Treatment of withdrawal headache in patients with medication overuse headache: a pilot study.

BACKGROUND: Drug withdrawal still remains the key element in the treatment of Medication Overuse Headache (MOH), but there is no consensus about the withdrawal procedure. Still debated is the role of the steroid therapy. The aim of this study was to evaluate the effectiveness of methylprednisolone or paracetamol in the treatment of withdrawal headache in MOH. METHODS: We performed a pilot, randomized, single-blinded, placebo controlled trial. MOH patients, unresponsive to a 3 months prophylaxis, underwent withdrawal therapy on an inpatient basis. Overused medications were abruptly stopped and methylprednisolone 500 mg i.v (A) or paracetamol 4 g i.v. (B) or placebo i.v. (C) were given daily for 5 days. Patients were monitored at 1 and 3 months. RESULTS: Eighty three consecutive MOH patients were enrolled. Fifty seven patients completed the study protocol. Nineteen patients were randomized to each group. Withdrawal headache on the 5th day was absent in 21.0% of group A, in 31.6% of group B and in 12.5% of group C without significant differences. Withdrawal headache intensity decreased significantly after withdrawal without differences among the groups. Rregardless of withdrawal treatment, 52% MOH patients reverted to an episodic migraine and 62% had no more medication overuse after 3 months. CONCLUSIONS: This study suggests that in a population of severe MOH patients, withdrawal headache decreased significantly in the first 5 days of withdrawal regardless of the treatment used. Methylprednisolone and paracetamol are not superior to placebo at the end of the detoxification program.

Biofeedback in the prophylactic treatment of medication overuse headache: a pilot randomized controlled trial.

BACKGROUND: Medication overuse headache (MOH) is a major clinical concern and a common health risk. Recent literature stressed the need to manage chronic headache by using integrated biobehavioral approaches. Few studies evaluated how biofeedback can be useful in MOH. The aim of the study is to evaluate in a randomized, controlled, single-blind trial the effects of biofeedback associated with traditional pharmacological therapy in the prophylactic treatment of MOH. METHOD: Twenty-seven subjects were randomized to frontal electromyographic (EMG) biofeedback associated with prophylactic pharmacological therapy (Bfb Group) or to pharmacological treatment alone (Control Group). The primary outcome was to evaluate the number of patients that return episodic after treatment. Secondly we evaluate the effects of frontal EMG BFB on frequency of headache and analgesic intake. Changes in coping strategies and in EMG frontalis tension were also evaluated. ANOVA was performed on all the variables of interest. RESULTS: Our results indicate that at the end of treatment the number of patients that returned episodic in the Bfb group was significantly higher than in the Control group. Patients in the Bfb group differed from the Control group in headache frequency, amount of drug intake and active coping with pain. These outcomes were confirmed also after 4 months of follow-up. No significant effects were observed in EMG recordings. CONCLUSIONS: Biofeedback added to traditional pharmacological therapy in the treatment of MOH is a promising approach for reducing headache frequency and analgesic intake. Modification of coping cognitions in the Bfb group, as an adjunct mechanism of self-regulation, needs more evaluations to understand the role of biofeedback in changing maladaptive psychophysiological responses.

Nocturnal melatonin regulation in post-traumatic vegetative state: a possible role for melatonin supplementation?

Circadian rhythms were recently proposed as a measure of physiological state and prognosis in disorders of consciousness (DOC). So far, melatonin regulation was never assessed in vegetative state (VS). Aim of our research was to investigate the nocturnal melatonin levels and light-induced melatonin suppression in a cohort of VS patients. We assessed six consecutive patients (four men, age 33.3 ± 9.3 years) with post-traumatic VS and nine age-matched healthy volunteers (five men, age 34.3 ± 8.9 years) on two consecutive nights: one baseline and one light exposure night. During baseline, night subjects were in bed in a dim (<5 lux) room from 10 pm to 8 am. Blood samples were collected hourly 00:30-3:30 am (00:30 = MLT1; 1:30 = MLT2; 2:30 = MLT3; and 3:30 = MLT4). Identical setting was used for melatonin suppression test night, except for the exposure to monochromatic (470 nm) light from 1:30 to 3:30 am. Plasma melatonin levels were evaluated by radioimmunoassay. Magnitude of melatonin suppression was assessed by melatonin suppression score (caMSS) and suppression rate. We searched for group differences in melatonin levels, differences between repeated samples melatonin concentrations during baseline night and light exposure night, and light-induced suppression of melatonin secretion. During baseline night, controls showed an increase of melatonin (MLT4 vs MLT1, p = 0.037), while no significant changes were observed in VS melatonin levels (p = 0.172). Baseline night MLT4 was significantly lower in VS vs controls (p = 0.036). During light-exposure night, controls displayed a significant suppression of melatonin (MLT3 and MLT4 vs MLT2, p = 0.016 and 0.002, respectively), while VS patients displayed no significant changes. The magnitude of light-induced suppression of melatonin levels was statistically different between groups considering control adjusted caMSS (p = 0.000), suppression rate (p = 0.002) and absolute percentage difference (p = 0.012). These results demonstrate for the first time that VS patients present an alteration in night melatonin secretion and reduced light-induced melatonin suppression. These findings confirm previous studies demonstrating a disruption of the circadian system in DOC and suggest a possible benefit from melatonin supplementation in VS.

Personality traits in chronic daily headache patients with and without psychiatric comorbidity: an observational study in a tertiary care headache center.

BACKGROUND: Previous studies suggest that patients with Chronic Daily Headache (CDH) have higher levels of anxiety and depressive disorders than patients with episodic migraine or tension-type headache. However, no study has considered the presence of psychiatric comorbidity in the analysis of personality traits. The aim of this study is to investigate the prevalence of psychiatric comorbidity and specific personality traits in CDH patients, exploring if specific personality traits are associated to headache itself or to the psychiatric comorbidity associated with headache. METHODS: An observational, cross-sectional study. Ninety-four CDH patients with and without medication overuse were included in the study and assessed by clinical psychiatric interview and Mini International Neuropsychiatric Interview (M.I.N.I.) as diagnostic tools. Minnesota Multiphasic Personality Inventory-2 (MMPI-2), Hamilton Depression Rating Scale (HAM-D) were afterwards administered. Patients with and without psychiatric comorbidity were compared. Further analyses were made by splitting the whole group according to the headache diagnosis and the presence or not of medication overuse. RESULTS: Psychiatric comorbidity was detected in 44 patients (46.8%) (group A) and was absent in the remaining 50 patients (53.2%) (group B). Mood and anxiety disorders were the most frequently diagnosed (43.6%).In the overall group, mean scores of MMPI-2 showed a high level in the so-called neurotic triad; in particular the mean score in the Hypochondriasis subscale was in the pathologic area (73.55 ± 13.59), while Depression and Hysteria scores were moderate but not severe (62.53 and 61.61, respectively). In content scales, score in Health Concern was also high (66.73).Group A presented higher scores compared to Group B in the following MMPI-2 subscales: Hypochondriasis (p= .036), Depression (p= .032), Hysteria (p< .0001), Hypomania (p= .030). Group B had a high score only in the Hypochondriasis subscale. No significant differences were found between chronic migraine (CM)-probable CM (pCM) plus probable medication overuse headache (pMOH) and chronic tension-type headache (CTTH)-probable CTTH (pCTTH) plus pMOH patients or between patients with and without drug overuse. CONCLUSIONS: The so-called "Neurotic Profile" reached clinical level only in CDH patients with psychiatric comorbidity while a high concern about their general health status was a common feature in all CDH patients.

Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies.

Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. The mammalian eye contains a light detection system based on a subset of retinal ganglion cells containing the photopigment melanopsin. These cells give origin to the retinohypothalamic tract and support the non-image-forming visual functions of the eye, which include the photoentrainment of circadian rhythms, light-induced suppression of melatonin secretion and pupillary light reflex. We studied the integrity of the retinohypothalamic tract in five patients with Leber hereditary optic neuropathy, in four with dominant optic atrophy and in nine controls by testing the light-induced suppression of nocturnal melatonin secretion. This response was maintained in optic neuropathy subjects as in controls, indicating that the retinohypothalamic tract is sufficiently preserved to drive light information detected by melanopsin retinal ganglion cells. We then investigated the histology of post-mortem eyes from two patients with Leber hereditary optic neuropathy and one case with dominant optic atrophy, compared with three age-matched controls. On these retinas, melanopsin retinal ganglion cells were characterized by immunohistochemistry and their number and distribution evaluated by a new protocol. In control retinas, we show that melanopsin retinal ganglion cells are lost with age and are more represented in the parafoveal region. In patients, we demonstrate a relative sparing of these cells compared with the massive loss of total retinal ganglion cells, even in the most affected areas of the retina. Our results demonstrate that melanopsin retinal ganglion cells resist neurodegeneration due to mitochondrial dysfunction and maintain non-image-forming functions of the eye in these visually impaired patients. We also show that in normal human retinas, these cells are more concentrated around the fovea and are lost with ageing. The current results provide a plausible explanation for the preservation of pupillary light reaction despite profound visual loss in patients with mitochondrial optic neuropathy, revealing the robustness of melanopsin retinal ganglion cells to a metabolic insult and opening the question of mechanisms that might protect these cells.

Increased prevalence of sleep disorders in chronic headache: a case-control study.

OBJECTIVES: The aim of our study was to investigate the prevalence of sleep disorders in chronic headache patients and to evaluate the role of psychiatric comorbidity in the association between chronic headache and sleep complaints. BACKGROUND: The prevalence of sleep disorders in chronic headache has been seldom investigated, although from the earliest description chronic headache has been associated with sleep disturbances. On the contrary, mood disorders are commonly associated with both sleep disturbances and chronic headache--each of which are, in turn, core features of mood disorders. Therefore, it may be important to discriminate between sleep problems that can be attributed to a comorbid psychiatric disorder, and those specifically associated with headache. Only a few studies investigating the association of chronic headache with sleep difficulties have also taken into account to consider the possible role of anxiety and depression. PATIENTS AND METHODS: A total of 105 consecutive patients with daily or nearly daily headache and 102 patients with episodic headache, matched by age, sex, and type of headache at onset, underwent a structured direct interview about their sleep habits and psychiatric diseases. RESULTS: In total, 80 out of 105 patients with chronic headache received a diagnosis of medication overuse headache, 21 patients were classified as chronic migraine and 4 as chronic tension-type headache without drug overuse. PATIENTS: Patients with chronic headache showed a high prevalence of insomnia, daytime sleepiness, and snoring with respect to controls (67.7% vs 39.2%, 36.2% vs 23.5%, and 48.6% vs 37.2%, respectively). Forty-five patients with chronic headache (42.9%) had psychiatric comorbidity (anxiety and/or depressive disorders), vs 27 episodic headache patients (26.5%). Multivariate analysis disclosed that low educational level, lower mean age at headache onset, and insomnia are independently associated with chronic headache. CONCLUSIONS: Patients with chronic headache had a high prevalence of sleep complaints. Insomnia may thus represent an independent risk factor for headache chronification. Recognition of sleep disorders, alone or in association with depression or anxiety, may be useful in episodic headache patients to prevent chronification.

Self-help group and medication overuse headache: preliminary data.

The objective of the study is to investigate the benefits of joining a self-help group for patients with medication overuse headache (MOH). A self-help group is a voluntary gathering of a small number of persons who share a common problem. Little is known about support groups for people with chronic non-malignant pain such as MOH. Eight patients with refractory MOH attended a self-help group twice a month. During the meetings, patients were asked to focus on their headache experiences. Our data showed an increase in resourcefulness in coping with pain and a reduction in cephalalgiophobia. All patients reported general benefits in sharing their headache-related problems. No differences were found for headache frequency or analgesic overuse. To our knowledge, this is the first report on a self-help group for patients with MOH. Joining a self-help group can help patients develop positive attitudes to managing pain.

Family history for chronic headache and drug overuse as a risk factor for headache chronification.

OBJECTIVES: To assess whether family history for chronic headache (CH) and drug overuse could represent a risk factor for headache chronification. BACKGROUND: Among factors investigated as risk factors for chronification of headache disorders, familial liability for CH and drug overuse has been rarely investigated. PATIENTS AND METHODS: A total of 105 consecutive patients with daily or nearly daily headache, and 102 consecutive patients with episodic headache matched by age, sex, and type of headache at onset, underwent a structured direct interview about family history for episodic headache, CH with and without medication overuse, substance abuse/dependence, and psychiatric disorders. RESULTS: In total, 80 out of 105 patients with CH received a diagnosis of medication overuse headache (MOH), 21 patients were classified as chronic migraine (CM), and 4 as chronic tension-type headache (CTTH) without drug overuse. Some 38.1% of CH patients reported family history for CH vs only 13.7% of episodic headaches (P = .001). Familiality for CH with medication overuse was reported by 25.7% of cases vs 9.8% of controls (P = .0028). A familial history of substance abuse was reported by 20% of patients vs 5.9% of controls (P = .0026). In all, 28.7% of MOH patients reported family history for CH with medication overuse (P = .0014) and 21.2% for substance abuse (P = .002). Relatives of patients with MOH were more likely than control relatives to suffer from CH (OR = 4.19 [95% CI 2.05-8.53]), drug overuse (OR = 3.7 [95% CI 1.66-8.24]), and substance abuse (OR = 4.3 [95% CI 1.65-11.19]). No differences regarding family history for episodic headache and for psychiatric disorders were found. No differences in family history for CH with drugs overuse and for substance abuse were found between CH patients without overuse and controls. Fifteen CH patients reported family history for alcohol abuse (P = .0003). CONCLUSIONS: The significantly increased familial risk for CH, drug overuse, and substance abuse suggests that a genetic factor is involved in the process of headache chronification.

Late recovery from post-traumatic vegetative state.

AIM: Late recovery of consciousness after 12 months in vegetative state is very rare and is almost invariably associated with severe disability. The aim of this study was to report that late recovery with moderate disability is possible, even after several months in vegetative state. CASE REPORT: This study describes the case of a 22-year-old male student who recovered consciousness from vegetative state 19 months after a traumatic brain injury which had occurred in December 2000. A further slow recovery of motor and cognitive functions up to a moderate disability was observed over 7 years after the brain injury. The patient now lives in the community, speaks, walks and undertakes daily living as well as outdoor leisure activities independently, has resumed his previous university studies and has a part-time non-competitive job. CONCLUSIONS: This case demonstrates that attaining a condition of independent living is possible even after more than 1 year of post-traumatic vegetative state, with an improvement of motor and cognitive functions that can continue for years. Cranioplasty and long-term rehabilitation programmes may be among the variables potentially influencing this unexpected recovery.

Quality of life, eating and mood disorders in menstrual migraine: a case-control study.

The aim of this study was to evaluate the prevalence of mood and eating disorders in patients with menstrual migraine. Quality of life and disability were also assessed. The study confirmed the presence of significant disability and poor quality of life due to migraine even in a selected subgroup of patients affected with menstrual migraine. In contrast with the previous literature we did not find any difference in the prevalence of mood and eating disorders.

Reliability of a driving simulation task for evaluation of sleepiness.

Driving Simulators reproduce situations that require tracking and visual searching, the main features of real driving. This study measured the reliability of a monotonous driving scenario to detect the circadian variations of alertness in healthy subjects. Five men and five women underwent a monotonous 30 min driving simulation task every 2 h. Before each driving task subjects completed the Stanford Sleepiness Scale (SSS) and the Visual Analogue Scale (VAS) to correlate the subjective measurements of sleepiness to the objective data of the simulator. Driving performances deteriorated or improved according to the circadian variation of alertness. The scenario is suitable to detect the consequences of sleepiness related to the circadian variations of alertness. The standard deviation of lane position, comparing the differences among the 10 min blocks in each task is the parameter most significant for the evaluation of sleepiness.