ABSTRACT
INTRODUCTION: The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS), in people suffering from cognitive decline in Down syndrome (DS). In this review, we analyzed available data on the diagnostic and therapeutic management of individuals with LOMEDS. METHODS: We performed a systematic search of the literature to identify the diagnostic and therapeutic management of patients with LOMEDS. The following databases were used: PubMed, Google Scholar, EMBASE, CrossRef. The protocol was registered on PROSPERO (registration code: CRD42023390748). RESULTS: Data from 46 patients were included. DS was diagnosed according to the patient's clinical and genetic characteristics. Diagnosis of Alzheimer's dementia (AD) preceded the onset of epilepsy in all cases. Both myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were reported, the latter preceding the onset of MS in 28 cases. EEG was performed in 45 patients, showing diffuse theta/delta slowing with superimposed generalized spike-and-wave or polyspike-and-wave. A diffuse cortical atrophy was detected in 34 patients on neuroimaging. Twenty-seven patients were treated with antiseizure medication (ASM) monotherapy, with reduced seizure frequency in 17 patients. Levetiracetam and valproic acid were the most used ASMs. Up to 41% of patients were unresponsive to first-line treatment and needed adjunctive therapy for seizure control. CONCLUSIONS: AD-related pathological changes in the brain may play a role in LOMEDS onset, although the mechanism underlying this phenomenon is still unknown. EEG remains the most relevant investigation to be performed. A significant percentage of patients developed a first-line ASM refractory epilepsy. ASMs which modulate the glutamatergic system may represent a good therapeutic option.
Subject(s)
Alzheimer Disease , Down Syndrome , Epilepsies, Myoclonic , Epilepsy, Generalized , Epilepsy , Humans , Down Syndrome/complications , Down Syndrome/drug therapy , Epilepsy/drug therapy , Epilepsies, Myoclonic/diagnosis , Epilepsies, Myoclonic/drug therapy , Levetiracetam/therapeutic use , Seizures/diagnosis , Seizures/etiology , Seizures/therapy , Electroencephalography/methods , Anticonvulsants/therapeutic use , Epilepsy, Generalized/diagnosis , Epilepsy, Generalized/drug therapy , Epilepsy, Generalized/etiologyABSTRACT
A long-term goal of tissue engineering is to exploit the ability of supporting materials to govern cell-specific behaviors. Instructive scaffolds code such information by modulating (via their physical and chemical features) the interface between cells and materials at the nanoscale. In modern neuroscience, therapeutic regenerative strategies (i.e., brain repair after damage) aim to guide and enhance the intrinsic capacity of the brain to reorganize by promoting plasticity mechanisms in a controlled fashion. Direct and specific interactions between synthetic materials and biological cell membranes may play a central role in this process. Here, we investigate the role of the material's properties alone, in carbon nanotube scaffolds, in constructing the functional building blocks of neural circuits: the synapses. Using electrophysiological recordings and rat cultured neural networks, we describe the ability of a nanoscaled material to promote the formation of synaptic contacts and to modulate their plasticity.
Subject(s)
Nanotubes, Carbon , Nerve Net/physiology , Neurons/physiology , Synapses/physiology , Tissue Scaffolds , Animals , Cell Membrane/physiology , Cells, Cultured , Cerebral Cortex/chemistry , Cerebral Cortex/physiology , Electrophysiological Phenomena , Excitatory Postsynaptic Potentials/physiology , Female , Fluorescent Antibody Technique , Hippocampus/cytology , Male , Microscopy, Confocal , Microscopy, Electron, Transmission , Nanostructures , Nerve Net/cytology , Neuronal Plasticity/physiology , Patch-Clamp Techniques , Rats , Thermogravimetry , gamma-Aminobutyric Acid/physiologyABSTRACT
Carbon nanotubes have been applied in several areas of nerve tissue engineering to probe and augment cell behaviour, to label and track subcellular components, and to study the growth and organization of neural networks. Recent reports show that nanotubes can sustain and promote neuronal electrical activity in networks of cultured cells, but the ways in which they affect cellular function are still poorly understood. Here, we show, using single-cell electrophysiology techniques, electron microscopy analysis and theoretical modelling, that nanotubes improve the responsiveness of neurons by forming tight contacts with the cell membranes that might favour electrical shortcuts between the proximal and distal compartments of the neuron. We propose the 'electrotonic hypothesis' to explain the physical interactions between the cell and nanotube, and the mechanisms of how carbon nanotubes might affect the collective electrical activity of cultured neuronal networks. These considerations offer a perspective that would allow us to predict or engineer interactions between neurons and carbon nanotubes.
