Objective: We used transcranial magnetic stimulation (TMS) paradigms reflecting GABA_A, GABA_B, cholinergic and glutamatergic transmission at the motor cortex level, to investigate pathophysiology of different TME symptoms.

Background: Toxic-metabolic encephalopathies (TME) present with (sub)acute cognitive impairment and negative myoclonus. These symptoms are thought to arise from disbalance in GABA_Aergic and glutamatergic neurotransmission. Alterations in the cholinergic system have been implicated in the animal models.

Method: We included 10 patients with hepatic encephalopathy (HE), 11 patients with liver cirrhosis without encephalopathy (LC), 5 patients with medications induced toxic encephalopathy (TE) and 23 healthy controls (HC). We measured corticospinal excitability: resting and active motor thresholds (RMT, AMT), resting and active input-output (IO) curves; intracortical inhibition: short interval intracortical inhibition (SICI), cortical silent period (CSP), long interval intracortical inhibition, short latency afferent inhibition (SAI); and intracortical facilitation. In patients with TME, EMG from wrist extensors was recorded to determine the duration of EMG silence, corresponding to negative myoclonus. Mini-Mental State Exam (MMSE) and Montreal Cognitive Assessment (MoCA) were performed in all patients.

Results: There was no significant difference in the duration of EMG silence between HE (91 ms +/-21 ms) and TE (110 ms +/-30 ms) patients and no correlation between EMG silence and CSP duration. Compared to HC, patients with TME had lower RMT (p=0.05), decreased slope of active IO curve (p<10^-3), longer CSP (p<10^-3), less effective SICI (p<10^-3) and less effective SAI (p=0.004). HE patients had longer CSP (p=0.007) and less effective SICI (p=0.01) compared to LC patients. In the patients group, delayed recall on MoCA examination negatively correlated with SAI (p=0.02; R_s=-0.49).

Conclusion: The electrophysiologic features of TME are: a) reduced corticospinal excitability, reflecting the shift of equilibrium between inhibition and facilitation toward stronger inhibition; b) disbalance between GABA_A and GABA_B intracortical inhibition, in favor of decreased GABA_A and increased GABA_B inhibition; c) reduced cholinergic inhibition, which correlates with memory impairment. The results of our study on neurophysiological disturbances in TME may have therapeutic implications.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/electrophysiological-correlates-of-neurological-deficits-in-toxic-metabolic-encephalopathy/