Nature of Parkinsonian features in multiple system atrophy.

Objectives: For this observational study, we evaluated the clinical profile of Parkinsonian features in multiple system atrophy (MSA), as there is no clarity about the specifics of these features in this disease compared to progressive supranuclear palsy (PSP) and Parkinson's disease (PD). Materials and Methods: Here, we selected 57 patients with MSA based on standard criteria and grouped them into two categories - Parkinsonian variant of MSA (MSA-P) and cerebellar variant of MSA (MSA-C). However, researchers did not distinguish among patients based on the nature of extrapyramidal syndrome or levodopa responsiveness. Then, we examined the patients at the time of their first visit to outpatient clinics or indoor wards and recorded and analyzed the specific extrapyramidal features or their variations. Results: The extrapyramidal features including levodopa responsiveness were highly variable among MSA-C as well as MSA-P patients. A subset of patients presented with features resembling PSP (symmetry [56.1%], axial rigidity [52.6%], backward falls [28.1%], and down-gaze restriction [17.5%]), while others presented with features resembling PD (asymmetry [43.9%], tremors [71.9%], and peripheral rigidity [40.4%]). After grouping patients based on predominant extrapyramidal features, 36.8% of patients had PD-like, 19.3% had PSP-like, and 43.9 % had mixed presentation. Moreover, 86% of patients had a perceptible levodopa response, including a sustained response for more than six months in 64% of patients. Conclusion: Extrapyramidal features in MSA patients may be PD-like, PSP-like, or mixed. Moreover, an initial presentation resembling PSP or PD may be deceptive and one must follow it up for MSA.

Developmental Changes in Genome Replication Progression in Pluripotent versus Differentiated Human Cells.

DNA replication is a fundamental process ensuring the maintenance of the genome each time cells divide. This is particularly relevant early in development when cells divide profusely, later giving rise to entire organs. Here, we analyze and compare the genome replication progression in human embryonic stem cells, induced pluripotent stem cells, and differentiated cells. Using single-cell microscopic approaches, we map the spatio-temporal genome replication as a function of chromatin marks/compaction level. Furthermore, we mapped the replication timing of subchromosomal tandem repeat regions and interspersed repeat sequence elements. Albeit the majority of these genomic repeats did not change their replication timing from pluripotent to differentiated cells, we found developmental changes in the replication timing of rDNA repeats. Comparing single-cell super-resolution microscopic data with data from genome-wide sequencing approaches showed comparable numbers of replicons and large overlap in origins numbers and genomic location among developmental states with a generally higher origin variability in pluripotent cells. Using ratiometric analysis of incorporated nucleotides normalized per replisome in single cells, we uncovered differences in fork speed throughout the S phase in pluripotent cells but not in somatic cells. Altogether, our data define similarities and differences on the replication program and characteristics in human cells at different developmental states.

Normotensive state during acute phase of hypertensive intracerebral hemorrhage.

Objectives: Hypertensive hemorrhage is a leading cause of intracerebral haemorrhage (ICH), although some of these patients may not present with high blood pressure (BP) at the time of ICH. Materials and Methods: This retrospective study included patients with history of hypertension presenting with ICH. Patients with systolic BP recording of more than 140 mmHg were included in hypertension group (group I). Patients whose BP rose to hypertension range after fluid correction were included in group II and patients with BP <140 mmHg on consecutive 1-week BP recordings were included in group III. Clinical features including volume of ICH of all the three groups were noted. Outcome in the form of mortality was analyzed. Chi-square test was used for categorical variables and independent t-test for continuous variables. P < 0.05 was considered significant. Results: Ninety-two ICH patients with history of hypertension were included in the study. Of them, 20 patients (22%) presented with BP <140 mmHg systolic at the time of ICH. After fluid correction, it rose to hypertensive range in 9 (10%) but remained normal in 11 patients (12%) during consecutive recordings for 1-week post-admission. On comparing normotensive and hypertensive groups, significant difference was seen in survival and volume of ICH. Conclusion: There is a subset of hypertensive patients who may present with normal BP recording during acute ICH. The BP rises subsequently with the correction of hypovolemia in some. The volume of hemorrhage in normotensives is relatively small but whether this translates into better prognosis needs further studies.

Analysis of Cell Cycle and DNA Compaction Dependent Subnuclear Distribution of Histone Marks.

In eukaryotes, the organization of DNA wrapped around histones regulates DNA-dependent processes. Changes in epigenetic modifications modulate the compaction of DNA into chromatin and, thus, regulate DNA metabolism in time and space. Hence, to catalog the spatiotemporal epigenetic information and its relation to the dynamic nuclear landscape is of paramount importance. Here, we present a method, based on FiJi and the statistical image analysis tool nucim(R), to classify in 3D the nuclear DNA compaction in single interphase cells. We, furthermore, mapped the distribution of (epi)genetic marks and nuclear proteins/processes to the compaction classes along with their dynamics over the cell cycle. These techniques allow to catalog and quantify the dynamic changes in the epigenome in space and time and in single cells.

A New Surface Technique for Phrenic Nerve Conduction Study.

Objective: To report a new patient friendly and convenient technique for phrenic nerve conduction with alternative sites of stimulation and recording. Methods: Phrenic nerve conduction was performed in forty volunteers and ten patients of peripheral neuropathy. Active recording electrode was placed in tenth intercostal space 2.5 cm away from para-spinal muscles (mid-scapular line), reference electrode in eighth intercostal space just medial to subcostal margin with ground between stimulating and recording electrode. Stimulation was done at the level of crico-thyroid space near or under the posterior margin of sternocleidomastoid muscle. This new method was compared with existing ones. Analysis: Data was analysed using SPSS 23 version. Correlation between height, weight, body mass index, age, and chest expansion was done using bi-variate correlation. Mean latency and amplitude of the study method were compared with other methods using MANNOVA test. Results: Total of forty subjects were studied. Thirty-seven were male subjects. Mean age was 28.03 ± 9.63 years, height 168.0 ± 9.60 cm and chest expansion 3.53 ± 0.64 cm. Right sided phrenic nerve mean latency was 5.99 ± 0.629 ms and amplitude 1.088 ± 0.178 mV. Left sided phrenic nerve conductions showed mean latency of 6.02 ± 1.82 ms, amplitude of 1.092 ± 0.2912 mV. These standard deviations were smaller than what were observed with other methods suggesting increased consistency of our results. There was no correlation between phrenic nerve conduction with age, height, gender or chest expansion. Conclusion: This study method gave a better as well as consistent morphology, higher amplitude and required lower amount of current strength. It was superior to previously reported methods in consistency of normative data.

Osteo-Cutaneous Trophic Changes in Complex Regional Pain Syndrome and their Reversal with Steroids.

Background: Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by autonomic and inflammatory features. There is paucity of data regarding sustained benefits of any treatment modality. We aimed to document the effect of steroids in CRPS on long-term basis. Materials and Methods: We came across five patients of CRPS in Out Patient clinics of super-speciality Institutes in North India. All five cases fulfilled the Budapest criteria for the diagnosis of CRPS. All of them received prednisolone and were prospectively followed up for 2 years. Treatment outcome was carefully recorded in all affected modalities. Results: All five cases were found to have excruciating neuropathic pain in defined regions along with cutaneous manifestations. Osseous changes in the form of surface erosion of underlying bones in four cases and marked marrow edema leading to considerable increase in bone thickness in one case were noted. All these features improved considerably following steroid therapy. Bone marrow edema and bone resorption showed improvement on serial imaging. Conclusion: Apart from pain relief, steroids therapy is capable of reversing the osteo-cutaneous autonomic changes of CRPS type I.

Sinusitis among Patients Undergoing CT Scan of Paranasal Sinuses in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Computed tomography imaging provides detailed information about the paranasal sinuses and is now well established as an alternative to standard radiographs in evaluating patients with sinusitis. Sinusitis can have dangerous complications which can even lead to death if not diagnosed and treated on time. This study aimed to find the prevalence of sinusitis among the patients undergoing Computed Tomography scan of paranasal sinuses in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted in the Department of Radiology at a tertiary care hospital from 1 October 2021 to 30 April 2022 after taking ethical approval from the Institutional Review Committee (Reference Number: 023-078/079). The patients undergoing Computed Tomography paranasal sinuses and meeting the eligibility criteria were enrolled for the study after taking informed consent. Convenience sampling was done. Point estimate and 95% Confidence Interval were calculated. Results: Among 113 patients, 109 (96.46%) (93.05-99.87, 95% Confidence Interval) patients had sinusitis. The most common subtype was found to be acute sinusitis in 63 (57.79%) individuals. Conclusions: The prevalence of sinusitis was higher than in other studies done in similar settings. Keywords: computed tomography; paranasal sinuses; sinusitis.

Increased Great Saphenous Vein Diameter at the Level of Knee among Patients with Varicose Veins in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Colour Doppler ultrasonography plays an important role in determining the morphological and hemodynamic information of the venous system. This study aimed to find out the prevalence of increased great saphenous vein diameter at the level of the knee among patients with varicose veins in a tertiary care centre. Methods: A descriptive cross-sectional study was carried out in the Department of Radiology at a tertiary care centre from 30 October 2021 to 31 March 2022 after taking ethical approval from the Institutional Review Committee (Reference number: 028-077/078). A convenience sampling technique was used for the study. The study group consisted of patients over 18 years, coming for ultrasonography examination of the lower limb with the clinical symptoms and signs of varicose veins. The great saphenous vein diameter was measured at the level of the medial femoral condyle of the knee using the software in the ultrasonography unit. B mode, colour Doppler and spectral analysis were done. A cut-off value of 5 mm for the diameter of the great saphenous vein was taken to indicate the presence or absence of varicosity and saphenofemoral reflux. Point estimate and 90% Confidence Interval were calculated. Results: Among 72 patients with varicose veins, the diameter of the great saphenous vein was increased in 59 (81.94%) (74.50-89.38, 90% Confidence Interval) patients. Conclusions: The mean diameter of the great saphenous vein in our study was similar when compared to other studies conducted in similar settings. Keywords: saphenous vein; ultrasonography; varicose veins.

Cardiovascular and sudomotor dysfunction in Hirayama disease.

Hirayama disease is a disease of young males causing atrophy of small muscles of the affected hand and forearm. Localized autonomic dysfunction of the affected upper limb such as cold skin and excessive sweating has been described in some patients. In this study, we looked for local as well as systemic involvement of autonomic nervous system in patients with Hirayama disease. Forty-four patients with a median duration of illness of 3 years were included in the study. Assessment of symptom profile and evaluation of autonomic nervous system were done at the time of enrolment. The mean age at presentation was 21.9 (10-32) years, with a delay in seeking medical attention of around 3 (1-11) years. Localized clinical autonomic dysfunction was present in 39 (88.6%) patients, while objective generalized autonomic dysfunction was present in 33 (75%) patients. Cold skin and excessive sweating showed good correlation with the presence of objective autonomic dysfunction (P < 0.05). In three patients, sympathetic skin response (SSR) could not be recorded in one of the four limbs. Compared to controls, the SSR results in patients with Hirayama disease showed increased latency (1.64 ± 0.21 vs. 1.57 ± 0.14, P 0.04) and decreased amplitude in upper limbs (0.65 ± 0.19 vs. 0.86 ± 0.40, P 0.01). Hirayama disease has both localized and systemic dysautonomia. Careful longitudinal evaluation during the progressive phase of the disease may help in diagnosing subtle systemic autonomic dysfunction.

Respiratory Assessment of Myasthenia Gravis Patients Using Repetitive Nerve Stimulation of Phrenic and Intercostal Nerves.

BACKGROUND: We evaluated decremental response from phrenic and intercostal nerves using slow repetitive nerve stimulation test (RNST) to look for its diagnostic significance in sero-negative predominantly bulbar myasthenia gravis (MG) with normal peripheral or cranial nerve RNST. METHODS: RNST from phrenic and intercostal nerves was performed along with standard RNST from abductor digiti minimi (ADM), trapezius, nasalis and orbicularis oculi muscles in 10 normal individuals (group I), 10 patients with neurological disorders other than MG (group II) and 10 patients with MG (group III). We evaluated the presence of positive response in first two groups (group I and II) and absence of negative response in group III. Spirometry was also performed in MG patients. RESULTS: Mean baseline decrement in I/C RNST in three groups was -2.06±1.33 %, -2.5±2.18% and -27.1±17.9 % respectively. One minute post exercise decrement in I/C RNST in three groups was -2.9±1.36%,-2.9±1.36% and -32.9±17.9% respectively. RNST of phrenic nerve showed mean baseline decrement of -2.1±2.3%, -3.2±2.6 % and -18.3±30.3% in three groups respectively. One minute post exercise decrement percentage were -2.2±1.18% in group I, -4.8±2.18% in group II and -29.2±19.2% in group III. RNST of peripheral nerves were negative in two patients who were bulbar sero-negative MG, however, significant decrement was seen in intercostal and phrenic nerve RNST. CONCLUSION: Intercostal and phrenic nerve RNST are a better test for assessing respiratory involvement specially in patients presenting with bulbar symptoms and having negative RNST of peripheral nerves.

Study of accumulation behaviour of tungsten based composite using electron probe micro analyser for the application in bone tissue engineering.

In this research, a proto-type study we have conducted, where we have synthesized tungsten based composite materials which are tungsten along with combined oxides of other elements like calcium, scandium, barium, and aluminium in the form of powder with bones powder of mice devised by high energy ball mill and later on fabricating high dense pellets by sintering by spark plasma. The particle sizes of the composite materials are found to be 1-2 µm, as evidenced by the electron microscope, suggesting synthesized materials are of micron size. The quantitative and qualitative analysis of sintered pellets are well confirmed by electron probe micro analyzer (EPMA) and energy dispersive X-ray spectrometer (EDS) which illustrate the greater percentage of tungsten presents in the profound scan areas with other elements of the composite. The absence of pores across the 3D geometry suggesting dense sample, which is quite revealed by the X-ray tomography inspection. The prepared sintered pellets from the tungsten based composites are found to be ≈ 99.5% density with the observation of tungsten to be accumulated uniformly across the scan regions along with focussed hot spots as implied by EPMA. This study paves the way, to examine how the tungsten accumulation and the distribution with the other elements for future understanding in bone tissue engineering application and the in vivo specification of tungsten.

PSP-FTD Complex: A Possible Variant of PSP.

INTRODUCTION: This study tried to find out type of lobar features found in patients with progressive supranuclear palsy (PSP) and whether they differ from those of frontotemporal dementia (FTD) as both of these are tauopathies. METHODS: We studied lobar functions of 45 patients with PSP. RESULTS: Five (11.1%) patients had no lobar feature; 11 (24.4%) had PSP-like features like apathy, frontal release signs, impaired motor Luria written sequences, and fist-edge-palm test; and 29 (64.4%) patients had FTD-like lobar features like disinhibition, poor naming, and word finding difficulty. Among features resembling FTD, behavioural variant type occurred in 31.1%, primary progressive aphasia type occurred in 58.6%, 3.4% patients had semantic dementia type features, and 6.9% were unclassified. CONCLUSIONS: Hence, patients with PSP with lobar features may fall in the middle of PSP-FTD spectrum with frontal lobe features typical of PSP (PSP-frontal like) and those with frontal lobe features resembling FTD (PSP-FTD complex) in between.

Steroid Responsiveness in Duchenne Muscular Dystrophy - Predictive Value of Epigenetic Regulator Histone Deacetylase 2.

OBJECTIVE: To find the role of an epigenetic regulator histone deacetylase (HDAC-2) in predicting steroid responsiveness in patients with Duchenne muscular dystrophy (DMD). METHODS: Peripheral blood mononuclear cells were isolated from three milliliters of venous blood sample of patients with DMD for estimation of HDAC-2 levels. The patients were then given prednisolone at 0.75 mg/kg/d and followed up for response. Improvement in muscle power and timed function tests were evaluated 2 monthly for 6 mo. Side- effects of steroids were also noted. RESULTS: HDAC-2 values showed a linear correlation with improvement in muscle power at 6 mo as reflected in direct assessment and in various functional tests. When ≥3 point change from baseline was considered in power of various muscle groups at 6 mo as cut off to distinguish good responders (GR) from poor responders (PR) of steroid, a HDAC-2 value of ≥4.40 seemed to be 92.6% sensitive and 100% specific to distinguish GRs. CONCLUSIONS: The degree of improvement in power and various timed function tests at 6 mo could be predicted from the HDAC-2 value of the individual patient recorded at baseline. HDAC-2 levels at baseline might be a good biomarker for predicting steroid response in patients with DMD.

Lumpy skin disease (LSD) outbreaks in cattle in Odisha state, India in August 2019: Epidemiological features and molecular studies.

Lumpy skin disease (LSD) caused by lumpy skin disease virus (LSDV) inflicts significant economic losses in cattle production with impact on livelihoods of smallholders. This study reports the first occurrence of LSD in cattle in India and analyses epidemiological and genetic characterization data from LSD outbreaks in five districts of Odisha state in August 2019. In all, 182 of 2,539 cattle were affected with an apparent morbidity rate of 7.1% and no mortality. Out of 102 samples from 60 LSD suspected and 17 asymptomatic in-contact cattle tested, 29.87% cattle were positive by capripoxvirus generic PCR and 37.66% were positive by LSDV real-time PCR. All the in-contact cattle tested were negative for LSDV. Among affected cattle, LSDV genome was detected more in scabs (79.16%) than blood (31.81%) and frozen bull semen (20.45%). Differential diagnosis by PCR was negative for pseudo-LSD, buffalopox, cowpox, pseudo-cowpox and bovine papular stomatitis. Five selected PCR and real-time PCR-positive LSDV DNA were sequenced in three genomic regions, P32 (LSDV074), F (LSDV117) and RPO30 (LSDV036). Phylogenetic analysis based on partial P32 and F gene sequences and complete RPO30 gene sequences showed that all the five Indian LSDV strains were identical and clustered with other field strains of LSDV circulating globally. However, the F and RPO30 gene sequence analyses revealed that Indian LSDV strains are genetically closer to the South African NI2490/KSGP-like strains than the strains detected in Europe, which was rather surprising. The present study established the existence of LSDV in India and involvement of LSDV field strains in the outbreaks. Additionally, we provided evidence of LSDV shedding in semen of naturally infected bulls. Further studies are required to determine the source of LSD introduction, extent of spread, modes of transmission and impact on dairy cattle production in India and effective control measures must be undertaken urgently.

Neurocysticercosis or tuberculoma - Which one has more epileptic potential?

PURPOSE: The duration of antiepileptic drug (AED) treatment in the management of seizures due to ring enhancing lesions (REL) remains a matter of debate. We undertook a prospective cohort study to look into the seizure patterns and incidence of recurrence in association with two of the most common causes of RELs after gradually stopping AEDs at least 18 months after acheiving seizure control. METHODS: Ninety patients with neurocysticercosis (NCC) and twenty-nine patients with tuberculoma were treated with anti-helminthic and anti-tubercular drugs according to current recommended guidelines, and followed up for a minimum of 2 years after the last seizure free day. In every patient included in the study, AEDs were tapered within six months of attaining a seizure-free interval of 18 months. We looked at the incidence of recurrent seizures after stopping AEDs in both groups of patients. RESULTS: The frequency of baseline seizures (2.1 vs 1.5 per year, p < 0.001) and number of antiepileptic drugs (2.12 vs 1.48, p < 0.001) were greater in patients with NCC than those with tuberculoma. Patients with NCC had a greater incidence of recurrent seizures (1.17 vs 0.07 in the next six months, p < 0.001) after stopping the AEDs. The median interval to seizure recurrence after stopping AEDs was 2.2 months in patients with NCC. CONCLUSIONS: Among RELs, NCC lesions have a greater epileptogenic potential than tuberculomas. AEDs can be tapered in patients with tuberculoma after a seizure free period of 18 months with a very low risk of recurrence.

Step-Headache: A Distinct Symptom of Migraine.

Objectives The diagnosis of migraine depends on various characteristics of headache with their associated constitutional symptoms such as nausea, vomiting, photophobia, and phonophobia. Relatively severe intensity, throbbing character, unilaterality, and aggravation with physical activity are the key features of migraine headache. We did this study to describe a new symptom (step-headache) in migraine in which some patients complained of uncomfortable or painful thump over the head with each footstep during walking or running. Materials and Methods Self-designed proforma was filled in each clinically diagnosed patient of migraine or tension-type headache in an outpatient clinic setting. The symptom designated here as step-headache was evaluated in 150 patients of migraine including 26 patients with overlapping headache and 244 patients of tension-type headache. Binary logistic regression was used for association analysis of step-headache with subgroups of migraine and with other migraine features. Statistical Analysis Frequency distributions were expressed as numbers (percentages) or mean ± standard deviation. Binary logistic regression was used for association analysis of step-headache with subgroups of migraine and with other migraine features. Results Step-headache was experienced by 97 (64.67%) migraine patients with nearly equal distribution among the two clinical subtypes (61.5% for migraine with aura and 65.3% for migraine without aura) but with high prevalence among perimenopausal onset migraine. Of all the patients who had this symptom, 77.32% experienced it during all the migraine attacks. The step-headache was differentiable from throbs of migraine and their exacerbation during physical activity by its synchrony with footsteps and its presence during nonpulsatile headaches or nonheadache phases of migraine. Sensitivity of this symptom was 64.67% while specificity was 100%. Conclusion Among primary headaches, step-headache is a less well-known but common and distinct symptom of migraine. It has good sensitivity and high specificity for migraine.

Antibody Negative Autoimmune Encephalitis- Does it Differ from Definite One?

CONTEXT: Autoimmune encephalitis (AE) is an emerging cause of non-infective encephalitis, presentations of which vary widely. Traditionally the diagnosis of AE is based on detection of antibodies in a patient with clinical picture suggestive of AE. AIM: To evaluate the clinical characteristics and response to immunotherapy in patients with antibody negative autoimmune encephalitis and to compare them with definite cases. SETTINGS AND DESIGN: A prospective follow-up study was done in patients presenting with presumptive symptoms of AE from January 2017 to January 2019. The study was done in a tertiary care institute of Northern India. PATIENTS AND METHODS: Demographic and clinical parameters were noted and relevant investigations for management were done according to well-defined protocol. The patients were treated with immunomodulatory therapy in the form of steroids and/or intravenous immunoglobulins (IVIg). They were followed up for treatment response and relapse at 2 monthly intervals. STATISTICAL ANALYSIS USED: The data was expressed as either proportions or mean/median. Chi-square test/Independent T test was used to compare antibody positive and antibody negative group. RESULTS: Out of 31 patients with presumptive AE, 16 patients tested positive for autoimmune antibodies (definite AE). Incidences of seizure, behavioral abnormalities, dementia and altered sensorium were similar between the 2 groups (p > 0.05). Complete or partial response was seen in all treated patients in both groups with no significant difference (p 0.716). CSF protein concentration and cellularity were higher in the definite group although only high protein concentration could reach statistical significance (p 0.002). Malignancy could be confirmed after extensive search in 2 out of 16 patients with definite AE and in 1 out of 15 antibody negative AE patients. CONCLUSIONS: Clinical presentation of antibody negative cases does not differ significantly from definite ones. Since treatment response is also similar in both the groups, starting immunotherapy in a patient presenting with presumptive symptoms of AE, while ruling out other common mimickers, seems to be the need of the hour in the management of this evolving entity.

Autistic features in Unverricht-Lundborg disease.

We studied three patients with Unverricht-Lundborg disease for autistic features along with other clinical features associated with progressive myoclonus epilepsy. We diagnosed this disease based on noise and touch sensitive myoclonus, ataxia, cognitive decline, typical EEG features, normal MRI of the brain and applied Children's Global Assessment Scale and Childhood Autism Spectrum Test to these children. The CGAS score was 35 in two and 50 in one of them. CAST scores were above 15 in all of three of them. Autistic features may be an important clinical feature of this disease. History and physical examination for myoclonus should probably be taken in autistic children.