Abnormal structural connectivity in progressive supranuclear palsy-Richardson syndrome.

OBJECTIVES: Progressive supranuclear palsy-Richardson syndrome (PSP-RS) is characterized by symmetrical parkinsonism with postural instability and frontal dysfunction. This study aims to use the whole brain structural connectome (SC) to gain insights into the underlying disconnectivity which may be implicated in the clinical features of PSP-RS. METHODS: Sixteen patients of PSP-RS and 12 healthy controls were recruited. Disease severity was quantified using PSP rating scale (PSPRS), and mini-mental scale was applied to evaluate cognition. Thirty-two direction diffusion MRIs were acquired and used to compute the structural connectome of the whole brain using deterministic fiber tracking. Group analyses were performed at the edge-wise, nodal, and global levels. Age and gender were used as nuisance covariates for all the subsequent analyses, and FDR correction was applied. RESULTS: Network-based statistics revealed a 34-edge network with significantly abnormal edge-wise connectivity in the patient group. Of these, 25 edges were cortical connections, of which 68% were frontal connections. Abnormal deep gray matter connections were predominantly comprised of connections between structures of the basal ganglia. The characteristic path length of the SC was lower in PSP-RS, and nodal analysis revealed abnormal degree, strength, local efficiency, betweenness centrality, and participation coefficient in several nodes. CONCLUSIONS: Significant alterations in the structural connectivity of the whole brain connectome were observed in PSP-RS. The higher degree of abnormality observed in nodes belonging to the frontal lobe and basal ganglia substantiates the predominant frontal dysfunction and parkinsonism observed in PSP-RS. The findings of this study support the concept that PSP-RS may be a network-based disorder.

Unusual Complication of Paraplegia Following Intracranial Aneurysm Clipping in a Patient with Undiagnosed Coarctation of Aorta.

We report a case of subarachnoid hemorrhage in a 38-year-old male, diagnosed to have the right middle cerebral artery aneurysm on computed tomography (CT) cerebral angiogram. He was a known hypertensive for 17 years and was on irregular treatment. Craniotomy and clipping of the aneurysm were done. Postoperatively, the patient had high blood pressure of 200/120 mmHg. Treatment of hypertension in the postoperative period resulted in paraplegia. CT angiogram of aorta revealed coarctation-postductal type. He underwent balloon dilatation for the coarctation of aorta followed by coarctopalsty and stenting with the improvement in motor power in both lower limbs.

Hepatitis E Virus-Associated Acute Encephalitic Parkinsonism.

Hepatitis E virus (HEV) is a common infection worldwide and is an emerging infectious disease in the developed countries. The unique characteristics of HEV is that it displays different epidemiological and clinical characteristics between developing and developed countries. Neurological disorders are emerging extra hepatic manifestations of both acute and chronic Hepatitis E virus infection. We report a 17 year old sportsman presenting with acute encephalitic Parkinsonism concurrent with acute hepatitis. Serology was positive for Hepatitis E virus (HEV) and HEV RNA was confirmed. Patient improved completely with symptomatic treatment. We suggest offering diagnostic testing for Hepatitis E virus in patients of neurological disorders with concurrent liver impairment.

Acute Ischaemic Stroke as a Manifestation of Pituitary Apoplexy in a Young Lady.

Pituitary Apoplexy (PA) is defined as a clinical syndrome comprising headache, visual deficits and altered sensorium, which can result from haemorrhage or infarction of the pituitary gland. Acute ischaemic stroke following PA is very rare. We are presenting a 35-year-old young otherwise healthy lady who presented with neuro ophthalmological and vascular symptoms on a background of PA. Imaging revealed a pituitary macro adenoma with parasellar extension with internal bleed. Cerebral angiography revealed that the mass compressed the bilateral cavernous sinuses (left more than right), resulting in obliteration of the cavernous portion of the left Internal Carotid Artery (ICA). She was treated with steroids and surgical debulking of the tumour through trans-sphenoidal approach and postoperative imaging showed recanalization of the ICA with reduction of the tumour size. The histopathological diagnosis was consistent with pituitary macro adenoma. Patient improved in level of sensorium, eye movement and the patient showed almost full recovery after the operation. PA resulting in ICA occlusion is very rare. Early intervention is required for reducing mortality and morbidity and to improve quality of life.

Role of Corpus Callosum Volumetry in Differentiating the Subtypes of Progressive Supranuclear Palsy and Early Parkinson's Disease.

BACKGROUND AND OBJECTIVE: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder. Classic PSP or Richardson-Steele phenotype (PSP-RS) and parkinsonian phenotype (PSP-P) are the common subtypes of PSP. At the early stage, differentiating the subtypes of PSP as well as differentiating PSP from other parkinsonian disorders, especially Parkinson's disease (PD) is challenging. Microstructural abnormalities of corpus callosum (CC) have been reported both in PSP and PD. The objective of this study was to compare the volumes of various segments of CC between patients with PSP-P, PSP-RS, and early PD. METHODOLOGY: This study included 32 patients with PSP (RS: 18, P: 14), 20 patients with early PD, and 25 controls. All subjects underwent 3-Tesla MRI. An automated surface-based analysis package (FreeSurfer) was used to divide CC into five segments: anterior (CC1), midanterior (CC2), central (CC3), midposterior (CC4), and posterior (CC5). Volumes of these segments were compared among the four groups. RESULTS: The PSP-RS group had significantly lower CC volume in all segments except in CC1 and CC5, whereas the volumes of the five segments of CC were comparable among PSP-P, PD and controls. The PSP-RS group had lower CC3 volume compared to the PSP-P group, and the PSP-RS group had lower volume of both CC2 and CC3 compared to the PD group. CONCLUSIONS: The lower volume of the central segment of CC (CC3) might help in differentiating PSP-RS from PSP-P. There is no significant difference in the pattern of CC atrophy in PSP-P and early PD. Studies with higher sample sizes are warranted to confirm the results of our study.

Correlation between qualitative balance indices, dynamic posturography and structural brain imaging in patients with progressive supranuclear palsy and its subtypes.

OBJECTIVES: To compare the clinical, balance, and radiological profile of progressive supranuclear palsy (PSP) of Richardson type (PSP-R) and Parkinsonian type (PSP-P). MATERIALS AND METHODS: Twenty-nine patients with PSP (PSP-R: 17, PSP-P: 12) satisfying the probable/possible National Institute of Neurological Disorders and Stroke-PSP criteria were recruited and assessed with Unified Parkinson's Disease Rating Scale-III, PSP rating scale (PSPRS), Berg balance scale (BBS), Tinetti performance-oriented mobility assessment gait and total (TPG and TPT) score, dynamic posturography (DP), and magnetic resonance imaging. Data were compared with 30 age- and gender-matched healthy controls. RESULTS: The mean ages of PSP-R, PSP-P, and controls were comparable (62.5 ± 6.6, 59 ± 8.9, and 59.8 ± 7.6 years). The PSP group had significantly poor DP scores and more radiological abnormalities than controls. The PSPRS, TPG, and TPT scores were significantly more impaired in PSP-R compared to PSP-P (P = 0.045, P = 0.031, and P = 0.037, respectively). In DP, the limits of overall stability were most significant (P < 0.001) and PSP-R had lower scores. PSP-R compared to PSP-P had more often "Humming Bird" sign (P < 0.001), "Morning Glory" sign (P < 0.008), and generalized cortical atrophy (P < 0.001). The area of midbrain (P < 0.002) and midbrain/pons ratio (P < 0.013) was significantly lower in PSP-R. In PSP-P, the overall balance index significantly correlated with BBS, TPG, and TPT (r = -0.79, P = 0.002; r = -0.772, P = 0.003; and r = -0.688, P = 0.013) and the midbrain axial anterior-posterior diameter significantly correlated with the TPG and TPT (r = 0.74, P = 0.01; r = 0.66, P = 0.018). CONCLUSIONS: While balance and radiological abnormalities were more severe in PSP-R, the qualitative and quantitative measurements of severity of balance in PSP-P rather than PSP-R was a better reflection of the pathology of the midbrain.

A voxel based comparative analysis using magnetization transfer imaging and T1-weighted magnetic resonance imaging in progressive supranuclear palsy.

AIMS: In progressive supranuclear palsy (PSP) tissue damage occurs in specific cortical and subcortical regions. Voxel based analysis using T1-weighted images depict quantitative gray matter (GM) atrophy changes. Magnetization transfer (MT) imaging depicts qualitative changes in the brain parenchyma. The purpose of our study was to investigate whether MT imaging could indicate abnormalities in PSP. SETTINGS AND DESIGN: A total of 10 patients with PSP (9 men and 1 woman) and 8 controls (5 men and 3 women) were studied with T1-weighted magnetic resonance imaging (MRI) and 3DMT imaging. Voxel based analysis of T1-weighted MRI was performed to investigate brain atrophy while MT was used to study qualitative abnormalities in the brain tissue. We used SPM8 to investigate group differences (with two sample t-test) using the GM and white matter (WM) segmented data. RESULTS: T1-weighted imaging and MT are equally sensitive to detect changes in GM and WM in PSP. Magnetization transfer ratio images and magnetization-prepared rapid acquisition of gradient echo revealed extensive bilateral volume and qualitative changes in the orbitofrontal, prefrontal cortex and limbic lobe and sub cortical GM. The prefrontal structures involved were the rectal gyrus, medial, inferior frontal gyrus (IFG) and middle frontal gyrus (MFG). The anterior cingulate, cingulate gyrus and lingual gyrus of limbic lobe and subcortical structures such as caudate, thalamus, insula and claustrum were also involved. Cerebellar involvement mainly of anterior lobe was also noted. CONCLUSIONS: The findings suggest that voxel based MT imaging permits a whole brain unbiased investigation of central nervous system structural integrity in PSP.

The prelude on novel receptor and ligand targets involved in the treatment of diabetes mellitus.

Metabolic disorders are a group of disorders, due to the disruption of the normal metabolic process at a cellular level. Diabetes Mellitus and Tyrosinaemia are the majorly reported metabolic disorders. Among them, Diabetes Mellitus is a one of the leading metabolic syndrome, affecting 5 to 7 % of the population worldwide and mainly characterised by elevated levels of glucose and is associated with two types of physiological event disturbances such as impaired insulin secretion and insulin resistance. Up to now, various treatment strategies are like insulin, alphaglucosidase inhibitors, biguanides, incretins were being followed. Concurrently, various novel therapeutic strategies are required to advance the therapy of Diabetes mellitus. For the last few decades, there has been an extensive research in understanding the metabolic pathways involved in Diabetes Mellitus at the cellular level and having the profound knowledge on cell-growth, cell-cycle, and apoptosis at a molecular level provides new targets for the treatment of Diabetes Mellitus. Receptor signalling has been involved in these mechanisms, to translate the information coming from outside. To understand the various receptors involved in these pathways, we must have a sound knowledge on receptors and ligands involved in it. This review mainly summarises the receptors and ligands which are involved the Diabetes Mellitus. Finally, researchers have to develop the alternative chemical moieties that retain their affinity to receptors and efficacy. Diabetes Mellitus being a metabolic disorder due to the glucose surfeit, demands the need for regular exercise along with dietary changes.

Antifertility activity of Artemisia vulgaris leaves on female Wistar rats.

AIM: To evaluate the antifertility activity of Artemisia vulgaris leaves on female Wistar rats. METHOD: The plant extract was tested for its effect on implant formation at two dose levels, 300 and 600 mg·kg⁻¹, respectively. The effective methanolic plant extract was further studied for estrogenic potency on ovariectomised immature female Wistar rats. RESULTS: The data presented in this study demonstrate the antifertility potential of Artemisia vulgaris methanolic leaf extract, which shows a strong and significant decrease in implant formation (100%), and a strong estrogenic effect resulting in a significant increase in uterine weight in immature ovariectomised rats. These observations suggest that the methanolic extract of Artemisia vulgaris leaves has strong anti-implantation activity and estrogenic activity. CONCLUSION: The methanolic plant extract of A. vulgaris has antifertility activity.

Direction specific preserved limits of stability in early progressive supranuclear palsy: a dynamic posturographic study.

OBJECTIVES: To quantitatively detect the nature of balance impairment in patients with progressive supranuclear palsy (PSP) using dynamic posturography. METHODS: Twenty clinically diagnosed PSP patients (8 women, 12 men; age: 62.1 ± 7.7 years; duration: 2.6 ± 1.3 years) and 20 healthy controls were studied. All subjects were right side dominant. They were evaluated by dynamic posturography (Biodex, USA). The measurements included (i) balance indices: ability to control balance in all directions (overall balance index, OBI), front to back (anterior-posterior index, API) and side-to-side (medio-lateral index, MLI), and (ii) the limits of stability (LOS) in 8 directions: forward (FW), backward (BW), right (RT), left (LT), forward-right (FW-RT), forward-left (FW-LT), backward-right (BW-RT) and backward-left (BW-LT). RESULTS: Compared to controls, patients showed significantly higher OBI (p<0.001), API (p=0.003) and MLI (p<0.001), implying impaired balance. The total LOS score was significantly lower (implying poor stability) in PSP than in controls (18.3 ± 7.3 vs. 28.4 ± 8.5, p<0.001). Patients took significantly longer time to complete LOS test (262.7 ± 33.0 s vs. 135.4 ± 20.6 s, p<0.001). Direction-wise analysis showed that PSP patients had significantly lower LOS scores in FW, BW, RT, FW-RT, BW-RT and BW-LT directions compared to controls. However the scores in LT and FW-LT did not differ significantly. CONCLUSIONS: PSP patients showed impaired balance indices and decreased overall LOS compared to controls. Though LOS is affected in PSP, the scores in the left (non-dominant side) and forward-left (non-dominant forward diagonal) directions were preserved.

In vivo evaluation of white matter pathology in patients of progressive supranuclear palsy using TBSS.

INTRODUCTION: The purpose of this research is to study white matter (WM) changes in patients of progressive supranuclear palsy (PSP) using automated analysis of diffusion tensor imaging (DTI) indices. METHODS: This was a prospective study comprising of 24 patients of PSP and 26 matched healthy controls. Fractional anisotropy, mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD) changes were studied in the WM of the PSP patients using an automated analysis technique, tract-based spatial statistics (TBSS). Two subtypes of PSP, i.e., classic Richardson's syndrome (PSP-RS) and parkinsonian type (PSP-P), were also compared among themselves to identify relative severity of WM changes as well as identify spatial distribution of the differences. Clinicoradiological correlation was done to determine the strength of correlation between WM abnormalities identified using TBSS and clinical scores. RESULTS: There were areas of significant abnormality seen in the frontoparietal cerebral WM, thalamus, midbrain tectum, superior cerebellar peduncle, and cerebellar WM. The abnormalities were more spatially widespread on MD and RD maps. Compared to PSP-P, the patients of PSP-RS had more spatial abnormalities localized to the frontal WM. There was no correlation between the observed WM changes and clinical rating scales. CONCLUSIONS: The TBSS analysis showed widespread WM abnormalities in PSP patients including areas which have been shown to be involved in previous pathological studies. PSP-RS showed more severe white matter abnormality compared to the PSP-P subtype.