Dysphagia in Huntington's Disease: Correlation with Clinical Features.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by motor impairment, cognitive decline and psychiatric disorders. Dysphagia is a pathologic condition that increases morbidity and mortality of the affected people. Our aim was to evaluate dysphagia in a group of HD patients in view of motor, cognitive and functional decline. Thirty-seven genetically confirmed HD patients were submitted to clinical evaluations of swallowing. Bedside Swallowing Assessment Scale (BSAS) was used. Dysphagia Outcome and Severity Scale (DOSS) was applied for a preliminary classification of swallowing difficulties. All patients were also evaluated by the Unified Huntington's Disease Rating Scale (UHDRS). A group of 39 controls comparable for sex and age were recruited for BSAS scores normalisation. The BSAS scores indicated that in our HD cohort, 32.4% presented relevant or severe dysphagia. The DOSS levels were significantly correlated with main clinical features, such as age, disease duration and motor impairment, with special regard to lingual protrusion ability, dysarthria and bradykinesia. The total functional capacity (TFC) and cognitive scales did not show significant correlation with DOSS levels. The results of clinical examination of swallowing indicated that dysphagia is a prevalent motor symptom of HD.

Clinical features of headache patients with fibromyalgia comorbidity.

Our previous study assessed the prevalence of fibromyalgia (FM) syndrome in migraine and tension-type headache. We aimed to update our previous results, considering a larger cohort of primary headache patients who came for the first time at our tertiary headache ambulatory. A consecutive sample of 1,123 patients was screened. Frequency of FM in the main groups and types of primary headaches; discriminating factor for FM comorbidity derived from headache frequency and duration, age, anxiety, depression, headache disability, allodynia, pericranial tenderness, fatigue, quality of life and sleep, and probability of FM membership in groups; and types of primary headaches were assessed. FM was present in 174 among a total of 889 included patients. It prevailed in the tension-type headache main group (35%, p < 0.0001) and chronic tension-type headache subtype (44.3%, p < 0.0001). Headache frequency, anxiety, pericranial tenderness, poor sleep quality, and physical disability were the best discriminating variables for FM comorbidity, with 81.2% sensitivity. Patients presenting with chronic migraine and chronic tension-type headache had a higher probability of sharing the FM profile (Bonferroni test, p < 0.01). A phenotypic profile where headache frequency concurs with anxiety, sleep disturbance, and pericranial tenderness should be individuated to detect the development of diffuse pain in headache patients.

Effects of high-frequency repetitive transcranial magnetic stimulation of primary motor cortex on laser-evoked potentials in migraine.

The aim of this study was to examine the effects of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex (M1) on subjective pain and evoked responses induced by laser stimulation (LEPs) of the contralateral hand and supraorbital zone in a cohort of migraine patients without aura during the inter-critical phase, and to compare the effects with those of non-migraine healthy controls. Thirteen migraine patients and 12 sex- and age-matched controls were evaluated. Each rTMS session consisted of 1,800 stimuli at a frequency of 5 Hz and 90% motor threshold intensity. Sham (control) rTMS was performed at the same stimulation position. The vertex LEP amplitude was reduced at the trigeminal and hand levels in the sham-placebo condition and after rTMS to a greater extent in the migraine patients than in healthy controls, while the laser pain rating was unaffected. These results suggest that HF rTMS of motor cortex and the sham procedure can both modulate pain-related evoked responses in migraine patients.

Pain perception and laser evoked potentials during menstrual cycle in migraine.

The association between estrogens "withdrawal" and attacks of migraine without aura is well-known. The aim of the study was to examine the features of laser evoked potentials (LEPs), including habituation, in women suffering from migraine without aura versus healthy controls, during the pre-menstrual and late luteal phases. Nine migraine without aura and 10 non-migraine healthy women, were evaluated during the pre-menstrual phase and late luteal phase. The LEPs were recorded during the inter-critical phase. The right supraorbital zone and the dorsum of the right hand were stimulated. Three consecutive series of 20 laser stimuli were obtained for each stimulation site. Laser pain perception was rated by a 0-100 VAS after each stimulation series. Migraine patients exhibited increased LEPs amplitude and reduced habituation compared to normal subjects. Laser-pain perception was increased during the pre-menstrual phase in both patients and controls. Migraine patients and controls showed increased P2 and N2-P2 amplitude in the pre-menstrual phase, on both stimulation sites. During the pre-menstrual phase the N2-P2 habituation appeared to be reduced in both migraine and healthy women. The estrogen withdrawal occurring during the menstrual cycle may favor reduced habituation of nociceptive cortex, which may facilitate pain symptoms and migraine in predisposed women.

Effects of topiramate and levetiracetam vs placebo on habituation of contingent negative variation in migraine patients.

Migraine is characterized by reduced habituation of multimodal evoked potentials, which in turn reflects an abnormal pattern of cortical excitability. We assessed the effects of a 2-month treatment with topiramate or levetiracetam vs placebo on contingent negative variation (CNV) habituation and amplitude in a cohort of migraine without aura (MO) patients. Forty-five MO patients were selected from a university-based outpatient clinic and randomly assigned to 100mg topiramate or 1000mg levetiracetam or placebo in a double-blind design. Twenty-four control subjects were also recruited. The initial CNV (iCNV) amplitude and habituation were assessed by Cz/A1-A2 derivation recordings in the basal condition (T0) and after 2 months of treatment (T1). Both topiramate and levetiracetam produced a significant reduction in migraine frequency compared to placebo, they also reversed the abnormal iCNV habituation pattern which characterized the MO patients in the basal condition and which was not present in controls. For migraine patients, the reduced migraine frequency and habituation index following treatment were significantly correlated. A lack of habituation of evoked responses is an interictal endophenotypic marker in migraine, the reversion of which may improve disease outcome. These results suggest a role for neurophysiological methods in the management of migraine.

Influence of aesthetic perception on visual event-related potentials.

The aim of the study was to assess the effects of visual aesthetic perception on event-related potentials (ERPs). Eight subjects assigned an aesthetic judgment (beautiful, neutral, or ugly) and a 10-step beauty estimation to the target stimuli, consisting of famous artistic pictures and geometric shapes. In a further task, the subjects performed a motor response to the previously judged pictures and geometric shapes. ERPs were recorded through 54 scalp electrodes during both tasks. The P3b amplitude was increased during the categorization of the geometric shapes compared to the artistic figures and during the vision of the beautiful targets preceding the motor response. The categorization of the aesthetic qualities of geometrical shapes seems to induce a higher level of attention, while a higher arousal variation was elicited by the recognition of beauty, in any form that was presented.

Effects of levetiracetam vs topiramate and placebo on visually evoked phase synchronization changes of alpha rhythm in migraine.

OBJECTIVE: Recent theories about migraine pathogenesis have outlined an abnormal central processing of sensory signals, also suggested by an abnormal pattern of EEG hyper-synchronization under visual stimulation. The aim of the present study was to test the efficacy of topiramate and levetiracetam vs placebo in a double blind project observing the effects of the three treatments on the EEG synchronization in the alpha band under sustained flash stimulation. METHODS: Forty-five migraine without aura outpatients (MO) were selected and randomly assigned to 100mg topiramate, 1000 mg levetiracetam or placebo treatment. In addition, 24 non-migraine healthy controls were submitted to EEG analysis. The EEG was recorded by 19 channels: flash stimuli with a luminosity of 0.2J were delivered, in a frequency range from 3 to 30 Hz. We evaluated the phase synchronization index, that we previously applied in migraine, after EEG signals filtering in the alpha band. Our approach was based on the Hilbert transform. RESULTS: Both levetiracetam and topiramate significantly decreased migraine frequency, compared with placebo. MO patients displayed increased alpha-band phase synchronization as an effect of stimulus frequency; on the other hand the stimuli had an overall desynchronizing effect on control subjects. The phase synchronization index separates the two stages, before and after the treatment, only for levetiracetam, at stimulus frequencies of 9, 18, 24 and 27 Hz. CONCLUSIONS: An abnormal alpha band synchronization under visual stimuli was confirmed in migraine; this phenomenon was reversed by levetiracetam preventive treatment. SIGNIFICANCE: These results confirmed in humans the inhibiting action of levetiracetam on neuronal hyper-synchronization.

Effects of low and high frequency repetitive transcranial magnetic stimulation of the primary motor cortex on contingent negative variations in normal subjects.

The state of primary motor cortex (M1) excitability is crucial for the processing of voluntary movement. We aimed to test the modulation induced by 1 Hz and 5 Hz repetitive transcranial magnetic stimulation (rTMS) of M1 on both early and late components of the contingent negative variation (CNV) and on the motor reaction in normal subjects. The CNV was evaluated in basal, and after 15 min of real or sham 1 Hz and 5 Hz stimulation of the left motor cortex in 7 right handed volunteers. Inhibition of motor cortex, due to rTMS stimulation, resulted in an amplitude increase of early and late components of CNV, and a slight reducing effect on motor reaction times, while 5 Hz stimulation did not change CNV amplitude. In normal subjects transient inhibition of motor cortex causes an increase of cortical events preceding external-cued voluntary movements, as a probable compensatory phenomena able to maintain an efficient motor performance.

Abnormal spinal cord pain processing in Huntington's disease. The role of the diffuse noxious inhibitory control.

OBJECTIVES: Our study is aimed to evaluate the spinal cord pain processing in Huntington's disease (HD) by testing both the temporal summation threshold (TST) of the nociceptive withdrawal reflex (NWR) and the functional activity of the diffuse noxious inhibitory control (DNIC) as form of supraspinal control of pain. METHODS: We enrolled 19 HD patients and 17 healthy controls. We measured threshold (Th), Area, TST and related psychophysical pain sensations of the NWR, at baseline and during and after activation of the DNIC by means of cold pressor test (CPT) as heterotopic noxious conditioning stimulation. RESULTS: In HD patients we found a significantly higher Th and TST as well as a lower Area when compared to controls. During the CPT, a significant inhibition of reflex and psychophysical pain responses were found in both HD patients and controls when compared to baseline, without differences between the groups in CPT results. CONCLUSIONS: Our study demonstrated an abnormal spinal cord pain processing in HD patients. Abnormalities in pain processing are not apparently linked to a dysfunctional DNIC inhibitory projection system in HD patients. SIGNIFICANCE: Our findings support the hypothesis that the striatum could play a role in pain modulation and that its atrophy could affect pain processing without change the DNIC efficiency.

Suggestion and pain in migraine: a study by laser evoked potentials.

Belief and expectation are part of placebo effect. Migraine patients are characterized by a dysfunctional modulation of pain processing, though a clear placebo effect emerges in clinical trials. The aim of the study was to evaluate the effect of visual and verbal suggestion on subjective pain sensation and cortical responses evoked by CO2 painful laser stimuli in migraine without aura patients vs healthy controls. Twenty-six patients were recorded during the inter-ictal phase and compared to 26 sex and age-matched controls. The right hand and the right supraorbital zone were stimulated during a not conditioned and a conditioned task, where laser stimuli were delivered after a verbal and visual cues of decreased (D), increased (I) or basal (B) intensity, which was left unmodified during the entire task. In control subjects pain rating changed, according to the announced intensity, while in migraine patients the basal hyper-algesia remained unmodified. The N1 and N2 amplitudes tended to change coherently with the stimulus cue in controls, while an opposite paradoxical increase in decreasing condition emerged in migraine. The P2 amplitude modulation was also reduced in migraine, differently from controls. The altered pattern of pain rating and N2 amplitude modulation concurred with frequency of migraine, disability and allodynia. In controls suggestion influenced cortical pain processing and subjective pain rating, while in migraine a peculiar pattern of cortical activation contrasted external cues in order to maintain the basal hyper-algesia. This scarce influence of induced suggestion on pain experience seemed to characterize patients with more severe migraine and central sensitization.

Management of Huntington's disease: role of tetrabenazine.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by progressive involuntary movements, neuropsychiatric disturbances, and cognitive impairment. The use of tetrabenazine (TBZ), a specific inhibitor of vesicular monoamine transporter, is approved for chorea in HD patients. We aimed to review the medical literature concerning the efficacy and tolerability of TBZ in the treatment of HD patients and to report our personal experience about TBZ use in a cohort of HD patients. We searched PubMed (1960 to July 2010) using the following keywords: "tetrabenazine" + "huntington's disease + chorea". We included randomized controlled trials, open-label trials, and retrospective studies. We excluded case reports and studies conducted on fewer than 20 patients. In addition, we retrospectively evaluated 2 years' follow-up of TBZ treatment on motor and cognitive performances and functional abilities in 28 HD patients, compared with 10 patients treated by other neuroleptics (clotiapine). Only four papers fulfilled the requested criteria. In the first study, which included 84 randomized outpatients, TBZ showed a significant improvement of chorea compared with placebo. In the open-label study extension, TBZ confirmed its efficacy on chorea, with a frequent occurrence of withdrawals due to side effects. In a retrospective study of long-term efficacy, 63 patients under TBZ therapy for an average period of 34 months showed a stable effect on chorea, despite a slight reduction of effect over time. In a telephone survey conducted on a total of 118 patients affected by different movement disorders, TBZ showed the most favorable effect for the 28 included HD patients. Our HD patients showed a slight deterioration of motor performances over time that was nonsignificant compared with TBZ or clotiapine treatments. Despite the fact that the global effect of TBZ seems positive in HD, more attention on evaluating symptomatic treatments for cognitive and psychiatric deterioration as well as motor deterioration would alleviate this devastating disorder until a neuroprotective treatment becomes available.

Lack of effects of low frequency repetitive transcranial magnetic stimulation on alpha rhythm phase synchronization in migraine patients.

The study aimed to test the modulation induced by 1 Hz repetitive Transcranial Magnetic Stimulation (rTMS) of the occipital cortex on the alpha phase synchronization under repetitive flash stimuli in 15 migraine without aura patients compared to 10 controls. The EEG was recorded by 7 channels, while flash stimuli were delivered at 9, 18, 21 and 24 Hz in basal, rTMS (15 min of 1 Hz stimulation of the occipital cortex) and sham conditions. Migraine patients displayed increased alpha-band phase synchronization under visual stimulation, while an overall desynchronizing effect was evident in controls. The rTMS resulted in a slight increase of synchronization index in migraine patients, which did not cause significant differences in respect to the basal and sham conditions. The synchronizing-desynchronizing changes of alpha rhythm under repetitive flash stimulation, seem independent from the state of occipital cortex excitability. Other mechanisms beyond cortical excitability may contribute to explain migraine pathogenesis.

Laser evoked potentials in carpal tunnel syndrome.

OBJECTIVES: The aim of this study was to evaluate the function of Adelta fibers at the hand level in patients with clinical symptoms of Carpal Tunnel Syndrome (CTS) using CO(2) laser evoked potentials (LEPs), in light of the intensity and distribution of sensory symptoms and pain. METHODS: Thirty-four CTS outpatients (62 hands) were compared to 23 sex- and age-matched control subjects (46 hands). The periungueal skin of the first, second, third and fifth fingers, and the dorsum of the hands were stimulated in random order. The latency and amplitude of the N2, P2 and N1 components were evaluated with respect to the Nerve Conduction Study (NCS) data, clinical scales, pain intensity and glove-like symptoms distribution. RESULTS: The amplitude of the N2-P2 complex was significantly reduced in CTS hands compared to normal hands after stimulation of the second and third fingers, even in patients with mild nerve conduction impairment. No significant fifth finger LEP abnormalities were found in patients with glove-like distribution symptoms. The N2-P2 amplitude at the second and third fingers was positively correlated with the severity of sensory symptoms. CONCLUSIONS: The involvement of median nerve Adelta fibers in CTS seems to be an early phenomenon, which concurs with the impairment of large motor and sensory afferents and is linked to the severity of the disease. SIGNIFICANCE: The finding of reduced sensory symptoms in patients with severe thin afferents damage, may suggest a slight expression of central sensitisation phenomena in the advanced stage of CTS syndrome.

Effects of distraction versus spatial discrimination on laser-evoked potentials in migraine.

OBJECTIVES: To evaluate whether migraine patients exhibit less inhibition to painful stimuli when distracted from pain as compared to healthy subjects, testing the spatial discrimination of painful stimuli, the performance during the mental arithmetic task used to contrast the discrimination performance and the behavior of N1 and N2-P2 laser-evoked potentials (LEPs) amplitudes during spatial discrimination and during distraction. METHODS: Eight migraine patients and 8 healthy controls were examined. During repetitive series of painful laser stimulation of the hand, they had to (1) perform a spatial discrimination task, contrasted by (2) a mental arithmetic task that served as distraction. RESULTS: Patients made 50% to 100% more mistakes than controls in the spatial discrimination task (P < .001) as well as during mental arithmetic (P < .05). Whereas healthy subjects showed a marked decrease of the LEP vertex potential amplitudes during distraction compared to the discrimination task, no such attenuation of LEPs was seen in migraine patients (group x task interaction, P < .05). N1 amplitude exhibited a left-hemisphere dominance in both groups, significantly smaller amplitude in migraine patients, but no significant task modulation. CONCLUSION: Migraine patients exhibited reduced inhibition by attentional modulation of pain processing, accompanied by impaired spatial discrimination of painful stimuli.

Effects of remote cutaneous pain on trigeminal laser-evoked potentials in migraine patients.

The present study aimed to evaluate heat pain thresholds and evoked potentials following CO(2) laser thermal stimulation (laser-evoked potentials, LEPs), during remote application of capsaicin, in migraine patients vs. non-migraine healthy controls. Twelve outpatients suffering from migraine without aura were compared with 10 healthy controls. The LEPs were recorded by 6 scalp electrodes, stimulating the dorsum of the right hand and the right supraorbital zone in basal condition, during the application of 3% capsaicin on the dorsum of the left hand and after capsaicin removal. In normal subjects, the laser pain and the N2-P2 vertex complex obtained by the hand and face stimulation were significantly reduced during remote capsaicin application, with respect to pre-and post-capsaicin conditions, while in migraine LEPs and laser pain were not significantly modified during remote painful stimulation. In migraine a defective brainstem inhibiting control may coexist with cognitive factors of focalised attention to facial pain, less sensitive to distraction by a second pain.

Influence of MTHFR genotype on contingent negative variation and MRI abnormalities in migraine.

BACKGROUND: The MTHFR C677T genotype has been associated with increased risk of migraine, particularly of migraine with aura (MA) in selected clinical samples and with elevated homocysteine. The hyper-homocysteinemia may favor the vascular and neuronal mechanism underlying migraine, and the risk of stroke. OBJECTIVE: The first aim of the present study was to examine the Contingent Negative Variation (CNV) amplitude and habituation pattern in a migraine sample versus non-migraine subjects, at the light of the MTHFR genotype, according to an unrelated and clinical based case-control panel. The second aim was to compare the frequency of Magnetic Resonance Imaging (MRI) subclinical brain lesions across the different C677 genotypes in the same migraine sample, selected for the young age and the absence of any cardiovascular risk factor. METHODS: One hundred and five 18-45 year old out-patients, 90 affected by migraine without aura (MO) and 15 by MA, and 97 non-migraine healthy subjects, age and sex matched, were selected for the genetic analysis. All subjects had a common ethnic origin from Puglia. Sixty-four migraine subjects and 33 control subjects were submitted to the recording of the CNV. All migraine subjects underwent the MRI evaluation. RESULTS: The frequency of homozygosis was 14.33% in normal subjects, versus 25.7% in MA + MO group (chi2-test: 10.80 P= .001). The frequency of homozygosis in MO patients, was 25.5% (MA versus N: chi2-test: 9 P= .003), in MA group it was 26.6%. Considering the MTHFR genotype in migraine patients and controls, the C677TT subjects exhibited a reduced habituation index of the early CNV (iCNV), in respect with both C677TC and C677CC; in the migraine group, there was a significant decrease of CNV habituation in patients with homozygosis and a positive correlation between the habituation index values and the homocysteine levels. Nineteen migraine patients exhibited subclinical brain lesions (18.05%): patients with C677T homozygosis did not exhibit a higher risk for MRI abnormalities. CONCLUSIONS: This unrelated and clinical based case-control study showed that genetically induced hyper-homocysteinemia may favor the neuronal factors predisposing to migraine, while it does not influence the presence of subclinical vascular brain lesions probably linked with increased risk of stroke.