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Fulltext Tolerability, safety and intermediary pharmacological effects of cilostazol and isosorbide mononitrate, alone and combined, in patients with lacunar ischaemic stroke: The LACunar Intervention-1 (LACI-1) trial, a randomised clinical trial

Blair GW, Appleton JP, Flaherty K, Doubal F, Sprigg N, Dooley R, et al.

EClinicalMedicine, 2019 04 24;11:34-43.
PMID: 31317131 DOI: 10.1016/j.eclinm.2019.04.001

Background: Lacunar stroke, a frequent clinical manifestation of small vessel disease (SVD), differs pathologically from other ischaemic stroke subtypes and has no specific long-term secondary prevention. Licenced drugs, isosorbide mononitrate (ISMN) and cilostazol, have relevant actions to prevent SVD progression.
Methods: We recruited independent patients with clinically confirmed lacunar ischaemic stroke without cognitive impairment to a prospective randomised clinical trial, LACunar Intervention-1 (LACI-1). We randomised patients using a central web-based system, 1:1:1:1 with minimisation, to masked ISMN 25 mg bd, cilostazol 100 mg bd, both ISMN and cilostazol started immediately, or both with start delayed. We escalated doses to target over two weeks, sustained for eight weeks. Primary outcome was the proportion achieving target dose. Secondary outcomes included symptoms, safety (haemorrhage, recurrent vascular events), cognition, haematology, vascular function, and neuroimaging. LACI-1 was powered (80%, alpha 0.05) to detect 35% (90% versus 55%) difference between the proportion reaching target dose on one versus both drugs at 55 patients. Registration ISRCTN12580546.
Findings: LACI-1 enrolled 57 participants between March 2016 and August 2017: 18 (32%) females, mean age 66 (SD 11, range 40-85) years, onset-randomisation 203 (range 6-920) days. Most achieved full (64%) or over half (87%) dose, with no difference between cilostazol vs ISMN, single vs dual drugs. Headache and palpitations increased initially then declined similarly with dual versus single drugs. There was no between-group difference in BP, pulse-wave velocity, haemoglobin or platelet function, but pulse rate was higher (mean difference, MD, 6.4, 95%CI 1.2-11.7, p = 0.02), platelet count higher (MD 35.7, 95%CI 2.8, 68.7, p = 0.03) and white matter hyperintensities reduced more (Chi-square p = 0.007) with cilostazol versus no cilostazol.
Interpretation: Cilostazol and ISMN are well tolerated when the dose is escalated, without safety concerns, in patients with lacunar stroke. Larger trials with longer term follow-up are justified.
Funding: Alzheimer's Society (AS-PG-14-033).

Matched MeSH terms: Neuroimaging
Acute necrotising encephalopathy of childhood: A review of two cases

Ong SCL, Nur Azidawati AH, Liew YH, Anita S

Med J Malaysia, 2017 10;72(5):311-313.
PMID: 29197889 MyJurnal

Acute necrotising encephalopathy of childhood (ANEC) is an uncommon disease with characteristic clinical and imaging findings. We present two cases of ANEC secondary to Respiratory Syncytial Virus (RSV) and mycoplasma infections. An eight-month-old boy presented with features of gastroenteritis but soon developed multiple episodes of seizures. Blood and CSF cultures were negative but nasopharyngeal aspirate immunofluorescence was positive for RSV. A nine-year-old girl presented with abnormal behaviour following two days of prodromal symptoms. Her serological markers implicated mycoplasma (IgM titre 1: 640). CT brain of both patients showed bilateral symmetrical thalamic hypodensities, while MRI revealed more extensive white matter involvements.

Matched MeSH terms: Neuroimaging
Fulltext A multi-resolution textural approach to diagnostic neuropathology reporting

Fauzi MF, Gokozan HN, Elder B, Puduvalli VK, Pierson CR, Otero JJ, et al.

J Neurooncol, 2015 Sep;124(3):393-402.
PMID: 26255070 DOI: 10.1007/s11060-015-1872-4

We present a computer aided diagnostic workflow focusing on two diagnostic branch points in neuropathology (intraoperative consultation and p53 status in tumor biopsy specimens) by means of texture analysis via discrete wavelet frames decomposition. For intraoperative consultation, our methodology is capable of classifying glioblastoma versus metastatic cancer by extracting textural features from the non-nuclei region of cytologic preparations based on the imaging characteristics of glial processes, which appear as anisotropic thin linear structures. For metastasis, these are homogeneous in appearance, thus suitable and extractable texture features distinguish the two tissue types. Experiments on 53 images (29 glioblastomas and 24 metastases) resulted in average accuracy as high as 89.7 % for glioblastoma, 87.5 % for metastasis and 88.7 % overall. For p53 interpretation, we detect and classify p53 status by classifying staining intensity into strong, moderate, weak and negative sub-classes. We achieved this by developing a novel adaptive thresholding for detection, a two-step rule based on weighted color and intensity for the classification of positively and negatively stained nuclei, followed by texture classification to classify the positively stained nuclei into the strong, moderate and weak intensity sub-classes. Our detection method is able to correctly locate and distinguish the four types of cells, at 85 % average precision and 88 % average sensitivity rate. These classification methods on the other hand recorded 81 % accuracy in classifying the positive and negative cells, and 60 % accuracy in further classifying the positive cells into the three intensity groups, which is comparable with neuropathologists' markings.

Matched MeSH terms: Neuroimaging
Fulltext Classification of Targets and Distractors Present in Visual Hemifields Using Time-Frequency Domain EEG Features

Sweeti, Joshi D, Panigrahi BK, Anand S, Santhosh J

J Healthc Eng, 2018;2018:9213707.
PMID: 29808111 DOI: 10.1155/2018/9213707

This paper presents a classification system to classify the cognitive load corresponding to targets and distractors present in opposite visual hemifields. The approach includes the study of EEG (electroencephalogram) signal features acquired in a spatial attention task. The process comprises of EEG feature selection based on the feature distribution, followed by the stepwise discriminant analysis- (SDA-) based channel selection. Repeated measure analysis of variance (rANOVA) is applied to test the statistical significance of the selected features. Classifiers are developed and compared using the selected features to classify the target and distractor present in visual hemifields. The results provide a maximum classification accuracy of 87.2% and 86.1% and an average classification accuracy of 76.5 ± 4% and 76.2 ± 5.3% over the thirteen subjects corresponding to the two task conditions. These correlates present a step towards building a feature-based neurofeedback system for visual attention.

Matched MeSH terms: Neuroimaging
Fulltext Leptomeningeal Carcinomatosis With Optic Nerve Metastasis Secondary to Breast Cancer

Chew C, Wan Hitam WH, Ahmad Tajudin LS

Cureus, 2021 Mar 31;13(3):e14200.
PMID: 33936906 DOI: 10.7759/cureus.14200

Leptomeningeal carcinomatosis (LC) and optic nerve metastasis are uncommon occurrences in breast cancer. We report a rare case of LC with optic nerve infiltration secondary to breast cancer. A 45-year-old lady who was a known case of treated right breast carcinoma six years ago presented with a blurring of vision in both eyes, floaters, and diplopia for one month. She also had recurrent attacks of seizure-like episodes, headache, and vomiting. Examination revealed high blood pressure with tachycardia. Her right eye visual acuity was counting fingers at two feet and 6/36 in the left eye. She had right abducens nerve palsy. Fundoscopy showed bilateral optic disc swelling with pre-retinal, flame-shaped haemorrhages and macular oedema. CT scan of brain and orbit was normal. She was admitted for further investigations. While in the ward, her vision deteriorated further. Her visual acuity in both eyes was at the level of no perception to light. She also developed bilateral abducens nerve palsy and right facial nerve palsy. Subsequently, she started having bilateral hearing loss. There were few episodes of fluctuations in conscious awareness. MRI brain showed mild hydrocephalus. Both optic nerves were thickened and enhanced on T1-weighted and post-gadolinium. Lumbar puncture was performed. There was high opening pressure. Cerebrospinal fluid cytology showed the presence of malignant cells. Family members opted for palliative care in view of poor prognosis. Unfortunately, she succumbed after a month's stay in hospital. Diagnosis of LC and optic nerve infiltration presents a formidable challenge to clinicians especially in the early stages where neuroimaging appears normal and lumbar puncture has high false negatives. Multiple high-volume taps are advised if clinical suspicion of LC is high.

Matched MeSH terms: Neuroimaging
A rare case of methicillin resistant Staphylococcus aureus (MRSA) cerebral abscess secondary to conjunctivitis

Gan YK, Azmi AZ, Ghani SA, Samsudin A

Med J Malaysia, 2017 06;72(3):197-198.
PMID: 28733571 MyJurnal

This case report discusses the rare association of cerebral abscess related to conjunctivitis in an otherwise healthy child. A 6 year old boy presented with conjunctivitis was treated with topical antibiotics and resolved after a week. Conjunctival swab cultures grew MRSA. A month later he developed status epileptics and CT scans revealed a large cerebral abscess. He was treated with intravenous antibiotics which covered for MRSA, along with an incision and drainage for the cerebral abscess. Pus cultures grew MRSA. The patient recovered well with no disturbance in visual acuity or visual field. On post-operative follow ups, he had no other neurological deficit apart from a slight limp.

Matched MeSH terms: Neuroimaging
Fulltext Chloral hydrate as a sedating agent for neurodiagnostic procedures in children

Fong CY, Tay CG, Ong LC, Lai NM

Cochrane Database Syst Rev, 2017 Nov 03;11(11):CD011786.
PMID: 29099542 DOI: 10.1002/14651858.CD011786.pub2

BACKGROUND: Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure.
OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children.
SEARCH METHODS: We used the standard search strategy of the Cochrane Epilepsy Group. We searched MEDLINE (OVID SP) (1950 to July 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 7, 2017), Embase (1980 to July 2017), and the Cochrane Epilepsy Group Specialized Register (via CENTRAL) using a combination of keywords and MeSH headings.
SELECTION CRITERIA: We included randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo for children undergoing non-invasive neurodiagnostic procedures.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data, mean difference (MD) for continuous data, with 95% confidence intervals (CIs).
MAIN RESULTS: We included 13 studies with a total of 2390 children. The studies were all conducted in hospitals that provided neurodiagnostic services. Most studies assessed the proportion of sedation failure during the neurodiagnostic procedure, time for adequate sedation, and potential adverse effects associated with the sedative agent.The methodological quality of the included studies was mixed, as reflected by a wide variation in their 'Risk of bias' profiles. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 13 studies had high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in single small studies.Children who received oral chloral hydrate had lower sedation failure when compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study, moderate-quality evidence). Children who received oral chloral hydrate had a higher risk of sedation failure after one dose compared to those who received intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study, low-quality evidence), but after two doses there was no evidence of a significant difference between the two groups (RR 3.00, 95% CI 0.33 to 27.46; 1 study, very low-quality evidence). Children who received oral chloral hydrate appeared to have more sedation failure when compared with music therapy, but the quality of evidence was very low for this outcome (RR 17.00, 95% CI 2.37 to 122.14; 1 study). Sedation failure rates were similar between oral chloral hydrate, oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam.Children who received oral chloral hydrate had a shorter time to achieve adequate sedation when compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study, moderate-quality evidence), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study, moderate-quality evidence), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study, moderate-quality evidence), and rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study, low-quality evidence) and intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study, moderate-quality evidence).No data were available to assess the proportion of children with successful completion of neurodiagnostic procedure without interruption by the child awakening. Most trials did not assess adequate sedation as measured by specific validated scales, except in the comparison of chloral hydrate versus intranasal midazolam and oral promethazine.Compared to dexmedetomidine, chloral hydrate was associated with a higher risk of nausea and vomiting (RR 12.04 95% CI 1.58 to 91.96). No other adverse events were significantly associated with chloral hydrate (including behavioural change, oxygen desaturation) although there was an increased risk of adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study, low-quality evidence).
AUTHORS' CONCLUSIONS: The quality of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was very variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine for children undergoing paediatric neurodiagnostic procedures. The sedation failure was similar for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. When compared with intravenous pentobarbital and music therapy, oral chloral hydrate had a higher sedation failure rate. However, it must be noted that the evidence for the outcomes for the comparisons of oral chloral hydrate against intravenous pentobarbital and music therapy was of very low to low quality, therefore the corresponding findings should be interpreted with caution.Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially the risk of major adverse effects such as bradycardia, hypotension, and oxygen desaturation.

Matched MeSH terms: Neuroimaging