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WONDERFUL WORLD OF NEUROLOGY:  SEIZURES, TREMOR AND TWITCHES

Dr Laurent Garosi  DVM, Dip ECVN, MRCVS
RCVS & European Specialist in Veterinary Neurology
Head of neurology/neurosurgery, Davies Veterinary Specialists

Involuntary movement disorders result in some of the most dramatic neurological presentations and certainly in the most distressing ones for the owner.  While some movement disorders are persistent, others are only episodic with occurrence being associated with periods of inactivity or voluntary movements.  Involuntary movement disorders are less well classified in animals than in humans.  They certainly represent a significant diagnostic challenge in term of identifying the type of disorder present, the part of the nervous or musculosekeletal systems involved and, even more, the potential underlying causs. 

The saying “a picture is worth a thousand words” cannot best apply with this type of presentation and if the movement disorder is not present at the time of evaluation, owners should be encouraged to videotape the events.  Seizures are one of the most frequently encountered involuntary movement disorders.  While most dogs and cats present with ‘typical’ generalized seizures, others may present with a range of unusual seizure activity.  Recognition of such ‘atypical’ presentations and differentiation with other involuntary movement disorders is a pre-requisite in the diagnostic approach. 

Tests such as electroencephalography (EEG) should in theory be performed to recognize the event as being epileptic.  Tremor is an involuntary, rhythmical oscillation of all or part of the body that results from alternating or synchronous contraction of agonist-antagonist muscles.  It is frequently associated with a variety of diseases in animals.  However, unlike human beings, many tremor disorders of animals resist strict classification and have a poorly defined aetiology.  Myokymia is defined as a contraction of independent small bands or strips of muscle fibres which induce an undulating movement of the overlying skin (twitches).  The aim of this short article is to discuss some of the most common type of seizures, tremor and twitches seen in our companion animals.

Seizures, epileptic seizures and epilepsy
A seizure can be defined as a non-specific, paroxysmal, abnormal event of the body.  An epileptic seizure (ES) is the clinical manifestation of excessive and/or hypersynchronous abnormal neuronal activity in the cerebral cortex.  ES types can be classified into two major categories:  partial and generalised.&nsbp; In dogs, generalised ES are the most common type.  They indicate initial involvement of both cerebral hemispheres.  Consciousness is impaired and motor manifestations are bilateral.  Compared to dogs, cats commonly exhibit partial ES.  This type of seizure indicates abnormal neuronal activity in one region of the cerebral hemisphere.  Any portion of the body can be involved during a focal seizure depending on the region of the brain affected.  The focal nature of this seizure type is associated with a higher incidence of focal intracranial pathologic change in cats.  Compared to dogs, cats tend to experience high ES frequency regardless of the underlying cause.  Epilepsy is not a specific disease but a chronic condition characterised by recurrent ES.  A patient having a single ES does not have epilepsy as the ES are not recurrent.  An ES is not a disease entity in itself but a clinical sign generally indicative of a forebrain disorder. 

Causes of seizures can be classified as being intracranial or extracranial in origin.  Seizures secondary to extra-cranial causes are often classified as reactive epileptic seizures.  They represent a reaction of a normal brain to transient systemic insult or physiological stresses.  They differ from epilepsy, as primary chronic brain disorder does not underlie the seizure.  Causes of seizures found outside the brain (extra-cranial) may be found outside the body (toxic disorder) or inside the body (metabolic disorder).  Common metabolic causes of seizures include hepatic encephalopathy, hypothyroidism, hypoglycemia, ionic imbalance, renal encephalopathy, polycythemia and hyperlipidemia.  Relatively common toxins encountered as causes of seizures include lead poisoning, ethylene glycol, methaldehyde, strychnine, organophosphates.  In both instances, the animal may have normal or abnormal neurological examination in the interictal period. 

If neurological signs are seen, they are typically symmetrical and non-localising in term of anatomic diagnosis.  Intracranial causes of epileptic seizures can further be divided into functional and structural forebrain disorder.  Seizures secondary to structural intra-cranial diseases are often classified as secondary (or symptomatic) epileptic seizures while seizures secondary to a functional forebrain disorder are classified as primary epileptic seizures.  Potentially any intracranial disease can be a cause of seizure (cerebrovascular accident, primary or metastatic brain tumour, inflammatory or infectious CNS disease, head trauma…).  Most animals with structural forebrain disorder show neurological signs in the interictal period.  These signs are often asymmetric and can localise the lesion.  The exception to this is a structural lesion in a “silent area” of the brain (region of the brain which causes only seizures with no other localising signs such as the olfactory lobe or prefrontal lobes) or in the early stage of an enlarging (and eventually slowly growing) mass.  The term primary (or idiopathic) epilepsy implies a functional forebrain disorder causing recurrent epileptic seizures with a normal interictal period and no identifiable toxic, metabolic or structural intracranial causes.  This type of epilepsy is considered less common in cats as compared to dogs. 

The diagnosis of primary epilepsy is unfortunately a diagnosis of exclusion.  There is to date no definitive diagnostic test to confirm this diagnosis.  Primary epilepsy is considered the most common cause of seizures in dogs having their onset of seizures between 1 and 5 years of age.  Breed predilection is also recognised in Labrador retriever, Golden retriever, Border collie, German Shepherd dog, Keeshound, Belgian Tervueren, Vizla and Shetland sheepdog.  True idiopathic epilepsy is much less common in the cat due to the more diverse genetic background of most cats.  The sequence of diagnostic testing for any animal with seizures should include from the least invasive to the more invasive tests:  CBC, serum biochemistry, urinalysis and blood pressure measurement, infectious titres, imaging of the brain with CT or MRI and CSF analysis. 

Tremor
Tremor is the most common movement disorder in human and likely so in veterinary patients.  In human medicine, tremors are classified on the basis of their location, association with rest or voluntary muscle contraction, frequency and amplitude of the oscillatory movements.  Tremors can be divided into resting tremors and action-related (also known as kinetic) tremors.  Resting tremor is present only during rest. 

The most common example in humans is Parkinson’s disease secondary to degeneration of the substantia nigra.  The condition has not been recognised in domestic animals.  Action-related tremor occurs following initiation of voluntary movement and worsens with increasing levels of activity while it disappears with rest.  Action-related tremor can be classified in veterinary patient as postural or kinetic.  Other forms of action tremor related in human to specific movement of the hands and arms such as isometric or task-specific tremor are not recognised in our canine and feline patients.  Intention tremor is a form of kinetic tremor.  It is typically associated with cerebellar disease in small animals and usually observed with other cerebellar signs such as bilaterally symmetrical ataxia without decreased level of voluntary movement (paresis), vestibular signs (head tilt, nystagmus, loss of balance…), broad-based stance, dysmetria and absent menace response with normal visual placing and normal vision.  Cerebellar-related tremor is usually the consequence of diffuse cerebellar disease process and predominantly affects the head with initiation of voluntary head movement.  This type of tremor disappears when the animal is totally relaxed or sleeping.  Generalised tremor can occur secondary to congenital disorders of myelination, metabolic conditions (hypocalcemia, hypo- and hypernatremia…), intoxications (metaldehyde, lead, pyrethrins, organophosphates, bromethalin, ivermectin, some mycotoxins…), storage diseases and inflammatory CNS diseases.  Generalised tremors without other definable systemic cause are most often secondary to inflammatory brain disease.  Such condition is most common in small white canine breeds (especially West Highland white terrier and Maltese) which has been the reason for the name “white shaker syndrome” initially given to this condition.  However, dogs of any colour, size or breed can be affected and therefore the term ‘generalised tremor syndrome’ is now preferred.  The onset is usually sudden with signs generally seen between 9 months and 2 years of age.  On occasion, mild vestibular or cerebellar ataxia or other neurological signs accompany the diffuse whole-body tremor. 

Imaging studies are usually normal and CSF may be normal or reveal a slight elevation of lymphocytes and protein.  The few histologic studies of the CNS of affected dogs have revealed a mild, non-suppurative meningo-encephalitis in some.  Postural tremor involves muscles that participate in maintaining the body against gravity (also known as postural muscles).  The best postural tremor described so far in veterinary medicine is the orthostatic tremor (OT) occurring in giant breed of dogs such as Great Danes, Deerhound and Newfoundland.    OT causes dramatic tremors that are visible only when the animal is standing.  The tremors typically begin in the lower aspects of the legs, but can also involve the muscles of the head and face. The tremors are usually first apparent at a young age (1-2 years), and are unique in that affected dogs often appear reluctant to lie down and demonstrate what appears to be a constant “shivering” while standing suggestive almost of an involuntary dance.  OT is different from other causes of tremors in that the tremors that are characteristic of the disease completely disappear when the dog walks, runs, leans against an object, or lies down.  The tremors can be totally abolished when a standing dog is lifted off of the ground.  Dogs with OT appear otherwise healthy on physical examination, and generally do not have any significant abnormalities that are detectable on routine blood tests, radiographic examinations, spinal fluid analysis, and even have normal MRI examinations of their brains. 

Definitive diagnosis of OT requires documentation of the characteristic tremor pattern during a conscious electromyographic (EMG) examination.  Intermittent head ‘bobbing’ is another less understood type of postural tremor affecting the head and neck postural muscles and causes a rapid head and neck tremor.  The head ‘bobbing’ can be in the vertical or horizontal plane and typically disappears when the dog is distracted or lay down.  It can occur as an idiopathic disorder or as a consequence of structural brain disease (especially with pathology affecting the thalamus).  In older dogs, benign, rapid, postural tremor may occasionally be seen in the pelvic limbs.  This tremor is only present when the dog is standing and disappears during voluntary movement.  The aetiology and pathogenesis of this syndrome remains unknown.

Twitches
Myokymia is defined as a contraction of independent small bands or strips of muscle fibres which induce an undulating movement of the overlying skin (twitches).  Compared to tremor, this involuntary muscle activity persists even during sleep and under anaesthesia.  Generalised and focal forms of myokymia have been recognised in veterinary medicine with the focal form most commonly affecting the face.  These myokymia can be caused by a wide variety of disorders of the CNS and peripheral nervous system (Distemper, demyelinating conditions, axonal voltage-gated potassium channels abnormality…).

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