Relative preservation of thalamic centromedian nucleus in parkinsonian patients with dystonia

Abstract

To determine whether variable thalamic degeneration in Parkinson's disease (PD) contributes to less drug responsive clinical features. Formalin-fixed thalami from longitudinally followed patients with PD and early dystonia (N = 6), early falls (N = 5) or no dystonia or falls (N = 6) and age-matched controls without neuropathology (N = 10) were serially sectioned, stained, and analyzed. Neurons in the centromedian parafascicular (CM-Pf) nucleus were quantified using the optical disector method and analysis of variance with post hoc testing used to determine variability in neurodegeneration between groups. Patients with PD were confirmed to have significant neurodegeneration in the CM-Pf complex, with no difference in the degree of neurodegeneration between patients with PD with early falls compared with patients with no history of falls or dystonia. In contrast, patients with PD with early dystonia had significantly less neurodegeneration of the CM but not the Pf than patients without this feature. Preservation of the CM in patients with PD with early dystonia would result in a relative increase in CM activity through the direct basal ganglia pathway and increased primary motor cortex activity. Overall this data provides evidence for pathway-specific neurodegeneration as an underlying feature of the clinical variability observed in patients with PD.

Unusual α‐synuclein and cerebellar pathologies in a case of hereditary myoclonus‐dystonia without SGCE mutation

“…Decreased basal ganglia function, from both overt damage to the caudal intralaminar thalamus (projects to the basal ganglia where terminal amyloid‐β plaque deposition was observed) and nigral inclusion bodies (correlate with decreased striatal dopamine production) [14], would appear to be significant. It is of interest that cell loss in the caudal intralaminar thalamus has been observed previously in patients with Parkinson's disease and early dystonia [15], but perhaps the cerebellar pathology may be more important for the symptoms observed. Animal models show that restricted Purkinje cell abnormalities are sufficient to cause dystonia [16], although dystonia was not a feature in our patient, but is prominent in subsequent generations.…”

Progression of brain atrophy in the early stages of Parkinson's disease: A longitudinal tensor‐based morphometry study in de novo patients without cognitive impairment

“…This classic view assumes that there is no structural damage to the thalamus itself. However, more recently, several studies revealed that the thalamus is one of select targets of extranigral inclusion body pathology and that it undergoes significant neuronal loss in PD (Brooks and Halliday ; Halliday, ; Henderson et al, ; Rüb et al, ; Truong et al, ).…”

“…This classic view assumes that there is no structural damage to the thalamus itself. However, more recently, several studies revealed that the thalamus is one of select targets of extranigral inclusion body pathology and that it undergoes significant neuronal loss in PD Halliday, 2009;Henderson et al, 2000;R€ ub et al, 2002;Truong et al, 2009). Furthermore, recent views posit that the thalamus is more than just a relay for information coming from the basal ganglia and instead that it actively modulates the function of both the basal ganglia and cortical neurons (Halliday, 2009;Sherman, 2007).…”

The primate thalamostriatal systems: Anatomical organization, functional roles and possible involvement in Parkinson’s disease

“…Evidence from postmortem human brain studies demonstrates that the CM/PF complex presents a 30 to 40% cell loss in PD [132–134]. This thalamic degeneration appears to be specific to CM/PF because neighboring thalamic nuclei remain intact [133].…”