Piera Paladino

Elevated cerebrospinal fluid and plasma homocysteine levels in ALS

Background:  High cerebrospinal fluid (CSF) and plasma levels of homocysteine (HC) have been reported in certain neurodegenerative disorders, such as Alzheimer’s, Parkinson’s diseases and, recently, amyotrophic lateral sclerosis (ALS).

Cyclical changes of cortical excitability and metaplasticity in migraine: evidence from a repetitive transcranial magnetic stimulation study.

Summary Insight is provided into the pathophysiological mechanisms underlying the abnormal regulation of cortical function and its periodicity in episodic and chronic migraine. ABSTRACT The primary brain dysfunctions leading to the onset of a migraine attack remain largely unknown. Other important open questions concern the mechanisms of initiation, continuation, and termination of migraine pain, and the changes in brain function underlying migraine transformation. Brief trains of high‐frequency repetitive transcranial magnetic stimulation (rTMS), when applied to the primary motor cortex at suprathreshold intensity (≥120% of resting motor threshold [RMT]), elicit in healthy subjects a progressive, glutamate‐dependent facilitation of the motor evoked potentials (MEP). Conversely, in conditions of increased cortical excitability, the rTMS trains induce inhibitory MEP responses likely mediated by cortical homeostatic mechanisms. We enrolled 66 migraine‐without‐aura patients, 48 migraine‐with‐aura patients, 14 patients affected by chronic migraine (CM), and 20 healthy controls. We assessed motor cortical response to 5‐Hz rTMS trains of 10 stimuli given at 120% RMT. Patients with episodic migraine were studied in different phases of the migraine cycle: interictal, preictal, ictal, and postictal states. Results showed a facilitatory MEP response during the trains in patients evaluated in the preictal phase, whereas inhibitory responses were observed during and after a migraine attack, as well as in CM patients. In the interictal phase, different responses were observed, depending on attack frequency: facilitation in patients with low and inhibition in those with high attack recurrence. Our findings suggest that changes in cortical excitability and fluctuations in the threshold for inhibitory metaplasticity underlie the migraine attack recurrence, and could be involved in the process of migraine transformation.

Transcranial direct current stimulation preconditioning modulates the effect of high-frequency repetitive transcranial magnetic stimulation in the human motor cortex

Experimental studies emphasize the importance of homeostatic plasticity as a mean of stabilizing the properties of neural circuits. In the present work we combined two techniques able to produce short‐term (5‐Hz repetitive transcranial magnetic stimulation, rTMS) and long‐term (transcranial direct current stimulation, tDCS) effects on corticospinal excitability to evaluate whether and how the effects of 5‐Hz rTMS can be tuned by tDCS preconditioning. Twelve healthy subjects participated in the study. Brief trains of 5‐Hz rTMS were applied to the primary motor cortex at an intensity of 120% of the resting motor threshold, with recording of the electromyograph traces evoked by each stimulus of the train from the contralateral abductor pollicis brevis muscle. This interventional protocol was preconditioned by 15 min of anodal or cathodal tDCS delivered at 1.5 mA intensity. Our results showed that motor‐evoked potentials (MEPs) increased significantly in size during trains of 5‐Hz rTMS in the absence of tDCS preconditioning. After facilitatory preconditioning with anodal tDCS, 5‐Hz rTMS failed to produce progressive MEP facilitation. Conversely, when 5‐Hz rTMS was preceded by inhibitory cathodal tDCS, MEP facilitation was not abolished. These findings may give insight into the mechanisms of homeostatic plasticity in the human cerebral cortex, suggesting also more suitable applications of tDCS in a clinical setting.

Visual cortex hyperexcitability in migraine in response to sound-induced flash illusions

Objective: Sound-induced flash illusions depend on visual cortical excitability. In this study, we explored whether sound-induced flash illusions are perceived differently in migraine, a condition associated with pathologic cortical hyperexcitability. Methods: Sound-induced flash illusions were examined in 59 migraine patients (mean age = 32 ± 16 years; 36 females), 32 without aura and 27 with aura, and in 24 healthy controls (mean age = 42 ± 17 years; 16 females). Patients were studied during attacks and interictally. Visual stimuli (flashes) accompanied by sounds (beeps) were presented in different combinations: a single flash with multiple beeps was given to induce the perception of multiple flashes (“fission” illusion), and multiple flashes with a single beep were used to reduce the number of perceived flashes (“fusion” illusion). Results: For migraineurs, the fission illusion was reduced, especially during the attack, and almost abolished when a single flash was combined with 2 beeps (except for those without aura tested interictally); the fusion illusion was less consistently reported in both migraine groups, but not completely disrupted. Conclusions: Results from this study add novel clues to our understanding of visual cortex hyperexcitability in migraine, especially migraine with aura. Furthermore, these analyses underscore how pathologic changes in cortical excitability affect multisensory interactions. Cross-modal illusions represent a valid tool for exploration of functional connectivity between sensory areas, which likely has an important role in the pathophysiology of migraine.

Cerebrospinal fluid tau protein is not a biological marker in amyotrophic lateral sclerosis

Background:  Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to progressive motor neuron cell death. Etiopathogenesis is still imperfectly known and much effort have been undertaken to find a biological marker that could help in the early diagnosis and in the monitoring of disease progression. Cerebrospinal fluid (CSF) concentrations of tau, an axonal microtubule‐associated protein, have been measured in ALS with levels found increased in some studies and unchanged in others.

Reduced threshold for inhibitory homeostatic responses in migraine motor cortex? A tDCS/TMS study.

Neurophysiological studies in migraine have reported conflicting findings of either cortical hyper‐ or hypoexcitability. In migraine with aura (MwA) patients, we recently documented an inhibitory response to suprathreshold, high‐frequency repetitive transcranial magnetic stimulation (hf‐rTMS) trains applied to the primary motor cortex, which is in contrast with the facilitatory response observed in the healthy subjects. The aim of the present study was to support the hypothesis that in migraine, because of a condition of basal increased cortical responsivity, inhibitory homeostatic‐like mechanisms of cortical excitability could be induced by high magnitude stimulation. For this purpose, the hf‐rTMS trains were preconditioned by transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique able to modulate the cortical excitability state.

Effects of transcranial direct current stimulation on esophageal motility in patients with gastroesophageal reflux disease.

OBJECTIVE To evaluate the effects of transcranial direct current stimulation (tDCS) on esophageal peristalsis in patients with gastroesophageal reflux disease (GERD). METHODS Patients with GERD preliminary diagnosis were included in a randomized double-blind sham-controlled study. Esophageal manometry was performed before and during transcranial direct current stimulation (tDCS) of the right precentral cortex. Half of patients were randomly assigned to anodal, half to sham stimulation. Distal waves amplitude and pathological waves percentage were measured, after swallowing water boli, for ten subsequent times. Last, a 24h pH-bilimetry was done to diagnose non-erosive reflux disease (NERD) or functional heartburn (FH). The values obtained before and during anodal or sham tDCS were compared. RESULTS Sixty-eight patients were enrolled in the study. Distal waves mean amplitude increased significantly only during anodal tDCS in NERD (p=0.00002) and FH subgroups (p=0.008) while percentage of pathological waves strongly decreased only in NERDs (p=0.002). CONCLUSIONS Transcranial stimulation can influence cortical control of esophageal motility and improve pathological motor pattern in NERD and FH but not in erosive reflux disease (ERD) patients. SIGNIFICANCE Pathophysiological processes in GERD are not only due to peripheral damage but to central neural control involvement as well. In ERD patients dysfunctions of the cortico-esophageal circuit seem to be more severe and may affect central nervous system physiology.

O069. Menstrual cycle affects cortical excitability differently in females with migraine and in healthy controls: a new perspective by cross modal sound induced flash illusions

The sound-induced flash illusions (SIFI) represent a valid tool to explore multimodal perception and are critically dependent on visual and acoustic cortical excitability [1, 2]. In a previous study [3], we observed a significant reduction of illusions in migraine patients with respect to healthy controls, probably due to a condition of visual cortex hyperexcitability. Aim of the present study was to evaluate SIFI perceptions in healthy women and patients with menstrual migraine and to describe the effects of cyclical change of steroid hormones and cortical responsiveness.

EHMTI-0220. Cortical excitability in episodic cluster headache

Methods Twenty-five patients with episodic CH and thirteen healthy subjects underwent an experimental session where we evaluated, in both hemispheres, motor-cortical response to: 1) single-pulse TMS: i.e. motor threshold (MT); input-output (IO) curves and cortical silent period (CSP) and 2) paired-pulse TMS: i.e. intracortical facilitation (ICF) and short intracortical inhibition (SICI). Thirteen patients were evaluated outside bout, while the remaining twelve patients were inside bout at the time of recording.

Changes in glutamatergic neurotransmission within the migraine cycle

Background Although some neurophysiological studies have showed cortical excitability changes during different phases of the migraine cycle, the pathophysiological mechanisms underlying attacks recurrence remain unknown. Here we evaluated the response of the migraine motor-cortex to brief trains of 5-Hz repetitive transcranial magnetic stimulation (rTMS) in order to study, indirectly, presynaptic mechanisms of glutamatergic neurotransmission across the different phases of the migraine cycle.