Approach to Generalized Tremors

Dr. Chloe Karson, BVMS, DACVIM (Neurology)

Learning Objectives

• Identify the characteristics and variable phenotypes of tremor activity
• Review important historical information that may suggest etiopathogenesis of tremor activity
• Consider signalment when developing a differential list
• Understand the most common causes of tremor activity and the most beneficial preliminary diagnostics
• Know when to escalate cases requiring advanced care and diagnostics

Tremors

• Involuntary, rhythmic, oscillatory movement of a body part
• Tremor phenotype usually homogenous
• Features of different tremor activity
• Postural: activated upon gravity
• Action-related kinetic: worse with excitement and movement
• Episodic vs. continuous
• Accompanied by intention tremors

Tremor phenotypes

• Most tremor activity is continuous (87%) rather than episodic (13%)
• Tremors may include intention head tremors, palpebral tremors, or mandibular tremors
• The presence, intensity, and character of tremor activity may change in response to:
• Postural changes
• Weight-bearing changes
• Excitement or noise
• Walking
• Coordinated movement (i.e. eating)
• General anaesthesia
• Tremors are typically physiologic (i.e. present in low amplitudes in normal animals) or pathologic (i.e. impair motor function)

Tremor phenotypes

Resting tremor: tremor of a body that is completely supported against gravity and not voluntarily activated

Action tremor: tremor that is produced by a voluntary contraction of the muscle

• Postural - present while voluntarily maintaining position against gravity
• Kinetic - during voluntary movement. May be target directed (i.e. intention) or non-target directed (i.e. simple)
• Intention - present during a target directed voluntary movement (e.g. visually or olfactory guided movement) with the amplitude of the tremor occasionally increasing as the target is reached

Most common causes of tremor activity

Toxin ingestion (48%)

Inflammatory (29.8%)

Metabolic (16.7%)

Degenerative (2.5%)

Tetanus (2%)

Idiopathic (2%)

Neoplastic (1%)

Toxin differentials

• Unknown agent suspected approximately one third of toxin cases
• Most common tremorgenic agents include:
• Mycotoxins
• Metaldehyde
• Avermectins
• Cannabinoids
• Others - strychnine, insecticides (i.e. organophosphates, pyrethrin), metaldehyde, zinc phosphide, bromethalin, methylxanthines (caffeine, chocolate), amphetamines, cocaine, sago palm, xylitol

Mycotoxins - tremorgenic

• Dogs, rarely cats
• May have ingested moldy food or compost
• Toxic agent = penitrem A or roquefortine
• Signs may occur within 30 minutes of toxic dose
• Clinical signs
• Early signs - panting, hyperactivity, vomiting, ataxia/incoordination, weakness, tachycardia, rigidity
• Hyper-responsive to stimuli
• Prolonged muscle tremors or seizures
• May lead to hyperthermia, hypoglycemia, dehydration, and anorexia
• Death in severe cases
• Liver necrosis - reported experimentally

Mycotoxins - tremorgenic

• Minimum database - CBC, chemistry panel, UA
• Can test stomach contents for penitrem A or roquefortine
• Induce emesis (if no contraindications exist)
• Administer activated charcoal
• Medical intervention and IV fluids
• Diazepam IV PRN or midazolam CRI to control seizures
• Consider addition of phenobarbital or levetiracetam if necessary to control seizures
• Methocarbamol IV q8-12 for persistent tremor activity
• 50-220mg/kg IV, do not exceed 330 mg/kg/day
• Give half rapidly, rest to effect
• Sodium bicarbonate if acid/base imbalance
• Symptomatic care as needed
• Monitor for hyperthermia, dehydration, acid/base imbalance, liver damage, rhabdomyolysis, and respiratory distress
• Prognosis is good - complete recovery typically within 24-48 hours

Metaldehyde toxicosis

• Found in slug/snail bait
• Usually dogs, less commonly cats
• Disrupts GABA → facilitates excitation
• Multisystem toxin
• Neuromuscular → seizures and muscle tremors
• Convulsions and hyperthermia → multiorgan failure
• Clinical signs within 4 hours of ingestion:
• Anxiety and restlessness
• Salivating, vomiting, diarrhea
• Tachycardia and tachypnea
• Hyperthermia, often >106° F
• Multi-organ failure and DIC
• Tremors, seizures, hyperesthesia, depression, mydriasis, nystagmus (especially cats)

Metaldehyde toxicosis

• No specific antidote or diagnostic features
• May see increase in muscle enzyme activity, changes in hepatic and renal values, or metabolic acidosis due to hyperthermia and tremors
• Induce emesis
• Single dose of activated charcoal
• Medical intervention and IV fluids
• Manage hyperthermia (prevent organ failure and DIC)
• Manage convulsions (benzos, pheno, levetiracetam)
• Methocarbamol to control tremors
• Hepatoprotectants if large amount ingested
• Prognosis good to excellent provided patient survives >24 hours
• Recheck liver panel 72 hours post discharge if large amount ingested

Metaldehyde toxicosis - hyperthermia

Typically corrects with resolution of convulsions/tremors, however severe temperature elevations require treatment.

• Place on cool surface and administer room temperature IVF
• Cold IV fluids will cause vasoconstriction
• Active cooling (fan)
• Continuous temperature monitoring during this time
• Stop active cooling once temperature reaches 102-103.5ºF to prevent rebound hypothermia
• Things that are controversial:
• Alcohol on the paw pads - causes peripheral vasoconstriction → reduces heat loss (even if goal is evaporative cooling)
• Ice packs or ice baths - results in local vasoconstriction → reduces heat loss (now considered contraindicated)
• Covering patient with wet towels - wet hair can act as insulation

Avermectins

• Ivermectin, milbemycin, moxidectin, selamectin, etc.
• Toxicity if >10-15x normal dosage ingested
• Neurologic signs:
• Tremors
• Depression, disorientation, non-responsiveness
• Drooling, salivation, vomiting
• Mydriasis, blindness
• Ataxia, weakness, recumbency
• Bradycardia, hypoventilation
• Coma and death
• No specific diagnostic findings or antidote
• CNS depression / coma may last weeks

Inflammatory differentials

• Steroid-responsive tremor syndrome (SRTS)
• Most common inflammatory cause of tremors (~83%)
• Also called idiopathic generalized tremor syndrome
• Previously called “little white shaker” syndrome; misleading, affect a variety of sizes and coat colors
• Meningoencephalomyelitis of unknown origin (MUO)
• Uncommon cause of tremors (~15%)
• Acute idiopathic polyradiculoneuritis
• Rare cause of tremors (<2%)
• Results in LMN dysfunction in addition to tremors

Steroid-responsive tremor syndrome

• Affects dogs and cats of various breeds and coat colors
• Mixed breeds
• Cocker spaniels
• West Highland White Terriers
• Maltese
• Signalment
• Usually <5 years of age
• Usually <15kg
• Acute onset (<72 hours), generalised “fine” tremors that are rapid and low amplitude
• May worsen with excitement, stress, and/or exercise
• Usually not incapacitating
• Improves with sleep
• May include vestibulocerebellar signs, paresis, and (rarely) seizures
• Ataxia
• Head tilt
• Reduce to absent menace response
• Nystagmus
• Ocular tremors
• Occasionally presents with pyrexia and gastrointestinal signs

Steroid-responsive tremor syndrome

• Suspected to be immune-mediated
• MRI usually normal
• CSF may show minimal to moderate lymphocytic pleocytosis
• Histopathologic changes throughout the CNS, most notably in cerebellum
• Treatment: immunosuppressive corticosteroids
• 1-2 mg/kg q12 until resolution of neurologic signs, followed by a gradual taper over 1-3 months
• Prognosis is excellent
• 80% of affected dogs will respond to corticosteroids within 3 days
• May relapse during taper and require chronic, low dose therapy

Meningoencephalomyelitis of unknown origin (MUO)

• Immune-mediated inflammatory disease of the CNS involving any combination of the brain, spinal cord, and meninges
• Usually young to middle-aged dogs
• Clinical signs are highly variable and typically acute in onset
• Forebrain: seizures, behavior changes, circling, blindness, ataxia/paresis, etc.
• Cerebellovestibular: nystagmus/strabismus, head tilt, ataxia, blindness, etc.
• Brainstem: reduced mentation, cranial nerve deficits, paresis/ataxia, vital abnormalities, etc.
• MRI and CSF required for presumptive diagnosis
• Histopathology required for definitive diagnosis
• Prognosis is guarded to poor
• Fatal without treatment
• Long-term survival typically around 60% regardless of protocol

Acute idiopathic polyradiculoneuritis (i.e. coonhound paralysis)

• Idiopathic inflammatory disorder involving axons/myelin and primarily affecting ventral nerve roots → motor impairment
• Similar to Guillain-Barré syndrome in humans
• Uncertain pathogenesis, suspect autoimmune
• Reported secondary to racoon exposure
• Results in rapidly progressive LMN tetraparesis/plegia within 10 days of initial symptoms
• Diagnosis is presumptive and based on history, signalment, and clinical signs
• No specific therapy other than time and supportive care, although immunoglobulin therapy is promising
• Median time to ambulation without assistance:
• Immunoglobulin therapy - 27.5 days
• Without immunoglobulin therapy - 75.5 days

Metabolic

• Most common metabolic cause of tremors is hypocalcemia (~40%)
• Other differentials include:
• Hypoglycemia (~18%)
• Hypercalcemia (~15%)
• Hepatic encephalopathy, usually PSS (~12%)
• Diabetic neuropathy
• Hypernatremia
• Hyperammonemia
• Addison’s disease
• Hypercatecholemia (phaechromocytoma)

Neurodegenerative disease

• Neurodegenerative disease is classically chronic, progressive, and nonpainful
• Usually hereditary
• Usually does not respond to medical management
• Signalment: chronic and progressive neurologic dysfunction, unresponsive to steroids, and usually in patients <2-3 years of age
• Examples include:
• Spinocerebellar ataxia (KCNJ10)
• Subacute necrotizing encephalopathy (demyelinating disease)
• Lysosomal storage disease
• Cerebellar cortical degeneration
• Mitochondrial encephalopathy
• MRI and CSF may be suggestive of neurodegenerative disease, but definitive diagnosis requires histopathology +/- genetic testing
• No treatment available

Many Neurodegenerative Diseases Breed Predispositions

Idiopathic conditions resulting in tremors

Primary orthostatic tremors

Benign idiopathic rapid postural tremors

Idiopathic head tremor syndrome

Primary orthostatic tremors

• Onset usually 1-2 years of age
• Adult large and giant breed dogs
• Great Dane, Mastiff, Scottish Deerhound predispose
• Tremors of thoracic and/or pelvic limbs while standing without fatigue
• “Quivering” or “shivering” of the limbs with fine rippling of musculature
• Face and head may be involved
• Tremors disappear during recumbency, walking/running, leaning against objects, or when picked up
• Tremors can be induced in patients lying in lateral recumbency by applying pressure proximally to the bottom of the paw
• Normal neurologic exam and advanced diagnostics

Benign idiopathic rapid postural tremors

• Rapid tremor of the pelvic limbs while standing
• Unknown cause
• May be intermittent
• Usually older dogs, terriers predisposed
• Benign, may progress gradually with age
• Worse during excitement or following exercise
• Other names: essential tremor, senile tremor, benign postural myoclonus tremor
• No treatment necessary

Idiopathic head tremor syndrome

• Episodic, rapid, repetitive myoclonus → uncontrolled head tremors that start and stop spontaneously
• Horizontal (“no”), vertical (“yes”), and rotary manifestations
• Purebred dogs predisposed
• Bulldogs (most common)
• Boxers
• Labrador
• Dobermans
• Any age, but most dogs have their first episode at <4 years
• Majority are alert and responsive during episode
• May be standing, sitting, or laying
• A minority may appear anxious, disoriented, or lethargic
• Most episodes last less than an hour (can be up to 12-48 hours)
• Variable frequency but may be induced by illness, trauma, or stress

Idiopathic head tremor syndrome

In contrast to seizures and pathologic tremors, episodes of idiopathic head tremor syndrome can be stopped via several mechanisms:

• Voluntary turning of the head from side to side
• Calling the dog by its name
• Offering food
• Making a sound to distract/startle
• Asking the dog to perform a task

Approximately 85% of dogs will respond to one or more distractors

There is no effective treatment for this condition, although anecdotal improvement has been reported with phenobarbital or diazepam therapy

Diagnostic Approach and Critical Evaluation

• Thorough history essential
• Toxin ingestion most common
• Discuss access to moldy food, mulch, or compost to exclude mycotoxin ingestion
• Ask about presence of snail/slug bait and insecticides (including flea/tick)
• Rule out recreational and/or controlled substances
• Consider urine drug screen if available
• Consider signalment - is this potentially a benign or idiopathic condition?
• Perform a minimum database to exclude metabolic disease
• Particular attention to calcium, glucose, and hepatic parameters suggestive of PSS
• Any evidence of diabetes mellitus or hypoadrenocorticism?
• Consider advanced neurodiagnostics if indicated
• Are the patients signs restricted to pathologic tremors, or does the neurologic exam suggest abnormalities suggestive of intracranial disease?
• Patients with a history/signalment concerning for MUO → MRI, CSF +/- infectious panel

Symptomatic treatment of tremor activity

• Almost half of tremor cases are due to toxin ingestion → when in doubt, treat symptomatically and monitor closely
• The toxic agent is unknown in a majority of cases - monitor vital parameters and blood pressure regularly to identify complications early and provide rapid intervention
• If no improvement with symptomatic care, consider corticosteroid trial if history, signalment, and neurologic exam suggests SRTS
• Reconsider advanced neurodiagnostics if previously declined
• MRI/CSF will identify MUO, the second most common inflammatory cause of tremors
• May identify signs consistent with congenital or neurodegenerative disease process
• Neoplasia rarely presents with tremors as a sole clinical sign
• Reported with a single case of CNS lymphoma and a single pituitary mass

Initial approach to tremors:

CBC/Chem/T4/UA always recommended

Neurologic

Metabolic

🗹Calcium

🗹Glucose

🗹Hepatic

MRI/CSF

Lecture Points

• Intoxication and steroid-responsive tremor syndrome are the most frequently reported causes of tremor activity
• Routine bloodwork and urinalysis are the most beneficial diagnostics to identify common differentials for tremor activity
• Baseline imaging (radiographs, ultrasound) should be considered if indicated by metabolic abnormalities
• Hypoglycemia → insulinoma? GI perforation and sepsis?
• Hypocalcemia → eclampsia?
• Hypercalcemia → neoplasia?
• Pheochromocytoma?
• Advanced neurodiagnostics necessary to exclude steroid-responsive tremor syndrome and MUO

Continued reading

• Schenck PA, Chew DJ, Nagode LA, Rosol TJ. Disorders of calcium: hypercalcemia and hypocalcemia. In: DiBartola SP, editor. Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice. 4th ed. St. Louis, MO: Elsevier Saunders (2012). p. 120–94. doi: 10.1016/B978-1-4377-0654-3.00013-5
• Dewey, Curtis W., and Ronaldo C. da Costa, editors. A Practical Guide to Canine and Feline Neurology. 3rd ed., John Wiley & Sons, Inc., 2016.
• Tilley, Larry P., and Francis W. K. Smith, Jr., editors. Blackwell’s Five-Minute Veterinary Consult: Canine and Feline. 6th ed., John Wiley & Sons, Inc., 2015.
• Lorenz, Michael D., Joan R. Coates, and Marc Kent. Handbook of Veterinary Neurology. 5th ed., Elsevier Saunders, 2011.
• Platt, Simon R., and Natasha J. Olby, editors. BSAVA Manual of Canine and Feline Neurology. 4th ed., British Small Animal Veterinary Association, 2013.
• Theofanis Liatis, Sofie F. M. Bhatti, Steven De Decker, Generalized Tremors in Dogs: 198 Cases (2003–2023), Journal of Veterinary Internal Medicine, Volume 39, Issue 3, May-June 2025, jvim70062, https://doi.org/10.1111/jvim.70062