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The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 05/2013; 40(3):429-30. · 0.97 Impact Factor
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ABSTRACT: The experimental and clinical evidence in support of "rational polytherapy" is sparse, and to date, no clear evidence-based indications can be made to help physicians in their choice of a specific drug combination against specific forms of epilepsy. This article briefly reviews the data available in the literature and obtained from studies conducted in humans to evaluate which main AED combinations might possess supraadditive, synergistic effects in terms of efficacy, with infraadditive toxicity. By far, the most documented association resulting in supraadditive anticonvulsant effects against focal seizures is that of VPA and LTG. There are some indications that combinations of drugs with different primary mechanisms of action may be more effective than combining drugs with the same mechanisms of action. However, further animal and human research studies that focus both on toxicity and anticonvulsant effects of various combinations of AEDs are required.
Epilepsy & Behavior 04/2013; 27(3):439-442. · 2.34 Impact Factor
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ABSTRACT: Rapid eye movement (REM) sleep behavior disorder (RBD) is a clinical condition characterized by an intermittent or complete loss of muscle atonia and an increase of phasic muscular activity during REM sleep (or Stage R), leading to complex nocturnal motor behaviors. Correct and early diagnosis is important because RBD may lead to serious injuries and is a well-treatable disorder. Since the characteristic electrophysiologic finding in patients with RBD is the increased electromyographic tone during REM sleep/Stage R, simultaneous video/polysomnography recording is essential for diagnosing this parasomnia. Moreover, several neurophysiological techniques have been used to improve our knowledge and understanding of this troubling sleep disorder. We reviewed the most important studies employing quantitative electroencephalography, event-related potentials, transcranial magnetic stimulation, brainstem reflexes and cortico-muscular coherence analysis. All these neurophysiological techniques have proven to provide a valuable tool to gain insight into the pathophysiological mechanisms underlying RBD. The review concludes with a brief discussion on the possible future implications for improving therapeutic approaches.
Neuroscience Research 03/2013; · 2.25 Impact Factor
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ABSTRACT: Plastic changes of neural circuits occur after spinal cord injury (SCI) at various level of the central nervous system. In this review we will focus on delineating the pathophysiological mechanisms of the brain plasticity changes following SCI, based on the existing neuroimaging and neurophysiological evidence in experimental models and humans. In animal experiments, reorganization of the sensory topography as well as of the topographical map of primary motor and premotor cortices have been reported in several studies. Brain imaging revealed that cortical representation in response to spared forelimb stimulation early enlarges and invades adjacent sensory-deprived hind limb territory. Electrophysiological studies demonstrated that the deafferentation due to SCI can immediately change the state of large cortical networks within 1hour, and that these changes play a critical role in the functional reorganization after SCI. In humans neuroimaging also showed shifts of functional motor and sensory cortical representations that relate to the severity of SCI. In patients with cervical SCI, cortical forearm motor representations, as assessed by means of transcranial magnetic stimulation, may reorganize towards the intrinsic hand motor representation to maximize output to muscles of the impaired forearm. Excessive or aberrant reorganisation of cerebral cortex may also have pathological consequences, such as phantom sensations or neuropathic pain. Integrated neuroimaging and neurophysiological approaches may also lead to the development of new therapeutic strategies, which have the potential of enhancing sensorimotor recovery in patients with SCI.
Brain research 02/2013; · 2.46 Impact Factor
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ABSTRACT: OBJECTIVES: To report values of optic nerve sheath diameter (ONSD) and optic disc elevation (ODE) obtained with optic nerve sonography (US) in the diagnosis and monitoring of treatment efficacy in an adult with idiopathic intracranial hypertension (IIH). METHODS: Serial measurements of the ONSD and ODE using B mode US were performed in a 45-years-old woman with IIH before and during after treatment with acetazolamide and diet. RESULTS: At first evaluation US showed a significantly enlarged ONSD (.68 cm right; .66 cm left side) and the presence of increased ODE (.1 cm right; .15 cm left side). Post-punctural assessments showed a bilateral decrease of ONSD (.58 cm right; .58 cm left side), without changes in ODE values. After 12 months of treatment with acetazolamide and diet ODE completely normalized (0 cm on both sides). ODE values correlated directly with ONSD, and both ODE and ONSD values correlated directly with BMI. Correlations were statistically significant. ONSD changes occurred rapidly after the lumbar puncture, whereas the papilloedema required longer to reduce. CONCLUSIONS: US of ONSD and ODE was useful to support the diagnosis of IIH and to monitor the efficacy of diet and pharmacological treatment. Further studies are required to evaluate whether this promising technique may be considered a reliable and accurate method to longitudinally evaluate patients with increased ICP secondary to IIH.
Journal of neuroimaging: official journal of the American Society of Neuroimaging 01/2013; · 1.72 Impact Factor
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ABSTRACT: Seizures may frequently occur during tuberculous meningitis. We describe a patient with an apparent generalised tonic-clonic seizure, initially not associated with any magnetic resonance imaging (MRI) abnormality, which was the presenting symptom of tuberculous meningitis. Follow-up MRI, performed after gadolinium administration, showed signs of meningeal involvement. Seizures may be the presenting symptoms of tuberculous meningitis even in the absence of evident intracerebral lesions on MRI. Therefore, contrast-enhanced brain MRI should be performed in the diagnostic workup for each first seizure, especially in patients with a clinical suspicion of CNS infectious disease. The term "heraldic seizure", indicating a subset of acute symptomatic seizures presenting at the onset of a brain/systemic injury or preceding the full clinical manifestation of a cerebral insult, may be helpful to classify these seizures retrospectively, based initially on unknown aetiology.
Epileptic disorders: international epilepsy journal with videotape 08/2012; 14(3):329-33. · 1.50 Impact Factor
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ABSTRACT: Acute and chronic consumption of alcohol have direct effects on central nervous system by altering predominantly gamma-aminobutyric acidergic and glutamatergic neurotransmission. Abnormalities in these neurotransmitter systems can be demonstrated by changes in cortical excitability parameters assessed with transcranial magnetic stimulation (TMS). Furthermore, integrated approaches utilizing TMS combined with electroencephalography (EEG) enable the evaluation of the focal effects of alcohol on the human cortex, providing useful information, different from that obtained using other functional brain imaging modalities. Alcohol was found to modulate EEG responses evoked by motor-cortex TMS, predominantly at the right prefrontal cortex, indicating that ethanol alters the functional connectivity between motor and prefrontal areas. Alcohol decreases amplitudes of EEG responses of anterior parts of the cortex after left prefrontal TMS, suggesting a decrease of prefrontal cortical excitability. High-frequency repetitive TMS (rTMS) revealed significant changes in short-term plasticity of the primary motor cortex after acute ethanol intake and in patients with chronic alcohol abuse. TMS findings also support the recently emerged theory that abnormal function of glutamate receptors plays a relevant role in the development of alcohol dependence and manifestation of the alcohol withdrawal syndrome. Finally, initial studies provide evidence that non-invasive brain stimulation techniques (rTMS and transcranial direct current stimulation) might represent a potential therapeutic tool to reduce alcohol craving. Future studies with larger sample size evaluating the clinical effects of these neuromodulatory approaches are required to confirm and extend the preliminary findings.
Neuroscience Research 08/2012; · 2.25 Impact Factor
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ABSTRACT: Central cholinergic dysfunction has been reported in patients with Parkinson's disease (PD) and hallucinations by evaluating short latency afferent inhibition (SAI), a transcranial magnetic stimulation protocol which gives the possibility to test an inhibitory cholinergic circuit in the human brain. REM sleep behavior disorder (RBD) was also found to be associated with cognitive impairment in PD patients. The objective of the study was to assess the cholinergic function, as measured by SAI, in PD patients with RBD (PD-RBD) and PD patients without RBD (PD-nRBD). We applied the SAI technique in 10 PD-RBD patients, in 13 PD-nRBD patients and in 15 age-matched normal controls. All PD patients and control subjects also underwent a comprehensive battery of neuropsychological tests. Mean SAI was significantly reduced in PD-RBD patients when compared with PD-nRBD patients and controls. Neuropsychological examination showed mild cognitive impairment in 9 out of the 10 PD-RBD patients, and in 5 out of the 13 PD-nRBD. SAI values correlated positively with neuropsychological tests measuring episodic verbal memory, executive functions, visuoconstructional and visuoperceptual abilities. Similar to that previously reported in the idiopathic form of RBD, SAI abnormalities suggest a cholinergic dysfunction in PD patients who develop cognitive impairment, and present findings indicate that RBD is an important determinant of MCI in PD.
Acta Neurovegetativa 08/2012; · 2.73 Impact Factor
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ABSTRACT: Impaired cognitive profile and electroencephalography (EEG) slowing have been reported in patients with REM sleep behavior disorder (RBD), but the neurobiological significance of these findings remains unknown. The cholinergic system is known to play a key role in all attentional processes and cognitive functions. A transcranial magnetic stimulation (TMS) protocol may give direct information about the function of some cholinergic circuits in the human brain; this technique relies on short latency afferent inhibition (SAI) of the motor cortex. The objective of this study was to test the hypothesis that cognitive performance and cortical activation in RBD patients are associated with a dysfunction of the cholinergic system.
We applied the SAI technique in a group of 10 patients with idiopathic RBD (iRBD) and compared the data with those from a group of 15 age-matched healthy subjects. All the iRBD patients and the control subjects also underwent an extensive neuropsychological evaluation.
Mean SAI was significantly reduced in patients with iRBD when compared with controls. Neuropsychological examination showed mild cognitive impairment in six out of the 10 iRBD patients. SAI values correlated strongly with tests measuring episodic verbal memory and executive functions.
These results support the hypothesis of cholinergic dysfunction in some patients with iRBD who develop cognitive impairment. Our findings raise the possibility that the presence of SAI abnormalities may indicate increased risk of cognitive impairment in patients diagnosed with iRBD.
Sleep Medicine 06/2012; 13(7):919-25. · 3.40 Impact Factor
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ABSTRACT: It has been recently shown that 20 min of mechanical flutter stimulation induces lasting motor cortical excitability changes, as assessed by transcranial magnetic stimulation in relaxed hand muscles. The present functional magnetic resonance imaging (fMRI) study aims to examine if such neuromodulatory changes are reflected in the BOLD signal during a motor test. Therefore, two groups were recruited: one group receiving whole-hand flutter stimulation with a frequency of 25 Hz (FSTIM group, n = 22) and a second group receiving no stimulation (NOSTIM group, n = 22). As motor test finger-to-thumb tapping was performed to activate a wide sensorimotor network during the fMRI measurements. Three fMRI measurements were obtained with this test: before stimulation (PRE), after stimulation (POST1), and 1 h after stimulation (POST2). Three regions of interest (ROIs) were defined: primary motor area (M1), primary somatosensory area (S1), and supplementary motor area. In the absence of baseline differences between both groups, the FSTIM group showed increased movement-related brain activations compared with the NOSTIM group, both at POST1 and POST2. ROI analysis revealed increased blood-oxygenation-level-dependent (BOLD) responses within contralateral S1 (+20%) and M1 (+25%) at POST1, which lasted until POST2. These poststimulatory effects within S1 and M1 obviously reflect neuroplastic changes associated with augmented cortical excitability. These findings are of high clinical relevance, for example, to improve the treatment of stroke patients. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
Human Brain Mapping 05/2012; · 5.88 Impact Factor
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ABSTRACT: 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.
Acta Neurovegetativa 04/2012; 115(11):1557-1562. · 2.73 Impact Factor
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ABSTRACT: We report a patient showing isolated phonological agraphia after an ischemic stroke involving the left supramarginal gyrus (SMG). In this patient, we investigated the effects of focal repetitive transcranial magnetic stimulation (rTMS) given as theta burst stimulation (TBS) over the left SMG, corresponding to the Brodmann area (BA) 40. The patient and ten control subjects performed a dictational words and nonwords writing task before, and 5 and 30 min after they received excitatory intermittent TBS (iTBS) over the left BA 40, the right hemisphere homologous to BA 40, the Wernicke's area, or the primary visual cortex. ITBS over the left SMG lead to a brief facilitation of phonological non-words writing to dictation. This case study report illustrates that rTMS is able to influence, among other language functions, the phonological loading processes during the written language production in stroke patients.
Brain and Language 01/2012; 120(3):422-6. · 3.12 Impact Factor
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ABSTRACT: Available pharmacological treatments for Alzheimer disease (AD) have limited effectiveness, are expensive, and sometimes induce side effects. Therefore, alternative or complementary adjuvant therapeutic strategies have gained increasing attention. The development of novel noninvasive methods of brain stimulation has increased the interest in neuromodulatory techniques as potential therapeutic tool for cognitive rehabilitation in AD. In particular, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are noninvasive approaches that induce prolonged functional changes in the cerebral cortex. Several studies have begun to therapeutically use rTMS or tDCS to improve cognitive performances in patients with AD. However, most of them induced short-duration beneficial effects and were not adequately powered to establish evidence for therapeutic efficacy. Therefore, TMS and tDCS approaches, seeking to enhance cognitive function, have to be considered still very preliminary. In future studies, multiple rTMS or tDCS sessions might also interact, and metaplasticity effects could affect the outcome.
International journal of Alzheimer's disease. 01/2012; 2012:687909.
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ABSTRACT: 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.
Acta Neurovegetativa 10/2011; 119(4):463-71. · 2.73 Impact Factor
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ABSTRACT: Little attention has been given to the fetal-type posterior circle of Willis (FTP) in the literature; also symptomatic basilar artery (BA) hypoplasia has been rarely reported. We aimed to illustrate that the association of a hypoplastic vertebrobasilar system (VBS) with the FTP may lead to posterior circulation ischemia. Magnetic resonance imaging and three-dimensional time-of-flight magnetic resonance angiography were performed in 88 consecutive patients with ischemic stroke or TIA in the VBS. Thirteen patients were identified with either stroke or TIA in the context of a hypoplastic VBS and a fetal origin of the posterior cerebral arteries. All patients had unilateral or bilateral FTP, hypoplastic BA and at least one hypoplastic vertebral artery. Transcranial color-coded duplex revealed decreased flow velocity and increased pulsatility index along the BA. A hypoplastic VBS may be accompanied by the FTP and its simultaneous occurrence can predispose to ischemic events in the posterior circulation.
Neurological Sciences 09/2011; 32(6):1143-6. · 1.32 Impact Factor
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Clinical neurology and neurosurgery 08/2011; 113(9):779-81. · 1.30 Impact Factor
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ABSTRACT: Central cholinergic circuits of human brain can be tested non-invasively by coupling electrical peripheral stimulation with transcranial magnetic stimulation (TMS) of the motor cortex. The short-latency afferent inhibition (SAI) is reduced in cholinergic forms of dementia, such as Alzheimer disease (AD) and dementia with Lewy bodies, while it is normal in non-cholinergic forms of dementia, such as frontotemporal dementia. This finding suggests that this method can be used as a non-invasive additional tool for discriminating between cholinergic and non-cholinergic forms of dementia. Interestingly, SAI was also found to be significantly smaller in early AD patients. Identification of SAI abnormalities that occur early in the course of AD will allow earlier diagnosis and treatment with cholinergic drugs. In patients with vascular dementia, SAI responses varied widely; the number of patients with abnormal SAI conceivably reflects the percentage of subjects with a significant cholinergic dysfunction. It has recently been demonstrated that brain microbleeds have an impact on SAI that is independent of the extent of associated white matter changes and ischemic stroke. Since SAI can be increased by acetylcholinesterase inhibitors, TMS may help in identifying the patients who would be suitable for long-term treatment with cholinergic agents.
Dementia and Geriatric Cognitive Disorders 08/2011; 32(1):18-25. · 2.14 Impact Factor
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ABSTRACT: We report a case of acute disseminated encephalomyelitis preceding measles virus infection. Brain magnetic resonance imaging revealed signal intensity abnormalities in the basal ganglia and cortex consistent with acute disseminated encephalomyelitis. Fever and the first Koplik spots appeared 8 and 10 days later, respectively. This case supports the hypothesis that the immune-mediated demyelinating process may occur before the symptomatic phase of a viral infection. Therefore, children without history of infectious disorders should also have acute disseminated encephalomyelitis included in the differential considerations.
Journal of child neurology 07/2011; 26(12):1590-2. · 1.59 Impact Factor
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ABSTRACT: In a previous transcranial magnetic stimulation (TMS) study we demonstrated that suprathreshold mesh-glove (MG) whole-hand stimulation elicits lasting changes in motor cortical excitability. Currently, there is no consensus with regard to the optimal parameters for the induction of sensorimotor cortical plasticity using peripheral electrical stimulation. Thus, in the present study we explore the modulatory effects of MG stimulation at different stimulus intensities and different frequencies in order to identify an optimal stimulation protocol.
MG stimulation was performed on 12 healthy subjects in separate sessions at different stimulation levels: sub-sensory at 50 Hz, sensory at 50 Hz and motor at 2 Hz. To verify if stimulation at lower frequencies is less effective, an additional experiment at sensory level with 2 Hz was performed. TMS was used to assess motor threshold (MT), motor evoked potentials (MEPs) recruitment curve (RC), short latency intracortical inhibition (SICI) and intracortical facilitation (ICF) to paired-pulse TMS at baseline (T0), immediately after (T1) and 1h (T2) after 30 min of MG stimulation. F-wave studies were performed to assess spinal motoneuron excitability.
MG stimulation at sub-sensory/50 Hz and sensory/2 Hz level determines no significant cortical excitability changes; at sensory/50 Hz level and at motor/2 Hz level we found decreased MT, increased MEP RC as well as reduced SICI and increased ICF at T1 and T2.
MG stimulation at sensory/50 Hz and motor/2 Hz level induces similar long-lasting modulatory effects on motor cortical excitability. Both the strength of the corticospinal projections and the intracortical networks are influenced to the same extend.
The study provides further evidence that stimulation intensity and frequency can independently modulate motor cortical plasticity. The selection of optimal stimulation parameters has potentially important implications for the neurorehabilitation of patients after brain damage (e.g. stroke, traumatic brain injury) with hand motor deficits.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 07/2011; 123(1):193-9. · 3.12 Impact Factor
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ABSTRACT: 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.
Acta Neurovegetativa 04/2011; 118(9):1349-58. · 2.73 Impact Factor
