Francesca Cortese

Adaptive deep brain stimulation in a freely moving parkinsonian patient

The future of deep brain stimulation (DBS) for Parkinsons disease (PD) lies in new closed‐loop systems that continuously supply the implanted stimulator with new settings obtained by analyzing a feedback signal related to the patients current clinical condition.1 The most suitable feedback for PD is subthalamic local field potential (LFP) activity recorded from the stimulating electrode itself.2, 3, 4 This closed‐loop technology known as adaptive DBS (aDBS) recently proved superior to conventional open‐loop DBS (cDBS) in patients with PD.2

De novo FTL mutation: A clinical, neuroimaging, and molecular study

Neuroferritinopathy is a progressive movement disorder associated with autosomal dominant mutations in the ferritin light chain gene (FTL) and is characterized by the presence of focal spherical inclusions in the brain and other organs, including the liver and muscle, that stain positive for iron, ferritin, and ubiquitin. Although the onset of the clinical symptoms usually occurs in adulthood, distinctive neuroimaging features indicating iron deposition are thought to appear decades before symptomatic presentation. We studied a 42-year-old Italian man who first sought neurological advice at age 32 because of hand tremor, even

Triptans and CGRP blockade – impact on the cranial vasculature

The trigeminovascular system plays a key role in the pathophysiology of migraine. The activation of the trigeminovascular system causes release of various neurotransmitters and neuropeptides, including serotonin and calcitonin gene-related peptide (CGRP), which modulate pain transmission and vascular tone. Thirty years after discovery of agonists for serotonin 5-HT1B and 5-HT1D receptors (triptans) and less than fifteen after the proof of concept of the gepant class of CGRP receptor antagonists, we are still a long way from understanding their precise site and mode of action in migraine. The effect on cranial vasculature is relevant, because all specific anti-migraine drugs and migraine pharmacological triggers may act in perivascular space. This review reports the effects of triptans and CGRP blocking molecules on cranial vasculature in humans, focusing on their specific relevance to migraine treatment.

Adaptive behaviour of the spinal cord in the transition from quiet stance to walking

BackgroundModulation of nociceptive withdrawal reflex (NWR) excitability was evaluated during gait initiation in 10 healthy subjects to investigate how load- and movement-related joint inputs activate lower spinal centres in the transition from quiet stance to walking. A motion analysis system integrated with a surface EMG device was used to acquire kinematic, kinetic and EMG variables. Starting from a quiet stance, subjects were asked to walk forward, at their natural speed. The sural nerve was stimulated and EMG responses were recorded from major hip, knee and ankle muscles. Gait initiation was divided into four subphases based on centre of pressure and centre of mass behaviours, while joint displacements were used to categorise joint motion as flexion or extension. The reflex parameters were measured and compared between subphases and in relation to the joint kinematics.ResultsThe NWR was found to be subphase-dependent. NWR excitability was increased in the hip and knee flexor muscles of the starting leg, just prior to the occurrence of any movement, and in the knee flexor muscles of the same leg as soon as it was unloaded. The NWR was hip joint kinematics-dependent in a crossed manner. The excitability of the reflex was enhanced in the extensor muscles of the standing leg during the hip flexion of the starting leg, and in the hip flexors of the standing leg during the hip extension of the starting leg. No notable reflex modulation was observed in the ankle muscles.ConclusionsOur findings show that the NWR is modulated during the gait initiation phase. Leg unloading and hip joint motion are the main sources of the observed modulation and work in concert to prepare and assist the starting leg in the first step while supporting the contralateral leg, thereby possibly predisposing the lower limbs to the cyclical pattern of walking.

Eight-hours adaptive deep brain stimulation in patients with Parkinson disease.

Objectives To assess the feasibility and clinical efficacy of local field potentials (LFPs)–based adaptive deep brain stimulation (aDBS) in patients with advanced Parkinson disease (PD) during daily activities in an open-label, nonblinded study. Methods We monitored neurophysiologic and clinical fluctuations during 2 perioperative experimental sessions lasting for up to 8 hours. On the first day, the patient took his/her daily medication, while on the second, he/she additionally underwent subthalamic nucleus aDBS driven by LFPs beta band power. Results The beta band power correlated in both experimental sessions with the patients clinical state (Pearson correlation coefficient r = 0.506, p < 0.001, and r = 0.477, p < 0.001). aDBS after LFP changes was effective (30% improvement without medication [3-way analysis of variance, interaction day × medication p = 0.036; 30.5 ± 3.4 vs 22.2 ± 3.3, p = 0.003]), safe, and well tolerated in patients performing regular daily activities and taking additional dopaminergic medication. aDBS was able to decrease DBS amplitude during motor “on” states compared to “off” states (paired t test p = 0.046), and this automatic adjustment of STN-DBS prevented dyskinesias. Conclusions The main findings of our study are that aDBS is technically feasible in everyday life and provides a safe, well-tolerated, and effective treatment method for the management of clinical fluctuations. Classification of evidence This study provides Class IV evidence that for patients with advanced PD, aDBS is safe, well tolerated, and effective in controlling PD motor symptoms.

Non-invasive cerebellar stimulation in cerebellar disorders

BACKGROUND & OBJECTIVE Non-invasive brain stimulation (NIBS) might be a valuable therapeutic approach for neurological diseases by modifying the cortical activity in the human brain and promoting neural plasticity. Currently, researchers are exploring the use of NIBS on the cerebellum to promote functional neural changes in cerebellar disorders. In the presence of cerebellar dysfunction, several movement disorders, such as kinetic tremor, ataxia of gait, limb dysmetria and oculomotor deficits, become progressively more disabling in daily life, and no pharmacological treatments currently exist. CONCLUSION In the present mini-review, we report the main evidence concerning the use of NIBS in three specific cerebellar dysfunctions, cerebellar ataxias (CA), essential tremor (ET) and ataxic cerebral palsy, in which abnormalities of neuroplasticity and cortical excitability can be important pathophysiological factors.

Cognitive safety of eight-hours adaptive deep brain stimulation (aDBS) in Parkinson's disease

Objective: The aim of this work is to evaluate clinimetric properties of a method for measuring Parkinson’s disease (PD) upper limb temporal irregularities during spiral drawing tasks.Background: B ...Basic Science Abstracts - Session Title: Parkinsons Disease: Pathophysiology: abstract no. 518

Bladder filling attenuates spinal cord nociceptive reflexes in humans.

OBJECTIVE To examine the viscerosomatic interaction between bladder afferents and somatic nociception we evaluated the effect of bladder filling on the nociceptive withdrawal reflex (NWR) in 21 healthy subjects. METHODS NWR was evoked in the lower and upper limbs by stimulating the sural and index finger digital nerves, respectively, while simultaneously recording EMG activity in the biceps femoris and biceps brachialis. NWR pain-related perception was quantified on a 10-point pain scale. Bladder filling was evaluated with suprapubic bladder sonography. Subjects were examined during empty bladder, medium and high level of bladder filling sessions. RESULTS NWR magnitude in both upper and lower limbs and perceived pain for the upper limb were significantly decreased at higher levels of bladder filling compared to empty bladder sessions. CONCLUSIONS Reduced NWR magnitude in both upper and lower limbs during bladder filling strongly indicates that bladder control and nociception share common modulatory descending pathways. Bladder afferents may activate these pathways to suppress the micturition reflex, but they may also inhibit spinal reflexes to maintain continence during pain stimuli. SIGNIFICANCE The effect of bladder filling on the NWR may represent a useful tool to investigate interactions between the neural pathways controlling the bladder and pain.

Cerebellar direct current stimulation modulates hand blink reflex: implications for defensive behavior in humans

The cerebellum is involved in a wide number of integrative functions. We evaluated the role of cerebellum in peripersonal defensive behavior, as assessed by the so‐called hand blink reflex (HBR), modulating cerebellar activity with transcranial direct current stimulation (tDCS). Healthy subjects underwent cerebellar (sham, anodal, and cathodal tcDCS) and motor cortex tDCS (anodal or cathodal; 20′, 2 mA). For the recording of HBR, electrical stimuli were delivered using a surface bipolar electrode placed on the median nerve at the wrist and EMG activity recorded from the orbicularis oculi muscle bilaterally. Depending on the hand position respective to the face, HBR was assessed in four different conditions: “hand‐far,” “hand‐near” (eyes open), “side hand,” and “hand‐patched” (eyes closed). While sham and cathodal cerebellar stimulation had no significant effect, anodal tcDCS dramatically dampened the magnitude of the HBR, as measured by the area under the curve (AUC), in the “hand‐patched” and “side hand” conditions only, for ipsilateral (F(4,171) = 15.08, P < 0.0001; F(4,171) = 8.95, P < 0.0001) as well as contralateral recordings (F(4,171) = 17.96, P < 0.0001); F4,171) = 5.35, P = 0.0004). Cerebellar polarization did not modify AUC in the “hand‐far” and “hand‐near” sessions. tDCS applied over the motor area did not affect HBR. These results seem to support a role of the cerebellum in the defensive responses within the peripersonal space surrounding the face, thus suggesting a possible cerebellar involvement in visual‐independent defensive behavior.

Migraine and cluster headache – the common link

Although clinically distinguishable, migraine and cluster headache share prominent features such as unilateral pain, common pharmacological triggers such glyceryl trinitrate, histamine, calcitonin gene-related peptide (CGRP) and response to triptans and neuromodulation. Recent data also suggest efficacy of anti CGRP monoclonal antibodies in both migraine and cluster headache. While exact mechanisms behind both disorders remain to be fully understood, the trigeminovascular system represents one possible common pathophysiological pathway and network of both disorders. Here, we review past and current literature shedding light on similarities and differences in phenotype, heritability, pathophysiology, imaging findings and treatment options of migraine and cluster headache. A continued focus on their shared pathophysiological pathways may be important in paving future treatment avenues that could benefit both migraine and cluster headache patients.