Interobserver variation in the evaluation of neurological signs: observer dependent factors.

Introduction - Interobserver variation among four observers in evaluation of eight selected neurological signs was investigated. Material & methods - Two hundred and two consecutive unselected inpatients were examined by two senior neurologists and two trainees, all without knowledge of the neurological case history. The signs examined were: anisocoria, jerky eye movements, facial palsy, elbow extension force, finger-nose test, Barré sign, knee jerk, and extensor plantar reflex. Observed agreement rates and kappa coefficients were calculated in order to compare the interobserver variability among neurologists and trainees, and to evaluate differences in the interobserver variability between signs. Results - Observed agreement rates varied from 0.80 to 0.95 for neurologists and from 0.65 to 0.98 for trainees. For neurologists kappa coefficients ranged from 0.40 to 0.67 and for trainees from 0.22 to 0.81. The neurologists had higher kappa values than the trainees in 5 signs, but this difference was only statistically significant for jerky eye movements. For the individual signs the observed agreement rates were between 0.50 and 0.93 for all four examiners combined, and overall kappa values varied from 0.32 to 0.71 with highest agreement for facial palsy and lowest for knee jerk. Conclusion - The magnitude of the interobserver and intersign variation indicates that the interpretation of the neurological signs tested, without knowledge of the case history, should be done with some caution.     

An occipito-temporal syndrome in adolescents with optimally controlled hyperphenylalaninaemia

Summary The study included 16 adolescents with optimally controlled hyperphenylalaninaemia (McKusick 26160), of whom six did not require treatment according to conventional criteria. All except the two patients with lowest median serum phenylalanine level throughout childhood (most values at 200–300 µmol/L) had white matter abnormalities detectable with magnetic resonance imaging. The lesions were particularly prominent in the watershed regions between the posterior and middle cerebral arteries. In most patients with moderate or severe hyperphenylalaninaemia frontal white matter lesions were present as well. Normal proton magnetic resonance spectra indicated that the lesions were stable. Occipital EEG abnormalities were frequent, and deficient performance on a pattern-recognition test was a characteristic neuropsychological finding. Serum phenylalanine levels at about 300 µmol/L or below throughout childhood and early adolescence may be required to avoid lesions. The present study demonstrates the limitations of even an optimally controlled dietary regimen in hyperphenylalaninaemia.     

The role of macrophages in demyelination

Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS). In particular in the CsA-induced chronic relapsing form (CREAE), pronounced demyelination occurs, in temporal association with relapses. It is still a matter of discussion which cell type ultimately is responsible for the actual process of demyelination. Macrophages, cytotoxic T lymphocytes and also astrocytes are possible candidates. In this short overview, the role of macrophages in the pathogenesis of EAE is discussed. It is shown that in particular, newly recruited macrophages play a crucial role in the generation of clinical signs. Possible mechanisms by which macrophages are involved in the pathogenesis of demyelinating diseases are presented.     

Bone disorders following total gastrectomy

Bone disorders following gastrectomy were studied by measuring absolute and relative bone mineral density of the Wards triangle, serum 1,25-(OH)₂-D, alkaline phosphatase, and total serum calcium. The subjects were 20 males who had undergone total gastrectomy not more than three months previously (group A₁). Seventeen of these patients were reviewed three years later (group A₂). Absolute and relative bone density were significantly lower in group A₂ than in A₁ (0.52 ± 0.011 g/cm² versus 0.6 ± 0.014 g/cm²,P<0.01 and 85.5 ± 1.4% age-matched control versus 95 ± 1.3%,P<0.01). 1,25-(OH)₂-D was significantly lower in group A₂ than in group A₁ (14.3 ± 0.97 pg/ml versus 20.6 ± 1.02 pg/ml,P<0.01). There was no difference in alkaline phosphatase and calcium serum concentration. The mean weight loss was 6.26 ± 0.57% over the follow-up period, and weight loss correlated with absolute and relative bone density (r=–0.74,P<0.01). There was a positive correlation between 1,25-(OH)₂-D and absolute or relative bone density (r=0.67,r=0.62 andP<0.01). These data suggest that bone density decrease has already occurred three years after total gastrectomy and is positively correlated to 1,25-(OH)₂-D deficiency. As no differences in serum alkaline phosphatase and serum calcium concentration were found, these factors are of little value for the early detection of postgastrectomy bone disorders, whereas weight loss is a valuable screening parameter.     

Establishing a cancer center data bank and biorepository for multidisciplinary research.

The establishment of a biorepository with linkage to clinical and epidemiologic data will provide an invaluable resource for cancer research, including studies of cancer etiology, progression, and prognosis, as well as development of biomarkers for early detection. Developing an infrastructure for a biorepository linked to clinical, pathologic, and epidemiologic data requires significant efforts in strategic planning for efficient means to ascertain, identify, and consent participants, as well as guidelines for blood collection, processing, and storage while maintaining participant privacy rights. In this report, we present an approach to developing a Data Bank and Biorepository at our own institution, with discussion of elements to be considered when establishing such a bank.     

Unlabeled uses of botulinum toxins: a review, part 1.

PURPOSE: Efficacy and safety data regarding the unlabeled uses of botulinum toxins are reviewed, and the pharmacology, adverse effects, and characteristics of commercially available botulinum toxins are discussed. SUMMARY: More than 300 articles have been published on the use of botulinum toxins, particularly botulinum toxin type A, to treat conditions characterized by excessive smooth or skeletal muscle spasticity. Botulinum toxins are synthesized by Clostridium botulinum and cause temporary local paralysis of the injected muscle by inhibiting acetylcholine release at the neuromuscular junction. While botulinum toxins have Food and Drug Administration-approved labeling to treat a limited number of spasticity disorders, including cervical dystonia and blepharospasm, the toxins have more than 50 reported therapeutic uses. Among these uses, the most rigorously studied indications include achalasia, essential tremors, palmar hyperhidrosis, chronic anal fissures, headache prophylaxis, and limb spasticity. The main adverse effects of the toxins are pain and erythema at the injection site, although unintended paralysis of muscles adjacent to the site of toxin injection may also occur. CONCLUSION: Clinical studies support the use of botulinum toxins for certain conditions, although more studies are needed to establish the role of the drug relative to conventional therapies and to determine patient predictors of response. Although botulinum toxins are generally well tolerated, a patient-specific risk-benefit assessment should precede any decision to use them for unlabeled indications.