Familial amyloidotic polyneuropathy: long-term follow-up of abdominal fat tissue aspirate in patients with and without liver transplantation.

To estimate the evolution of amyloid in tissue, we studied abdominal fat aspirates of cases with familial amyloidotic polyneuropathy (FAP) longitudinally at regular intervals between 1994 and 2006. In 22 cases (13 carriers and nine patients) not yet transplanted median follow-up was 3.3 years (range 0.4-11.3). We found a significant increase in the amyloid grade of fat tissue from 2+ to 4+ and from 0 to 4+ in two of three subjects with follow-ups of >7 years, after 7 and 11 years, respectively. All other subjects remained negative or did not show a significant change. In 11 liver transplant patients, follow-up with fat aspirate was available with a median duration of 3.1 years (range 1.0-10.1). A comparison was made with cardiac amyloid as judged by the cardiac septum diameter and the serum NT-ProBNP (N-terminal pro-B-type natriuretic peptide) level. No stable increase of amyloid in fat was seen in any patient. A stable decrease of amyloid grade was seen in one patient 5 years after transplantation. In contrast, the cardiac septum diameter increased >or=4 mm in six of the 11 transplant patients. Our study shows the diagnostic utility of a regularly repeated fat aspirate in carriers at risk for the development of ATTR amyloidosis. Evolution of amyloid deposition in fat tissue is very gradual. After liver transplantation, amyloid deposition in fat tissue seems to stabilize and may even decrease in the long term, whereas amyloid deposition in cardiac tissue appears to be progressive.     

The validity of a separate classification of cryptogenic localization related epilepsy amongst childhood epilepsies.

INTRODUCTION: One-third of children with epilepsy are classified as having a cryptogenic localization related epilepsy (CLRE). In cohort studies CLRE is often grouped together with either symptomatic localization related epilepsy (SLRE) or idiopathic generalized epilepsy (IGE). Therefore, this categorization is not specific enough and will not lead to prognostic or treatment information. We objectified the classification differences between these categories. METHODS: A total of 114 children admitted to our epilepsy centre underwent a standardized clinical analysis, which yielded age at onset, duration of the epilepsy, seizure frequency, seizure type, percentage of interictal epileptiform activity on EEG (IEA), type of treatment, and full scale IQ. These variables are regarded the characteristics of the epilepsy, and used in a discriminant function analysis. RESULTS: IEA was found to be the only variable to distinguish between groups of epilepsy. SLRE could easily be distinguished significantly from IGE and CLRE, while the latter two did not differ significantly. Discriminant function analysis combined the variables into two functions, applicable to classify the children. By applying this statistical analysis method, the groups clinically classified as SLRE and IGE were mostly classified as SLRE (71.4%) and IGE (57.9%). However, CLRE appeared difficult to classify (49.2%), and most children were classified as either SLRE (19%) or IGE (31.7%). CONCLUSION: The current opinion that CLRE is 'probably symptomatic' cannot be confirmed in all cases in this study. It is most likely that the current CLRE population consists of both children with eventually SLRE, as well as yet to be described syndromes to be classified as idiopathic epilepsies. We emphasize the need for separate studies regarding children with 'probably symptomatic' (cryptogenic) localization related epilepsy, as this will maximally help children, caretakers and treating physicians to achieve the best possible outcome.     

Clinical aspects and immune reactions in sarcoidosis*

Introduction: Sarcoidosis is a granulomatous disorder of unknown aetiology, affecting young adults and frequently involving the lungs. Objective: The aim of the present review was to give an overview of the clinical aspects in sarcoidosis. Results: The majority of patients recover, but some develop a chronic disease that may result in fibrosis and respiratory failure. Besides the lungs, peripheral lymph nodes, the skin, the liver and the eyes are commonly affected as well. The genetic background, as well as environmental factors, is of importance for developing sarcoidosis. The incidence varies in different populations, in the Nordic countries approximately with 20/100 000 new patients yearly. Sarcoidosis is diagnosed when clinical and radiological findings are supported by histological evidence in the form of non‐caseating epithelioid cell granulomas, and when other causes of these features are excluded. Patients in need of treatment are usually treated with corticosteroids, topically or as oral steroids. A clinical effect of immunomodulatory drugs blocking tumour necrosis factor (TNF)α has been suggested from several case reports, while two controlled studies showed only minor effects; however, with a tendency to a more pronounced effect on patients with a more severe disease. The immune response in sarcoidosis, with a typical accumulation of CD4+ T‐cells to the lungs, indicate the existence of specific antigens in this disease. Recently, antigens derived from infectious agents such as Mycobacteria and Proprionibacterium acnes have come into focus. Lymphocyte populations with immunoregulatory functions have recently been investigated and seem to be dysfunctional in sarcoidosis, opening the possibility of developing new treatment strategies in this disease. Conclusion: Recent technical developments have provided better tools, enabling detailed and more thorough analyses of the inflammatory process in sarcoidosis. Please cite this paper as: Grunewald J. Clinical aspects and immune reactions in sarcoidosis. The Clinical Respiratory Journal 2007; 1:64–73.     

Assessment of autonomic dysfunction in Parkinson's disease: the SCOPA-AUT.

We developed a questionnaire to assess autonomic symptoms in patients with Parkinson's disease (PD) and evaluated its reliability and validity. Based on the results of a postal survey in 46 PD patients, 21 multiple system atrophy patients, and 8 movement disorders specialists, items were included according to their frequency, burden, and clinical relevance. The questionnaire was evaluated in 140 PD patients and 100 controls, and test-retest reliability was established in a sample of 55 PD patients. The SCOPA-AUT consists of 25 items assessing the following regions: gastrointestinal (7), urinary (6), cardiovascular (3), thermoregulatory (4), pupillomotor (1), and sexual (2 items for men and 2 items for women) dysfunction. Test-retest reliability was good. Autonomic problems increased significantly with increasing disease severity for all autonomic regions, except sexual dysfunction. We conclude that SCOPA-AUT is a reliable and valid questionnaire that evaluates autonomic dysfunction in PD.     

Serological investigation of canine encephalitozoonosis in Norway

Encephalitozoon cuniculi, a microsporidian parasite of vertebrates, is considered a health risk to AIDS patients and other immunocompromised human beings. In most hosts, infection with the parasite runs a subclinical course. In some carnivore species, however, clinical disease affecting whole litters arises from intrauterine transmission of the parasite. In both blue foxes (Alopex lagpus) and dogs (Canis familiaris), outbreaks of encephalitozoonosis can be severe. Canine encephalitooonosis has been reported from various parts of the world, including South Africa and the United States. In Norway, there have been large outbreaks of the disease in blue fox farms, affecting also mink, but there have been no reports of encephalitozoonosis in dogs. Infection in dogs would represent a zoonotic problem, due to the close social relationship between dog and man. The purpose of the present study was to investigate the possible occurrence of E. cuniculi infection in Norwegian dogs by serological methods. In the study, 1,104 canine serum samples, originally submitted for biochemical analysis by veterinary practitioners throughout Norway, were screened by enzyme-linked immunosorbent assay for antibodies to E. cuniculi. Samples from 237 of the dogs were tested also by the indirect fluorescent antibody test. All samples were concluded as negative. The results indicate that the likelihood of occurrence of E. cuniculi infection in Norwegian dogs is small.     

Raised intracranial pressure,the syndrome of inappropriate antidiuretic hormone secretion,and arginine vasopressin in tuberculous meningitis

Intracranial pressure (ICP) monitored shortly after admission over a period of 1 h in 31 children with tuberculous meningitis (TBM) was significantly higher (median 22.5 mm Hg, range 8.4–50.9 mmHg) in 19 children with laboratory evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) than in 12 children without such evidence (median 16.2 mmHg, range 5.8–42.5 mmHg; P = 0.027). Neither plasma nor cerebrospinal fluid arginine vasopressin (AVP) was related to ICP (r = 0.33 and 0.13 respectively). Mean arterial pressure (MAP) was measured in 23 children and a moderate correlation was found with plasma AVP (r = 0.62; P = 0.0019). In TBM, plasma AVP may be secreted as a response to raised ICP in an effort to raise MAP and maintain cerebral perfusion pressure. In this setting excess fluid may be inappropriately retained, leading to hyponatremia and hypo-osmolemia.     

Minimal displacement of novel self-anchoring catheters suitable for temporary prostate implants.

Catheters were developed that can be fixed in the prostate gland by self-expanding parts for use in PDR brachytherapy. Daily CT-scans were made to investigate the magnitude of catheter displacement. The mean absolute displacement during the 3 day treatment was 1.2 mm. The resulting minor alterations in dose-volume parameters were of no clinical importance.