Efficacy and Safety of adjunctive Perampanel in a prospective, real-world, Phase IV study in Indian patients aged ≥12 years for Treatment of focal-onset Epilepsy: Study 508.

OBJECTIVE: ESPRITE (Study 508; NCT03836924) evaluated the real-world safety, tolerability, and efficacy of adjunctive perampanel in patients aged ≥12 years with focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS), in India. METHODS: ESPRITE was a prospective, multicenter, single-arm, observational, Phase IV study with a 6-month Treatment Period. Patients were aged ≥12 years and had been prescribed perampanel for adjunctive treatment of FOS, with or without FBTCS. Assessments included incidence of treatment-emergent adverse events (TEAEs; primary endpoint), median percent reduction in seizure frequency per 28 days from baseline, 50% responder rates, and seizure-freedom rates. RESULTS: Overall, 200 patients were enrolled (199 patients in the Safety Analysis Set and 174 patients who completed all visits in the main efficacy analyses). TEAEs (all mild or moderate in severity) were reported in 18.1% (n = 36/199) of patients (the most common were dizziness [3.0%] and irritability [2.0%]). TEAEs leading to discontinuation of perampanel were reported in 2.0% of patients; no deaths or serious TEAEs occurred. At 6 months, median percent reduction in seizure frequency was 100.0%, 50% responder rate was 83.3%, and seizure-freedom rate was 49.4%. SIGNIFICANCE: Adjunctive perampanel (at a mean daily dose of 4 mg/day) was shown to be well tolerated and effective in patients aged ≥12 years with FOS, with or without FBTCS, from India. PLAIN LANGUAGE SUMMARY: Many patients do not receive adequate treatment for epilepsy and need effective seizure control medications. In this 6-month clinical study, 199 patients from India, aged 12 years or older, added perampanel to the anti-seizure medications they were already taking. At 6 months, 49% of patients experienced no seizures since starting perampanel and seizure frequency was reduced by half in 83% of patients. Side effects occurred in 18% of patients (most commonly dizziness and irritability) and caused 2% to stop perampanel; no deaths were reported. Perampanel was an effective and generally safe added medication for patients with epilepsy from India.

Parapharyngeal space carcinoma disguised as temporomandibular joint disorder: A clinical report.

Parapharyngeal space neoplasms tend to have a considerable volume by the time of diagnosis because of their deep location in the neck and may have a relatively long progression before becoming symptomatic. Common presenting signs and symptoms of parapharyngeal space neoplasms include swelling in the neck, intraoral mass, dysphagia, dysphonia, heaviness in the ear, otalgia, and rarely, trismus. Some of these signs and symptoms could be mistaken for signs of temporomandibular disorder (TMD). This clinical report presents the incidental discovery of parapharyngeal space carcinoma initially presenting as TMD. A thorough clinical examination of the temporomandibular joints, supported by their magnetic resonance imaging, led to early detection of the neoplasm, thereby improving the patient's post-treatment survival probability.

Efficacy and Tolerability of Erenumab for Prevention of Episodic Migraine in India.

Background: EMPOwER, a 12-week, double-blind (DB), randomized, placebo-controlled study evaluated the efficacy and safety of erenumab in adult patients with episodic migraine (EM) from Asia, the Middle East, and Latin America. This study analyzes the Indian experience for the use of erunumab for prevention of episodic migraine. Objective: The study aimed to evaluate the efficacy and tolerability of erenumab (70 mg and 140 mg) in EM patients from India. Methods: Randomized patients received monthly subcutaneous injections of placebo and erenumab 70 mg or 140 mg for 3 months. The primary endpoint was a change from the baseline in monthly migraine days (MMDs) at month 3. Other endpoints included achievement of ≥50%, ≥75%, and 100% reduction in MMD; a change in monthly acute migraine-specific medication treatment days; a change in patient-reported outcomes; and safety assessment. Results: Of the 539 patients screened, 351 patients were randomized (erenumab, 70 mg: n = 133 and 140 mg: n = 94; placebo: n = 124). The mean (±SD) age, disease duration, and MMD were 35.1 (±8.6) years, 6.77 (±6.01) years, and 7.82 (±2.89) days, respectively. The placebo-adjusted difference in mean MMD for erenumab 70 mg was -0.88 (95% CI, -2.16, 0.39; P = 0.174) days, and that for erenumab 140 mg was -1.01 (-2.42, 0.41; P = 0.164) days versus placebo. Secondary and exploratory endpoints demonstrated consistently better results in both erenumab dosage groups versus placebo. Treatment-emergent adverse events were comparable across groups (erenumab, 70 mg: 22.7% and 140 mg: 24.5%; placebo: 25.2%). Conclusion: Both doses of erenumab showed numerical improvement for efficacy endpoints and were well-tolerated in the Indian population. No new safety signals were reported.

Rhino-Orbito-Cerebral Mycosis and COVID-19: From Bad to Worse?

Background: There has been an increase an alarming rise in invasive mycoses during COVID-19 pandemic, especially during the second wave. Aims: Compare the incidence of invasive mycoses in the last three years and study the risk factors, manifestations and outcomes of mycoses in the COVID era. Methodology: Multicentric study was conducted across 21 centres in a state of western India over 12-months. The clinico-radiological, laboratory and microbiological features, treatment and outcomes of patients were studied. We also analysed yearly incidence of rhino-orbito-cerebral mycosis. Results: There was more than five-times rise in the incidence of invasive mycoses compared to previous two-years. Of the 122 patients analysed, mucor, aspergillus and dual infection were seen in 86.9%, 4.1%, and 7.4% respectively. Fifty-nine percent had simultaneous mycosis and COVID-19 while rest had sequential infection. Common presenting features were headache (91%), facial pain (78.7%), diplopia (66.4%) and vison loss (56.6%). Rhino-orbito-sinusitis was present in 96.7%, meningitis in 6.6%, intracranial mass lesions in 15.6% and strokes in 14.8%. A total of 91.8% patients were diabetic, while 90.2% were treated with steroids during COVID-19 treatment. Mortality was 34.4%. Conclusion: Invasive fungal infections having high mortality and morbidity have increased burden on already overburdened healthcare system. Past illnesses, COVID-19 itself and its treatment and environmental factors seem responsible for the rise of fungal infection. Awareness and preventive strategies are the need of hours and larger studies are needed for better understanding of this deadly disease.

Epidemic of Mucormycosis in COVID-19 Pandemic: A Position Paper.

During the second wave of COVID-19 pandemic, there is a sudden increase in number of cases mucormycosis infection in India. This communication by the Tropical Neurology subsection expert group of the Indian Academy of Neurology (IAN) describes the clinical and diagnostic features, treatment of the disease and gives recommendations about the ways forward.

Cerebrovascular Involvement in Mucormycosis in COVID-19 Pandemic.

BACKGROUND: Many countries have seen an unprecedented rise of cases of coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM). Cerebrovascular involvement in CAM has not been studied so far. We describe clinico-radiological manifestations of cerebrovascular complications observed in CAM. METHODS: In this multicentric retrospective observational study from India, patients with CAM who developed cerebrovascular involvement were studied. Their demographics, risk factors, clinical manifestations, imaging, laboratory profile and outcomes were noted. RESULTS: Out of 49 subjects with cerebrovascular involvement, 71.4% were males while average age was 52.9 years. Ischemic stroke was commonest (91.8%) followed by intracranial haemorrhage (6.1%) and subarachnoid haemorrhage (2%). The incidence of cerebrovascular complications in CAM was found to be 11.8% in one center. Cerebrovascular symptoms appeared a median of 8.3 days from the onset of mucormycosis. Commonest presentation of mucormycosis was rhino-orbito-cerebral syndrome in 98%. Diabetes mellitus was present in 81.7%. Forty percent developed stroke despite being on antiplatelet agent and/or heparin. Amongst subjects with ischemic strokes, location of stroke was unilateral anterior circulation (62.2%); bilateral anterior circulation (17.8%); posterior circulation (11.1%) and combined anterior and posterior circulation (8.9%). Vascular imaging revealed intracranial occlusion in 62.1%; extracranial occlusion in 3.4% and normal vessels in 34.5%. Mortality was 51% during hospital stay. CONCLUSIONS: Cerebrovascular involvement was seen in 11.8% patients of CAM. Angio-invasive nature of the fungus, prothrombotic state created by COVID-19, and diabetes were important causative factors. Subjects with CAM should be screened for involvement of the brain as well as its vessel. Antiplatelet agents/heparin did not seem to provide complete protection from this type of stroke.

Neurological Manifestations in COVID-19 in Three Waves of the Pandemic: An Inpatient Study from India.

Background: Though severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) virus primarily affects respiratory system, neurological involvement is well known. Aims: To describe the neurological manifestations of coronavirus disease 2019 (COVID-19) during three waves of the pandemic. Methodology: This was an ambispective observational single-centre study to describe the neurological manifestations of COVID-19 infection among inpatients from a tertiary care referral centre in Western India from March 2020 to January 2022. Results: Out of 14,822 patients admitted with COVID-19, 307 (2.07%) had neurological manifestations. Neurological manifestations were seen in 1.87% in first wave (onset to 10 Feb 21); 2.37% in second wave (Feb 11, 2021 to Dec 31, 2021) and 6.26% in third wave (Jan 1, 2022 to Jan 31, 2022). The most common neurological manifestations were encephalopathy (34.5%), ischemic stroke (32.1%), and acute symptomatic seizures (8.8%). Encephalopathy (p = 0.028) was more common in first wave while seizures were more common in third wave (p = 0.001). In patients with encephalopathy, hypoxia (p = 0.0001), shock (p = 0.001), renal involvement (p = 0.002), and sepsis (p = 0.033) were associated with higher mortality; while those with no systemic involvement had better survival (p = 0.0001). Among patients with ischemic stroke, 32.1% did not have any traditional vascular risk factors. These patients were 9 years younger and required 6 days less hospitalization than patients of stroke with vascular risk factors. Conclusion: SARS-CoV-2 produces many central and peripheral nervous system manifestations. Encephalopathy was more common in first wave while acute symptomatic seizures were more common in third wave. Encephalopathy was most common neurological manifestation with progressively higher mortality with increased number of systemic comorbidities. Ischemic stroke was seen in patients who had vascular risk factors as well as in patients without them.

Acute haemorrhagic leukoencephalitis (AHLE) - our experience and a short review.

BACKGROUND: Acute haemorrhagic leukoencephalitis (AHLE), a rare variant of acute disseminated encephalomyelitis (ADEM), often presents differently from classical ADEM, thereby posing a diagnostic challenge to the clinician. AIM: To report AHLE, its clinic-radiological manifestations, process of diagnosis and prognosis. METHOD AND RESULTS: Eight patients presented with altered sensorium, acute focal deficits with or without seizures. Initial workup showed evidence of haemorrhagic lobar or thalamic lesions in seven patients. All patients underwent extensive evaluation for collagen vascular disease and vasculitis profile, autoimmune encephalitis panel and aquaporin-4 antibody, which were found to be normal. Cerebrospinal fluid (CSF) biochemistry and microscopy was non-contributory and CSF viral PCRs, toxoplasma antibodies, cryptococcal antigen were also negative. All patients had progressively worsening sensorium and neurological deficits. Repeat MRIs showed increase in oedema in the lesions and appearance/expansion of haemorrhage in the thalamic/hemispherical lesions. All patients received intravenous methylprednisolone (IVMP) without any benefit. Four patients underwent plasmapheresis (PLEX), one received intravenous immunoglobulin (IVIG) and one received both second line immunotherapies, without significant improvement. Brain biopsy (performed in three patients) showed inflammatory demyelination and areas of haemorrhage, thus confirming the diagnosis. Six patients succumbed in 7-30 days of the illness, despite aggressive treatment and only two survived, albeit with a significant disability. CONCLUSION: AHLE is a rare, yet very severe variant of ADEM. MRI shows lesions with haemorrhages, oedema and mass effect and histology findings reveal inflammatory infiltrates, haemorrhagic foci and fibrinoid necrosis of vessel walls. Prognosis is worse as compared to the classic ADEM, with a high mortality rate. To the best of our knowledge, this is one of the largest series of AHLE to have been reported anywhere in the world. KEYMESSAGE: Acute encephalopathy, multifocal deficits accompanied by haemorrhagic CNS demyelinating lesions with oedema and mass effect are the key features of AHLE. It is a rare, yet very severe form of ADEM with very high morbidity and mortality.

Neurosyphilis, A True Chameleon of Neurology.

BACKGROUND: Neurosyphilis (NS) is a rarely encountered scenario today. Manifestations are heterogeneous, and their characteristics have changed in the antibiotic era. A differential diagnosis of NS is not commonly thought of even with relevant clinical-radiological features, as it mimics many common neurological syndromes. OBJECTIVES: To study the manifestations of NS in the present era and the process of diagnosis. METHOD: The data of ten patients with NS was collected and analyzed. Their background data, clinical features, investigations, the process of reaching the diagnosis, management and outcomes were recorded. OBSERVATIONS AND RESULTS: The manifestations of NS in our cohort included six patients with cognitive decline/encephalopathy and one each with meningitis with cranial nerve palsies, cerebellar ataxia, myelitis and asymptomatic NS. The presence of Argyll Robertson pupil helped to clinch diagnosis in one patient. Treponemal tests were ordered in two patients only after alternative etiologies were looked at, to begin with, whereas in six patients treponemal test was requested as a part of standard workup for dementia/ataxia. CONCLUSIONS: NS dementia and behavior changes are mistaken for degenerative, vascular, nutritional causes, autoimmune encephalitis or prion disease. Meningitis has similarities with infective (tubercular), granulomatous (sarcoidosis, Wegener's), collagen vascular disease and neoplastic meningitis, and myelitis simulates demyelination or nutritional myelopathy (B12 deficiency). Rarely, NS can also present with cerebellar ataxia. Contemplate NS as one of the rare causes for such syndromes, and its early treatment produces good outcomes.

An Epidemiological Case Control Multi-centre Trial on Cerebral Venous Sinus Thrombosis in Western Maharashtra, India.

INTRODUCTION: Cerebral Sino-Venous thrombosis (CSVT) is common in India; this country has a heterogeneous population. Genetically and physio-gnomically this population differs in their diet as well as in their environment. Despite these differences CSVT has been described from all quarters of India; a common factor embracing all these patients could be nutrition. OBJECTIVES: An epidemiological, case- control, multi-centre trial was carried out in patients of CSVT. A common factor underlying this could be nutrition which has not been highlighted in several studies. Hence, we studied the nutritional aspects of these patients. METHOD: 63 patients of CSVT and 62 controls enrolled prospectively and followed for a year were investigated with special emphasis on their nutritional status. RESULTS: The triceps skin fold thickness, energy baseline, serum Proteins, Albumin, Hemogram and Platelet counts were lower in patients than in the controls while serum Homocysteine, carbohydrates and fats were higher in patients than in controls. CONCLUSION: The results of this study confirm nutritional deficiencies in patients of CSVT and it begs the question of whether nutrition in any way is causal in CSVT. Larger multi-centric trials will help establishing causality. The study also shows that routine evaluation of thrombophilia factors and immunological tests are not necessary in CSVT.

Outcome of COVID-19 Infection in Cancer Patients in Pune.

Introduction We document our data on the course of the coronavirus disease 2019 (COVID-19) infection in cancer patients in an attempt to help optimize their management in India and globally. Material and Methods Between February 2020 and January 2021, participating oncologists from Pune (members of the Oncology Group of Pune) documented effect of COVID-19 infection in their cancer patients. Binomial logistic regression analysis as well as correlation analysis was done using Pearson Chi-square test to determine significance of clinical factors. Results A total of 29 oncologists from 20 hospitals contributed their data involving 147 cancer patients who developed COVID-19 infections. COVID-19 infection resulted in higher deaths (likelihood ratio of 4.4) amongst patients with hematological malignancies (12/44 = 27.2%) as compared with those with solid tumors (13/90 = 14.4%, p = 0.030). Patients with uncontrolled or progressive cancer (11/34 = 32.4%) when they got infected with COVID-19 had higher mortality as compared with patients whose cancer was under control (14/113 = 12.4%; p = 0.020). Complication of thromboembolic episodes (seen in eight patients; 5.4% cases) was associated with higher risk (25.6 times) of death (five-eighths; 62.5%) as compared with those who did not develop it (20/139;14.4%; p <0.001). Discussion Patients with cancer should be advised to take strict precautions to reduce the risk of being infected with COVID-19. They should also be given priority for COVID-19 vaccination. If infected with COVID-19, patients with hematological malignancy and uncontrolled cancer are at higher risk of morbidity and mortality. When they are being treated (OPD or inpatient basis), additional precautions are necessary to ensure their exposure to potential COVID-19 virus is minimized. If they get infected with COVID-19, they should be given aggressive treatment to prevent complications, especially thromboembolic episodes. If they develop any thromboembolic complication, their risk of dying are significantly higher, and management should be modified accordingly.

Myelin Oligodendrocyte Glycoprotein (MOG)-IgG Associated Demyelinating Disease: Our Experience with this Distinct Syndrome.

BACKGROUND: Discovery of serum myelin oligodendrocyte glycoprotein (MOG) antibody testing in demyelination segregated MOG-IgG disease from AQ-4-IgG positive NMOSD. AIMS: To study clinico-radiological manifestations, pattern of laboratory and electrophysiological investigations and response to treatment through follow up in MOG-IgG positive patients. METHOD: Retrospective data of MOG-IgG positive patients was collected. Demographics, clinical manifestations at onset and at follow up and relapses, anti AQ-4-IgG status, imaging and all investigations were performed, treatment of relapses and further immunomodulatory therapy were captured. RESULTS: In our 30 patients, F: M ratio was 2.75:1 and adult: child ratio 4:1. Relapses at presentation were optic neuritis {ON}(60%), longitudinally extensive transverse myelitis {LETM}(20%), acute disseminated encephalomyelitis {ADEM}(13.4%), simultaneous ON with myelitis (3.3%) and diencephalic Syndrome (3.3%). Salient MRI features were ADEM-like lesions, middle cerebellar peduncle fluffy infiltrates, thalamic and pontine lesions and longitudinally extensive ON {LEON} as well as non-LEON. Totally, 50% patients had a relapsing course. Plasma exchange and intravenous immunoglobulin worked in patients who showed a poor response to intravenous methylprednisolone. Prednisolone, Azathioprine, Mycophenolate and Rituximab were effective attack preventing agents. CONCLUSIONS: MOG-IgG related manifestations in our cohort were monophasic/recurrent/simultaneous ON, myelitis, recurrent ADEM, brainstem encephalitis and diencephalic Syndrome. MRI features suggestive of MOG-IgG disease were confluent ADEM-like lesions, middle cerebellar peduncle fluffy lesions, LETM, LEON and non-LEON. Where indicated, patients need to go on immunomodulation as it has a relapsing course and can accumulate significant disability. Because of its unique manifestations, it needs to be considered as a distinct entity. To the best of our knowledge, this is the largest series of MOG-IgG disease reported from India.

Neurological Manifestations of Dengue Fever.

BACKGROUND: Dengue is a common endemic infection in India. Neurological complications involving various parts of the neuro-axis have been reported. We report neurological complications amongst dengue patients admitted to a tertiary hospital in Western India. MATERIALS AND METHODS: Patients admitted in a tertiary hospital in Western India with dengue infection and having neurological symptoms were included in this study. Their history, physical examination, laboratory investigations and imaging studies were obtained from the inpatient records and analysed. RESULTS: Between January 2014 to December 2019, a total of 5821 patients were diagnosed with dengue. Of these, 154 (2.64%) had neurological manifestations. Encephalopathy in a setting of multisystem involvement was seen in 31.2% patients, encephalitis with focal features, abnormal imaging and/or abnormal cerebrospinal fluid (CSF) examination was seen in 15.6%, syncope in 27.3% and acute symptomatic seizure in 11.0%. Less common presentations were intracranial haemorrhage (4.5%), Guillain-Barre syndrome (GBS) (3.2%), optic neuritis (1.9%), myositis (1.3%), hypokalemic paralysis (1.3%), ischemic stroke (0.6%), posterior reversible encephalopathy syndrome (PRES) (0.6%), myoclonus (0.6%) and brachial plexopathy (0.6%). CONCLUSIONS: In this study of patients admitted with dengue, neurological complications due to dengue were seen in 2.64%. Encephalopathy, encephalitis and syncope were the commonest manifestations, followed by acute symptomatic seizures, intracranial haemorrhage and GBS. The entire neuroaxis can be involved in dengue infection. To the best of our knowledge, this is the largest reported study of neurological complications of dengue.

In vitro fracture resistance of zirconia, glass-fiber, and cast metal posts with different lengths.

AIM: Post-and-core restorations require sufficient length of the post for retention of the prosthesis and root strength. The effect of different lengths of prefabricated zirconia posts (ZPs) on the fracture strength of endodontically treated teeth needs evaluation. Hence, the aim of this study was to evaluate the in vitro fracture resistance of endodontically treated incisors restored with ZP, glass-fiber (GFP), and cast posts (CP) of different lengths. SETTINGS AND DESIGN: Comparative in-vitro study. MATERIALS AND METHODS: Sixty extracted incisors were endodontically treated, tooth preparations were carried out, and the impression of the coronal portion of each prepared tooth was made using polyvinyl siloxane impression material loaded in copper tubes. The coronal portion of each tooth was removed, maintaining a 2 mm ferrule. The teeth were restored with one of the three posts: CPs, GFP, or ZPs, with intraradicular lengths of either 6 or 8 mm (n = 10). The CP and core patterns were fabricated using post space impressions and core buildup and cast using Nickel-Chromium alloy. After composite resin core buildup of GFP and ZPs treated teeth using the previously made copper tube impressions, the teeth were loaded to fracture in an oblique direction in the universal testing machine. STATISTICAL ANALYSIS USED: Data were analyzed using two-way ANOVA and Tukey-Kramer tests (α = 0.05). RESULTS: The highest and lowest values of fracture resistance were reported with ZP8 and GFP6 groups, respectively. There was no significant difference in fracture resistance between the posts of length 6 mm and 8 mm in CP, GFP, and ZP groups. There was no significant difference (P = 0.953) in fracture resistance between CP (284.8 N) and ZP (258.31 N) groups, while the GFP group (160.61 N) had a significantly lower value of fracture resistance than the CP and ZP groups. Two-way ANOVA test for fracture resistance of the post systems and post lengths showed that there was no significant correlation between the post systems and post length on the fracture resistance. There was a greater percentage of favorable fractures in GFP and ZP groups (65% each), than the CP group (20%). CONCLUSION: For the post systems tested, extending the post length does not significantly increase the fracture resistance of the restored teeth. The ZP represents a viable alternative to the cast metal post during the esthetic restoration of endodontically treated anterior teeth.

Soil quality assessment of coastal salt-affected acid soils of India.

Soil salinity and acidity are some of the major causes of land degradation and have a negative impact on agricultural productivity. Assessing soil quality (SQ) of soils affected by soil salinity and acidity is required for their sustainable utilization for agricultural production. The aim of the present study was to evaluate the SQ of the salt-affected acid soils of the Indian West Coastal region using the additive and weighted soil quality indices (SQIs). The SQIs were developed using a total dataset (TDS) and a minimum dataset (MDS). The TDS comprised of 15 different soil properties as electrical conductivity (EC), pH, bulk density, soil available nitrogen (N), phosphorus (P), potassium (K), sulfur (S), boron (B), iron (Fe), manganese (Mn), copper (Cu), zinc (Zn) and exchangeable calcium (Ca), magnesium (Mg), and sodium (Na) measured on 300 soil samples (depth 0-0.15 m). Based on principal component analysis and correlation analysis, an MDS with soil properties like soil pH, EC, Na, Cu, Mn, and BD was formed. Using two approaches (additive and weighted), two datasets (TDS and MDS), and two scoring methods (linear and non-linear), eight SQIs were developed. The MDS-based linear weighted and non-linear weighted SQI found suitable to evaluate SQ of salt-affected acid soils and SQI had a significant and negative correlation of - 0.83 and - 0.70 (p < 0.01) with EC, respectively. Thus, it is clear that the SQ considerably reduces with an increase in soil salinity. The performance of the MDS-based SQIs was better than the TDS to discriminate different soil salinity classes. The agreement between the linear and non-linear scoring method of SQI had a linear relationship with a coefficient of determination (R2) of 0.91-0.96. Thus, assessing the SQ of salt-affected acid soils using MDS, linear scoring, and weighted approach of the soil quality indexing could save the time and cost involved.

Constraining the complexity of promoter dynamics using fluctuations in gene expression.

Gene expression is an inherently stochastic process with transcription of mRNAs often occurring in bursts: short periods of activity followed by typically longer periods of inactivity. While a simple model involving switching between two promoter states has been widely used to analyze transcription dynamics, recent experimental observations have provided evidence for more complex kinetic schemes underlying bursting. Specifically, experiments provide evidence for complexity in promoter dynamics during the switch from the transcriptionally inactive to the transcriptionally active state. An open question in the field is: what is the minimal complexity needed to model promoter dynamics and how can we determine this? Here, we show that measurements of mRNA fluctuations can be used to set fundamental bounds on the complexity of promoter dynamics. We study models wherein the switching time distribution from transcriptionally inactive to active states is described by a general waiting-time distribution. Using approaches from renewal theory and queueing theory, we derive analytical expressions which connect the Fano factor of mRNA distributions to the waiting-time distribution for promoter switching between inactive and active states. The results derived lead to bounds on the minimal number of promoter states and thus allow us to derive bounds on the minimal complexity of promoter dynamics based on single-cell measurements of mRNA levels.

Primary Central Nervous System Burkitt Lymphoma in HIV Positive Pediatric Patient: A Rare Case Report.

Burkitt lymphoma is a high-grade B-cell lymphoma with aggressive course of disease and primarily systemic nodal involvement. Primary Burkitt lymphoma with isolated central nervous system (CNS) involvement and that too in pediatric population has been rarely reported. Here, we present a case of a primary Burkitt lymphoma involving brain in an human immunodeficiency virus-positive pediatric patient who was on antiretroviral therapy. Currently, there are no established protocols or guidelines for management of primary CNS Burkitt lymphoma thus posing challenges in the management of such cases. Our patient was successfully treated by surgical resection followed by chemotherapy and radiotherapy.