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.

Objective: The aim of our study was to investigate whether an antiretroviral regimen including ABC and AZT can be used to improve or maintain neuropsychological and neurophysiological parameters and effectively suppress HIV Viral Load (VL) in the Cerebrospinal Fluid (CSF). Design: An open prospective observational study Methods: 11 HIV-infected patients of all disease stages were assessed at four visits: before combined antiretroviral treatment (cART) was started or changed as well as 6, 12 and 24 months later. At each visit subjects underwent comprehensive neuropsychological (NP) testing as well as neurological and neurophysiological exam. HIV VL was measured in paired plasma and CSF samples. NP results were compared to a historical untreated matched control group and correlated to HIV duration, viral load as well as CD4 nadir. Results: 3 patients fulfilled the criteria of Asymptomatic Neurocognitive Impairment (ANI) at baseline. A group comparison to the untreated control group at baseline revealed significantly worse results in the study population in 4 cognitive domains: executive and visuoperceptual functions, figural memory and verbal fluency. Executive function correlated significantly with the CSF viral load. At the end of the observational time all treated study patients showed normal NP performance while the untreated controls deteriorated in motor functions. Conclusions: HIV-individuals, who were treated with the CNS penetrating drugs ABC and AZT, have shown neurocognitive improvement compared to an untreated control group suggesting that this treatment may prevent neurocognitive impairment in HIV infection.

Cognitive deficits are often observed during the acute stage of encephalitis. It is presumed, that they persist and influence the long-term outcome, but data are very limited. Forty-seven patients with a definite or highly probable diagnosis of acute encephalitis were identified through retrospective analysis and prospectively followed up 6-84 months after the acute illness. P3 was carried out by oddball auditory paradigm, and P3 latency was measured as a marker of cognitive impairment. Healthy people, who matched the patients in age, were used as controls (n = 39). Statistical group analysis revealed no significant difference of the P3 latency between the patient and the control group. However a subgroup analysis showed significant longer P3 latencies in patients with a more unfavorable functional outcome at the time of follow-up. Patients with Herpes simplex virus (HSV) encephalitis had also more often abnormal P3 values compared to other etiologic subgroups, potentially indicating a higher percentage of patients with unfavorable cognitive outcome in this subgroup.

Acute encephalitis is a rare disease mainly occurring sporadically. Only limited data as to the long-term prognosis in particular for the regeneration of cognition is available. This study investigated prospectively what influence encephalitis has on cognitive parameters. People who matched the patients in age, gender and level of education were used as a control group. The period between the acute illness and the follow-up investigation amounted to 6 to 93 months. The study showed a favourable outcome in most of the patients. Impaired executive and motivation functions were the most common findings independent of the cause of encephalitis. Post-encephalitis epilepsy revealed to have a negative effect on cognitive rehabilitation.

Akute Enzephalitiden sind seltene Erkrankungen. Es existieren nur wenige Untersuchungen bezüglich der kognitiven Langzeiterholung dieser Patienten. Nachfolgende neuropsychologische Studie untersuchte prospektiv kognitive Langzeitfolgen in Patienten nach einer durchgemachten akuten Enzephalitis und verglich sie mit Alters- Geschlechts- und Bildungsgematchten Kontrollpersonen. Die Zeit zwischen Untersuchung und Akutereignis betrug 6 – 93 Monate. Die Ergebnisse zeigten in der Mehrzahl eine positive kognitive Erholung. Im Vordergrund standen unabhängig von der Ätiologie der Enzephalitis Störungen des Antriebs und der Exekutivfunkionen. Eine postenzephalitische Epilepsie erwies sich als negativer Risikofaktor für die kognitive Rehabilitation.

Purpose: Acute encephalitis is a rare disease mainly occurring sporadically. Only limited data as to the long-term prognosis, in particular for impact on quality of life, is available. Methods: Patients with a definite or highly probable diagnosis of acute encephalitis were identified through retrospective analysis and invited to undertake a structured interview and to fill in questionnaires regarding their quality of life. People who matched the patients in age, sex, and level of education were used as controls. Results: Seventy-two patients and 57 controls were included. The period between the acute illness and the follow-up amounted to 6 to 93 months. The study showed a favorable outcome with complete or far-reaching functional recovery in most of the patients (83.3%). In cases that progressed in an unfavorable way such that cognitive handicaps were dominant, only 4% were left with extreme physical handicaps. Approximately 22% had postencephalitic epilepsy, which was correlated to a significantly more unfavorable outcome (P < 0.05). Women who have had encephalitis were significantly more depressive than men (P < 0.001) and also noticeably more depressive than female control subjects (P < 0.01). Furthermore, postencephalitic epilepsy was linked with significantly stronger likelihood of depression (P < 0.05). Conclusions: In this study, most patients had a favorable outcome with complete or far-reaching functional recovery. Postencephalitic epilepsy is a risk factor for an unfavorable outcome and a factor that might hinder coping with the sequelae of acute encephalitis in the long term and that has a negative effect on mood.

Background The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question. Design GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage. Conclusion 372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients. Trial Registration Current Controlled Trials ISRCTN45122933

to the left due to paresis of the left pterygoid muscle. The corneal refl ex was positive on both sides. All other neurological systems were regular. In particular, there were no sensory disturbances and no signs of polyneuropathy. Electromyography did not detect pathological spontaneous activity (most probably due to massive atrophy and chronicity of the process), but showed a single unit interference pattern during maximal voluntary contraction in the left masseter muscle and motor unit action potentials with amplitudes of 4 mV. Myopathic changes were absent. Other laboratory parameters were regular, e.g., C-reactive protein, creatine kinase, myoglobin, and blood cell count. A brain magnetic resonance imaging (MRI) scan did not detect any pathology, in particular no lesion of the pons or the mandibular trigeminal nerve branch. However, pronounced left-sided masseteric atrophy was clearly depictable on MRI images ( fi g. 1 ). Altogether, there was massive atrophy and paresis of the left jaw muscles without any sensory facial disturbances, indicating pure motor trigeminal neuropathy. Electromyography confi rmed chronic denervation of the left masseter muscle. Lumbar puncture was declined. Dear Sir, Facial asymmetry often occurs because of unilateral facial nerve paresis. Here, we report on a HIV-positive patient with progressive facial asymmetry due to unilateral motor trigeminal neuropathy.

Prognosis of patients with ischemic stroke requiring mechanical ventilation (MV) has been reported to be poor. However, longterm survival and functional outcome have scarcely been studied and nothing is known about the prevalence of cognitive impairment or depression in survivors and their quality of life (QoL). We identified all patients treated for acute ischemic stroke on a Neurological Intensive Care Unit during 3.5 years who required MV for more than 24 hours. Early mortality rate at 2 months and survival rates at 1 and 2 years were determined. Survivors were examined for functional outcome (modified Rankin Scale (mRS), Barthel Index), cognitive impairment (Mini Mental State Examination (MMSE)), depression (Beck Depression Inventory, BDI) and QoL (Short Form-36). Clinical characteristics on admission were analyzed for prognostic significance. Of 101 consecutive patients, 44% died within 60 days. Survival rates at 1 and 2 years were 40% and 33%, respectively. Age > 60 years (p = 0.002) and Glasgow Coma Scale score < 10 on admission (p = 0.002) were independent predictors of early and late mortality. History of myocardial infarction (p = 0.007) independently predicted late mortality at 2 years. Of 33 surviving patients, nine (27%) had a good functional outcome (mRS 0-2). Of 27 survivors who could be interviewed, 17 (63%) had no cognitive impairment (MMSE > 24) and 20 (74%) did not suffer from relevant depression (BDI < 19). In conclusion, longer-term survival of patients with ischemic stroke requiring MV was 33% and every fourth survivor resumed an independent life without dementia or depression. Older patients comatose on admission and with concomitant cardiovascular disease had the lowest probability of a favorable outcome.

Neurological complications are very frequent in patients with infective endocarditis (20–40 %). In these patients it is unclear at what time a valve replacement should be performed. In order to develop a data based recommendation we studied 12 patients of our own and analyzed 228 patients from the literature. We included patients with valve replacement after a neurological complication of endocarditis and documented the time between manifestation and operation and the outcome. Based on these 240 patients we calculated the risk of neurological deterioration after the valve replacement. After brain infarction this risk is 20% within three days, 20–50% between day 4 and 14, but declines to < 10% after 14 days and < 1% after 4 weeks. Valve replacement within the first four weeks after intracranial hemorrhage has been reported to be successful only in individual cases. The risk of deteriorating declines later to 15%. Based on these limited data we suggest that valve replacement in patients with brain infarction should be considered within the first 72 hours if they have severe heart failure, otherwise after four weeks. Only a few selected patients with intracranial hemorrhage and progressive heart failure might benefit from valve replacement within the first four weeks. For all other neurological complications there are no reliable data. We propose a structured approach depending on cardiac and neurological complications and the time course of the disease.

We have recorded postural performance in 50 HIV-infected patients in different stages of the disease (Walter Reed (WR) stages I–VI) by means of a force measuring platform. The results were compared with 50 age-matched controls. A significant instability was particularly evident when standing on an unstable foot support. In patients standing with “eyes closed”, postural sway was significantly higher in every patient group (WR I–II:P<0.02, WR III–V:P<0.001, WR VI:P<0.001). Patients in stage WR I–II showed no relevant neurological abnormalities. In agreement with other neurophysiological data in the literature we suggest that postural imbalance could be an early sign of central nervous system penetration of HIV. No correlation with electromyographic or cerebrospinal fluid findings could be found.

Zwei Jahre nach Gottliebs Erstbeschreibung (1981) des erworbenen Immundefektsyndroms (AIDS) berichteten Snider et al. (1983) über neurologische Komplikationen bei 50 AIDS-Patienten. Dem folgten zahllose Einzelfalldarstellungen wie auch mehrere Untersuchungen an größeren Kollektiven, wovon insbesondere die Arbeiten von Levy et al. (1985) sowie Enzensberger u. Fischer (1987) zu erwähnen sind.