The C-reflex, also referred to as the pathological long-latency reflex (LLR), is a critical neurophysiological marker used to diagnose cortical reflex myoclonus by demonstrating an exaggerated response within the transcortical loop. It is considered one of the primary electrophysiological criteria for identifying a cortical generator of myoclonic jerks.

Mechanism and diagnostic utility

The C-reflex is a muscle response mediated by transcortical pathways that assess the excitability of the sensorimotor cortex.

• Presence at rest: One of the most important diagnostic features of the C-reflex is its presence at rest in patients with cortical myoclonus. In healthy individuals, the physiological counterpart (LLR-I) can typically only be observed during active muscle contraction.
• Sensorimotor correlation: Research has shown that the time interval between a cortical spike (detected via EEG) and the resulting myoclonic jerk is almost identical to the interval between the N33 component of a giant somatosensory evoked potential (SEP) and the C-reflex. This temporal linkage confirms that the C-reflex represents the neurophysiological correlate of the myoclonic jerk.
• Testing application: Evaluation of the C-reflex is considered an "elementary procedure" that should be performed both at rest and during motor activation to ensure a precise diagnosis.

Prevalence and statistical data

The frequency with which the C-reflex is recorded varies depending on the specific disorder and study population, generally occurring in 56% to 100% of patients suspected of having cortical myoclonus.

Statistics by condition (Latorre et al. 2023):

• Progressive myoclonus epilepsy (PME): Positive rate of approximately 69% (22/32 patients).
• Olivopontocerebellar atrophy (OPCA): Recorded in 70% of patients (16/23).
• Mixed patient samples (PME, AD, CBS): One study reported the C-reflex in 100% of tested subjects (12/12) during voluntary contraction.
• General neurodegenerative samples: A study of 18 patients with conditions like MSA, CBS, and BAFME found a C-reflex in 56% of cases (10/18).
• Parkinson's Disease: Patients with small-amplitude myoclonus exhibited a C-reflex rate of 100% during contraction.

Latency data

The latency of the C-reflex provides information on the speed of the transcortical loop. While physiological LLR-I latency is approximately 40 ms, the pathological C-reflex can range from 39 ms to 55.3 ms.

• PME studies: Reported a mean latency of 39 ms (range: 35–42 ms).
• OPCA studies: Reported a mean latency of 39.9 ms (range: 30–50 ms).
• MSA and Parkinsonism: Latencies can be longer, reaching a mean of 55.3 ms in some parkinsonian multiple system atrophy (MSA-P) cohorts.
• Central pathways: Analysis suggests that central conduction pathways account for roughly 24 ms of the total LLR response time.

The role of the cerebellum in C-reflex heightening

The cerebellum plays a significant role in adjusting the gain of long-latency stretch reflexes (LLSR). If cerebellar drive is impaired, the gain of sensorimotor connections increases, which often results in heightened LLSRs and the appearance of reflex myoclonus.

• Atrophy evidence: Patients with cerebellar cortex atrophy demonstrate significantly enhanced LLSRs.
• CTC projection: It is proposed that abnormal activity in the cerebello-thalamo-cortical (CTC) projection changes the gain of sensorimotor connections, thereby driving the cortical reflex myoclonus and the C-reflex.

Diagnostic limitations

• Specificity concerns: The C-reflex is not exclusively limited to cortical myoclonus; it has been recorded in other movement disorders such as essential tremor, dystonia, and reticular myoclonus (a subcortical form).
• Interference: Pharmacological treatments, such as antiseizure medications, can reduce cortical hyperexcitability and thus decrease the amplitude of the C-reflex, potentially masking it during diagnostic testing.
• Latency outliers: In conditions like corticobasal syndrome (CBS), the C-reflex may have abnormally short latencies that do not fully represent a standard transcortical reflex circuit, complicating the diagnosis.