Bringing door-to-needle times within the European benchmarks results in better stroke patients outcomes in a spoke hospital from the Apulian Region.

INTRODUCTION: Door-to-needle time (DNT) is a key factor in acute stroke treatment success. We retrospectively analysed the effects of a new protocol aimed at reducing treatment delays in our single-centre observational series over a 1-year period (from October 1st 2021 to September 30th 2022). METHODS: The time frame was divided into two semesters as a new protocol was started at the beginning of the second semester to ensure a rapid evaluation, imaging, and intravenous thrombolysis in all stroke patients attending our spoke-hospital serving 200,000 inhabitants. Logistics and outcome measures were obtained for each patient and compared before and after implementation of the new protocol. RESULTS: A total of 215 patients with ischemic stroke attended our hospital within a 1-year period (109 in the first semester, 96 in the second semester). Seventeen percent and 21% of all patients underwent acute stroke thrombolysis in the first and second semesters, respectively. DNTs were strongly reduced in the second semester (from 90 to 55 min), bringing this value below the Italian and European benchmarks. This resulted in better short-term outcomes (an average of 20%) as measured by both Δ NIHSS scores at 24 h and at discharge with respect to baseline.

Lemierre's syndrome complicated by cerebral venous sinus thrombosis: A life threatening and rare disease successfully treated with empiric antimicrobial therapy and conservative approach.

Lemierre's syndrome (LS) is a "forgotten" condition characterized by septic thrombophlebitis of the jugular vein that follows an otolaryngological infection. Fusobacterium necrophorum is the aetiological agent responsible for the syndrome in adolescents and young adults whereas in older people even common bacteria are involved. Complications arise from spreading of septic emboli distally, i.e. to the brain, lungs, bones and internal organs everywhere in the body. We report a middle-aged woman who presented with headache and bilateral sixth cranial nerve palsy following a sphenoidal sinusitis and left mastoiditis. Imaging revealed thrombotic involvement of the left internal jugular vein as well as of several cerebral venous sinuses thrombosis (CVT). Currently, precise management protocols of LS with CVT complication do not exist although a combination of macrolides and second or third-generation cephalosporins, as well as anti-coagulants represent the mainstream of therapeutics. Surgical drainage is associated to remove septic foci but is burdened by severe complications and side effects. Complete recovery was achieved following pharmacological treatment in our patient. This report adds further evidence that LS complicated by CVT may be effectively treated adopting a conservative approach thus avoiding surgical drainage and severe complications.

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.

A case of unilateral burning mouth syndrome of neuropathic origin.

The neuropathic origin of a case of unilateral burning mouth syndrome, previously diagnosed as psychogenic, was ascertained by intra-oral mucosa biopsy, which showed a severe sensory fibers damage, probably caused by maxillary anesthetic block and dental surgery.

A case of early-onset and monophasic trigeminal autonomic cephalalgia: could it be a SUNCT?

A 2-year-old female came to the Neurological Emergency Room of "Giovanni XXIII" Hospital in Bari, 6 h after the onset of severe facial pain, which occurred soon after awakening. Stabbing pain affected the right frontal and periorbital area, with ipsilateral conjunctival injection, swelling of the eyelids and tearing. Except the duration, from 5 to 30 s., the attacks were stereotyped including the occurrence and features of autonomic signs. Based on the typical clinical findings and the normal magnetic resonance imaging (MRI), we diagnosed short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing syndrome (SUNCT). The spontaneous remission within a few hours made prophylactic therapy unnecessary. At the last follow-up, after 3 months, the patient was still symptom free. In our case, after an active period lasting 2 days the disease disappeared completely. However the typical features of the disease (unilateral pain, short duration and high frequency of the attacks, autonomic signs ipsilateral to pain, numbers of attacks) were all present. While the diagnostic criteria of the International Headache Society classification for SUNCT did not include the duration of disease, it is likely that the active period lasting 2 days could be an expression of the clinical variability of the disease.

Laser evoked potentials in amyotrophic lateral sclerosis.

The pathophysiological mechanism of the pain in ALS is still unclear. The aim of the study was to evaluate the laser evoked potentials (LEPs) in ALS patients in relation to their clinical features. Twenty-four ALS patients were selected. Pain features were assessed and their intensity was measured by a 0-10 VAS. LEPs were recorded in all patients and in 23 healthy subjects. The dorsum of both hands was stimulated, at laser stimuli intensity of 7.5 W, with 10s inter-stimulus interval and 25 ms duration. Four electrodes were placed at Cz, T3, T4 and Fz positions, with the reference electrode at the nasion; T3 and T4 electrodes were referred off-line to Fz, in order to detect the N1 component. Latencies of N2, P2 and N1 waves were significantly higher in ALS than in controls. N1 amplitude was significantly increased in ALS patients compared to controls, with a similar trend for the N2-P2 complex. No correlation was found between LEP abnormalities, pain intensity and clinical features. A degeneration of subcortical structures may subtend a delay in the afferent input to the nociceptive cortex in ALS. On the other hand, an increase of pain processing at the cortical level may derive from a potential sensory compensation to motor cortex dysfunction.

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.

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.

Electrophysiological study in 2 children with transient hypohidrosis induced by topiramate.

OBJECTIVE: Hypohidrosis, often associated with hyperthermia, has been reported, mostly in children, as a rare and reversible adverse effect of topiramate, an anticonvulsant drug with a broad spectrum of antiepileptic activity. The aim of our study is to detect a possible skin innervation involvement as the mechanism underlying hypohidrosis in children treated with topiramate. METHODS: A neurophysiological study has been performed on 2 children who have developed hypohidrosis under topiramate treatment. Electrophysiological data have been recorded during topiramate treatment and compared with a control group. Sympathetic skin responses have been recorded during topiramate assumption and after its discontinuation. RESULTS: In our 2 cases with hypohidrosis related to topiramate, electrophysiological study showed normal function of both beta and delta sensory fibers and absent sympathetic skin responses that recovered to normal after topiramate discontinuation. CONCLUSIONS: Our findings confirm that topiramate might induce a transitory specific carbonic anhydrase block at the level of sweat glands, without involvement of peripheral nervous system.

Aesthetic value of paintings affects pain thresholds.

Pain is modulated by cognitive factors, including attention and emotions. In this study we evaluated the distractive effect of aesthetic appreciation on subjectively rated pain (visual analogue scale;VAS) and multi-channel evoked potentials induced by CO(2) laser stimulation of the left hand in twelve healthy volunteers. Subjects were stimulated by laser in the absence of other external stimulation (baseline condition) and while looking at different paintings they had previously rated as beautiful, neutral or ugly. The view of paintings previously appreciated as beautiful produced lower pain scores and a clear inhibition of the P2 wave amplitude, localized in the anterior cingulate cortex; the inhibition of P2 wave amplitude was lesser or not significant during the presentation of the ugly or neutral paintings, respectively. Dipole source localization analysis of the LEP peaks showed significant changes during different conditions, with a shift from the posterior to the anterior right cingulated cortex while looking at paintings previously rated as beautiful. Our results provide evidence that pain may be modulated at cortical level by the aesthetic content of the distracting stimuli.

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.

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.

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 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.

Intra-oral orthosis vs amitriptyline in chronic tension-type headache: a clinical and laser evoked potentials study.

BACKGROUND: In the present study, we examined clinical and laser-evoked potentials (LEP) features in two groups of chronic tension-type headache (CTTH) patients treated with two different approaches: intra-oral appliance of prosthesis, aiming to reduce muscular tenderness, and 10 mg daily amitriptyline. METHODS: Eighteen patients with diagnosed CTTH participated in this open label, controlled study. A baseline evaluation was performed for clinical features, Total Tenderness Score (TTS) and a topographic analysis of LEPs obtained manually and the pericranial points stimulation in all patients vs. healthy subjects. Thereafter, patients were randomly assigned to a two-month treatment by either amitriptyline or intra-oral appliance. RESULTS AND DISCUSSION: Both the intra-oral appliance and amitriptyline significantly reduced headache frequency. The TTS was significantly reduced in the group treated with the appliance. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment.Both therapies were effective in reducing headache severity, the appliance with a prevalent action on the pericranial muscular tenderness, amitriptyline reducing the activity of the central cortical structures subtending pain elaboration CONCLUSION: The results of this study may suggest that in CTTH both the interventions at the peripheral and central levels improve the outcome of headache.

Topographic analysis of laser evoked potentials in chronic tension-type headache: correlations with clinical features.

In the present study, we examined clinical and laser-evoked potentials (LEP) features in a group of chronic tension-type headache (CTTH) patients, in order to perform a topographic analysis of Laser evoked potentials (LEPs) and a correlation with clinical features. Eighteen patients suffering from CTTH [Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders 2nd ed. Cephalalgia 2004; 24 Suppl 1, 1-159.] participated in the study. Twelve age- and sex-matched controls were also examined. We performed a basal evaluation of clinical features, Total Tenderness Score (TTS) and a topographic analysis of LEPs obtained by the hand and the pericranial points stimulation in all patients vs healthy subjects. The later LEPs, especially the P2 component, were significantly increased in amplitude in the CTTH group, specially when the pericranial points were stimulated. The P2 wave amplitude was correlated with TTS levels and anxiety scores. The results of this study confirm that pericranial tenderness is a phenomenon initiating a self-sustaining circuit, involving central sensitization at the level of the cortical nociceptive areas devoted to attentional and emotional components of pain.

Capsaicin failed in suppressing cortical processing of CO2 laser pain in migraine patients.

The aim of this study was to compare the properties of the nociceptive system in eight migraine without aura patients in the pain-free phase with 10 healthy controls, by evaluating the topography and the source of the CO2 laser-evoked potentials (LEPs) obtained by the right supraorbital skin, during and after capsaicin topical application. In healthy subjects the acute cutaneous pain induced by capsaicin reduced the amplitude of the vertex LEPs and induced a posterior shifting of the P2 wave dipolar source within the anterior cingulate cortex. These functional changes seemed significantly reduced in migraine patients, for a disturbed pattern of pain modulation at the cortical level, which may subtend the onset and persistence of migraine.

Lack of habituation of nociceptive evoked responses and pain sensitivity during migraine attack.

OBJECTIVE: The aim of the present study was to investigate the habituation of subjective pain sensation to CO(2) laser stimulus, in relation to the amplitude modifications of the cortical evoked responses (LEPs), during both the migraine attack and the not symptomatic phase. METHODS: Fourteen migraine patients were selected and compared with 10 healthy controls. Eight patients were evaluated during both the pain-free and the attack phases. Three following series of 20 averaged LEPs were recorded, stimulating the hands and the supraorbital zones: during the attack, two consecutive series of 20 averaged LEPs were carried out. The subjective sensation was requested for each laser stimulus, using a 0-10 points Verbal Rating Scale (VRS). RESULTS: In normal subjects the N2-P2 waves amplitude showed habituation across the three repetitions, which correlated with the habituation of the subjective rating of the stimulus. During the not symptomatic phase, patients showed a lack of habituation of the N2-P2 amplitude when the hand and the face was stimulated, with a pattern of increase of the pain rating across the three repetitions; in addition there was a lack of correlation between the LEPs amplitude and the subjective sensation. During the attack, the LEPs amplitude and the pain rating were increased when the face was stimulated, but they did not habituate across the two repetitions, likely the pain-free condition. The percent LEPs amplitude variation across the three repetitions correlated with the main indices of migraine severity, mainly when the supraorbital zone was stimulated. CONCLUSIONS: The abnormal cortical excitability in migraine could condition an anomalous behavior of nociceptive cortex during the interictal phase of migraine: it persists during the acute phase, and correlates with the frequency and duration of migraine. SIGNIFICANCE: The reduced habituation of the nociceptive cortex may concur with the onset and evolution of headache.

Nitroglycerin induces migraine headache and central sensitization phenomena in patients with migraine without aura: a study of laser evoked potentials.

In migraineurs nitroglycerin (NTG) induces severe delayed headache, resembling spontaneous migraine attacks. The aim of the present study was to evaluate NTG laser evoked potentials (LEP) features amplitude and pain sensation to laser stimuli during NTG-induced headache. Nine patients were selected. Headache was induced by oral administration of 0.6 mg of NTG; signals were recorded through disk electrodes placed at the vertex and referred to linked earlobes. CO(2)-LEPs delivered by stimulation of the dorsum of both hands and the right and left supraorbital zones were evaluated after the onset of moderate or severe headache resembling spontaneous migraine and at least 72 h after the end of the headache phase. Patients exhibited a significant heat pain threshold reduction and an LEPs amplitude increment during headache when both the supraorbital zones were stimulated. NTG appeared to support a reliable experimental model of migraine, based on the neuronal effects on the integrative-nociceptive structures. The LEPs facilitation during NTG-induced headache may be subtended by a hyperactivity of nociceptive cortex as well as by a failure of pain-inhibitory control.