A multicentre verification study of the QuantiFERON®-TB Gold Plus assay.

OBJECTIVES: The aim of this verification study was to compare the QuantiFERON®-TB Gold Plus (QFT-Plus) to the QuantiFERON®-TB Gold In Tube (QFT-GIT). The new QFT-Plus test contains an extra antigen tube which, according to the manufacturer additionally elicits a CD8+ T-cell response above the CD4+ T-cell response. We assessed the value of this tube in detecting recent latent tuberculosis infections. METHODS: Between May 2015 and December 2016, 1031 subjects underwent QFT-Plus and QFT-GIT test. Overall agreement between both tests and performance for different test indications and/or immune states was assessed. A difference of >0.6 IU/mL interferon-γ release between the two antigen tubes of the QFT-Plus assay was considered a true difference and used as estimation for CD8+ T-cell response. RESULTS: Analysis of the QuantiFERON tests resulted in an overall agreement between assays of 95%. Subjects considered to be recently exposed to tuberculosis had significantly more often a true difference in interferon-γ release compared to all other subjects (p = 0.029). CONCLUSION: Results of QFT-Plus are highly comparable to QFT-GIT. Although there is an indication that a true difference in interferon-γ release between the antigen tubes is associated with recent latent tuberculosis infection, the QFT-Plus could not be used to exclude recent exposure.

Predictive value of Borrelia burgdorferi IgG antibody levels in patients referred to a tertiary Lyme centre.

A two-step testing strategy is recommended in serological testing for Lyme borreliosis; positive and indeterminate enzyme-linked immunosorbent assay (ELISA) results are confirmed with immunoblots. Several ELISAs quantify the concentration of antibodies tested, however, no recommendation exists for an upper cut-off value at which an IgG ELISA is sufficient and the immunoblot can be omitted. The study objective was to determine at which IgG antibody level an immunoblot does not have any additional predictive value compared to ELISA results. Data of adult patients who visited a tertiary Lyme centre between 2008 and 2014 were analysed. Both an ELISA (Enzygnost Lyme link VlsE IgG) and immunoblot (recomLine blot Borrelia) were performed. Clinical data were extracted from the patient's digital medical record. Positive predictive values (PPVs) for either previous or active infection with Borrelia burgdorferi s.l. were calculated for different cut-off ELISA IgG antibody levels where the immunoblot was regarded as reference test. In total, 1454 patients were included. According to the two-step test strategy, 486 (33%), 69 (5%) and 899 (62%) patients had positive, indeterminate and negative Borrelia IgG serology, respectively. At IgG levels of 500 IU/ml and higher, all immunoblots were positive, resulting in a 100% PPV (95% CI: 97.0-100). At IgG levels of 200 IU/ml and higher, the PPV was 99.3% (95% CI: 97.4-99.8). In conclusion, at IgG levels of 200 IU/ml and higher, an ELISA was sufficient to detect antibodies to Borrelia burgdorferi s.l. At those IgG levels, a confirmatory immunoblot may be omitted in patients referred to a tertiary Lyme centre. Before these results can be implemented in routine diagnosis of Lyme borreliosis, confirmation of the results is necessary in other patient populations and using other quantitative ELISAs and immunoblots.

The application of an enzyme-linked immunosorbent assay or an immunofluorescent assay test leads to different estimates of seroprevalence of Coxiella burnetii in the population.

The diagnosis and epidemiological studies of Q fever depend on serology. Among the main methods employed are the enzyme-linked immunosorbent assay (ELISA) and the immunofluorescent assay test (IFAT). We show that two commercial assays representing the two methods with two different cut-off titres can lead to significant differences in diagnostic and seroprevalence estimates. This in turn emphasizes the need for a standardized gold method to compare the various assays; whether this standard is 'in-house' or commercially obtained.

Management of brachial plexus injuries.

Most brachial plexus lesions are traction injuries sustained during birth, but in adolescents and older people they are usually caused by traffic accidents or following a fall in the home. A minority are the result of penetrating injury after civilian assault or trauma encountered during wartime. Birth palsy cases (obstetric brachial plexus palsy) and the remaining cases (traumatic briachial plexus palsy) are viewed differently with regard to treatment and outcome and so these two groups are usually discussed in separate chapters. In this paper we treat both groups in parallel because as far as primary (= nerve) surgery is concerned, many treatment problems and solutions are present in both groups and are therefore comparable.

[Guideline 'Diagnosis and treatment of carpal tunnel syndrome']. / Richtlijn 'Diagnostiek en behandeling van het carpale-tunnelsyndroom'.

--Carpal tunnel syndrome (CTS) is the most frequently encountered peripheral nerve entrapment: about 10% of adult women and less than 1% of adult men in the Netherlands have a clinically and electrophysiologically confirmed CTS. --All medical and paramedical disciplines involved in the diagnosis and treatment of CTS in the Netherlands contributed to the development of a guideline for the diagnosis and treatment ofCTS. --Clinical diagnosis of CTS is based on a history of nocturnal pins and needles, numbeness and/or pain in the median nerve innervated area of the fingers and hand, which often causes the patient to awake. --Provocative tests do not contribute to the clinical diagnosis of CTS. --If invasive therapy is considered, such as corticosteroid injection or surgery, the clinical diagnosis must be confirmed by abnormal findings in electrophysiological tests. --Ultrasound or MRI of the wrist may be of diagnostic value when structural abnormalities in the carpal tunnel are suspected. Given the special expertise needed for ultrasound testing and the limited availability of MRI for CTS diagnostic purposes, these methods are not the first preference. --Depending on the degree of impact on daily functioning, treatment for CTS may be expectative, conservative (wrist splint or local steroid injections) or surgical (endoscopic or open techniques). --If CTS does not restrict daily functioning, adjustment of the working conditions will do. --Furthermore measures aimed at CTS prevention and treatment of an already existing work-related CTS are discussed.

Motor evoked potentials after transcranial magnetic stimulation support hypothesis of coexisting central mechanism in obstetric brachial palsy.

Six infants with obstetric brachial palsy, ranging from 4 to 7 months of age, were investigated. One was suspected of having extensive brachial plexus lesions and five were suspected of having a unilateral lesion of both roots C5 and C6. All were referred to our center to investigate the possibility for reconstructive surgery. In all infants, even at this age, transcranial magnetic stimulation resulted in motor evoked potentials (MEP) in the biceps (in one, in the brachioradial) muscles. Averaging could not be done because of the intraindividual variation in latency. The MEP was easier to recognize if evoked when the infant had the arm bent. In all five infants suspected of upper brachial plexus lesion with avulsion of both roots C5 and C6 and/or complete rupture of the upper trunk, proven in four, an MEP on the lesioned side could be evoked. Combined with earlier investigations showing (almost) normal EMG and somatosensory evoked potentials in infants with upper plexus lesion, this leads us to the conclusion that the paralysis of these infants cannot only be attributed to the peripheral axonal damage alone but that central plasticity must also play an important role. As this is a slow process, some infants might not yet be able to use the paralytic muscles. Some theoretic issues are discussed.

Swine-like hepatitis E viruses are a cause of unexplained hepatitis in the Netherlands.

Hepatitis E virus (HEV) infections in developed countries are recognized as an imported disease related to travel to endemic regions. However, increasing evidence suggests that HEV infection may also occur in the developed countries and that swine may act as a possible reservoir. To investigate the indigenous transmission of HEV in the Netherlands, sera from 50 blood donors and 1027 sera from patients with acute hepatitis were screened with an ELISA for HEV-specific IgG and IgM. Because the Netherlands is considered a nonendemic region, all positive ELISA results were confirmed by immunoblot to exclude false-positive results. Evidence of recent HEV infection was detected in 0% of the blood donors and 4.4% of the cases, based on combined positive IgM and IgG responses. The serodiagnosis was confirmed by a positive polymerase chain reaction (PCR) in 24 patients with hepatitis (2.3% overall, 51% of confirmed IgM+/IgG+ cases). IgG antibodies alone were detected in 4.2% of patients. We found related sequences to virus strains detected in Dutch pigs (genotype 3, 91-97% homology) in 89% of PCR-confirmed HEV patients. The detection of unique swine-like HEV sequences in 16 indigenous hepatitis patients without a recent travel history suggests that HEV is endemic in the Netherlands. We recommend including HEV tests in unexplained acute hepatitis patients, despite their travel history.

Results of carpal tunnel release.

We evaluated, by means of a prospective study, the results of carpal tunnel release both clinically and electrophysiologically in 188 patients with a carpal tunnel syndrome. A questionnaire was completed by patient and surgeon pre- and post-operatively (6 and 12 months after operation), when physical examination, electromyography and nerve conduction tests were also performed. Full pre- and post-operative results were available for 136 patients and 82% of the patients were satisfied with the results of the operation. Symptoms caused by median nerve compression showed the greatest improvement and no fixed patterns with regard to unsatisfactory results were found. If pain persisted in the wrist, many patients considered the operation to have been unsuccessful. Electrophysiological improvement occurred in all patients and at 12 months follow-up, median nerve conduction was normal in 21% of cases. Thus distal sensory latency remained abnormal in 79% of the patients, emphasizing the need for caution when recurrence of carpal tunnel syndrome is diagnosed in such cases.

Stereotactic treatment of intracerebral hematoma by means of a plasminogen activator: a multicenter randomized controlled trial (SICHPA).

BACKGROUND AND PURPOSE: Treatment of intracerebral hematoma (ICH) is controversial. An advantage of neurosurgical intervention over conservative treatment of ICH has not been established. Recent reports suggest a favorable effect of stereotactic blood clot removal after liquefaction by means of a plasminogen activator. The SICHPA trial was aimed at investigating the efficacy of this treatment. METHODS: A stereotactically placed catheter was used to instill urokinase to liquefy and drain the ICH in 6-hour intervals over 48 hours. From 1996 to 1999, 13 centers entered 71 patients into the study. Patients were randomized into a surgical group (n=36) and a nonsurgical group (n=35). Admission criteria were the following: age >45 years, spontaneous supratentorial ICH, Glasgow Eye Motor score ranging from 2 to 10, ICH volume >10 cm3, and treatment within 72 hours. The primary end point was death at 6 months. As secondary end points, ICH volume reduction and overall outcome measured by the modified Rankin scale were chosen. The trial was prematurely stopped as a result of slow patient accrual. RESULTS: Seventy patients were analyzed. Overall mortality at day 180 after stroke was 57%; this included 20 of 36 patients (56%) in the surgical group and 20 of 34 patients (59%) in the nonsurgical group. A significant ICH volume reduction was achieved by the intervention (10% to 20%, P<0.05). Logistic regression analysis indicated the possibility of efficacy for surgical treatment (odds ratio, 0.23; 95% confidence interval, 0.05 to 1.20; P=0.08). The odds ratio of mortality combined with modified Rankin scale score 5 at 180 days was also not statistically significant (odds ratio, 0.52; 95% confidence interval, 1.2 to 2.3; P=0.38). CONCLUSIONS: Stereotactic aspiration can be performed safely and in a relatively uniform manner; it leads to a modest reduction of 18 mL of hematoma reduction over 7 days when compared with control, which has a 7-mL reduction, and therefore may improve prognosis.

Extensive somatosensory innervation in infants with obstetric brachial palsy.

In the pre-operative screening of infants with obstetric brachial palsy (OBP), the results of routine electromyography are often overly optimistic when compared to the peri-operative findings. This prompted us to include investigation of the sensory innervation of these infants using the N20 (the first cortical response to a peripheral stimulation) of the somatosensory evoked potentials (SSEP). Three to seven months after birth, SSEP were recorded at the skull after stimulation of the thumb and middle finger in infants with obstetric rupture of the upper trunk or avulsion of roots C5, C6, or C7, and in whom no clinical improvement of motor function was observed in the biceps brachii and deltoid muscles. In most infants, a normal N20 could be evoked, indicating the existence of peripheral sensory pathways. From the thumb, these sensory pathways would necessarily bypass the upper trunk and dorsal roots of spinal nerves C5 and C6, and from the middle finger bypass the middle trunk and dorsal root C7, before extending into the dorsal column and projecting toward the thalamus and cerebral cortex. These data suggest that in infancy the segmental sensory innervation of the hand is more diverse than is described in most textbooks.

TP53 mutations in human meningiomas.

Overexpression of p53 has been reported to play a role in the development of neoplasms of the central nervous system. Meningiomas are generally benign intracranial tumors originating from the meninges. Overexpression of the p53 protein in meningiomas and an association with histological type and recurrence has been reported. Mutation of the TP53 gene leads to a more stable p53 protein in quantities high enough for detection by immunohistochemistry. In the search for these mutations the core domain of the TP53 gene of meningiomas has been analyzed. Only a very low incidence of mutations was reported. The apparent discordance between overexpression of p53 protein and TP53 gene mutations may be explained by mutations located outside the core domain. This issue was addressed in the present study. All 11 exons of 17 meningiomas were analyzed for DNA alterations by PCR single-strand conformation polymorphism (PCR-SSCP) analysis with subsequent sequencing. PCR-SSCP analysis showed a various number of band shifts and nucleotide alterations, caused either by alterations in the flanking introns or common polymorphisms (codon 36 and 72). The allele frequencies of the polymorphisms found in this small population of tumors resemble the frequencies reported in the literature. In addition, three nucleotide changes located in introns 2, 3 and 7 were found in 11, 3 and 4, respectively, of 17 specimens. Based on this study and on reports by others we conclude that it is not very likely that TP53 mutations are involved in the etiology of meningiomas.

Progesterone receptor, bc1-2 and bax expression in meningiomas.

Meningiomas are generally benign central nervous system neoplasms, which frequently express progesterone receptor (PR) and only rarely express the estrogen receptor (ER). For breast cancer, a relation between steroid hormone receptors and proteins involved in the apoptotic process has been described. For meningiomas, the exact relation between PR and these proteins is not known. In this study, ER, PR, bcl-2 and bcl-2-associated x protein (Bax) expression levels were determined in meningioma cytosols. As a reference for our experimental conditions, we also determined these proteins in breast cancer cytosols. PR and ER were determined with a ligand-binding assay and scatchard-plot analysis. The expression levels of the anti- and pro-apoptotic proteins, bcl-2 and Bax, respectively, were determined by immunoblotting. In 65% of the meningioma, bcl-2 expression was found in variable amounts. In contrast to breast cancer, a significant negative association between PR and bcl-2 was found (P < 0.01). Bax expression appeared constitutive, not related to PR, and 2.6 times higher than breast cancer. As both PR and bcl-2 appear positively associated with prognosis, the negative relationship between bcl-2 and PR found in this study might have some biological and clinical significance.

[Ataxia and pruritus in a pony due to a cervical vertebral fracture]. / Ataxie en pruritus bij een pony als gevolg van een halswervelfractuur.

A mini-Shetland stallion was referred with bilateral pruritus localized to the anterior neck. More detailed clinical examination also revealed ataxia, and diagnostic imaging, including pre- and post-contrast computed tomography, revealed an old fracture of C2. Spinal cord compression was diagnosed. The probable causal relation between the fracture, the ataxia, and the localized pruritus seems comparable to the 'contusio cervicalis posterior' in humans, in which spinal cord trauma may cause pruritus in the associated dermatome.

Validation of an electromyography and nerve conduction study protocol for the analysis of brachial plexus lesions in 184 consecutive patients with traumatic lesions.

OBJECTIVES: To validate a concentric needle electromyography (EMG) and nerve conduction study (NCS) protocol for the preoperative analysis of brachial plexus lesions.METHODS. 184 consecutive patients with traumatic brachial plexus lesions were analyzed. The results of the neurophysiological studies were compared with the final diagnoses based on the results of computed tomography-myelography and findings during the operation. RESULTS: The protocol proved reliable in the analysis of these lesions in 84% of cases. Limitations were that extraforaminal lesions may mask root avulsion or central lesions; paraspinal sampling is of limited value in multiple root lesions because of the overlap in innervation; and sometimes normal sensory nerve action potentials (SNAPs) could occur in an extra foraminal lesion. Lesions outside the plexus were found in 21% of the patients, most of which would not have been expected on clinical grounds. CONCLUSION: With this protocol, a reliable analysis of traumatic brachial plexus lesions can be made in 84% of the patients, even finding lesions outside the brachial plexus not expected on clinical grounds in 2l degrees of the patients.

Economic evaluation in stroke research : a systematic review.

BACKGROUND AND PURPOSE: The purpose of this review is to provide insight into the quality of economic evaluation in the field of cerebrovascular diseases (CVD) on the basis of a systematic analysis. METHODS: A literature search was performed using several sources. Trial-based full economic evaluation studies, were included in this review. The quality of the studies was independently assessed by 2 reviewers using a checklist. RESULTS: Twenty-three articles were found to comply with our inclusion and exclusion criteria. Only a few studies mentioned the perspective of the study, and in these cases it was always the societal perspective. The majority of the studies were cost-minimization and cost-effectiveness analyses based on cohort studies. All studies included healthcare costs, and in some instances patient and family costs were considered. Costs were usually measured by tariffs. Clinical end points and mortality were used to measure effects. Cost and effect measurements were based on hospital records. CONCLUSIONS: Only a few full economic evaluations have been undertaken in the domain of CVD. In most of the studies, the technical execution and methodology were limited.

The findings in paediatric obstetric brachial palsy differ from those in older patients: a suggested explanation.

An EMG and nerve-conduction-study protocol has been developed and used in all patients with brachial plexus lesions since 1985. The findings of EMG and nerve-conduction studies in obstetric brachial palsy (OBP) mostly suggest a falsely optimistic prognosis. To analyse this, all subjects were selected with complete avulsion of both roots C5 and C6 and/or complete rupture of the upper trunk verified during operation from a group of 162 infants with OBP (aged 4 to 14 months) and a group of 184 child and adult patients (aged 6 to 74 years) with a traumatic brachial plexus lesion. Fourteen infants, approximately 4 months old, with OBP, and 19 adults (aged 16 to 30 years) met the selection criteria. The infants from the group with OBP had at 4 months a nearly normal recruitment pattern of motor units in the biceps brachii and deltoid muscles, with little or no denervation. However, in the older group with traumatic brachial palsy, the same lesion caused complete denervation of both muscles. From the group with OBP, a third group (N=3) with the same lesion plus an additional lesion of C7 or a rupture of the middle trunk was selected. This additional lesion resulted in nearly complete denervation of both muscles. This means that C7 largely contributes to the innervation of both muscles at the time of birth, but this innervation is lost during later life in normally developing individuals (apoptosis). A central mechanism might be responsible for the clinical palsy and later spontaneous improvement which is always found in the infants with OBP.

The truncated estrogen receptor alpha variant lacking exon 5 is not involved in progesterone receptor expression in meningiomas.

Human meningioma tissues are mostly estrogen receptor (ER) negative and progesterone receptor (PR) positive in ligand binding and enzyme immuno assays. To explain this apparently ER independent PR expression, we investigated the existence of a 'hidden' ER variant, which would be capable of activating transcription of the PR gene. Total RNA of seven meningiomas, two breast cancer tissues and of MCF7 cells was analyzed by RT-PCR using primers situated in exon 4 and exon 6. Differential hybridization of the PCR transcripts with probes in exon 4 and 5 respectively, revealed a wild type ER (wtER) fragment and an exon 5 deleted ER variant (ERDelta5). PCR products of two meningiomas were cloned for sequence analysis. The result confirmed the existence of a wtER and ERDelta5.RT-PCR followed by Southern analysis was performed on mRNA of 23 meningiomas to determine the amount of ERDelta5 relative to wtER, which was compared to the PR content of the tissues. In contrast to our initial hypothesis and literature data on breast cancer, there was no relationship between the ERDelta5/wtER ratio and PR protein concentration. It is therefore concluded that ERDelta5 mRNA does not play the dominant role in PR synthesis in meningioma tissue.