Dentatorubral-pallidoluysian atrophy: a rare cause of epilepsy, ataxia and chorea.

A 34-year-old woman presented with insidious onset and gradually progressive cerebellar ataxia over 10 years, with generalised convulsions. On examination, there were myoclonic jerks, choreiform movements and cerebellar syndrome. Her family history suggested an autosomal dominant inheritance with anticipation. Genetic analysis for trinucleotide repeat disorders led to a diagnosis of dentatorubral-pallidoluysian atrophy (60 CAG repeats in the atrophin-1 gene). This rare spinocerebellar ataxia should be considered in the differential diagnosis of inherited ataxia when combined with seizures and chorea. Other features suggesting a repeat expansion disorder are variable phenotypes within the same family and possible anticipation.

Feasibility and Efficacy of Telephone Based Follow-up in Patients with Headache - A Longitudinal Cohort Study.

BACKGROUND: Chronic headache greatly affects the quality of life and also constitutes a significant burden on the health system. OBJECTIVE: The objective of this study was to evaluate the feasibility of telephone-based follow-up in a cohort of headache patients in India. MATERIALS AND METHODS: This was a longitudinal cohort study of patients with episodic headache with one physical visit in the neurology outpatient services in the last year. Two neurologists conducted the telephone follow up (TFU) of included patients 12 weeks apart. We evaluated the following: (1) objective characterization of headache, (2) coexistent depression and anxiety, (3) patient satisfaction, (4) treatment adherence, and (5) changes in medications. RESULTS: A total of 214 out of 274 eligible patients were included in the cohort. The mean age was 31.74 ± 7.77 years (18-45), and 164 (77%) were females. Migraine without aura was the most common diagnosis in 159 (74%). The mean disease duration was 78.01 ± 70.15 months (8-360). Concurrent depression and anxiety were noted in 87 (40.6%) and 45 (21%) of the patients, respectively. There was a significant improvement in the headache frequency (23.82 vs. 1.06, P < 0.001), severity (7.21 vs. 2.62, P = 0.032), and Headache Impact 6-item score (58.12 vs. 38.01, P = 0.014) at baseline and second follow-up. The satisfaction level to TFU in the first and second interviews was 94.4% and 97.2%, respectively. CONCLUSION: Telephone-based follow-up is a feasible alternative for repeat outpatient consultation of headache patients.

Dissecting the Phenotype and Genotype of PLA2G6-Related Parkinsonism.

BACKGROUND: Complex parkinsonism is the commonest phenotype in late-onset PLA2G6-associated neurodegeneration. OBJECTIVES: The aim of this study was to deeply characterize phenogenotypically PLA2G6-related parkinsonism in the largest cohort ever reported. METHODS: We report 14 new cases of PLA2G6-related parkinsonism and perform a systematic literature review. RESULTS: PLA2G6-related parkinsonism shows a fairly distinct phenotype based on 86 cases from 68 pedigrees. Young onset (median age, 23.0 years) with parkinsonism/dystonia, gait/balance, and/or psychiatric/cognitive symptoms were common presenting features. Dystonia occurred in 69.4%, pyramidal signs in 77.2%, myoclonus in 65.2%, and cerebellar signs in 44.6% of cases. Early bladder overactivity was present in 71.9% of cases. Cognitive impairment affected 76.1% of cases and psychiatric features 87.1%, the latter being an isolated presenting feature in 20.1%. Parkinsonism was levodopa responsive but complicated by early, often severe dyskinesias. Five patients benefited from deep brain stimulation. Brain magnetic resonance imaging findings included cerebral (49.3%) and/or cerebellar (43.2%) atrophy, but mineralization was evident in only 28.1%. Presynaptic dopaminergic terminal imaging was abnormal in all where performed. Fifty-four PLA2G6 mutations have hitherto been associated with parkinsonism, including four new variants reported in this article. These are mainly nontruncating, which may explain the phenotypic heterogeneity of childhood- and late-onset PLA2G6-associated neurodegeneration. In five deceased patients, median disease duration was 13.0 years. Brain pathology in three cases showed mixed Lewy and tau pathology. CONCLUSIONS: Biallelic PLA2G6 mutations cause early-onset parkinsonism associated with dystonia, pyramidal and cerebellar signs, myoclonus, and cognitive impairment. Early psychiatric manifestations and bladder overactivity are common. Cerebro/cerebellar atrophy are frequent magnetic resonance imaging features, whereas brain iron deposition is not. Early, severe dyskinesias are a tell-tale sign. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Antifungal and defense elicitor activity of Potassium phosphite against fungal blast disease on ptxD-OE transgenic indica rice and its acceptor parent.

In rice farming, the blast disease caused by Magnaporthe oryzae (T.T. Hebert) M.E. Barr. is one of the primary production constraints worldwide. The current blast management options such as blast-resistant varieties and spraying fungicides are neither durable nor commercially and environmentally compatible. In the present study, we investigated the antifungal and defense elicitor activity of potassium phosphite (Phi) against M. oryzae on elite rice cultivar BPT5204 (popularly known as Samba Mahsuri in India) and its transgenic rice variant (ptxD-OE) over-expressing a phosphite dehydrogenase enzyme. The Phi was evaluated both preventively and curatively on rice genotypes where the preventive spray of Phi outperformed the Phi curative application with significant reductions in both rice blast severity (35.67-60.49%) and incidence (22.27-53.25%). Moreover, the application of Phi increased the levels of photosynthetic pigments (Chlorophyll and Carotenoids) coupled with increased activity of defense enzymes (PAL, SOD, and APx). Besides, Phi application also induced the expression of defense-associated genes (OsCEBiP and OsPDF2.2) in the rice leaf. Furthermore, the Phi application reduced the reactive Malondialdehyde (lipid peroxidation) to minimize the cellular damage incited by Magnaporthe in rice. Overall, the present study showed the potential of Phi for blast suppression on rice as an alternative to the current excessive use of toxic fungicides.

Seronegative panencephalitis complicated by viral encephalomyelitis in a case of Good's syndrome - a neuropathological report.

BACKGROUND: The role of thymus in the immune cascade of the body is still under active clinical scrutiny. Meanwhile, there is an unravelling of myriad presentations of thymoma with effects on various organ systems. These effects arise both due to autoimmunity or a paraneoplastic process secondary to thymoma. However, an occasional patient can be a conundrum and may give no clue regarding the pathogenesis and etiology of its clinical profile. MATERIAL AND METHODS: We present an enigmatic case of a 30-year-old male presenting with superficial fungal infections followed by multiaxial neurological involvement against a background of thymoma. Extensive workup for bacterial, viral, autoimmune and paraneoplastic etiologies were negative. Thymectomy confirmed thymoma (Type AB) but failed to ameliorate the progression of symptoms. He developed recurrent episodes of severe sepsis which remitted with sensitive antibiotics only to reappear again. Immunological profile showed complete absence of peripheral circulating B-cells with reversal of CD4/CD8 ratio, findings compatible with Good's syndrome. Radiological findings showed only progressive brain atrophy without any hyperintensity. He was also treated with intravenous immunoglobulins but failed to respond with the same. RESULTS: Autopsy revealed features of panencephalitis (neuronophagia, neuronal loss, perivascular lymphocytic cuffing and microglial nodules) with virus particles detected ultrastructurally. Although the distinction between seronegative autoimmune encephalitis versus a viral encephalomyelitis often blurs histologically, we speculated viral encephalomyelitis to have happened toward the latter part of his long illness. To our knowledge, this is a case of Good's syndrome presenting with seronegative autoimmune panencephalitis superimposed with a viral infection.

How to Cope with the Challenges of Environmental Stresses in the Era of Global Climate Change: An Update on ROS Stave off in Plants.

With the advent of human civilization and anthropogenic activities in the shade of urbanization and global climate change, plants are exposed to a complex set of abiotic stresses. These stresses affect plants' growth, development, and yield and cause enormous crop losses worldwide. In this alarming scenario of global climate conditions, plants respond to such stresses through a highly balanced and finely tuned interaction between signaling molecules. The abiotic stresses initiate the quick release of reactive oxygen species (ROS) as toxic by-products of altered aerobic metabolism during different stress conditions at the cellular level. ROS includes both free oxygen radicals {superoxide (O2•-) and hydroxyl (OH-)} as well as non-radicals [hydrogen peroxide (H2O2) and singlet oxygen (1O2)]. ROS can be generated and scavenged in different cell organelles and cytoplasm depending on the type of stimulus. At high concentrations, ROS cause lipid peroxidation, DNA damage, protein oxidation, and necrosis, but at low to moderate concentrations, they play a crucial role as secondary messengers in intracellular signaling cascades. Because of their concentration-dependent dual role, a huge number of molecules tightly control the level of ROS in cells. The plants have evolved antioxidants and scavenging machinery equipped with different enzymes to maintain the equilibrium between the production and detoxification of ROS generated during stress. In this present article, we have focused on current insights on generation and scavenging of ROS during abiotic stresses. Moreover, the article will act as a knowledge base for new and pivotal studies on ROS generation and scavenging.

The Genetics of Ethambutol-Induced Optic Neuropathy: A Narrative Review.

Tuberculosis (TB) is a global health problem with the major brunt of disease occurring in developing countries. The cornerstone of treatment of TB is anti-tubercular therapy (ATT), which includes rifampicin, isoniazid, pyrazinamide and ethambutol. Because of emerging drug resistance, treatment failures, defaulters and increasing incidence of disseminated and extrapulmonary TB, the guidelines have been modified in some countries. Ethambutol is prescribed for longer times (in some cases >8 months) and hence the incidence of ethambutol-induced optic neuropathy (EtON) is expected to rise. The fundamental question which needs explanation is why only a small subset of patients on ethambutol are prone to develop loss of vision. This review focuses on available genetic studies which provide evidence that mitochondria are the likely substrates involved in the final pathway of reactive oxidative damage of the papillo-macular bundle. Genetic analysis of mitochondrial mutations encoding genes involved in oxidative phosphorylation pathways may help in isolating the subset of patients who are genetically susceptible. If the groups having high risk of developing EtON are recognised then prolonged duration of ethambutol treatment can be avoided in these susceptible individuals. A better understanding of the pathophysiology will also pave the way for the development of management strategies in this condition.

Plant mineral transport systems and the potential for crop improvement.

MAIN CONCLUSION: Nutrient transporter genes could be a potential candidate for improving crop plants, with enhanced nutrient uptake leading to increased crop yield by providing tolerance against different biotic and abiotic stresses. The world's food supply is nearing a crisis in meeting the demands of an ever-growing global population, and an increase in both yield and nutrient value of major crops is vitally necessary to meet the increased population demand. Nutrients play an important role in plant metabolism as well as growth and development, and nutrient deficiency results in retarded plant growth and leads to reduced crop yield. A variety of cellular processes govern crop plant nutrient absorption from the soil. Among these, nutrient membrane transporters play an important role in the acquisition of nutrients from soil and transport of these nutrients to their target sites. In addition, as excess nutrient delivery has toxic effects on plant growth, these membrane transporters also play a significant role in the removal of excess nutrients in the crop plant. The key function provided by membrane transporters is the ability to supply the crop plant with an adequate level of tolerance against environmental stresses, such as soil acidity, alkalinity, salinity, drought, and pathogen attack. Membrane transporter genes have been utilized for the improvement of crop plants, with enhanced nutrient uptake leading to increased crop yield by providing tolerance against different biotic and abiotic stresses. Further understanding of the basic mechanisms of nutrient transport in crop plants could facilitate the advanced design of engineered plant crops to achieve increased yield and improve nutrient quality through the use of genetic technologies as well as molecular breeding. This review is focused on nutrient toxicity and tolerance mechanisms in crop plants to aid in understanding and addressing the anticipated global food demand.

Carbamazepine versus levetiracetam in epilepsy due to neurocysticercosis.

BACKGROUND: The choice of antiepileptic drug (AED) in newly diagnosed neurocysticercosis (NCC) patients with epilepsy continues to be arbitrary. We compared efficacy and side effect profile of levetiracetam (LEV) and carbamazepine (CBZ) for the treatment of seizures in newly diagnosed patients with NCC. PATIENTS AND METHODS: This was an open-labeled randomized comparative monotherapy study including newly diagnosed drug naïve patients of NCC (n = 99) presenting with seizures who were randomized in 1:1 ratio using computed generated numbers. All patients were followed up for at least six months after start of treatment. The primary outcome measure was seizure control over six months following start of AEDs. RESULTS: Fifteen (15.2%) patients [CBZ- 4(8.2%); LEV- 11(22%)] developed recurrence of seizures. A trend (p = 0.09) was found toward better control of seizures in CBZ compared to LEV. Two (4%) patients in LEV group and 17 (34.6%) patients in CBZ group developed drug-related minor side effects (p < 0.0001). Three patients in CBZ group needed discontinuation of therapy due to skin rash. Eleven patients who relapsed while on LEV did not have any recurrence of seizures after switching over to CBZ. Out of 3 patients who relapsed while receiving CBZ and were changed to LEV, two developed seizures during follow-up. CONCLUSION: CBZ and LEV could be used as alternatives in newly diagnosed patients of NCC at the behest of minor side effects in the CBZ group.

Metal-based nanoparticles, sensors, and their multifaceted application in food packaging.

Due to the global rise of the human population, one of the top-most challenges for poor and developing nations is to use the food produces safely and sustainably. In this regard, the storage of surplus food (and derived products) without loss of freshness, nutrient stability, shelf life, and their parallel efficient utilization will surely boost the food production sector. One of the best technologies that have emerged within the last twenty years with applications in the packaging of food and industrial materials is the use of green mode-based synthesized nanoparticles (NPs). These NPs are stable, advantageous as well as eco-friendly. Over the several years, numerous publications have confirmed that these NPs exert antibacterial, antioxidant, and antifungal activity against a plethora of pathogens. The storage in metal-based NPs (M-NPs) does not hamper the food properties and packaging efficiency. Additionally, these M-NPs help in the improvement of properties including freshness indicators, mechanical properties, antibacterial and water vapor permeability during food packaging. As a result, the nano-technological application facilitates a simple, alternate, interactive as well as reliable technology. It even provides positive feedback to food industries and packaging markets. Taken together, the current review paper is an attempt to highlight the M-NPs for prominent applications of antimicrobial properties, nanosensors, and food packaging of food items. Additionally, some comparative reports associated with M-NPs mechanism of action, risks, toxicity, and overall future perspectives have also been made.

Vim stereotactic radiosurgical thalamotomy for drug-resistant idiopathic Holmes tremor: a case report.

We share our experience with stereotactic gamma knife thalamotomy (GKT) for medically refractory Holmes tremor (HT). A 22-year-old patient underwent gamma knife thalamotomy at ventrointermediate nucleus for disabling HT of the right upper limb. A single 4-mm isocenter was used to target the ventral intermediate nucleus with 130 Gy radiation. At 4 months follow up, we observed 84% improvement in his Fahn-Tolosa-Marin (FTM) rating scale with significant improvement in the right upper limb dystonic tremor. There was only subtle improvement in the ataxic component of the right lower limb. At 1 year after stereotactic GKT, there was sustained neurological improvement with no side effect, We present the stereotactic GKT as a treatment modality for drug-resistant HT. Moreover, it may be considered an alternate treatment modality especially in patients reluctant or contraindicated for any invasive surgical technique. CLINICAL TRIAL REGISTRATION NUMBER: Not required.

Tuberculomas in "Critical" Locations of the Visual Pathway-A Masquerader.

Tuberculosis never stops fascinating physicians. The burden of tuberculosis is a major cause of disability. While drugs are often blamed when patients develop new focal deficits on treatment, the deterioration in these patients can have a myriad of causes including the development of new tuberculomas. Recognizing the critically located tuberculomas as potential causes of vision loss is indispensable. Here, we report two patients with strategic tuberculomas leading to vision loss. In one patient, the cause of visual morbidity was compression of the optic pathways; in the other patient, cortical vision loss was noted due to strategic location of tuberculomas.

Cerebellar ataxia due to Leptospirosis- a case report.

BACKGROUND: Leptospirosis involves nervous system in around 10-15% of the cases, the commonest presentation being aseptic meningitis. Most of the clinical features of neuroleptospirosis are due to capillary endothelial damage and vasculitis. Ataxia is an extremely uncommon manifestation of Leptospirosis occuring in <5% of cases. CASE PRESENTATION: A 28 year old female from North India presented with a short febrile illness followed by an acute onset cerebellar ataxia, anemia, thrombocytopenia and transaminitis. Leptospira serology showed high titres of IgM (ELISA) and MAT (microscopic agglutination test titre >1:800) . She was treated with intravenous ceftriaxone for 14 days following which she showed marked recovery. CONCLUSION: The clinical features of neuroleptospirosis are varied, most of them resulting from endothelial damage and vasculitis. Immune mediated phenomenon with no structural damage is another possible mechanism leading to cerebellar ataxia. Cerebellar ataxia due to common tropical infections should be ruled out in the appropriate setting, as early institution of treatment can abate neurological morbidity. The case report highlights the importance of identifying a reversible cause of cerebellar ataixa due to a tropical infection, possibly due to a immune mediated phenomenon, and would be of interest to both internists and neurologists.

Glioblastoma multiforme masquerading as a tumefactive demyelinating lesion: Lessons learned at autopsy.

Tumefactive demyelinating (TD) lesions are extremely challenging lesions to diagnose during their histopathological examination and are often misdiagnosed as tumors. On the contrary, a glioblastoma multiforme is rarely misdiagnosed as a TD unless the two coexist. We present a case of a 60-year old man who was diagnosed as having tumefactive demyelination on a stereotactic biopsy. At autopsy, however, the lesion revealed a grade IV glioblastoma. The myelin loss along the periphery of the lesion was erroneously interpreted as TD during the histopathological examination. We have described the imaging, the biopsy, and the autopsy findings of this instructive case. It is pertinent to recognize its histology to prevent a misdiagnosis.

Electroclinical characteristics of new-onset seizures associated with neurocysticercosis.

PURPOSE: Although seizures are the most common presentation of neurocysticercosis (NCC), the electroclinical characteristics of the seizures have not been adequately studied. MATERIALS AND METHODS: The study cohort included 308 consecutive patients presenting with a new-onset seizure, both acute symptomatic or unprovoked. They were divided into two groups: Group 1 (NCC group), those in whom imaging studies revealed active or inactive NCC (N = 184 (59.7%)) and group 2 (non-NCC group), those in whom either imaging was normal or revealed abnormalities other than NCC or the diagnosis was idiopathic generalized epilepsy (N = 124 (40.3%)). RESULTS: Clinical features significantly associated with group 1 included focal seizures (specifically, aphasic seizures (P < 0.05)), seizure clusters (P < 0.0001), postictal Todd's paresis (P < 0.05), and peri-ictal headaches (P < 0.008). In addition, somatosensory and visual seizures, and focal-clonic and focal-tonic were more frequent in this group. Generalized clonic seizures (P < 0.05) were significantly more common in the group 2. The findings of regional epileptiform abnormalities (P = 0.0001) and primary generalized epilepsy (P < 0.0001) on electroencephalography were significantly more common in group 2. SIGNIFICANCE: In patients presenting with new-onset seizure, aphasic seizures, seizure clusters, postictal Todd's palsy and peri-ictal headaches might augur the finding of NCC, both active and inactive lesions, on imaging.