Physiology-Based Treatment of Myoclonus

Abstract

Myoclonus can cause significant disability for patients. Myoclonus has a strikingly diverse array of underlying etiologies, clinical presentations, and pathophysiological mechanisms. Treatment of myoclonus is vital to improving the quality of life of patients with these disorders. The optimal treatment strategy for myoclonus is best determined based upon careful evaluation and consideration of the underlying etiology and neurophysiological classification. Electrophysiological testing including EEG (electroencephalogram) and EMG (electromyogram) data is helpful in determining the neurophysiological classification of myoclonus. The neurophysiological subtypes of myoclonus include cortical, cortical-subcortical, subcortical-nonsegmental, segmental, and peripheral. Levetiracetam, valproic acid, and clonazepam are often used to treat cortical myoclonus. In cortical-subcortical myoclonus, treatment of myoclonic seizures is prioritized, valproic acid being the mainstay of therapy. Subcortical-nonsegmental myoclonus may be treated with clonazepam, though numerous agents have been used depending on the etiology. Segmental and peripheral myoclonus are often resistant to treatment, but anticonvulsants and botulinum toxin injections may be of utility depending upon the case. Pharmacological treatments are often hampered by scarce evidence-based knowledge, adverse effects, and variable efficacy of medications.

Myoclonus in older Cavalier King Charles Spaniels

“…For both cortical and subcortical myoclonus, which is suspected in the 39 CKCS in this study, if no inciting cause has been identified, levetiracetam has been proposed as a first‐line treatment in humans 2‐4,6,7 . Levetiracetam is unique compared to other AEDs, binding the synaptic protein SV2A 4,23‐25 instead of having a direct effect on GABA receptors.…”

“…Cortical myoclonus might be responsive to medication decreasing cortical excitability, such as standard antiepileptic drugs (AEDs), [2][3][4] although phenobarbital has been shown to be rarely effective in humans. 3 Out of 9 dogs in this study that showed generalized seizure activity, 5 received a first-line antiepileptic medication (imepitoin or phenobarbitone), the remainder did not receive any.…”

“…2,4,[7][8][9] It is of utmost importance to take a thorough clinical history to determine if a possible genetic link exists or the myoclonus is associated with medication or toxins. 2,4,7,9 Further, blood tests to exclude metabolic causes, MRI, EEG and multisurface EMG to determine the originating site within the nervous system, 2,4,7,9 but this has yet to be more advanced in veterinary medicine. We have performed widely available diagnostic steps in our study population (advanced diagnostic imaging, blood, and CSF sampling), to exclude an underlying pathology as much as possible and proposed a step-by-step approach for the veterinary patient with myoclonus.…”

“…Secondary myoclonus encompasses a myriad of etiologies including neurodegenerative disorders, inflammatory/metabolic conditions, intoxication and drug‐induced 2,4,7 . The physiological categorization is based on electrodiagnostic tests, enabling differentiation between cortical, subcortical/nonsegmental, segmental, and peripheral myoclonus 3,4,7 . Myoclonus can originate in the cortex, subcortical structures (thalamus, brainstem), spinal cord, or peripherally 2‐4,6 .…”

Therapeutic Advances in Movement Disorders

“…Pena and Caviness then review a physiology-based treatment of myoclonus, a symptom that is often resistant to treatment. Myoclonus is currently best managed by identifying the underlying etiology and using medications that best address the neurophysiological subtype [23]. Tourette syndrome is a heterogeneous neurobehavioral disorder, which develops in childhood, presenting with motor and phonic tics but frequently accompanied by behavioral comorbidities that require a tailored management approach.…”