Cardiopulmonary transit time: A novel PET imaging biomarker of in vivo physiology for risk stratification of heart transplant recipients.

BACKGROUND: Myocardial blood flow (MBF) can be quantified using dynamic PET studies. These studies also inherently contain tomographic images of early bolus displacement, which can provide cardiopulmonary transit times (CPTT) as measure of cardiopulmonary physiology. The aim of this study was to assess the incremental prognostic value of CPTT in heart transplant (OHT) recipients. METHODS: 94 patients (age 56 ± 16 years, 78% male) undergoing dynamic 13N-ammonia stress/rest studies were included, of which 68 underwent right-heart catherization. A recently validated cardiac allograft vasculopathy (CAV) score based on PET measures of regional perfusion, peak MBF and left-ventricular (LV) ejection fraction (LVEF) was used to identify patients with no, mild or moderate-severe CAV. Time-activity curves of the LV and right ventricular (RV) cavities were obtained and used to calculate the difference between the LV and RV bolus midpoint times, which represents the CPTT and is expressed in heartbeats. Patients were followed for a median of 2.5 years for the occurrence of major adverse cardiac events (MACE), including cardiovascular death, hospitalization for heart failure or acute coronary syndrome, or re-transplantation. RESULTS: CPTT was significantly correlated with cardiac filling pressures (r = .434, P = .0002 and r = .439, P = .0002 for right atrial and pulmonary wedge pressure), cardiac output (r = - .315, P = .01) and LVEF (r = - .513, P < .0001). CPTT was prolonged in patients with MACE (19.4 ± 6.0 vs 14.5 ± 3.0 heartbeats, P < .001, N = 15) with CPTT ≥ 17.75 beats showing optimal discriminatory value in ROC analysis. CPTT ≥ 17.75 heartbeats was associated with a 10.1-fold increased risk (P < .001) of MACE and a 7.3-fold increased risk (P < .001) after adjusting for PET-CAV, age, sex and time since transplant. CONCLUSION: Measurements of cardiopulmonary transit time provide incremental risk stratification in OHT recipients and enhance the value of multiparametric dynamic PET imaging, particularly in identifying high-risk patients.

Galectin-3: an emerging biomarker in stroke and cerebrovascular diseases.

The carbohydrate-binding molecule galectin-3 has garnered significant attention recently as a biomarker for various conditions ranging from cardiac disease to obesity. Although there have been several recent studies investigating its role in stroke and other cerebrovascular diseases, awareness of this emerging biomarker in the wider neurology community is limited. We performed a systematic search in PubMed, Embase, Scopus, CINAHL, Clinicaltrials.gov and the Cochrane library in November and December 2016 for articles related to galectin-3 and cerebrovascular disease. We included both human and pre-clinical studies in order to provide a comprehensive view of the state of the literature on this topic. The majority of the relevant literature focuses on stroke, cerebral ischemia and atherosclerosis, but some recent attention has also been devoted to intracranial and subarachnoid hemorrhage. Higher blood levels of galectin-3 correlate with worse outcomes in atherosclerotic disease as well as in intracranial and subarachnoid hemorrhage in human studies. However, experimental evidence supporting the role of galectin-3 in these phenotypes is not as robust. It is likely that the role of galectin-3 in the inflammatory cascade within the central nervous system following injury is responsible for many of its effects, but its varied physiological functions and multiple sites of expression mean that it may have different effects depending on the nature of the disease condition and the time since injury. In summary, experimental and human research raises the possibility that galectin-3, which is closely linked to the inflammatory cascade, could be of value as a prognostic marker and therapeutic target in cerebrovascular disease.

Cardiogenic shock from atypical Takotsubo cardiomyopathy attributed to acute disseminated encephalomyelitis lesion involving the medulla.

We present here a case of atypical Takotsubo cardiomyopathy arising as a result of a lesion in the medulla oblongata. The patient was diagnosed with acute disseminated encephalomyelitis, and had improvement with intravenous steroids.

Olfaction in Parkin single and compound heterozygotes in a cohort of young onset Parkinson's disease patients.

BACKGROUND: Parkin related Parkinson's disease (PD) is differentiated from idiopathic PD by absent or sparse Lewy bodies, and preserved olfaction. The significance of single Parkin mutations in the pathogenesis of PD is debated. OBJECTIVES: To assess olfaction results according to Parkin mutation status. To compare the prevalence of Parkin single heterozygous mutations in patients diagnosed with PD to the rate in healthy controls in order to establish whether these single mutations could be a risk factor for developing PD. METHODS: Parkin gene mutation testing was performed in young onset PD (diagnosed <50 years old) to identify three groups: Parkin homozygous or compound heterozygote mutation carriers, Parkin single heterozygote mutation carriers, and non-carriers of Parkin mutations. Olfaction was tested using the 40-item British version of the University of Pennsylvania smell identification test (UPSIT). RESULTS: Of 344 young onset PD cases tested, 8 (2.3%) were Parkin compound heterozygotes and 13 (3.8%) were Parkin single heterozygotes. Olfaction results were available in 282 cases (eight compound heterozygotes, nine single heterozygotes, and 265 non-carriers). In Parkin compound heterozygotes, the median UPSIT score was 33, interquartile range (IQR) 28.5-36.5, which was significantly better than in single Parkin heterozygotes (median 19, IQR 18-28) and non-carriers (median score 22, IQR 16-28) (ANOVA P < 0.001). These differences persisted after adjusting for age, disease duration, gender, and smoking (P < 0.001). There was no significant difference in UPSIT scores between single heterozygotes and non-carriers (P = 0.90). CONCLUSIONS: Patients with Parkin compound heterozygous mutations have relatively preserved olfaction compared to Parkin single heterozygotes and non-carriers. The prevalence of Parkin single heterozygosity is similar to the 3.7% rate reported in healthy controls.

Characteristics of progressive supranuclear palsy presenting with corticobasal syndrome: a cortical variant.

AIMS: Since the first description of the classical presentation of progressive supranuclear palsy (PSP) in 1963, now known as Richardson's syndrome (PSP-RS), several distinct clinical syndromes have been associated with PSP-tau pathology. Like other neurodegenerative disorders, the severity and distribution of phosphorylated tau pathology are closely associated with the clinical heterogeneity of PSP variants. PSP with corticobasal syndrome presentation (PSP-CBS) was reported to have more tau load in the mid-frontal and inferior-parietal cortices than in PSP-RS. However, it is uncertain if differences exist in the distribution of tau pathology in other brain regions or if the overall tau load is increased in the brains of PSP-CBS. METHODS: We sought to compare the clinical and pathological features of PSP-CBS and PSP-RS including quantitative assessment of tau load in 15 cortical, basal ganglia and cerebellar regions. RESULTS: In addition to the similar age of onset and disease duration, we demonstrated that the overall severity of tau pathology was the same between PSP-CBS and PSP-RS. We identified that there was a shift of tau burden towards the cortical regions away from the basal ganglia; supporting the notion that PSP-CBS is a 'cortical' PSP variant. PSP-CBS also had less severe neuronal loss in the dorsolateral and ventrolateral subregions of the substantia nigra and more severe microglial response in the corticospinal tract than in PSP-RS; however, neuronal loss in subthalamic nucleus was equally severe in both groups. CONCLUSIONS: A better understanding of the factors that influence the selective pathological vulnerability in different PSP variants will provide further insights into the neurodegenerative process underlying tauopathies.

Cessation in root development: ramifications of 'Stevens-Johnson' syndrome.

The case presented here is of a 15-year-old girl in whom nearly all the teeth except for lower first molars and lower central incisors showed short roots as observed through panoramic radiograph. At the same time there was difference in the length of roots of various teeth. The patient suffered an acute attack of Stevens-Johnson syndrome (SJS) at the age of 8 years and since no other possible explanation for the short roots anomaly could be found, it could be concluded that the cessation in root development may have been caused by the destruction or damage of the epithelial root sheath during the SJS disease.

Cytochrome P450 2S1 depletion enhances cell proliferation and migration in bronchial epithelial cells, in part, through modulation of prostaglandin E(2) synthesis.

Cytochromes P450 (P450s) contribute to the metabolic activation and inactivation of various endogenous substrates. Despite years of research, the physiological role of CYP2S1 remains unknown. CYP2S1 has demonstrated NADPH P450-reductase-independent metabolism of cyclooxygenase (COX)-derived prostaglandins [e.g., prostaglandin G(2) (PGG(2))] at nanomolar concentrations. Arachidonic acid is converted to prostaglandin precursors [PGG(2) and prostaglandin H(2) (PGH(2))] through COX. These precursors are used to synthesize numerous prostanoids, including PGE(2). Prostaglandin E(2) (PGE(2)) promotes cell proliferation and cell migration and inhibits apoptosis. CYP2S1 metabolism of PGG(2) presumably sequesters PGG(2) and PGH(2), making them unavailable for synthesis of prostanoids such as PGE(2). Whether CYP2S1 contributes to prostaglandin metabolism and influences cell physiological remains to be determined. The purpose of this study was to evaluate the physiological role of CYP2S1, if any, in human bronchial epithelial cells [SV40-derived bronchial epithelial cell line (BEAS-2B)]. To do this, we used small interfering RNA to deplete CYP2S1 mRNA and protein by approximately 75% and evaluated the impact of CYP2S1 depletion on cell proliferation and migration. CYP2S1 depletion enhanced both cell proliferation and migration in BEAS-2B cells. Consistent with the proposed role of CYP2S1 in PGE(2) synthesis, the reduction in CYP2S1 expression doubled intracellular PGE(2) levels. Pharmacological administration of PGE(2) enhanced cell proliferation in BEAS-2B cells but failed to promote migration. Our data reveal an important role for CYP2S1 in the regulation of cell proliferation and migration, occurring in part through modulation of prostaglandin synthesis.

Accuracy of subjective and objective handwriting assessment for differentiating Parkinson's disease from tremulous subjects without evidence of dopaminergic deficits (SWEDDs): an FP-CIT-validated study.

Handwriting examinations are commonly performed in the analysis of tremor and Parkinson's disease (PD). We analyzed the accuracy of subjective and objective assessment of handwriting samples for distinguishing 27 PD cases, 22 with tremulous PD, and five with akinetic-rigid PD, from 39 movement-disorder patients with normal presynaptic dopamine imaging (subjects without evidence of dopamine deficiency or SWEDDs; 31 with dystonic tremor (DT), six indeterminate tremor syndrome, one essential tremor, one vascular parkinsonism). All handwriting analysis was performed blind to clinical details. Subjective classification was made as: (1) micrographia, (2) normal, or (3) macrographia. In addition, a range of objective metrices were measured on standardized handwriting specimens. Subjective assessments found micrographia more frequently in PD than SWEDDs (p = 0.0352) and in akinetic-rigid than tremulous PD (p = 0.0259). Macrographia was predominantly seen in patients with dystonic tremor and not other diagnoses (p = 0.007). Micrographia had a mean sensitivity of 55 % and specificity of 84 % for distinguishing PD from SWEDDs and mean sensitivity of 90 % and specificity of 55 % for distinguishing akinetic-rigid PD from tremulous PD. Macrographia had a sensitivity of 26 % and specificity of 96 % for distinguishing DT from all other diagnoses. The best of the objective metrices increased sensitivity for the distinction of SWEDDs from PD with a reduction in specificity. We conclude that micrographia is more indicative of PD than SWEDDs and more characteristic of akinetic-rigid than tremulous PD. In addition, macrographia strongly suggests a diagnosis of dystonic tremor.

Dependence and psychosis with 4-methylmethcathinone (mephedrone) use.

'Legal highs' are recreational drugs sold over the internet and the so-called 'head shops' all over the UK. They are freely available to buy and use as they are not covered by the Misuse of Drugs Act 1971. Mephedrone (4-methylmethcathinone) was sold as a 'legal high' until 17 April 2010 when it was made a class B drug under the Misuse of Drugs Act 1971. Numerous deaths and self-harm has been associated with mephedrone use. Effects of mephedrone are reported to be empathogenic similar to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and stimulant properties similar to cocaine. Not much is known of the effects of mephedrone on mental health. We present a case of dependence and psychosis in a patient using mephedrone (4-methylmethcathinone). The patient needed inpatient hospital care, was treated with antipsychotic olanzapine and recovered well.

Bilateral retinoblastoma in early infancy: a case report.

Retinoblastoma is the most common primary intraocular tumour of childhood. Though congenital, it is not diagnosed at birth, and is usually seen between 1-2 years of age. We here report a case of bilateral retinoblastoma with early presentation at the age of one month.

Internal carotid artery dissection presenting with ipsilateral tenth and twelfth nerve palsies and apparent mass lesion on MRI.

We report the case of a 47-year-old man who presented with a few months' history of right-sided headache and dysphagia, with ipsilateral tenth and twelfth cranial nerve palsies on examination. The initial MRI showed an enhancing mass lesion in relation to the right carotid sheath and jugular foramen, and was reported as a possible paraganglioma. Subsequent angiography performed to assess tumour vascularity demonstrated a dissection involving a tonsillar loop of the right internal carotid artery (ICA). Imaging findings at MRI and angiography and the presentations and mechanisms of ICA dissection are briefly discussed.

Familial adult onset of Krabbe's disease resembling hereditary spastic paraplegia with normal neuroimaging.

Krabbe's disease (globoid cell leucodystrophy) is a disorder involving the white matter of the peripheral and central nervous systems. Mutations in the gene for the lysosomal enzyme galactocerebrosidase (GALC) result in low enzymatic activity and decreased ability to degrade galactolipids found in myelin. The disease is classically of infantile onset, but adult onset cases have been reported. Magnetic resonance imaging (MRI) of the brain shows characteristic abnormalities. A unique family with Krabbe's disease is described, with proven GALC deficiency but normal MRI. A neurological phenotype is present in heterozygotes and the family shows the extent of homozygotic phenotypic diversity that can be seen in this disorder.

Acute transverse myelitis and Guillain-Barré overlap syndrome with serological evidence for mumps viraemia.

Both acute transverse myelitis (ATM) and Guillain-Barré syndrome (GBS) occur as rare associations with mumps viraemia but to our knowledge, concurrent ATM and GBS related to mumps has only been reported once previously. We describe the case of a young woman presenting with confusion and collapse 2 weeks after a flu-like illness. An initial diagnosis of transverse myelitis was made on the basis of the clinical findings and radiological evidence of a swollen spinal cord with uniform high signal change on T2 weighted MRI. The patient was treated with intravenous methylprednisolone without significant recovery. The diagnosis was later revised to include GBS on the basis of worsening facial diplegia in the setting of a flaccid tetraparesis, and neurophysiological evidence of a sensorimotor axonal polyradiculoneuropathy. Acute mumps viraemia was confirmed on serological grounds. The patient made an improvement in ventilatory capacity with intravenous immunoglobulin treatment.