Title: Rage syndrome

{{short description|Neurological problem in dogs}}
{{Distinguish|Idiopathic aggression}}
{{Infobox medical condition
 |name            = Rage syndrome
 |synonyms        = A22, episodic dyscontrol, stimulus-responsive psychomotor epilepsy, Mental lapse aggression syndrome
 |image           = MalinoisMWDwithHandler.jpg 
 |image_size      = 
 |alt             = A happy Belgian Malinois interacting with their handler. As a military working dog bred for and trained to utilize aggression, they wear a &quot;DO NOT PET&quot; patch on their collar. Their handler looks into their eyes.
 |image_thumbtime = 
 |caption         = The Malinois was the first breed to have a specific genetic polymorphism linked to rage syndrome.
 |width           = 250px
 |image2          = 
 |image_size2     = 
 |alt2            = 
 |image_thumbtime2 =
 |caption2        = 
 |width2          = 
 |pronounce       = 
 |pronounce 2     = 
 |specialty       = [[Neurology]]
 |symptoms        = {{hlist|[[Fatal dog attacks|Lethal dog attacks]]|[[Dog bites]]|[[Seizures]]}}
 |complications   = Behavioral euthanasia
 |onset           = 1–3 years old
 |duration        = Lifelong
 |types           = 
 |cause           = Unknown
 |risks           = PolyA(22) (in Malinois), DAT-VNTR (in Malinois), likely other genetic factors, breed, other seizures
 |diagnosis       = [[EEG]], with complete exclusion of other medical conditions via thorough medical testing
 |differential    = Any untreated illness (Pathophysiological aggression) or behavioral condition
 |prevention      = Selective breeding, [[Genetic testing|Health testing]] (PolyA(22) test, in Malinois)
 |management       = [[Anticonvulsants]], muzzling, barrier use, lifestyle changes
 |medication      = [[Antiepileptic drugs]] ([[Phenobarbital]])
 |prognosis       = Generally poor
 |frequency       = &lt;!-- also |incidence= or |prevalence= --&gt;
 |deaths          = 
 |named after     = &lt;!-- or |eponym= --&gt;
}}

'''Rage syndrome''' is a rare [[Epilepsy|seizure disorder]] in dogs, characterized by explosive aggression.&lt;ref name=&quot;Beaver 1980&quot;/&gt;&lt;ref name=&quot;Reisner 2005&quot;/&gt;&lt;ref name=&quot;Amat 2009&quot;/&gt; 

It is frequently confused with [[Idiopathic disease|idiopathic aggression]], a term for aggression with no identifiable cause. Rage syndrome is most often a misdiagnosis of dogs with an unrelated, but more common, form of aggression. Although the scientific evidence is limited, it is thought to be genetic in origin, and is heritable.&lt;ref name=&quot;Dodman 1992&quot;/&gt; It is treated with [[antiepileptics]].&lt;ref name=&quot;Bowen 2005&quot;/&gt;

==Names==
Rage syndrome has been known by a variety of names since it was discovered.&lt;ref name=&quot;Beaver 1980&quot;/&gt;&lt;ref name=&quot;Amat 2009&quot;/&gt; Rage syndrome is a colloquial term most often preferred by dog trainers, handlers, and some behavior consultants. Alternative names used by researchers, veterinary scientists, and behavior specialists include mental lapse syndrome (MLS) and episodic dyscontrol.&lt;ref name=&quot;Beaver 1980&quot;/&gt;

Rage syndrome is also sometimes termed a form of epilepsy, particularly limbic epilepsy.&lt;ref name=&quot;Breitschwerdt 1979&quot;/&gt;&lt;ref name=&quot;Hoerlein 1971&quot;/&gt; The term limbic epilepsy for rage syndrome has been used synonymously with the terms psychomotor epilepsy, automatic epilepsy, rhinencephalic epilepsy, behavioral epilepsy, temporal lobe epilepsy, and autonomic epilepsy.&lt;ref name=&quot;Breitschwerdt 1979&quot;/&gt;&lt;ref name=&quot;Hoerlein 1971&quot;/&gt;&lt;ref name=&quot;Lennox 1951&quot;/&gt;&lt;ref name=&quot;Ettinger 1975&quot;/&gt;&lt;ref name=&quot;Parry 1949&quot;/&gt; In addition, depending on the professional's discretion the word &quot;seizure&quot; may be substituted for &quot;epilepsy&quot; in a given study or resource.&lt;ref name=&quot;Hoerlein 1971&quot;/&gt; Edward B. Breitschwerdt, a researcher and veterinarian, wrote that this &quot;profusion of synonyms makes it difficult to clearly ascertain the results of either clinical or research investigations of limbic epilepsy in the dog&quot;.&lt;ref name=&quot;Breitschwerdt 1979&quot;/&gt;

Rage syndrome is frequently confused with [[Idiopathic disease|idiopathic aggression]], a term for aggression with no identifiable cause, due to sharing a name with it in its earliest studies before being identified as a discrete condition. In early research rage syndrome was sometimes referred to as sudden-onset idiopathic aggression (SOIA) to distinguish it from [[idiopathic disease]], and later as sudden-onset aggression (SOA).

Rage syndrome has no medical connection to rabies, for which its name is sometimes mistaken (from the Latin noun {{Lang|la|rabiēs}}, meaning &quot;rage&quot;).

==Characteristics==
Aggression in rage syndrome is characterized by its severity and often [[Fatal dog attacks|fatal to dogs, animals, or people]] it is targeted towards.&lt;ref name=&quot;Beaver 1980&quot;/&gt;  Episodes may cause life-threatening injuries and result in [[disability]] or [[disfigurement]].&lt;ref name=&quot;Beaver 1980&quot;/&gt; 

Dogs with rage syndrome typically have their first rage episode during adolescence, between 1 and 3 years old, similar to dogs with [[Epilepsy in animals|idiopathic epilepsy]].&lt;ref name=&quot;Beaver 1980&quot;/&gt; 

Interictal [[Electroencephalography|EEGs]] under [[general anesthesia]] typically show low-voltage rapid discharges characteristic of [[focal seizures]].&lt;ref name=&quot;Beaver 1980&quot;/&gt;&lt;ref name=&quot;de Curtis 2009&quot;/&gt;&lt;ref name=&quot;Wendling 2003&quot;/&gt; Seizure foci are in the [[temporal lobe]], most often the [[Cerebral hemisphere|left]] temporal lobe.&lt;ref name=&quot;Beaver 1980&quot;/&gt;&lt;ref name=&quot;Bergamasco 2003&quot;/&gt;

==Outcomes== 
Prognosis for treatment of rage syndrome is guarded.&lt;ref name=&quot;Beaver 1980&quot;/&gt; It is treated with [[antiepileptics]].&lt;ref name=&quot;Bowen 2005&quot;/&gt;

==Associated breeds==
{{multiple image
 | width = 120
 | footer = The English Cocker Spaniel, Belgian Malinois, and English Springer Spaniel have been associated with Rage syndrome. 
 | image1 = AKC English Cocker Spaniel Dog.png 
 | alt1 = English Cocker Spaniel
 | image2 = Malinois portrait.jpg
 | alt2 = Belgian Malionis
 | image3 = Black and White English Springer Spaniel.png
 | alt3 = English Springer Spaniel 
}}

=== English Springer Spaniel ===
The [[English Springer Spaniel]] is the origin of the term &quot;Springer Rage&quot; frequently used in the 1970s and 1980s.

English Springer Spaniels were the breed most often referred to [[Animal behavior consultant|dog behavior consultants]] for aggression in the 1980s.&lt;ref name=&quot;Reisner 2005&quot;/&gt;&lt;ref name=&quot;Landsberg 1991&quot;/&gt;&lt;ref name=&quot;Reisner 1989-92&quot;/&gt;

[[Pat Miller (dog trainer)|Pat Miller]] wrote in ''Beware of the Dog: Positive Solutions for Aggressive Behavior in Dogs'' in 2017: &quot;[Rage syndrome] captured the imagination of the dog world, and soon every dog with episodes of sudden, explosive aggression was tagged with the unfortunate &quot;rage syndrome&quot; label, especially if it was a Spaniel of any type.&quot;&lt;ref name=&quot;Miller 2016 non-biomedical&quot;/&gt;

=== Other breeds ===
Bull terriers have also been used in research studies on breed-specific hereditary focal seizures, sometimes including [[aggressive]] symptoms.&lt;ref name=&quot;Dodman 1996&quot;/&gt;

==Diagnosis==

Rage syndrome is diagnosed by EEG.&lt;ref name=&quot;Beaver 1980&quot;/&gt;&lt;ref name=&quot;Dodman 1992&quot;/&gt;&lt;ref name=&quot;Bergamasco 2003&quot;/&gt;

Thyroid function is [[Thyroid function tests|tested]] during typical diagnostic workups as thyroid conditions, most commonly [[Hypothyroidism|hypo-]] and [[hyperthyroidism]], have been suggested to cause pathophysiological aggression that may present similarly to Rage syndrome.&lt;ref name=&quot;Beaver 1980&quot;/&gt;&lt;ref name=&quot;Fatjó 2002&quot;/&gt;
==In other animals==
In 2002 a 4-month-old tigress was reported with symptoms analogous to rage syndrome.&lt;ref name=&quot;Bergamasco 2003&quot;/&gt; The tigress had episodes between 30 seconds and a minute long of explosive self-directed aggression and self-mutilation, in addition to occasional [[generalized seizures|generalized tonic-clonic seizures]] and both [[Focal neurologic signs|focal]] and generalized neurologic symptoms such as episodes of continuously walking in circles to the right and [[Cortical blindness|epileptic blindness]]. Her EEG showed left frontal-temporal epileptiform activity, confirming a diagnosis of complex partial seizures. [[Lumbar puncture|Cerebrospinal fluid testing]], [[Hematology|hematologic testing]], [[Serology|serotologic testing]], and serum biochemistry profile were all normal aside from [[Pandy's test|faintly elevated CSF proteins]]. The tigress was the result of a [[Inbreeding|consanguineous breeding]] and one of her littermates was diagnosed with generalized seizures. She was successfully treated with [[phenobarbital]] (2.5 mg/kg by mouth twice a day, bringing her within the therapeutic range at a blood concentration of 24 mg/dl).&lt;ref name=&quot;Bergamasco 2003&quot;/&gt;

==Superseded theories== 
In 1980 it was suggested that [[electroconvulsive therapy]], [[Lobotomy|prefrontal lobotomy]], and [[Cerebral hypoxia|partial cerebral hypoxia (hypoxic-anoxic brain injury)]] be used to treat rage syndrome.&lt;ref name=&quot;Beaver 1980&quot;/&gt; A 1974 study on prefrontal lobotomy of aggressive dogs found that 50% of lobotomized dogs died of complications.&lt;ref name=&quot;Allen 1974&quot;/&gt; Surviving dogs developed [[seizures]], [[Fecal incontinence|fecal]] and [[urinary incontinence]], [[confusion]], [[memory loss]], [[Seroma|seromas]], [[emotional dysregulation]], focal neurologic symptoms, [[paresis|weakness]], and [[weight loss]].&lt;ref name=&quot;Allen 1974&quot;/&gt; 40% of surviving dogs did not have a reduction in existing aggression, and some dogs' aggression worsened after the procedure.&lt;ref name=&quot;Allen 1974&quot;/&gt; The treatments were described as [[heroic measures]] which caused further damage to the dogs' health but were undertaken as a last resort to preserve the lives of the dogs. Multiple dogs which did not die from the procedure itself were euthanized anyway.&lt;ref name=&quot;Allen 1974&quot;/&gt;

==See also==
* [[Phenobarbital]]
* [[List of fatal dog attacks]]
* [[Causes of seizures]]
* [[Animal euthanasia]]

==References==
&lt;references&gt;

&lt;ref name=&quot;Beaver 1980&quot;&gt;{{cite journal | last=B.V. | first=Beaver | title=Mental lapse aggression syndrome [Dogs]. | journal=Journal of the American Animal Hospital Association | date=1980 | issn=0587-2871 | url=https://agris.fao.org/agris-search/search.do?recordID=US19820738566 | access-date=21 May 2023 | page=937-939 }}&lt;/ref&gt;

&lt;ref name=&quot;Dodman 1992&quot;&gt;{{Cite journal | pmid = 1289339 | year = 1992 | author1 = Dodman | first2 = K. A. | first3 = K. | first4 = J. G. | first5 = L. | title = Phenobarbital-responsive episodic dyscontrol (rage) in dogs | volume = 201 | issue = 10 | pages = 1580–1583 | journal = Journal of the American Veterinary Medical Association | last2 = Miczek | last3 = Knowles | last4 = Thalhammer | last5 = Shuster| doi = 10.2460/javma.1992.201.10.1580 }}&lt;/ref&gt;

&lt;ref name=&quot;Reisner 2005&quot;&gt;{{cite journal | last1=Reisner | first1=Ilana R. | last2=Houpt | first2=Katherine A. | last3=Shofer | first3=Frances S. | title=National survey of owner-directed aggression in English Springer Spaniels | journal=Journal of the American Veterinary Medical Association | volume=227 | issue=10 | date=1 Nov 2005 | issn=0003-1488 | doi=10.2460/javma.2005.227.1594 | pages=1594–1603| pmid=16313036 }}&lt;/ref&gt;

&lt;ref name=&quot;Amat 2009&quot;&gt;{{cite journal | last1=Amat | first1=Marta | last2=Manteca | first2=Xavier | last3=Mariotti | first3=Valentina M. | last4=Ruiz de la Torre | first4=José Luís | last5=Fatjó | first5=Jaume | title=Aggressive behavior in the English cocker spaniel | journal=Journal of Veterinary Behavior | volume=4 | issue=3 | year=2009 | issn=1558-7878 | doi=10.1016/j.jveb.2008.08.010 | pages=111–117}}&lt;/ref&gt;

&lt;ref name=&quot;Bergamasco 2003&quot;&gt;{{cite journal | last1=L | first1=Bergamasco | last2=A | first2=Accatino | last3=S | first3=Cizinauskas | last4=A | first4=Jaggy | title=Bit-mapped quantitative EEG analysis in a tiger (Tiger felis) with partial seizures: a case report | journal=Functional Neurology | year=2003 | volume=18 | issue=1 | pages=35–38 | issn=0393-5264 | pmid=12760412 }}&lt;/ref&gt;

&lt;ref name=&quot;de Curtis 2009&quot;&gt;{{cite journal | last1=de Curtis | first1=Marco | last2=Gnatkovsky | first2=Vadym | title=Reevaluating the mechanisms of focal ictogenesis: The role of low-voltage fast activity | journal=Epilepsia | volume=50 | issue=12 | year=2009 | issn=0013-9580 | doi=10.1111/j.1528-1167.2009.02249.x | pages=2514–2525| pmid=19674056 | s2cid=19159688 | doi-access=free }}&lt;/ref&gt;

&lt;ref name=&quot;Wendling 2003&quot;&gt;{{cite journal | last1=Wendling | first1=F. | last2=Bartolomei | first2=F. | last3=Bellanger | first3=J. J. | last4=Bourien | first4=J. | last5=Chauvel | first5=P. | title=Epileptic fast intracerebral EEG activity: evidence for spatial decorrelation at seizure onset | journal=Brain | volume=126 | issue=6 | year=2003 | issn=1460-2156 | doi=10.1093/brain/awg144 | pages=1449–1459| pmid=12764064 | pmc=2040489 }}&lt;/ref&gt;

&lt;ref name=&quot;Parry 1949&quot;&gt;{{cite journal | last=Parry | first=H.B. | date=15 Jan 1949 | title=Epileptic states in the dog, with special reference to canine-hysteria | journal=The Veterinary Record | volume=61 | issue=3 | pages=23–31 | issn=0042-4900 | pmid=18111927 }}&lt;/ref&gt;

&lt;ref name=&quot;Lennox 1951&quot;&gt;{{cite journal | last=Lennox | first=W. G. | title=Phenomena and Correlates of the Psychomotor Triad | journal=Neurology | volume=1 | issue=9–10 | date=1 Sep 1951 | issn=0028-3878 | doi=10.1212/wnl.1.9-10.357 | pages=357–371| pmid=14863538 | s2cid=37537725 }}&lt;/ref&gt;

&lt;ref name=&quot;Fatjó 2002&quot;&gt;{{cite journal | last1=Fatjó | first1=J. | last2=Stub | first2=C. | last3=Manteca | first3=X. | title=Four cases of aggression and hypothyroidism in dogs | journal=Veterinary Record | volume=151 | issue=18 | year=2002 | issn=0042-4900 | doi=10.1136/vr.151.18.547 | pages=547–548| pmid=12448494 | s2cid=27110605 }}&lt;/ref&gt;

&lt;ref name=&quot;Breitschwerdt 1979&quot;&gt;{{cite journal | last1=E.B. | first1=Breitschwerdt | last2=J.E. | first2=Breazile | last3=J.J. | first3=Broadhurst | title=Clinical and electroencepahlographic findings associated with ten cases of suspected limbic epilepsy in the dog. | journal=Journal of the American Animal Hospital Association | date=1979 | issn=0587-2871 | url=https://agris.fao.org/agris-search/search.do?recordID=US19800522296 | access-date=4 Jun 2023 | page=}}&lt;/ref&gt;

&lt;ref name=&quot;Ettinger 1975&quot;&gt;{{cite book | last=Ettinger | first=S.J. | title=Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat | publisher=Saunders | issue=v. 2 | year=1975 | isbn=978-0-7216-3425-8 | url=https://books.google.com/books?id=tUptAAAAMAAJ | access-date=4 Jun 2023 | page=375-400 }}&lt;/ref&gt;

&lt;ref name=&quot;Landsberg 1991&quot;&gt;{{cite journal | last=Landsberg | first=G.M. | title=The distribution of canine behavior cases at three behavior referral practices | journal=Veterinary Medicine | date=1991 | issn=8750-7943 | url=https://agris.fao.org/agris-search/search.do?recordID=US9145217 | access-date=3 Jun 2023 | page=}}&lt;/ref&gt;

&lt;ref name=&quot;Reisner 1989-92&quot;&gt;{{cite journal | last1=IR | first1=Reisner | last2=HN | first2=Erb | last3=KA | first3=Houpt | title=Risk factors for behavior-related euthanasia among dominant-aggressive dogs: 110 cases (1989-1992) | journal=Journal of the American Veterinary Medical Association | date=15 September 1994  | volume=205 | issue=6 | pages=855–863 | doi=10.2460/javma.1994.205.06.855 | issn=0003-1488 | pmid=7829381 }}&lt;/ref&gt;

&lt;ref name=&quot;Allen 1974&quot;&gt;{{cite journal | last1=BD | first1=Allen | last2=JF | first2=Cummings | last3=A | first3=De Lahunta | title=The effects of prefrontal lobotomy on aggressive behavior in dogs  | journal=The Cornell Veterinarian | date=April 1974 | volume=64 | issue=2 | pages=201–216 | issn=0010-8901 | pmid=4207830 }}&lt;/ref&gt;

&lt;ref name=&quot;Miller 2016 non-biomedical&quot;&gt;{{cite book | last=Miller | first=P. | title=Beware of the Dog: Positive Solutions for Aggressive Behavior in Dogs | publisher=Dogwise Publishing | year=2016 | isbn=978-1-61781-193-7 | url=https://books.google.com/books?id=JSUpvgAACAAJ | access-date=4 Jun 2023 | page=}}&lt;/ref&gt;

&lt;ref name=&quot;Hoerlein 1971&quot;&gt;{{cite book | last=Hoerlein | first=B. F. | title=Canine Neurology, Diagnosis and Treatment | date=1971 | publisher=Saunders | isbn=0-7216-4711-1 }}&lt;/ref&gt;

&lt;ref name=&quot;Bowen 2005&quot;&gt;{{Cite book|last=Bowen|first=Jon|author2=Heath, Sarah |title=Behaviour problems in small animals: practical advice for the veterinary team|url=https://archive.org/details/behaviourproblem00bowe|url-access=limited|edition=Paperback|date=October 2005|publisher=Saunders Ltd|isbn=0-7020-2767-7|page=[https://archive.org/details/behaviourproblem00bowe/page/n52 55]}}&lt;/ref&gt;

&lt;ref name=&quot;Dodman 1996&quot;&gt;{{cite journal | title=Behavioral changes associated with suspected complex partial seizures in bull terriers  |last1=NH | first1=Dodman | last2=KE | first2=Knowles | last3=L | first3=Shuster | last4=AA | first4=Moon-Fanelli | last5=AS | first5=Tidwell | last6=CL | first6=Keen | journal=Journal of the American Veterinary Medical Association |date=March 1996 | volume=208 | issue=5 |pages=688–691 |doi=10.2460/javma.1996.208.05.688 | issn=0003-1488 | pmid=8617623 }}&lt;/ref&gt;

&lt;/references&gt;

== Further reading ==
* {{cite journal | last1=Van Buren | first1=Samantha L. | last2=Oberbauer | first2=Anita M. | last3=Minor | first3=Katie M. | last4=Belanger | first4=Janelle M. | last5=Furrow | first5=Eva | title=Association analysis of dopamine transporter gene ( SLC6A3 ) variants with risk for seizures and aggression in Border Collies | journal=Animal Genetics | volume=52 | issue=4 | date=3 Jun 2021 | issn=0268-9146 | doi=10.1111/age.13097 | pages=573–574 | pmid=34081804 | pmc=8274409 }}
* {{cite journal | last1=Lit | first1=Lisa | last2=Belanger | first2=Janelle M. | last3=Boehm | first3=Debby | last4=Lybarger | first4=Nathan | last5=Oberbauer | first5=Anita M. | title=Differences in Behavior and Activity Associated with a Poly(A) Expansion in the Dopamine Transporter in Belgian Malinois | journal=PLOS ONE | volume=8 | issue=12 | date=23 Dec 2013 | issn=1932-6203 | doi=10.1371/journal.pone.0082948 | article-number=e82948 | pmid=24376613 | pmc=3871558 | bibcode=2013PLoSO...882948L | doi-access=free }}
* {{cite journal | last1=Lit | first1=Lisa | last2=Belanger | first2=Janelle M | last3=Boehm | first3=Debby | last4=Lybarger | first4=Nathan | last5=Haverbeke | first5=Anouck | last6=Diederich | first6=Claire | last7=Oberbauer | first7=Anita M | title=Characterization of a dopamine transporter polymorphism and behavior in Belgian Malinois | journal=BMC Genetics | volume=14 | issue=1 | date=30 May 2013 | issn=1471-2156 | doi=10.1186/1471-2156-14-45 | page=45 | pmid=23718893 | pmc=3680094 | s2cid=255789870 | doi-access=free }}
* {{cite journal | last1=Lit | first1=Lisa | last2=Belanger | first2=J. M. | last3=Boehm | first3=D. | last4=Lybarger | first4=N. | last5=Oberbauer | first5=A. M. | title=Dopamine transporter single nucleotide polymorphisms (SNPs) in Belgian Malinois dogs | journal=Animal Genetics | volume=44 | issue=5 | date=9 Apr 2013 | issn=0268-9146 | doi=10.1111/age.12040 | pages=604–605 | pmid=23565797 | url=https://onlinelibrary.wiley.com/doi/10.1111/age.12040 | url-access=subscription }}
* {{cite journal | first1=NH | last1=Dodman | first2=KE | last2=Knowles | first3=L | last3=Shuster | first4=AA | last4=Moon-Fanelli | first5=AS | last5=Tidwell | first6=CL | last6=Keen | journal=Journal of the American Veterinary Medical Association | volume=208 | issue=5 | issn=0003-1488 | pmid=8617623 | title=Behavioral changes associated with suspected complex partial seizures in bull terriers | date=1 Mar 1996| pages=688–691 | doi=10.2460/javma.1996.208.05.688 }}
* {{cite journal | pmid = 1289339 | year = 1992 | author1 = Dodman | first2 = K. A. | first3 = K. | first4 = J. G. | first5 = L. | title = Phenobarbital-responsive episodic dyscontrol (rage) in dogs | volume = 201 | issue = 10 | pages = 1580–1583 | journal = Journal of the American Veterinary Medical Association | last2 = Miczek | last3 = Knowles | last4 = Thalhammer | last5 = Shuster | doi = 10.2460/javma.1992.201.10.1580 }}
* {{cite journal | last=B.V. | first=Beaver | title=Mental lapse aggression syndrome [Dogs]. | journal=Journal of the American Animal Hospital Association | date=1980 | issn=0587-2871 | url=https://archive.org/details/sim_journal-of-the-american-animal-hospital-association_november-december-1980_16_6/mode/1up?view=theater | access-date=22 May 2023 |volume=16 |issue=6 | page=937-939 }}

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[[Category:Neurological disorders]]
[[Category:Syndromes in dogs]]
[[Category:Disorders causing seizures]]