Effects of Botulinum Toxin Type A on the Nociceptive and Lemniscal Somatosensory Systems in Chronic Migraine: An Electrophysiological Study.

(1) Background: OnabotulinumtoxinA (BoNT-A) is a commonly used prophylactic treatment for chronic migraine (CM). Although randomized placebo studies have shown its clinical efficacy, the mechanisms by which it exerts its therapeutic effect are still incompletely understood and debated. (2) Methods: We studied in 15 CM patients the cephalic and extracephalic nociceptive and lemniscal sensory systems using electrophysiological techniques before and 1 and 3 months after one session of pericranial BoNT-A injections according to the PREEMPT protocol. We recorded the nociceptive blink reflex (nBR), the trigemino-cervical reflex (nTCR), the pain-related cortical evoked potential (PREP), and the upper limb somatosensory evoked potential (SSEP). (3) Results: Three months after a single session of prophylactic therapy with BoNT-A in CM patients, we found (a) an increase in the homolateral and contralateral nBR AUC, (b) an enhancement of the contralateral nBR AUC habituation slope and the nTCR habituation slope, (c) a decrease in PREP N-P 1st and 2nd amplitude block, and (d) no effect on SSEPs. (4) Conclusions: Our study provides electrophysiological evidence for the ability of a single session of BoNT-A injections to exert a neuromodulatory effect at the level of trigeminal system through a reduction in input from meningeal and other trigeminovascular nociceptors. Moreover, by reducing activity in cortical pain processing areas, BoNT-A restores normal functioning of the descending pain modulation systems.

A Hypothalamic Mechanism Regulates the Duration of a Migraine Attack: Insights from Microstructural and Temporal Complexity of Cortical Functional Networks Analysis.

The role of the hypothalamus and the limbic system at the onset of a migraine attack has recently received significant interest. We analyzed diffusion tensor imaging (DTI) parameters of the entire hypothalamus and its subregions in 15 patients during a spontaneous migraine attack and in 20 control subjects. We also estimated the non-linear measure resting-state functional MRI BOLD signal's complexity using Higuchi fractal dimension (FD) and correlated DTI/fMRI findings with patients' clinical characteristics. In comparison with healthy controls, patients had significantly altered diffusivity metrics within the hypothalamus, mainly in posterior ROIs, and higher FD values in the salience network (SN). We observed a positive correlation of the hypothalamic axial diffusivity with migraine severity and FD of SN. DTI metrics of bilateral anterior hypothalamus positively correlated with the mean attack duration. Our results show plastic structural changes in the hypothalamus related to the attacks severity and the functional connectivity of the SN involved in the multidimensional neurocognitive processing of pain. Plastic changes to the hypothalamus may play a role in modulating the duration of the attack.

Hypothalamic structural integrity and temporal complexity of cortical information processing at rest in migraine without aura patients between attacks.

The hypothalamus has been attributed an important role during the premonitory phase of a migraine attack. Less is known about the role played by the hypothalamus in the interictal period and its relationship with the putative neurocognitive networks previously identified in the pathophysiology of migraine. Our aim was to test whether the hypothalamic microstructure would be altered during the interictal period and whether this co-existed with aberrant connectivity at cortical level. We collected multimodal MRI data from 20 untreated patients with migraine without aura between attacks (MO) and 20 healthy controls (HC) and studied fractional anisotropy, mean (MD), radial (RD), and axial diffusivity of the hypothalamus ROI as a whole from diffusion tensor imaging (DTI). Moreover, we performed an exploratory analysis of the same DTI metrics separately for the anterior and posterior hypothalamic ROIs bilaterally. From resting-state functional MRI, we estimated the Higuchi's fractal dimension (FD), an index of temporal complexity sensible to describe non-periodic patterns characterizing BOLD signature. Finally, we correlated neuroimaging findings with migraine clinical features. In comparison to HC, MO had significantly higher MD, AD, and RD values within the hypothalamus. These findings were confirmed also in the exploratory analysis on the sub-regions of the hypothalamus bilaterally, with the addition of lower FA values on the posterior ROIs. Patients showed higher FD values within the salience network (SN) and the cerebellum, and lower FD values within the primary visual (PV) network compared to HC. We found a positive correlation between cerebellar and SN FD values and severity of migraine. Our findings of hypothalamic abnormalities between migraine attacks may form part of the neuroanatomical substrate that predisposes the onset of the prodromal phase and, therefore, the initiation of an attack. The peculiar fractal dimensionality we found in PV, SN, and cerebellum may be interpreted as an expression of abnormal efficiency demand of brain networks devoted to the integration of sensory, emotional, and cognitive information related to the severity of migraine.

Direct anterior approach for total hip arthroplasty: Hip biomechanics and muscle activation during three walking tasks.

BACKGROUND: Total hip replacement with minimally invasive direct anterior approach using the "Smith Petersen" interval is an alternative technique to conventional surgery aimed at preserving the integrity of the muscles around the hip joint. This study aimed to observe hip biomechanics, gait variables, hip muscle activation and locomotor performance during three locomotor tasks (forward, lateral, and backward walking), in subjects who undergo total hip arthroplasty with direct anterior approach. METHODS: Fourteen patients with primary osteoarthritis who underwent direct anterior approach were included in the study. The optoelectronic 3-D motion analysis system integrated with an electromyography surface device was used to acquire the biomechanics of patients before surgery and at 3 and 6 months post-surgery. Spatio-temporal, dynamic, and hip muscle electromyographic parameters were analyzed and compared whit those of healthy controls. FINDINGS: Almost all gait parameters improved after surgery. The majority of gait variables neared to the control group at 6 months, while the hip joint range of motion did not. The abnormally increased activation of the muscles around the hip joint was reduced at 6 months post-surgery during all three locomotor tasks. Conversely, the altered gait phase-related electromyographic pattern did not change after the surgery. INTERPRETATION: Our results indicate that hip and gait function during several locomotor tasks improved after surgery, while simultaneously either preserve or restore the muscle activation around the hip joint. A full biomechanical evaluation of the hip function during locomotion may aid physicians and surgeons in optimizing the management of patients before and after hip replacement surgery.

Thalamo-cortical networks in subtypes of migraine with aura patients.

BACKGROUND: We searched for differences in resting-state functional connectivity (FC) between brain networks and its relationship with the microstructure of the thalamus between migraine with pure visual auras (MA), and migraine with complex neurological auras (MA+), i.e. with the addition of at least one of sensory or language symptom. METHODS: 3T MRI data were obtained from 20 patients with MA and 15 with MA + and compared with those from 19 healthy controls (HCs). We collected resting state data among independent component networks. Diffusivity metrics of bilateral thalami were calculated and correlated with resting state ICs-Z-scores. RESULTS: As compared to HCs, both patients with MA and MA + disclosed disrupted FC between the default mode network (DMN) and the right dorsal attention system (DAS). The MA + subgroup had lower microstructural metrics than both HCs and the MA subgroup, which correlated negatively with the strength of DMN connectivity. Although the microstructural metrics of MA patients did not differ from those of HCs, these patients lacked the correlation with the strength of DAS connectivity found in HCs. CONCLUSIONS: The present findings suggest that, as far as MRI profiles are concerned, the two clinical phenotypes of migraine with aura have both common and distinct morpho-functional features of nodes in the thalamo-cortical network.

Pathophysiological Bases of Comorbidity in Migraine.

Despite that it is commonly accepted that migraine is a disorder of the nervous system with a prominent genetic basis, it is comorbid with a plethora of medical conditions. Several studies have found bidirectional comorbidity between migraine and different disorders including neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metaboloendocrine, and immunological conditions. Each of these has its own genetic load and shares some common characteristics with migraine. The bidirectional mechanisms that are likely to underlie this extensive comorbidity between migraine and other diseases are manifold. Comorbid pathologies can induce and promote thalamocortical network dysexcitability, multi-organ transient or persistent pro-inflammatory state, and disproportionate energetic needs in a variable combination, which in turn may be causative mechanisms of the activation of an ample defensive system with includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system. This strategy is designed to maintain brain homeostasis by regulating homeostatic needs, such as normal subcortico-cortical excitability, energy balance, osmoregulation, and emotional response. In this light, the treatment of migraine should always involves a multidisciplinary approach, aimed at identifying and, if necessary, eliminating possible risk and comorbidity factors.

Visual Evoked Potential Responses after Photostress in Migraine Patients and Their Correlations with Clinical Features.

In the past few years, researchers have detected subtle macular vision abnormalities using different psychophysical experimental tasks in patients with migraine. Recording of visual evoked potential (VEP) after photostress (PS) represents an objective way to verify the integrity of the dynamic properties of macular performance after exposure to intense light. VEPs were recorded before and after PS in 51 patients with migraine (19 with aura (MA) and 22 without aura (MO) between attacks, and 10 recorded during an attack (MI)) and 14 healthy volunteers. All study participants were exposed to 30 s of PS through the use of a 200-watt bulb lamp. The P100 implicit time and N75-P100 amplitude of the baseline VEP were compared with those collected every 20 s up to 200 s after PS. VEP parameters recorded at baseline did not differ between groups. In all groups, the VEP recordings exhibited a significant increase in implicit times and a reduction in amplitude at 20 s after the PS. In migraine, the percentage decrease in amplitudes observed at 20 s after photostress was significantly lower than in healthy volunteers, in both MO and MA patients, but not in MI patients. When data for MO and MA patients were combined, the percentage of amplitude change at 20 s was negatively correlated with the number of days that had elapsed since the last migraine attack, and positive correlated with attack frequency. We showed dynamic changes of recovery of VEP after PS depending on the migraine cycle. This finding, in conjunction with those previously attained with other neuromodulatory interventions using VEPs, leads us to argue that migraine-disease-related dysrhythmic thalamocortical activity precludes amplitude suppression by PS.

Migraine during COVID-19: Data from Second Wave Pandemic in an Italian Cohort.

OBJECTIVES: The study aims to assess the impact of the second COVID-19 pandemic wave on migraine characteristics. METHODS: This is an observational cross-sectional study conducted on migraine patients previously interviewed during the first Italian pandemic outbreak. A second structured telephone interview was conducted between 20 November 2020 and 18 January 2021. We compared migraine characteristics among T0 (before pandemic), T1 (during the first pandemic phase), and T2 (during the second pandemic phase). RESULTS: Among the 433 patients interviewed during the first pandemic phase, 304 cases were finally considered. One hundred forty-eight patients had a control visit between March 2020 and December 2020, 120 had an in-person visit, 14 by phone, the remainder used telemedicine software provided by the hospital. Frequency of headache, number of symptomatic drugs and headache intensity worsened during T2, compared to T0 and T1, especially in episodic migraine. Headache intensity increased relating to the negative emotional impact of the pandemic. Migraine management during the pandemic did not influence the clinical outcome. CONCLUSION: The prolongation of the pandemic seems to have a negative impact on migraine evolution. The arousal and negative psychological behavior toward the COVID-19 outbreak seem to worsen migraine.

An artificial neural network approach to detect presence and severity of Parkinson's disease via gait parameters.

INTRODUCTION: Gait deficits are debilitating in people with Parkinson's disease (PwPD), which inevitably deteriorate over time. Gait analysis is a valuable method to assess disease-specific gait patterns and their relationship with the clinical features and progression of the disease. OBJECTIVES: Our study aimed to i) develop an automated diagnostic algorithm based on machine-learning techniques (artificial neural networks [ANNs]) to classify the gait deficits of PwPD according to disease progression in the Hoehn and Yahr (H-Y) staging system, and ii) identify a minimum set of gait classifiers. METHODS: We evaluated 76 PwPD (H-Y stage 1-4) and 67 healthy controls (HCs) by computerized gait analysis. We computed the time-distance parameters and the ranges of angular motion (RoMs) of the hip, knee, ankle, trunk, and pelvis. Principal component analysis was used to define a subset of features including all gait variables. An ANN approach was used to identify gait deficits according to the H-Y stage. RESULTS: We identified a combination of a small number of features that distinguished PwPDs from HCs (one combination of two features: knee and trunk rotation RoMs) and identified the gait patterns between different H-Y stages (two combinations of four features: walking speed and hip, knee, and ankle RoMs; walking speed and hip, knee, and trunk rotation RoMs). CONCLUSION: The ANN approach enabled automated diagnosis of gait deficits in several symptomatic stages of Parkinson's disease. These results will inspire future studies to test the utility of gait classifiers for the evaluation of treatments that could modify disease progression.

Impaired short-term visual paired associative plasticity in patients with migraine between attacks.

ABSTRACT: A common experimental neurophysiological method to study synaptic plasticity is pairing activity of somatosensory afferents and motor cortical circuits, so-called paired associative stimulation (PAS). Dysfunctional inhibitory and excitatory PAS mechanisms within the sensorimotor system were described in patients with migraine without aura (MO) between attacks. We have recently observed that the same bidirectional PAS rules also apply to the visual system. Here, we have tested whether dysfunctioning associative plasticity might characterize the visual system of patients with MO. In 14 patients with MO between attacks and in 15 healthy volunteers, we performed a previously validated visual PAS (vPAS) protocol by coupling 90 black-and-white checkerboard reversals with low-frequency transcranial magnetic stimulation pulses over the occipital cortex at 2 interstimulus intervals of -25/+25 ms around the visual-evoked potential (VEP) P1 latency. We recorded VEPs (600 sweeps) before, immediately after, and 10 min after each vPAS session. We analysed VEP N1-P1 amplitude and delayed habituation. Although vPAS-25 significantly enhanced and vPAS + 25 reduced VEP amplitude habituation in healthy volunteers, the same protocols did not significantly change VEP amplitude habituation in MO between attacks. We provide evidence for lack of habituation enhancing and habituation suppressing visual PAS mechanisms within the visual system in interictal migraine. This finding, in combination with those previously obtained studying the sensorimotor system, leads us to argue that migraine disease-related dysrhythmic thalamocortical activity prevents the occurrence of physiological bidirectional synaptic plasticity induced by vPAS.

A dataset of visible - short wave infrared reflectance spectra collected in-vivo on the dorsal and ventral aspect of arms.

Advancement of technology and device miniaturization have made near infrared spectroscopy (NIRS) techniques cost-effective, small-sized, simple, and ready to use. We applied NIRS to analyze healthy human muscles in vivo, and we found that this technique produces reliable and reproducible spectral "fingerprints" of individual muscles, that can be successfully discriminated by chemometric predictive models. The dataset presented in this descriptor contains the reflectance spectra acquired in vivo from the ventral and dorsal aspects of the arm using an ASD FieldSpec® 4 Standard-Res field portable spectroradiometer (350-2500 nm), the values of the anthropometric variables measured in each subject, and the codes to assist access to the spectral data. The dataset can be used as a reference set of spectral signatures of "biceps" and "triceps" and for the development of automated methods of muscle detection.

Investigating the Effects of COVID-19 Quarantine in Migraine: An Observational Cross-Sectional Study From the Italian National Headache Registry (RICe).

Background: Previous studies during SARS and Ebola pandemics have shown that quarantine is associated with several negative psychological effects, such as post-traumatic stress symptoms, confusion, and anger. These conditions may affect the course of many diseases, including migraine. Although it is possible that the quarantine measures for the current COVID-19 pandemic affect migraine burden, no information is currently available on this issue. Aim: In this study, we aimed to: (1) explore the possible changes in migraine frequency, severity, and days with acute medication intake during quarantine period; (2) evaluate possible differences in migraine outcomes in consideration of lifestyle changes, emotions, pandemic diffusion, and COVID-19 infection. Methods: We interviewed patients who were included in the observational Italian Headache Registry (Registro Italiano Cefalee, RICE), retrospectively collecting information on main headache features, lifestyle factors, emotions, individual infection status, and perception of COVID-19 for 2 months before (pre-quarantine) and after the beginning of the quarantine (quarantine). Inclusion criteria were: age > 18, diagnosis of migraine without aura, migraine with aura and chronic migraine, last in-person visit more than 3 months preceding the beginning of quarantine. Results: A total of 433 migraine subjects agreed to be interviewed. We found an overall reduction in headache frequency (9.42 ± 0.43 days with headache vs. 8.28 ± 0.41) and intensity (6.57 ± 0.19 vs. 6.59 ± 0.21) during the quarantine, compared to pre-quarantine. There was a correlation between improvement and number of days of stay-at-home. When results were stratified for geographic area, we found a tendency toward worsening of headache frequency in northern Italy. Disgust regarding viral infection corresponded to a minor improvement in migraine. Conclusions: Migraine patients showed a mild improvement of migraine features, probably attributable to resilient behavior toward pandemic distress. Disgust regarding the contagion whereas potentially favoring defensive behavior, could potentially worsen migraine. The spontaneous limitation of migraine burden during quarantine could favor patient follow-up via the use of telemedicine visits, reliable diaries, and frequent remote contacts.

Haemodynamic activity characterization of resting state networks by fractal analysis and thalamocortical morphofunctional integrity in chronic migraine.

BACKGROUND: Chronic migraine (CM) can be associated with aberrant long-range connectivity of MRI-derived resting-state networks (RSNs). Here, we investigated how the fractal dimension (FD) of blood oxygenation level dependent (BOLD) activity may be used to estimate the complexity of RSNs, reflecting flexibility and/or efficiency in information processing in CM patients respect to healthy controls (HC). METHODS: Resting-state MRI data were collected from 20 untreated CM without history of medication overuse and 20 HC. On both groups, we estimated the Higuchi's FD. On the same subjects, fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from diffusion tensor imaging and correlated with the FD values. RESULTS: CM showed higher FD values within dorsal attention system (DAS) and the anterior part of default-mode network (DMN), and lower FD values within the posterior DMN compared to HC. Although FA and MD were within the range of normality, both correlated with the FD values of DAS. CONCLUSIONS: FD of DAS and DMN may reflect disruption of cognitive control of pain in CM. Since the normal microstructure of the thalamus and its positive connectivity with the cortical networking found in our CM patients reminds similar results obtained assessing the same structures but with the methods of neurophysiology, in episodic migraine during an attack, this may be yet another evidence in supporting CM as a never-ending migraine attack.

Patients with chronic migraine without history of medication overuse are characterized by a peculiar white matter fiber bundle profile.

BACKGROUND: We investigated intracerebral fiber bundles using a tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) data to verify microstructural integrity in patients with episodic (MO) and chronic migraine (CM). METHODS: We performed DTI in 19 patients with MO within interictal periods, 18 patients with CM without any history of drug abuse, and 18 healthy controls (HCs) using a 3 T magnetic resonance imaging scanner. We calculated diffusion metrics, including fractional anisotropy (FA), axial diffusion (AD), radial diffusion (RD), and mean diffusion (MD). RESULTS: TBSS revealed no significant differences in the FA, MD, RD, and AD maps between the MO and HC groups. In comparison to the HC group, the CM group exhibited widespread increased RD (bilateral superior [SCR] and posterior corona radiata [PCR], bilateral genu of the corpus callosum [CC], bilateral posterior limb of internal capsule [IC], bilateral superior longitudinal fasciculus [LF]) and MD values (tracts of the right SCR and PCR, right superior LF, and right splenium of the CC). In comparison to the MO group, the CM group showed decreased FA (bilateral SCR and PCR, bilateral body of CC, right superior LF, right forceps minor) and increased MD values (bilateral SCR and right PCR, right body of CC, right superior LF, right splenium of CC, and right posterior limb of IC). CONCLUSION: Our results suggest that chronic migraine can be associated with the widespread disruption of normal white matter integrity in the brain.

Impairment of Global Lower Limb Muscle Coactivation During Walking in Cerebellar Ataxias.

The aim of this study was to investigate the time-varying multi-muscle coactivation function (TMCf) in the lower limbs during gait and its relationship with the biomechanical and clinical features of patients with cerebellar ataxia. A total of 23 patients with degenerative cerebellar ataxia (16 with spinocerebellar ataxia, 7 with adult-onset ataxia of unknown etiology) and 23 age-, sex-, and speed-matched controls were investigated. The disease severity was assessed using the Scale for the Assessment and Rating of Ataxia (SARA) in all patients. During walking, simultaneous acquisition of kinematic, kinetic, and electromyography data was performed using a motion analysis system. The coactivation was processed throughout the gait cycle using the TMCf, and the following parameters were measured: synthetic coactivation index, full width at half maximum, and center of activity. Spatiotemporal (walking speed, stance duration, swing duration, first and second double-support durations, step length, step width, stride length, Center of Mass displacement), kinetic (vertical component of GRFs), and energy consumption (total energy consumption and mechanical energy recovered) parameters were also measured. The coactivation variables were compared between patients and controls and were correlated with both clinical and gait variables. A significantly increased global TMCf was found in patients compared with controls. In addition, the patients showed a significant shift of the center of activity toward the initial contact and a significant reduction in energy recovery. All coactivation parameters were negatively correlated with gait speed, whereas the coactivation index and center of activity were positively correlated with both center-of-mass mediolateral displacement values and SARA scores. Our findings suggest that patients use global coactivation as a compensatory mechanism during the earliest and most challenging subphase (loading response) of the gait cycle to reduce the lateral body sway, thus improving gait stability at the expense of effective energy recovery. This information could be helpful in optimizing rehabilitative treatment aimed at improving lower limb muscle control during gait in patients with cerebella ataxia.

Short-latency afferent inhibition and somato-sensory evoked potentials during the migraine cycle: surrogate markers of a cycling cholinergic thalamo-cortical drive?

BACKGROUND: Short-latency afferent inhibition (SAI) consists of motor cortex inhibition induced by sensory afferents and depends on the excitatory effect of cholinergic thalamocortical projections on inhibitory GABAergic cortical networks. Given the electrophysiological evidence for thalamo-cortical dysrhythmia in migraine, we studied SAI in migraineurs during and between attacks and searched for correlations with somatosensory habituation, thalamocortical activation, and clinical features. METHODS: SAI was obtained by conditioning the transcranial magnetic stimulation-induced motor evoked potential (MEP) with an electric stimulus on the median nerve at the wrist with random stimulus intervals corresponding to the latency of individual somatosensory evoked potentials (SSEP) N20 plus 2, 4, 6, or 8 ms. We recruited 30 migraine without aura patients, 16 between (MO), 14 during an attack (MI), and 16 healthy volunteers (HV). We calculated the slope of the linear regression between the unconditioned MEP amplitude and the 4-conditioned MEPs as a measure of SAI. We also measured SSEP amplitude habituation, and high-frequency oscillations (HFO) as an index of thalamo-cortical activation. RESULTS: Compared to HV, SAI, SSEP habituation and early SSEP HFOs were significantly reduced in MO patients between attacks, but enhanced during an attack. There was a positive correlation between degree of SAI and amplitude of early HFOs in HV, but not in MO or MI. CONCLUSIONS: The migraine cycle-dependent variations of SAI and SSEP HFOs are further evidence that facilitatory thalamocortical activation (of GABAergic networks in the motor cortex for SAI), likely to be cholinergic, is reduced in migraine between attacks, but increased ictally.

The function of the lateral inhibitory mechanisms in the somatosensory cortex is normal in patients with chronic migraine.

OBJECTIVE: To study lateral inhibition and habituation/sensitization in the somatosensory cortex of patients with chronic migraine (CM) and to identify correlations with clinical migraine features. METHODS: Sixteen patients with CM without medication overuse, and 17 healthy volunteers (HVs) received somatosensory evoked potentials (SSEPs) elicited by separate electrical stimulation of the right median (M) and ulnar (U) nerves at the wrist and by simultaneous nerve stimulation (MU). We measured the N20-P25 amplitudes and calculated the lateral inhibition (LI) percentage using the formula {100-[MU/(M + U) * 100]}. We also calculated sensitization (SSEP amplitude during block 1) and delayed habituation to M-nerve stimulation. RESULTS: The percentage of LI did not differ between the groups (40.2% in HV, 47.4% in CM, p = 0.276) and was negatively correlated with the monthly headache-day number (r = -0.532, p = 0.034). Patients showed a generalized increase in SSEP amplitudes compared to HVs and habituated normally. CONCLUSIONS: We showed a pattern of somatosensory response in CM similar to that observed during attacks of episodic migraine. SIGNIFICANCE: In the transition process between episodic migraine and CM, LI attempts to physiologically counteract the mounting increase in attack frequency, but this is insufficient to allow patients to exit the chronic phase.

Developing an objective evaluating system to quantify the degree of upper limb movement impairment in patients with severe Friedreich's ataxia.

BACKGROUND: The use of standardized tools and objective measurements is essential to test the effectiveness of new drugs or rehabilitative protocols. Friedreich's ataxia (FRDA) patients with severe disease are often unable to perform the quantitative measurement tests currently used. AIM: The purpose of our study was to develop an easy-to-use application, for touchscreen devices, able to quantify the degree of upper limb movement impairment in patients with severe Friedreich's ataxia. The APP, which we named "Twelve-Red-Squares App-Coo-Test" (12-RSACT), assesses the upper limb ataxia by measuring the test execution time. METHODS: All patients were clinically evaluated using the Composite Cerebellar Functional Severity (CCFS) and the Scale for the Assessment and Rating of Ataxia (SARA). We recruited 92 healthy subjects and 36 FRDA patients with a SARA mean value of 28.8.1 ± 8.2. All participants in our study underwent upper limb movement assessment using the new 12-RSACT, the Click Test, and a well-established system, i.e., the Nine-Hole Peg Test (9HPT). RESULTS: We observed a strong linear correlation between the measurements obtained with the 12-RSACT and those obtained with 9HPT, Click Test, CCFS, and SARA. The 12-RSACT was characterized by excellent internal consistency and intra-rater and test-retest reliability. The minimal detectable change (MDC%) was excellent too. Additionally, the 12-RSACT turned out to be faster and easier to perform compared with the 9HPT. CONCLUSION: The 12-RSACT is an inexpensive test and is easy to use, which can be administered quickly. Therefore, 12-RSACT is a promising tool to assess the upper limb ataxia in FRDA patients and even those with severe diseases.

Genetics Influences Drug Consumption in Medication Overuse Headache, Not in Migraine: Evidence From Wolframin His611Arg Polymorphism Analysis.

Background: The Wolframin His611Arg polymorphism can influence drug consumption in psychiatric patients with impulsive addictive behavior. This cross-sectional study aims to assess the prevalence of the Wolframin His611Arg polymorphism in MOH, a secondary headache belonging to the spectrum of addictive disorders, episodic migraine (EM), and healthy subjects (HS), and its influence on drug consumption. Methods: One-hundred and seventy-two EM, 107 MOH, and 83 HS were enrolled and genotyped for the Wolframin His611Arg polymorphism. Subjects were classified as homozygous for allele His (H/H subjects), homozygous for allele Arg (R/R subjects), and heterozygous (H/R subjects), regrouped as R/R and carriers of allele H (non-R/R), and matched for clinical data. Results: There were no differences in allelic distributions between the three groups (p = 0.19). Drug consumption and other clinical characteristics were not influenced by the Wolframin His611Arg polymorphism (p = 0.42; ß = 0.04) in the EM group. Among the MOH population, R/R subjects consumed more analgesics (p < 0.0001; ß = -0.38), particularly combination drugs (p = 0.0001; d = 2.32). Discussion: The Wolframin His611Arg polymorphism has a similar prevalence between the MOH, EM, and HS groups. The presence of the R/R genotype does not influence symptomatic drug consumption in EM, whereas it determines an increased use of symptomatic drugs in the MOH group, in particular combination drugs (i.e., drugs containing psychoactive compounds). Conclusions: Our findings are consistent with the hypothesis that the Wolframin His611Arg polymorphism plays its effect only in the MOH population, influencing the impulsivity control underlying addictive behavior.

Developing a smartphone application, triaxial accelerometer-based, to quantify static and dynamic balance deficits in patients with cerebellar ataxias.

BACKGROUND: Cerebellar ataxia is characterized by difficulty in the planning of movement and lack of anticipatory postural adjustments, which can result in deficits of balance. Being able to have quantitative measurements in clinical practice, to detect any improvements on balance resulting from new rehabilitation treatments or experimental drugs is very important. AIM: The purpose of this study was to develop an application (APP) able to assess static and dynamic balance in patients with cerebellar ataxias (CA). The APP that works by a wearable device (smartphone) placed at the breastbone level and immobilized by an elastic band, measures the body sway by means of a triaxial accelerometer. METHODS: We investigated 40 CA patients and 80 healthy subjects. All patients were clinically evaluated using the "Berg Balance Scale" (BBS) and the "Scale for the Assessment and Rating of Ataxia" (SARA). Balance impairment was quantitatively assessed using a validated static balance evaluating systems, i.e., Techno-body Pro-Kin footboard. All participants underwent static and dynamic balance assessments using the new APP. RESULTS: We observed a strong correlation between the APP measurements and the score obtained with the BBS, SARA, and Pro-Kin footboard. The intra-rater reliability and the test-retest reliability of the APP measurements, estimated by intraclass correlation coefficient, were excellent. The standard error of measurement and the minimal detectable change were small. No learning effect was observed. CONCLUSIONS: We can state that the APP is an easy, reliable, and valid evaluating system to quantify the trunk sway in a static position and during the gait.