Cerebrospinal fluid markers of neuronal and glial cell damage to monitor disease activity and predict long-term outcome in patients with autoimmune encephalitis.

BACKGROUND AND PURPOSE: Clinical symptoms and long-term outcome of autoimmune encephalitis are variable. Diagnosis requires multiple investigations, and treatment strategies must be individually tailored. Better biomarkers are needed for diagnosis, to monitor disease activity and to predict long-term outcome. The value of cerebrospinal fluid (CSF) markers of neuronal [neurofilament light chain protein (NFL), and total tau protein (T-tau)] and glial cell [glial fibrillary acidic protein (GFAP)] damage in patients with autoimmune encephalitis was investigated. METHODS: Demographic, clinical, magnetic resonance imaging, CSF and antibody-related data of 25 patients hospitalized for autoimmune encephalitis and followed for 1 year were retrospectively collected. Correlations between these data and consecutive CSF levels of NFL, T-tau and GFAP were investigated. Disability, assessed by the modified Rankin scale, was used for evaluation of disease activity and long-term outcome. RESULTS: The acute stage of autoimmune encephalitis was accompanied by high CSF levels of NFL and T-tau, whereas normal or significantly lower levels were observed after clinical improvement 1 year later. NFL and T-tau reacted in a similar way but at different speeds, with T-tau reacting faster. CSF levels of GFAP were initially moderately increased but did not change significantly later on. Final outcome (disability at 1 year) directly correlated with CSF-NFL and CSF-GFAP levels at all time-points and with CSF-T-tau at 3 ± 1 months. This correlation remained significant after age adjustment for CSF-NFL and T-tau but not for GFAP. CONCLUSION: In autoimmune encephalitis, CSF levels of neuronal and glial cell damage markers appear to reflect disease activity and long-term disability.

Serum and cerebrospinal fluid urate levels in synucleinopathies versus tauopathies.

BACKGROUND: Low levels of serum urate are associated with a higher risk of Parkinson's disease (PD). Higher serum and cerebrospinal fluid (CSF) urate levels are associated with slower rates of clinical decline in PD and in multiple system atrophy (MSA). AIMS: To compare CSF and blood urate levels in healthy controls, patients with synucleinopathies and with tauopathies. METHODS: We investigated urate levels in serum and CSF from 18 healthy controls, 19 patients with synucleinopathies (six patients with PD and 13 with MSA), and 24 patients with tauopathies (18 with progressive supranuclear palsy and six with corticobasal degeneration). None of the patients were treated with dopaminergic medications. RESULTS: No significant differences were seen when comparing serum and CSF urate levels from controls across the parkinsonian diagnostic groups. However, in men, serum urate levels were significantly lower in the synucleinopathy group compared with the tauopathy group (P = 0.046), although with a broad overlap. CONCLUSION: Our study suggests that urate levels might provide new insights into the potential pathophysiological mechanisms underlying Parkinsonism and thereby contribute to the future management of these disorders.

Computed tomographic findings in dogs with suspected aspiration pneumonia: 38 cases (2014-2019).

OBJECTIVES: To describe computed tomographic (CT) findings in dogs diagnosed with aspiration pneumonia and to assess for any correlation with patient outcome. MATERIALS AND METHODS: Retrospective analysis of 38 cases with a presumptive diagnosis of aspiration pneumonia at two UK referral centres. Medical records were reviewed for signalment, history, physical examination and clinicopathologic data. CT examinations of the thorax were reviewed by the European College of Veterinary Diagnostic Imaging board-certified radiologist for all dogs to describe the characteristics and distribution of the pulmonary lesions. RESULTS: The most common CT findings were lung lobe consolidation associated with air bronchograms (100%) followed by ground-glass attenuation (89.4%), bronchial wall thickening (36.8%), bronchiolectasis (31.5%) and bronchiectasis (15.7%). Large-breed dogs were overrepresented. Duration of hospitalisation ranged between 0 and 8 days (mean 3 days). Overall, 89.4% of dogs survived the aspiration event and were discharged from the hospital. The four dogs that did not survive to discharge had five or more lobes affected on CT. CLINICAL SIGNIFICANCE: CT findings in dogs with aspiration pneumonia are described. CT is a useful imaging modality to diagnose aspiration pneumonia.

Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson's disease.

OBJECTIVES: Cerebrospinal fluid (CSF) levels of neurofilament triplet protein (NFL), a non-specific marker of neuronal damage, are normal in Parkinson's disease (PD) but increased after brain trauma and in several neurological disorders. Using longitudinal CSF-NFL measurements as an indicator of neuronal damage, this study investigated the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the brain, directly following the surgical intervention and in chronically treated patients with PD. MATERIALS AND METHODS: CSF-NFL levels were measured consecutively in eight patients with PD before and after STN-DBS treatment. RESULTS: CSF-NFL levels were normal prior to STN-DBS and increased sharply during the first 2 weeks post-operatively, but normalized after 12 months or more. CONCLUSION: The STN-DBS procedure leads to an acute but limited neuronal damage, as expected. However, normal CSF-NFL levels at 12 months post-operatively and beyond suggest the absence of any long-term neuronal damage caused by long-term STN-DBS stimulation.

Multidisciplinary management and outcome in subdural empyema--a case report.

Cranial subdural empyema (SDE), a localized septic intracranial collection, occurs mostly as a complication of sinusitis, otitis or mastoiditis. Although relatively rare, SDE requires an increased attention for early recognition, cerebral imagery being mandatory in any suspected case. Any delay in treatment can lead to coma with a fatal outcome. The authors report the case of a young boy, who developed a severe, important cerebral edema, thin subdural collection with minimal displacement of the median line. Repeated cerebral MRI showed an enlarged subdural collection with higher median line shift and imposed rapid surgical intervention. The collection proved to be empyema. Other findings on MRI are pansinusitis, mild mastoiditis and transverse sinus thromboflebitis. The recovery was accompanied by the need for long course of antibiotherapy, secondary epilepsy treatment and kinetotherapy for hemiparesis. The patient also developed intracerebral cysts expanding the brain through the postoperative cranial defect which later needed surgical intervention, for both neurological and esthetic improvement. The management of the case implied strong interdisciplinary collaboration between infectionist, neurologist, neurosurgeon, microbiologist and imagist.

Comparison of apomorphine and levodopa infusions in four patients with Parkinson's disease with symptom fluctuations.

BACKGROUND: Motor fluctuations in patients with advanced Parkinson's disease may be successfully treated with subcutaneous apomorphine infusion or intraduodenal levodopa/carbidopa infusion. No comparative trials of these two alternatives were performed. AIMS OF THE STUDY: We present a subanalysis from a randomized crossover clinical trial where levodopa infusion as monotherapy was compared with any other combination of pharmacotherapy in fluctuating patients. Four patients used apomorphine infusion and oral levodopa in the comparator arm. The results of these four patients are presented in detail. METHODS: The duration of the trial was 3 + 3 weeks. Patients were video-recorded half-hourly on two non-consecutive days of both treatment arms. Blinded video ratings were used. Patient self-assessments of motor function and quality-of-life (QoL) parameters were captured using an electronic diary. RESULTS: Ratings in moderate to severe "off" state ranged 0-44% on apomorphine infusion and 0-6% on levodopa infusion. Moderate to severe dyskinesias were not recorded in any of the treatments. QoL was reported to be improved in all patients on duodenal levodopa infusion. CONCLUSIONS: Monotherapy with duodenal infusion of levodopa was more efficacious and brought greater QoL than combination therapy with apomorphine infusion in these fluctuating patients.

Neuronal differentiation and long-term culture of the human neuroblastoma line SH-SY5Y.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in industrialized countries. Present cell culture models for PD rely on either primary cells or immortal cell lines, neither of which allow for long-term experiments on a constant population, a crucial requisite for a realistic model of slowly progressing neurodegenerative diseases. We differentiated SH-SY5Y human dopaminergic neuroblastoma cells to a neuronal-like state in a perfusion culture system using a combination of retinoic acid and mitotic inhibitors. The cells could be cultivated for two months without the need for passage. We show, by various means, that the differentiated cells exhibit, at the molecular level, many neuronal properties not characteristic to the starting line. This approach opens the possibility to develop chronic models, in which the effect of perturbations and putative counteracting strategies can be monitored over long periods of time in a quasi-stable cell population.

Urate as a marker of development and progression in Parkinson's disease.

Urate, a natural antioxidant and iron chelator, has emerged as a potentially promising compound that might prevent neurodegenerative disorders. However, hyperuricemia may cause gout and is associated with increased cardiovascular morbidity. This paper summarizes the impact of urate in the context of Parkinson's disease (PD). It reviews the association of serum urate with the risk of PD, the clinical progression in PD, cognitive, dietary and gender aspects, the relationship between gout and PD, and potential therapeutic implications for the future.

[Peptic ulcer disease in liver cirrhosis: role of Helicobacter pylori infection and therapeutic approach]. / Maladia peptica in ciroza hepatica: rolul infectiei cu Helicobacter pylori si conduita terapeutica.

Peptic ulcer has frequently been associated with liver cirrhosis. The death rate for peptic ulcer in cirrhotics has been reported to be five times higher than in general population. The underlying mechanisms are poorly understood. Different factors have been claimed to be involved, such as alterations in serum gastrin level, gastric acid secretions, mucosal blood flow and decreased prostaglandin production in gastric mucosa. Moreover, Helicobacter pylori infection, when accurately assessed, is detectable in most peptic ulcer cirrhotics. Since the H. pylori infection strongly correlates with peptic ulcer in general population, it is necessary to clarify the role of H. pylori in the pathogenesis of peptic ulcer in cirrhosis before eradication can be proposed as a preventive measure.

Efficacy of Helicobacter pylori eradication therapy in cirrhotic patients with peptic ulcer disease.

UNLABELLED: Few studies have been focused on the role of Helicobacter pylori eradication in cirrhotic patients with peptic ulcer and the reported results are conflicting. AIM: To evaluate the efficacy of proton pump inhibitor (PPI)-based triple therapy on peptic ulcer course in patients with liver cirrhosis. MATERIAL AND METHODS: This prospective study was carried out in a tertiary-care hospital. Of the 63 consecutive cirrhotic patients with peptic ulcer identified by endoscopy 39 (22 males, 14 females, aged 53 to 62 years) entered the study. The patients with peptic ulcer and H. pylori infection received eradication therapy, while H. pylori negative patients received PPI treatment. H. pylori eradication was confirmed by rapid urease test and histological examination. Follow-up endoscopies were performed at 6 and 12 months. The patients with peptic ulcer recurrence were treated with PPI. RESULTS: Of the 39 selected patients 22 (56.4%) were H. pylori positive, and 17 (43.6%) were H. pylori negative. H. pylori was eradicated in 63.6% (14/22) of the patients. During the follow-up period 2 H. pylori negative patients died from variceal bleeding and hepatic encephalopathy, respectively, and one H. pylori positive patient did not return for further assessment). Ulcers recurring within 1 year were found in 14 of 36 (38.8%) patients. Peptic ulcer recurred in 4 of 21 (19.0%) H. pylori positive patients and in 10 of 15 (47.6%) H. pylori negative patients at study entry. Patients' age (p = 0.018), Child-Pugh stage (p = 0.019), peptic ulcer site (p = 0.008), and H. pylori negative status (p = 0.004) were significantly related to ulcer recurrence. CONCLUSIONS: Eradication of H. pylori infection in patients with liver cirrhosis and peptic ulcer disease could be helpful, but does not protect all cirrhotic patients from peptic ulcer recurrence. Most relapsed ulcers were gastric ulcers in H. pylori negative patients.

[Some unedited scientific letters to the Physicians' and Naturalists' Society of Iasi, in the period of 1830-1860]. / Aspecte inedite ale corespondentei stiintifice catre societatea de medici si naturalisti din Iasi în perioada 1830-1860.

The princely Moldavian Society of Natural Sciences and Medicine in Jassy received many foreign letters from correspondent members during the period of 1830 through to 1860. Most of the letters received were from German speaking countries and were addressed to one of the most famous members of the mentioned society in Jassy, Dr. Jacob von Czihak. He was born in Aschaffenburg in Bavaria to Czech parents and was educated in German schools. He went on to the University of Heidelberg. The multiplicities of letters that arrived in Jassy and that were found in the Romanian state archive in our time make it impossible to mention in detail, in a singe article. Therefore, I have chosen only three of them to analyze now. They are the letters from Mr. Prof. J.J. Berzelius (Stockholm), Mr. Dr. P. J. Cretzschmar (Frankfurt am Main) and Mr. Prof. J.B. Wilbrand (Giessen). The full list of correspondent members to the society in Jassy can be read in the who-is-who of the scientific world of there time. The reason I have chosen to mention these letters in my article was that they were exemplary to most I found and analyzed. They helped the members of the society in Jassy to keep contact with the scientific people during the beginning of the scientific awakening of the western European world.

Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030.

Based on published prevalence studies, we used two different methodologies to project the number of individuals with Parkinson disease (PD) in Western Europe's 5 most and the world's 10 most populous nations. The number of individuals with PD over age 50 in these countries was between 4.1 and 4.6 million in 2005 and will double to between 8.7 and 9.3 million by 2030.

Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease.

OBJECTIVES: To compare daytime intraduodenal levodopa/carbidopa infusion as monotherapy with individually optimized conventional combination therapies in patients with advanced Parkinson disease (PD) for motor fluctuations and quality of life (QoL). METHODS: Twenty-four patients with motor fluctuations and dyskinesia were studied in a randomized crossover design to compare individualized conventional treatment and intraduodenal infusion of a levodopa/carbidopa gel for 3 + 3 weeks. Video scoring of motor function was assessed by blinded assessors on a global Treatment Response Scale from -3 to 0 to +3 (from severe "off" to "on" to "on" with severe dyskinesia). Patient self-assessment of motor performance and QoL was done using an electronic diary. RESULTS: Median percentage of ratings in a functional "on" interval (-1 to +1) was increased from 81 to 100% by infusion therapy (p < 0.01). This improvement was accompanied by a decrease in "off" state (p < 0.01) and no increase in dyskinesia. Median Unified Parkinson's Disease Rating Scale score decreased from 53 to 35 in favor of infusion (p < 0.05). QoL was improved, using the two instruments: Parkinson's Disease Questionnaire-39 and 15D Quality of Life Instrument (p < 0.01). Adverse events were similar for both treatment strategies. CONCLUSIONS: Continuous intraduodenal infusion of the levodopa/carbidopa enteral gel as monotherapy is safe and clinically superior to a number of individually optimized combinations of conventional oral and subcutaneous medications in patients with motor fluctuations. Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease.

[Nonalcoholic and alcoholic steatohepatitis]. / Steatohepatita nonalcoolica si alcoolica.

NASH (Nonalcoholic Steatohepatitis) and ASH (Alcoholic Steatohepatitis) are both diseases with increase frequency which may complicate up to 50% of liver cirrhosis. They are considered as risk factors for liver carcinoma. In order to diminish the incidence of liver cancer, NASH and ASH need a close follow-up. These two entities need to be known not only by gastroenterologist, but also by general practitioners, endocrinologists, nutritionists and cardiologists.