Monica Ulivelli

Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive–compulsive disorder (OCD) and Tourette's syndrome (TS)

There is evidence that motor and premotor cortex are hyperexcitable in obsessive-compulsive disorder (OCD) and Tourettes syndrome (TS). We tested whether low-frequency repetitive transcranial magnetic stimulation (rTMS) could normalize overactive motor cortical regions and thereby improve symptoms. Subjects with OCD or TS were treated with active rTMS to the supplementary motor area (SMA) for 10 daily sessions at 1 Hz, 100% of motor threshold, 1200 stimuli/day. Suggestions of clinical improvement were apparent as early as the first week of rTMS. At the second week of treatment, statistically significant reductions were seen in the YBOCS, YGTSS, CGI, HARS, HDRS, SAD, BDI, SCL-90, and SASS. Symptoms improvement was correlated with a significant increase of the right resting motor threshold and was stable at 3 months follow-up. Slow rTMS to SMA resulted in a significant clinical improvement and a normalization of the right hemisphere hyperexcitability, thereby restoring hemispheric symmetry in motor threshold.

Seizures after spontaneous supratentorial intracerebral hemorrhage.

Summary:  Purpose: To characterize seizures after intracerebral hemorrhage (ICH), evaluating the risk of occurrence and relapse, predisposing factors, and prognostic significance, and to assess the utility of antiepileptic drug (AED) therapy as used in clinical practice.

The influence of diabetes and hyperglycemia on clinical course after intracerebral hemorrhage

Objective: To determine whether diabetes and admission hyperglycemia in nondiabetic patients influence outcome and the occurrence of cerebral and medical complications after intracerebral hemorrhage (ICH). Methods: The study sample included 764 patients with ICH. The effects of diabetes and admission hyperglycemia were examined in relation to 30-day and 3-month mortality using Cox regression models controlling for potential confounders. The analysis was conducted for the entire sample of patients and repeated in comatose and noncomatose patients. Results: Among comatose patients, neither diabetes nor admission hyperglycemia contributed significant predictive information, as nearly all patients died. In noncomatose patients, diabetes was an independent predictor of 30-day (odds ratio [OR] 1.31; 95% CI 1.08 to 1.58) and 3-month (OR 1.30; 95% CI 1.08 to 1.56) mortality and was associated with a greater incidence of infectious (OR 1.24; 95% CI 1.03 to 1.49) and cerebral (OR 1.42; 95% CI 1.10 to 1.83) complications. Among nondiabetic patients with Glasgow Coma Scale score of >8, hyperglycemia was an independent predictor of 30-day (OR 1.29; 95% CI 1.05 to 1.58) and 3-month (OR 1.27; 95% CI 1.05 to 1.53) mortality and was associated with a greater incidence of cerebral complications (OR 1.47; 95% CI 1.12 to 2.94). Conclusions: Both diabetes and admission hyperglycemia in nondiabetic patients are predictors of poor outcome after supratentorial ICH. This may be related to the greater incidence of cerebral and infectious complications in diabetic patients and of cerebral complications in hyperglycemic nondiabetic patients.

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.

Citalopram as treatment of depression in patients with epilepsy.

Objectives:To assess the safety of citalopram as a treatment of depression in patients with epilepsy. Methods:This is an open, multicentered, uncontrolled study. Depressed epileptic patients on antiepileptic drugs (AEDs) took part in the study. Patients who had a mild frequency of seizures in the 4 previous months underwent treatment with citalopram (20 mg/d) for 4 consecutive months. A change in seizure frequency from the baseline was chosen as the primary measure for the safety of citalopram and efficacy against depressive symptoms was taken as secondary measure. Depression was rated using the Montgomery–Åsberg and Zung depression rating scales. Clinical assessments were performed at baseline, and at 2 and 4 months of citalopram therapy. Results:Forty-five patients were enrolled. Six patients dropped out of the study early: none of them because of a deterioration of seizure frequency. An overall improvement in seizure frequency was observed in the 39 patients who completed the study. Plasma AED concentrations were unchanged during therapy, and depressive symptoms improved markedly. Twenty-two patients complained of adverse effects, mainly headache, nausea, dizziness, somnolence, and fatigue. Conclusions:In this open, multicentered, uncontrolled study, 4 months’ of treatment with citalopram (20 mg/d) were associated with an improvement in depressive symptoms and reduction in seizure frequency.

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.

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.

Suprathreshold 0.3 Hz repetitive TMS prolongs the cortical silent period: potential implications for therapeutic trials in epilepsy.

OBJECTIVE To investigate the after-effects of 0.3 Hz repetitive transcranial magnetic stimulation (rTMS) on excitatory and inhibitory mechanisms at the primary motor cortex level, as tested by single-pulse TMS variables. METHODS In 9 healthy subjects, we studied a wide set of neurophysiological and behavioral variables from the first dorsal interosseous before (Baseline), immediately after (Post 1), and 90 min after (Post 2) the end of a 30 min long train of 0.3 Hz rTMS delivered at an intensity of 115% resting motor threshold (RMT). Variables under investigation were: maximal M wave, F wave, and peripheral silent period after ulnar nerve stimulation; RMT, amplitude and stimulus-response curve of the motor evoked potential (MEP), and cortical silent period (CSP) following TMS; finger-tapping speed. RESULTS The CSP was consistently lengthened at both Post 1 and Post 2 compared with Baseline. The other variables did not change significantly. CONCLUSIONS These findings suggest that suprathreshold 0.3 Hz rTMS produces a relatively long-lasting enhancement of the inhibitory mechanisms responsible for the CSP. These effects differ from those, previously reported, of 0.9-1 Hz rTMS, which reduces the excitability of the circuits underlying the MEP and does not affect the CSP. This provides rationale for sham-controlled trials aiming to assess the therapeutic potential of 0.3 Hz rTMS in epilepsy.

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.