THE THALAMUS AND Parkinson's Disease: The Uncertainty of It All

Abstract

We enjoyed reading the recent article in JMRI entitled, "Structural and Functional Thalamic Changes in Parkinson's Disease With Mild Cognitive Impairment" by Li et al. 1 The authors demonstrated specific thalamic volume loss and functional connectivity alterations in patients with Parkinson's disease (PD), which probably plays an important role in the clinical characteristics and also in the patterns of disease progression. 1 Considering that PD is now widely recognized to be a multisystem disorder, we would like to add some thoughts that may open the debate about the possible role of the thalamus on sudden unexpected death in PD (SUDPAR). PD is one of the most frequent age-related neurodegenerative disorders, has no cure, and the mortality of PD is higher when compared to the general population. 2-4 Thus, a series of recent studies suggested that SUDPAR could contribute to the mortality in PD. 3,4 SUDPAR could be defined as the unexpected death of a PD patient without any satisfactory cause of death as determined by autopsy. 3,4 Potential risk factors of SUDPAR are age at onset, disease duration, gender, motor severity, sleep disorder, concomitant cardiac and pulmonary disease, and polypharmacy. 3,4 The precise pathomechanisms of SUDPAR remain unknown; however, cardiac involvement is assumed to play a "direct" role, since there is evidence associating PD with structural and functional heart change. 3,5 An issue not deeply explored is the existence of a "cerebral" focus that triggers SUDPAR. Although the presence of brain structural abnormalities in PD is well demonstrated, 1 only in the last decade have important advances been made in understanding the cerebral structures directly or indirectly affecting the heart, called "cardiovascular" areas. 6 Since stimulation of certain cerebral areas can lead to morphological and functional cardiovascular alterations, 6-8 we believe that this issue should be further investigated. The first clue in this direction was described in the late 1970s, demonstrating that bilateral injection of kainic-acid into the lateral posterior thalamic nuclei (LP) of rats led to myocardial necrosis, suggesting that this specific nucleus has a direct relationship with the cardiovascular system. 7,8 Later accumulated experimental and clinical evidence demonstrated that some structural changes are potentially associated with sudden death in epilepsy (SUDEP) and volume reduction of the posterior thalamus appears to be a risk factor for SUDEP. 7,9 Likewise, the same findings regarding LP were also described in individuals with schizophrenia. 8 Importantly, it is already known that the pathology in the thalamus itself contributes to the abnormal neural activity characteristic of PD and this role of the thalamus in the course of PD correlates with its extensive projection to the cortex and other areas, including the basal ganglia, cerebellum, and hippocampus. 10 As some of the structures connected with the thalamus are considered potential biomarkers for SUDEP, 9 it is quite reasonable to consider ...