Search

Beyond the classic clinical description, recent studies have quantitatively evaluated gait and balance dysfunction in cerebellar ataxias by means of modern motion analysis systems. These systems have the aim of clearly and quantitatively describing the differences, with respect to healthy subjects, in kinematic, kinetic, and surface electromyography variables, establishing the basis for a rehabilitation strategy and assessing its efficacy. The main findings which characterize the gait pattern of cerebellar patients are: increased step width, reduced ankle joint range of motion with increased coactivation of the antagonist muscles, and increased stride-to-stride variability. Whereas the former is a compensatory strategy adopted by patients to keep the center of mass within the base of support, the latter indicates the inability of patients to maintain dynamic balance through a regular walking pattern and may reflect the primary deficit directly related to cerebellar dysfunction and the consequent lack of muscle coordination during walking. Moreover, during the course of the disease, with the progressive loss of walking autonomy, step length, and lower-limb joint range of motion are drastically reduced. As to the joint coordination defect, abnormal intralimb joint coordination during walking, in terms of both joint kinematics and interaction torques, has been reported in several studies. Furthermore, patients with cerebellar ataxia show a poor intersegmental coordination, with a chaotic coordinative behavior between trunk and hip, leading to increased upper-body oscillations that affect gait performance and stability, sustaining a vicious circle that transforms the upper body into a generator of perturbations. The use of motion analysis laboratories allows a deeper segmental and global characterization of walking impairment in these patients and can shed light on the nature of both the primary specific gait disorder and compensatory mechanisms. Such deeper understanding might reasonably represent a valid prerequisite for establishing better-targeted rehabilitation strategies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective To study the influence of the migraine aura on the trigeminal nociception, we investigated the habituation of the nociceptive blink reflex (nBR) R2 responses in aura with migraine headache (AwMH) and comparatively in migraine without aura (MWoA) and healthy subjects (HS). Background A clear deficit of habituation in trigeminal nociceptive responses has been documented in MWoA; however, similar data in MWA are lacking. Methods Seventeen AwMH, 29 MWoA, and 30 HS were enrolled and a nonrandomized clinical neurophysiological study examining nBR habituation by clinical diagnosis was devised. We delivered a series of 26 electrical stimuli, at different stimulation frequencies (SF) (0.05, 0.1, 0.2, 0.3, 0.5, and 1 Hz), subsequently subdivided in five blocks of five responses for each SF. The mean area values of the second to the fifth block expressed as the percentage of the mean area value of the first block were taken as an index of habituation for each SF. Results A significant lower mean percentage decrease of the R2 area across all blocks was found at 1, 0.5, 0.3, and 0.2 Hz SF in MWoA and at 0.3 and 0.2 Hz SF in AwMH, when compared to HS. In the most representative fifth block of responses, we found in MWoA vs HS at 1 Hz, 57.0 ± 27.8 vs 30.6 ± 12.0; at 0.5 Hz, 54.8 ± 26.1 vs 32.51 ± 17.7; at 0.3 Hz, 44.7 ± 21.6 vs 27.6 ± 13.2; at 0.2 Hz, 61.3 ± 29.5 vs 32.6 ± 18.0, and in AwMH vs HS at 0.3 Hz, 52.7 ± 24.7 vs 27.6 ± 13.2; at 0.2 Hz, 69.3 ± 38.6 vs 32.6 ± 18.0 as mean ± SD of the R2 area percentage of the first block, respectively. Interestingly, AwMH subjects did not show differences in mean percentage decrease of the R2 area at 1 and 0.5 Hz SF when compared to HS. No differences between groups were found at 0.1 and 0.05 Hz SF. Conclusions We demonstrated in AwMH a deficit of habituation of the nBR R2 responses after repeated stimulations, although less pronounced than that observed in MWoA of comparable clinical severity. We hypothesize that AwMH and MWoA share some pathogenetic aspects, and also that migraine aura physiopathology may play a modulating role on the excitability of the nociceptive trigeminal pathways. [ABSTRACT FROM AUTHOR]

Background: Resting state magnetic resonance imaging allows studying functionally interconnected brain networks. Here we were aimed to verify functional connectivity between brain networks at rest and its relationship with thalamic microstructure in migraine without aura (MO) patients between attacks. Methods: Eighteen patients with untreated MO underwent 3 T MRI scans and were compared to a group of 19 healthy volunteers (HV). We used MRI to collect resting state data among two selected resting state networks, identified using group independent component (IC) analysis. Fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from a previous diffusion tensor imaging study on the same subjects and correlated with resting state ICs Z-scores. Results: In comparison to HV, in MO we found significant reduced functional connectivity between the default mode network and the visuo-spatial system. Both HV and migraine patients selected ICs Z-scores correlated negatively with FA values of the thalamus bilaterally. Conclusions: The present results are the first evidence supporting the hypothesis that an abnormal resting within networks connectivity associated with significant differences in baseline thalamic microstructure could contribute to interictal migraine pathophysiology. [ABSTRACT FROM AUTHOR]

Abstract: In cluster headache (CH), pathogenesis has been emphasized the role of the posterior hypothalamus. It is part of a supraspinal network involved in the descending control of pain, including the diffuse noxious inhibitory control (DNIC), which in turn modulates the pain processing. We hypothesized that CH during the active phase facilitated temporal pain processing supported by abnormal functioning of the DNIC. We studied the functional activity of the DNIC by evaluating the effect of the cold pressor test (CPT) on the temporal summation threshold (TST) of the nociceptive withdrawal reflex. Ten subjects with episodic CH (2 women, 8 men) and 10 healthy subjects were recruited. Each subject underwent neurophysiological evaluation (nociceptive withdrawal reflex TST and related painful sensation) at baseline, then before (control session), during (pain session), and 5min after (aftereffect) the CPT (immersing hand in a 4°C water bath for 4–5min). Patients had been studied during both the active and remission phases. During the active phase, CH revealed a significant facilitation in temporal processing of pain stimuli (reduction of TST), which reverted during the remission phase. The CPT activating the DNIC did not produce any significant inhibitory effect of pain responses in CH during the active phase, whereas it induced a clear inhibition during the remission phase. We hypothesized that in CH, a dysfunction of the supraspinal control of pain related to the clinical activity of the disease, possibly supported by an abnormal hypothalamic function, leads to a facilitation in pain processing and a predisposition to pain attacks. [Copyright &y& Elsevier]

Abstract: Objective: Trigemino-cervical reflexes (TCRs) are electromyographic responses induced by electrical stimulation of the trigeminal nerve and recorded in the neck muscles. Trigemino-cervical reflexes are detectable in Parkinson’s disease, whereas they are absent in progressive supranuclear palsy (PSP), an atypical parkinsonism associated with brainstem degeneration. To date, no study has investigated TCRs in multiple system atrophy (MSA), another atypical parkinsonism associated with brainstem involvement, which resembles PSP. Methods: To understand whether TCRs are helpful in differentiating PSP from MSA, we compared the TCRs recorded in 10 PSP patients with those obtained from 10 patients diagnosed as having probable MSA, parkinsonian type (MSA-P). Results: Trigemino-cervical reflexes were not recorded in any of the PSP patients, while they were clearly detectable in all the MSA-P patients. Conclusions: Trigemino-cervical reflex recording is a rapid neurophysiological method, which could assist in the differential diagnosis between PSP and MSA-P. Significance: This study further improves our understanding of the different neuronal functioning of extrapyramidal disorders. TCRs monitoring may be useful to support the diagnosis of atypical parkinsonisms especially when clinical evidence is uncertain. [Copyright &y& Elsevier]

Abstract: Nitric-oxide donor glyceryl-trinitrate (GTN) modulates cerebral and spinal regions that are involved in migraine and pain processing. We hypothesized that in migraineurs, the susceptibility to develop a migraine attack after GTN administration should parallel with an high sensitivity to GTN-induced change in the pain processing at spinal level. We used the temporal summation threshold (TST) of the lower limb nociceptive withdrawal reflex (NWR) and the related pain sensation to study in parallel the time-course of the effect of the GTN administration on the pain processing at spinal level in migraine and healthy subjects. Twenty-eight (21 F; 7M; mean age 34.2±8.2) migraine and 15 (11 F; 4M; mean age 35.9±8.9) healthy subjects were recruited in a double-blind, placebo-controlled, cross-over trial. Neurophysiological examinations were carried out before (baseline) and 30′, 60′, 120′, 180′ and 240′ after GTN (0.9mg sublingual) or placebo administration during two different sessions. In migraineurs, GTN administration was associated to a significant facilitation in temporal summation of pain (reduced TST and increased painful sensation) 60′, 120′ and 180′ after drug intake when compared to baseline, to placebo condition and to controls after GTN intake. Furthermore, in migraineurs who developed migraine after GTN, a significant facilitation in temporal summation of pain was detected 60′, 120′ and 180′ after drug intake when compared to patients without clinical response. In migraineurs the susceptibility to develop migraine attack after GTN administration seems to be a specific trait of a subgroup of patients linked to a supersensitivity of the pain system to GTN. [Copyright &y& Elsevier]

Abstract: Objective: Electrical stimulation of the supraorbital trigeminal nerve branch induces trigeminocervical reflex responses (TCRs) in the neck muscles. The purpose of this study was to elicit more nociceptive TCR responses through preferential activation of the nociceptive afferents with a concentric surface electrode. Methods: We recorded TCRs in 10 healthy subjects using both a standard (sTCR) and a nociceptive (nTCR) concentric surface electrode. We compared the baseline parameters, stimulus intensity/response, recovery, and habituation curves recorded for the two types of electrode, and assessed the effects of local anaesthesia. Results: Compared with the sTCRs, nTCRs showed a significantly longer latency of the late reflex component, as well as lower pain and higher reflex thresholds. They also showed a different recovery cycle and stimulus intensity/response curve, but similar habituation rate. Local anaesthesia attenuated by 85% the late reflex response to stimulation by the concentric electrode, and by only 15% the response to standard electrode stimulation. Conclusions: The differences observed stimulating with these two electrode types may be due to their different activation of the afferent fibres. Significance: If this study were extended to patients affected by primary headaches, TCR monitoring could emerge as a sensitive tool for detecting changes in nociceptive transmission at the level of trigeminocervical complex. [ABSTRACT FROM AUTHOR]

Abstract: The flexion or flexor reflex (FR) recorded in the lower limbs in humans (LLFR) is a widely investigated neurophysiological tool. It is a polysynaptic and multisegmental spinal response that produces a withdrawal of the stimulated limb and resembles (having several features in common) the hind-paw FR in animals. The FR, in both animals and humans, is mediated by a complex circuitry modulated at spinal and supraspinal level. At rest, the LLFR (usually obtained by stimulating the sural/tibial nerve and by recording from the biceps femoris/tibial anterior muscle) appears as a double burst composed of an early, inconstantly present component, called the RII reflex, and a late, larger and stable component, called the RIII reflex. Numerous studies have shown that the afferents mediating the RII reflex are conveyed by large-diameter, low-threshold, non-nociceptive A-beta fibers, and those mediating the RIII reflex by small-diameter, high-threshold nociceptive A-delta fibers. However, several afferents, including nociceptive and non-nociceptive fibers from skin and muscles, have been found to contribute to LLFR activation. Since the threshold of the RIII reflex has been shown to correspond to the pain threshold and the size of the reflex to be related to the level of pain perception, it has been suggested that the RIII reflex might constitute a useful tool to investigate pain processing at spinal and supraspinal level, pharmacological modulation and pathological pain conditions. As stated in EFNS guidelines, the RIII reflex is the most widely used of all the nociceptive reflexes, and appears to be the most reliable in the assessment of treatment efficacy. However, the RIII reflex use in the clinical evaluation of neuropathic pain is still limited. In addition to its nocifensive function, the LLFR seems to be linked to posture and locomotion. This may be explained by the fact that its neuronal circuitry, made up of a complex pool of interneurons, is interposed in motor control and, during movements, receives both peripheral afferents (flexion reflex afferents, FRAs) and descending commands, forming a multisensorial feedback mechanism and projecting the output to motoneurons. LLFR excitability, mediated by this complex circuitry, is finely modulated in a state- and phase-dependent manner, rather as we observe in the FR in animal models. Several studies have demonstrated that LLFR excitability may be influenced by numerous physiological conditions (menstrual cycle, stress, attention, sleep and so on) and pathological states (spinal lesions, spasticity, Wallenberg''s syndrome, fibromyalgia, headaches and so on). Finally, the LLFR is modulated by several drugs and neurotransmitters. In summary, study of the LLFR in humans has proved to be an interesting functional window onto the spinal and supraspinal mechanisms of pain processing and onto the spinal neural control mechanisms operating during posture and locomotion. [Copyright &y& Elsevier]

The study of CNS painmodulating pathways has led to important discoveries about the role of central nociceptive structures such as PAG and hypothalamus in the pathophysiology of episodic and chronic primary headaches. Functional neuroimaging studies have revealed that primary headaches are characterised by different patterns of activation of central pain modulatory structures. A future model of headache pathophysiology investigating the contribution of CNS pain–modulating pathways will probably increase our understanding of pain processing in primary headaches. Herein we review the neurophysiological approaches to assess central pain modulation in primary headaches with emphasis on the diffuse noxious inhibitory control, a form of endogenous pain inhibition. In addition, patients’ data will be presented that highlights the utility of such methods for primary headache’s pathophysiology and clinical monitoring. [ABSTRACT FROM AUTHOR]

Objective.—To evaluate trigemino-cervical-spinal reflexes (TCSRs) in a group of migraine patients during the pain-free period. Background.—TCRSs are part of a complex nocifensive response involving the cervical and the upper limb muscles, and are modulated by supraspinal inhibitory pathways; it may, thus, be possible to use TCRSs to explore the trigeminal system in migraineurs. Methods.—A total of 43 migraine patients without aura (MWoA, 32 patients) or with typical aura (MWA, 11 patients) and 30 age- and sex-matched healthy subjects took part in the study. TCRSs were obtained by stimulating the supraorbital nerve and recorded from the semispinalis capitis muscle and the biceps brachii. The latency (L, msec), area (A, mVms) and recovery cycle of the reflexes were recorded. The effects of heterotopic painful stimulation on the neurophysiological parameters were studied by a validated cold pressor test (CPT). Results.—No significant changes were found between either migraine patients and controls or MWoA and MWA patients in the mean values in the L and A of TCRSs ( t-test, P > .05). The recovery curve of the trigemino-cervical reflexes (TCRs) was significantly faster in migraine patients than in controls, while no differences were found in the trigemino-spinal reflexes (TSRs) ( t-test, P < .01). Activation of the diffuse inhibitory controls through the CPT induced a significant reduction in the TCRs and TSRs area in both migraine patients and controls (paired t-test, P < .01), though the extent of this reduction did not differ significantly between migraineurs and controls ( t-test, P > .05). Comments.—Our data suggest that the pain-free period in migraine patients is characterized by a hyperexcitability of the trigeminal pathways and of their anatomical and functional connections with the upper cervical cord neurons, and that this abnormal hyperexcitability does not appear to be due to a lack of a supraspinal inhibitory modulation. ( Headache 2005;45:1061-1068) [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the effects of diffuse noxious inhibitory controls (DNICs) on the temporal summation of the nociceptive flexion reflex (RIII reflex) in humans. Recordings were obtained from 36 healthy adults (16 M, 20 F), and the area and temporal summation threshold (TST) of the RIII reflex were measured. The subjective intensity of the painful sensation was rated on an 11-point visual analogue scale (VAS). Neurophysiological and VAS measurements were recorded after activation of DNICs by means of the cold pressor test (CPT), which involved immersing the hand in cold water (2–4°C). A slight significant lower TST was found in the females versus the males. In all the subjects, the CPT induced a significant TST increase and RIII area reduction compared with the control session. The VAS results paralleled those of the RIII reflex area and TST. During the CPT, a significant difference in the percentage TST increase emerged between females and males, being lower in the former. Similarly, we found a significantly lower percentage reduction of the RIII area in women than in men during the CPT. To summarize, activation of DNICs through the CPT significantly increased the TST of the RIII reflex in healthy subjects. This inhibitory effect was gender-specific. Whereas other findings are based on psychophysical evaluations, the results of this experimental study provide an objective neurophysiological demonstration that DNICs attenuate temporal summation in humans and confirm the presence of significant differences in pain modulation mechanisms between men and women. [Copyright &y& Elsevier]

Background: The purpose of this review is to provide a comprehensive overview of the findings of clinical electrophysiology studies aimed to investigate changes in information processing of migraine with aura patients. Main body: Abnormalities in alpha rhythm power and symmetry, the presence of slowing, and increased information flow in a wide range of frequency bands often characterize the spontaneous EEG activity of MA. Higher grand-average cortical response amplitudes, an increased interhemispheric response asymmetry, and lack of amplitude habituation were less consistently demonstrated in response to any kind of sensory stimulation in MA patients. Studies with single-pulse and repetitive transcranial magnetic stimulation (TMS) have reported abnormal cortical responsivity manifesting as greater motor evoked potential (MEP) amplitude, lower threshold for phosphenes production, and paradoxical effects in response to both depressing or enhancing repetitive TMS methodologies. Studies of the trigeminal system in MA are sparse and the few available showed lack of blink reflex habituation and abnormal findings on SFEMG reflecting subclinical, probably inherited, dysfunctions of neuromuscular transmission. The limited studies that were able to investigate patients during the aura revealed suppression of evoked potentials, desynchronization in extrastriate areas and in the temporal lobe, and large variations in direct current potentials with magnetoelectroencephalography. Contrary to what has been observed in the most common forms of migraine, patients with familial hemiplegic migraine show greater habituation in response to visual and trigeminal stimuli, as well as a higher motor threshold and a lower MEP amplitude than healthy subjects. Conclusion: Since most of the electrophysiological abnormalities mentioned above were more frequently present and had a greater amplitude in migraine with aura than in migraine without aura, neurophysiological techniques have been shown to be of great help in the search for the pathophysiological basis of migraine aura. [ABSTRACT FROM AUTHOR]

Objective Pain is a frequent non-motor feature in Parkinsonism but mechanistic data on the alteration of pain processing are insufficient to understand the possible causes and to define specifically-targeted treatments. Methods we investigated spinal nociception through the neurophysiological measure of the threshold (TR) of nociceptive withdrawal reflex (NWR) and its temporal summation threshold (TST) comparatively in 12 Progressive Supranuclear Palsy (PSP) subjects, 11 Multiple System Atrophy (MSA) patients, 15 Parkinson’s disease (PD) subjects and 24 healthy controls (HC). We also investigated the modulatory effect of L-Dopa in these three parkinsonian groups. Results We found a significant reduction in the TR of NWR and in the TST of NWR in PSP, MSA and PD patients compared with HC. L-Dopa induced an increase in the TR of NWR in the PSP group while TST of NWR increased in both PSP and PD. Conclusions Our neurophysiological findings identify a facilitation of nociceptive processing in PSP that is broadly similar to that observed in MSA and PD. Specific peculiarities have emerged for PSP. Significance Our data advance the knowledge of the neurophysiology of nociception in the advanced phases of parkinsonian syndromes and on the role of dopaminergic pathways in the control on pain processing. [ABSTRACT FROM AUTHOR]

Abstract: Despite intensive neurophysiological research, evidence is lacking to show whether abnormal cortical excitability in migraine reflects a primary cortical disturbance or reduced control by thalamo-cortical loops. One way to contribute to the scientific discussion on this topic is to deliver transcranial magnetic stimulation (TMS) and test the cortical silent period (SP) recorded in facial muscles. The facial-muscle SP is a purely cortical phenomenon that reflects the excitability of inhibitory interneurons, and can disclose changes in cortical inhibition even in patients without documented primary lesions of the motor cortices. To test the interictal excitability of cortical motor inhibitory interneurons in migraine, we investigated the facial-SP in patients with migraine with and without aura between attacks. In 26 patients and 15 age-matched controls, high-intensity magnetic stimuli were delivered with a round coil centered at the vertex during a maximal muscle contraction. Electromyographic responses were recorded from surface electrodes placed over the subjects’ perioral muscles. Facial SPs were significantly shorter in patients than in controls. The SP shortening provides neurophysiological evidence showing hypoexcitability of cortical inhibitory neurons in patients with migraine between attacks. Despite a possible primary deficit of cortical inhibitory interneurons in migraine, we favor the interpretation of a secondary disfacilitation by hypoactive thalamo-cortical loops. Based on this interpretation, the interictal reduced cortical inhibition documented by the shortened SP could be considered the motor counterpart of the reduced preactivation excitability level in the sensory cortices purported to explain why cortical evoked responses habituate poorly in patients with migraine. [Copyright &y& Elsevier]