Mapping Purkinje Cell Placement Along the Purkinje Cell Layer: an Analysis of Postmortem Tissue from Essential Tremor Patients vs. Controls

Louis, Elan D.; Rabinowitz, Daniel; Choe, Matthew; Tate, William J.; Kelly, Geoffrey C.; Kuo, Sheng‐Han; Faust, Phyllis L.

doi:10.1007/s12311-015-0742-0

Cited by 10 publications

(3 citation statements)

References 27 publications

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“…Patients and healthy participants were excluded when they had additional neurologic (in particular Parkinson’s disease or dementia), psychiatric, developmental or severe visual or auditory perception disorders. Patients with essential tremor were included on the basis of recent neuropathological findings demonstrating that this common disorder is associated with a pathology of Purkinje cells (Louis et al , 2016; Kuo et al , 2017). Two additional individuals (one from each group) were removed from the final analysis because they failed these exclusion criteria.…”

Section: Methodsmentioning

confidence: 99%

The role of the cerebellum in reconstructing social action sequences: a pilot study

Overwalle

Coninck

Heleven

et al. 2019

Social Cognitive and Affective Neuroscience

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Recent research has revealed that the cerebellum plays a critical role in social reasoning and in particular in understanding false beliefs and making trait attributions. One hypothesis is that the cerebellum is responsible for the understanding of sequences of motions and actions, which may be a prerequisite for social understanding. To investigate the role of action sequencing in mentalizing, we tested patients with generalized cerebellar degenerative lesions on tests of social understanding and compared their performance with matched healthy volunteers. The tests involved understanding violations of social norms making trait and causal attributions on the basis of short behavioral sentences and generating the correct chronological order of social actions depicted in cartoons (picture sequencing task). Cerebellar patients showed clear deficits only on the picture sequencing task when generating the correct order of cartoons depicting false belief stories and showed at or close to normal performance for mechanical stories and overlearned social scripts. In addition, they performed marginally worse on trait attributions inferred from verbal behavioral descriptions. We conclude that inferring the mental state of others through understanding the correct sequences of their actions requires the support of the cerebellum.

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Section: Methodsmentioning

confidence: 99%

The role of the cerebellum in reconstructing social action sequences: a pilot study

Overwalle

Coninck

Heleven

et al. 2019

Social Cognitive and Affective Neuroscience

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“…5C ). The distance between Purkinje cells ranged from 158 to 2 710 µm, while a normal gap of 174 ± 41 µm is observed in control subjects 5 ( Fig. 5C ), indicating an extensive Purkinje cells loss.…”

Section: Resultsmentioning

confidence: 90%

Immunopathogenesis and proposed clinical score for identifying Kelch-like protein-11 encephalitis

Vogrig

Péricart

Pinto

et al. 2021

Brain Communications

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In this study, we report the clinical features of Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome, design and validate a clinical score to facilitate the identification of patients that should be tested for Kelch-like protein 11 antibodies, and examine in detail the nature of the immune response in both the brain and the tumour samples for a better characterization of the immunopathogenesis of this condition. The presence of Kelch-like protein 11 antibodies was retrospectively assessed in patients referred to the French Reference Center for paraneoplastic neurological syndrome and autoimmune encephalitis with (i) antibody-negative paraneoplastic neurological syndrome [limbic encephalitis (n = 105), cerebellar degeneration (n = 33)] and (ii) antibody-positive paraneoplastic neurological syndrome [Ma2-Ab encephalitis (n = 34), antibodies targeting N-methyl-D-aspartate receptor encephalitis with teratoma (n = 49)]. Additionally, since 1 January 2020, patients were prospectively screened for Kelch-like protein 11 antibodies as new usual clinical practice. Overall, Kelch-like protein 11 antibodies were detected in 11 patients [11/11, 100% were male; their median (range) age was 44 (35–79) years], 9 of them from the antibody-negative paraneoplastic neurological syndrome cohort, 1 from the antibody-positive (Ma2-Ab) cohort and 1 additional prospectively detected patient. All patients manifested a cerebellar syndrome, either isolated (4/11, 36%) or part of a multi-system neurological disorder (7/11, 64%). Additional core syndromes were limbic encephalitis (5/11, 45%) and myelitis (2/11, 18%). Severe weight loss (7/11, 64%) and hearing loss/tinnitus (5/11, 45%) were common. Rarer neurologic manifestations included hypersomnia and seizures (2/11, 18%). Two patients presented phenotypes resembling primary neurodegenerative disorders (progressive supranuclear palsy and flail arm syndrome, respectively). An associated cancer was found in 9/11 (82%) patients; it was most commonly (7/9, 78%) a spontaneously regressed (‘burned-out’) testicular germ cell tumour. A newly designed clinical score (MATCH score: male, ataxia, testicular cancer, hearing alterations) with a cut-off ≥4 successfully identified patients with Kelch-like protein 11 antibodies (sensitivity 78%, specificity 99%). Pathological findings (three testicular tumours, three lymph node metastases of testicular tumours, one brain biopsy) showed the presence of a T-cell inflammation with resulting anti-tumour immunity in the testis and one chronic, exhausted immune response—demonstrated by immune checkpoint expression—in the metastases and the brain. In conclusion, these findings suggest that Kelch-like protein 11 antibody paraneoplastic neurological syndrome is a homogeneous clinical syndrome and its detection can be facilitated using the MATCH score. The pathogenesis is probably T-cell mediated, but the stages of inflammation are different in the testis, metastases and the brain.

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“…Evidence points to the cerebellum as a potential inception site for tremor, with studies showing that disrupted function of the Purkinje cell microcircuit (with the upstream inferior olive and downstream cerebellar nuclei) contributes to the pathophysiology [ 18 , 57 ]. Postmortem studies of human patients with essential tremor have also shown anatomical abnormalities in the cerebellar cortex [ 58 ]. Consistent with these data, it is thought that cerebellar circuits are sufficient to drive tremor [ 59 , 60 ].…”

Section: Introductionmentioning

confidence: 99%

Propranolol Modulates Cerebellar Circuit Activity and Reduces Tremor

Zhou

Heijden

Leon

et al. 2022

Cells

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Tremor is the most common movement disorder. Several drugs reduce tremor severity, but no cures are available. Propranolol, a β-adrenergic receptor blocker, is the leading treatment for tremor. However, the in vivo circuit mechanisms by which propranolol decreases tremor remain unclear. Here, we test whether propranolol modulates activity in the cerebellum, a key node in the tremor network. We investigated the effects of propranolol in healthy control mice and Car8wdl/wdl mice, which exhibit pathophysiological tremor and ataxia due to cerebellar dysfunction. Propranolol reduced physiological tremor in control mice and reduced pathophysiological tremor in Car8wdl/wdl mice to control levels. Open field and footprinting assays showed that propranolol did not correct ataxia in Car8wdl/wdl mice. In vivo recordings in awake mice revealed that propranolol modulates the spiking activity of control and Car8wdl/wdl Purkinje cells. Recordings in cerebellar nuclei neurons, the targets of Purkinje cells, also revealed altered activity in propranolol-treated control and Car8wdl/wdl mice. Next, we tested whether propranolol reduces tremor through β1 and β2 adrenergic receptors. Propranolol did not change tremor amplitude or cerebellar nuclei activity in β1 and β2 null mice or Car8wdl/wdl mice lacking β1 and β2 receptor function. These data show that propranolol can modulate cerebellar circuit activity through β-adrenergic receptors and may contribute to tremor therapeutics.

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Mapping Purkinje Cell Placement Along the Purkinje Cell Layer: an Analysis of Postmortem Tissue from Essential Tremor Patients vs. Controls

Cited by 10 publications

References 27 publications

The role of the cerebellum in reconstructing social action sequences: a pilot study

The role of the cerebellum in reconstructing social action sequences: a pilot study

Immunopathogenesis and proposed clinical score for identifying Kelch-like protein-11 encephalitis

Propranolol Modulates Cerebellar Circuit Activity and Reduces Tremor

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