Levetiracetam in the prophylactic treatment of episodic migraine: A prospective open label study.

BACKGROUND: The prophylactic treatment of migraine includes anticonvulsant drugs such as valproic acid and topiramate. However, these substances are often poorly tolerated by migraine patients. So far levetiracetam has hardly been studied as an episodic migraine prophylactic agent in adults. OBJECTIVE: To perform a prospective pilot study for the evaluation of the efficacy and tolerability of levetiracetam in the prophylactic treatment of episodic migraine. METHODS: Fifty patients with episodic migraine were enrolled in this prospective, open label study. After a baseline period of four weeks, patients received 1,000 mg (starting dose 500 mg) bid levetiracetam for 12 weeks. Migraine frequency and accompanying symptoms were recorded in a headache diary. The primary endpoint was the comparison of attack frequency during the baseline with attack frequency during the last four weeks of treatment (treatment period 3). RESULTS: In the Intent-To-Treat analysis, 46% of the patients had a migraine reduction of more than 50% in the third period as compared to the baseline period. The mean number of migraine attacks decreased from 5.2 +/- 2.1 (baseline) to 3.4 +/- 2.7 (period 3). The most frequently reported side effects were somnolence, nausea, and weight gain; all were mild and transient. In a post-hoc comparison, responders to levetiracetam had significantly less migraine attacks at baseline and had significantly more often migraine with aura. CONCLUSION: The data suggest that levetiracetam has some potential in the prophylactic treatment of episodic migraine which seems, however, to be not superior to that of other anticonvulsant drugs. Levetiracetam was well tolerated and showed better efficacy in patients with migraine with aura and in less affected migraine patients. A larger placebo-controlled, double-blind study in adults seems justified on the basis of these data.

Botulinum Toxin A Treatment in HIV Infected Patients-A Long-Term Observational Study.

OBJECTIVE: It is unknown whether interactions between HIV infection and the safety of botulinum toxin A (BTX) exist. METHODS: We studied eight patients with HIV infection who were treated with BTX every three months for up to nine years. All patients were on antiretroviral treatment. The efficacy and safety of BTX were evaluated. RESULTS: Indications for BTX treatment (including off-label use), dosage of BTX, and frequency of application did not differ as compared to non-HIV infected patients. BTX treatment was effective in all HIV infected patients during a long-term observation period without loss of efficacy and without clinically relevant side effects. Only one of the eight patients showed mild side effects due to BTX, and no clinical signs of antibody development were noted. We also observed no signs of interaction with antiretroviral treatment. CD4+ cell count and viral load remained stable during the observation period. CONCLUSIONS: We conclude that BTX treatment is safe and effective in the treatment of HIV infected patients who suffer also from a condition which can be treated by BTX. It is a therapeutic option in addition to oral medication for HIV infected patients.

CGRP release in an experimental human trigeminal pain model.

BACKGROUND: Migraine and trigemino-autonomic cephalalgia attacks are associated with an increase of α-calcitonin-gene related peptide levels in the ipsilateral jugular vein. It is however unknown whether trigeminal pain stimulation in healthy subjects without headache disorders also induces increase of calcitonin-gene related peptide levels. FINDINGS: We measured α-calcitonin-gene related peptide levels in eight healthy subjects after subcutaneous injection of capsaicin in the forehead and in the mandibular region and after injection of sodium chloride in the forehead. We observed a significant increase of α-calcitonin-gene related peptide level only after injection of capsaicin in the forehead (i.e. first trigeminal branch). We also observed trigemino-autonomic activation (lacrimation, rhinorrhea etc.) only after injection of capsaicin in the forehead. CONCLUSION: Increase of α-calcitonin-gene related peptide levels do not only occur in primary headache attacks but also after experimental trigeminal pain of the first branch. This finding suggests that α-calcitonin-gene related peptide elevation is, at least an additional, unspecific effect of first trigeminal branch stimulation following pain activation and not a specific mechanism of idiopathic headache disorders.

Very young age of onset in trigemino-autonomic cephalalgias - case report and review of the literature.

BACKGROUND: Trigemino-autonomic cephalalgias are very rare disorders and even rarer in children and adolescents. We report the onset of paroxysmal hemicrania in a very young girl and reviewed the scientific literature for similar cases. FINDINGS: We describe the case of a 1.6-year-old girl with left-sided headache attacks fulfilling the criteria of paroxysmal hemicrania including prompt responsiveness to indomethacin. In addition, we detected at least two children for every trigemino-autonomic cephalalgias subtype with an age of under 7 years at the onset of the trigemino-autonomic cephalalgias. Remarkable features were a vast majority of chronic course from onset on and left-sided attacks. CONCLUSION: Although very rare, trigemino-autonomic cephalalgias can occur even in very young children under the age of 6 years. This should be known in neuropaediatrics.

Primary headache and migraine in headache specialists - does personal history of doctors matter?

OBJECTIVE: Migraine is a common disorder affecting more than 10% of the population. The prevalence of migraine among physicians and, in particular, among headache specialists is widely unknown as is the impact of suffering from migraine on the attitudes towards migraine and on treatment recommendations of physicians. We designed a survey among headache specialists and neurologists and compared the results to general pain specialists and general practitioners. METHODS: A standardized interview in randomly selected samples of these four groups of physicians was performed. The interview included data on the prevalence of migraine and other primary headache disorders in the physician groups, self-report on their own treatment, attitudes towards migraine, and treatment recommendations for migraine. The prevalence rates were also compared to an age- and sex-matched German general population sample. RESULTS: The lifetime prevalence of migraine was higher in headache specialists (53.0%) than in general neurologists (43.0%), pain specialists (21.7%), general practitioners (19.3%), and in the general age- and sex-matched population (16.8%). Cluster headache prevalence was high in neurologists (1.9%) and in headache specialists (1.3%); episodic tension-type headache prevalence was significantly lower in general practitioners (19.5%). One reason, among others, was that being a migraine (or cluster headache) patient more often prompted the sufferers to become a specialist in neurology. Physicians with migraine rated the biopsychosocial concept of lower importance for migraine than did physicians without migraine. The self-treatment of migraine in physicians differs from the treatment recommendations to the patients. For example, only 36.4% of the headache specialists with migraine take triptans whereas 94.4% recommend triptans to their patients. CONCLUSIONS: We conclude that being a headache specialist or a neurologist is associated with an increased migraine or cluster headache prevalence. This personal history of migraine leads to a more somatic view of migraine as a disorder and to different treatment recommendations as compared to self-treatment.

Evaluation of guideline-adherent treatment in cluster headache.

BACKGROUND: Several treatment guidelines exist for cluster headache. However, it is not yet known how many cluster headache patients are treated according to these guidelines. METHODS: We enrolled 434 cluster headache patients with confirmed diagnosis referred to two tertiary pain centers. The history of treatment was registered and analyzed according to the treatment guidelines of the European Federation of Neurological Societies. RESULTS: Regarding acute attack treatment, 62.1% of the episodic and 71.0% of the chronic cluster headache patients were treated according to the guidelines. The efficacy rate was above 92% in both groups. Regarding prophylactic treatment, 31.3% of the episodic and 50.9% of the chronic cluster headache patients were treated according to the guidelines. The efficacy rate was 92.8% for episodic and 70.9% for chronic cluster headache. CONCLUSION: The rate of guideline-adherent treatment in cluster headache is about 70% for acute treatment and about 35% for prophylactic treatment. The efficacy of this treatment is significantly higher than the efficacy of non-guideline-adherent treatment.

Musical ability is associated with enhanced auditory and visual cognitive processing.

BACKGROUND: Musical ability has always been linked to enhanced cognitive and intellectual skills. We were interested in the relation between musical ability and short-time cognitive processing as measured by event-related potentials, in particular in visual processing, since previous studies have already suggested such a link for acoustic cognitive processing. We measured auditory and visual event-related potentials as elicited by an oddball paradigm in 20 healthy subjects (10 musicians and 10 non-musicians; 10 female; mean age 24 ± 2 years). In addition, the Seashore test and a test developed by the authors to detect relevant amusia, the latter one with a high ceiling effect, were also applied. RESULTS: The most important finding was that there is a significant linear correlation between musical ability as measured by these tests and the P3 latencies of both the auditory and visual event-related potentials. Furthermore, musicians showed shorter latencies of the event-related potentials than non-musicians. CONCLUSIONS: We conclude that musical ability as measured by neuropsychological tests is associated with improved short-time cognitive processing both in the auditory and, surprisingly, also in the visual domain.

Sleep apnea in patients with cluster headache: a case-control study.

OBJECTIVE: Polysomnographic investigations have shown an unspecific association between cluster headache and obstructive sleep apnea syndrome. The aim of this study was to investigate this association in a cluster episode compared with a symptom free interval, and to further characterize this association. METHODS: We investigated 42 patients with episodic (n = 26) or chronic (n = 16) cluster headache by means of polygraphic screening for sleep apnea and compared the data to 28 healthy control subjects matched according to age, sex, and BMI. The patients with episodic cluster headache were screened twice, once in a cluster episode and once in a symptom free interval. RESULTS: Patients with active cluster headache showed a significantly higher respiratory distress index (8.6 ± 16.0) compared with healthy control subjects (3.4 ± 2.1; p = 0.002). More patients fulfilled the criteria for an obstructive sleep apnea syndrome (29%) than control subjects (7%; p = 0.018). Patients only, but not the control subjects, had central apneas. These differences were only significant when measured during an active cluster episode but not during a symptom free interval. CONCLUSION: Cluster headache is associated with a sleep apnea syndrome only in the active cluster episode. The increased rate of central apneas might be a result of involvement of the hypothalamus in the pathophysiology of cluster headache. Out of five anecdotal cases treated with nasal continuous positive airway pressure, only one patient showed benefit with respect to cluster headache attack frequency.

Exploding head syndrome: six new cases and review of the literature.

BACKGROUND: Exploding head syndrome (EHS) is characterized by attacks of a sudden noise or explosive feeling experienced in the head occurring during the transition from wake to sleep or from sleep to wake. METHODS: We present six new cases extending the clinical experience with the syndrome. We also reviewed all available cases from the scientific literature and evaluated the typical features of EHS. RESULTS: The female to male ratio is 1.5 to 1. The median age at onset is 54. In average, one attack per day to one attack per week occurs. Some patients suffer from several attacks per night. In about half of all patients, a chronic time course can be observed but episodic or sporadic occurrence is also common. The most frequent accompanying symptoms beside the noise are fear and flashes of light. Polysomnographic studies do not reveal any specific sleep pattern associated with EHS. Tricyclic antidepressants are helpful in some patients. However, most patients do not need treatment because of the benign nature of the syndrome. CONCLUSION: EHS is a well-defined disease entity with a benign nature.

The impact of temporal lobe epilepsy on musical ability.

PURPOSE: Patients with temporal lobe epilepsy (TLE) often show impairment of cognitive processing in different domains. We aimed to evaluate whether also musical ability is impaired in TLE. METHODS: We enrolled patients with lesional TLE and without any other neurological or psychiatric disorder. The side and the etiology of the epilepsy were confirmed by EEG and by MRI. We applied a self-developed test of musical ability which evaluates the ability to identify melodies, pitch, rhythm, and emotional content of music. In addition, we compared the results of the patients to the results of age and sex matched healthy control subjects. All patients and subjects were without specific musical training. RESULTS: Patients with left TLE showed a significantly lower score in melody recognition, patients with right TLE showed a significantly lower score in identification of emotion in music. In all other aspects of music ability, no significant difference between left and right TLE could be found. We observed a significantly lower total score in patients with left TLE, but not with right TLE, as compared to healthy subjects. There were no differences with respect to sex. CONCLUSION: Our data confirm that the recognition of melodies shows left hemisphere dominance whereas the identification of emotions in music shows right hemisphere dominance in patients without musical training. Furthermore, our data show that the impairment of cognitive processing in TLE is reflected even in higher cognitive functions such as music processing. However, this impairment was mild.

Hypothalamic dopaminergic stimulation in cluster headache.

BACKGROUND: Cluster headache is associated with structural abnormalities of the hypothalamus. We were interested in the association of cluster headache with endocrinological functional abnormalities. Therefore, we applied the apomorphine challenge test, which is a specific test of hypothalamic dopaminergic activation. METHODS: We enrolled 13 patients with cluster headache outside the bout and without medication. They were stimulated with 0.005 mg/kg of body weight subcutaneous apomorphine hydrochloride. After 45 and 60 minutes, growth hormone (GH), prolactin and cortisol were measured. The test was also applied to 14 sex- and age-matched healthy control subjects. RESULTS: There were significantly higher GH levels in healthy subjects as compared to cluster headache patients 45 minutes after injection (10.8 ± 10.8 versus 4.4 ± 7.4 ng/ml; P = 0.038). Only in cluster headache, the GH level after 60 minutes was not significantly different from the baseline. The levels of prolactin and cortisol did not show any significant differences between cluster headache patients and in healthy subjects. DISCUSSION: Our data suggest that cluster headache is associated with an impaired dopaminergic stimulation. This finding supports the body of evidence that cluster headache is associated with a functional abnormality of the hypothalamus and that this association is a primary (i.e. idiopathic) and not a secondary phenomenon during the bout.

The impact of sexual activity on idiopathic headaches: an observational study.

BACKGROUND: Headache associated with sexual activity is a well-known primary headache disorder. In contrast, some case reports in the literature suggest that sexual activity during a migraine or cluster headache attack might relieve the pain in at least some patients. We performed an observational study among patients of a tertiary headache clinic. METHODS: A questionnaire was sent to 800 unselected migraine patients and 200 unselected cluster headache patients. We asked for experience with sexual activity during a headache attack and its impact on headache intensity. The survey was strictly and completely anonymous. RESULTS: In total, 38% of the migraine patients and 48% of the patients with cluster headache responded. In migraine, 34% of the patients had experience with sexual activity during an attack; out of these patients, 60% reported an improvement of their migraine attack (70% of them reported moderate to complete relief) and 33% reported worsening. In cluster headache, 31% of the patients had experience with sexual activity during an attack; out of these patients, 37% reported an improvement of their cluster headache attack (91% of them reported moderate to complete relief) and 50% reported worsening. Some patients, in particular male migraine patients, even used sexual activity as a therapeutic tool. CONCLUSIONS: The majority of patients with migraine or cluster headache do not have sexual activity during headache attacks. Our data suggest, however, that sexual activity can lead to partial or complete relief of headache in some migraine and a few cluster headache patients.

Event related potentials in patients with transient global amnesia--a prospective controlled study.

OBJECTIVE: The aim of this study is to evaluate changes in the latencies and amplitudes of event-related potential (ERP) components as well as cognitive habituation in patients with transient global amnesia (TGA) in order to further characterize the pathology of this syndrome. METHODS: Clinical data of 43 consecutive patients with TGA was collected at a university neurology department. Follow-up examination was performed at an average of 17months after TGA. Results were compared to 43 age- and sex-matched healthy control subjects. RESULTS: All ERP latencies of patients examined within 10days after the TGA period were significantly increased, and the P3 amplitude was significantly decreased as compared to healthy control subjects. The rate of pathological P3 latencies was significantly higher in TGA patients. A normal P3 latency habituation was detected in 84% of all healthy controls (mean habituation 10ms) and in 33% of all TGA patients (mean habituation -6ms). There was no significant improvement of all latencies and the other ERP parameters, including the loss of habituation, after a mean observation period of 17months. The data of three patients who were measured during the TGA period suggest a severe impairment of ERP during this period. CONCLUSIONS: Our findings give new insight into the pathology of TGA and put into question if TGA is an event of a simple transient character. In this first investigation of cognitive habituation in patients with TGA, we found a characteristic loss of cognitive habituation similar to observations in migraine.

Serum from interferon-ß-1b-treated patients with early multiple sclerosis stabilizes the blood-brain barrier in vitro.

Interferon-ß (IFN-ß) stabilizes the blood-brain barrier (BBB) in vitro. Here we investigated the effect of serum from 15 IFN-ß-1b-treated multiple sclerosis (MS) patients on the permeability read-outs of small solutes in an in vitro BBB model consisting of human brain microvascular endothelial cells in co-culture with rat astrocytes. The addition of sera from IFN-ß-treated patients resulted in a significantly (p < 0.05) reduced permeability as compared with untreated patients. Our findings show that sera from IFN-ß-1b-treated MS patients have a stabilizing effect on the in vitro BBB. We suggest an unknown potentially pro-inflammatory factor in the serum of MS patients that may lead to a BBB dysfunction and can be modulated by IFN-ß.

Sexual headache in young adolescence: a case report.

We present the case of a boy who first experienced typical primary headache associated with sexual activity, orgasmic type, at age 12. Neurological examination and brain imaging were normal. A family history of migraine existed. The case shows the broad age spectrum of this primary headache disorder.

Treatment of cremaster synkinesias with botulinum toxin A: a video case report.

Synkinesias secondary to nerve lesions and aberrant re-innervation are well-known phenomena especially after lesions of the facial nerve. Synkinesias can successfully be treated with botulinum toxin A (BTx A). Synkinesias of the cremaster muscle have not been described or treated to date. We present the case of a 62-year-old man who developed synkinesias of both cremaster muscles after extensive laparatomy for esophageal cancer. Treatment of synkinesias with various oral medications had been unsuccessful. Electromyography-guided injections of BTx A in both cremaster muscles (15 MU on the right and 10 on the left) led to significant symptom relief for an average of 8 weeks. We present the case including pre- and posttreatment video clips.

Recent advances in the treatment of headaches.

PURPOSE OF REVIEW: In past years, important advances have been made in the treatment of idiopathic headache disorders. New controlled trials have been published for the acute and the prophylactic drug and non-drug therapies. Furthermore, new headache entities have been described by the International Headache Society for which treatment recommendations can be given. RECENT FINDINGS: Triptans and non-steroidal anti-inflammatory drugs are still the drugs of first choice for the treatment of migraine attacks. Recent studies show that early treatment is clearly effective in migraine and that differential therapy with triptans can be helpful. New drugs with new mechanisms are being developed such as a calcitonin gene-related peptide antagonist. For the prophylaxis of migraine, topiramate has been introduced as an effective new drug. Botulinum toxin did not show convincing evidence of efficacy in migraine and tension-type headache. For migraine and cluster headache, surgical procedures such as the closure of the patent foramen ovale (migraine) and neurostimulation of the hypothalamus (cluster headache) are also under evaluation. A group of miscellaneous headaches (group 4 of the International Headache Society classification) is also described, for which treatment recommendations, in particular indomethacin in most cases, can now be given although no placebo-controlled trials have been performed. SUMMARY: Recent advances in headache treatment comprise growing evidence for an appropriate drug administration and for differential drug therapy rather than the development of new drugs or procedures. Surgical and other non-drug treatment procedures are under discussion and might be an additional tool for headache treatment in future years.

Prevention of AIDS dementia by HAART does not depend on cerebrospinal fluid drug penetrance.

The impact of the cerebrospinal fluid (CSF) penetrance properties of different highly active antiretroviral therapy (HAART) regimes on cognitive processing in AIDS dementia is still undetermined. We therefore designed a retrospective cross-sectional and prospective longitudinal analysis of event-related potentials in HIV-infected patients with different combinations of HAART or without antiretroviral treatment. A total of 353 consecutive patients without secondary CNS manifestation of HIV infection were enrolled in the cross-sectional study and 135 consecutive patients without secondary CNS manifestations of HIV infection were enrolled in the longitudinal study. HAART in different combinations (n = 306) or no antiretroviral treatment (n = 47) was given for at least 6 months in the retrospective cross-sectional study. HAART in different combinations (n = 110) or no antiretroviral treatment (n = 25) was given for 1 year in the prospective longitudinal study. We evaluated the latency and amplitude of the P3 component of visually evoked event-related potentials and mean choice reaction time as measures of cognitive processing. Patients receiving HAART had decreased P3 latencies as compared to those patients not receiving HAART but P3 latency and P3 amplitude were not correlated with the amount of CSF penetrance of the different HAART combinations in either statistical analysis. However, mean choice reaction time was significantly correlated with the amount of CSF penetrance. In HIV-infected patients, the CSF penetrance properties of HAART do not have any significant influence on cognitive processing as measured by event-related potentials.

Impact of antimigraine compounds on cognitive processing: a placebo-controlled crossover study.

OBJECTIVE: To evaluate potential cognitive impairment caused by acute antimigraine drugs. METHODS: We conducted a placebo-controlled, double-blind, crossover study to detect the short-term impact of sumatriptan, zolmitriptan, and ergotamine tartrate on cognitive processing as measured by event-related potentials and a d2 test. Sixteen healthy subjects were enrolled in the study and given placebo, sumatriptan 100 mg, zolmitriptan 2.5 mg, and ergotamine tartrate 2 mg on different days and in random order. Before and 2 hours after drug administration, visually evoked event-related potentials and a d2 test were measured. RESULTS: The N2 latency was significantly increased after ergotamine intake. No other significant differences could be observed in all other event-related potential parameters. In the d2 test, the GZ value was unchanged after ingestion of zolmitriptan and ergotamine, but improved significantly after taking placebo and sumatriptan. The number of relative errors and the concentration value did not change significantly. All results fell within the reference values for the d2 test in all examinations. CONCLUSION: Our data suggest that there may be a slight cognitive decline 2 hours after ingestion of ergotamine tartrate and, to an even lesser extent, zolmitriptan, but not after ingestion of sumatriptan or placebo. All changes recorded were very mild and unlikely to be clinically relevant.

The cerebral hemodynamics of headache associated with sexual activity.

Headache associated with sexual activity is an idiopathic headache disorder and regarded to be a vascular headache but no pathophysiological studies have been performed to date to elucidate the underlying mechanisms. We investigated 12 patients with the explosive type of sexual headache according to the criteria of the International Headache Society during a headache-free state by means of acetazolamide test and of stress Doppler sonography. Twelve age-matched migraine patients and 14 healthy subjects served as control groups. Changes of blood pressure, cerebral blood flow velocity (CBFV), and pulsatility index (PI) were evaluated. Patients with sexual headache showed a significantly higher increase of blood pressure during standardized physical exercise as compared to healthy subjects and migraine patients. Changes of CBFV by physical exercise were not different between the three examination groups. After 1g acetazolamide, CBFV showed a significantly higher increase in patients with sexual headache (plus 66%+/-16%) than in healthy subjects (plus 46%+/-18%), and PI showed a significantly lower decrease as compared to healthy subjects and migraine patients. These data suggest that in patients with sexual headache the metabolic rather than the myogenic component of the cerebral vasoneuronal coupling is impaired.