Quantification and prospective evaluation of serum NfL and GFAP as blood-derived biomarkers of outcome in acute ischemic stroke patients.

Identification of reliable and accessible biomarkers to characterize ischemic stroke patients' prognosis remains a clinical challenge. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are markers of brain injury, detectable in blood by high-sensitive technologies. Our aim was to measure serum NfL and GFAP after stroke, and to evaluate their correlation with functional outcome and the scores in rehabilitation scales at 3-month follow-up. Stroke patients were prospectively enrolled in a longitudinal observational study within 24 hours from symptom onset (D1) and monitored after 7 (D7), 30 ± 3 (M1) and 90 ± 5 (M3) days. At each time-point serum NfL and GFAP levels were measured by Single Molecule Array and correlated with National Institute of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), Trunk Control Test (TCT), Functional Ambulation Classification (FAC) and Functional Independence Measure (FIM) scores. Serum NfL and GFAP showed different temporal profiles: NfL increased after stroke with a peak value at D7; GFAP showed an earlier peak at D1. NfL and GFAP concentrations correlated with clinical/rehabilitation outcomes both longitudinally and prospectively. Multivariate analysis revealed that NfL-D7 and GFAP-D1 were independent predictors of 3-month NIHSS, TCT, FAC and FIM scores, with NfL being the biomarker with the best predictive performance.

Milestones and Timescale of Poststroke Recovery: A Cohort Study.

BACKGROUND: Progressive increase of an aging population in Western countries will result in a growth of stroke prevalence. As many stroke survivors chronically show severe disability, increase in economic, social, and medical burden could be expected in the future. Objective and subjective measures of poststroke recovery are necessary to obtain predictive information, to improve the treatments, and to better allocate resources. AIM: To explore a measure of the temporal dimension of poststroke recovery, to search for predictive association with multiple clinical variables, and to improve tailoring of poststroke treatments. METHOD: In this observational monocentric cohort study, 176 poststroke inpatients at their first cerebrovascular event were consecutively enrolled. A novel measure based on the time needed to reach the main milestones of motor recovery was proposed. Moreover, two commonly used outcome measures, a measure of global functioning (Functional Independence Measure (FIM™)) and a measure of neurological poststroke deficit (Fugl-Meyer scale), were collected for the investigations of possible predictors. RESULTS: The patients showed a substantial increase in Fugl-Meyer and FIM scores during the rehabilitative treatment. The acquisition of three milestones was significantly associated with female sex (autonomous standing), length of stay and Fugl-Meyer initial score (autonomous walking), and Fugl-Meyer initial score (functional arm). These findings provided quantitative data on motor milestone reacquisition in a sample of poststroke patients. It also demonstrated the value of the Fugl-Meyer score in predicting the acquisition of two motor milestones, relevant for daily life activities. CONCLUSION: Systematic recording of the timescale of poststroke recovery showed that motor milestone reacquisition happens, on average and when attainable, in less than 30 days in our sample of patients. The present study underscores the importance of the Fugl-Meyer score as a possible predictor for better improvement in reacquisition times of milestone functional recovery.

Effect of overuse of the antimigraine combination of indomethacin, prochlorperazine and caffeine (IPC) on the disposition of its components in chronic headache patients.

BACKGROUND: The combination of indomethacin, prochlorperazine and caffeine (IPC) is one of the most utilized formulations for the treatment of migraine attacks in Italy. Several patients suffering from chronic headache overuse this symptomatic medication in the attempt to control their headache. OBJECTIVE: To verify whether overuse of IPC combination by chronic headache patients is associated with modified disposition of its components. METHODS: We studied indomethacin, prochlorperazine, and caffeine disposition in 34 female subjects suffering from primary headaches, subdivided into four groups: eight migraine patients occasionally using IPC combination suppositories-group 1; nine patients with chronic headache and probable medication-overuse headache, daily taking one or more suppositories of the IPC combination-group 2; 11 migraine patients occasionally using "mild" suppositories of the IPC combination-group 3; six migraine patients occasionally taking tablets of the IPC combination-group 4. The IPC combination habitually used was administered to each patient. Blood samples were taken at baseline and at fixed intervals up to 6h after administration. Plasma levels of indomethacin and prochlorperazine were assayed by high-pressure liquid chromatographic (HPLC) method; caffeine levels were assayed by enzyme multiplied immunoassay test (EMIT). Pharmacokinetic parameters were calculated by means of a computer software (P K Solutions 2.0. Summit Research Services, Montrose, CO, USA). RESULTS: Half-life of indomethacin was longer, and clearance lower, in group 2 than in the other groups; AUC of indomethacin in group 2 was twice that in group 1 (P<0.05, Newman-Keuls' test). Peak concentrations and AUC(0-->infinity) of caffeine were significantly higher in group 2 than in the other groups (P<0.05, Newman-Keuls' test). We could not define prochlorperazine disposition because it was not detectable in the majority of blood samples. CONCLUSION: Overuse of IPC combination in chronic headache patients is associated with increased plasma levels of indomethacin and caffeine, and with delayed elimination of indomethacin; the high and sustained concentrations of these drugs may cause rebound headache, organ damages, and perpetuate medication-overuse headache.

A CARE: pathway in medication-overuse headache: the experience of the Headache Centre in Pavia.

Medication-overuse headache (MOH) is one of the headache forms that most frequently prompts patients to consult a specialist headache centre. The prevalence of this form in the general population is approximately 1-2%. Around 40% of patients seen at headache centres present with a chronic form of headache and 80% of this chronic headache patients make excessive use of symptomatic drugs. MOH shows a clinical improvement, accompanied by a reduction in the consumption of analgesic drugs, if patients are submitted to detoxification therapy. But detoxification is only the first stage in a long and complex course of care and global approach demands adequate follow-up visit to prevent early relapses. At the Headache Centre of the C. Mondino Institute of Neurology in Pavia, a course of care (CARE: ) has been developed for the complete management of patients with MOH both during Hospitalization and during the subsequent follow-up period. CARE: IS designed to trace the clinical, psychopathological and pharmacological profile of MOH in the short-, medium- and long-term; to look for factors possibility predictive of relapse; to assess the direct costs linked to overuse-headache in the year leading up to and following detoxification; and to evaluate disability, in terms of working days lost, before and after detoxification.

Report of eight new cases of hypnic headache and mini-review of the literature.

Hypnic headache is a rare condition first described by Raskin in 1988. This headache is not included in the first edition of the International Headache Society classification (IHC 1st Edition). We describe eight new Italian hypnic headache cases and consider our findings in the light of literature data. Our cases do not completely fulfil the diagnostic criteria for the syndrome proposed in 1997 by Goadsby and Lipton: four of our patients reported an attack duration longer than 60 minutes (ranging from 3 to 10 hours) and five reported unilateral pain. These data are in line with an analysis of all 61 cases published in the literature to date, which reveals a pain duration of over 60 minutes in 45.9% of the cases and unilateral attacks in 36%. Hypnic headache will be included in the fourth chapter (Other Primary Headaches) of the revised edition of the above-mentioned classification (IHC 2nd Edition).