Domenico Restuccia

Electrical stimulation of upper limb nerves evokes a train of high‐frequency wavelets (high‐frequency oscillations, HFOs) on the human scalp. These HFOs are related to the influence of arousal‐promoting structures on somatosensory input processing, and are generated in the primary somatosensory cortex (post‐synaptic HFOs) and the terminal tracts of thalamocortical radiations (pre‐synaptic HFOs). We previously reported that HFOs do not undergo habituation to repeated stimulations; here, we verified whether HFOs could be modulated by external sensitizing stimuli. We recorded somatosensory evoked potentials (SSEPs) in 15 healthy volunteers before and after sensitization training with an auditory stimulus. Pre‐synaptic HFO amplitudes, reflecting somatosensory thalamic/thalamocortical activity, significantly increased after the sensitizing acoustic stimulation, whereas both the low‐frequency N20 SSEP component and post‐synaptic HFOs were unaffected. Cross‐talk between subcortical arousal‐related structures is a probable mechanism for the pre‐synaptic HFO effect observed in this study. We propose that part of the ascending somatosensory input encoded in HFOs is specifically able to convey sensitized inputs. This preferential involvement in sensitization mechanisms suggests that HFOs play a critical role in the detection of potentially relevant stimuli, and act at very early stages of somatosensory input processing.

Copper deficiency myelopathy represents an often underdiagnosed, acquired neurological syndrome, clinically characterized by posterior column dysfunction. The main causes of copper deficiency are bariatric surgery, increased consumption of zinc, and malabsorption. However, even after a careful history taking and extensive laboratory researches, the etiology of copper deficiency remains undetermined in a significant percentage of cases. Patients affected by copper deficiency myelopathy usually present with sensory ataxia due to dorsal column dysfunction and sometimes with mild leg spasticity. In such patients, spinal cord magnetic resonance imaging (MRI) may show hyperintense lesions in T2-weighted sequences involving the posterior columns of cervical and thoracic cord. These MRI findings are not distinguishable from those of subacute combined degeneration associated with vitamin B12 deficiency. Here, we describe two patients with gait ataxia and sensory symptoms in which a diagnosis of copper deficiency myelopathy was made. Both patients showed a significant clinical, neuroradiological, and neurophysiological improvement after proper supplementation therapy. The patients herein described underline the importance to include serum copper and ceruloplasmin levels as part of the myelopathy diagnostic workup, especially in the cases of otherwise unexplained subacute myelopathy involving the posterior columns. Since copper deficiency myelopathy is a progressive syndrome, early diagnosis is mandatory in order to promptly provide a proper supplementation therapy and, thus, prevent an irreversible neurological damage.

Background: Habituation deficit, suggesting a deregulation of cortical excitability, represents a typical hallmark of interictal stages of migraine. We previously demonstrated that several neurophysiological markers of altered cortical excitability are significantly correlated to spontaneous clinical fluctuations of migraine. We therefore aimed at verifying whether clinical fluctuations are correlated to specific patterns of somatosensory evoked potential (SEP) habituation. Methods: We analyzed habituation after median nerve stimulation of both high-frequency oscillations (HFOs) and N20 SEP in 25 migraine patients and 18 healthy volunteers. Subjects underwent six consecutive series of 500 stimuli. Results: Migraine patients as a whole showed a significant habituation deficit of the N20 response. Moreover, spontaneously worsening patients show a clear potentiation of this wave in the last block of stimuli, whereas in spontaneously improving patients the N20 amplitude remained stable. Presynaptic HFOs were smaller in worsening patients and larger in improving ones, but they did not undergo habituation in patients as well as in healthy subjects. Conclusions: Potentiation of the N20 response in spontaneously worsening migraineurs confirms that the reduction of the thalamocortical drive plays a major role in migraine pathogenesis. Moreover, the stable pattern we observed in spontaneously improving patients suggests that compensatory mechanisms can also play an important role. The normal response to repeated stimuli of HFOs in migraineurs might indicate that, although its initial amount depends on clinical conditions, high-frequency thalamocortical drive remains stable during the stimulation and probably reflects the activity of a buffer mechanism.

Background: In a previous study we demonstrated that high-frequency oscillations (HFOs) elicited by median nerve stimulation are significantly correlated to clinical fluctuations of migraine. We aimed at verifying whether clinical fluctuations and HFO changes are correlated to N20 somatosensory evoked potential (SEP) recovery cycle, which is likely to reflect the functional refractoriness of primary somatosensory cortex neurons. Methods: We analysed both HFOs and N20 SEP recovery cycle to paired stimulation in 21 migraine patients and 18 healthy volunteers. Results: Shortened recovery cycle correlated with low-amplitude HFOs as well as with clinical worsening. By contrast, prolonged recovery cycle correlated with enhanced HFOs, as well as with spontaneous clinical improvement. Conclusions: In our migraine patients the strict relationship between presynaptic HFO amplitude and N20 recovery function suggests that changes of both parameters might be caused by modifications of the thalamo-cortical drive. Our findings suggest that the thalamo-cortical drive during interictal stages could fluctuate from abnormally high to abnormally low levels, depending on mechanisms which reduce cortical excitability in spontaneously improving patients, and increase cortical excitability in spontaneously worsening ones.