المؤلفون: Elke Pucks-Faes, Raffaele Nardone, Eugen Trinka, Stefan Golaszewski, Luca Sebastianelli, Leopold Saltuari, Francesco Brigo, Viviana Versace

المصدر: Journal of Neural Transmission. 127:1209-1215

مصطلحات موضوعية: 0301 basic medicine, Baclofen, medicine.medical_specialty, Neurology, Consciousness, medicine.medical_treatment, Disorders of consciousness, 03 medical and health sciences, Glutamatergic, chemistry.chemical_compound, 0302 clinical medicine, Intrathecal baclofen administration, GABAB, medicine, Humans, Spasticity, Injections, Spinal, gamma-Aminobutyric Acid, Biological Psychiatry, Muscle Relaxants, Central, business.industry, medicine.disease, Transcranial magnetic stimulation, Psychiatry and Mental health, 030104 developmental biology, nervous system, chemistry, Muscle Spasticity, GABAergic, Hypertonia, Neurology (clinical), medicine.symptom, business, Neuroscience, 030217 neurology & neurosurgery

الوصف: Baclofen is a structural analogue of gamma-amino-butyric acid (GABA), which reduces spastic hypertonia of striated muscle due to a mechanism of GABAB-ergic inhibition of mono- and polysynaptic reflexes at the spinal level. There are reports of patients with severe disorders of consciousness that presented a substantial improvement following intrathecal baclofen (ITB) administration for severe spasticity. The neural mechanisms underlying the clinical recovery after ITB have not yet been clarified. Baclofen could modulate sleep-wake cycles that may be dysregulated and thus interfere with alertness and awareness. The diminished proprioceptive and nociceptive sensory inputs may relieve thalamo-cortical neural networks involved in maintaining the consciousness of the self and the world. ITB treatment might also promote the recovery of an impaired GABAergic cortical tone, restoring the balance between excitatory and inhibitory cortical activity. Furthermore, glutamatergic synapses are directly or indirectly modulated by GABAB-ergic receptors. Neurophysiological techniques (such as transcranial magnetic stimulation, electroencephalography, or the combination of both) can be helpful to explore the effects of intrathecal or oral baclofen on the modulation of neural cortical circuits in humans with disorders of consciousness.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f8c07d640abb0264564b2c34a950816Test
https://doi.org/10.1007/s00702-020-02233-8Test

المؤلفون: Arne C. Bathke, Eugen Trinka, Yvonne Höller, Frediano Tezzon, Piergiorgio Lochner, Peter Höller, Raffaele Nardone, Francesco Brigo

المصدر: Journal of Neural Transmission. 122:873-876

مصطلحات موضوعية: Male, medicine.medical_specialty, Neurology, medicine.medical_treatment, education, Prodromal Symptoms, Subjective memory, Synaptic Transmission, Alzheimer Disease, medicine, Humans, In patient, Neurons, Afferent, Cognitive impairment, Biological Psychiatry, Aged, Memory Disorders, medicine.disease, Transcranial Magnetic Stimulation, Cholinergic Neurons, Transcranial magnetic stimulation, Psychiatry and Mental health, Biomarker (medicine), Cholinergic, Female, Perception, Neurology (clinical), Alzheimer's disease, Psychology, Neuroscience

الوصف: Subjective memory impairment (SMI) is being increasingly recognized as a preclinical phase of Alzheimer disease (AD). Short latency afferent inhibition (SAI) is helpful in demonstrating dysfunction of central cholinergic circuits, and was reported to be abnormal in patients with AD and amnestic multiple domain mild cognitive impairment. In this study, we found normal SAI in 20 subjects with SMI. SAI could be a useful biomarker for identifying, among individuals with memory complaints, those in whom cholinergic degeneration has occurred.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74f2496e5fb93b2444e8945a192ea9e2Test
https://doi.org/10.1007/s00702-014-1344-6Test

المؤلفون: Nardone, Raffaele^1,2,3,4 (AUTHOR) raffaele.nardone@asbmeran-o.it, Sebastianelli, Luca^5,6 (AUTHOR), Brigo, Francesco^1,7 (AUTHOR), Golaszewski, Stefan^2,4 (AUTHOR), Trinka, Eugen^2,8,9 (AUTHOR), Pucks-Faes, Elke¹⁰ (AUTHOR), Saltuari, Leopold^5,6 (AUTHOR), Versace, Viviana^1,6 (AUTHOR)

المصدر: Journal of Neural Transmission. Sep2020, Vol. 127 Issue 9, p1209-1215. 7p.

مصطلحات موضوعية: *TRANSCRANIAL magnetic stimulation, *STRIATED muscle, *CONSCIOUSNESS disorders, *SLEEP-wake cycle, *NEURAL circuitry

مستخلص: Baclofen is a structural analogue of gamma-amino-butyric acid (GABA), which reduces spastic hypertonia of striated muscle due to a mechanism of GABAB-ergic inhibition of mono- and polysynaptic reflexes at the spinal level. There are reports of patients with severe disorders of consciousness that presented a substantial improvement following intrathecal baclofen (ITB) administration for severe spasticity. The neural mechanisms underlying the clinical recovery after ITB have not yet been clarified. Baclofen could modulate sleep–wake cycles that may be dysregulated and thus interfere with alertness and awareness. The diminished proprioceptive and nociceptive sensory inputs may relieve thalamo-cortical neural networks involved in maintaining the consciousness of the self and the world. ITB treatment might also promote the recovery of an impaired GABAergic cortical tone, restoring the balance between excitatory and inhibitory cortical activity. Furthermore, glutamatergic synapses are directly or indirectly modulated by GABAB-ergic receptors. Neurophysiological techniques (such as transcranial magnetic stimulation, electroencephalography, or the combination of both) can be helpful to explore the effects of intrathecal or oral baclofen on the modulation of neural cortical circuits in humans with disorders of consciousness. [ABSTRACT FROM AUTHOR]

المؤلفون: Yvonne Höller, Peter Höller, Eugen Trinka, Piergiorgio Lochner, Stefan Golaszewski, Aljoscha Thomschewski, Raffaele Nardone, Francesco Brigo

المصدر: Journal of Neural Transmission. 122:279-295

مصطلحات موضوعية: Serotonin, business.industry, Brain, Nerve injury, medicine.disease, Spinal cord, Serotonergic, Synaptic Transmission, Denervation supersensitivity, Psychiatry and Mental health, medicine.anatomical_structure, Neurology, medicine, Animals, Humans, Neurology (clinical), Rostral ventromedial medulla, Brainstem, Spasticity, medicine.symptom, business, Neuroscience, Spinal cord injury, Spinal Cord Injuries, Biological Psychiatry

الوصف: Changes in descending serotonergic innervation of spinal neural activity have been implicated in symptoms of paralysis, spasticity, sensory disturbances and pain following spinal cord injury (SCI). Serotonergic neurons possess an enhanced ability to regenerate or sprout after many types of injury, including SCI. Current research suggests that serotonine (5-HT) release within the ventral horn of the spinal cord plays a critical role in motor function, and activation of 5-HT receptors mediates locomotor control. 5-HT originating from the brain stem inhibits sensory afferent transmission and associated spinal reflexes; by abolishing 5-HT innervation SCI leads to a disinhibition of sensory transmission. 5-HT denervation supersensitivity is one of the key mechanisms underlying the increased motoneuron excitability that occurs after SCI, and this hyperexcitability has been demonstrated to underlie the pathogenesis of spasticity after SCI. Moreover, emerging evidence implicates serotonergic descending facilitatory pathways from the brainstem to the spinal cord in the maintenance of pathologic pain. There are functional relevant connections between the descending serotonergic system from the rostral ventromedial medulla in the brainstem, the 5-HT receptors in the spinal dorsal horn, and the descending pain facilitation after tissue and nerve injury. This narrative review focussed on the most important studies that have investigated the above-mentioned effects of impaired 5-HT-transmission in humans after SCI. We also briefly discussed the promising therapeutical approaches with serotonergic drugs, monoclonal antibodies and intraspinal cell transplantation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c18f0a30524a8bbe4f00947df8ceb0a2Test
https://doi.org/10.1007/s00702-014-1241-zTest

المؤلفون: Piergiorgio Lochner, Raffaele Nardone, Stefan Golaszewski, Yvonne Höller, Francesco Brigo, Eugen Trinka, Alexander Kunz, Aljosha Thomschewski

المصدر: Journal of Neural Transmission. 121:1313-1320

مصطلحات موضوعية: medicine.medical_specialty, Neurology, Dopamine, Dopamine Agents, CADASIL, Levodopa, Leukoencephalopathy, Alzheimer Disease, medicine, Humans, Dementia, Vascular dementia, Biological Psychiatry, Aged, Afferent Pathways, Dopaminergic, Brain, Neural Inhibition, Evoked Potentials, Motor, medicine.disease, Transcranial Magnetic Stimulation, Acetylcholine, Psychiatry and Mental health, Cholinergic, Neurology (clinical), Alzheimer's disease, Psychology, Neuroscience

الوصف: Short-latency afferent inhibition (SAI) technique gives the opportunity to non-invasively test an inhibitory circuit in the human cerebral motor cortex that depends mainly on central cholinergic activity. Important SAI abnormalities have been reported in both patients with Alzheimer disease (AD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a model of "pure" vascular dementia (VD). Interestingly, a normalization of SAI was observed in AD after levo-dopa (L-dopa) administration. We aimed to determine whether the pharmacological manipulation of the dopaminergic system can also interfere with SAI test in CADASIL patients, compared with AD patients and healthy controls. SAI was found to be significantly reduced in both patient groups. L-Dopa significantly increased SAI in the AD patients, while it failed to restore SAI abnormality in CADASIL patients. Therefore, L-dopa-mediated changes on SAI in AD patients seem to be a specific effect. The present study supports the notion that relationship between acetylcholine and dopamine systems may be specifically abnormal in AD. L-Dopa challenge may thus be able to differentiate the patients with AD or a mixed form of dementia from those with "pure" VD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4d3e734c2f515cd0787c5ff216de0087Test
https://doi.org/10.1007/s00702-014-1195-1Test

المؤلفون: Nardone, Raffaele^1,2,3 (AUTHOR) raffaele.nardone@asbmeran-o.it, Golaszewski, Stefan^2,3 (AUTHOR), Schwenker, Kerstin^2,3 (AUTHOR), Brigo, Francesco^1,4 (AUTHOR), Maccarrone, Miriam¹ (AUTHOR), Versace, Viviana^5,6 (AUTHOR), Sebastianelli, Luca^5,6 (AUTHOR), Saltuari, Leopold^5,6,7 (AUTHOR), Höller, Yvonne⁸ (AUTHOR)

المصدر: Journal of Neural Transmission. Aug2019, Vol. 126 Issue 8, p1073-1080. 8p.

مصطلحات موضوعية: *TRANSCRANIAL magnetic stimulation, *HYDROCEPHALUS, *NEUROPSYCHOLOGICAL tests, *SURGICAL anastomosis

مستخلص: The pathophysiological mechanisms of cognitive and gait disturbances in subjects with normal-pressure hydrocephalus (NPH) are still unclear. Cholinergic and other neurotransmitter abnormalities have been reported in animal models of NPH. The objective of this study was to evaluate the short latency afferent inhibition (SAI), a transcranial magnetic stimulation protocol which gives the possibility to test an inhibitory cholinergic circuit in the human brain, in subjects with idiopathic NPH (iNPH). We applied SAI technique in twenty iNPH patients before ventricular shunt surgery. Besides SAI, also the resting motor threshold and the short intracortical inhibition to paired stimulation were assessed. A significant reduction of the SAI (p = 0.016), associated with a less pronounced decrease of the resting motor threshold and the short latency intracortical inhibition to paired stimulation, were observed in patients with iNPH at baseline evaluation. We also found significant (p < 0.001) correlations between SAI values and the gait function tests, as well as between SAI and the neuropsychological tests. These findings suggest that the impairment of cholinergic neurons markedly contributes to cognitive decline and gait impairment in subjects with iNPH. [ABSTRACT FROM AUTHOR]

المؤلفون: Raffaele Nardone, Stefan Golaszewski, Eugen Trinka, Gunther Ladurner, Francesca Caleri, Jürgen Bergmann, Monica Christova, Frediano Tezzon

المصدر: Journal of Neural Transmission. 119:463-471

مصطلحات موضوعية: Male, Oncology, medicine.medical_specialty, Neurology, medicine.medical_treatment, Electromyography, Neuropsychological Tests, behavioral disciplines and activities, Internal medicine, mental disorders, Reaction Time, medicine, Humans, Cognitive Dysfunction, Donepezil, Biological Psychiatry, Aged, Analysis of Variance, medicine.diagnostic_test, Motor Cortex, Neural Inhibition, Middle Aged, Evoked Potentials, Motor, medicine.disease, Transcranial Magnetic Stimulation, Transcranial magnetic stimulation, Psychiatry and Mental health, medicine.anatomical_structure, Cholinergic, Female, Amnesia, Neurology (clinical), Analysis of variance, Alzheimer's disease, Psychology, human activities, Neuroscience, medicine.drug, Motor cortex

الوصف: Mild cognitive impairment (MCI) is considered a transitional stage between normal aging and a diagnosis of clinically probable Alzheimer disease (AD). The role of the cholinergic system in MCI is not clearly defined and needs to be further investigated. A transcranial magnetic stimulation (TMS) protocol, the short latency afferent inhibition (SAI), may give direct information about the function of some cholinergic pathways in the human motor cortex. We aimed to evaluate in the present study the relationship of SAI to the specific clinical subtypes of MCI. SAI was examined in 20 patients with amnestic MCI (10 SD, 10 MD), twenty patients with nonamnestic MCI (10 SD, 10 MD) and ten control subjects. Motor threshold, central motor conduction time, intracortical inhibition and facilitation to paired-TMS were also evaluated. Mean SAI was significantly reduced in amnestic MCI-MD patients when compared with the controls, while it was not significantly different in amnestic MCI-SD patients and in nonamnestic patients. SAI was increased after administration of a single dose of donepezil in a subgroup of four amnestic MCI-MD patients. The other TMS parameters did not differ significantly between the four MCI groups and the control group. We demonstrated that this putative marker of central cholinergic activity differs among MCI subtypes. The amnestic-MD type of MCI might be a phenotype of incipient AD. However, this hypothesis would be better addressed in a longitudinal study of individual patients. TMS studies may be useful in identifying MCI individuals in whom cholinergic degeneration is occurred and therefore at increased risk of conversion to AD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::66f069d54dbc6f6d2609712c58860ee3Test
https://doi.org/10.1007/s00702-011-0725-3Test

المؤلفون: Frediano Tezzon, Pierpaolo De Blasi, Raffaele Nardone, Gunther Ladurner, M. Seidl, Eugen Trinka, Francesca Caleri, Yvonne Höller, Stefan Golaszewski

المصدر: Journal of Neural Transmission. 118:1349-1358

مصطلحات موضوعية: Male, medicine.medical_specialty, Neurology, medicine.medical_treatment, Audiology, Synaptic Transmission, medicine, Humans, Subcortical vascular dementia, Dementia, Cognitive decline, Biological Psychiatry, Aged, Cerebral Hemorrhage, Mini–Mental State Examination, medicine.diagnostic_test, Dementia, Vascular, Microcirculation, Cognition, Human brain, Middle Aged, medicine.disease, Acetylcholine, Hyperintensity, Microbleeds, Transcranial magnetic stimulation, Short latency afferent inhibition, Mini-Mental State Examination, Psychiatry and Mental health, medicine.anatomical_structure, Physical therapy, Female, Neurology (clinical), Cognition Disorders, Psychology

الوصف: There has been little investigation on the association between cognitive impairment and the microbleeds (MBs) frequently seen in subcortical vascular dementia (SVaD). One possible mechanism of cognitive decline in individuals with SVaD could be disruption of cholinergic fibers by vascular lesions. Central cholinergic circuits in human brain can be tested non-invasively by means of a transcranial magnetic stimulation (TMS) protocol named short latency afferent inhibition (SAI) of motor cortex. In the present study, we used this test in SvaD patients with and without MBs. SAI was evaluated in 13 SVaD patients with MBs (MB-positive group) and the data were compared with those from a group of 15 SVaD patients without MBs (MB-negative group) and with those from 20 healthy subjects. Moreover, we studied covariation of individual SAI values with the Mini-Mental State Examination (MMSE) total score and subscores. SAI was significantly reduced in the MB-positive group when compared with the MB-negative group and the control subjects. Total MMSE score, "attention and calculation" and "orientation" subscores were significantly lower in the MB-positive group than in the MB-negative group; SAI showed a positive correlation with total MMSE score. Adjustment for age, gender, education, presence of lacunae, severe white matter hyperintensities or severe periventricular hyperintensities did not affect these findings. This study provides novel physiological evidence that MBs have an impact on central cholinergic function that is independent of the extent of associated white matter changes and ischaemic stroke. This finding shows that TMS have potential diagnostic and therapeutic implications. TMS studies may help in evaluating the causes of cognitive impairment in cerebrovascular diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a90f8b76bd183476d762f7c7e149822Test
https://doi.org/10.1007/s00702-011-0650-5Test

المؤلفون: Stefanie Klein, Jürgen Bergmann, Alexander Kunz, Stefan Golaszewski, Martin Kronbichler, Gunther Ladurner, Raffaele Nardone, Frediano Tezzon, Francesca Caleri

المصدر: Journal of Neural Transmission. 115:1557-1562

مصطلحات موضوعية: Male, medicine.medical_specialty, Neurology, medicine.medical_treatment, Disease, Pathogenesis, Alzheimer Disease, Parasympathetic Nervous System, Afferent, Peripheral Nervous System, medicine, Humans, Short latency, Biological Psychiatry, Aged, Psychiatric Status Rating Scales, Electroshock, Motor Cortex, Middle Aged, Transcranial Magnetic Stimulation, Transcranial magnetic stimulation, Psychiatry and Mental health, medicine.anatomical_structure, Cholinergic, Female, Neurology (clinical), Psychology, Neuroscience, Motor cortex

الوصف: The pathogenesis of Alzheimer's disease (AD) appears to involve several different mechanisms, the most consistent of which is an impairment of cholinergic neurotransmission; however, there is controversy about its relevance at the early stage of disease. A transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with motor cortex TMS (short latency afferent inhibition, SAI) may give direct information about the function of some cholinergic pathways in the human motor cortex. We evaluated SAI in a group of patients with early diagnosis of AD and compared the data with that from a control group. The amount of SAI was significantly smaller in early AD patients than in controls. This study first provides physiological evidence that a central cholinergic dysfunction occurs in the earlier stages of AD. Identification of SAI abnormalities that occur early in the course of AD will allow earlier diagnosis and treatment with cholinergic drugs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::80087ed2dad0791c3705e28052a1915aTest
https://doi.org/10.1007/s00702-008-0129-1Test

المؤلفون: Stefan Golaszewski, Raffaele Nardone, Jürgen Bergmann, Frediano Tezzon, Gihither Ladurner

المصدر: Journal of Neural Transmission. 115:737-743

مصطلحات موضوعية: Male, medicine.medical_specialty, Neurology, medicine.medical_treatment, Neuropsychological Tests, Statistics, Nonparametric, Neurochemical, Reaction Time, medicine, Humans, Dementia, Vascular dementia, Biological Psychiatry, Aged, Dementia, Vascular, Motor Cortex, Human brain, Middle Aged, Evoked Potentials, Motor, medicine.disease, Transcranial Magnetic Stimulation, Electric Stimulation, Transcranial magnetic stimulation, Psychiatry and Mental health, medicine.anatomical_structure, Cholinergic, Female, Neurology (clinical), Psychology, Neuroscience, Motor cortex

الوصف: Little is known about the neurochemical pathology of vascular dementia (VD); it was suggested that cholinergic mechanisms play a role in the pathogenesis of VD, as well as been established for Alzheimer's disease (AD). A recently devised test of motor cortex excitability, the short latency afferent inhibition (SAI), has been proven to depend upon the activity of cholinergic circuits in the human brain. To evaluate, in vivo, the functional role of the cholinergic system in the cognitive dysfunction associated with VD, we used this test in 20 patients with subcortical ischemic VD (SIVD) and in 25 control subjects. Mean SAI was significantly reduced in the SIVD patients; however, individual data varied widely, with SAI responses ranging from normal to markedly reduced values. These findings provide physiological evidence for an important role for cholinergic mechanisms in the pathogenesis of VD. The evaluation of SAI, similar to that described in AD patients, could help in identifying those patients who are more likely to respond to treatment with cholinergic drugs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::28cb081e5bc0ed9a8c9eafcf984524faTest
https://doi.org/10.1007/s00702-007-0003-6Test