History
A 10-year-old 29.3-kg spayed female Akita Inu was referred to the neurology service of a referral veterinary hospital because of a 6-year history of difficulty in walking and trembling in the pelvic limbs. The tremors progressed, mildly involving the thoracic limbs in the last 4 months.
At the time of presentation, the general physical examination was unremarkable. The dog was fed with a commercial diet and was regularly vaccinated.
Assessment
Anatomic diagnosis
The presence of tremors affecting predominantly the limbs, triggered by standing and discontinuing after keeping the pelvic limbs air-floating and during lie-down position, was suggestive of orthostatic tremors (OTs; Supplementary Video S1). Considering the recent literature, an involvement of spinal cord (ventral gray column, α-motor neurons, and/or spinal cord gray matter interneurons) and/or intracranial structures (brainstem and cerebellum) has been suspected.
Likely location of the lesion
In humans with OTs, the presence of a central generator, called the “central oscillator,” has been demonstrated and has been located predominantly in the cerebellum and brainstem. However, other areas seem to be involved in this circuit, creating a ponto-cerebello-thalamo-motor cortical activation, with the activation of the pontine tegmental area playing an important role. Multilevel changes of neuronal excitability during upright stance may serve as triggers for activation of the orthostatic tremor circuit.
Etiologic diagnosis
Potential neurologic differential diagnoses for a 10-year-old Akita Inu with a chronic history of standing tremors and difficulty in lying down, including OTs, benign idiopathic rapid postural tremors, tremors due to paresis as a consequence of a neuromuscular disease causing exercise intolerance and weakness, or a degenerative lumbosacral stenosis causing cauda equina compression and sciatic nerve malfunction. Other nonneurologic differential diagnoses could include chronic orthopedic problems, such as hip dysplasia.
The benign idiopathic rapid postural tremors appear in older dogs; they are not associated with any type of difficulty in lying down and usually do not disappear with a weight-bearing lifting test. The neurologic evaluation of spinal reflexes was unremarkable, making a neuromuscular disorder unlikely. Furthermore, the lumbosacral area palpation, the perineal reflex, and the extension of the lumbosacral joint (also called “lordosis test”) were unremarkable, allowing us to exclude a lumbosacral problem as a degenerative lumbosacral stenosis.
The initial diagnostic plan included a CBC, biochemical serum analysis, coagulation profile and urinalysis, orthopedic evaluation to rule out nonneurologic causes for the difficulty in lying down, and a conscious surface electromyographic (EMG) examination of the affected limb muscles, as the OTs are characterized by pathognomonic high-frequency tremors, with characteristic 13- to 18-Hz tremors (although, in a recent population of dogs affected by OTs, a frequency from 18 to 21 Hz has been described).
Diagnostic Test Findings
The CBC revealed slight leukopenia (WBCs, 4.39; reference range 5.49 to 8.23 thousands/μL). Serum biochemistry testing revealed a few mild changes (ferritin, 302 ng/mL [reference range, 84 to 247 ng/mL]; cholesterol, 339 mg/dL [reference range, 151 to 249 mg/dL]). Overall, these alterations were considered very mild and not clinically relevant. The orthopedic evaluation in this dog was unremarkable.
Conscious electromyography while standing was performed using the NeMus 2 electrodiagnostic system (EB Neuro) with a concentric needle. Tested muscles included the tibialis cranialis, gastrocnemicus, quadriceps femoris, and gluteus medius in the pelvic limbs and the extensor carpi radialis, triceps brachii, supraspinatus and infraspinatus in the thoracic limbs. Normal insertion activity was observed with no spontaneous electric discharge abnormalities when the dog was recumbent, and no tremors were seen. During a standing position, high-frequency rhythmic spontaneous discharges of 20 Hz were recorded in all tested limbs (Figure 1). In this case, the definitive diagnosis was primary OTs.
Conscious electromyography test displaying rhythmic high-frequency electric discharges indicative of orthostatic tremors in a 10-year-old Akita Inu.
Citation: Journal of the American Veterinary Medical Association 261, 6; 10.2460/javma.23.01.0029
Conscious electromyography test displaying rhythmic high-frequency electric discharges indicative of orthostatic tremors in a 10-year-old Akita Inu.
Citation: Journal of the American Veterinary Medical Association 261, 6; 10.2460/javma.23.01.0029
Conscious electromyography test displaying rhythmic high-frequency electric discharges indicative of orthostatic tremors in a 10-year-old Akita Inu.
Citation: Journal of the American Veterinary Medical Association 261, 6; 10.2460/javma.23.01.0029
Comments
Primary OT is a benign, rare, involuntary movement disorder usually reported in young giant- or large-breed dogs.1 The disease is characterized by a progressive, involuntary high-frequency tremor in the pelvic limbs, affecting them predominantly during the standing position. The disease can progress to involve most frequently the thoracic limbs but also the trunk and head. Dogs are usually young (between 9 months and 2 years old), although in Retrievers it seems to appear later in life. Affected dogs appear reluctant to lie down and can show difficulty in sitting and standing, with tremors that can be confused with weakness or exercise intolerance. A typical feature is the disappearance of tremor when the affected legs are raised from the ground or during walking, sitting, or lying down. A quick test to evaluate these tremors during a neurologic evaluation is the weight-bearing lifting test, giving a decrease or complete resolution of the tremors.1–4 OTs are classified as action-related postural tremors, as they occur during voluntary movement of the muscle in its attempt to maintain a posture against gravity. OTs can be divided into primary OT, considered idiopathic, and OT-plus, the latter being characterized by the presence of OT in dogs with other concomitant neurological disease. The diagnosis of primary OTs is based on typical clinical presentation, a positive weight-bearing lifting test, conscious EMG performed on a weight-bearing posture showing high-frequency (18 to 21 Hz) tremors, and the presence of the “helicopter sign,” which is defined as the sound resembling a distant helicopter during auscultation with a stethoscope over the tremoring limb.1–4 Although the exact pathophysiology is currently unknown, the presence of a central generator, called the “central oscillator,” has been demonstrated in human patients with OTs, which has been located predominantly in the cerebellum and brainstem.
Regarding the treatment options, in human medicine, clonazepam represents the first choice, while gabapentin, primidone, sodium valproate, carbamazepine, and phenobarbital are considered second-line options. Regardless of medication, the response in humans is often scarce and minimal, and deep brain stimulation has been used successfully.1,3,4 In dogs, the medical options appear to give a higher rate of improvement despite humans, with gabapentin and phenobarbital described as used in the majority of cases recently published. However, the improvement is usually partial, with a low number of dogs showing resolution of the symptoms. The overall prognosis in dogs with OTs is considered to be good, as the disease is benign and slowly progressive.
In the present case report, a trial with gabapentin at 3 mg/kg, PO, twice daily, was started and was slowly increased to 5 mg/kg twice daily. Unfortunately, the owner reported no improvement of the clinical signs after 3 months of therapy and the dog started showing drowsiness. For this reason, the owner declined other medical options and gabapentin was stopped. After 1-year follow-up, the clinical signs were still the same as described during the first consultation.
Supplementary Materials
Supplementary materials are posted online at the journal website: avmajournals.avma.org
Acknowledgments
No funding was received for this study. The authors declare that there were no conflicts of interest.
References
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Liatis T, Gutierrez-Quintana R, Mari L, et al. Primary orthostatic tremor and orthostatic tremor-plus in dogs: 60 cases (2003-2020). J Vet Intern Med. 2022;36(1):179–189.
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Lowrie M, Garosi L. Classification of involuntary movements in dogs: tremors and twitches. Vet J. 2016;214:109–116.
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Platt SR, De Stefani A, Wieczorek L. Primary orthostatic tremor in a Scottish deerhound. Vet Rec. 2006;159(15):495.
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Garosi LS, Rossmeisl JH, de Lahunta A, Shelton GD, Lennox G. Primary orthostatic tremor in Great Danes. J Vet Intern Med. 2005;19(4):606–609.
