| Part one: History, physical examination, and clinical syndrome classification |
| Full history |
| Time course of myoclonus onset (acute, subacute, or chronic) |
| Presence of other neurological problems including seizures |
| Drug or toxin exposure |
| Other medical problems |
| Family history |
| Physical examination |
| Distribution (may be focal, segmental, multifocal, hemi, generalized) |
| Temporal profile (includes rhythmic or irregular) |
| Continuous |
| Intermittent (sporadic or trains) |
| Activation profile |
| Rest (spontaneous myoclonus) |
| Voluntary movement (action myoclonus) |
| Reflex stimuli (any combination of touch, light, sound, or muscle stretch) |
| Determine major clinical syndrome category: |
| Physiologic (normal subjects) |
| Essential (primary symptom, nonprogressive history) |
| Epileptic (associated with a chronic seizure disorder or syndrome) |
| Symptomatic (secondary, but not defined by occurrence of seizures) |
| Part two: Ancillary testing |
| Electrolytes |
| Glucose |
| Renal function tests |
| Hepatic function tests |
| Thyroid antibodies and function |
| Drug and toxin screen (if history suggests) |
| Paraneoplastic antibodies |
| Brain imaging |
| Spine imaging (if focal or segmental) |
| Cerebrospinal fluid analysis (eg, for infectious and inflammatory disorders, prion disease) |
| Part three: Clinical neurophysiology testing to determine physiologic classification (see text) |
| Electroencephalography (EEG) |
| Surface electromyography (EMG) |
| Simultaneous electroencephalography-electromyography polygraphy (EEG-EMG polygraphy) |
| Somatosensory evoked potentials (SEPs) |
| Jerk-locked back-averaging of EEG transients and/or SEPs to EMG discharges |
| Long latency EMG responses to peripheral nerve stimulation (eg, C reflex) |
| Part four: Testing for uncommon and rare diagnoses |
| If not otherwise ruled out, the following should be considered: |
| Body imaging for occult cancer, even in the absence of paraneoplastic antibodies |
| Evaluation for malabsorption disorders such as Celiac sprue and Whipple disease |
| Enzyme assays for neuraminidase deficiency (sialidosis) and biotinidase deficiency (multiple carboxylase deficiency) |
| Evaluation for Wilson disease |
| Evaluation for ataxia-telangiectasia |
| Genetic testing (and tissue biopsy if indicated) for inherited disorders, such as Unverricht-Lundborg disease (EPM1 gene), Lafora body disease (EPM2A and EPM2B genes), neuronal ceroid lipofuscinosis, and Huntington disease |
| Evaluation for mitochondrial disorders, including serum lactate, muscle biopsy, and genetic testing |
| Next generation DNA sequencing for all genes associated with myoclonus |
