Xue Ming1, Nithisha Prasad2, Venkatraman Thulasi3, Kathryn Elkins4, Veeresh Kumar N Shivamurthy5. 1. Department of Neurology, Rutgers New Jersey Medical School, University Hospital, 90 Bergen Street, DOC 8100, Newark, NJ 07103, United States. Electronic address: mingxu@njms.rutgers.edu. 2. Department of Neurology, Rutgers New Jersey Medical School, University Hospital, 90 Bergen Street, DOC 8100, Newark, NJ 07103, United States. Electronic address: nyp15@njms.rutgers.edu. 3. Department of Neurology, Rutgers New Jersey Medical School, University Hospital, 90 Bergen Street, DOC 8100, Newark, NJ 07103, United States. Electronic address: vthulasi@njms.rutgers.edu. 4. Department of Neurology, Emory University School of Medicine, 201 Dowman Drive, Atlanta, GA 30322, USA. Electronic address: kelkins@emory.edu. 5. Department of Neurology, Saint Francis Hospital and Medical Center, Trinity Health Of New England, Hartford, CT 06105, United States. Electronic address: veeresh.kumar@trinityhealthofne.org.
Abstract
OBJECTIVE: We hypothesize that loss of inhibition from the cerebellum can lead to cortical activation and seizures. BACKGROUND: The traditional model for development of seizures purports that the source of seizures is increased electrical activity originating from cerebral cortical neurons. Studies have shown a decrease in inhibition results in a shift of cortical activity to a hyperexcitable state, which may lead to seizures. Interestingly, a 1978 study suggested the term "disorder of disinhibition" as a way to describe epilepsy from studies of chronic cerebellar stimulation. DESIGN/ METHODS: Cases and experimental studies in which cerebellar lesions have been implicated in the development of seizures were reviewed. Cases in which cerebellar inhibition has been targeted in the treatment of seizures were also included. Twenty-six studies and case reports are presented for this report. RESULTS: The cases show cerebellar lesions can lead to cortical epileptiform activity. Purkinje cell loss is linked to the occurrence of seizures in animals. The majority of patients with cerebellar lesions were seizure free after complete resection, while less than half of patients were seizure free after partial resection. Novel treatments using deep-brain stimulation targeting cerebellar structures demonstrated therapeutic benefits for seizures. CONCLUSIONS: Although pathophysiology is not well-understood, the cerebellum likely plays an inherent role in inhibiting aberrant cortical epileptogenesis. Cerebellar lesions may cause seizures due to loss of the inhibition of cortical areas or through intrinsic epileptic activity. Treatments enhancing cerebellar stimulation have shown therapeutic benefits in treating seizures, which could potentially provide another avenue for treatment.
OBJECTIVE: We hypothesize that loss of inhibition from the cerebellum can lead to cortical activation and seizures. BACKGROUND: The traditional model for development of seizures purports that the source of seizures is increased electrical activity originating from cerebral cortical neurons. Studies have shown a decrease in inhibition results in a shift of cortical activity to a hyperexcitable state, which may lead to seizures. Interestingly, a 1978 study suggested the term "disorder of disinhibition" as a way to describe epilepsy from studies of chronic cerebellar stimulation. DESIGN/ METHODS: Cases and experimental studies in which cerebellar lesions have been implicated in the development of seizures were reviewed. Cases in which cerebellar inhibition has been targeted in the treatment of seizures were also included. Twenty-six studies and case reports are presented for this report. RESULTS: The cases show cerebellar lesions can lead to cortical epileptiform activity. Purkinje cell loss is linked to the occurrence of seizures in animals. The majority of patients with cerebellar lesions were seizure free after complete resection, while less than half of patients were seizure free after partial resection. Novel treatments using deep-brain stimulation targeting cerebellar structures demonstrated therapeutic benefits for seizures. CONCLUSIONS: Although pathophysiology is not well-understood, the cerebellum likely plays an inherent role in inhibiting aberrant cortical epileptogenesis. Cerebellar lesions may cause seizures due to loss of the inhibition of cortical areas or through intrinsic epileptic activity. Treatments enhancing cerebellar stimulation have shown therapeutic benefits in treating seizures, which could potentially provide another avenue for treatment.
Authors: Jan Claudius Schwitalla; Johanna Pakusch; Brix Mücher; Alexander Brückner; Dominic Alexej Depke; Thomas Fenzl; Chris I De Zeeuw; Lieke Kros; Freek E Hoebeek; Melanie D Mark Journal: Cell Mol Life Sci Date: 2022-03-19 Impact factor: 9.207
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