Treatment of immigrants and residents suffering from neuro-AIDS on a neurological intensive care unit: epidemiology and predictors of outcome.

This study aimed at determining the clinical features and predictors for the outcome of patients with Neuro-Aids treated on a neurological intensive care unit (NICU) using retrospective analysis of all patients treated for Neuro-Aids in a tertiary Department of Neurology between 1996 and 2011. Chart review of the patients including the characteristics of intensive care was performed. As negative outcome, "death on the NICU or within 2 months following completion of NICU treatment" was defined. In total, 462 patients were identified of whom 87 were immigrants. 67 of all patients required NICU treatment (mean age 40.2 ± 0.8 years; 64% male). The median of the duration between diagnosis of HIV infection and the onset of treatment on NICU was 8 days for immigrants and 10 years for residents (p < 0.001). 34 of the patients on the NICU died due to severe neuromanifestations. Negative predictors for death were: (1) artificial ventilation; (2) antiretroviral-naïve immigrant; (3) primary cerebral lymphoma; (4) missing antiretroviral therapy upon admission to the NICU. Gender, age, ethnicity, CD4+ cell count, and viral load were no predictors of a negative outcome. The results indicated that the rate of death during treatment on a NICU is much higher as compared with treatment on an internal medicine ICU. A lot of research and effort will be necessary to improve this outcome especially for immigrants with Neuro-Aids.

[Treatment of neuro-AIDS on a neurological intensive care unit: epidemiology and predictors of outcome]. / Behandlung von Neuro-Aids auf der neurologischen Intensivstation : Epidemiologie, Outcome und Prädiktoren des Verlaufs.

BACKGROUND: Investigations concerning the outcome for patients suffering from neuro-AIDS treated on a neurological intensive care unit and specific predictors indicating "dead" were analyzed. MATERIAL AND METHODS: A total of 56 patients with a mean age of 39 ± 0.7 years, a mean CD4+ cell count of 130 ± 166 CD4+ cells/µl and viral load of 146,520 ± 198,059 copies/ml were treated on a neurological intensive care unit due to different forms of neuro-AIDS. RESULTS: Of the patients, 34% were immigrants of whom 74% came from sub-Saharan regions. In 57% of the patients the diagnosis of HIV infection was made during therapy on the neurological intensive care unit. The median for the time between diagnosis of HIV infection and the treatment on the neurological intensive care unit was 8 days for immigrants and 10 years for residents. The most common manifestations of neuro-AIDS were cerebral toxoplasmosis, cryptococcosis and progressive multifocal leukoencephalopathy (PML). Fifty per cent of the patients (n=28) died during treatment on the neurological intensive care unit. Negative predictors for the outcome "dead" were (a) artificial ventilation, (b) antiretroviral naïve immigrant, (c) primary cerebral lymphoma and (d) missing antiretroviral therapy as a result of admission to the intensive care unit. DISCUSSION: The rate of death during treatment of neuro-AIDS on a neurological intensive care unit is much higher than during treatment of internal medicine problems of HIV infection. Antiretroviral naïve immigrants show a much higher rate of death compared to residents in Germany. A lot of research and effort is necessary to improve the availability of the Highly Active Anti-Retroviral Therapy (HAART) worldwide in order to improve the outcome especially for immigrants with neuro-AIDS treated on a neurological intensive care unit.

Increased dopaminergic neurotransmission in therapy-naïve asymptomatic HIV patients is not associated with adaptive changes at the dopaminergic synapses.

Central dopaminergic (DA) systems are affected during human immunodeficiency virus (HIV) infection. So far, it is believed that they degenerate with progression of HIV disease because deterioration of DA systems is evident in advanced stages of infection. In this manuscript we found that (a) DA levels are increased and DA turnover is decreased in CSF of therapy-naïve HIV patients in asymptomatic infection, (b) DA increase does not modulate the availability of DA transporters and D2-receptors, (c) DA correlates inversely with CD4+ numbers in blood. These findings show activation of central DA systems without development of adaptive responses at DA synapses in asymptomatic HIV infection. It is probable that DA deterioration in advanced stages of HIV infection may derive from increased DA availability in early infection, resulting in DA neurotoxicity. Our findings provide a clue to the synergism between DA medication or drugs of abuse and HIV infection to exacerbate and accelerate HIV neuropsychiatric disease, a central issue in the neurobiology of HIV.

Cluster headache and Alpha 1-antitrypsin deficiency.

Little is known about the pathophysiology of cluster headache (CH), one of the most debilitating primary headaches. Interestingly, associations of lung affecting diseases or lifestyle habits such as smoking and sleep apnoea syndrome and CH have been described. Certain genotypes for alpha 1-antitrypsin (alpha(1)-AT) are considered risk factors for emphysema. Our aim was to investigate possible associations between common genotypes of the SERPINA1 gene and CH. Our study included 55 CH patients and 55 controls. alpha(1)-AT levels in serum and the genotype were analysed. Patients CH characteristics were documented. We could not detect any association between CH and a genotype that does not match the homozygous wild type for alpha(1)-AT. Interestingly, there is a significant difference of CH attack frequency in patients who are heterozygous or homozygous M allele carriers. We conclude that the presence of an S or Z allele is associated with higher attack frequency in CH.

[Severe aseptic leucoencephalopathy. Manifested as immune reconstitution inflammatory syndrome in Caucasian and African patients]. / Schwere Leukenzephalopathie. Manifestationsform des aseptischen Immune-reconstitution-inflammatory-Syndroms bei Kaukasiern und Afrikanern.

BACKGROUND: We hypothesize that CNS immune reconstitution inflammatory syndrome (IRIS) after highly active antiretroviral therapy (HAART) in HIV-1-positive patients may become manifest without any opportunistic infection as an aseptic leucoencephalopathy. This opens a window of opportunity for successful treatment with corticosteroids. DESIGN: We describe a case series of immunocompromised HIV-1-positive patients who were started on HAART. All of them had clinical laboratory follow-up tests and cerebral MRI in order to investigate the course and the underlying pathophysiology of this aseptic form of IRIS. One African patient died and we performed a neuropathological examination. RESULTS: No infectious agent was detected before and during HAART. Three of four immunocompromised patients were successfully treated with corticosteroids while HAART was never interrupted and have survived up to now. One African patient died within 2 days despite intensive care due to cerebral oedema. CONCLUSIONS: Starting HAART, HIV-1-positive patients may develop an aseptic type of IRIS of the CNS without any detectable opportunistic infection, a finding that has not yet been published. This makes them susceptible for successful treatment with corticosteroids. Perhaps IRIS has a higher incidence in African patients and the patients have a poorer outcome than Caucasians.

Long-term tracking of neurological complications of encephalopathy and myopathy in a patient with nephropathic cystinosis: a case report and review of the literature.

INTRODUCTION: Cystinosis is a hereditary storage disease resulting in intracellular accumulation of cystine and crystal formation that causes deterioration of the function of many organs. The major clinical symptom is renal failure, which progresses and necessitates renal transplantation at the beginning of the second decade of life. Encephalopathy and distal myopathy are important neurological long-term complications with a major impact on the quality of life of these patients. Application of cysteamine is the only specific therapy available; it decreases the intracellular cystine level and delays or may even prevent the failure of organ functions. CASE PRESENTATION: We present the case of a 38-year-old woman with cystinosis and the long-term tracking of her neurological symptoms under cysteamine treatment. CONCLUSION: This case report describes a long observation period of neurological complications in a person with cystinosis who had strikingly different courses of encephalopathy and myopathy while on cysteamine treatment. Although encephalopathy was initially suspected, this did not develop, but distal myopathy progressed continuously despite specific therapy.

[Magnetic resonance imaging findings of the brain in adult HIV and AIDS patients]. / Magnetresonanztomografische Befunde des Gehirns bei adulten Patienten mit HIV und AIDS.

The spectrum of pathology affecting the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome (AIDS) includes not only the human immunodeficiency virus (HIV) infection itself but also opportunistic infections and tumors secondary to AIDS. Despite progress in antiretroviral therapy and the subsequent decrease in the incidence of associated diseases, opportunistic infections and tumors secondary to the HIV infection continue to be the limiting factor in terms of survival with AIDS. Therefore, the therapeutic aim is permanent antiretroviral therapy as well as early diagnosis and treatment of opportunistic infections. Magnetic resonance imaging is often the diagnostic method of choice in suspected CNS pathology of HIV patients. In the following, the typical clinical and radiological features of several AIDS-related pathologies are presented and discussed.

[Primary CNS lymphoma in azathioprine therapy for autoimmune diseases: review of the literature and case report]. / Primäres ZNS-Lymphom während der Behandlung von Autoimmunerkrankungen mit Azathioprin. Kasuistik und Literaturübersicht.

We present a 31-year-old female patient with primary non-Hodgkin's lymphoma of the CNS after immunosuppressive therapy. Colitis ulcerosa had been diagnosed 2 years previously. Prophylactic therapy with azathioprine over 9 months was stopped after the development of listeria meningitis which was treated successfully with antibiotics. At this time native CCT was normal. Three months later the patient developed an epileptic seizure and multiple cerebral lesions were detected in CCT and MRI. Although antibiotic therapy was started, the cerebral lesions showed no regression. Stereotactic biopsy revealed immunochemical and histologic high-grade malignant B cell lymphoma. The risk of primary CNS lymphoma under azathioprine treatment for an autoimmune disease with a possible congenital immunodeficiency is presented and the literature is reviewed.

Recommendations for the classification of HIV associated neuromanifestations in the German DRG system.

HIV associated neuromanifestations are of growing importance in the in-patient treatment of HIV infected patients. In Germany, all in-patients have to be coded according to the ICD-10 classification and the German DRG-system. We present recommendations how to code the different primary and secondary neuromanifestations of HIV infection. These recommendations are based on the commentary of the German DRG procedures and are aimed to establish uniform coding of neuromanifestations.

[Requirements for an interdisciplinary lecture on pain. Results from a survey of medical students]. / Anforderungen an eine interdisziplinäre Schmerzvorlesung. Ergebnisse einer Umfrage unter Studierenden der Medizin.

BACKGROUND: Pain therapy is not an obligatory subject of undergraduate medical education in Germany. METHODS: In order to evaluate the expectations of undergraduate medical students regarding pain therapy as a lecture, a questionnaire was distributed to students visiting a faculty lecture on pain therapy. RESULTS: The main topics voted by the students as very interesting to them were pain syndromes such as low back pain, headache, and cancer pain. Furthermore, pharmacotherapy and the structure of pain therapy units were voted as interesting. Female students were significantly more interested in pain problems of specific patient groups (women, children, older patients, HIV-infected patients). Case reports on paper or with patient presentations were regarded as the most important didactic elements of such lectures. CONCLUSIONS: An analysis of the published undergraduate curricula in pain therapy revealed that the curriculum of the IASP and of the EFIC are too long and too theoretical, respectively. The curriculum of the DGSS meets many expectations of the students in this survey. Concepts of pain therapy education in undergraduate medical schools should consider the wishes of students regarding knowledge of pain syndromes and didactic methods.

[Correlation between clinical apparatus-based differential diagnosis and neuropathological diagnosis in patients with AIDS]. / Zur Korrelation klinisch-apparativer Differenzialdiagnosen mit neuropathologischen Diagnosen bei Patienten mit AIDS.

BACKGROUND: During the course of HIV infection, the majority of patients develop opportunistic cerebral neuro-manifestations. If conventional diagnostic tools are not sufficient, a stereotactic biopsy is often necessary. PATIENTS AND METHODS: In order to evaluate the correctness of the clinical diagnosis of cerebral neuro-manifestations in HIV-infected patients, we compared the results of cerebral biopsy or autopsy with the previous clinical diagnosis. A total of 19 biopsies and 49 autopsies could be analyzed. RESULTS: Except for HIV-associated encephalopathy, we detected a very high conformity between the clinical and the neuropathological diagnoses. We obtained the best sensitivity for progressive multifocal leukoencephalopathy (PML), whereas for cerebral toxoplasmosis the worst sensitivity and specificity was identified. CONCLUSION: We conclude that the diagnosis of PML can be made on clinical grounds alone, whereas the diagnosis of cerebral toxoplasmosis and lymphoma often requires a biopsy, which should be performed early.

[Phantom pain after eye enucleation]. / Phantomschmerz nach Enucleatio bulbi.

BACKGROUND: Phantom pain is a well known and extensively documented complication after limb amputation. Nearly all surgical disciplines have to deal with phantom symptoms related to different anatomical regions and organs but limited data is available about phantom eye pain (PEP) after enucleation. Only one pilot study is present in literature. It was the aim of this study to analyze a group of patients with a standardized surgical procedure of enucleation concerning the incidence of PEP and its relation to further preoperative and postoperative data. PATIENTS AND METHODS: A standardized questionnaire was sent to all enucleation patients with primary orbital implant performed between 1/1/1986 and 12/31/1995 at Münster University. Data of 94 patients could be analyzed with regard to PEP, perioperative pain symptoms and further ophthalmological and surgical data. RESULTS: 24 of 94 patients reported PEP after enucleation. The frequency of PEP was less than once per month in the majority of patients (71%). 2 of 24 patients suffered from PEP on more than 4 days/month. Perioperative pain symptoms (ocular pain [OP], preoperative and postoperative headache) were reported with a higher proportion (each p<0.0025) in patients with PEP compared to those not affected by PEP. All patients with a preoperative history of OP longer than 5 years and 75% of patients with OP longer than 12 months of pre-enucleation OP were affected by PEP. CONCLUSIONS: Phantom eye pain is present in nearly 1/4 of patients after enucleation and is significantly related to other perioperative pain symptoms.

Phantom eye syndrome: Its prevalence, phenomenology, and putative mechanisms.

This study presents data on the clinical characteristics and possible mechanisms of the phantom eye syndrome in 112 patients after removal of one eye. The prevalence of phantom eye pain was 26%, nonpainful phantom sensations 29%, and visual hallucinations 31%. Headaches and preoperative eye pain were associated with the presence of phantom experiences. These results suggest that pain is an important cofactor for the development of phantom eye phenomena.

[HIV-associated cerebral toxoplasmosis -- review and retrospective analysis of 36 patients]. / HIV-assoziierte zerebrale Toxoplasmose. Ubersicht und retrospektive Analyse von 36 Patienten.

Highly active antiretroviral therapy (HAART) has resulted in a reduction of morbidity and mortality in HIV-associated cerebral opportunistic infection. Before HAART, up to 50% of all HIV-infected patients in Europe developed cerebral toxoplasmosis, an encephalitis caused by reactivation of Toxoplasma gondii infection. Although potent therapeutical options exist, the prognosis is still poor. We describe the course of 36 AIDS patients with cerebral toxoplasmosis and present a review of clinical signs, diagnosis, therapy, and survival times. The main criteria for differential diagnosis from other secondary neuromanifestations such as primary CNS lymphoma, progressive multifocal leukencephalopathy, abscesses, and ischemic infarctions are described. Indications and problems of stereotactic biopsy are discussed.

[Progressive multifocal leukoencephalopathy (PML) in chronic lymphatic leukemia (CLL). Review of the literature and case report]. / Progressive multifokale Leukoenzephalopathie (PML) bei chronisch lymphatischer Leukämie (CLL). Literaturübersicht und Fallbeschreibung.

Progressive multifocal leukoencephalopathy (PML) is an infectious disease of the central nervous system caused by the JC virus. Progressive multifocal leukoencephalopathy represents a reactivation of the JC virus after long-standing immunosuppression. Also, PML plays an important role as an opportunistic infection in patients with AIDS. The average time of survival in patients with PML in combination with chronic lymphatic leukemia (CLL) (n = 17 in the literature) is 4.3 months, and therapeutic options are not established. We report the case of a patient with CLL and PML. Clinical symptoms are slight hemiparesis of the right side, mainly appearing as a disturbance of motor function. In MRI, a typical subcortical lesion was shown, and JC virus DNA was positive in the CSF by PCR. Because of first positive results in treatment of PML in patients with AIDS, therapy with cidofovir was started. After treatment for 16 months, symptoms are stable, the PML-induced lesions in MRI are in regression, and JC virus DNA is not detectable in the CSF.

[Primary central nervous system lymphoma as a neurological manifestation of AIDS stage]. / Primäres Lymphom des zentralen Nervensystems als Neuromanifestation im AIDS-Stadium.

In patients infected with human immunodeficiency virus (HIV), the risk of developing non-Hodgkin's lymphoma is over 100 times greater than with noninfected persons. Primary central nervous system lymphoma as a complication of the acquired immunodeficiency syndrome (AIDS) occurs in up to 2.4% of all cases and is strongly associated with the Epstein-Barr virus. The prognosis is very poor, with a mean survival time of 21 to 27 days without therapy and up to 119 days with radiation therapy. We describe the course of seven AIDS patients with histologically proven primary central nervous system lymphoma and present a review of clinical symptoms, diagnosis, and therapy. The main criteria for differential diagnosis from other secondary neuromanifestations such as cerebral toxoplasmosis, progressive multifocal leukoencephalopathy, abscesses, and infarctions are described.

[Pain therapy in HIV-associated polyneuropathy]. / Schmerztherapie bei HIV-assoziierter Polyneuropathie.

Only some patients with HIV-infection receive an adequate pain therapy. In later stages of HIV-infection up to 50% 6 of patients perform extraordinary doctor visits because of pain. Principally primary and secondary neuromanifestations of HIV-infection have to be differentiated. Rare forms of HIV-associated polyneuropathies represent mononeuropathy or mononeuritis multiple acute and chronic inflammatory demyelinating polyneuropathy and polyneuropathy caused by opportunistic infections. HIV-associated distal-symmetric polyneuropathy represents the most common form during HIV-infection with a prevalence up to 50%. Typical clinical symptoms and signs are pain, hyp- and dysaesthesia, diminuted deep tendon reflexes, motor deficits and autonomic disturbances. Always neurological examination and neurophysiologic investigation on the sural and peronaeal nerve are necessary for monitoring progression of polyneuropathy and as basics before starting antiretroviral therapy with neurotoxic substances. According to momentary opinion, HIV-associated distal-symmetric polyneuropathy represents no indication for antiretroviral therapy. Symptomatic therapy includes antiepileptic medication as gabapentine, antidepressive drugs as amitiptyline and additionally retarded opiates. Depressive disorders ma y accentuate pain problems a n d need psychotherapeutic and thymoleptic therapy. Special problems occur when neurotoxic substances evoke or deteriorate polyneuropathy. In these cases an individual therapeutic proceeding about continuation or discontinuation of neurotoxic medication is necessary. Symptoms of myopathy during HIV-infection are muscle pain, elevation of CK and typical changes of motor units detected by electromyography. In most cases biopsy is necessary for diagnosis of specific forms of HN-associated myopathy. HIV-associated polymyositis is treated by non-steroid analgetics, corticoids, immunoglobulines and plasmapheresis, myopathy induced by neurotoxic medication analogous to polyneuropathy.

[Acute psychiatric symptoms as the initial manifestation of HIV-infection: differential diagnosis, therapy and medico-legal issues]. / Psychiatrische Akutsymptomatik als Erstmanifestation einer HIV-Infektion. Differentialdiagnostische, therapeutische und medizinrechtliche Probleme.

The prevalence of psychiatric symptoms and disorders in HIV-infected patients is high. The differential diagnosis includes psychoreactive disorders, acute psychiatric symptoms of an HIV-associated encephalopathy, and symptomatic psychotic illnesses due to secondary neurologic manifestations such as opportunistic central nervous infections and intracerebral lymphoma. Clinical aspects and psychopathological findings are not sufficient for differential diagnosis and identification of primarily psychiatric disorders. Secondary neurologic manifestations causing a symptomatic psychosis must be excluded as soon as possible by brain imaging (CT, MRI) and analysis of the cerebrospinal fluid. In emergency situations, however, German law imposes strict regulations, especially in the case of sectioned patients. These medical and medicolegal questions are illustrated by case reports and propositions for an effective strategy are made.