Immune-Mediated Cerebellar Ataxias: Clinical Diagnosis and Treatment Based on Immunological and Physiological Mechanisms

Since the first description of immune-mediated cerebellar ataxias (IMCAs) by Charcot in 1868, several milestones have been reached in our understanding of this group of neurological disorders. IMCAs have diverse etiologies, such as gluten ataxia, postinfectious cerebellitis, paraneoplastic cerebellar degeneration, opsoclonus myoclonus syndrome, anti-GAD ataxia, and primary autoimmune cerebellar ataxia. The cerebellum, a vulnerable autoimmune target of the nervous system, has remarkable capacities (collectively known as the cerebellar reserve, closely linked to plasticity) to compensate and restore function following various pathological insults. Therefore, good prognosis is expected when immune-mediated therapeutic interventions are delivered during early stages when the cerebellar reserve can be preserved. However, some types of IMCAs show poor responses to immunotherapies, even if such therapies are introduced at an early stage. Thus, further research is needed to enhance our understanding of the autoimmune mechanisms underlying IMCAs, as such research could potentially lead to the development of more effective immunotherapies. We underscore the need to pursue the identification of robust biomarkers.

A quality parameter for the detection of the intentionality of movement in patients with neurological tremor performing a finger-to-nose test.

The identification of the intentionality of movement is a key-aspect for the development of brain-computer interfaces (BCIs) applicable to daily life in neurological patients. We present a novel method of processing of electroencephalography (EEG) signals for the extraction of movement intention in neurological patients with upper limb tremor. This method is based on event-related EEG desynchronization, considering α (8-12 Hz), ß (13-30 Hz), and γ (30-40 Hz) bands. We have analyzed the EEG signals from the sensorimotor areas of 4 neurological patients presenting an upper limb tremor (grade 1 to 3/4) and executing successive finger-to-nose movements. A Quality Parameter (QP) for the detection of intentionality of movement has been extracted, by considering: (a) the changes in the ß²/α and ß/α ratio (representing bursts of ß-γ frequencies) during the pre-movement period; (b) an appropriate threshold predicting the movement; (c) the number of movements executed. This QP allows the prediction of the voluntary movement with a probability between 70% and 90%. This method could be implemented in a wearable BCI to detect the intentionality of movement and could be used, for instance, to trigger the electrical stimulation in selected muscles of upper limbs with the aim of blocking the emergence of tremor.

Hemicerebellectomy blocks the enhancement of cortical motor output associated with repetitive somatosensory stimulation in the rat.

Repetitive peripheral stimulation is associated with an enhancement of the intensity of corticomotor responses. We analysed the effects of hemicerebellectomy on the modulation of cortical motor output associated with repetitive electrical stimulation of the sciatic nerve in the rat. Hemicerebellectomy blocked the enhancement of the corticomotor response. The cerebellum is a key player in this form of short-term plasticity.