Q&A neurological causes of intermittent collapse

Laurent Garosi
lsg@vetspecialists.co.uk
1- How do you differentiate a movement disorder from an epileptic seizure?
Movement disorders (also called paroxysmal dyskinesia or dystonia) are the main
differential of epileptic seizures. The most common clinical presentation is dystonia
(involuntary sustained contraction of a group of muscles producing abnormal posture)
involving the hindlimbs, which clinically appears as increased extensor tone of the
limbs. Episodes are often triggered by excitement, stress or exercise. Loss of
consciousness, loss of awareness or autonomic signs (salivation, involuntary urination
and/or defecation) are not features of these conditions. Finally, duration of the event
itself can last for a few minutes to up to 30-60 minutes while an epileptic seizure
rarely last more than 4 to 5 minutes (unless status epilepticus).
2- Is there any test to diagnose movement disorder?
Diagnosis of movement disorder can represent a real challenge. Functional
deficiencies in neurotransmitters or their receptors are implicated in the pathogenesis
of these disorders. Structural lesions are usually absent which implies that diagnostic
tests such as MRI scan of the brain and CSF analysis will be normal. Aside for
hypertonicity in Cavalier King Charles Spaniels (also known as collapsing Cavalier
or episodic falling), diagnosis is essentially made based on clinical description of the
event by the owner or video footage and ruling-out structural lesions. In CKCS, an
inactivating microdeletion affecting BCAN gene, encoding the brain-specific
extracellular matrix proteoglycan brevican, has recently been associated with this
condition. The discovery of this mutation forms the genetic basis for a DNA test that
is now available from Lablokin or the Animal Health Trust. It is likely that the
genetic basis of other breed specific movement disorders will be discovered in the
near future. I am currently inviting veterinarian to submit to me videos and EDTA
blood (if the video was diagnostic) of Border terrier with the so-called canine
epileptoid cramping syndrome and of Scottie cramp for that purpose.
3- Is there any treatment for movement disorder?
Unfortunately treatment of most movement disorders remains a challenge. The only
exception is hypertonicity in Cavalier King Charles Spaniels (also known as
collapsing Cavalier or episodic falling). Affected CKCS respond very well to oral
acetazolamide (4-8 mg/kg q8-12h). Oral clonazepam can be used as add-on to

acetazolamide in refractory cases, but its effects may not be lifelong, as functional
tolerance tends to develop. Scottie cramp may respond to fluoxetine (selective
serotonin reuptake inhibitor) (1-2 mg/kg q12-24h). Some Border terriers with so
called canine epileptoid cramping syndrome (also known as Spikes disease) have
responded to hypoallergenic diet. For cases of suspected movement disorder in other
breeds, I usually only consider treating if the episodes are frequent enough (at least
once every two weeks). I sequentially try these dogs on phenobarbitone (3 mg/kg
q12h), clonazepam (0.5 mg/kg 18-12h), acetazolamide (4-8 mg/kg q8-12h),
dantrolene (0.5 to 2 mg/kg q12h) and carbamazepine (4-8 mg/kg q8-12h). Finally,
episodes of movement disorder can be trigger by excitement or stressful
event/activity in some dogs. Avoiding these triggers is sometime the only and most
effective way to control their occurrence.
4- What treatment do you use for narcolepsy?
Narcolepsy is not life threatening; however, the cataplectic attacks (sudden loss of
muscle tone associated with the loss of consciousness) can be debilitating.
Management of cataplectic attacks is the main aim and consists in the use of tricyclic
antidepressant clomipramine (3.0-6.0 mg/kg q24h), imipramine (0.5-1.0 mg/kg q812h), desipramine (3 mg/kg q12h) and the alpha-2 antagonist yohimbine (0.05-0.3
mg/kg q12h). A recent report has described the successful use of venlafaxine (2.5
mg/kg q24h), which is an arylalkanolamine serotonin-norepinephrine reuptake
inhibitor.
5- What are the most common neuromuscular causes of intermittent collapse?
Acquired myasthenia gravis (AMG) and idiopathic immune-mediated inflammatory
myopathy (polymyositis) are the two most common neuromuscular causes of
intermittent weakness. AMG is diagnosed based on positive serum titre for antiacetylcholine receptor antibody. Polymyositis is diagnosed on muscle histopathology
and negative infectious agent titres (Toxoplasma gondii, Neospora caninum and tickrelated disease when appropriate in dogs).
6- How do you diagnose the so-called exercise-induced collapse (EIC) in
Labrador retriever?
EIC affects most commonly young (7 months 2 years) Labrador Retrievers. This
condition has been described also in other breeds such as Chesapeake Bay Retrievers,
Curly-coated Retrievers, Border Collie and Welsh Pembroke Corgis. Affected
animals are normal at rest and have normal levels of physical activity. Episodes are
often triggered by combination of high level of excitement and high level of physical
activity. Diagnosis is exclusional and based on clinical findings, as laboratory,
electrophysiological and histopathological tests are normal. Recently a mutation of
the Dinamin 1 gene (DNM1), responsible for a molecule essential in synaptic vesicle
endocytosis, has been associated with the syndrome of exercise-induced collapse.

Clinical signs of EIC have been observed in homozygous state. Interestingly, Border
collie with clinical signs compatible with EIC are negative for Dinamin 1 gene
mutation. No specific treatments have as yet been proven beneficial. Exercise
Important Questions About The Episodic
Weakness, Collapse or Paroxysmal Event

1.

What did the event look like?

Implications

It may be difficult to distinguish the event from seizure activity, and some may be
seizure events, but it will be important to establish that these events are not due to a
metabolic or cardiovascular crisis.

2.

Has this happened before?

Episodic or paroxysmal events that warrant investigation should be recurrent

3.

How often has this happened?

The answer will provide insight into the progressive nature of the disease and will
serve as a marker for response to therapy

4.

Has it always had the same

Paroxysmal events are usually stereotypical

characteristics?

5.

Is the animal normal immediately

A seizure may be followed by a period of confusion, visual dysfunction,

after these events?

compulsion or even aggression. Neuromuscular disorders, movement disorders and

syncopal events, usually have no such associations.

6.

Is there any type of trigger factor that

Excitement or eating which often causes a loss of consciousness and/or collapse

can be identified?

should prompt the thought of narcolepsy/cataplexy. Several documented events

occur during sleep such as the rapid eye movement sleep disorder.
Exercise/excitement may be the trigger for the syndromes described in Cavaliers
and Scotties as well as many neuromuscular diseases and hypoglycaemic related
collapse. Rarely, seizure events will be triggered by a specific noise or action.
Events seen more than 8 hours after last feeding may suggest hypoglycaemic
collapse.

7.

Is the animal normal in between the

Any abnormalities described in-between the episodes could indicate a structural

events?

CNS or neuropathic or myopathic disease. Metabolic and cardiovascular diseases

may be associated with a waxing and waning clinical course with some
abnormalities detectable in between the acute events.

restriction is necessary to avoid relapses.

7- What important historical questions will you consider when approaching a
case of intermittent collapse?
8.

Are any other littermates known to be

Breed-associated events may be seen in related siblings; however, underlying

affected?

infectious diseases and toxicities should not be ignored.

9.

Is the animal stiff or floppy at the time

Stiffness at the time of the event would often imply either a seizure event, a

of the event?

movement disorder or a myopathy. A floppy animal at the time of the event could
also be a myopathy, but could also implicate a cardiovascular or metabolic disease.

10. Are the gums pale at the time of the

event?

Mucous membrane pallour could well indicate a cardiovascular disease; however,

metabolic diseases such as Addisons should also be considered.