Clinical characteristics, treatment and long-term prognosis in patients with anti-NMDAR encephalitis.

OBJECTIVES: We aimed to (i) analyse the clinical characteristics, treatment outcome and long-term prognosis of anti-NMDAR encephalitis and (ii) study the differences between paediatric and adult patients. METHODS: This was a chart review of all patients with anti-NMDAR encephalitis. RESULTS: There were 28 patients with 18 patients belonging to the paediatric (<18 years) age group. There was female (94%) preponderance in the paediatric age group, while in adult patients, there was no gender predilection (p=0.006). There was no significant difference in clinical feature, outcome or number of relapses between paediatric and adult population groups. MRI brain was abnormal in 53% of patients. Among the 15 patients with MRI abnormalities at the onset, 53% had poor functional outcome at 1 year, while in 12 patients with normal initial MRI brain, only 8% had poor functional outcome at 1 year (p =0.01). Nearly 53% of patients with abnormal MRI at presentation had at least one clinical relapse within 2 years while in patients with normal MRI at presentation, 15% had a clinical relapse (p=0.037). EEG abnormalities were noticed in 71% of patients; among them, 40 and 15% had poor functional outcome at 1 and 2 years respectively. In comparison, those with normal first EEG at onset, 12% had poor functional outcome at 2 years (p=0.57). CONCLUSIONS: Both paediatric and adult patients presented with similar clinical features but the paediatric population had female preponderance. The functional outcome and number of relapse were comparable in both the paediatric and adult groups. Patients with parenchymal changes on MRI and abnormal EEG showed poorer response compared to those with normal MRI and/or EEG at the onset. Patients have lesser severity of symptoms at relapse than in the first episode. An early diagnosis and treatment are essential for better long-term functional outcome.

Having caregiving responsibilities affects management of fragility fractures and bone health.

In this secondary analysis of six qualitative studies, we found that approximately one-quarter of individuals with fragility fracture were serving as informal caregivers. The caregiving role appeared to be a cause of the fracture for some and was prioritized over bone health, acting as a barrier to bone health management. INTRODUCTION: Among fragility fracture patients serving as informal caregivers, our objective was to examine how caregiving responsibilities were associated with, and possibly impacted by, the fracture experience and the resulting management of bone health. METHODS: We conducted a secondary analysis (amplified analysis) of six qualitative studies to understand caregiver responsibilities and the relationship between these responsibilities and patients' management of the fracture and bone health. The primary studies and the secondary analysis were conducted from a phenomenological approach. Eligible individuals in the primary studies were English-speaking men and women who were 45+ years old recruited from three settings (local, provincial, and national). RESULTS: Without being prompted to talk about their experience of caregiving, 33 of 145 (23%) individuals reported they were providing care to a family member or friend at the time of their fracture or during recovery post-fracture. The experience of having caregiving responsibilities was related to the fracture and bone health in two ways: (1) the caregiving role appeared to be a cause of the fracture in some participants and (2) caregiving was prioritized over participants' own bone health and was a barrier to bone health management. CONCLUSION: Fragility fracture is associated with, and potentially leads to an impairment of, an important social role in patients providing physical and emotional support and supervision for dependents as caregivers. Further, an important cause of fragility fracture can occur in the act of caregiving.

Intramedullary tumours and tumour mimics.

Spinal cord lesions are traditionally classified as either extradural or intradural extramedullary or of intramedullary origin. Intramedullary spinal cord tumours are histopathologically similar to cranial tumours with a diverse range of pathologies. Astrocytomas and ependymomas account for approximately 80% of all intramedullary tumours, with other primary and secondary lesions accounting for the remaining 20%. Magnetic resonance imaging is the preferred imaging modality for diagnosing and characterising spinal cord lesions; however, accurate characterisation of tumour histology can be challenging, and is further confounded by intramedullary non-neoplastic lesions, such as demyelinating vascular, inflammatory, infectious, or traumatic lesions. This review illustrates the spectrum of intramedullary tumours and tumour mimics with emphasis on the imaging findings.

Three-dimensional neuromelanin-sensitive magnetic resonance imaging of the substantia nigra in Parkinson's disease.

BACKGROUND AND PURPOSE: The aim was to investigate the diagnostic utility of signal intensity measurement of the substantia nigra pars compacta (SNc) using three-dimensional (3D) neuromelanin-sensitive magnetic resonance imaging (MRI), for discrimination of patients with Parkinson's disease (PD) from healthy controls. METHODS: T1-weighted neuromelanin-sensitive images of 16 patients with PD and 15 controls were quantitatively analyzed by placing circular 10 mm2 regions of interest over the central and lateral parts of the bilateral SNc and anterior to the cerebral aqueduct at three levels of the midbrain. Signal intensities and contrast ratios (CRs) were calculated, after which significant differences, correlations, sensitivity and specificity were calculated. RESULTS: The CRs of the central and lateral SNc were significantly lower in patients with PD. Lateral CRs were lower than the central CRs in both groups and significantly correlated with duration of illness. CRs of central and lateral parts of the SNc also correlated with the Unified Parkinson's Disease Rating Scale III OFF state scores. Receiver operating characteristic analysis revealed lateral CRs to be more sensitive and central CRs to be more specific for the discrimination of patients with PD from controls. CONCLUSIONS: Contrast ratio analysis of the SNc using 3D neuromelanin-sensitive MRI may serve as a quick and accurate tool to discern between patients with PD and healthy controls.

Multiparametric imaging-based differentiation of lymphoma and glioblastoma: using T1-perfusion, diffusion, and susceptibility-weighted MRI.

AIM: To compare the diagnostic performance of T1 perfusion magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and susceptibility-weighted imaging (SWI) for differentiating primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM). MATERIALS AND METHODS: This retrospective study comprised a cohort of 70 patients with glioblastoma and 30 patients with PCNSL. T1 perfusion MRI-derived rCBV_corr (leakage corrected relative cerebral blood volume), apparent diffusion coefficient (ADC) derived from DWI, and intratumoural susceptibility signals intensity (ITSS) measured on SWI were evaluated in these 100 patients. The Mann-Whitney U-test was used for pairwise comparison between groups. The diagnostic performance for differentiating PCNSL from glioblastoma was evaluated by using univariate and multivariable logistic regression analyses and receiver operating characteristic (ROC) analysis. RESULTS: Minimum ADC, maximum rCBVs_corr, kep (back flux exchange rate), and ITSS scores were significantly lower in patients with PCNSL than in those with glioblastoma (p<0.05). On ROC analysis, ITSS showed the best discrimination ability for differentiation of GBM and PCNSL with an area under the ROC curve (AUC) of 0.80. rCBV_corr and ADC showed AUCs of 0.68 and 0.63, respectively. Multiparametric assessment using ADC, rCBV_corr, kep, and ITSS scores significantly increased the diagnostic ability for differentiating PCNSL from GBM as compared to mean ADC, mean rCBV_corr, and ITSS alone or a combination of these parameters. The multiparametric model could correctly discriminate 84% of tumours with a sensitivity and specificity of 90% and 70% with an AUC of 0.92. CONCLUSION: Multiparametric MRI evaluation using DWI, T1 perfusion MRI, and SWI enabled reliable differentiation of PCNSL and GBM in the majority patients, and these results support an integration of advanced MRI techniques for the diagnostic work-up of patients with these tumours.

A study of structural and functional connectivity in early Alzheimer's disease using rest fMRI and diffusion tensor imaging.

BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is a progressive neurodegenerative condition where in early diagnosis and interventions are key policy priorities in dementia services and research. We studied the functional and structural connectivity in mild AD to determine the nature of connectivity changes that coexist with neurocognitive deficits in the early stages of AD. METHODS: Fifteen mild AD subjects and 15 cognitively healthy controls (CHc) matched for age and gender, underwent detailed neurocognitive assessment and magnetic resonance imaging (MRI) of resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Rest fMRI was analyzed using dual regression approach and DTI by voxel wise statistics. RESULTS: Patients with mild AD had significantly lower functional connectivity (FC) within the default mode network and increased FC within the executive network. The mild AD group scored significantly lower in all domains of cognition compared with CHc. But fractional anisotropy did not significantly (p < 0.05) differ between the groups. CONCLUSION: Resting state functional connectivity alterations are noted during initial stages of cognitive decline in AD, even when there are no significant white matter microstructural changes.

Clinical and imaging characteristics of 16 patients with autoimmune neuronal synaptic encephalitis.

OBJECTIVES: Autoimmune neuronal synaptic encephalitis (AIE) encompasses a heterogeneous group of disorders characterized by immune-mediated neuronal cell destruction. In this study, we aim to study the clinical features, imaging profile and treatment outcome of patients with AIE. METHODS: This is a chart review of 16 (M: F-3:13) patients with AIE from 2011 to 2015. RESULTS: Among the patients, 10 had anti-NMDA, 4 had anti-TPO, and 2 had anti-VGKC antibody positivity. Cognitive impairment and seizures were the predominant symptoms present in nearly all patients, followed by psychiatric disturbances (87.5%), mutism (62.5%), movement disorders (62.5%), myoclonic jerks (37.5%) and visual hallucinations (18.75%). Magnetic resonance imaging (MRI) of the brain was available in 15 patients; it was abnormal in 53.3% patients. Abnormalities were seen in all patients with anti-VGKC positivity; and, 60% of patients with anti-NMDA positivity. Imaging was normal in 26.7% of the patients (3: anti-NMDA; and, 1: anti-TPO positivity); and, diffuse cerebral atrophy was noted in rest of the 20% (3: anti-TPO positivity) patients. All patients improved gradually with immunomodulation. CONCLUSIONS: All patients with anti-VGKC, anti-NMDA and anti-TPO antibody positivity presented with a triad of behavioral changes, impaired cognition and seizures. Mutism was a predominant symptom in patients with an anti-NMDA antibody positivity, which may help in the early identification of this disorder. MRI brain showed changes restricted to limbic structures in anti-NMDA and anti-VGKC antibody positivity. An early diagnosis and treatment of autoimmune encephalitis is essential for a better outcome and for prevention of long-term sequel.

Association between cortical volume loss and cognitive impairments in essential tremor.

BACKGROUND AND PURPOSE: Impairment of cognitive functions occurs in essential tremor (ET) although the mechanism is largely unknown. A possible association between cognitive performance and brain atrophy in ET patients was examined using neuropsychological tests and voxel-based morphometry (VBM). METHODS: Twenty-five patients with ET and 25 matched healthy controls were evaluated. ET was diagnosed using the National Institutes of Health collaborative genetic criteria. Severity of tremor was assessed using the Fahn-Tolosa-Marin (FTM) tremor rating scale. Subjects were assessed using a structured neuropsychological battery. Brain images were acquired using a 3T magnetic resonance imaging scanner. VBM analysis was performed using Statistical Parametric Mapping 8. RESULTS: The age of the patients was 45.0 ± 10.7 years and of controls 45.4 ± 10.7 years. Tremor duration was 9.84 ± 6.63 years and total FTM score was 37.34 ± 17.67. Patients were divided into two groups: ETCI with cognitive impairment (three or more abnormal neuropsychological tests, 1.5 standard deviation criterion) and ETNCI without cognitive impairment. Compared with controls, the ETCI group had significantly impaired performance in neuropsychological tests. One-way analysis of variance was performed between the three groups (ETCI, ETNCI, controls) followed by the two-sample t test. Compared with controls, grey matter volume (GMV) loss was observed in ETCI in the cerebellum (anterior and posterior lobes) and medial frontal gyrus. GMV loss was observed in ETCI compared with ETNCI in the medial frontal gyrus, post central gyrus, anterior cingulate and insula. Impairment in neuropsychological tests significantly correlated with GMV of the medial frontal gyrus, superior parietal lobe, middle temporal gyrus, occipital lobe, lentiform nucleus, insular and cingulate cortices and cerebellum posterior lobe in ETCI. CONCLUSIONS: A correlation between neurocognitive deficits in ETCI and GMV was observed suggesting that grey matter atrophy appears to be a correlate of cognitive impairment in ET.

Evolution of MRI changes in Rasmussen's encephalitis.

PURPOSE: We studied the MRI findings in 16 patients with Rasmussen's encephalitis (RE), further analysed serial MRI changes in 11 of them and correlated it with clinical features. METHODOLOGY: The diagnosis of RE was based on the European consensus statement (Brain, 128, 2005, 454). Details related to demographical, clinical, MRI observations were analysed. RESULTS: Forty MRIs of brain of 16 patients were reviewed. Eleven patients had undergone serial brain MRIs ranging from two to five occasions. All the patients had unihemispheric focal cortical atrophy, predominantly in the perisylvian region (n = 13). Other features were white matter signal changes (n = 14), and ipsilateral caudate (n = 6) and putamen (n = 4) atrophy. Signal alterations in putamen and caudate were noted in four each. In all the 11 patients with serial MRI, there was progression of cerebral atrophy and a trend towards increase in MRI staging. The MRI signal changes remained same in five patients, resolved in three patients, differential change in two patients and increased in one patient. Diffusion-weighted imaging showed facilitated diffusion (n = 5), and MR spectroscopy showed reduced N-acetyl-aspartate and elevated lactate (n = 2). CONCLUSIONS: Pattern recognition of MRI findings and the changes in serial MRI might serve as a surrogate marker of disease viz. unihemispheric progressive focal cortical atrophy and signal changes predominantly in the perisylvian distribution and caudate followed by putamen involvement. This might assist in understanding and monitoring of the disease progression.

Subcortical structures in progressive supranuclear palsy: vertex-based analysis.

BACKGROUND AND PURPOSE: To study the abnormalities of deep grey matter (GM) structures in patients with progressive supranuclear palsy (PSP) using MR volumetry and shape analysis techniques. METHODS: Twenty-eight patients with PSP and 25 matched controls (all were right handed) were evaluated using standard clinical scales. MRI was performed on a 3 tesla MRI scanner using standard protocol which included T1-3D Turbo Field-Echo images with 1-mm slice thickness. The volumes of GM and white matter, total brain and the deep subcortical GM structures, including hippocampus, amygdala, caudate, putamen, globus pallidus and thalamus were extracted using a fully automated tool. Univariate analysis of covariance, adjusted for intracranial volume (ICV), sex and age, was used to explore group differences. Shape analysis was also performed using automated software with age, sex and total brain volume as covariates of no interest in the statistical design at P < 0.05 (FDR corrected). RESULTS: The patients with PSP had significantly lower volumes of bilateral thalami, hippocampus, pallidum and brainstem. Shape analysis of GM structures showed significant surface reduction in bilateral thalami and head of right caudate nucleus. CONCLUSIONS: MR volumetry showed abnormalities of various deep GM structures. Shape analysis also revealed focal surface contractions in multiple subcortical structures. Our study highlights the usefulness of this novel technique in detecting abnormalities of deep GM structures.

Tumefactive demyelination: clinical, imaging and follow-up observations in thirty-nine patients.

PURPOSE: We describe the clinical, neuroimaging and pathological features and therapeutic outcome in a large cohort of 39 patients with tumefactive demyelination. MATERIALS AND METHODS: A retrospective audit of 39 patients with 'tumefactive demyelination' was performed. The demographic, clinical, MR imaging and pathological details were reviewed. RESULTS: The clinical course was monophasic (n = 22) or relapsing-remitting (n = 17). Common neurological manifestations at presentation included hemiparesis - 27; ataxia - 11; vomiting - 10; headache -9; ophthalmoplegia - 7; seizure - 5; impaired vision - 4; aphasia - 4; visual field defects - 3; papilloedema - 5; extrapyramidal - 5; intellectual decline - 5; behavioural disturbances - 3; altered sensorium - 5. MRI revealed fronto-parietal lesions, which were isolated in 14 (36%) patients. Moderate perilesional oedema and/or mass effect was noted in 12 (30.8%) patients. Post-contrast MR sequences revealed partial ring enhancement in 15, complete ring in seven, patchy enhancement in six, uniform enhancement in two and lack of enhancement in nine cases. Clinical and MR characteristics did not help distinguish between monophasic and relapsing-remitting subgroups. In the monophasic group, 53.8% had complete recovery, while 38.5% had partial improvement (follow-up duration, 8.31 ± 9.3 months). In the relapsing-remitting subgroup, the median time to relapse was 4 months (n = 12, follow-up, 37.8 ± 39.4 months). Patients with monophasic course or single relapse received steroids. Patients with more than one relapse received cyclophosphamide (2), mycophenolate (1), azathioprine (1) or methotrexate (1). CONCLUSIONS: A high proportion of cases of tumefactive demyelination follow a relapsing course, thus necessitating a long-term follow-up. MRI, although helpful in diagnosis, does not predict monophasic or relapsing-remitting course. Guidelines for the management of acute episodes and prevention of relapses are required.

Comparison of 3 agar media in Fung double tubes and Petri plates to detect and enumerate Clostridium spp. in broiler chicken intestines.

Clostridium perfringens is an anaerobic, spore-forming bacterium that may lead to necrotic enteritis, resulting in poor feed efficiency and increased mortality in chickens. It is estimated that C. perfringens infects almost 1 million people in the United States every year. The objective of this research was to compare the Fung double tube (FDT) and conventional Petri plates using 3 different media to detect and enumerate Clostridium spp. in chicken intestines. Nine Cobb 500 broilers were randomly selected and euthanized at 21 and 42 d of age for a total of 18 samples. The jejunum and ileum from each broiler were harvested and studied in 2 methods and 3 media combinations, utilizing a 2 × 3 factorial totaling 6 treatments. The 2 methods were FDT and conventional Petri plates, and the 3 media were Shahidi-Ferguson Perfringens (SFP) with egg yolk supplement, polymyxin B, and kanamycin (E); SFP with polymyxin B and kanamycin (P); and SFP with d-cycloserine (C). Enumerations were performed after 24 h of incubation at 37°C. At 21 d, counts using medium C with FDT (4.51 log10 cfu/g) and plates (2.38 log10 cfu/g) were higher (P < 0.05) than using media E or P. On d 42, there were no differences among plate treatments and medium E had the highest counts (0.98 log10 cfu/g). Of all the FDT, medium C (5.35 log10 cfu/g) had the highest counts (P < 0.05), followed by medium P (3.54 log10 cfu/g). This study illustrates that the FDT method is able to enumerate Clostridium spp. at higher levels (P < 0.001) than the conventional Petri plate method; therefore, the FDT should be implemented and further explored.

The impact of chemotherapy on quality of life in advanced-stage lung cancer patients.

Background: Most patients with lung cancer are diagnosed at advanced stages of the disease, where chemotherapy plays an important role. This prospective study was conducted to determine the impact of palliative chemotherapy on quality of life (QOL) in advanced-stage lung cancer patients. Methods: QOL in lung cancer out-patients was assessed at diagnosis and end of treatment using the EORTC QLQ-C30 questionnaire. Changes in mean QOL scores were calculated. The correlation between patients' tumor response and change in QOL scores was also studied. Scoring was done according to the EORTC manual and results were analyzed using SPSS statistical package. Results: Out of 52 patients, 46 (88.46%) were men and six (11.54%) were women. After chemotherapy, patients' overall QOL score improved significantly (P = 0.005). Cognitive functioning significantly worsened (P = 0.01). Physical functioning (PF) and emotional functioning (EF) scores improved, while role functioning (RF) and social functioning (SF) scores worsened. Pain, dyspnea, and sleep significantly improved (P = 0.001, P = 0.001, and P = 0.005 respectively). On the other hand, nausea, vomiting (P = 0.000), diarrhea (P = 0.004), and financial difficulties (P = 0.009) worsened. Overall QOL improved in patients with partial tumor response (PR) and stable disease (SD) (P = 0.044 and P = 0.000, respectively), but worsened in progressive disease group (PD) (P = 0.648). Symptom scores improved markedly in PR and SD groups. Chemotherapy toxicity was maximum in PD group (P = 0.028). Conclusion: Global quality of life and symptom control significantly improved in lung cancer patients after chemotherapy. Deterioration of cognitive functioning, increased financial burden, and chemotherapy-related toxicity were noteworthy. Changes in QOL were coherent with patients' tumor response.

Comparison of the diagnostic yield of transbronchial lung biopsies by forceps and cryoprobe in diffuse parenchymal lung disease.

Background: Transbronchial lung cryobiopsy (TBLC) in the diagnosis of diffuse parenchymal lung disease (DPLD) has shown a promising yield in recent times, with low post-procedural mortality and morbidity. Objectives: To compare the yield of TBLC and conventional transbronchial forceps lung biopsy (TBLB). Methods: A prospective study was carried out in patients with DPLD over a period of 1 year in a tertiary respiratory care institute in New Delhi, India. All 87 patients enrolled underwent both TBLB and TBLC. The procedures were performed in the bronchoscopy suite under conscious sedation and local anaesthesia, with an attempt to take a minimum of three biopsy specimens by conventional TBLB followed by TBLC. A 1.9 mm cryoprobe with a freezing time of 4 - 5 seconds was used. An Arndt endobronchial blocker was used to control bleeding along with locally administered medications. Results: TBLB and TBLC led to a definitive diagnosis in 27 (31.0%) and 69 (79.3%) cases, respectively. The commonest diagnoses were hypersensitivity pneumonitis, sarcoidosis and pulmonary tuberculosis. TBLC led to additional diagnoses in 42 cases (48.3%). Pneumothorax was observed in 12 cases (13.8%), and moderate bleeding occurred in 63 (72.4%). There were no procedure-related deaths. Conclusion: TBLC had a better diagnostic yield than conventional TBLB in DPLD. It has the potential to become a safe day-care procedure in a resource-limited setting, if certain precautions are taken. Study synopsis: What the study adds. Compared with transbronchial forceps lung biopsy, transbronchial lung cryobiopsy (TBLC) led to additional diagnoses in 42 (48.3%) of 87 patients with clinicoradiological features of diffuse parenchymal lung disease. Pneumothorax was observed in 12 cases (13.8%) and moderate bleeding in 63 (72.4%). TBLC without rigid bronchoscopy or advanced airway devices under conscious sedation had a good diagnostic yield with an acceptable adverse events profile.Implications of the findings. TBLC under conscious sedation is not resource intensive and can be carried out in settings with limited resources.

Temporal resolution deficits in patients with refractory complex partial seizures and mesial temporal sclerosis (MTS).

We studied the temporal resolution ability in patients with refractory complex partial seizures and mesial temporal sclerosis (MTS) using Gaps-In-Noise (GIN) test in a prospective cross-sectional study. Thirteen patients with right MTS (age: 31±7.67 years; M:F=8:5) and 13 patients with left MTS (age: 25.76±8.26 years; M:F=9:4) having normal hearing and mini-mental state examination (MMSE) score of >23/30 were recruited. Fifty healthy volunteers (26.3±5.17 years; M:F=28:22) formed the control group. Gaps-In-Noise test demonstrated impaired temporal resolution: 69.2% of patients with right MTS (RMTS) and 76.9% of patients with left MTS (LMTS) had abnormal scores in the right ear for gap detection threshold (GDT) measure. Similarly, 53.8% of patients in the RMTS group and 76.9% of patients in the LMTS group had abnormal scores in the left ear. In percentage of correct identification (PCI), 46.1% of patients with RMTS and 69.2% of patients with LMTS had poorer scores in the right ear, whereas 46.1% of patients with RMTS and 61.5% of patients with LMTS had poorer scores in the left ear. Both patient groups, viz., RMTS and LMTS, demonstrated bilateral temporal resolution deficits.

Insights from Magnetic Evoked Field Analysis in Patients with Wilson's Disease.

Aims: To study the latency, amplitude, and source localization of magnetic evoked field (MEF) responses to visual, auditory, and somatosensory stimuli in Wilson's disease (WD) using magnetoencephalography (MEG) and compare it with "healthy" controls, and correlate the observations with disease severity and brain MRI. Methods: MEF of 28 patients with neurological WD (age: 22.82 ± 5.8 years; M:F = 12:16) and 21 matched controls (age: 25.0 ± 4.6 years; M:F = 10:11) were recorded using MEG. Source localization was performed using standard models on the components of M100, M20, and M100 for visual, somatosensory, and auditory evoked fields, respectively and its latency/amplitude was correlated with disease severity. Results: There were significant differences in source location between control and WD during visual evoked field (VEF) and auditory evoked field (AEF) studies. Latencies of M20 (right-p = 0.02; left-p = 0.04) and M32 (right-p = 0.01) components of SSEF were significantly prolonged. The amplitude of M20 was significantly reduced in patients bilaterally (P = 0.001). There was a trend for the prolonged latency of M100 of VEF in patients (P = 0.09). Five patients had reduced right M145 compared to 8 controls. The left somatosensory evoked fields (SSEF) latency correlated with disease severity (P = 0.04). There was no significant correlation between major components of other MEF with disease severity or MRI score. Conclusions: This study, first of its kind to use MEF analysis in a large cohort of patients with WD, detected subclinical but a variable degree of abnormalities, most consistently of SSEF. It provides valuable insights of functioning and localization of various pathways in a disease known to have protean clinical manifestations and widespread MRI changes.

COVID-19 vaccine associated demyelination & its association with MOG antibody.

BACKGROUND: ChAdOx1-S (Covishield™/Vaxzervria, AstraZeneca) and BBV152 (Covaxin) SARS-CoV-2 vaccines are proven to be safe and effective, but rare complications have been reported. OBJECTIVE: To describe reports of central nervous system (CNS) demyelination following ChAdOx1-S and BBV152 vaccinations. METHODS & RESULTS: We report 29 (17 female; mean 38 years) cases of CNS demyelination; twenty-seven occurred in temporal association with ChAdOx1-S vaccine; two in association with BBV152 vaccine. Eleven patients had presentation with myelitis, six patients developed optic neuritis, five had acute demyelinating encephalomyelitis, three presented with brainstem demyelination, and four had multiaxial involvement. Myelin oligodendrocyte glycoprotein (MOG) antibodies were positive in ten patients. One patient with ADEM and tumefactive demyelinating lesions died after a prolonged intensive care unit stay and superimposed infection. As compared to the control group (87); the postvaccinial cases were found to have a significantly higher mean age, presence of encephalopathy (p value:0.0007), CSF pleocytosis (p value: 0.0094) and raised CSF protein (p value: 0.0062). CONCLUSIONS: It is difficult to establish a causal relationship between vaccination and neurological adverse events such as demyelination. The temporal association with the vaccination and the presence of MOG antibodies raises the possibility of an immunogenic process triggered by the vaccine in susceptible individuals.

Efficacy of capecitabine versus 5-fluorouracil in colorectal and gastric cancers: a meta-analysis of individual data from 6171 patients.

BACKGROUND: To compare the effects of oral capecitabine-containing chemotherapy regimens with i.v. 5-fluorouracil (5-FU)-containing chemotherapy regimens on overall survival in patients with gastrointestinal cancers. METHODS: A meta-analysis, based on individual patient data from six randomised non-inferiority trials, was carried out at the request of regulatory authorities to compare the effects of single-agent capecitabine or capecitabine-containing chemotherapy versus matched 5-FU-based regimens in terms of overall survival in patients with stage III colon, metastatic colorectal or advanced gastric cancer. RESULTS: Data from a total of 6171 patients with stage III colon cancer (n = 1987), metastatic colorectal cancer (n = 3868) or advanced gastric cancer (n = 316) were included. A total of 3097 patients were treated with capecitabine-containing chemotherapy and 3074 patients with 5-FU-containing chemotherapy. The unadjusted hazard ratio for overall survival for capecitabine-containing chemotherapy versus 5-FU-containing chemotherapy was 0.94 (95% confidence interval 0.89-1.00; P = 0.0489). CONCLUSIONS: Oral capecitabine is at least equivalent to i.v. 5-FU in terms of overall survival in patients with gastrointestinal cancers. Capecitabine and 5-FU can be used interchangeably in these patient populations.

Clinical, neuroimaging and pathological features of 5-nitroimidazole-induced encephalo-neuropathy in two patients: Insights into possible pathogenesis.

We report two patients manifesting with involvement of central and peripheral nervous system with brain magnetic resonance imaging (MRI) changes and pathological features of neuropathy possibly due to harmful and chronic use of various nitroimidazole group of medications for recurrent diarrheal illness. Patient 1, a 21-year-old man with obsessive-compulsive disorder, impulsive behavior and harmful use of substance (tinidazole), had developed encephalopathy and biopsy-proven neuropathy with partial remission. The MRI of brain showed involvement of bilateral caudate, lentiform and dentate nuclei, and splenium, with contrast enhancement of the caudate and putaminal lesions and restricted diffusion of the splenial lesion. Patient 2 was a 50-year-old woman with irritable bowel syndrome and was on harmful use of tinidazole and metronidazole. She manifested with encephalopathy, ataxia, and neuropathy. Her MRI of brain revealed involvement of bilateral putamen, dentate nuclei and periventricular white matter with restricted diffusion. Sural nerve biopsy revealed evidence of vasculitic neuropathy. At follow-up, there was definite, though incomplete, recovery in both the patients. The MRI alterations improved completely in patient 2 and substantially in patient 1. Increasing awareness among the physicians may enable early recognition of potentially reversible neurotoxicity and avoid unwarranted prescription of such medications.

Differentiation of tubercular infection and metastasis presenting as ring enhancing lesion by diffusion and perfusion magnetic resonance imaging.

BACKGROUND AND PURPOSE: As both tuberculoma and metastasis can manifest as solitary or multiple ring-enhancing intra-axial lesions that are difficult to differentiate by conventional magnetic resonance imaging (MRI), we hypothesized that the use of diffusion and perfusion MRI would make differentiation of these pathologies possible. MATERIALS AND METHODS: Diffusion and T2*-weighted dynamic contrast-enhanced perfusion MRI scans from 11 patients with histologically proven tuberculoma or metastasis were retrospectively reviewed by two radiologists who were blinded to the pathology. All patients had a ring-enhancing lesion on conventional MRI. Apparent diffusion coefficient (ADC) values and regional cerebral blood volume (rCBV) were calculated from the walls of the lesions. RESULTS: Lesions showed different perfusion characteristics depending on whether they were due to tuberculosis or metastasis. The mean rCBV ratio between the lesion periphery and normal white matter was inferior to one for tubercular lesions and greater than five for metastases. However, ADC values were similar. CONCLUSION: Measuring rCBV obtained by T2*-weighted dynamic contrast-enhanced perfusion MRI can help in differentiating intracranial tubercular mass lesions and metastases.