Neurological comorbidity and severity of COVID-19

Journal of Neurology - Neurological symptoms of COVID-19 patients have been recently described. However, no comprehensive data have been reported on pre-existing neurological comorbidities and...     

Efficacy of safinamide as add-on therapy after subthalamic nucleus deep brain stimulation in Parkinson disease

Neurological Sciences - Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective surgical treatment for advanced Parkinson’s disease (PD). However, some patients still experience...     

When words are painful: unraveling the mechanisms of the nocebo effect

The nocebo effect is a phenomenon that is opposite to the placebo effect, whereby expectation of a negative outcome may lead to the worsening of a symptom. Thus far, its study has been limited by ethical constraints, particularly in patients, as a nocebo procedure is per se stressful and anxiogenic. It basically consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening. Although some natural nocebo situations do exist, such as the impact of negative diagnoses upon the patient and the patient's distrust in a therapy, the neurobiological mechanisms have been understood in the experimental setting under strictly controlled conditions. As for the placebo counterpart, the study of pain has been fruitful in recent years to understand both the neuroanatomical and the neurochemical bases of the nocebo effect. Recent experimental evidence indicates that negative verbal suggestions induce anticipatory anxiety about the impending pain increase, and this verbally-induced anxiety triggers the activation of cholecystokinin (CCK) which, in turn, facilitates pain transmission. CCK-antagonists have been found to block this anxiety-induced hyperalgesia, thus opening up the possibility of new therapeutic strategies whenever pain has an important anxiety component. Other conditions, such as Parkinson's disease, although less studied, have been found to be affected by nocebo suggestions as well. All these findings underscore the important role of cognition in the therapeutic outcome, and suggest that nocebo and nocebo-related effects might represent a point of vulnerability both in the course of a disease and in the response to a therapy.     

Subcutaneous immunoglobulin in CIDP and MMN: a short-term nationwide study

This multi-center Italian prospective observational study reports the 4 months follow-up data of 87 patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) shifted from intravenous to subcutaneous immunoglobulin treatment. A therapeutic shift from intravenous to subcutaneous immunoglobulin was performed in 87 patients (66 CIDP; 21 MMN) affected by immune-mediated peripheral neuropathies with evidence of a sustained clinical response to intravenous immunoglobulin. Patients were evaluated by means of the Overall Neuropathy Limitation Scale, Medical Research Council Scale and Life Quality Index questionnaire, both at the time of therapeutic shift and after 4 months of subcutaneous immunoglobulin treatment. A sustained clinical efficacy was observed after the switch to subcutaneous immunoglobulin: the Overall Neuropathy Limitation Scale score improved in the group of 66 CIDP patients (P = 0.018), with only one subject reporting a worsening of 1 point, and remained stable in the group of 21 MMN patients (P = 0.841), with one subject reporting a worsening of two points. An improvement in the patient’s perception of therapeutic setting was reported in both groups. This large multi-center study confirms the short-term clinical equivalence of subcutaneous versus intravenous immunoglobulin and a possible improvement in the patient’s perception of therapeutic setting with the subcutaneous administration. However, further studies are required to extend the results to a longer observational period.     

Dissociation between time reproduction of actions and of intervals in patients with Parkinson’s disease

Alterations in temporal estimation have been observed in patients with Parkinson’s disease (PD) and have been associated to dopaminergic dysfunction. Nevertheless, levodopa treatment and deep brain stimulation of the subthalamic nucleus (DBS-STN) have been shown to improve motor deficits and temporal estimation skills in such patients. So far, temporal estimation tasks in PD patients have evaluated the ability to reproduce intervals of time, but never the duration of an action. Here we investigated: (1) the ability of PD patients to reproduce the duration of their previous actions as compared to their ability to reproduce intervals of time and (2) the effect that DBS-STN has on both skills. Nineteen PD patients with DBS-STN and 19 controls were requested to reproduce the duration of an action and that of an interval of time. The patients were tested in the following treatment conditions: on stimulation/off medication, off stimulation/off medication and off stimulation/on medication. The results demonstrated that patients in the off stimulation/off medication condition under-reproduced the duration of their actions while accurately reproducing the duration of time intervals. The accuracy of the performance improved significantly in both treatment regimens. Our results indicate that in PD patients the ability to reproduce motor acts can be dissociated from that of reproducing time intervals and that it can be improved by the administration of medical or surgical treatment.     

Deep brain stimulation of the subthalamic nucleus in PD: an analysis of the exclusion causes

OBJECTIVE: Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) represents a proper choice for the treatment of advanced Parkinson's disease (PD). A correct selection of the patients as candidates for the surgery is essential for a good outcome. In this study, we analyzed the exclusion causes of a series of PD patients hospitalized for the selection protocol. METHODS: Ninety-eight PD patients as potential candidates for the STN DBS were studied. All patients were hospitalized and underwent a clinical evaluation of the PD stage, a levodopa challenge, a MR of the brain and a neuropsychological assessment. RESULTS: The percentage of subjects considered not suitable for the surgery was 29.6%. A single cause of exclusion was present in 65.5% of not suitable patients, while multiple causes were present in 34.5%. The most frequent cause of exclusion was the finding of neuropsychological or psychic disorders (48.3%); in 37.9% of the patients, the motor disability was not severe enough to justify the surgery, while in 31%, we found relevant abnormalities at the brain MR. Three patients (10.3%) were poorly motivated for the surgery, while in three others (10.3%), we found a significant illness other than PD. CONCLUSIONS: The finding that about 30% of the PD patients potentially suitable for STN DBS presents some exclusion causes underlines the importance of a careful selection of the candidates for this surgery.     

Autonomic and emotional responses to open and hidden stimulations of the human subthalamic region

We performed a microstimulation study of the subthalamic region of Parkinsonian patients who underwent bilateral electrode implantation in the subthalamic nuclei and whose heart rate and heart rate variability were recorded. The stimulation of the dorsalmost region, which includes the zona incerta and the dorsal pole of the subthalamic nucleus, produced autonomic responses that were constant over time. In fact, hidden stimulations (the patient is not aware of being stimulated) and open stimulations (the patient is aware of being stimulated) always induced the same responses. By contrast, the stimulation of the ventralmost region, which includes the ventral pole of the subthalamic nucleus and the substantia nigra pars reticulata, produced autonomic and emotional responses that were inconstant over time and varied according to the condition. In fact, different responses were elicited with hidden and open stimulations. These data suggest that the dorsal subthalamic nucleus and/or the zona incerta are involved in autonomic control, whereas the ventral subthalamic nucleus and/or the substantia nigra reticulata are involved in associative/limbic-related autonomic activity. The difference between the open and hidden stimulations in the ventral subthalamic region can explain previous studies in which open and hidden stimulations produced different therapeutic outcomes.