Clinical and methodological challenges for assessing freezing of gait: Future perspectives

Freezing of gait, defined as sudden and usually brief episodes of inability to produce effective stepping, often results in falls and is both disabling and common in parkinsonism. In this narrative review, sprung from the 2nd International Workshop on freezing of gait in Leuven, we summarize the latest insights into clinical and methodological challenges for assessing freezing of gait. We also highlight the role of emerging wearable technology to improve the management of this debilitating symptom. © 2019 International Parkinson and Movement Disorder Society     

Automated algorithm for reconstruction of the complete spine from multistation 7T MR data

Recent technical developments in high‐field MRI have enabled high‐resolution imaging of the whole spine within clinically acceptable times. However, analysis of such data requires intensity inhomogeneity correction and volume stitching, both of which are typically performed manually. In this work, an automated method for reconstruction of the complete spine from multistation 7T MR data is presented. The method consists of a number of image processing steps, in particular intensity inhomogeneity correction and image registration for recovery of unknown interscan bed translations, which result in high‐quality spine volume reconstructions. The registration performance of the developed algorithm was validated on 18 datasets acquired in two or three stations. In all the test cases, our algorithm was able to produce correct reconstruction of the spine volume. The resulting mean registration error (0.53 mm) is found to be lower than the pixel size, demonstrating robustness and accuracy of the proposed method. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Fetal duodenal obstructions: increased risk of prenatal sudden death.

OBJECTIVES: The aim of this study was to describe the outcome of fetuses with duodenal obstruction diagnosed prenatally and to compare the outcome with the results of studies of newborns. METHODS: All fetuses with a prenatal diagnosis of duodenal obstruction were registered and evaluated prospectively from January 1985 to December 2000. RESULTS: Duodenal obstruction was found in 29 fetuses at a mean gestational age of 29+2 weeks. Polyhydramnios was found in 24 cases (83%). Six fetuses (21%) had trisomy 21. Associated anomalies, including trisomy 21, were found in 18 cases (62%). Four fetuses with normal karyotype died in utero at 31-35 gestational weeks. Two of them had associated anomalies, but the anomalies could not explain the prenatal deaths and the deaths occurred suddenly and unexpectedly. Three infants died postnatally; all three had associated anomalies. Four infants with normal karyotype had neurological impairment suggesting that they might have had intrauterine asphyxia. CONCLUSIONS: The present study indicates that duodenal obstruction is a more serious condition than previously believed, with an increased risk of prenatal asphyxia and death, even when the karyotype is normal and no associated anomalies are present. We consider the possibility that it could be caused by bradycardia/asystole following vagal overactivity due to distension of the upper gastrointestinal tract.     

High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome

Background

In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown.

Methods

Mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for JPS (typical JPS) and 15 were suspected to have JPS.

Results

By direct sequencing of the two genes, point mutations were identified in 30 patients (46% of typical JPS). Using MLPA, large genomic deletions were found in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Mutation analysis of the PTEN gene in the remaining 41 mutation negative cases uncovered a point mutation in two patients (5%). SMAD4 mutation carriers had a significantly higher frequency of gastric polyposis (73%) than did patients with BMPR1A mutations (8%) (p<0.001); all seven cases of gastric cancer occurred in families with SMAD4 mutations. SMAD4 mutation carriers with gastric polyps were significantly older at gastroscopy than those without (p<0.001). In 22% of the 23 unrelated SMAD4 mutation carriers, hereditary hemorrhagic telangiectasia (HHT) was also diagnosed clinically. The documented histologic findings encompassed a wide distribution of different polyp types, comparable with that described in hereditary mixed polyposis syndromes (HMPS).

Conclusions

Screening for large deletions raised the mutation detection rate to 60% in the 65 patients with typical JPS. A strong genotype‐phenotype correlation for gastric polyposis, gastric cancer, and HHT was identified, which should have implications for counselling and surveillance. Histopathological results in hamartomatous polyposis syndromes must be critically interpreted.Juvenile polyposis syndrome (JPS, OMIM 174900) is an autosomal dominant disorder characterised by the occurrence of multiple juvenile polyps in the gastrointestinal tract, specifically in the stomach, small intestine, colon and rectum.^1,2,3 Pathogenic germline mutations in the SMAD4 (MADH4) gene have been identified in around 20% of patients with JPS, and another 20% of patients were found to exhibit a mutation in the BMPR1A gene.^1,4,5,6 A higher frequency of gastric polyposis in carriers of SMAD4 mutations compared with carriers of BMPR1A mutations has been reported.^6,7,8 Most SMAD4 or BMPR1A germline mutations published to date are small insertions/deletions and single base substitutions leading to nonsense, splice‐site or missense mutations (Human Gene Mutation Database). Recently, germline deletions encompassing the contiguous genes BMPR1A and PTEN on chromosome 10q have been reported in five cases of juvenile polyposis of infancy.^9,10 These deletions have been found by absence of parental alleles in the children, quantitative PCR or fluorescence in situ analysis.Large genomic deletions or duplications encompassing ⩾1 exons have been found in several genes using the multiplex ligation‐dependent probe amplification (MLPA) assay.^{11,12,13,14,15} Using the recently developed MLPA test kit for quantitative evaluation of genes involved in JPS, we examined whether large SMAD4 or BMPR1A deletions or duplications are present in patients with JPS with as yet unknown germline mutations, and verified the genotype–phenotype correlation with respect to gastric polyposis.     

Pericarditis as primary manifestation of Mycobacterium bovis SSP. caprae infection

A 76-year-old white male presented with progressive malaise, weight loss and dyspnea at rest. Echocardiography revealed a circular pericardial effusion and global hypokinesia. Pericardiocentesis showed a purulent exudate and microbiologic examination revealed Mycobacterium bovis fully sensitive to isoniazid, streptomycin, ethambutol, rifampin, and pyrazinamide. By spoligotyping the isolate could be further differentiated to M. bovis ssp. caprae. Antimycobacterial therapy was initiated but 3 weeks later the patient's circulation and renal function deteriorated and he died with clinical signs of sepsis despite intensive care treatment. Pericarditis is a rare manifestation of tuberculosis and can be fatal even when diagnosed and treated appropriately. In low incidence countries diagnosis is often delayed and even overlooked.