I W Husstedt's research while affiliated with University of Münster and other places

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.

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.

ZUSAMMENFASSUNG Ds Geschlecht hat einen besonderen Einfluss auf den Verlauf, die Manifestationen und die Behandlung einer HIV-Infektion. Es ist aber nur wenig bekannt über den spezifischen Einfluss des Geschlechts auf die Neuromanifestation. Wir wollten daher Unterschiede in der Prävalenz und in dem Grad der Neuromanifestationen zwischen Frauen und Männern mit HIV-Infektionen evaluieren und haben deshalb eine Fall-Kontroll-Studie mit konsekutiven HIV-infizierten Frauen (n = 167) and Männern (n = 169) durchgeführt, die für die Dauer der Infektion gematcht waren. Die Studie wurde an einer überregionalen HIV-Ambulanz einer neurologischen und an einer medizinischen Klinik durchgeführt. Es wurden die demografischen, klinischen, neurologischen, neurophysiologischen (ereigniskorrelierte Potenziale, Neurografie) und Bildgebungsdaten verglichen. Frauen waren zum Zeitpunkt der Infektion signifikant jünger als Männer. Sie zeigten weniger fortgeschrittene Stadien der HIV-Infektion und eine höhere CD4+-Zellzahl. Frauen erhielten seltener eine antiretrovirale Therapie. Die Nervenleitgeschwindigkeiten und Latenzen der ereigniskorrelierten Potenziale waren signifikant besser bei Frauen. Sie hatten eine signifikant niedrigere Rate einer Polyneuropathie und von generalisierten opportunistischen Infektionen. Außerdem zeigte sich ein Trend zu einer geringeren Rate einer HIV-assoziierten Enzephalopathie bei Frauen. Zusammenfassend zeigten Frauen einen besseren immunologischen Status und eine geringere Rate von Neuromanifestationen im Vergleich zu Männern mit derselben Infektionsdauer.

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.

Das Zika-Virus ist ein Arbovirus aus der Familie der Flaviviren, welches durch die Stechmücke Aedes aegyptii übertragen wird, aber auch durch die Asiatische Tigermücke Aedes albopticus. Die bisher größte beobachtete Zika-Virus-Epidemie findet momentan in Nord- und Südamerika, in der Karibik, im Süden der USA und in Südostasien statt. Meistens verläuft die Infektion als unspezifische, akute, fiebrige Erkrankung. Neurologische Manifestationen bestehen in der Hauptsache in einer Mikrozephalie bei Neugeborenen und einem Guillain-Barré-Syndrom, aber auch andere, seltenere Manifestationen sind in der Zwischenzeit bekannt geworden, wie eine Meningoenzephalitis und eine Myelitis. Es liegt daher nahe, dass das Zika-Virus, ähnlich wie andere Flaviviren, neuropathogene Eigenschaften aufweist. Insbesondere der drastische Anstieg der Mikrozephaliefälle in Brasilien hat große Forschungsaktivitäten induziert. Das Virus wird perinatal übertragen und kann im Fruchtwasser, in der Plazenta und im Gehirngewebe des Neugeborenen nachgewiesen werden. Eine Impfung oder eine kausale Therapie existierten bislang nicht. Der signifikante Anstieg des durch das Zika-Virus induzierten Guillain-Barré-Syndroms wurde schon während früherer Ausbrüche beobachtet. In der Zwischenzeit haben sich wissenschaftlich klare Verbindungen zwischen einer Zika-Virus-Infektion und diesen neurologischen Manifestationen gezeigt. Durch Langzeitstudien und Tiermodelle kann erreicht werden, die Pathomechanismen dieser Erkrankung besser zu verstehen.

The modern antiretroviral treatment of human immunodeficiency virus (HIV-1) infection has considerably lowered the incidence of opportunistic infections. With the exception of the most severe dementia manifestations, the incidence and prevalence of HIV-associated neurocognitive disorders (HAND) have not decreased, and HAND continues to be relevant in daily clinical practice. Now, HAND occurs in earlier stages of HIV infection, and the clinical course differs from that before the widespread use of combination antiretroviral treatment (cART). The predominant clinical feature is a subcortical dementia with deficits in the domains concentration, attention, and memory. Motor signs such as gait disturbance and impaired manual dexterity have become less prominent. Prior to the advent of cART, the cerebral dysfunction could at least partially be explained by the viral load and by virus-associated histopathological findings. In subjects where cART has led to undetectable or at least very low viral load, the pathogenic virus-brain interaction is less direct, and an array of poorly understood immunological and probably toxic phenomena are discussed. This paper gives an overview of the current concepts in the field of HAND and provides suggestions for the diagnostic and therapeutic management.

We showed previously that higher levels in CSF dopamine in HIV patients are associated with the presence of the dopamine transporter (DAT) 10/10-repeat allele which was also detected more frequently in HIV-infected individuals compared to uninfected subjects. In the current study, we investigated further whether other genetic dopamine (DA)-related polymorphisms may be related with changes in CSF DA levels and frequency of HIV infection in HIV-infected subjects. Specifically, we studied genetic polymorphisms of brain-derived neurotrophic factor, catechol-O-methyltransferase, and dopamine receptors DRD2, DRD3, and DRD4 genetic polymorphisms in uninfected and HIV-infected people in two different ethnical groups, a German cohort (Caucasian, 72 individuals with HIV infection and 22 individuals without HIV infection) and a South African cohort (Xhosan, 54 individuals with HIV infection and 19 individuals without HIV infection). We correlated the polymorphisms with CSF DA levels, HIV dementia score, CD4⁺ T cell counts, and HIV viral load. None of the investigated DA-related polymorphisms was associated with altered CSF DA levels, CD4⁺ T cell count, viral load, and HIV dementia score. The respective allele frequencies were equally distributed between HIV-infected patients and controls. Our findings do not show any influence of the studied genetic polymorphisms on CSF DA levels and HIV infection. This is in contrast to what we found previously for the DAT 3′UTR VNTR and highlights the specific role of the DAT VNTR in HIV infection and disease.

Dysfunction of dopaminergic neurotransmission has been implicated in HIV infection. We showed previously increased dopamine (DA) levels in CSF of therapy-naïve HIV patients and an inverse correlation between CSF DA and CD4 counts in the periphery, suggesting adverse effects of high levels of DA on HIV infection. In the current study including a total of 167 HIV-positive and negative donors from Germany and South Africa (SA), we investigated the mechanistic background for the increase of CSF DA in HIV individuals. Interestingly, we found that the DAT 10/10-repeat allele is present more frequently within HIV individuals than in uninfected subjects. Logistic regression analysis adjusted for gender and ethnicity showed an odds ratio for HIV infection in DAT 10/10 allele carriers of 3.93 (95 % CI 1.72–8.96; p = 0.001, Fishers exact test). 42.6 % HIV-infected patients harbored the DAT 10/10 allele compared to only 10.5 % uninfected DAT 10/10 carriers in SA (odds ratio 6.31), whereas 68.1 versus 40.9 %, respectively, in Germany (odds ratio 3.08). Subjects homozygous for the 10-repeat allele had higher amounts of CSF DA and reduced DAT mRNA expression but similar disease severity compared with those carrying other DAT genotypes. These intriguing and novel findings show the mutual interaction between DA and HIV, suggesting caution in the interpretation of CNS DA alterations in HIV infection solely as a secondary phenomenon to the virus and open the door for larger studies investigating consequences of the DAT functional polymorphism on HIV epidemiology and progression of disease.

Objectives: Little is known about the influence of control beliefs on antiretroviral drug adherence in patients who migrated from sub-Saharan Africa to Europe. The aim of this study was to explore the differences in health locus of control and control beliefs between HIV infected patients from sub-Saharan Africa with and without a lifetime experience of migration. Methods: A sample of 62 HIV infected consecutive patients referred to the HIV clinics at the University Hospital of Münster (Germany) and at the Rubaga Hospital Kampala (Uganda) were enrolled into this study. We compared three groups of patients: sub-Saharan African migrants, German patients, and local Ugandan patients. We used the German health and illness related control beliefs questionnaire (KKG), the Competence and control beliefs questionnaire (FKK), and the Powe Fatalism Inventory-HIV/AIDS-Version (PFI-HIV/AIDS-Version) and translated these scales into English and Luganda. In addition, the patients' sociodemographic, acculturation, clinical, and immunological data were registered. Results: Significant results were shown in HIV related external locus of control between migrated sub-Saharan African and local Ugandan patients compared to German patients. General control beliefs showed no significant differences. In the PFI-HIV-Version, there was a significant difference between migrated sub-Saharan African and Ugandan patients compared to German patients. Conclusions: Our data suggest that the experience of migration does not influence the locus of control. Compared to German HIV patients, African patients in general showed a significantly higher external health locus of control which might have implications for drug adherence.

With modern antiretroviral drug regimens, HIV-infected people are living longer and HIV has transformed into a chronic illness. The review summarizes pathophysiological as well as clinical aspects of a chronic infection from a neurological point of view including neurocognitive impairment, depression, neuropathies and myopathies. It also draws attention to comorbidities such as syphilis and hepatitis C. They are of particular neurological interest because of the interaction of the pathogens. © Georg Thieme Verlag KG Stuttgart · New York.