Myoclonus

Diagnosis

Differential Diagnosis
When evaluating the patient with a possible diagnosis of myoclonus, it is important to rule out other movement disorders, including tremor, tics, chorea, and dystonia; however, patients may certainly have a combination of myoclonus and these other hyperkinetic movement disorders. The movements of myoclonus are most often confused with those of tremor, although the rapid speed and brief duration of myoclonus are definitive for the disorder. Brief tics may appear to be myoclonic movements, but their suppressibility and waxing and waning nature are not indicative of myoclonus.

√ Tremor
√ Tics
√ Chorea
√ Hyperexplexia
√ Dystonia

Temporal Onset of Symptoms
Factors related to the temporal onset of the symptoms and recent institution of dietary, pharmacologic, or homeopathic remedies, including recent or long-term exposure to toxins, should be noted. Time of day when symptoms occur most commonly must be identified.

Because treatments, and therefore outcomes, are predicated upon the type of myoclonus, an accurate diagnosis, including identification of temporal onset of symptoms, specific provocative factors, and source of the movements (cortical, subcortical, spinal, or peripheral), are of paramount importance.

Diagnostic Approach: Questions to be Answered

Is the myoclonus spontaneous?
Answering this question requires observation, which may sometimes be prolonged. Attempts to provoke the movements may be necessary. Provocation may be attempted by asking patients to sit with their arms outstretched. Observe whether the movements are induced via action or whether a flapping motion, indicative of asterixis, is present. Clinician evaluators may also clap their hands and note the patients' response or may flick the patients' distal finger joints and observe responsive movement.
What is the distribution of the movements?
Evaluators should note whether the movements are focal, segmental, multifocal, or generalized.
Are there any associated systemic or neurologic abnormalities such as tremor, dystonia, epilepsy, or chorea?
Are the movements positive or negative?

Diagnostic Approach: Clinical Assessment
The clinical assessment of the patient with myoclonus includes a thorough physical examination and a history of both the patient and family members. (Often times, when myoclonus is mild, family members may have a subclinical form of the disorder, and the family history that is upon first glance negative, is in reality positive for the presence of myoclonus). Testing may include a variety of laboratory, imaging and neurophysiologic studies, as well as genetic testing.

Diagnostic Approach: Unified Myoclonus Rating Scale
Seventy-three items comprise the eight components of the recently developed and validated Unified Myoclonus Rating Scale. These items allow the clinician to conduct a standardized interview and assessment and to evaluate the patient's response to antimyoclonic therapy. Eighteen members of the Myoclonus Study Group validated the rating scale by reviewing videotapes, in a blinded fashion, of 20 patients with a variety of chronic myoclonic diagnoses. Each rater viewed tapes from half of the patients. According to the Cronbach alpha scores that resulted, the rating scale "possesses excellent interrater reliability." Completing the rating scale requires minimal time—less than 15 minutes—and is sensitive to change in myoclonus, thereby allowing a quantifiable response to treatment.1

Patient questionnaire
Myoclonus at rest
Stimulus-sensitivity
Action myoclonus
Functional testing
Physician global rating
Negative myoclonus
Negative myoclonus severity

Diagnostic Approach: Laboratory and Imaging Studies
Laboratory studies that may be beneficial in evaluating the patient with myoclonus include measurements of serum electrolytes and glucose, assessment of renal and hepatic function, and screening studies for drugs, toxins, and antibodies.

The purpose of conducting imaging studies is to identify precipitant pathology, including cortical myoclonus in the brain and reticular myoclonus in the brainstem. An MRI of the brainstem should be obtained in patients who exhibit palatal myoclonus.

Diagnostic Approach: Neurophysiologic Studies
Neurophysiologic studies used in diagnosing and evaluating myoclonus include EEG, EMG, EEG-EMG back-averaging, and evoked potentials. EEG is used to identify myoclonus of cortical origin, including epileptic syndromes and epilepsia partialis continua, and to identify symptomatic syndromes such as Creutzfeldt-Jakob disease. Any child with sudden severe myoclonus or paroxysmal changes warrants study with an EEG.2

EMG establishes the chronologic order of movements in myoclonus and localizes the lesion in spinal myoclonus. In cortical myoclonus, the movements have a typical duration of less than 100 milliseconds and spread rostral to caudal. In subcortical myoclonus, the duration is again less than 100 milliseconds, with the spread either rostral or caudal from the brainstem. In spinal myoclonus, whether focal or propriospinal, the duration is usually more than 200 milliseconds, and the spread is rostral or caudal from the spinal cord level.

EEG-EMG back-averaging, in which EMG recordings are tied to the preceding movement recorded on the EEG, increases the signal-to-noise ratio and is used to localize the source of the movements. However, this technique is not routinely available in most healthcare settings.

In cortical myoclonus, the relationship is transient and time-locked. In subcortical myoclonus, the relationship may or may not be transient, and the movements are not constantly time-locked. In spinal or propriospinal myoclonus, there is no relationship between the EMG and EEG recordings.

Both motor and somatosensory evoked potentials may be used to assess the characteristics of myoclonus. Motor evoked potentials can localize lesions, and SEP can identify myoclonus of a cortical origin, which typically shows giant waves. However, the waves are not enlarged in Lafora body disease.

Diagnostic Approach: Genetic Testing
Genetic testing may be undertaken to identify associated conditions such as myoclonus dystonia, Huntington disease, any of the SCAs, myoclonic epilepsy, and dentatorubralpallidoluysian atrophy.