Myoclonus is defined as a sequence of repeated, short-lasting, shock-like jerks arising from sudden involuntary contraction or relaxation of one or more muscles. In human medicine, the condition has been extensively classified along two axes: one covering clinical characterization and the other covering etiology. Within that framework, metabolic disturbances such as hypoglycemia, hyperglycemia, renal failure, hepatic failure, and hyponatremia are recognized causes of acquired myoclonus, generally presumed to be of cortical–subcortical origin and often reversible once the underlying metabolic problem is corrected. Veterinary medicine, by contrast, has classified myoclonus more simply, according to its topographic distribution—focal or generalized—and its presumptive association with epilepsy.

Until now, hypoglycemia had never been documented as an underlying cause of myoclonus in dogs, even though numerous other etiologies have been reported. These include degenerative encephalopathies such as Lafora disease and neuronal ceroid lipofuscinosis, myoclonic epileptic seizures including juvenile myoclonic epilepsy linked to a DIRAS1 gene mutation, drug-induced myoclonus from opioids or propofol, encephalitis associated with canine distemper virus, intoxication with substances such as fluralaner or marijuana, cervical myelopathies, and acute post-hypoxic myoclonus. The new study set out to describe, for the first time, myoclonus as a neurological manifestation of hypoglycemia in dogs, along with associated diagnostic findings, treatment, and outcomes.

The researchers conducted an observational retrospective multicenter case series, collecting cases from colleagues who had anecdotally reported potential instances of myoclonus in hypoglycemic dogs. Inclusion criteria required complete medical records, acute-onset episodes of myoclonus occurring while the dog was in a hypoglycemic state—defined as a blood glucose concentration below 3.3 mmol/L—and available video footage of the episodes. Exclusion criteria ruled out insufficient clinical characterization, blood glucose measurements taken with human-specific portable glucometers, and samples that were not immediately analyzed with in-house veterinary point-of-care chemistry analyzers or collected in sodium fluoride tubes for external laboratory submission. These strict criteria were designed to minimize the risk of including spuriously low glucose readings caused by sample handling artifacts, which are commonly described in dogs.

Ten dogs met the inclusion criteria, with cases drawn from four veterinary institutions and private hospitals. Five dogs were male and five were female, with a median age at onset of myoclonus of 109 months, or roughly nine years. Breeds included Border Collies, an Australian Shepherd, a Belgian Malinois, a Bernese Mountain Dog, a Braque Français, a French Bulldog, a Jack Russell terrier, and a Shih Tzu. Median body weight was 18 kilograms. All dogs were presented because of acute-onset myoclonic episodes, and owners reported that during episodes at home, the dogs showed obtundation in 80 percent of cases, generalized body tremors in 60 percent, and weakness in 50 percent.

Neurological examination was abnormal in half of the dogs and normal in the other half. Among the abnormal findings were myoclonus itself, obtundation, ambulatory tetraparesis, reduced to absent menace responses, and reduced to absent postural reactions. All dogs had neuroanatomical localization consistent with a forebrain lesion, with half showing multifocal localization involving the forebrain and brainstem. Notably, the localization was based not only on abnormalities identified during the neurological examination but also on abnormalities observed in the video recordings, an approach that captured dogs that appeared neurologically normal at the time of examination but exhibited signs of neurological disease during recorded episodes. All examinations and video analyses were performed by a board-certified neurologist or a neurology resident under direct supervision of a board-certified neurologist.

The semiology of the myoclonic episodes was striking. Myoclonus was generalized, affecting the whole body, in 80 percent of dogs and focal, affecting only the head, in 20 percent. Episodes could be observed during rest and while standing or walking in 70 percent of dogs, and in 30 percent only while in lateral recumbency. A tendency to fall backward, over, or to the side during episodes was reported in 70 percent of dogs. The episodes were not distractible by tactile or auditory stimuli in any dog, but some degree of environmental awareness was preserved in all of them, with 40 percent appearing fully conscious during the episodes. No signs of autonomic dysfunction were observed during the myoclonic episodes themselves. In half of the dogs, myoclonus progressed to generalized tonic–clonic epileptic seizures, which were accompanied by autonomic manifestations including urination and hypersalivation, along with loss of consciousness.

Diagnostic evaluation revealed that all dogs had blood glucose concentrations below 3.3 mmol/L after feed withdrawal, with a median of 2.07 mmol/L and a range of 1.1 to 3.2 mmol/L. In 90 percent of dogs, the blood sample was obtained while myoclonic episodes were actively present. Insulinoma—a rare functional pancreatic beta cell neoplasm that secretes excessive insulin, causing hyperinsulinemia-induced hypoglycemia—was initially suspected in 90 percent of dogs. Among dogs that underwent computed tomography of the thorax and abdomen, half had nodular thickening of a pancreatic lobe and one had a larger pancreatic mass lesion, all consistent with insulinoma. One dog also had a pulmonary nodule considered compatible with metastasis. Insulin concentrations after feed withdrawal were measured in five dogs and were increased in 80 percent, with a median of 792 pmol/L. According to predefined diagnostic criteria, one dog was classified as having suspected insulinoma, five as presumptive, and three as definitive, confirmed by histopathology.

One dog stood apart from the rest. This youngest individual in the study, at 24 months of age, was presented to an emergency service due to a window entrapment trauma and developed marked biochemical abnormalities, including severely elevated creatinine, urea, creatine kinase, aspartate aminotransferase, alkaline phosphatase, and hyperkalemia. To correct the hyperkalemia, the dog received multiple glucose boluses followed by a constant rate infusion of 5 percent glucose, combined with intravenous administration of fast-acting human insulin. The dog then acutely developed obtundation and episodes of generalized myoclonus, at which point blood glucose was measured and found to be low at 2.7 mmol/L. Iatrogenic hypoglycemia secondary to fast-acting insulin administration was suspected, and an absolute insulin overdose was considered most likely. The myoclonic episodes resolved completely after adjustment of the glucose infusion and reduction of the insulin dose.

Treatment of the underlying cause of hypoglycemia led to short-term improvement in myoclonus frequency in all treated dogs. Medical treatment included prednisolone, diazoxide, and therapeutic diets formulated for glycemic control, along with feeding multiple small meals daily to support glycemic stability. Surgical treatment consisted of resection of the pancreatic mass. Among dogs with a presumptive diagnosis of insulinoma that received medical treatment alone, three were eventually euthanized due to clinical deterioration associated with recurrent hypoglycemia and recurrence of neurological signs, mainly myoclonic episodes. One dog that underwent combined medical and surgical treatment was euthanized six months after surgery because of recurrent hypoglycemia, myoclonic episodes, and generalized tonic–clonic epileptic seizures. Control glucose concentrations after treatment were available for seven dogs and were within reference intervals during the periods they remained myoclonic episode free.

Before the hypoglycemia was diagnosed, 40 percent of the dogs had been treated with antiseizure medications, including levetiracetam or phenobarbital. Notably, none of these dogs responded to therapy, and all continued to experience generalized tonic–clonic epileptic seizures or myoclonus during the hypoglycemic state. In contrast, correction of hypoglycemia resulted in improvement of clinical signs in all dogs, even in the absence of antiseizure medications, which were subsequently discontinued in all individuals. The researchers point out that although antiseizure therapy is recommended for management of cortical–subcortical myoclonus in humans, myoclonus associated with metabolic disturbances such as hypoglycemia might persist despite antiseizure medication administration. However, the retrospective nature of the study prevents concrete conclusions regarding the efficacy of these medications in the affected dogs.

The pathophysiology underlying these episodes is thought to involve widespread, abnormal bidirectional neuronal activity between cortical and subcortical circuits, resulting in diffuse excitation. Because excitation over the sensorimotor cortex is simultaneously widespread, the resulting myoclonus is typically generalized. In the study, acute myoclonus was the most consistent finding, occurring in all dogs and classified as generalized in 80 percent. The myoclonus was considered reactive in nature, occurring secondary to the metabolic disturbance caused by hypoglycemia. The researchers suggest that the occurrence of episodes in various postures, including standing and during gait, which in some dogs resulted in transient falls, is likely related to sudden alterations in consciousness caused by diffuse cortical excitability, a hallmark of cortical–subcortical myoclonus.

Differentiating myoclonus from other paroxysmal disorders can be challenging, particularly when not evaluated by a neurologist. The researchers note that twitches arising from peripheral nerve hyperexcitability can closely mimic tremors, making the distinction clinically difficult, and that the term tremor is sometimes used in the veterinary literature as an umbrella term encompassing both true tremors and twitches. Unlike true tremors, which are characterized by a regular, rhythmic, and sinusoidal oscillation of uniform frequency, twitches exhibit an irregular frequency, variable amplitude, and erratic pattern. Twitches resulting from peripheral nerve hyperexcitability can be distinguished from myoclonus by the absence of movement in the affected body segment. It is possible that myoclonus has been overlooked or misclassified as other involuntary movements, such as tremors or twitches, in previous studies of hypoglycemic dogs.

Magnetic resonance imaging of the brain was performed in two dogs while they were still exhibiting myoclonic episodes and other neurological signs, but no abnormalities were identified. Both examinations used low-field MRI scans, and diffusion-weighted imaging was not acquired, which might have limited detection of subtle or diffuse metabolic brain lesions. In humans, brain MRI findings in hypoglycemic encephalopathy typically include diffuse cortical diffusion restriction, often accompanied by sulcal effacement and mild diffuse cerebral edema, changes consistent with global metabolic brain injury. Electroencephalography was not performed in any of the dogs in the study, preventing a more precise classification of the myoclonus as epileptic or nonepileptic, although the progression to generalized tonic–clonic epileptic seizures in half of the cases would classify these episodes as epileptic myoclonus according to current veterinary classification.

The researchers acknowledge several limitations of their study, including its retrospective design, the limited number of cases, and the inclusion of dogs from multiple facilities, which resulted in variability of diagnostic workup and treatment protocols. The retrospective nature also prevented accurate and consistent assessment of some valuable information, including the frequency and duration of myoclonic episodes in most cases. The diagnosis relied heavily on clinical observations by referring veterinarians and owners, as well as on the evaluation of video recordings. Despite these limitations, the findings suggest that myoclonus might represent an underrecognized neurological manifestation of hypoglycemia in dogs, expanding the spectrum of clinical signs, particularly in cases secondary to insulinoma.

The clinical implications are significant. Measurement of blood glucose concentrations during myoclonic episodes is a fundamental diagnostic approach for identifying hypoglycemia-related myoclonus, especially in older dogs. Medical and surgical treatment might lead to clinical improvement, but the duration of response is variable and dependent on the underlying cause. In dogs with insulinoma, the overall prognosis remains guarded, as clinical hypoglycemia frequently recurs due to tumor regrowth and the presence of metastasis. Surgical intervention is generally considered the most effective treatment for canine insulinoma and is associated with prolonged survival, although the combination with medical treatment seems to prolong survival even more, especially in relapsing cases. These findings should prompt clinicians to consider hypoglycemia as a differential diagnosis for acute myoclonus in dogs, potentially preventing misdiagnosis and inappropriate antiseizure treatment in affected animals.

Subject of Research: Myoclonus as a neurological manifestation of hypoglycemia in dogs

Article Title: Myoclonus as a neurologic manifestation of hypoglycemia in dogs

Article References: Polidoro, D., Liatis, T., Álvarez, P., & Bhatti, S. F. M. (2026). Myoclonus as a neurologic manifestation of hypoglycemia in dogs. Journal of Veterinary Internal Medicine, 40(5), Article aalag252. https://doi.org/10.1093/jvimsj/aalag252

Image Credits: AI Generated

DOI: 10.1093/jvimsj/aalag252

Keywords: myoclonus, hypoglycemia, dogs, insulinoma, veterinary neurology, seizures, blood glucose, pancreatic tumor, cortical-subcortical myoclonus, antiseizure medications, retrospective study, canine insulinoma