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The article describes the case of a 61-year-old male with progressive dysphagia, dysarthria, fatigable chewing difficulty and worsening limb weakness and was diagnosed of generalized Myasthenia gravis (MG). Topics discussed include clinical characteristics of MG, his treatment received, and findings of a review of MG-Morvan's syndrome (MoS) cases.

Background and Objectives: Cardiovascular magnetic resonance imaging (CMRI) is the noninvasive technique of choice for early detection of cardiac involvement in Duchenne and Becker muscular dystrophy (DMD and BMD, respectively), but is seldom used in routine clinical practice in the Indian context. We sought to determine the prevalence of CMRI abnormalities in patients with DMD and BMD and to compare the CMRI parameters with the phenotypic and genotypic characteristics. Methods: A prospective, observational study was conducted on patients genetically diagnosed with DMD and BMD who could complete CMRI between March 2020 and March 2022. Abnormal CMRI was the presence of any late gadolinium enhancement (LGE) that signifies myocardial fibrosis (LGE positivity), regional wall motion abnormality, or reduced left ventricular ejection fraction (LVEF <55%). Results: A total of 46 patients were included: 38 patients with DMD and eight with BMD. Cardiac abnormality was seen in 23 (50%) patients. LGE was more common than impaired LVEF in DMD (16, 42.1%), while impaired LVEF was more common in BMD (5, 62.5%). LGE was most frequently found in lateral wall (18/19) followed by inferior (6/19), septal (5/19), anterior (2/19), and apex (1/19). Among the various clinicodemographic parameters, only age (r = 0.495, P = 0.002) and disease duration (r = 0.407, P = 0.011) were found to significantly correlate with LGE in patients with DMD. No association was found between the various CMRI parameters and the genotype. Conclusions: The current study highlights the differences in myocardial fibrosis and LV dysfunction between DMD and BMD, along with other CMRI parameters. Notably, a genotype--CMRI correlation was not found in the current cohort, which needs to be further explored. [ABSTRACT FROM AUTHOR]

Background: Angiopoietin‐like 4 is a molecular hallmark that correlates with the growth and metastasis of head and neck squamous cell carcinoma, one of the most prevalent cancers worldwide. However, the molecular mechanisms by which angiopoietin‐like 4 promotes head and neck squamous cell carcinoma tumorigenesis are unclear. Methods: Using well‐characterized cell lines of head and neck squamous cell carcinoma development, including human normal oral keratinocytes, dysplastic oral keratinocytes, oral leukoplakia‐derived oral keratinocytes, and head and neck squamous cell carcinoma cell lines, HN13, HN6, HN4, HN12, and CAL27, we investigated the signaling pathways upstream and downstream of angiopoietin‐like 4‐induced head and neck squamous cell carcinoma tumorigenesis. Results: We found that both epidermal growth factor receptor ligands, epithelial growth factor, and amphiregulin led to angiopoietin‐like 4 upregulation in normal oral keratinocytes and dysplastic oral keratinocytes and cooperated with the activation of hypoxia‐inducible factor‐1 in this effect. Interestingly, amphiregulin and angiopoietin‐like 4 were increased in dysplastic oral keratinocytes and head and neck squamous cell carcinoma cell lines, and amphiregulin‐induced activation of cell proliferation was dependent on angiopoietin‐like 4. Although both p38 mitogen‐activated protein kinases (p38 MAPK) and protein kinase B (AKT) were activated by angiopoietin‐like 4, only pharmacological inhibition of p38 MAPK was sufficient to prevent head and neck squamous cell carcinoma cell proliferation and migration. We further observed that angiopoietin‐like 4 promoted the secretion of interleukin 11 (IL‐11), interleukin 12 (IL‐12), interleukin‐1 alpha (IL‐1α), vascular endothelial growth factor, platelet‐derived growth factor (PDGF), and tumour necrosis factor alpha (TNF‐α), cytokines and chemokines previously implicated in head and neck squamous cell carcinoma pathogenesis. Conclusion: Our results demonstrate that angiopoietin‐like 4 is a downstream effector of amphiregulin and promotes head and neck squamous cell carcinoma development both through direct activation of p38 kinase as well as paracrine mechanisms. [ABSTRACT FROM AUTHOR]

Background: Kennedy disease (KD) is a slowly progressive lower motor neuron degenerative disease. The prevalence of KD is unknown in India. Aim: To describe the phenotypic and laboratory features of an Indian cohort of KD patients. Methods: A retrospective study was done on seven genetically confirmed KD patients based on demographic, clinical and laboratory details. Results: Mean age at onset and presentation was 37 ± 11.9 and 44.6 ± 13.5 years respectively. Progressive asymmetric proximal and distal limb weakness was the commonest symptom (57.1%). All patients had motor symptoms along with non‐specific symptoms such as cramps from the onset. Easy fatigability, decremental response along with ptosis were noted in two patients, which was a novel finding. Gynaecomastia and tongue wasting with fasciculations were universal findings. All five patients with nerve conduction studies showed sensorimotor neuropathy. Magnetic resonance imaging muscle done in two patients showed a prominent moth‐eaten appearance in the thigh and posterior leg compartment in one patient. The mean cytosine‐adenine‐guanine repeats were 44 ± 3.7, and there was no association between age of onset or severity with repeat length. Only one patient required an assistive device for ambulation after 15 years of symptom onset. Conclusions: This study showed phenotypic heterogeneity in the Indian cohort. The age of onset was earlier with a slowly progressive indolent course as compared with other ethnic cohorts. This highlights the importance of considering the KD diagnosis in patients with the indolent course and suspected ALS diagnosis even with ptosis and fatigability in an appropriate clinical context. [ABSTRACT FROM AUTHOR]

DHTKD1 is a nuclear gene that encodes "dehydrogenase E1 and transketolase domain-containing 1", essential in mitochondrial metabolism. First identified in the patients of 2-amino-apidic and 2 oxoapidic aciduria, mutation in this gene has recently been implicated in CMT2Q and ALS. Here we report the case of a septuagenarian who presented with a 2 years progressive history of respiratory and neck muscle weakness without significant bulbar and limb involvement. Clinical and electrophysiological examination revealed lower motor neuron involvement with widespread chronic denervation and reinnervation. Clinical exome sequencing revealed a heterozygous nonsense variant in exon 8 of the DHTKD1 gene, which was previously described in CMT2Q. This report highlights the pleotropic phenotypic presentation of DHTKD1 mutation and the need for genetic testing even in sporadic cases of ALS presenting at a later age. [ABSTRACT FROM AUTHOR]

Energy and exergy analysis of solar devices has drawn the interest of researchers across the globe. Energy analysis is a criterion to assess the efficient usage of solar energy. Solar energy storage at its maximum is a big challenge. This challenge can be resolved with the help of a solar dryer storage unit, as it is compact and possesses high storage density. But the problem is minimizing the cost. A low-cost phase change material (PCM) solves this issue; sodium thiosulfate pentahydrate is a PCM of low cost with high latent heat of fusion and its melting point is within the desired temperature range. To determine the usefulness of stored energy using sodium thiosulfate pentahydrate as PCM, exergy analysis based on second law is required. In this paper, energy and exergy studies were done during charging and discharging periods of PCM with a heat input and different mass flow rates of heat transfer fluid. [ABSTRACT FROM AUTHOR]

Objectives: Clinical spectrum of mitochondrial myopathy extends beyond chronic progressive external ophthalmoplegia (CPEO). While information on encephalomyopathies is abundant, clinical data on predominant myopathic presentation of mitochondrial disorders are lacking. Materials and Methods: Clinical, electrophysiological, biochemical, and follow-up data of patients with predominant myopathic presentation and muscle biopsy confirmed primary mitochondrial myopathy was obtained. We excluded known syndromes of mitochondrial cytopathies and encephalomyopathies. Results: Among 16 patients, 7 had CPEO, 4 had CPEO with limb-girdle muscle weakness (LGMW), and 5 had isolated LGMW. Systemic features included seizures with photosensitivity (n = 3), diabetes (n = 1), cardiomyopathy (n = 1), and sensorineural hearing loss (n = 1) and were more common in isolated LGMW. Elevated serum creatine kinase (CK) and lactate levels and electromyography (EMG) myopathic potentials were more frequent with LGMW. During follow-up, LGMW had more severe progression of weakness. Conclusion: We identified three subsets of mitochondrial myopathy with distinct clinical features and evolutionary patterns. Isolated LGMW was seen in 30% of patients and would represent severe end of the spectrum. [ABSTRACT FROM AUTHOR]

Background and purpose: Measuring health‐related quality of life (QOL) is vital for understanding the disease impact, but the complex relationship between clinical parameters and QOL remains unclear. The objective was to determine the demographic and clinical factors that influence the QOL in adults with inherited and acquired myopathies. Methods: The study was of cross‐sectional design. Detailed demographic and clinical details were collected. Patients answered Neuro‐QOL and Patient‐Reported Outcomes Measurement Information System short‐form questionnaires. Results: Data was collected from 100 consecutive in‐person patient visits. Mean age of the cohort was 49.5 ± 20.1 (18–85) years, and the majority were male (53, 53%). Bivariate analysis between the various demographic and clinical features with the QOL scales revealed single simple question (SSQ), handgrip strength, Medical Research Council (MRC) sum score, female gender, and age to be nonuniformly associated with the QOL scales. There was no difference between inherited and acquired myopathies for any of the QOL scores, except for the poorer lower limb function domain in inherited myopathies (36.7 ± 7.3 vs. 40.9 ± 11.2, p = 0.049). Linear regression models revealed lower SSQ, lower handgrip strength, and lower MRC sum score to independently predict poor QOL. Conclusions: Handgrip strength and SSQ serve as novel predictors of QOL in myopathies. Handgrip strength has a significant impact on physical, mental, and social domains and deserves special attention with respect to rehabilitation. SSQ correlates well with QOL and can be employed as a quick and global assessment of a patient's well‐being. Differences in QOL scores between patients with inherited and acquired myopathies were minimal. [ABSTRACT FROM AUTHOR]

Purpose: Accurate assessment of dural sinus, deep and cortical venous thrombosis on MR imaging is challenging. The aim of this study is to evaluate the accuracy of 3D-T1 turbo spin echo (T1S), sequences in detecting venous thrombosis and comparing it with susceptibility-weighted imaging (SWI), magnetic resonance venography (MRV) and post contrast T1 magnetization-prepared rapid acquisition gradient echo (T1C). Methods: A blinded retrospective observational analysis of 71 consecutive patients evaluated for cerebral venous thrombosis (CVT) and 30 control patients was performed. Multimodality reference standard adopted included T1C, SWI with MRV. Sub-analyses in superficial, deep and cortical venous segments were performed in addition to correlation of signal intensity of thrombus with the clinical stage. Results: A total of 2222 segments in 101 complete MRI examinations were evaluated. Sensitivity/specificity/positive predictive value/negative predictive value/accuracy and precision of T1S for detection of cortical vein thrombosis was 0.994/1/1/0.967/0.995/1, 1/0.874/0.949/1/0.963/0.950 for detection of superficial venous sinus thrombosis and 1/1/1/1/1/1 for deep venous thrombosis. The AUC yield for T1S was 0.997 for cortical, 1 for deep and 0.988 for superficial venous segments. Conclusion: T1S paralleled the accuracy of conventional sequences in the overall detection of CVT but showed superior accuracy in the detection of cortical venous thrombosis. It makes a fitting addition to the CVT MRI protocol in scenarios demanding negation of gadolinium administration. [ABSTRACT FROM AUTHOR]

Dysferlinopathies are a group of limb-girdle muscular dystrophies causing significant disability in the young population. There is a need for studies on large cohorts to describe the clinical, genotypic and natural history in our subcontinent. To describe and correlate the clinical, genetic profile and natural history of genetically confirmed dysferlinopathies. We analysed a retrospective cohort of patients with dysferlinopathy from a single quaternary care centre in India. A total of 124 patients with dysferlinopathy were included (40 females). Median age at onset and duration of illness were 21 years (range, 13–50) and 48 months (range, 8–288), respectively. The average follow-up period was 60 months (range, 12–288). Fifty-one percent had LGMD pattern of weakness at onset; 23.4% each had Miyoshi and proximo-distal type while isolated hyperCKemia was noted in 1.6%. About 60% were born to consanguineous parents and 26.6% had family history of similar illness. Twenty-three patients (18.6%) lost ambulation at follow-up; the median time to loss of independent ambulation was 120 months (range, 72–264). Single-nucleotide variants (SNVs) constituted 78.2% of patients; INDELs 14.5% and 7.3% had both SNVs and INDELs. Earlier age at onset was noted with SNVs. There was no correlation between the other clinical parameters and ambulatory status with the genotype. Thirty-seven (45.7%) novel pathogenic/likely pathogenic (P/LP) variants were identified out of a total of 81 variations. The c.3191G > A variant was the most recurrent mutation. Our cohort constitutes a clinically and genetically heterogeneous group of dysferlinopathies. There is no significant correlation between the clinico-genetic profile and the ambulatory status. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is a chronic, fluctuating, antibody-mediated autoimmune disorder directed against the post-synaptic neuromuscular junctions of skeletal muscles, resulting in a wide spectrum of manifestations ranging from mild to potentially fatal. Given its unique natural course, designing an ideal trial design for MG has been wrought with difficulties and evidence in favour of several of the conventional agents is weak as per current standards. Despite this, acetylcholinesterases and corticosteroids have remained the cornerstones of treatment for several decades with intravenous immunoglobulins (IVIG) and therapeutic plasma exchange (PLEX) offering rapid treatment response, especially in crises. However, the treatment of MG entails long-term immunosuppression and conventional agents are viable options but take longer to act and have a number of class-specific adverse effects. Advances in immunology, translational medicine and drug development have seen the emergence of several newer biological agents which offer selective, target-specific immunotherapy with fewer side effects and rapid onset of action. Eculizumab is one of the newer agents that belong to the class of complement inhibitors and has been approved for the treatment of refractory general MG. Zilucoplan and ravulizumab are other agents in this group in clinical trials. Neisseria meningitis is a concern with all complement inhibitors, mandating vaccination. Neonatal Fc receptor (FcRn) inhibitors prevent immunoglobulin recycling and cause rapid reduction in antibody levels. Efgartigimod is an FcRn inhibitor recently approved for MG treatment, and rozanolixizumab, nipocalimab and batoclimab are other agents in clinical trial development. Although lacking high quality evidence from randomized clinical trials, clinical experience with the use of anti-CD20 rituximab has led to its use in refractory MG. Among novel targets, interleukin 6 (IL6) inhibitors such as satralizumab are promising and currently undergoing evaluation. Cutting-edge therapies include genetically modifying T cells to recognise chimeric antigen receptors (CAR) and chimeric autoantibody receptors (CAAR). These may offer sustained and long-term remissions, but are still in very early stages of evaluation. Hematopoietic stem cell transplantation (HSCT) allows immune resetting and offers sustained remission, but the induction regimens often involve serious systemic toxicity. While MG treatment is moving beyond conventional agents towards target-specific biologicals, lack of knowledge as to the initiation, maintenance, switching, tapering and long-term safety profile necessitates further research. These concerns and the high financial burden of novel agents may hamper widespread clinical use in the near future. [ABSTRACT FROM AUTHOR]

Objective: To investigate the contribution of duration and temporal dispersion (TD) of the distal compound muscle action potential (CMAP) in discriminating chronic inflammatory demyelinating polyneuropathy (CIDP) from diabetic sensorimotor polyneuropathy (DSP) and from CIDP+DSP. Methods: We performed a retrospective review of patients diagnosed with CIDP, DSP and CIDP+DSP (responsive to immunotherapy) and examined differences in CMAP duration and TD at baseline. Results: We included 59 subjects: 17 CIDP, 21 DSP and 21 CIDP+DSP. Of these, 16 (94.1%) CIDP, 18 (85.7%) CIDP+DSP and 1 (4.7%) DSP fulfilled the 2010 EFNS/PNS criteria for definite CIDP. There was no difference in CMAP duration or TD in all nerves (compound outcome) or in individual motor nerves. Patients with CIDP/CIDP+DSP had more conduction blocks, slower conduction velocities and more prolonged F wave latencies than those with DSP. Conclusion: Measures of CMAP duration and TD were not helpful in distinguishing CIDP, DSP or CIDP+DSP patients; however, parameters such as F-wave latencies, conduction blocks or the number of demyelinating parameters were useful in this separation. Significance: There are no definite nerve conduction criteria to distinguish patients with CIDP+DSP from DSP alone. Further studies focusing on measures of demyelination may provide stronger evidence to guide treatment decisions in CIDP + DSP patients. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Electromyography (EMG) can provide valuable insights into the pathophysiology of oropharyngeal muscles in various disease states, but the invasive nature of the conventional needle EMG (nEMG) has its limitations in this setting. We aimed to examine the inter‐rater reliability (IRR) of a novel transmembranous EMG (tmEMG) sensor as a non‐invasive technique for assessment of oral cavity and oropharyngeal muscles for neuromuscular pathology. Methods: The study was a prospective, cohort, pilot study with blinded data analysis in healthy participants (n = 6), patients with moderate to severe obstructive sleep apnea (OSA) (n = 5) and bulbar amyotrophic lateral sclerosis (ALS) (n = 5). Each patient underwent sampling from bilateral palatoglossus (PG) and genioglossus (GG), using both tmEMG and nEMG. IRR was expressed as percentage agreement and prevalence‐adjusted bias‐adjusted kappa coefficient (PABAK). Results: Substantial IRR was found for participants with ALS (81.6%, PABAK 0.63) and OSA (78.8%, PABAK 0.61), and in healthy participants (87.1%, PABAK 0.74). A better IRR was seen with tmEMG (95.7%, PABAK 0.92) than with nEMG (73.9%, PABAK 0.48) for healthy participants and also for those with OSA. Studies from GG had higher IRR than PG. Only one participant had a minor adverse event (sore throat). Discussion: The current study shows that analysis of PG and GG in both healthy and disease states using tmEMG has high IRR compared with nEMG analysis. Further validation studies can be undertaken to test its utility in analysis of oral cavity and oropharyngeal muscles. [ABSTRACT FROM AUTHOR]

A case study of a 57‑year‑old man presented with a one‑year history of progressive severe lower backache. Topics include constitutional symptoms or history to suggest immunosuppression with non‑contrast magnetic resonance imaging (MRI); and Presentation as polyradiculopathy and myelopathy is described with varying frequency in neurobrucellosis.

Introduction/Aims: The purpose of this study was to evaluate the clinical profile of myasthenia gravis (MG) in older patients and determine the impact of medical comorbidities on their MG status and outcome. Methods: This was a retrospective chart review of patients with a symptom onset of MG at or after 65 years of age. Correlations were made between demographics, clinical characteristics, the Myasthenia Gravis Foundation of America (MGFA) severity scale scores, and Myasthenia Gravis Impairment Index (MGII) scores with two outcome measures: MGFA Post‐Intervention Status (MGFA‐PIS) and Simple Single Question (SSQ). Results: The study population included 109 patients, with 90 of them having more than one follow‐up visit. Their mean age was 75.3 ± 6.9 years and sex distribution was even. Of these patients, 67.7% had generalized MG. Nine‐one percent of patients had one comorbidity. None of the demographic factors or comorbidities showed an association with MGFA‐PIS, SSQ, or MGII after correction for multiple comparisons. Seventy‐one percent of the patients improved with treatment, 12.4% remained unchanged, and 16.6% showed worsening at their last follow‐up visit. Discussion: Our study shows that patients with very‐late‐onset MG had a good prognosis and treatment response. None of the comorbidities had an impact on the severity of myasthenic symptoms or on outcome in these patients. [ABSTRACT FROM AUTHOR]

Introduction/aims: The aim of the study was to determine the association between the virtual Myasthenia Gravis Impairment Index (vMGII) with other patient-reported outcomes (PROs) of myasthenia gravis (MG) and its usefulness in telephone consultations with MG patients.Methods: This was a retrospective case series in which vMGII score along with virtual Single Simple Question (vSSQ), virtual Patient-Acceptable Symptom State PASS (vPASS) response, and patient disease status based on Myathenia Gravis Foundation of America postintervention status were collected during telephone consultation along with the MGII, SSQ, and PASS responses during the preceding in-person clinic visits.Results: In 214 patients, the mean difference of vMGII between the vPASS "Yes" and "No" groups was -14.2 ± 1.4 (95% confidence interval, -16.9 to -11.3; P < .001) with mean vMGII for vPASS "Yes" group being 6.4 ± 7.7 and vPASS "No" being 20.5 ± 11.5. A vMGII of 11.5 or higher predicted vPASS "yes" response with a sensitivity of 78.7% and specificity of 81.4%. A strong negative correlation was found between the vMGII and vSSQ (r = -.667; P < .001). The mean vMGII was 0.48 ± 1.42 for patients in remission, and 9.31 ± 10.93 for improved, 9.32 ± 8.79 for stable, and 22.58 ± 14.04 for worsened groups (P < .001). These associations were the same as those obtained during the preceding in-person clinic visit and the direction of change in MGII scores also indicated change in disease status.Discussion: vMGII is an effective measure to assess an MG patient's disease status in telephone consultations and relates well with other PRO measures. The vMGII remains reliable for assessing MG disease status even with removal of the physical examination component. [ABSTRACT FROM AUTHOR]

Introduction: There is limited evidence regarding the impact of World Health Organization (WHO) subtype of thymoma on post-thymectomy outcome of thymoma-associated myasthenia gravis (TAMG). The objective was to determine if the pathological subtypes of thymoma were associated with post-thymectomy outcomes of myasthenia gravis (MG), in patients with TAMG.Methods: We performed a retrospective study of consecutive patients with TAMG who attended the neuromuscular clinic between January 2018 and December 2019 with a minimum follow-up of 1 y after thymectomy. Outcome measures were MG Impairment Index (MGII), single-simple question (SSQ), Myasthenia Gravis Foundation of America post-intervention status (MGFA PIS) and non-responder MG status at last assessment.Results: Ninety-five patients were included; mean age at onset was 48.1 ± 12.1 y; 54(56.8%) were females. Thirteen patients developed MG post-thymectomy. The most common thymoma was WHO type B2 in 39 (41.1%). Most patients (40, 42.1%) had Masaoka stage II thymoma. There was no association of thymoma subtypes or Masaoka stage of disease with age, gender, MG phenotype, serology, post-thymectomy onset, interval from onset to thymectomy, MGII, SSQ, MGFA PIS, or non-responder status. Associations were found between positive serology and lower MGII (11.1 ± 14.2 vs 23 ± 12.9, P = .050), thymic follicular hyperplasia (TFH) and higher SSQ (89.3 ± 11.7 vs 80.1 ± 20.2, P-.043), and lack of recurrence and higher SSQ (84.1 ± 18 vs 72.5 ± 20, P = .037).Discussion: The WHO pathological subtype of thymoma did not correlate with MG outcomes. However, positive acetylcholine antibody serology, presence of TFH, and non-recurrence of thymoma predict a favorable outcome. [ABSTRACT FROM AUTHOR]

A low-shrinkage-stress (LSS), antibacterial and remineralizing nanocomposite was recently developed; however, validation of its long-term antibacterial potency in modulating human salivary-derived biofilm is an unmet need. This study aimed to evaluate the antibacterial effect of the bioactive LSS composite before and after aging in acidic solution for 90 days using a multi-species biofilm model, and to evaluate its cytotoxicity. The LSS composite consisted of urethane dimethacrylate (UDMA) and triethylene glycol divinylbenzyl ether (TEG-DVBE), 3% dimethylaminohexadecyl methacrylate (DMAHDM) and 20% nanoparticles of amorphous calcium phosphate (NACP). Biofilm colony-forming units (CFU), lactic acid production, and confocal laser scanning microscopy (3D biofilm) were evaluated before and after three months of aging. Cytotoxicity was assessed against human gingival fibroblasts (HGF). The new LSS composite presented the lowest biofilm CFU, lactic acid and biofilm biomass, compared to controls (n = 6, p < 0.05). Importantly, the new composite exhibited no significant difference in antibacterial performance before and after 90-day-aging, demonstrating long-term antibacterial activity (p > 0.1). The LSS antibacterial and remineralizing composite presented a low cell viability at original extract that has increased with further dilutions. In conclusion, this study spotlighted that the new bioactive composite not only had a low shrinkage stress, but also down-regulated the growth of oral biofilms, reduced acid production, maintained antibacterial activity after the 90-day-aging, and did not compromise the cytocompatibility. [ABSTRACT FROM AUTHOR]

The variants of chronic inflammatory demyelinating polyneuropathy (CIDP) differ not just in their clinical, pathological and electrophysiological characteristics, but often in their indifferent response to conventional immunosuppressive agents which are effective in typical CIDP. High quality evidence is lacking as far as the management of these atypical variants is concerned. In this review, we summarize the treatment approaches to each of these CIDP variants based on existing data. Distal acquired demyelinating symmetric polyneuropathy (DADS) has the phenotype of a symmetric, demyelinating sensory, length-dependent polyneuropathy and is frequently associated with paraproteinemia and anti myelin associated glycoprotein (MAG) antibodies. While the management of idiopathic DADS (DADS-I) is the same as CIDP, DADS-M responds suboptimally and has a favorable response to rituximab. Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) manifests as a chronic progressive demyelinating mononeuropathy multiplex which can evolve to a confluent pattern indistinguishable from CIDP. Evidence favors treating MADSAM with conventional immunomodulatory therapy (IMT), but this disorder responds less favorably than CIDP. Some patients present with purely sensory symptoms, known as pure sensory CIDP or chronic inflammatory sensory polyradiculoneuropathy (CISP), the latter localizing to a pre-ganglionic pathology. Both respond well to first line IMT, particularly to intravenous immunoglobulin (IVIG), but patients relapse without maintenance therapy. Pure motor CIDP resembles multifocal motor neuropathy with conduction block (MMNCB), but the previously reported worsening status after steroid treatment was not reproduced in recent studies, and IVIG remains the first-line therapy. Some focal forms of CIDP defy exact classification, but respond well to first-line IMT including IVIG. Overall, atypical CIDP responds to treatment with first-line IMT, but has a suboptimal response compared to CIDP. There is evidence for effectiveness with agents such as rituximab, especially in DADS-M, and this medication can also be used in cases refractory to conventional IMTs. Rituximab is also effective in CIDP with IgG4 antibodies which has distinct clinical features and is mostly refractory to first-line IMT. [ABSTRACT FROM AUTHOR]

Background: Cerebral microbleed (CMB) is a novel neuroimaging marker of cerebral small vessel disease.Objective: To determine the prevalence of CMB in the subtypes of acute ischemic minor stroke (AIS) and transient ischemic attack (TIA) and to identify the risk factors associated with location and number of CMB.Materials and Methods: Patients with AIS (National Institute of Health Stroke Scale of 5 or less) or TIA were included. CMB was characterized using the Microbleed Anatomical Rating Scale (MARS).Results: Of the 488 subjects [mean age (standard deviation): 57.5 years (14.4 years), males (77.7%)] recruited, CMB was noted in 140 (28.7%). About 35% with CMB had a lacunar stroke etiology, whereas LAA and CE subtype constituted 33.6 and 10.7%, respectively (P = 0.000). Lacunar subtype was more likely to harbor multiple CMB (four or more) and CMB in all locations (lobar, deep or infratentorial). On multivariate analysis, systemic hypertension [P = 0.025; odds ratio (OR) 0.33 (95% confidence interval (CI) 0.129-0.874)], serum triglyceride (TG) levels below 150 mg/dL [P = 0.001; OR 3.70 (95% CI 1.698-8.072)], and presence of white matter hyperintensities on magnetic resonance imaging brain [P = 0.026; OR 2.18 (95% CI 1.096-4.337)] were associated with the presence of CMB. Those with serum TG levels of less than 150 mg/dL were more likely to harbor lobar (P = 0.002) or infratentorial CMB (P = 0.022), whereas those with serum creatinine levels of more than1.5 mg/dL have lobar CMB (P = 0.033).Conclusion: Our study showed a differential distribution of CMB in ischemic stroke subtypes and association of risk factors with the presence, number and location of CMB. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is the prototypical autoimmune disorder caused by specific autoantibodies at the neuromuscular junction. Broad-based immunotherapies, such as corticosteroids, azathioprine, mycophenolate, tacrolimus, and cyclosporine, have been effective in controlling symptoms of myasthenia. While being effective in a majority of MG patients many of these immunosuppressive agents are associated with long-term side effects, often intolerable for patients, and take several months to be effective. With advances in translational research and drug development capabilities, more directed therapeutic agents that can alter the future of MG treatment have been developed. This review focuses on the aberrant immunological processes in MG, the novel agents that target them along with the clinical evidence for efficacy and safety. These agents include terminal complement C5 inhibitors, Fc receptor inhibitors, B cell depleting agents (anti CD 19 and 20 and B cell activating factor [BAFF)]inhibitors), proteosome inhibitors, T cells and cytokine based therapies (chimeric antigen receptor T [CART-T] cell therapy), autologous stem cell transplantation, and subcutaneous immunoglobulin (SCIG). Most of these new agents have advantages over conventional immunosuppressive treatment (IST) for MG therapy in terms of faster onset of action, favourable side effect profile and the potential for a sustained and long-term remission. [ABSTRACT FROM AUTHOR]

Deep cerebral venous thrombosis (DCVT) remains a very rare entity among the spectrum of cerebral venous thrombosis (CVT). Due to the bilateral draining territories, DCVT nearly invariably causes bilateral infarction with predictably dismal prognosis. However, rare instances of DCVT with unilateral infarction having favorable prognosis have been described, but pose a wide range of differentials to the clinician and require careful interpretation of clinical and radiological features for accurate diagnosis. Here, we report two unusual cases of DCVT with unilateral thalamic infarction with excellent outcome. We also report a rare case of CVT, with simultaneous deep and cortical vein thrombosis. Through a relevant review of the literature, we also examine the clinical presentations of unilateral infarction due to DCVT and their outcomes. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical profile, treatment response and predictors of outcome in patients with primary angiitis of the central nervous system (PACNS) from a single tertiary care center.Methodology: Retrospective analysis of consecutive patients diagnosed with PACNS from January 2000 to December 2015. Outcome was defined as poor when the 6-month modified Rankin scale (mRS) was ≥3.Results: The median age of the 45 patients included in this study was 36 (range 19-70) years at disease onset and 31 (68.9%) were males. The initial presentation was ischemic stroke in 15 (33.3%), hemorrhagic stroke in 4 (8.9%), headache in 11 (24.4%), seizures in 8 (17.8%) and cognitive dysfunction in 5 (11.1%) patients. Diagnosis was confirmed by a four vessel cerebral digital subtraction angiogram (DSA), biopsy and by both biopsy and DSA in 26 (57.8%), 15 (33.3%) and 4 (8.9%) patients, respectively. All patients received glucocorticoids and 14 patients received in addition either cyclophosphamide or azathioprine as their first treatment. The median duration of follow-up was 33.1 (0.7-356) months. A poor 6-month outcome was observed in 12 (26.7%) patients. Relapse occurred in 25 (55.6%) patients and 7 (15.6%) died. Predictors of a poor outcome consisted of cognitive dysfunction at diagnosis (80% vs 20%; P = 0.014) and NIHSS ≥5 (62.5% vs 37.5%; P <.0005). None of the patients with a normal EEG had a poor outcome (P = 0.046). Predictors of relapse were a higher NIHSS at admission (P =.032) and a normal DSA (P = 0.002).Conclusion: In this cohort, severe deficits and cognitive symptoms at onset and an abnormal EEG were associated with a poor 6-month outcome. [ABSTRACT FROM AUTHOR]

Mollaret's meningitis refers to the classical description by Pierre Mollaret of recurrent episodes of fever and meningism lasting 2-5 days, followed by spontaneous recovery. It remains a rare entity and most often is attributed to reactivation of latent Herpes Simplex virus (HSV)-2 virus. Though considered self-limiting and innocuous, there are exceptional cases in which neurological sequelae have been reported. From a clinician's perspective, narrowing down the diagnosis may not be straightforward and would require judicious use of investigations. Here we report two cases of Mollaret's meningitis, both of whom had negative cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for HSV. These reports also highlight an unusual pattern of presentation of this rare entity and the utility of CSF cytology in clinching the diagnosis. [ABSTRACT FROM AUTHOR]

Aim. Status epilepticus is a neurological emergency with significant morbidity and mortality. This study describes the clinical profile, treatment, and predictors of outcome of status epilepticus in a tertiary referral centre in a developing country and aims to highlight the similarities and differences from data available from the western world. Methods. A retrospective analysis of data of patients treated for status epilepticus was conducted from prospectively maintained records, between January 2000 and September 2010. The demographic data, clinical profile and investigations (including neuroimaging and EEG), aetiology, treatment, and outcomes were studied and compared with data available from the western world. Results. The analysis included 108 events in 84 patients. A single episode of status epilepticus was treated in 72 patients (86%) and multiple status epilepticus events, ranging from two to six per patient, were managed in 12 patients (14%). Mean age was 24.1±20.3 years and 63% were males. The types of status epilepticus included convulsive status in 98 (90.7%), non-convulsive status in seven (6.5%), and myoclonic status in three (2.8%). The majority of events (60%) were remote symptomatic, 16% were acute symptomatic, 16% were of unexplained aetiology, and 8% were progressive symptomatic. In 85 events (79%), status epilepticus could be aborted with first and second-line drugs. The remaining 23 events (21%) progressed to refractory status epilepticus, among which, 13 (56%) were controlled with continuous intravenous midazolam infusion. Case fatality rate was 11%, neurological sequelae were reported in 22%, and 67% returned to baseline. Acute symptomatic status, older age, altered sensorium at the time of admission, and delayed hospitalisation were predictors of poor outcome. Conclusions. Aetiology was the most important determinant of outcome of status epilepticus, as in reports from the western world, with remote symptomatic aetiology secondary to gliosis being the most common. Treatment delay was frequent and adversely affected the outcome. [ABSTRACT FROM AUTHOR]

Ocular neuromyotonia (ONM) is a rare disorder of ocular mal-alignment in which painless, transient spontaneous or gaze-induced abnormal deviation of the eye manifests as episodic diplopia. With only a few cases reported in the literature, ONM mostly follows months to years after cranial irradiation for sellar or suprasellar lesions. Here we present two patients with this rare ocular condition, secondary to brainstem demyelination, the association of which is hitherto unreported in the literature. Both patients were 15-year-old girls who presented to us with episodic forced-eye deviation with diplopia. Examination during these attacks revealed ONM involving the superior rectus and medial rectus in the first and second patient, respectively. There was clinical evidence of intrinsic brainstem involvement with downbeat nystagmus and skew deviation in one patient without any other cerebellar or long tract signs. MRI showed evidence of demyelination involving the brainstem in both, with CSF showing positive immunological markers and with positive aquaporin-4 antibody in one patient. Both patients responded remarkably to immunomodulatory therapy and are asymptomatic at follow-up. That ONM can occur with brainstem demyelination has not been reported in the literature. This association may help in explaining the pathophysiology of ONM as secondary to segmental demyelination. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 27-year-old lady with a history of headache, initially intermittent and subsequently progressing to persistent pain over the right parietal eminence. Her biopsy showed features of eosinophilic granuloma. Also mentioned are the clinical characteristics of eosinophilic granuloma, clinical presentation, and treatment for eosinophilic granuloma.

The article presents a case study of a 42-year-old manual laborer, with learning disabilities with delayed language milestones, presented with refractory seizures, which was started with a sensory aura over the left upper limb followed by its extensor posturing suggesting ictal onset. Information about bilateral perisylvian polymicrogyria is presented.

A letter to the editor is presented focusing on the reported diagnosis of Guillain-Barré syndrome with preceding hepatitis A (HA) infection in a 28-year old male patient.

Objective:In multicellular organisms, cell division is regulated by growth factors (GFs). In the absence of GFs, cells exit the cell cycle at a site in G1 referred to as the restriction point (R) and enter a state of quiescence known as G0. Additionally, nutrient availability impacts on G1 cell cycle progression. While there is a vast literature on G1 cell cycle progression, confusion remains – especially with regard to the temporal location of R relative to nutrient-mediated checkpoints. In this report, we have investigated the relationship between R and a series of metabolic cell cycle checkpoints that regulate passage into S-phase. Methods:We used double-block experiments to order G1 checkpoints that monitor the presence of GFs, essential amino acids (EEAs), the conditionally essential amino acid glutamine, and inhibition of mTOR. Cell cycle progression was monitored by uptake of [3H]-thymidine and flow cytometry, and analysis of cell cycle regulatory proteins was by Western-blot. Results:We report here that the GF-mediated R can be temporally distinguished from a series of late G1 metabolic checkpoints mediated by EAAs, glutamine, and mTOR – the mammalian/mechanistic target of rapamycin. R is clearly upstream from an EAA checkpoint, which is upstream from a glutamine checkpoint. mTOR is downstream from both the amino acid checkpoints, close to S-phase. Significantly, in addition to GF autonomy, we find human cancer cells also have dysregulated metabolic checkpoints. Conclusion:The data provided here are consistent with a GF-dependent mid-G1 R where cells determine whether it is appropriate to divide, followed by a series of late-G1 metabolic checkpoints mediated by amino acids and mTOR where cells determine whether they have sufficient nutrients to accomplish the task. Since mTOR inhibition arrests cells the latest in G1, it is likely the final arbiter for nutrient sufficiency prior to committing to replicating the genome. [ABSTRACT FROM AUTHOR]