Rage syndrome: Difference between revisions

Rage syndrome
Rage syndrome
Other names	A22, episodic dyscontrol, stimulus-responsive psychomotor epilepsy, Mental lapse aggression syndrome
	The Malinois was the first breed to have a specific genetic polymorphism linked to rage syndrome.
Specialty	Neurology
Symptoms	Lethal dog attacks; Dog bites; Seizures;
Complications	Behavioral euthanasia
Usual onset	1–3 years old
Duration	Lifelong
Causes	Unknown
Risk factors	PolyA(22) (in Malinois), DAT-VNTR (in Malinois), likely other genetic factors, breed, other seizures
Diagnostic method	EEG, with complete exclusion of other medical conditions via thorough medical testing
Differential diagnosis	Any untreated illness (Pathophysiological aggression) or behavioral condition
Prevention	Selective breeding, Health testing (PolyA(22) test, in Malinois)
Management	Anticonvulsants, muzzling, barrier use, lifestyle changes
Medication	Antiepileptic drugs (Phenobarbital)
Prognosis	Generally poor

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Rage syndrome is a rare seizure disorder in dogs, characterized by explosive aggression.^[1]^[2]^[3]

It is frequently confused with 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.^[4] It is treated with antiepileptics.^[5]

Names

Rage syndrome has been known by a variety of names since it was discovered.^[1]^[3] 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.^[1]

Rage syndrome is also sometimes termed a form of epilepsy, particularly limbic epilepsy.^[6]^[7] 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.^[6]^[7]^[8]^[9]^[10] In addition, depending on the professional's discretion the word "seizure" may be substituted for "epilepsy" in a given study or resource.^[7] Edward B. Breitschwerdt, a researcher and veterinarian, wrote that this "profusion of synonyms makes it difficult to clearly ascertain the results of either clinical or research investigations of limbic epilepsy in the dog".^[6]

Rage syndrome is frequently confused with 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 is 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 rabiēs, meaning "rage").

Characteristics

Aggression in rage syndrome is characterized by its severity and often fatal to dogs, animals, or people it is targeted towards.^[1] Episodes may cause life-threatening injuries and result in disability or disfigurement.^[1]

Dogs with rage syndrome typically have their first rage episode during adolescence, between 1 and 3 years old, similar to dogs with idiopathic epilepsy.^[1]

Interictal EEGs under general anesthesia typically show low-voltage rapid discharges characteristic of focal seizures.^[1]^[11]^[12] Seizure foci are in the temporal lobe, most often the left temporal lobe.^[1]^[13]

Outcomes

Prognosis for treatment of rage syndrome is guarded.^[1] It is treated with antiepileptics.^[5]

Associated breeds

The English Cocker Spaniel, Belgian Malinois, and English Springer Spaniel have been associated with Rage syndrome.

English Springer Spaniel

The English Springer Spaniel is the origin of the term "Springer Rage" frequently used in the 1970s and 1980s.

English Springer Spaniels were the breed most often referred to dog behavior consultants for aggression in the 1980s.^[2]^[14]^[15]

Pat Miller wrote in Beware of the Dog: Positive Solutions for Aggressive Behavior in Dogs in 2017: "[Rage syndrome] captured the imagination of the dog world, and soon every dog with episodes of sudden, explosive aggression was tagged with the unfortunate "rage syndrome" label, especially if it was a Spaniel of any type."^[16]

Other breeds

Bull terriers have also been used in research studies on breed-specific hereditary focal seizures, sometimes including aggressive symptoms.^[17]

Diagnosis

Rage syndrome is diagnosed by EEG.^[1]^[4]^[13]

Thyroid function is tested during typical diagnostic workups as thyroid conditions, most commonly hypo- and hyperthyroidism, have been suggested to cause pathophysiological aggression that may present similarly to Rage syndrome.^[1]^[18]

In other animals

In 2002 a 4-month-old tigress was reported with symptoms analogous to rage syndrome.^[13] The tigress had episodes between 30 seconds and a minute long of explosive self-directed aggression and self-mutilation, in addition to occasional generalized tonic-clonic seizures and both focal and generalized neurologic symptoms such as episodes of continuously walking in circles to the right and epileptic blindness. Her EEG showed left frontal-temporal epileptiform activity, confirming a diagnosis of complex partial seizures. Cerebrospinal fluid testing, hematologic testing, serotologic testing, and serum biochemistry profile were all normal aside from faintly elevated CSF proteins. The tigress was the result of a 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).^[13]

Superseded theories

In 1980 it was suggested that electroconvulsive therapy, prefrontal lobotomy, and partial cerebral hypoxia (hypoxic-anoxic brain injury) be used to treat rage syndrome.^[1] A 1974 study on prefrontal lobotomy of aggressive dogs found that 50% of lobotomized dogs died of complications.^[19] Surviving dogs developed seizures, fecal and urinary incontinence, confusion, memory loss, seromas, emotional dysregulation, focal neurologic symptoms, weakness, and weight loss.^[19] 40% of surviving dogs did not have a reduction in existing aggression, and some dogs' aggression worsened after the procedure.^[19] 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.^[19]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l B.V., Beaver (1980). "Mental lapse aggression syndrome [Dogs]". Journal of the American Animal Hospital Association: 937-939. ISSN 0587-2871. Retrieved 21 May 2023.
^ ^a ^b Reisner, Ilana R.; Houpt, Katherine A.; Shofer, Frances S. (1 November 2005). "National survey of owner-directed aggression in English Springer Spaniels". Journal of the American Veterinary Medical Association. 227 (10): 1594–1603. doi:10.2460/javma.2005.227.1594. ISSN 0003-1488. PMID 16313036.
^ ^a ^b Amat, Marta; Manteca, Xavier; Mariotti, Valentina M.; Ruiz de la Torre, José Luís; Fatjó, Jaume (2009). "Aggressive behavior in the English cocker spaniel". Journal of Veterinary Behavior. 4 (3): 111–117. doi:10.1016/j.jveb.2008.08.010. ISSN 1558-7878.
^ ^a ^b Dodman; Miczek, K. A.; Knowles, K.; Thalhammer, J. G.; Shuster, L. (1992). "Phenobarbital-responsive episodic dyscontrol (rage) in dogs". Journal of the American Veterinary Medical Association. 201 (10): 1580–1583. doi:10.2460/javma.1992.201.10.1580. PMID 1289339.
^ ^a ^b Bowen, Jon; Heath, Sarah (October 2005). Behaviour problems in small animals: practical advice for the veterinary team (Paperback ed.). Saunders Ltd. p. 55. ISBN 0-7020-2767-7.
^ ^a ^b ^c E.B., Breitschwerdt; J.E., Breazile; J.J., Broadhurst (1979). "Clinical and electroencepahlographic findings associated with ten cases of suspected limbic epilepsy in the dog". Journal of the American Animal Hospital Association. ISSN 0587-2871. Retrieved 4 June 2023.
^ ^a ^b ^c Hoerlein, B. F. (1971). Canine Neurology, Diagnosis and Treatment. Saunders. ISBN 0-7216-4711-1.
^ Lennox, W. G. (1 September 1951). "Phenomena and Correlates of the Psychomotor Triad". Neurology. 1 (9–10): 357–371. doi:10.1212/wnl.1.9-10.357. ISSN 0028-3878. PMID 14863538. S2CID 37537725.
^ Ettinger, S.J. (1975). Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. Saunders. p. 375-400. ISBN 978-0-7216-3425-8. Retrieved 4 June 2023.
^ Parry, H.B. (15 January 1949). "Epileptic states in the dog, with special reference to canine-hysteria". The Veterinary Record. 61 (3): 23–31. ISSN 0042-4900. PMID 18111927. Retrieved 4 June 2023.
^ de Curtis, Marco; Gnatkovsky, Vadym (2009). "Reevaluating the mechanisms of focal ictogenesis: The role of low-voltage fast activity". Epilepsia. 50 (12): 2514–2525. doi:10.1111/j.1528-1167.2009.02249.x. ISSN 0013-9580. PMID 19674056. S2CID 19159688.
^ Wendling, F.; Bartolomei, F.; Bellanger, J. J.; Bourien, J.; Chauvel, P. (2003). "Epileptic fast intracerebral EEG activity: evidence for spatial decorrelation at seizure onset". Brain. 126 (6): 1449–1459. doi:10.1093/brain/awg144. ISSN 1460-2156. PMC 2040489. PMID 12764064.
^ ^a ^b ^c ^d L, Bergamasco; A, Accatino; S, Cizinauskas; A, Jaggy (2003). "Bit-mapped quantitative EEG analysis in a tiger (Tiger felis) with partial seizures: a case report". Functional Neurology. 18 (1): 35–38. ISSN 0393-5264. PMID 12760412. Retrieved 22 May 2023.
^ Landsberg, G.M. (1991). "The distribution of canine behavior cases at three behavior referral practices". Veterinary Medicine. ISSN 8750-7943. Retrieved 3 June 2023.
^ IR, Reisner; HN, Erb; KA, Houpt (15 September 1994). "Risk factors for behavior-related euthanasia among dominant-aggressive dogs: 110 cases (1989-1992)". Journal of the American Veterinary Medical Association. 205 (6): 855–863. doi:10.2460/javma.1994.205.06.855. ISSN 0003-1488. PMID 7829381. Retrieved 3 June 2023.
^ Miller, P. (2016). Beware of the Dog: Positive Solutions for Aggressive Behavior in Dogs. Dogwise Publishing. ISBN 978-1-61781-193-7. Retrieved 4 June 2023.
^ NH, Dodman; KE, Knowles; L, Shuster; AA, Moon-Fanelli; AS, Tidwell; CL, Keen (March 1996). "Behavioral changes associated with suspected complex partial seizures in bull terriers". Journal of the American Veterinary Medical Association. 208 (5): 688–691. doi:10.2460/javma.1996.208.05.688. ISSN 0003-1488. PMID 8617623. Retrieved 20 June 2023.
^ Fatjó, J.; Stub, C.; Manteca, X. (2002). "Four cases of aggression and hypothyroidism in dogs". Veterinary Record. 151 (18): 547–548. doi:10.1136/vr.151.18.547. ISSN 0042-4900. PMID 12448494. S2CID 27110605.
^ ^a ^b ^c ^d BD, Allen; JF, Cummings; A, De Lahunta (April 1974). "The effects of prefrontal lobotomy on aggressive behavior in dogs". The Cornell Veterinarian. 64 (2): 201–216. ISSN 0010-8901. PMID 4207830. Retrieved 4 June 2023.

@@ Line 39: / Line 39: @@
 '''Rage syndrome''' is a rare [[Epilepsy|seizure disorder]] in dogs, characterized by explosive aggression.<ref name="Beaver 1980"/><ref name="Reisner 2005"/><ref name="Amat 2009"/>
-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. <ref name="Dodman 1992"/> It is treated with [[antiepileptics]].<ref name="Bowen 2005"/>
+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.<ref name="Dodman 1992"/> It is treated with [[antiepileptics]].<ref name="Bowen 2005"/>
 ==Names==
@@ Line 48: / Line 48: @@
 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 is 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 "rabiēs", meaning "rage").
+Rage syndrome has no medical connection to rabies, for which its name is sometimes mistaken (from the Latin noun {{Lang|la|rabiēs}}, meaning "rage").
 ==Characteristics==
@@ Line 60: / Line 60: @@
 Prognosis for treatment of rage syndrome is guarded.<ref name="Beaver 1980"/> It is treated with [[antiepileptics]].<ref name="Bowen 2005"/>
-==Risk factors==
+==Associated breeds==
 {{multiple image
  | width = 120
@@ Line 72: / Line 72: @@
 }}
+=== English Springer Spaniel ===
-===Associated breeds===
+The [[English Springer Spaniel]] is the origin of the term "Springer Rage" 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.<ref name="Reisner 2005"/><ref name="Landsberg 1991"/><ref name="Reisner 1989-92"/>
-====English Springer Spaniel====
-The [[English Springer Spaniel]] is the origin of the term "Springer Rage" frequently used in the 70s and 80s.
-English Springer Spaniels were the breed most often referred to [[Animal behavior consultant|dog behavior consultants]] for aggression in the 80s.<ref name="Reisner 2005"/><ref name="Landsberg 1991"/><ref name="Reisner 1989-92"/>
 [[Pat Miller (dog trainer)|Pat Miller]] wrote in ''Beware of the Dog: Positive Solutions for Aggressive Behavior in Dogs'' in 2017: "[Rage syndrome] captured the imagination of the dog world, and soon every dog with episodes of sudden, explosive aggression was tagged with the unfortunate "rage syndrome" label, especially if it was a Spaniel of any type."<ref name="Miller 2016 non-biomedical"/>
-====Other breeds====
+=== Other breeds ===
 Bull terriers have also been used in research studies on breed-specific hereditary focal seizures, sometimes including [[aggressive]] symptoms.<ref name="Dodman 1996"/>
@@ Line 90: / Line 86: @@
 Rage syndrome is diagnosed by EEG.<ref name="Beaver 1980"/><ref name="Dodman 1992"/><ref name="Bergamasco 2003"/>
-===Differential diagnosis===
-====Endocrine====
 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.<ref name="Beaver 1980"/><ref name="Fatjó 2002"/>
 ==In other animals==
+In 2002 a 4-month-old tigress was reported with symptoms analogous to rage syndrome.<ref name="Bergamasco 2003"/> 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).<ref name="Bergamasco 2003"/>
-===In other mammals===
-In 2002 a 4-month-old tigress was reported with symptoms analogous to Rage syndrome.<ref name="Bergamasco 2003"/> 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).<ref name="Bergamasco 2003"/>
 ==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.<ref name="Beaver 1980"/> A 1974 study on prefrontal lobotomy of aggressive dogs found that 50% of lobotomized dogs died of complications.<ref name="Allen 1974"/> 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]].<ref name="Allen 1974"/> 40% of surviving dogs did not have a reduction in existing aggression, and some dogs' aggression worsened after the procedure.<ref name="Allen 1974"/> 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 anyways.<ref name="Allen 1974"/>
+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.<ref name="Beaver 1980"/> A 1974 study on prefrontal lobotomy of aggressive dogs found that 50% of lobotomized dogs died of complications.<ref name="Allen 1974"/> 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]].<ref name="Allen 1974"/> 40% of surviving dogs did not have a reduction in existing aggression, and some dogs' aggression worsened after the procedure.<ref name="Allen 1974"/> 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.<ref name="Allen 1974"/>
 ==See also==
@@ Line 111: / Line 102: @@
 {{reflist|refs=
-<ref name="Beaver 1980">{{cite journal | last=B.V. | first=Beaver | title=Mental lapse aggression syndrome [Dogs]. | journal=Journal 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 }}</ref>
+<ref name="Beaver 1980">{{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 }}</ref>
-<ref name="Dodman 1992">{{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}}</ref>
+<ref name="Dodman 1992">{{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 }}</ref>
 <ref name="Reisner 2005">{{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 }}</ref>
@@ Line 121: / Line 112: @@
 <ref name="Bergamasco 2003">{{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 | url=https://pubmed.ncbi.nlm.nih.gov/12760412/ | access-date=22 May 2023 }}</ref>
-<ref name="de Curtis 2009">{{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 }}</ref>
+<ref name="de Curtis 2009">{{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 }}</ref>
 <ref name="Wendling 2003">{{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 }}</ref>
@@ Line 131: / Line 122: @@
 <ref name="Fatjó 2002">{{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 }}</ref>
-<ref name="Breitschwerdt 1979">{{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 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=}}</ref>
+<ref name="Breitschwerdt 1979">{{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=}}</ref>
-<ref name="Ettinger 1975">{{cite book | last=Ettinger | first=S.J. | title=Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat | publisher=Saunders | series=Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat | 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 }}</ref>
+<ref name="Ettinger 1975">{{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 }}</ref>
 <ref name="Landsberg 1991">{{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=}}</ref>
-<ref name="Reisner 1989-92">{{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 | issn=0003-1488 | pmid=7829381 | url=https://pubmed.ncbi.nlm.nih.gov/7829381/ | access-date=3 Jun 2023 }}</ref>
+<ref name="Reisner 1989-92">{{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 | url=https://pubmed.ncbi.nlm.nih.gov/7829381/ | access-date=3 Jun 2023 }}</ref>
 <ref name="Allen 1974">{{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 | url=https://pubmed.ncbi.nlm.nih.gov/4207830/ | access-date=4 Jun 2023 }}</ref>
@@ Line 143: / Line 134: @@
 <ref name="Miller 2016 non-biomedical">{{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=}}</ref>
-<ref name="Hoerlein 1971">{{cite book | last=Hoerlein | first=B. F. | title=Canine Neurology, Diagnosis and Treatment | date=1971 | isbn=0-7216-4711-1 }}</ref>
+<ref name="Hoerlein 1971">{{cite book | last=Hoerlein | first=B. F. | title=Canine Neurology, Diagnosis and Treatment | date=1971 | publisher=Saunders | isbn=0-7216-4711-1 }}</ref>
 <ref name="Bowen 2005">{{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]}}</ref>
-<ref name="Dodman 1996">{{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 | issn=0003-1488 | pmid=8617623 | url=https://pubmed.ncbi.nlm.nih.gov/8617623/ | access-date=20 Jun 2023 }}</ref>
+<ref name="Dodman 1996">{{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 | url=https://pubmed.ncbi.nlm.nih.gov/8617623/ | access-date=20 Jun 2023 }}</ref>
 }}
@@ Line 153: / Line 144: @@
 == 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 | page=e82948 | pmid=24376613 | pmc=3871558 | doi-access=free }}
+* {{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 | page=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 }}
+* {{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 }}
-* {{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 | url=https://pubmed.ncbi.nlm.nih.gov/8617623/ | access-date=4 Jun 2023 | title=Behavioral changes associated with suspected complex partial seizures in bull terriers | date=1 Mar 1996| pages=688–691 }}
+* {{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 | url=https://pubmed.ncbi.nlm.nih.gov/8617623/ | access-date=4 Jun 2023 | 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 | url=https://pubmed.ncbi.nlm.nih.gov/1289339/ | access-date=22 May 2023}}
+* {{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 | url=https://pubmed.ncbi.nlm.nih.gov/1289339/ | access-date=22 May 2023}}
-* {{cite journal | last=B.V. | first=Beaver | title=Mental lapse aggression syndrome [Dogs]. | journal=Journal 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 }}
+* {{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 }}
 {{Use dmy dates|date=August 2019}}

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