Recurrent Vertebrobasilar Strokes Associated With Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE).

INTRODUCTION: Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an ophthalmologic condition of likely immune origin. Typically, it presents as a chorioretinitis with bilateral visual disturbance and characteristic funduscopic lesions of the retinal pigment epithelium. APMPPE has been associated with several systemic and neurological complications, including cerebrovascular diseases. CASE REPORT: A 58-year-old woman presented with sudden right hemiparesis and dysarthria, with magnetic resonance imaging evidence of an acute ischemic lesion in the left pons. Five days later, she developed contralateral hemiparesis and evolved into a locked-in syndrome. A new lesion located at the right pontomedullary junction was detected by magnetic resonance imaging. The patient developed a visual deterioration that had started 1 week before admission. An ophthalmologic evaluation showed visual acuity loss (20/200 in both eyes) and characteristic yellow-white lesions in the posterior pole of both eyes. Laboratory analyses were remarkable for positive antinuclear antibodies, an elevated erythrocyte sedimentation rate, and C-reactive protein. The cerebrospinal fluid showed elevated protein levels, lymphocytic pleocytosis, and normal glucose levels. The fundoscopy findings together with recurrent strokes led to the diagnosis of APMPPE and appropriate immunomodulatory treatment with corticosteroids and azathioprine was started. CONCLUSIONS: This case illustrates the importance of careful evaluation and high clinical suspicion for this entity when dealing with patients with new-onset headache or stroke associated with visual impairment. Proper ophthalmologic evaluation is important so that adequate therapy is established.

Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia.

The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica) agents have distinct infection courses, but both require cholesterol for growth. They acquire cholesterol from the environment and process it to form cholesterol glycolipids that are incorporated onto their membranes. To determine whether higher levels of serum cholesterol could enhance the organ burdens of B. burgdorferi and the spirochetemia of B. hispanica in laboratory mice, apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)-deficient mice that produce large amounts of serum cholesterol were infected with both spirochetes. Both apoE- and LDLR-deficient mice infected with B. burgdorferi had an increased number of spirochetes in the joints and inflamed ankles compared with the infected wild-type (WT) mice, suggesting that mutations in cholesterol transport that result in high serum cholesterol levels can affect the pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient mice, the course of infection was indistinguishable from the WT mice. However, infection of apoE-deficient mice with B. hispanica resulted in a longer spirochetemia and increased mortality. Together, these results argue for the apoE deficiency, and not hypercholesterolemia, as the cause for the increased severity with B. hispanica. Serum hyperlipidemias are common human diseases that could be a risk factor for increased severity in Lyme disease.

[Challenges in the pharmacotherapeutic management of the hospitalised patient with Parkinson's disease]. / Desafíos en el manejo farmacoterapéutico del paciente ingresado con enfermedad de Parkinson.

Patients with Parkinson's disease (PD) are admitted to hospital more frequently and for a longer time than other patients from the same age group. The reason they are hospitalised is often different from their underlying baseline disease and they are usually attended in services with little knowledge of the disease. Both the errors made when administering levodopa and the inappropriate use of pharmacological agents with a central antidopaminergic action are relatively common during their stay in hospital. This study reports on an analysis of the literature available on the challenges and complications that patients with PD have to deal with when they are admitted to hospital, especially those that have to do with pharmacotherapy. Likewise, the authors also propose a series of strategies that lead to better care of the patients during the time they are in hospital, including aspects such as controlling the supplies of antiparkinsonian medication and establishing protocols for the therapeutic exchange of antiparkinsonian agents, as well as protocols for a suitable management of comorbidities in this kind of patients. Other strategies involve encouraging self-management of the antiparkinsonian treatment by the hospitalised patients, conducting follow-up studies to monitor inappropriate prescriptions or creating the figure of 'specialist in PD'. To do so, it will be necessary to raise the awareness of the healthcare staff at the hospital, as well as that of both patients and their relatives, about the problems derived from an inappropriate management of pharmacotherapy in PD.

TITLE: Desafios en el manejo farmacoterapeutico del paciente ingresado con enfermedad de Parkinson.Los pacientes con enfermedad de Parkinson (EP) ingresan en el hospital con mayor frecuencia y durante mas tiempo que los pacientes del mismo grupo etario. El motivo del ingreso es a menudo diferente de su enfermedad de base, y son habitualmente atendidos en servicios con un conocimiento pobre de la enfermedad. Tanto los errores en el momento de la administracion de levodopa como el uso inapropiado de farmacos con accion antidopaminergica central son relativamente comunes durante su estancia hospitalaria. En este estudio se lleva a cabo un analisis de la bibliografia disponible sobre los desafios y las complicaciones a los que se enfrentan los pacientes con EP cuando ingresan en el hospital, principalmente en aquellos relacionados con la farmacoterapia. Asimismo, se proponen una serie de estrategias que redunden en una atencion a los pacientes durante su ingreso hospitalario, que incluyen aspectos como el control de las existencias de medicamentos antiparkinsonianos y el establecimiento de protocolos de intercambio terapeutico de antiparkinsonianos, asi como de protocolos para el manejo adecuado de comorbilidades en este tipo de pacientes; el fomento de la autogestion del tratamiento antiparkinsoniano por parte de los pacientes ingresados; la realizacion de estudios de seguimiento de prescripciones inapropiadas o la creacion de la figura de 'especialista en EP'. Para ello sera necesario impulsar la concienciacion del personal sanitario del hospital, asi como de los pacientes y sus familiares, sobre los problemas derivados del manejo inapropiado de la farmacoterapia en EP.

Aprosodic speech with insular hyperintensities and 4R Tau pathology on autopsy.

We describe a 46-year-old woman who presented with a 2-year history of aprosodic speech together with apathy and disinhibition. Brain magnetic resonance imaging showed subcortical hyperintensities over both insular regions that later extended to both frontal and temporal cortices. The post-mortem exam showed a massive tau protein deposition throughout the brain. No mutation in the gene MAPT was detected. This case illustrates an atypical clinical-radiological presentation of a frontotemporal dementia with an unusual speech and abnormal signal of both insulae. Furthermore, it reinforces the crucial role of the insula in the development of symptoms in frontotemporal dementia.

Orbitofrontal dysfunction predicts poor prognosis in chronic migraine with medication overuse.

Chronic migraine patients are at risk of developing a medication overuse. Brain functional studies in these patients have demonstrated an orbitofrontal hypometabolism, persistent after overuse cessation. Orbitofrontal dysfunction is also present in addiction and thus could predispose migraineurs to medication overuse. The aim of this study was to investigate if orbitofrontal dysfunction can be demonstrated in patients with chronic migraine and medication overuse by performing a systematic neuropsychological evaluation focused on tests that assess frontal lobe function. Second, to establish whether it is related to the outcome of these patients. We prospectively studied 42 chronic migraine patients with medication overuse, 42 episodic migraineurs and 41 controls on a battery of neuropsychological tasks evaluating the orbitofrontal and dorsolateral functioning. Depression, anxiety, and personality traits were also assessed. Chronic migraineurs with medication overuse showed a significant impairment in orbitofrontal task performance and higher depression scores as compared to episodic migraineurs and controls. Dorsolateral dysfunction was present in both groups of migraneurs, who also had higher rates of anxiety as compared to controls. After 1 year of follow-up, migraine patient's outcome was classified according to their medication overuse status. A negative outcome that included persistent or new-onset medication overuse was present in 34% of migraineurs and was associated with baseline poor orbitofrontal task performance, and with mild dorsolateral dysfunction, higher rates of depression, anxiety and neuroticism-anxiety traits. Formal education and years with migraine did not influence outcome. Orbitofrontal dysfunction is present in patients with chronic migraine and medication overuse, and associates with a poor outcome at 1 year of follow-up. Neuropsychological evaluation in migraine may help to detect patients prone to overuse so that appropriate therapeutic attitudes can be taken.

Cholesterol lipids of Borrelia burgdorferi form lipid rafts and are required for the bactericidal activity of a complement-independent antibody.

Borrelia burgdorferi, the agent of Lyme disease, is unusual as it contains free cholesterol and cholesterol glycolipids. It is also susceptible to complement-independent bactericidal antibodies, such as CB2, a monoclonal IgG1 against outer surface protein B (OspB). We find that the bactericidal action of CB2 requires the presence of cholesterol glycolipids and cholesterol. Ultrastructural, biochemical, and biophysical analysis revealed that the bacterial cholesterol glycolipids exist as lipid raft-like microdomains in the outer membrane of cultured and mouse-derived B. burgdorferi and in model membranes from B. burgdorferi lipids. The order and size of the microdomains are temperature sensitive and correlate with the bactericidal activity of CB2. This study demonstrates the existence of cholesterol-containing lipid raft-like microdomains in a prokaryote, and we suggest that the temperature dependence of B. burgdorferi lipid raft organization may have significant implications in the transmission cycle of the spirochetes which are exposed to a range of temperatures.

Sleep improves sequential motor learning and performance in patients with prefrontal lobe lesions.

OBJECTIVES: Motor skill learning involves both practice and a latent, sleep-dependent process of consolidation that develops after training ("off-line" learning). Sleep consolidation is linked to reduced brain activation in prefrontal areas, along with strong involvement of parietal regions. The objective in this study was to investigate the influence of sleep on the consolidation process of a motor task in patients with prefrontal damage. PATIENTS AND METHODS: For that purpose 14 patients with acquired focal prefrontal lesions, 15 age-matched healthy controls, and five patients with parietal lesions were evaluated on a serial reaction time task, SRTT, before and after a night of monitored sleep. Verbal and working memory was also tested. We anticipated that patients with prefrontal lesions, who are impaired in the acquisition of motor tasks, would benefit greater from sleep than the other two groups, since consolidation does not depend on prefrontal regions. RESULTS: Prefrontal patients showed an erratic learning curve at night, with great inter- and intrasubject variability that normalized after sleep. They also showed higher overnight learning of the motor skill and improvement on speed performance on the SRTT. No differences in the other memory tests were found between sessions. CONCLUSION: Prefrontal-injured patients benefit from night sleep in terms of motor task learning and performance, likely related to an advantageous off-line learning. Sleep could play a role in motor rehabilitation programs in prefrontal patients.

Murine microglia are effective phagocytes for Borrelia burgdorferi.

Lyme disease is a multi-systemic infection that causes diverse neurologic dysfunction collectively known as neuroborreliosis. In the murine model of Lyme disease, Borrelia burgdorferi are seldom found in the nervous system indicating that the spirochetes are rapidly cleared from the brain and peripheral nerves. In the present study, we examined the interaction between microglia and B. burgdorferi. Murine microglia are efficient phagocytes and are capable of ingesting and killing spirochetes with or without opsonization.

Tissue plasminogen activator administration does not result in clinically relevant neuropsychological dysfunction in patients with myocardial ischemia.

BACKGROUND: Recent evidence from animal models has demonstrated that tPA can be neurotoxic to the hippocampus and cerebellum. Since tPA is used in patients with myocardial infarction and has been approved for the treatment of acute ischemic stroke, we carried out a pilot study to investigate whether its administration could result in any clinically relevant neuropsychological dysfunction, with particular attention to those structures most involved in the animal model. PATIENT AND METHODS: Patients with acute myocardial infarction (AMI) who were subjected to thrombolysis with r-tPA and without evidence of prior or concomitant neurological-neuropsychological damage, were eligible. Controls consisted of patients with AMI not candidate for thrombolysis or patients with severe angina admitted to the intensive care unit. A detailed neurological and neuropsychological evaluation was performed, which included mood, visual and verbal memory, psychomotor speed processing and motor dexterity and visuomotor sequence learning. RESULTS: Ten patients and 13 controls were included. No significant differences between both groups were found, although all the subjects performed in the lower limits of the normal range on the Purdue pegboard test (motor dexterity) and digit-symbol test (psychomotor speed). There was no evidence of depression, as assessed by the Hamilton scale, that could have interfered with performance. Declarative memory (Rey auditory-verbal learning test) as well as visual memory (Rey-Osterrieth figure copy) and visuomotor sequence learning (serial reaction time task) were normal, without between-group differences. CONCLUSIONS: tPA administration at the usual doses did not result in detectable neuropsychological abnormalities in patients with myocardial ischemia.