DEMENTIA-RELATED MYOCLONUS

The neurophysiology of myoclonus: a primer on identifying brain generators

1. Foundations: what is myoclonus?

Myoclonus is defined as sudden, involuntary, brief, shock-like movements. In clinical practice, these movements are categorised by the nature of the muscle activity:

Positive myoclonus: Brief movements caused by active muscular contractions.

Negative myoclonus (asterixis): Brief movements caused by a sudden, involuntary inhibition or cessation of ongoing muscular activity.

For the clinician, the core challenge lies in differentiating between benign, physiological phenomena (such as hypnic jerks or hiccups) and potentially life-threatening causes like metabolic encephalopathy or progressive genetic disorders. Because the aetiology ranges from self-limited to neurodegenerative, a stepwise approach to diagnosis is mandatory. This begins with a thorough history (medications, toxins, family predisposition) and physical examination, followed by basic testing (blood work, brain MRI), before proceeding to advanced neurophysiological mapping. Ultimately, the clinical presentation, i.e., the distribution and timing of the jerks, is dictated by the anatomical generator, the specific site in the nervous system where the abnormal discharge originates.

2. The anatomical map: cortical vs. subcortical origins

Identifying the anatomical source is the first step in directing therapy. Myoclonus can originate at any level of the central nervous system, from the neocortex to the spinal cord.

The craniocaudal progression

The speed and direction of the jerk spread provide vital clues regarding the generator.

Fast downward spread: If a jerk spreads from the head downward (proximal to distal) at a speed compatible with fast-conducting corticospinal tracts, it suggests a cortical origin.
Somatotopic mapping: In cortical forms, activity spreads along the sensorimotor cortex's "body map."

Clinical pearl

When evaluating axial jerks, the Bereitschaftspotential (readiness potential) is an essential tool. The presence of this pre-movement EEG activity helps differentiate propriospinal myoclonus from psychogenic mimicry. To "see" these pathways in action, we utilise specific diagnostic tools to confirm the anatomical origin.

3. Tool 1: Somatosensory evoked potentials (SEPs) and "giant" responses

Somatosensory evoked potentials (SEPs) are time- and phase-locked EEG responses that measure how the sensorimotor cortex processes incoming sensory information, typically following median nerve stimulation. In cortical reflex myoclonus, the brain’s response to sensory input is massively exaggerated, resulting in a "giant SEP".

Wave components: We analyse the P25 (primary somatosensory cortex) and N33 (precentral activation) components.
Numerical thresholds: A response is traditionally defined as "giant" if the P25 is >8.6 μV or the N33 is >8.4 μV.
Age nuance: As a senior clinician, one must remember that "giant" is relative. For patients >50 years old, thresholds can jump significantly (e.g., P25 >20.0 μV and N35 >14.8 μV).
The "so what?": A giant SEP indicates sensorimotor cortex hyperexcitability. However, it is not a perfect marker: only ~21–39% of suspected cortical myoclonus patients show giant SEPs. Furthermore, giant SEPs can occur without jerks in conditions like multiple sclerosis, progressive supranuclear palsy (PSP), or chronic pain. While SEPs track incoming sensory signals, the next tool looks "backwards" from the motor event.

4. Tool 2: Jerk-locked back averaging (JLBA)

Jerk-locked back averaging (JLBA) is used for spontaneous jerks lacking an external trigger. It utilises signal averaging to extract the cortical correlate from background EEG noise.

How it works

We record EEG and EMG simultaneously. A computer identifies the onset of the muscle burst (EMG) and looks "backwards" in time at the EEG. By averaging 50 to 200 events, random activity cancels out, revealing the electrical spike that triggered the jerk.

The cortical time-lag

For a jerk to be cortical, the EEG spike must precede the EMG burst by an interval compatible with corticospinal conduction:

Arm muscles: 10–20 ms.
Leg muscles: ~30 ms.

Note on "far-field" potentials: If the interval is too short (e.g., <15 ms for the hand), the EEG may be picking up a "far-field" potential, i.e., a signal generated subcortically but recorded at the scalp. This suggests the generator is actually deeper in the brain or brainstem.

5. Tool 3: The C-reflex (long-latency reflex)

The C-reflex is a pathological, exaggerated version of the normal long-latency reflex (LLR-I). It represents the "motor output" of the same hyperexcitability seen in the SEP.

Diagnostic hallmark: The C-reflex suggests a "short-circuit" where sensory input travels to the cortex and immediately triggers a motor jerk via a transcortical reflex arc.
Latency: In hand muscles, the latency is typically ~40 ms.
Testing conditions: It should be tested (1) at rest, where a response is highly abnormal, and (2) during motor activation, which often enhances the reflex. This tool provides the functional link between sensory "input" (SEP) and motor "output" (C-reflex).

6. Synthesis: integrating the evidence

No single neurophysiological marker is infallible. For instance, drug treatments (like perampanel) can reduce cortical excitability and dampen these markers even if the underlying generator remains cortical.

Expert pro-tip

The gold standard for diagnosis is the integration of multiple markers (JLBA, SEPs, C-reflex, and the Bereitschaftspotential) alongside the clinical history. Because giant SEPs can appear in non-myoclonic diseases and are absent in a majority of cortical cases, clinical nuance must always outweigh a single laboratory finding.