Postural muscle responses to multidirectional translations in patients with Parkinson's disease

The postural adaptation impairments of patients with Parkinson's disease (PD) suggest that the basal ganglia may be important for quickly modifying muscle activation patterns when the direction of perturbation or stance conditions suddenly change. It is unknown whether their particular instability to backward postural perturbations is due to specific abnormalities of parkinsonian postural muscle synergies in that direction and not present in other directions. In the present study, we test this hypothesis by comparing the patterns of leg and trunk muscle activation in 13 subjects with PD and 13 control subjects in response to eight randomly presented directions of horizontal surface translations while standing with either narrow or wide stance. The direction of maximum activation for each muscle was similar for PD and control subjects, suggesting that the basal ganglia is not critical for programming externally triggered postural synergies. However, antagonist muscle activation was earlier and larger in PD than in control subjects, resulting in coactivation. PD subjects also did not increase the magnitude of muscle activation as much as did control subjects when changing from wide to narrow stance. These results are consistent with the hypothesis that PD results in an inability to shape the pattern and magnitude of postural muscle responses for changes in perturbation direction and in stance position.     

Tumor necrosis factor-mediated inhibition of interleukin-18 in the brain: a clinical and experimental study in head-injured patients and in a murine model of closed head injury.

Tumor necrosis factor (TNF) and interleukin-(IL)-18 are important mediators of neuroinflammation after closed head injury (CHI). Both mediators have been previously found to be significantly elevated in the intracranial compartment after brain injury, both in patients as well as in experimental model systems. However, the interrelation and regulation of these crucial cytokines within the injured brain has not yet been investigated. The present study was designed to assess a potential regulation of intracranial IL-18 levels by TNF based on a clinical study in head-injured patients and an experimental model in mice. In the first part, we investigated the interrelationship between the daily TNF and IL-18 cerebrospinal fluid levels in 10 patients with severe CHI for up to 14 days after trauma. In the second part of the study, the potential TNF-dependent regulation of intracerebral IL-18 levels was further characterized in an experimental set-up in mice: (1) in a standardized model of CHI in TNF/lymphotoxin-alpha gene-deficient mice and wild-type (WT) littermates, and (2) by intracerebro-ventricular injection of mouse recombinant TNF in WT C57BL/6 mice. The results demonstrate an inverse correlation of intrathecal TNF and IL-18 levels in head-injured patients and a TNF-dependent inhibition of IL-18 after intracerebral injection in mice. These findings imply a potential new anti-inflammatory mechanism of TNF by attenuation of IL-18, thus confirming the proposed "dual" function of this cytokine in the pathophysiology of traumatic brain injury.     

Obsessive-compulsive bipolar comorbidity: focus on children and adolescents

BACKGROUND: Growing evidence documents the frequent co-morbidity between Obsessive Compulsive Disorder (OCD) and Bipolar Disorder (BP) in adults. The aim of the present study is to explore some clinical aspects of this interface in children and adolescents, as it appears in a setting of routine clinical practice. METHOD: The sample comprised 102 consecutively referred children and adolescents, both inpatients and outpatients, with BP, OCD or co-morbid BP-OCD during a 3-year period. The mean age was 14.2 (SD=3.2); 65 (63.7%) were males. Diagnoses and clinical features were collected by means of structured interview according to DSM-IV (DICA-R) and a rating scale for OCD (CY-BOCS). Clinical outcome was evaluated prospectively by means of clinical global impression (CGI) as part of routine clinical care, throughout the follow-up. RESULTS: Thirty-seven (36.3%) patients (21 males and 16 females) were diagnosed as BP, 35 (34.3%) patients (26 males and 9 females) were diagnosed as OCD and 30 (29.4%) patients (18 males and 12 females) were diagnosed as BP-OCD. BP II, was more frequent in the BP-OCD than in BP. When OCD was co-morbid with BP, age of onset was significantly earlier than in the 'pure' OCD patients. On the contrary, age of onset of BP was not affected by co-morbid OCD. According to CGI baseline scores, OCD patients were significantly less impaired than BP-OCD and BP patients, while the severity of the symptomatology was similar in the last two groups. Severity scores at the end of the follow-up were significantly higher in BP-OCD patients than in OCD patients. Patients with pure BP showed lower rates of panic disorder-agoraphobia than BP-OCD patients and higher rates of ADHD-conduct disorder. Pure OCD patients showed lower rates of ADHD and higher rates of Generalized Anxiety Disorder. The number of obsessions did not differentiate the two groups, whereas pure OCD patients showed significantly more compulsions. 'Other' obsessions-e.g., existential, philosophical, odd and/or superstitious-were significantly more frequent in BP-OCD than in pure OCD patients. Ordering compulsions were significantly more frequent in pure OCD patients. LIMITATIONS: Possible low reliability of children's and their parents' recall of past episodes of mental disorder. CONCLUSIONS: In a tertiary care center, co-morbidity between OCD and BP is a significant clinical problem affecting a large number of patients. The correct identification of OCD-bipolar co-morbidity has relevant clinical implications as far as other concomitant disorders, symptomatological features, course, complications, and treatment management and outcome are concerned.     

Effects of task difficulty and invested mental effort on peripheral vasoconstriction

We ran two experiments to investigate whether peripheral arterial tone reflects changes in mental effort. Finger pulse wave amplitude, interpulse interval, and pulse variability in the mid- and high-frequency bands were recorded by means of a newly developed finger plethysmograph during both rest and cognitive performance. Using a modified version of the Sternberg memory task, we selectively manipulated either the difficulty of the task (Experiment 1) or the subjects' level of engagement in the task (Experiment 2). We found a significant difference in finger pulse wave amplitude between rest and task periods, suggesting that the measure reflects changes in sympathetic activity due to task engagement. In addition, our results suggest that reduced pulse wave amplitude, signaling vasoconstriction, occurs when subjects are investing effort.     

The modification by ketotifen of respiratory responses to histamine and antigen in guinea-pigs

Aerosolized solutions of histamine or ovalbumin were administered to control or ovalbumin-sensitized guinea-pigs. The time to onset of respiratory distress (preconvulsion time) during challenge with these agents was measured using a force-displacement transducer on the animal's back. The preconvulsion time for each guinea-pig was compared with and without ketotifen pretreatment. Ketotifen administered both by aerosol and intraperitoneal injection (i.p.) significantly protected (p<0.001) each guinea-pig from the effects of aerosol challenge with histamine. Ovalbumin-sensitized animals were also protected from the effects of antigen aerosol challenge by ketotifen pretreatment. Sodium cromoglycate (DSCG), administered as an aerosol, did not protect sensitized animals from ovalbumin challenge. The Konzett-Rössler technique was used to measure the response to the intravenous injection (i.v.) of histamine in anaesthetized artificially ventilated guinea-pigs. Ketotifen was three times more potent than mepyramine in inhibiting the histamine-induced increase in air overflow volume.     

Neuroendocrine carcinoma of the thymus: Aspiration biopsy,immunocytochemistry, and clinicopathologic correlates

We report three cases of well-differentiated neuroendocrine carcinoma originating primarily in the anterior mediastinum which had been initially investigated by fine-needle aspiration cytology in conjunction with immunocytochemistry and subsequently recognized as thymic in origin. Aspirates consisted of loosely cohesive or aggregated medium sized elements with round to oval nuclei and scanty cytoplasm. in all cases the Romanowsky stain provided an excellent delineation of definite paranuclear inclusion-like structures having a semicircular or discoid appearance which appeared to contain cytokeratin by immunocytochemical studies and were very similar to the intermediate filament paranuclear “buttons” found in neuroendocrine Merkel cell carcinoma of the skin. This appears to be a novel cytologic observation for thymic neuroendocrine carcinoma. We discuss the significance of the above cytologic and immunocytochemical findings and their possible role in the diagnosis of thymic neuroendocrine carcinoma by fine-needle aspiration biopsy. © 1995 Wiley- Liss, Inc.     

Ultrastructural Changes Suggestive of Focal Segmental Glomerulosclerosis in Atypical Minimal Change Nephrotic Syndrome

In an attempt to recognize early stages of focal segmental glomerulosclerosis (FSGS) in patients with a clinical course suggesting a diagnosis other than minimal change disease (MCD) and normal histology, or minor, nondiagnostic changes on light microscopy (LM), we used a protocol for systematic and extensive electron microscopy (EM) examination of kidney biopsies obtained from such patients. By this method ultrastructural pathology was found in 8 patients. These changes were localized, involving only portions of single glomerular segments. The findings included mild to moderate increase of the mesangial matrix, focal wrinkling of the capillary basement membrane, and early obliteration of the normal architecture of individual capillary loops, as well as electron-dense deposits in a mesangial and subendothelial distribution. Of these 8 patients, 2 are at present in remission without therapy (in 1, following therapy with cyclophosphamide); 3 are in remission on steroid therapy; 1 developed massive proteinuria during pregnancy, after a spontaneous remission lasting almost 2 years; 1 patient advanced to terminal renal failure 3 1/2 years after biopsy; and 1 died of sepsis 1 month after biopsy. We believe that the ultrastructural changes found may represent early or mild FSGS and that the protocol described can add valuable information in clinically worrisome patients in whom renal histology appears normal.     

Epidemiology,characterization, and diagnosis of neuropsychiatric events in systemic lupus erythematosus

Introduction: Neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by a heterogeneity of clinical manifestations. The absence of diagnostic criteria and the lack of clinical trials is a challenge in clinical practice.

Areas covered: A literature review was performed to describe epidemiology, characterization (clinical, immunological, and imaging), diagnosis and treatment of NPSLE. Classification criteria have been the first step towards a uniform definition. More recently, different attribution models have been developed to help to determine if the NP event is due to SLE. Disease activity is a major risk factor for NP events. Cytokines and autoantibodies are associated with NP events, however, only a few studies have identified risk factors for individual NP events.

Expert opinion: Further research needs to search for and validate biomarkers for NPSLE and individual NP events, including neuroimaging findings, attribution models, and serologic markers. This will be a fundamental step in planning randomized control trials in the treatment of NPSLE to improve outcome.