;

== &lt;span id=&quot;Pug Dog encephalitis&quot;&gt;&lt;/span&gt; Pug dog encephalitis ==
'''Pug dog encephalitis''' ('''PDE''') is an idiopathic inflammatory disease primarily affecting the [[prosencephalon]] ([[forebrain]] and [[thalamus]]).  It is also known as [[necrotizing meningoencephalitis]].  The disease may be inherited in [[Pug]]s and [[Maltese (dog)|Maltese]] and has been diagnosed in other breeds as well ([[Yorkshire Terrier|Yorkie]]s, [[Chihuahua (dog)|Chihuahua]]s).&lt;ref name=Ettinger_1995/&gt;  The prevalence of PDE in pugs is about 1%.&lt;ref&gt;{{Cite journal|last1=Greer|first1=K. A.|last2=Wong|first2=A. K.|last3=Liu|first3=H.|last4=Famula|first4=T. R.|last5=Pedersen|first5=N. C.|last6=Ruhe|first6=A.|last7=Wallace|first7=M.|last8=Neff|first8=M. W.|date=April 2010|title=Necrotizing meningoencephalitis of Pug Dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis|journal=Tissue Antigens|volume=76|issue=2|pages=110–8|language=en|doi=10.1111/j.1399-0039.2010.01484.x|pmid=20403140}}&lt;/ref&gt; It differs in [[pathology]] from GME by more tissue breakdown and increased [[eosinophil granulocyte|eosinophil]]s (white blood cells).  CSF analysis is also unique among inflammatory CNS diseases in dogs in that the cells are predominantly [[lymphocyte]]s, instead of a mixed population of mononuclear cells.&lt;ref name=Kent&gt;{{cite journal | last = Higginbotham | first = Michael J. |author2=Kent, Marc |author3=Glass, Eric N. | title = Noninfectious Inflammatory Central Nervous System Diseases in Dogs | journal = Compendium on Continuing Education for the Practicing Veterinarian | volume = 29 | issue = 8 | pages = 488–497 | publisher = Veterinary Learning Systems |date=August 2007 | pmid = 17849703 }}&lt;/ref&gt;  In Maltese and Pugs, there is extensive [[necrosis]] and inflammation of the [[grey matter|gray matter]] of the [[cerebrum]] and subcortical [[white matter]].  The most common early symptoms are related to [[prosencephalon|forebrain]] disease and include [[seizure]]s and [[dementia]], and later circling, head tilt, and blindness with normal [[pupillary light reflex]]es may be seen. PDE has a poor prognosis.

==Necrotizing leukoencephalitis==
In [[Yorkshire Terrier]]s there can be severe mononuclear inflammation of the brainstem and [[Ventricular system|periventricular]] cerebral white matter.  Because the condition in this breed frequently affects only the white matter, it has been called necrotizing leukoencephalitis.  Symptoms of brainstem and central [[Vestibular system|vestibular]] disease predominate.&lt;ref&gt;{{cite web | last = Garosi | first = Laurent S. | title = CNS inflammatory (UK) problems: The neurologist's viewpoint, clinical approach and treatment | work = Proceedings of the 53° Congresso Nazionale Multisala SCIVAC | year = 2006 | url = http://www.ivis.org/proceedings/scivac/2006/garosi3_en.pdf?LA=1 | format = PDF | accessdate = 2007-02-18 }}&lt;/ref&gt;

==Other types of noninfectious meningoencephalitis==
*'''Steroid-responsive meningoencephalitis''' is any noninfectious meningoencephalitis that responds well to [[corticosteroid]]s and usually has an excellent [[prognosis]].  This could represent mild forms of GME or PDE, but there are two separate conditions recognized also.
**'''Steroid-responsive meningitis/arteritis''', also known as '''necrotizing vasculitis''', is seen most commonly in [[Beagle]]s, [[Boxer (dog)|Boxer]]s, [[Bernese Mountain Dog]]s, and [[German Shorthaired Pointer]]s younger than two years of age.&lt;ref name=Chrisman_2003&gt;{{cite book|author1=Chrisman, Cheryl |author2=Clemmons, Roger |author3=Mariani, Christopher |author4=Platt, Simon |title=Neurology for the Small Animal Practitioner|edition=1st|publisher=Teton New Media|year=2003|isbn=1-893441-82-2}}&lt;/ref&gt;  Many cases have fever, loss of appetite, and severe neck pain without other neurologic symptoms, although long-term cases may have incoordination and limb weakness or paralysis.  CSF analysis shows predominantly neutrophils.  In Beagles this condition is also known as '''Beagle pain syndrome'''.&lt;ref name=Braund/&gt;
**'''Eosinophilic meningoencephalomyelitis''' is seen mainly in [[Golden Retriever]]s.&lt;ref name=Chrisman_2003/&gt;  CSF analysis shows predominantly eosinophils.
*An acute progressive '''pyogranulomatous meningoencephalomyelitis''' is seen in mature [[Pointer (dog breed)|Pointer]] dogs.  There is monocytic and neutrophilic infiltration of the [[meninges|leptomeninges]].  Symptoms include incoordination, reluctance to move, and neck rigidity.&lt;ref name=Merck2&gt;{{cite web | title = Meningitis and Encephalitis: Introduction | work = The Merck Veterinary Manual | year = 2006 | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/101600.htm | accessdate = 2007-02-15 }}&lt;/ref&gt;

==See also==
*[[Encephalitis]]
*[[Meningitis]]

==References==
{{Reflist}}

[[Category:Dog diseases]]