Half sine, monophasic and biphasic transcranial magnetic stimulation of the human motor cortex.

OBJECTIVE: To compare half sine transcranial magnetic stimuli (TMS) with conventional monophasic and biphasic stimuli, measuring resting and active motor threshold, motor evoked potential (MEP) input/output curve, MEP latency, and silent period duration. METHODS: We stimulated the dominant hand representation of the motor cortex in 12 healthy subjects utilising two different MagPro stimulators to generate TMS pulses of distinct monophasic, half sine and biphasic shape with anteriorly or posteriorly directed current flow. RESULTS: The markedly asymmetric monophasic pulse with a posterior current flow in the brain yielded a higher motor threshold, a less steep MEP input/output curve and a longer latency than all other TMS types. Similar but less pronounced results were obtained with a less asymmetric half sine pulses. The biphasic stimuli yielded the lowest motor threshold and a short latency, particularly with the posterior current direction. CONCLUSIONS: The more asymmetric the monophasic pulse, the stronger the difference to biphasic pulses. The 3rd and 4th quarter cycle of the biphasic waveform make it longer than any other waveform studied here and likely contribute to lowering motor threshold, shortening MEP latency and reversing the influence of current direction. SIGNIFICANCE: This systematic comparison of 3 waveforms and two current directions allows a better understanding of the mechanisms of TMS.

Orientation-specific fast rTMS maximizes corticospinal inhibition and facilitation.

Specific stimulation of neuronal circuits may promote selective inhibition or facilitation of corticospinal tract excitability. Monophasic stimulation is more likely to achieve direction-specific neuronal excitation. In 10 healthy subjects, we compared four types of repetitive transcranial magnetic stimulation (rTMS), monophasic and biphasic stimuli with the initial current in the brain flowing antero-posteriorly ("posteriorly directed") or postero-anteriorly ("anteriorly directed"). We applied rTMS over the primary motor cortex contralateral to the dominant hand, using 80 stimuli at 5 Hz frequency at an intensity yielding baseline motor evoked potential (MEP) amplitudes of 1 mV. Monophasic stimulation was always more efficient than biphasic. Facilitation was induced by intracerebral anteriorly directed current flow and inhibition by posteriorly oriented current flow, although only initially for approximately 30 pulses. The early inhibition was absent when studied during a tonic muscle contraction. Several mechanisms could account for these findings. They include a more efficient excitation of inhibiting circuits by posteriorly oriented pulses, and a back-propagating D-wave inhibiting early I-waves and thus inducing early inhibition of MEP amplitude. In any case biphasic rTMS results can be explained by a mixture of monophasic opposite stimulations. We propose the use of monophasic pulses for maximizing effects during rTMS.

The role of opioids in restless legs syndrome: an [11C]diprenorphine PET study.

Opioids have been shown to provide symptomatic relief from dysaesthesias and motor symptoms in restless legs syndrome (RLS). However, the mechanisms by which endogenous opioids contribute to the pathophysiology of RLS remain unknown. We have studied opioid receptor availability in 15 patients with primary RLS and 12 age-matched healthy volunteers using PET and [11C]diprenorphine, a non-selective opioid receptor radioligand. Ligand binding was quantified by generating parametric images of volume of distribution (V(d)) using a plasma-derived input function. Statistical parametric mapping (SPM) was used to localize mean group differences between patients and controls and to correlate ligand binding with clinical scores of disease severity. There were no mean group differences in opioid receptor binding between patients and controls. However, we found regional negative correlations between ligand binding and RLS severity (international restless legs scale, IRLS) in areas serving the medial pain system (medial thalamus, amygdala, caudate nucleus, anterior cingulate gyrus, insular cortex and orbitofrontal cortex). Pain scores (affective component of the McGill Pain Questionnaire) correlated inversely with opioid receptor binding in orbitofrontal cortex and anterior cingulate gyrus. Our findings suggest that, the more severe the RLS, the greater the release of endogenous opioids within the medial pain system. We therefore discuss a possible role for opioids in the pathophysiology of RLS with respect to sensory and motor symptoms.

Impact of regular LDL apheresis on the development of restless legs syndrome.

We examined 25 hyperlipidaemic patients with coronary heart disease undergoing regular low-density lipoprotein apheresis (LA) treatment in weekly intervals. In this patient population, half were found to have concomitant restless legs syndrome (RLS). Laboratory investigations suggest that iron metabolism is modified by regular LA treatment and this change may be involved in the pathogenesis of this previously unrecognised form of secondary RLS. Substitution of iron therefore may be a promising line of treatment for LA-induced RLS.

Levodopa treatment does not affect low-dose apomorphine test in patients with Parkinson's disease.

Challenge with low-dose apomorphine causes a significant rise in growth hormone (GH) in patients with Parkinson's disease (PD) compared to controls and patients with multiple system atrophy (MSA) who have not previously received dopaminergic treatment. To date, it has not been demonstrated whether an apomorphine-induced rise in GH can still be detected in PD patients who are currently treated with levodopa. We investigated whether an ongoing treatment with levodopa influences the GH response to subcutaneously applied low-dose apomorphine in PD patients. We studied 44 patients with idiopathic PD using the low-dose apomorphine test. Twenty-three patients were under treatment with levodopa and 21 patients were without any dopaminergic therapy. GH and cortisol levels were analyzed at time of injection and 45 minutes and 60 minutes after subcutaneous apomorphine injection. Forty-five minutes after apomorphine injection, there was no significant difference between the mean rise in plasma GH in untreated PD patients compared with levodopa-treated patients (P = 0.235). There was no increase of cortisol levels in each treatment group. Age, sex, duration, and severity of the disease did not show a covariate effect with GH levels. A small group of PD patients (n = 8) treated with dopamine agonists and a small group of patients with MSA (n = 5) as well as patients with vascular parkinsonism (n = 5) did not show any increase of GH. Our data suggest that the apomorphine-induced rise in GH does not depend on previous levodopa treatment in PD patients but, as expected, is blocked by dopamine agonists and is not present in patients with other than idiopathic parkinsonian syndrome. Thus, the low-dose apomorphine test may also be a useful biological marker in the early differential diagnosis of PD patients who have already received levodopa treatment.

Peripheral paraneoplastic neuropathy, an uncommon clinical onset of sigmoid cancer. Case report and review of the literature.

A case of a 76-year-old man presenting with weakness of the lower legs and bilateral steppage gait is described. Neurological examination revealed a sensorimotor neuropathy with axonopathy and myelinic aspects. At the time of the diagnostic workup an episode of rectal bleeding occurred. Colonoscopy demonstrated an exophytic cancer of the sigmoid colon at 40 cm from the anal verge. At surgery the tumor adhered to the ileum, so a left hemicolectomy and ileo-ileal resection were performed. Tumor stage was Dukes' B, Jass III, Astler-Coller B2, T3N0M0. The patient underwent postoperative chemotherapy and was followed for the past three years. At present he is free of disease and the neuropathy has completely regressed without any dedicated therapy. As reported in the literature the appearance of a paraneoplastic neurological syndrome (PNS) may be the first sign of a malignancy that is occult at the time of clinical presentation. The most widely supported theory about its etiology is that of an autoimmune origin. The paraneoplastic neurological syndrome is considered to be at a point of intersection between tumor immunology, autoimmune neurological disease, and basic neurobiology. Previous experience has resulted in a pathogenic model and in a definition of a group of autoantibodies related to the disease. Small cell lung cancer (SCLC) is the neoplasm most frequently associated with PNS; other malignancies include lymphomas and various hematological malignancies. Some authors reported also that the percentage of patients with a high titer of neuronal autoantibodies is small and several of the autoantibodies are present at low levels without any accompanying clinical manifestation. In a clinical retrospective study of the Mayo Clinic Group 115,081 patients were examined over the period 1984-1993 and only 58 patients (0.05%) could be defined as being affected by a paraneoplastic neurological syndrome. Only five of these patients had colon tumors. The number of patients is so small and so widely scattered among publications that no statistical analysis is possible. Probably the only possibility for early identification of such a syndrome is a high degree of suspicion. In fact, these patients are usually first admitted and studied in a neurological unit, and the diagnosis of a tumor-associated disease is a delayed event.