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.

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.

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.

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.

In Vivo Evaluation of White Matter Abnormalities in Children with Duchenne Muscular Dystrophy Using DTI.

BACKGROUND AND PURPOSE: Duchenne muscular dystrophy is an X-linked disorder characterized by progressive muscle weakness and prominent nonmotor manifestations, such as a low intelligence quotient and neuropsychiatric disturbance. We investigated WM integrity in patients with Duchenne muscular dystrophy using DTI. MATERIALS AND METHODS: Fractional anisotropy and mean, axial, and radial diffusivity (DTI measures) were used to assess WM microstructural integrity along with neuropsychological evaluation in patients with Duchenne muscular dystrophy (n = 60) and controls (n = 40). Exon deletions in the DMD gene were confirmed using multiplex ligation-dependent probe amplification. Patients were classified into proximal (DMD Dp140+) and distal (DMD Dp140-) subgroups based on the location of the exon deletion and expression of short dystrophin Dp140 isoform. WM integrity was examined using whole-brain Tract-Based Spatial Statistics and atlas-based analysis of DTI data. The Pearson correlation was performed to investigate the possible relationship between neuropsychological scores and DTI metrics. RESULTS: The mean ages of Duchenne muscular dystrophy and control participants were 8.0 ± 1.2 years and 8.2 ± 1.4 years, respectively. The mean age at disease onset was 4.1 ± 1.8 years, and mean illness duration was 40.8 ± 25.2 months. Significant differences in neuropsychological scores were observed between the proximal and distal gene-deletion subgroups, with more severe impairment in the distal-deletion subgroup (P < .05). Localized fractional anisotropy changes were seen in the corpus callosum, parietal WM, and fornices in the patient subgroup with Dp140+, while widespread changes were noted in the Dp140- subgroup. The Dp140+ subgroup showed increased axial diffusivity in multiple WM regions relative to the Dp140- subgroup. No significant correlation was observed between clinical and neuropsychological scores and diffusion metrics. CONCLUSIONS: Widespread WM differences are evident in patients with Duchenne muscular dystrophy relative to healthy controls. Distal mutations in particular are associated with extensive WM abnormalities and poor neuropsychological profiles.

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.

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.

MN1 rearrangement in astroblastoma: study of eight cases and review of literature.

Astroblastomas are unique tumours with unresolved issues in terms of their origin, molecular biology, clinical behaviour, and response to treatment. To decipher the characteristics of this tumour, we reviewed cases histologically diagnosed as astroblastoma in our institute over the past 8 years, with immunohistochemistry, and performed fluorescence in situ hybridisation (FISH), for the newly emerged MN1 rearrangement which was reported in central nervous system high-grade neuroepithelial tumours. The mean age at diagnosis was 18.6 years with all cases seen in females and with supratentorial localisation. The tumours showed typical circumscription and bubbly appearance on imaging. The cohort included eight cases diagnosed as astroblastoma (two low grades; six anaplastic) based on histology and proliferative index. The tumours displayed characteristic astroblastic pseudorosettes with hyalinised vascular core and variable immunopositivity for glial fibrillary acidic protein, pan cytokeratin, and epithelial membrane antigen. MN1 break-apart by FISH was found in 5/8 of our cases (62.5%), which included 2 low-grade and 3 anaplastic tumours. Tumour recurrence was noted in three cases, with MN1 alteration in two. We account for one of the few series to study the MN1 rearrangement in astroblastoma and conclude that MN1 alteration is seen in a subset of these tumours.

High Tensile Ductility and Strength in Dual-phase Bimodal Steel through Stationary Friction Stir Processing.

The combination of high strength and good ductility are very desirable for advanced structural and functional applications. However, measures to enhance strength typically lead to ductility reduction due to their inverse correlation, nano-grained structures for an instance. Bi-modal grain structure is promising in this regard, but its realization is limited by multiple complex processing steps. Here, we demonstrate a facile single-step processing route for the development of bimodal grain structure in austenitic stainless steel, SS316L. The bimodal structure comprised of fine martensite grains (<500 nm) sandwiched between coarse austenite grains (~10 µm). The dual-phase bimodal structure demonstrated higher yield strength (~620 MPa) compared to ultra-fine grain structure (~450 MPa) concurrent with high uniform tensile ductility (~35%). These exceptional properties are attributed to unique dual-phase, bimodal grain structure which delayed the onset of plastic instability resulting in higher strength as well as larger uniform elongation and work-hardening rate. Our approach may be easily extended to a wide range of material systems to engineer superior performance.

Comparison of inhaled versus intravenous anesthesia for laryngoscopy and laryngeal electromyography in a rat model.

BACKGROUND: Propofol and remifentanil intravenous combination is one popular form of total intravenous anesthesia (TIVA) in mainstream clinical practice, but it has rarely been applied to a rat model for laryngoscopy and laryngeal electromyography (LEMG). Our objective was to establish a safe and reproducible general anesthetic protocol for laryngoscopy and endoscopic LEMG in a rat model. Our hypothesis is that TIVA allows a minimally morbid, and feasible laryngoscopy and LEMG. METHODS: Sprague Dawley rats were subjected to either inhalational anesthesia (IA) (isoflurane) or TIVA (propofol and remifentanil) and underwent laryngoscopy and LEMG. The primary outcome was a complete minimally interrupted rigid laryngoscopy and obtaining reproducible motor unit potentials from the posterior cricoarytenoid muscles. The secondary outcome was morbidity and mortality. RESULTS: Seventeen out of twenty-two rats underwent both TIVA and IA. Only two underwent IA only. All nineteen rats that underwent IA had a successful experiment. Seventeen rats underwent TIVA, however, only nine completed a successful experiment due to difficulty achieving a surgical plane, and respiratory events. Upon comparing the success of the two anaesthetic regimens, IA was superior to TIVA (P = 0.0008). There was no statistical difference between the amplitudes (p = 0.1985) or motor units burst duration (p = 0.82605) of both methods. Three mortalities were encountered, one of which was due to lidocaine toxicity and two were during anesthetic induction. Respiratory related morbidity was encountered in two rats, all seen with TIVA. CONCLUSIONS: TIVA is not an ideal anesthetic regimen for laryngeal endoscopy and LEMG in rat models. Contrary to our hypothesis, IA did not affect the quality of the LEMG and allowed a seamless rigid endoscopy.

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.

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.

Improvement of Diffusion Tensor Imaging (DTI) Parameters with Decoppering Treatment in Wilson's Disease.

OBJECTIVE: This study was undertaken to analyse serially the effects of decoppering therapy on the clinical features, disability and MRI brain including DTI metrics in patients with Wilson's disease. METHODS AND RESULTS: Thirty-five patients with clinically and serologically confirmed neuropsychiatric form of Wilson's disease (WD) on decoppering therapy were followed for a minimum duration of 1 year with serial assessment of their clinical features, disability status and serial MR imaging of the brain including DTI. The cohort included 18 treatment-naïve patients and 17 patients already on decoppering therapy (M/F = 2.18:1). The mean age at which they underwent baseline assessment for this study was 18.6 ± 7.6 years, and follow-up assessment was done after a mean duration of 23.5 ± 8.8 months (range, 12 to 45 months). Along with the overall clinical improvement noted at follow-up, the disability assessed using Chu staging and MSEADL showed significant reduction in the number of patients with severe disability and the mean NSS reducing from 9.74 to 6.37 (p = 0.002). The mean MRI scores showed significantly reduced disease burden from a baseline score of 5.9 (±4.2) to 4.9 (±4.7) in follow-up scans (p < 0.05). Voxel-wise comparison of serial DTI metrics on TBSS (tract-based spatial statistics) analysis showed that the entire cohort had significant (p < 0.05) improvement in all the four parameters (MD, FA, DA and RD) indicated by a decrease in MD, DA and RD values and increase in FA values. Comparison of whole-brain white matter DTI measures between pre- and posttreatment did not show any significant difference (p < 0.05). CONCLUSION: Patients with Wilson's disease on decoppering therapy showed clinical improvement accompanied with improvement in DTI metrics. Quantitative DTI metrics may be used as surrogate markers of clinical status following initiation of medical therapy in Wilson's disease.

Clinical, electrophysiological, imaging, pathological and therapeutic observations among 18 patients with Rasmussen's encephalitis.

We studied the clinical, electrophysiological, imaging and pathological features of 18 patients with Rasmussen's encephalitis (RE). This descriptive study included 18 patients (six males, 12 females) with RE who were evaluated for demographic and phenotypic details, electroencephalogram (EEG) results, MRI results, pathological features, virological markers and outcome. Radiological staging as per Bien et al. and pathological staging in accordance with Robitaille et al. were performed. Simple partial seizures were the most common initial manifestation. During the disease course, epilepsia partialis continua (EPC) developed in 15/18 (83.3%) and hemiparesis in 17/18 (94.4%) patients. EEG revealed hemispheric slowing (100%), interictal epileptiform discharges (100%) and ictal pattern (44.4%). Brain MRI revealed unihemispheric focal cortical atrophy (100%), white matter changes (88.2%), basal ganglia-ipsilateral caudate and putamen involvement (50.0%) and progression of atrophy on serial MRI (100%). Unusual presentations in this series included late onset (n=1), and isolated lingual EPC (n=1). Diagnostic biopsies in two patients revealed Robitaille stage 3 disease. The six hemispherotomy specimens showed stage 2 disease in one, stage 3 in three and stage 4 in two cases. Heterogeneity in disease stage in the different neuroanatomical regions and within the same cortical segment reflected progression of immune-mediated damage. Immunomodulation provided only temporary benefit. Patients who underwent functional hemispherotomy had reduction in seizure frequency and improved quality of life. The clinical, EEG and MRI findings are in accordance with the established literature. MRI staging was concordant with Robitaille pathological staging. Immunomodulation did result in transient reduction in seizure frequency while surgery in six produced reasonable benefit.

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.

White matter correlates of cognitive impairment in essential tremor.

BACKGROUND AND PURPOSE: Impairment of cognitive functions occurs in essential tremor, though the mechanism is largely unknown. The aim of this study was to find microstructural correlates of cognitive dysfunction seen in essential tremor by using DTI and neuropsychological assessment. MATERIALS AND METHODS: Fifty-five patients with essential tremor and 55 matched healthy controls were evaluated. Essential tremor was diagnosed by using the National Institutes of Health criteria. Subjects were assessed by using a structured neuropsychological battery. DTI data were acquired by using 3T MR imaging and were analyzed by using tract-based spatial statistics. Fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were analyzed. RESULTS: Patients were considered cognitively impaired when the test score was 1.5 SDs below or above the mean of healthy controls (depending on the type of test) in ≥3 neuropsychological tests. Patients with cognitive impairment had significantly higher mean diffusivity, radial diffusivity, and axial diffusivity values in the bilateral frontoparietal regions. In patients with cognitive impairment, mean diffusivity, radial diffusivity, and axial diffusivity showed correlations with various neuropsychological test scores. Executive function correlated with DTI measures of the frontal white matter, cingulum, inferior superior longitudinal and uncinate fasciculi, anterior thalamic radiations, and posterior lobe of the cerebellum. Visuospatial function correlated with the right parieto-occipital lobe, whereas visual-verbal memories correlated with the anterior thalamic radiations, inferior longitudinal and uncinate fasciculi, and the posterior lobe of the cerebellum. No significant correlations were found between fractional anisotropy and any of the neuropsychological test scores. CONCLUSIONS: The present study demonstrates a correlation between neuropsychological test scores and DTI measures, suggesting a neuroanatomic basis for cognitive impairment seen in patients with essential tremor.

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.

Clinico-pathological factors influencing surgical outcome in drug resistant epilepsy secondary to mesial temporal sclerosis.

BACKGROUND: Mesial temporal sclerosis (MTS) is the most common cause of drug resistant epilepsy amenable for surgical treatment and seizure control. METHODS: This study analyzed the outcome of patients with MTS following anterior temporal lobectomy and amygdalohippocampectomy (ATL-AH) over 10 years and correlated the electrophysiological and radiological factors with the post operative seizure outcome. RESULTS: Eighty seven patients were included in the study. Sixty seven (77.2%) patients had an Engel Class 1 outcome, 9 (11.4%) had Class 2 outcome. Engel's class 1 outcome was achieved in 89.9% at 1 year, while it reduced slightly to 81.9% at 2 years and 76.2% at 5 year follow up. Seventy seven (88.5%) patients had evidence of hippocampal sclerosis on histopathology. Dual pathology was observed in 19 of 77 specimens with hippocampal sclerosis, but did not influence the outcome. Factors associated with an unfavorable outcome included male gender (p=0.04), and a higher frequency of pre-operative seizures (p=0.005), whereas the presence of febrile seizures (p=0.048) and loss of hippocampal neurons in CA4 region on histopathology (p=0.040) were associated with favorable outcome. The effect of CA4 loss on outcome is probably influenced by neuronal loss in other subfields as well since isolated CA4 loss was rare. Abnormal post operative EEG at the end of 1 week was found to be a significant factor predicting unfavorable outcome (p=0.005). On multivariate analysis, the pre-operative seizure frequency was the only significant factor affecting outcome. CONCLUSIONS: The present study observed excellent seizure free outcome in a carefully selected cohort of patients with MTS with refractory epilepsy. The presence of dual pathology did not influence the outcome.

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.