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.

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.

Cerebrovascular events in HIV-infected patients: an analysis of a cohort of 3203 HIV+ patients during the times of cART.

PURPOSE/AIM: Cerebrovascular events (CVE) in HIV infected patients have become an increasingly relevant neurological complication. Data about the prevalence and clinical features of CVE in HIV infected patients since the introduction of combined Anti-Retroviral Therapy (cART) are rare. METHODS: A retrospective study of HIV-infected patients with a CVE was performed from 2002 to 2011. During this time period 3203 HIV-infected patients were admitted to the University hospital of Münster, Germany. All patients had access to regular and long term treatment with cART. The clinical features were analyzed and the prevalence of ischemic stroke (IS), transient ischemic attack (TIA) and intracerebral bleeding (ICB) was calculated. RESULTS: The total prevalence of all CVE was at 0.6% (95% CI: 0.3, 0.8) (0.4% for IS (95% CI: 0.2, 0.6), 0.2% for TIA (95% CI: 0.0, 0.3) and 0.1% for ICB (95% CI: 0.0, 0.2)) and the crude annual incidence rate at 59 per 100.000 for all events. The median CD4 cell count was 405/µl (25th to 75th percentile: 251-568). The majority of patients had AIDS. The median age was at 49 years (25th to 75th percentile: 40-69). Some events were associated with HIV-associated vasculopathy or viral co-infections. Most patients presented with multiple vascular risk factors. CONCLUSION: The study confirms that CVE occur in HIV-infected patients with a good immune status and at a young age. HIV infection has to be considered in young stroke patients. The rate of CVE in this study was constant when comparing to the pre-cART era. HIV associated vasculopathy and viral co-infections need to be considered in the diagnostics of stroke.

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.

Increases in CSF dopamine in HIV patients are due to the dopamine transporter 10/10-repeat allele which is more frequent in HIV-infected individuals.

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.

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.

Cytokine levels in CSF and neuropsychological performance in HIV patients.

HIV-associated dementia and its precursors are frequently observed complications of HIV infection, even in the presence of combination antiretroviral treatment (cART). The development, surveillance and treatment of this condition are still not completely understood. Cytokines, as immunological transmitters, may be one key to gaining a deeper understanding of the disease. A total of 33 HIV-positive male patients were evaluated by neuropsychological testing, lumbar and venous puncture, neuroimaging and neurological examination. The cytokine content in the CSF (cerebrospinal fluid) was examined by a solid-phase protein array. The Digit-Symbol Test, contraction time analysis, Rey-Osterrieth Figure and Grooved-Pegboard Test showed inferior results in the presence of an inflammatory CSF environment, whereas neuroprotective or anti-inflammatory conditions were correlated to better results in contraction time analysis. Higher CSF levels of cytokines were independently correlated with the duration of HIV infection. The study showed a correlation of cytokine levels in the CSF of HIV patients with test results of their neuropsychological functioning. The effect was pronounced with regard to the more complex executive tasks. Determining CSF cytokine levels may be a useful supplement to the assessment of HIV patients and contribute helpful information to predict neurocognitive performance. Therapeutic strategies to ameliorate a negative impact of an altered cytokine milieu may aid in slowing the evolution of neurocognitive dysfunction.

Early microstructural white matter changes in patients with HIV: a diffusion tensor imaging study.

BACKGROUND: Previous studies have reported white matter (WM) brain alterations in asymptomatic patients with human immunodeficiency virus (HIV). METHODS: We compared diffusion tensor imaging (DTI) derived WM fractional anisotropy (FA) between HIV-patients with and without mild macroscopic brain lesions determined using standard magnetic resonance imaging (MRI). We furthermore investigated whether WM alterations co-occurred with neurocognitive deficits and depression. We performed structural MRI and DTI for 19 patients and 19 age-matched healthy controls. Regionally-specific WM integrity was investigated using voxel-based statistics of whole-brain FA maps and region-of-interest analysis. Each patient underwent laboratory and neuropsychological tests. RESULTS: Structural MRI revealed no lesions in twelve (HIV-MRN) and unspecific mild macrostructural lesions in seven patients (HIV-MRL). Both analyses revealed widespread FA-alterations in all patients. Patients with HIV-MRL had FA-alterations primarily adjacent to the observed lesions and, whilst reduced in extent, patients with HIV-MRN also exhibited FA-alterations in similar regions. Patients with evidence of depression showed FA-increase in the ventral tegmental area, pallidum and nucleus accumbens in both hemispheres, and patients with evidence of HIV-associated neurocognitive disorder showed widespread FA-reduction. CONCLUSION: These results show that patients with HIV-MRN have evidence of FA-alterations in similar regions that are lesioned in HIV-MRL patients, suggesting common neuropathological processes. Furthermore, they suggest a biological rather than a reactive origin of depression in HIV-patients.

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.

Phantom testis syndrome: prevalence, phenomenology and putative mechanisms.

Chronic phantom pain has been found in up to 78% of limb amputees and is a major complication of limb amputation. Less is known about phantom phenomena after the amputation of other, i.e. visceral, parts of the body. In a retrospective design, we identified 539 patients in whom one testis was removed between 1995 and 2005. The operative technique was a unilateral standard radical inguinal orchiectomy. The underlying pathology in all cases was a testicular germ cell tumour. All patients received a detailed questionnaire asking about the occurrence of phantom testis pain (pain felt in the removed testis), phantom testis sensations (non-painful sensations as if the removed testis was still intact) and hallucinations (illusionary perceptions on the removed testis). Furthermore, we asked about the occurrence and clinical presentation of pain before and after surgery and about pre-operative testicular pain. Out of 238 respondents, 125 patients (53%) reported any kind of phantom experience. The prevalence of phantom testis pain was 25% (60/238), non-painful phantom sensations 16% (37/238) and male gonad hallucinations 12% (28/238). Patients with phantom symptoms reported pre-operative pain in the removed testis more often than patients without phantom symptoms. This study presents first data on the clinical characteristics and possible mechanisms of the phantom testis syndrome after surgical removal of one testis.

Hereditary amyloidosis of the Finnish type in a German family: clinical and electrophysiological presentation.

Hereditary amyloidosis of the Finnish type (HAF, or familial amyloid polyneuropathy type IV) is an autosomal dominant disease that has been described most commonly in the Finnish population but has also been found in some other countries. Herein we report the first German family whose members suffer from this condition. There are no known Finnish ancestors. We performed clinical and electrophysiological examinations in 22 members of this family. All symptomatic family members suffered from facial palsy, and most of them had peripheral neuropathy. One patient had confirmed corneal lattice dystrophy. Additional symptoms were hypoglossal nerve involvement in 5 patients and oculomotor nerve palsy in 1 patient. The lips of all older patients appeared thickened. The causative G654A mutation in the gelsolin gene was found in all affected family members.

Measurement of soluble inflammatory mediators in cerebrospinal fluid of human immunodeficiency virus-positive patients at distinct stages of infection by solid-phase protein array.

The objective of this study was to evaluate immune cytokine expression in cerebrospinal fluid (CSF) of patients with human immunodeficiency virus-1 (HIV-1)-associated dementia (HAD) using a novel cytokine array assay. HIV-1 induces a condition resembling classical subcortical dementia, known as HAD. The immune mechanisms contributing to HAD have not been elucidated. Cytokine expression in CSF was determined by solid-phase protein array in 33 neurologically asymptomatic HIV-positive male patients and were compared to levels in non-HIV controls and patients with HAD. Neurological examinations and lumbar and venous punctures were conducted in all patients and controls. Interleukin (IL)-1, IL-4, and IL-10, were up-regulated in all treated acquired immunodeficiency syndrome (AIDS) patients independent of neurological status compared to controls. In contrast, interferon gamma (IFN-gamma), IL-1alpha, IL-15, and tumor necrosis factor alpha (TNF-alpha) were highly expressed in patients with HAD compared to undemented HIV-positive patients. These results show that solid-phase protein array can detect immunological changes in patients infected with HIV. Cytokine expression levels differ in different disease stages and in patients on different treatment paradigms. Pending further validation on a larger number of patients, this method may be a useful tool in CSF diagnostics and the longitudinal evaluation of patient with HAD.

[Success of psychotherapy referral of a psychosomatic consultation service among neurologic inpatients]. / Erfolg von Psychotherapieempfehlungen bei psychosomatischen Konsiliarpatienten einer neurologischen Station.

OBJECTIVES: This study investigates the success of recommendations for psychotherapy given in a psychosomatic consultation service to neurological inpatients. METHODS: In 2005, a subset of 401 (55.7 %) former neurologic inpatients from the initial sample of 720 who underwent psychosomatic consultation between 1999 and 2004 completed follow-up questionnaires to telephone interviews. RESULTS: 279 (69.6 %) participants stated that they had received a recommendation for in- or outpatient psychotherapy during the psychosomatic consultation. Of these, 152 (54.5 %) followed this recommendation. No differences in age, gender, familial status, initial symptoms, and diagnoses were detected between those who underwent psychotherapy and those who did not. Patients who underwent psychotherapy reported significant improvement of symptoms, less impairment, and less disability. CONCLUSIONS: A psychosomatic consultation may be a useful adjunct to neurological diagnostics in order to determine the correct diagnosis and therapy for patients with pseudo-neurological symptoms or evidence of psychological problems.

Cidofovir in combination with HAART and survival in AIDS-associated progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy is a demyelinating disease with a high mortality caused by the JC virus and occurs in about 5% of HIV-infected patients. Highly active anti-retroviral therapy (HAART) has a proven efficacy in prolonging the survival of patients with AIDS-associated PML, but there are differing opinions about adding cidofovir to the treatment of PML. To investigate the benefit of HAART combined with cidofovir, we retrospectively analysed the survival of 33 patients with AIDS-associated PML proven by PCR in CSF, biopsy or at autopsy. Additionally, we also analysed 37 patients with probable PML. Seventeen (51.5%) of the patients with confirmed PML were treated with HAART and 14 (42.4%) with cidofovir in any combination. Of these patients, 13 (39.4%) were treated with HAART and cidofovir in combination, four (12.1%) patients received only HAART without cidofovir and one (3%) patient received only cidofovir without HAART. Fifteen patients did not receive HAART or cidofovir. The cumulative survival was significantly longer in patients with HAART than in patients without HAART (p = 0.006), independent whether cidofovir was given or not. In comparison with single therapy with HAART, the combination of HAART and cidofovir showed no significant increase in survival (p = 0.435). Therefore, a benefit for cidofovir in addition to HAART in the treatment of PML in HIV-infected patients could not be proven.

Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine.

BACKGROUND: Calcitonin gene-related peptide (CGRP) may have a causative role in migraine. We therefore hypothesized that a CGRP-receptor antagonist might be effective in the treatment of migraine attacks. METHODS: In an international, multicenter, double-blind, randomized clinical trial of BIBN 4096 BS, a highly specific and potent nonpeptide CGRP-receptor antagonist, 126 patients with migraine received one of the following: placebo or 0.25, 0.5, 1, 2.5, 5, or 10 mg of BIBN 4096 BS intravenously over a period of 10 minutes. A group-sequential adaptive treatment-assignment design was used to minimize the number of patients exposed. RESULTS: The 2.5-mg dose was selected, with a response rate of 66 percent, as compared with 27 percent for placebo (P=0.001). The BIBN 4096 BS group as a whole had a response rate of 60 percent. Significant superiority over placebo was also observed with respect to most secondary end points: the pain-free rate at 2 hours; the rate of sustained response over a period of 24 hours; the rate of recurrence of headache; improvement in nausea, photophobia, phonophobia, and functional capacity; and the time to meaningful relief. An effect was apparent after 30 minutes and increased over the next few hours. The overall rate of adverse events was 25 percent after the 2.5-mg dose of the drug and 20 percent for the BIBN 4096 BS group as a whole, as compared with 12 percent for placebo. The most frequent side effect was paresthesia. There were no serious adverse events. CONCLUSIONS: The CGRP antagonist BIBN 4096 BS was effective in treating acute attacks of migraine.

HIV-1-associated neurocognitive disorder: epidemiology, pathogenesis, diagnosis, and treatment.

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.

Control beliefs and health locus of control in Ugandan, German and migrated sub-Saharan African HIV infected individuals.

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.

Enucleation and development of cluster headache: a retrospective study.

BACKGROUND: Cluster headache (CH) is a neurovascular, primary headache disorder. There are, however, several case reports about patients whose CH started shortly after a structural brain disease or trauma. Motivated by a patient who developed CH 3 weeks after the removal of an eye and by similar case reports, we tested the hypothesis that the removal of an eye is a risk factor for CH. METHODS: A detailed headache questionnaire was filled out by 112 patients on average 8 years after enucleation or evisceration of an eye. RESULTS: While 21 % of these patients experienced previously unknown headaches after the removal of an eye, no patient fulfilled the diagnostic criteria for CH. CONCLUSION: Our data does not suggest that the removal of an eye is a major risk factor for the development of CH.

Capsaicin 8 % as a cutaneous patch (Qutenza™): analgesic effect on patients with peripheral neuropathic pain.

Evaluation of the analgesic effect after a single application of the capsaicin 8 % cutaneous patch (Qutenza™) in 37 patients suffering from painful, distal symmetric polyneuropathy (PNP) for an average of 5 years. Patients ranged from 40 to 78 years of age and 22 subjects were HIV-positive. Patients were observed 4 weeks prior to 12 weeks post administration. An evaluation of the therapeutic effect of capsaicin 8 % as a dermal patch in terms of pain reduction, change of sleeping behavior and social activities was performed and statistical analysis of data was conducted using non-parametric methods. Patients were selected according to clinical criteria. Numerical rating scale (NRS 0-10) was used to inquire pain intensity and a pain score was calculated using the painDETECT(©) questionnaire Freynhagen R (Curr Med Res Opin 22:1911-1920, [2006]). A significant reduction of pain was achieved for up to 12 weeks, with a maximum after 2-4 weeks post administration. After patient education and before application of capsaicin patch, a significant reduction of three levels on the NRS was observed. Symptoms of painful PNP decreased over the period of investigation and 8 patients reported a reduction of systemic pain medication. In patients with an HIV infection, a significant extension of sleep was achieved for 2, 4 and 8 weeks after application. Thus, the application of the capsaicin 8 % patch resulted in a significant relief of neuropathic pain, a prolongation of sleep, a reduction of oral pain medication and a resumption of social activities.

Neurocognitive decline in HIV patients is associated with ongoing T-cell activation in the cerebrospinal fluid.

OBJECTIVE: HIV-associated neurocognitive disorders (HAND) remain a challenge despite combination antiretroviral therapy (cART). Immune cell activation has been implicated to play a major role in the development of HAND. METHODS: In this study, we used multicolor flow cytometry on peripheral blood (PB) and cerebrospinal fluid (CSF) samples to determine the expression of HLA-DR and programmed death-1 (PD-1) on CD4+ and CD8+ T cells in patients with chronic HIV infection. Expression levels were correlated with HI virus load in PB and CSF, classification of HAND and severity of magnetic resonance imaging (MRI) signal abnormalities. RESULTS: In a cohort of 86 HIV patients we found that the grade of neurocognitive impairment and the severity of MRI signal abnormalities correlated with decreasing CD4/CD8-ratios and increased frequencies of HLA-DR expressing CD4+ and CD8+ T cells reaching the highest values in the CSF samples. Importantly, HLA-DR upregulation was still detectable in virologically suppressed HIV patients. Further, T-cell subpopulation analysis of 40 HIV patients showed a significant shift from naïve to effector memory (EM) T cells that was negatively correlated with the grade of neurocognitive impairment in the PB samples. Moreover, PD-1 was significantly increased on CD4+ memory T cells with highest levels on EM T cells in HIV patients with mild or severe neurocognitive alterations. INTERPRETATION: The CD4/CD8 ratio, the proportion of EM to naïve T cells and the immune activation profile of CD4+ and CD8+ T cells in PB and CSF might be useful parameters to monitor the efficacy of cART and to identify HIV patients at risk of further neurocognitive deterioration.