Objective-To determine the change of incidence and prevalence of neurological disorders caused by the human immunodeficiency virus (HIV) and opportunistic infections in HIV positive patients under treatment since the introduction of highly active antiretroviral therapy (HAART). Methods-The data of all HIV infected patients were retrospectively analysed, who were examined in the HIV outpatients clinic of the neurological department of the University Clinic Essen between 1995 and 1998 (n=563, total number of visits-=735). Data from identified patients were divided into two groups according to the time of examination from 1995 to 1996 (334 visits) and from 1997 to 1998 (401 visits). The incidence and prevalence of neurological disorders were statistically compared between both time intervals. Results-Significantly more patients received HAART in 1997-8 (p<0.001) and mean CD4+ cell count was significantly higher in 1997-8 (p<0.001). The prevalence of HIV associated dementia and HIV associated polyneuropathy were significantly lower in 1997-8 (both: p=0.02) and the incidence of toxoplasma encephalitis decreased from 5.7% in 1995-6 to 2.2% in 1997-8 (p=0.015). Based on the small number of patients significant changes in HIV associated myopathy, progressive multifocal leukoencephalopathy, cryptoccocal meningitis, and cytomegalovirusencephalitis could not be detected. Conclusion-The prevalence of the most frequent HIV associated neurological disorders and incidence of toxoplasma encephalitis decreased since the introduction of HAART. This may be due to the improvement of immunostatus by HAART as demonstrated by the higher CD4+ cell count in the later time interval. Direct antiretroviral eVects within the nervous system may be considered causative as well. The prevalence and incidence of HIV associated neurological disorders and opportunistic CNS infections decreased after introduction of HAART.

Summary:We retrospectively identified opportunistic CNS infections in 655 patients who had undergone allogeneic, syngeneic or autologous BMT or PBSCT between 1990 and 1997. Twenty-seven patients (4%) developed CNS infections. All CNS infections occurred in allogeneic BMT or PBSCT patients. The most common CNS infections were toxoplasma encephalitis (74%) and cerebral aspergillosis (18%). Furthermore, we identified one patient with candida encephalitis and one patient with viral encephalitis. Overall mortality of patients with opportunistic CNS infection was 67%. There were two different groups of toxoplasma encephalitis with a different appearance on MR imaging. The first group showed edema, but no gadolinium enhancement, whereas the second group exhibited typical MRI appearances with the exception of frequent hemorrhagic transformation. The first group had a significant shorter latency between BMT and onset of CNS infection (mean 45 days vs 180 days, P = 0.02), a significant higher daily dose of corticosteroids as treatment for graft-versus-host disease (GVHD) (P = 0.01), more severe GVHD and a higher mortality (71% vs 36%). This study shows that the most common CNS infections in our patient population are toxoplasma encephalitis and cerebral aspergillosis, that there are two distinct subgroups of toxoplasma encephalitis and that CNS infections occur after allogeneic BMT only. Keywords: CNS infection; cerebral toxoplasmosis; cerebral aspergillosis Both allogeneic and autologous BMT are associated with several neurologic complications secondary to the underlying disease and prolonged myelosuppression. [1][2][3][4] The use of immunosuppressive drugs such as corticosteroids and cyclosporine in order to avoid rejection of the allograft and to control graft-versus-host disease (GVHD) is another major risk factor for neurologic complications especially CNS infections. In previous studies the most common complications were cerebral hemorrhage, metabolic encephalopathy and CNS infection. 1-5 Neurologic complications were more frequent in patients when AML was the underlying disease than in other leukemia patients. 4

The aim of the study was to further determine the pathophysiology, clinical course, MRI-features and response to therapy of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), which has recently been proposed as a rare chronic inflammatory central nervous system disorder responsive to immunosuppressive therapy. Three patients with this rare entity underwent serial clinical and bimonthly MRI follow-up over a period of up to 16 months. Extensive laboratory work-up and brain biopsy were performed. Intravenous methylprednisolone or oral dexamethasone was administered as treatment, additionally cyclophosphamide in one patient. Clinically, diplopia, nystagmus, ataxia and facial paresthesia were the cardinal symptoms. Magnetic resonance imaging (MRI) disclosed patchy spot-like gadolinium enhancement in a "salt-and-pepper like appearance" in the pons, midbrain and cerebellum, in two cases with thalamic and in the other with spinal involvement. Brain biopsies demonstrated a predominantly angiocentric but also diffuse infiltration pattern by small mature lymphocytes. Treatment with steroids led to rapid clinical improvement and marked resolution of MRI lesions. As discontinuation of steroids led to clinical relapse, one patient was treated with a further course of steroids and the other with steroids and cyclophosphamide as immunosuppressive therapy. This led to stable remission with only mild clinical residue and normalization of MRI. Extensive laboratory and radiological work-up could not identify any other cause of the disease. Of note, in two cases a marked elevation of IgE in serum was found initially and throughout the course. CLIPPERS seems to be a distinct inflammatory central nervous system disorder. It shows characteristic MRI core features. Extrapontine involvement seems to be frequent. Histologically it is characterised by predominantly angiocentric infiltration by small mature lymphocytes. A pathogenetic relationship between the elevated IgE levels and the perivascular infiltrates can be presumed. It is responsive to immunosuppressive therapy and can require prolonged or maintenance treatment.

Cytomegalovirus (CMV) infection of the CNS occurs most commonly in patients with severe immunosuppression such as those with advanced HIV infection (i.e. AIDS) or those who have undergone bone marrow or solid organ transplantation. Immunocompetent patients are affected very rarely. The infection of the CNS may affect the brain (diffuse encephalitis, ventriculoencephalitis, cerebral mass lesions) or the spinal cord (transverse myelitis, polyradiculomyelitis). Diagnosis is very difficult and should be based on clinical presentation, results of imaging and virological markers. The most specific diagnostic tool is the detection of CMV DNA by polymerase chain reaction in the CSF. Treatment should be initiated promptly if CMV infection is suspected. Antiviral therapy consists of intravenous ganciclovir, intravenous foscarnet or a combination of both. Cidofovir is the treatment of second choice. Patients who experience clinical improvement or stabilisation during induction therapy should be given maintenance therapy. After immune reconstitution (in HIV-positive patients) or discontinuation of immunosuppressive therapy (in transplant recipients), maintenance therapy may be stopped. Despite therapy, the prognosis for long-term survival is very poor, especially in patients with AIDS.

To better describe seizure type, frequency, and electroencephalographic (EEG) findings in posterior reversible encephalopathy syndrome (PRES) and correlate these data with clinical and magnetic resonance imaging (MRI) data, we retrospectively assessed medical charts and EEG studies of patients with PRES treated between 2004 and 2011. Data collected included patients' underlying pathology, lesion distribution by MRI, seizure type and frequency, EEG pathologic background activity, focal pathology, and epileptogenic activity. Thirty-eight of 49 adults with PRES suffered from seizures; 17 underwent EEG and were included in the analysis. Perpetuating factors were similar to those reported in the literature. In 15 of 17 patients, MRI showed widespread involvement rather than purely occipital lesions. Nine patients had subcortical and cortical involvement. Seizures were single short grand mal (GM) in 11, serial GM in 2, recurrent GM in 2, and additional focal seizures in 2. No seizures were noted beyond the first day. After discontinuation of antiepileptic medication, no patients experienced seizure recurrence during 6-month follow-up. EEG showed diffuse theta/delta slowing in 13 patients and epileptogenic activity with focal sharp-wave and periodic lateralizing epileptiform discharges in 2 patients. Seizures in PRES are most commonly single GM and are usually of limited duration. EEG shows variable theta/delta slowing. Focal EEG pathology is seen in patients with focal seizures. Seizures occur early after disease onset and terminate spontaneously or under therapy during the first 24 h. Seizure recurrence beyond 24 h and chronic epilepsy were not seen. Seizures in PRES are frequent but appear to be uncomplicated and do not herald worse prognosis. EEG is helpful in evaluating the degree of encephalopathy and monitoring epileptic activity. Long-term antiepileptic medication does not appear to be warranted.