Sabina Bartalini

Effects of repetitive transcranial magnetic stimulation on chronic tinnitus: a randomised, crossover, double blind, placebo controlled study

Background: Chronic tinnitus is a disabling, almost untreatable, condition, usually accompanied by psychiatric distress. In patients with complex neuropsychiatric diseases, such as chronic pain, with which tinnitus shares pathophysiological similarities, placebo effects may be pronounced. Moreover, it may be difficult to distinguish actual repetitive transcranial magnetic stimulation (rTMS) induced clinical benefits beyond placebo effects in neuropsychiatric patients. Methods: 16 patients with chronic tinnitus underwent a randomised, double blind, crossover, placebo controlled trial of 1 Hz rTMS (120% of motor threshold; 1200 stimuli/day for 5 days) of the left temporoparietal region. Patients were screened for psychiatric comorbidity; additionally, anxiety and depression were monitored throughout the study. Moreover, an original placebo rTMS procedure produced the same activation of ipsilateral face muscles (a condition which may per se change the subjective rating of tinnitus) as the real rTMS. Results: There were 8 out of 14 responders. Two patients dropped out for transient worsening of tinnitus. Active rTMS induced an overall significant, but transient, improvement (35% of the basal score) of subjective tinnitus perception that was independent of either tinnitus laterality or mood or anxiety changes. No correlations were found between response to rTMS and tinnitus duration, initial subjective score or patient age. When asked after the study was over, 71.4% of patients failed to identify the temporal sequence of the real or sham rTMS interventions. Conclusion: The beneficial effects of rTMS on tinnitus are independent of mood changes. Moreover, they appear in the context of an original placebo stimulation designed to more closely replicate the somatic sensation of active stimulation. Because of the limited temporal duration of the clinical benefit, these neuromodulatory effects could be mediated by transient functional changes taking place in the neural circuits underlying tinnitus processing.

Slow Repetitive TMS for Drug-resistant Epilepsy: Clinical and EEG Findings of a Placebo-controlled Trial

Summary:  Purpose: To assess the effectiveness of slow repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for drug‐resistant epilepsy.

Intracranial Bleeding in Patients With Vertebrobasilar Dolichoectasia

Background and Purpose— Intracranial bleeding in patients with vertebrobasilar dolichoectasia (VBD) is considered uncommon, but there are no precise data to support this opinion. The purpose of this study was to examine the incidence and characteristics of intracranial hemorrhage in patients with VBD and to evaluate factors that may promote bleeding. Methods— We conducted a prospective study of 156 consecutive VDB patients followed-up for an average 9.35 years. The association of demographic, clinical, and imaging features with occurrence of intracranial bleeding was evaluated by multivariate analysis. Survival analysis was used to evaluate rates of incidence. Results— 32 hemorrhagic strokes were observed in 28 patients either as a diagnostic event (n=10) or during follow-up (n=22). Of the 32 hemorrhagic events, 6 were subarachnoid hemorrhage and 26 intraparenchymal hemorrhage. Multivariate analysis found an association between intracranial bleeding and maximum diameter of the basilar artery (OR, 4.29; P=0.009), degree of lateral displacement of the basilar artery (OR, 4.53; P=0.004), hypertension (OR, 4.74; P=0.024), use of antiplatelet or anticoagulant agents (OR, 3.07; P=0.033), and female sex (OR 6.33; P=0.001). The cumulative proportion of survivors free of hemorrhagic stroke was 88.6 at 5 years and 84.4 at 10 years. Conclusions— Our study showed that intracranial bleeding in patients with VBD is not as uncommon as usually believed. Its occurrence is associated with the degree of ectasia and elongation of the basilar artery and may be favored by hypertension and use of antiplatelet or anticoagulant agents.

Polysomnographic characterization of pergolide-induced sleep attacks in idiopathic PD

Abstract—Both dopamine agonists and levodopa may induce episodes termed “sleep attacks” in patients with PD. These episodes are well detailed behaviorally, but little is known about their neurophysiologic characterization. The authors performed a 24-hour polysomnography (PSG) in a PD patient taking pergolide in combination with levodopa, in which four of these diurnal sleep episodes occurred. PSG findings were followed up after pergolide withdrawal. Sleep episodes shared with narcolepsy both behavioral and EEG findings. However, pergolide partly restored a more physiologic sleep architecture, which was disrupted during therapy with levodopa alone.

Dysfunctions of Cortical Excitability in Drug-Naïve Posttraumatic Stress Disorder Patients

BACKGROUND The investigation of a wide set of transcranial magnetic stimulation (TMS)-related variables in both hemispheres might help to identify a pattern of cortical excitability changes in posttraumatic stress disorder (PTSD) patients, reflecting gamma-amino-butiric acid (GABA)/glutamate balance and dysfunction, and to determine whether some of these variables are related to clinical features. METHODS In 20 drug-naive PTSD patients without comorbidity and 16 matched healthy control subjects we tested bilaterally with standard TMS procedures: resting motor threshold (RMT) to single-pulse TMS (reflecting ion channel function), paired-pulse short-latency intracortical inhibition (SICI; mainly reflecting GABA(A) function) and intracortical facilitation (ICF; mainly reflecting glutamatergic function), single-pulse cortical silent period (CSP; mainly reflecting GABA(B)-ergic function), and paired-pulse short-latency afferent inhibition (SAI; reflecting cholinergic mechanisms and their presynaptic GABA(A)-mediated modulation). RESULTS The PTSD patients showed widespread impairment of GABA(A)-ergic SICI, which was reversed toward facilitation in both hemispheres in one-half of the patients, marked increase of glutamatergic ICF in the right hemisphere, and right-sided impairment of SAI. Illness duration and avoidance symptoms but not anxiety correlated with right-lateralized dysfunctions of cortical excitability. CONCLUSIONS Although the neurobiological complexity of each TMS variable makes current results theoretical, the pattern of cortical excitability accompanying PTSD symptoms suggests a bilateral decrease of the GABA(A)-ergic function. This prevails in the right hemisphere, in association with a relative prevalence of the glutamatergic tone, a new finding that current neuroimaging investigations cannot provide due to the lack of reliable glutamate tracers. Results might help to disclose new pathophysiological aspects of PTSD symptoms, providing a rationale for future neuromodulatory strategies of treatment.

Reduction of cortical myoclonus-related epileptic activity following slow-frequency rTMs. A case study

In a drug-resistant epilepsy patient with continuous forearm/hand positive myoclonia due to a focal cortical dysplasia of the right motor cortex, cortical jerk-related and electromyographic activity were recorded for 15 min before and after 1 Hz rTMS (15 min, 10% below the resting excitability threshold) of the right motor cortex. A stable negative cortical spike, time-locked with contralateral muscle jerks (60 > 100 μV), was detected only at perirolandic electrodes (maximal amplitudes: block 1 = 21.3 μV, block 2 = 22 μV, block 3 = 25.9 μV). After rTMS, only 20 muscle jerks accomplished the criterion of >100 μV; blind back-averaging of these disclosed a topographically similar cortical spike, but with amplitude reduced by at least 50% (11.2 μV). This represents in vivo evidence of the possibility to selectively modulate the activity of an epileptic focus by intervening with local low-frequency rTMS.

Distinct Olfactory Cross-Modal Effects on the Human Motor System

Background Converging evidence indicates that action observation and action-related sounds activate cross-modally the human motor system. Since olfaction, the most ancestral sense, may have behavioural consequences on human activities, we causally investigated by transcranial magnetic stimulation (TMS) whether food odour could additionally facilitate the human motor system during the observation of grasping objects with alimentary valence, and the degree of specificity of these effects. Methodology/Principal Findings In a repeated-measure block design, carried out on 24 healthy individuals participating to three different experiments, we show that sniffing alimentary odorants immediately increases the motor potentials evoked in hand muscles by TMS of the motor cortex. This effect was odorant-specific and was absent when subjects were presented with odorants including a potentially noxious trigeminal component. The smell-induced corticospinal facilitation of hand muscles during observation of grasping was an additive effect which superimposed to that induced by the mere observation of grasping actions for food or non-food objects. The odour-induced motor facilitation took place only in case of congruence between the sniffed odour and the observed grasped food, and specifically involved the muscle acting as prime mover for hand/fingers shaping in the observed action. Conclusions/Significance Complex olfactory cross-modal effects on the human corticospinal system are physiologically demonstrable. They are odorant-specific and, depending on the experimental context, muscle- and action-specific as well. This finding implies potential new diagnostic and rehabilitative applications.

Modulation of high-frequency (600 Hz) somatosensory-evoked potentials after rTMS of the primary sensory cortex.

Somatosensory inputs to the primary sensory cortex (S1) after median nerve stimulation include temporally overlapping parallel processing, as reflected by standard low‐frequency somatosensory‐evoked potentials (LF‐SEPs) and high‐frequency SEPs (HF‐SEPs), the latter being more sensitive to arousal and to other rapid adaptive changes. Experimental data suggest that cortical HF‐SEPs are formed by two successive pre‐ and postsynaptic components, respectively, generated in the terminal part of thalamo‐cortical radiation (early burst) and in specialized neuronal pools within S1 (later burst).

Uncommon findings in idiopathic hypertrophic cranial pachymeningitis

Abstract.Background:Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare, poorly understood, inflammatory disease, usually involving the dura mater of skull base, tentorium, and falx, and presenting with headache, progressive cranial nerve palsies, and cerebellar dysfunction.Patients and Methods:In four patients, the diagnosis of IHCP has been made on the basis of extensive clinical, and radiological investigation, and confirmed by dural biopsy in three patients. The clinical follow-up ranges from 24 to 120 months.Results :At diagnosis, all the patients complained of severe, progressively increasing headache, two had simple or complex partial seizures, but none had cranial nerve palsies. Two patients had electrophysiological evidence of axonal peripheral neuropathy, biopsy-proved in one of them. In all the patients, MRI showed linear or focal thickening of the dura mater of the tentorium and/or of the convexity, sparing the skull base. In one patient, MRI findings resembled chronic subdural hematoma. Dural biopsy demonstrated fibrosis and prominent CD4+ T-cells inflammatory infiltrate. Pachymeningitis was highly responsive to steroid therapy, as was the peripheral neuropathy. In three patients, temporary steroids withdrawal led to dramatic clinical worsening including status epilepticus in one.Conclusions :In the patients here reported, absence of cranial nerve impairment, seizures, MRI findings resembling chronic subdural hematoma, and association with polineuropathy were unusual findings of IHCP. Moreover, the type of inflammatory infiltrate, lacking in previous reported cases, suggests a probable pathogenetic role for cell-mediated immunity of unknown origin.

Temporal Dynamics of Memory Trace Formation in the Human Prefrontal Cortex

Event-related repetitive transcranial magnetic stimulation (rTMS) can dynamically interfere with the memory encoding of complex visual scenes. Here, we investigated the critical time elapsing from stimulus presentation to the formation of an effective memory trace by delivering rTMS (900 ms at 20 Hz) during the encoding of visual scenes at different poststimulus delays (from 100 to 500 ms) in 28 healthy volunteers. The stimulation delay showed a robust inverse correlation with the correct retrieval of encoded images. In particular, rTMS stimulation delivered with a delay of 500 ms and lasting for 400 ms after stimulus offset resulted in a huge drop in retrieval accuracy. Such a timing suggests that rTMS affects the formation of long-term memory through interference with postperceptual executive processes, rather than with perceptual analysis of the stimuli. The effect was specific for stimulation of the left dorsolateral prefrontal cortex (DLPFC), whereas rTMS applied to the right DLPFC, vertex (active control site), as well as sham stimulation (placebo) did not affect accuracy. These results confirm the crucial role of the left DLPFC in encoding and provide novel information about the critical timing of its engagement in the formation, consolidation, and maintenance of the memory trace.