Polyneuropathy in Critically Ill Mechanically Ventilated Children: Experience From a Tertiary Care Hospital in North India.

OBJECTIVES: To determine the prevalence of critical illness polyneuropathy and its risk factors in critically ill children mechanically ventilated for 7 days or more. DESIGN: Observational cohort study. SETTING: PICU of a tertiary care hospital from North India. PATIENTS: Children 1-15 years old admitted in PICU from June 2016 to September 2017, mechanically ventilated for 7 days or more, excluding those with diagnosed neuromuscular disease, stroke, or spinal pathology. INTERVENTION: Demographic details, diagnosis, treatment details, and anthropometry at admission and enrolment were recorded. Nerve conduction studies were performed after enrolment and repeated a week later, if the child was still in PICU. Medical Research Council scoring for muscle strength was performed in survivors. Risk factors including Pediatric Index of Mortality-2 score, sepsis, multiple organ dysfunction, hypoalbuminemia, use of steroids, neuromuscular-blocking agents, and vasopressors were recorded. Samples for the level of micronutrients (copper, zinc, folate, and vitamin B12) were collected at the time of enrolling the child and at the time of discharge. MEASUREMENTS AND MAIN RESULTS: Thirty-two children were enrolled, of whom 29 had features of critical illness polyneuropathy on evaluation at day 8 of mechanical ventilation (prevalence, 90.6% [95% CI, 80.5-100%]). The polyneuropathy was axonal in 26 (81.2%), mixed in one patient (3.1%), and uncharacterized in two (6.2%). Sepsis and multiple organ dysfunction were present in 31 subjects (96.9%). No risk factors for critical illness polyneuropathy could be identified although the study was not sufficiently powered to do so. The difference between serum micronutrient levels (copper, zinc, folate, and vitamin B12) between patients who developed polyneuropathy, and those who did not, was statistically insignificant. CONCLUSIONS: We observed a high prevalence of critical illness polyneuropathy in children in PICU, mechanically ventilated for 7 days or more; almost all of whom had underlying sepsis.

Pain Assessment and Management Practices via Education & Reinforcement (PAMPER): A Quality Improvement Initiative.

OBJECTIVES: To establish neonatal pain management practices as an essential developmental supportive measure at a tertiary care unit. METHODS: This quality improvement initiative was conducted as per Point-of-Care-Quality-Improvement Model over 6 mo, followed by 2 y of sustenance phase at a Neonatal Intensive Care Unit (NICU) in northern India. Infants of birth weight ≤1800 g were included and assessed for pain. Pain Assessment and Management Practices via Education and Reinforcement (PAMPER) group was created by resident doctors and nursing staff. The Premature Infant Pain Profile score was used for the assessment of pain. Limiting factors were analyzed using a fishbone diagram and interventions were done in multiple Plan-Do-Study-Act cycles. RESULTS: At the end of interventions, 100% of procedures were assessed for pain. The mean (standard deviation) documented pain score for the first seven days was reduced from 12.8 (0.3) in the baseline phase to 7 (2.5). These interventions helped to sustain the practice in >70% of infants in the next 2 y. CONCLUSIONS: Low-cost interventions improved the pain assessment and management policy of authors' NICU with the establishment of a standard protocol. Audits and reinforcement at regular intervals helped in its long-term sustenance.

Effects of non-invasive vagus nerve stimulation on clinical symptoms and molecular biomarkers in Parkinson's disease.

Non-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson's disease (PD) patients. In a subgroup of patients, we measured selected neurotrophins, inflammatory markers and markers of oxidative stress in serum. Thirty-three PD patients with freezing of gait (FOG) were randomized to either active nVNS or sham nVNS. After baseline assessments, patients were instructed to deliver six 2 min stimulations (12 min/day) of the active nVNS/sham nVNS device for 1 month at home. Patients were then re-assessed. After a one-month washout period, they were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters (speed, stance time and step length) were observed with active nVNS. While serum tumor necrosis factor- α decreased, glutathione and brain-derived neurotrophic factor levels increased significantly (p < 0.05) after active nVNS treatment. Here we present the first evidence of the efficacy and safety of nVNS in the treatment of gait in PD patients, and propose that nVNS can be used as an adjunctive therapy in the management of PD patients, especially those suffering from FOG. Clinical trial registration: identifier ISRCTN14797144.

Delivery Room Respiratory Stabilization of Preterm Neonates: A Randomized, Controlled Trial.

OBJECTIVE: To determine whether heated humidified high-flow nasal cannula (HHHFNC) is noninferior to NCPAP to provide DR respiratory support to preterm neonates of gestational age (GA) 28-36 wk. METHODS: This randomized, controlled, noninferiority trial included 124 spontaneously breathing preterm neonates who developed respiratory distress soon after birth and/or had a FiO2 requirement > 0.3. Primary outcome measure was treatment failure within 24 h. The absolute risk difference with 95% confidence interval (CI) were calculated with a noninferiority margin of 10%. Secondary outcome variables were temperature at admission, time to treatment failure, treatment failure at 72 h, need for surfactant, intubation, duration of respiratory support, and incidences of adverse events including mortality. Intention-to-treat analysis was done in Stata software. RESULTS: Both the groups were similar in baseline characteristics. There was no statistically significant difference between the treatment failure rates with HHHFNC (13.1%, n = 61) and NCPAP (11.1%, n = 63) (risk difference 2.0%, 95% CI - 9.9% to 14.07%, p = 0.73). However, noninferiority of HHHFNC to NCPAP could not be conclusively proved as the 95% CI crossed both 0 and the noninferiority margin of 10%. There were no significant differences in secondary outcomes. CONCLUSIONS: HHHFNC showed similar efficacy and safety as NCPAP irrespective of gestational age, though its noninferiority to NCPAP remained inconclusive. TRIAL REGISTRATION: Clinical Trial Registry of India, Registration no: CTRI/2019/10/021633, https://ctri.icmr.org.in/.

Neuroimaging Pearls from the MDS Congress Video Challenge. Part 2: Acquired Disorders.

The MDS Video Challenge continues to be the one of most widely attended sessions at the International Congress. Although the primary focus of this event is the presentation of complex and challenging cases through videos, a number of cases over the years have also presented an unusual or important neuroimaging finding related to the case. We reviewed the previous Video Challenge cases and present here a selection of those cases which incorporated such imaging findings. We have compiled these "imaging pearls" into two anthologies. The first focuses on pearls where the underlying diagnosis was a genetic condition. This second anthology focuses on imaging pearls in cases where the underlying condition was acquired. For each case we present brief clinical details along with neuroimaging findings, the characteristic imaging findings of that disorder and, finally, the differential diagnosis for the imaging findings seen.

Developmentally Supportive Positioning Policy for Preterm Low Birth Weight Infants in a Tertiary Care Neonatal Unit: A Quality Improvement Initiative.

OBJECTIVES: To improve developmentally supportive positioning practices by 50% in neonates weighing <1800 g, admitted in a neonatal intensive care unit over 6 months. METHODS: Infant Position Assessment Tool (IPAT) scores were used for assessment of the ideal position. Proportion of neonates with IPAT score ≥8 and improvement of average IPAT score were the process and the outcome measures, respectively. At baseline, 16.6% of infants had optimum position. After root cause analysis, interventions were done in multiple Plan-Do-Study-Act (PDSA) cycles of educational sessions, positioning audits, use of low-cost nesting aids, and training of mothers. RESULTS: Over 21 weeks, 74 neonates were observed at 714 opportunities. Over 6 months, mean (SD) IPAT score improved from 3.4 (1.4) to 9.2 (2.8). Optimum positioning was maintained in 83.3% neonates during sustenance phase. CONCLUSIONS: Low-cost interventions, awareness regarding standards of optimum positioning and involvement of primary caregiver can effectively improve infant positioning practices.

Agitated saline contrast to delineate central venous catheter position in neonates.

OBJECTIVE: Central venous catheter (CVC) insertion is required for the management of sick neonates. Ultrasonography/targeted neonatal echocardiography (TNE) with/without normal saline (NS) flush is used to identify CVC position. The present study compared the visibility and safety of agitated saline (AS) with normal saline (NS) flush. STUDY DESIGN: This prospective interventional study included 110 CVC insertions, both umbilical venous catheterization (UVC) and peripherally inserted central catheterization (PICC). Catheter position was monitored by real-time TNE. RESULTS: Overall visibility of catheter tip (combined UVC and PICC) was significantly better in AS (n = 55) compared with NS group (n = 55) [48/55 (87.2%) vs. 28/55 (50.9%); p < 0.0001]. Time to detect catheter tip by AS push was significantly less than that of NS push. There was no difference in the amount of saline flush required with either method. No major adverse effect was observed. CONCLUSIONS: AS push can be used as a safe method to delineate CVC position in neonates.

Oral Care with Mother's Own Milk in Sick and Preterm Neonates: A Quality Improvement Initiative.

OBJECTIVE: Oral care with mother's own milk (OC-MOM) in sick and preterm neonates provides immune protection, improves feed tolerance and helps in earlier achievement of full enteral nutrition. This quality improvement (QI) initiative was undertaken when authors documented scanty awareness regarding neonatal oral care practices among care-givers in their neonatal unit. The project aimed to improve the proportion of OC-MOM in sick and preterm neonates from the baseline of 5.9% to 80%. METHODS: The QI project was designed as per Point of Care Quality Improvement (POCQI) model and conducted over 6 mo (January 14, 2019 to July 12, 2019). Preterm and sick term neonates on enteral fasting or gavage feeding were included. Neonates with major congenital malformation and whose MOM was not available were excluded. An OC-MOM team was formed and baseline data were collected. Flow charts and fish-bone diagrams were used to analyse the problem and identify the key issues. Mouth assessment tool (MAT) was customized and adapted as one of the outcome measures. An OC-MOM protocol was designed and implemented as a part of routine neonatal care. RESULTS: Four Plan-Do-Study-Act (PDSA) cycles were conducted to achieve the target. After successful implementation of OC-MOM protocol, proportion of neonates receiving OC-MOM increased to 83.3% from a baseline of 5.9% and proportion of neonates having MAT score "0" improved to 94.4% from a baseline of 24.4%. CONCLUSIONS: This QI initiative using POCQI model resulted in a significant and sustained improvement in the proportion of neonatal oral care with MOM using locally available resources.

Non-invasive vagus nerve stimulation improves clinical and molecular biomarkers of Parkinson's disease in patients with freezing of gait.

Non-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled crossover trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson's disease (PD) patients. In a subgroup of patients, we measured selected neurotrophin levels and markers of inflammation and oxidative stress in serum, before and after the experimental intervention. Thirty-three PD patients with associated freezing of gait were randomised to either nVNS or sham. After baseline assessments, patients were instructed to deliver 6 two-minute stimulations (total 12 min/day) of the nVNS/sham device (electroCore, Inc. USA) for one month at home. Patients were then re-assessed. After a washout period of one month, the same patients were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters were observed with nVNS, including walking speed, stance time and step length, compared to sham. Similarly, overall motor function (MDS-UPDRS III) also improved significantly following nVNS stimulation. Serum Tumor Necrosis Factor (TNF)-α and glutathione levels decreased and brain-derived neurotrophic factor (BDNF) levels increased significantly (p < 0.05) after treatment with nVNS. Here we present the first double-blind sham-controlled trial evidence of the efficacy and safety of nVNS in the treatment of gait and motor function in patients with PD.

Inflammasome and α-synuclein in Parkinson's disease: A cross-sectional study.

BACKGROUND: Alpha-synuclein and inflammatory pathology are evident in Parkinson's disease (PD) but, their link to disease pathogenesis needs further elucidation. OBJECTIVES: To explore α-synuclein-mediated inflammation in the serum of PD patients and its link with disease severity. METHODS: Serum levels of IL-1ß, NLRP3, total and phosphorylated α-synuclein were compared. RESULTS: IL-1ß, NLRP3 levels were significantly increased in PD. We also observed a linear correlation of NLRP3 with α-synuclein. Phosphorylated α-synuclein levels were significantly elevated in later stages of PD. CONCLUSIONS: The α-synuclein-NLRP3 mediated inflammation may underline the pathophysiology of PD and might serve as a novel therapeutic target in PD.

A Novel Wearable Device for Motor Recovery of Hand Function in Chronic Stroke Survivors.

Background. In monkey, reticulospinal connections to hand and forearm muscles are spontaneously strengthened following corticospinal lesions, likely contributing to recovery of function. In healthy humans, pairing auditory clicks with electrical stimulation of a muscle induces plastic changes in motor pathways (probably including the reticulospinal tract), with features reminiscent of spike-timing dependent plasticity. In this study, we tested whether pairing clicks with muscle stimulation could improve hand function in chronic stroke survivors. Methods. Clicks were delivered via a miniature earpiece; transcutaneous electrical stimuli at motor threshold targeted forearm extensor muscles. A wearable electronic device (WD) allowed patients to receive stimulation at home while performing normal daily activities. A total of 95 patients >6 months poststroke were randomized to 3 groups: WD with shock paired 12 ms before click; WD with clicks and shocks delivered independently; standard care. Those allocated to the device used it for at least 4 h/d, every day for 4 weeks. Upper-limb function was assessed at baseline and weeks 2, 4, and 8 using the Action Research Arm Test (ARAT), which has 4 subdomains (Grasp, Grip, Pinch, and Gross). Results. Severity across the 3 groups was comparable at baseline. Only the paired stimulation group showed significant improvement in total ARAT (median baseline: 7.5; week 8: 11.5; P = .019) and the Grasp subscore (median baseline: 1; week 8: 4; P = .004). Conclusion. A wearable device delivering paired clicks and shocks over 4 weeks can produce a small but significant improvement in upper-limb function in stroke survivors.

The Relationship Between Enhanced Reticulospinal Outflow and Upper Limb Function in Chronic Stroke Patients.

BACKGROUND: Recent evidence from both monkey and human studies suggests that the reticulospinal tract may contribute to recovery of arm and hand function after stroke. In this study, we evaluated a marker of reticulospinal output in stroke survivors with varying degrees of motor recovery. METHODS: We recruited 95 consecutive stroke patients presenting 6 months to 12 years after their index stroke, and 19 heathy control subjects. Subjects were asked to respond to a light flash with a rapid wrist flexion; at random, the flash was paired with either a quiet or loud (startling) sound. The mean difference in electromyogram response time after flash with quiet sound compared with flash with loud sound measured the StartReact effect. Upper limb function was assessed by the Action Research Arm Test (ARAT), spasticity was graded using the Modified Ashworth Scale (MAS) and active wrist angular movement using an electrogoniometer. RESULTS: StartReact was significantly larger in stroke patients than healthy participants (78.4 vs 45.0 ms, P < .005). StartReact showed a significant negative correlation with the ARAT score and degree of active wrist movement. The StartReact effect was significantly larger in patients with higher spasticity scores. CONCLUSION: We speculate that in some patients with severe damage to their corticospinal tract, recovery led to strengthening of reticulospinal connections and an enhanced StartReact effect, but this did not occur for patients with milder impairment who could use surviving corticospinal connections to mediate recovery.

Abnormal Blink Reflex and Intermuscular Coherence in Writer's Cramp.

Background: Writer's cramp (WC) is a task-specific focal hand dystonia presenting with pain, stiffness and/or tremor while writing. We explored the involvement of cortical and brainstem circuits by measuring intermuscular coherence (IMC) and pre-pulse inhibition (PPI) of the blink reflex. Methods: IMC was measured in 10 healthy controls and 20 WC patients (10 with associated tremor) while they performed a precision grip task at different force levels. Blink responses were evaluated in 9 healthy controls and 10 WC patients by stimulating the right supraorbital nerve and recording surface EMG from the orbicularis oculi muscles bilaterally. PPI involved conditioning this stimulation with a prior shock to the right median nerve (100 ms interval), and measuring the reduction in the R2 component of the blink reflex. Results: Significant IMC at 3-7 Hz was present in WC patients, but not in healthy controls. Compared to healthy controls, in WC patients the R2 component of the blink reflex showed significantly less PPI. IMC at 3-7 Hz could reliably discriminate WC patients from healthy controls. Conclusion: Cortical or sub-cortical circuits generating theta (3-7 Hz) oscillations might play an important role in the pathogenesis of WC. Moreover, the lack of PPI implicates abnormalities in brainstem inhibition in the emergence of WC. IMC may merit further development as an electrodiagnostic test for focal dystonia.

Clinical Characterization of Genetically Diagnosed Cases of Spinocerebellar Ataxia Type 12 from India.

https://onlinelibrary.wiley.com/page/journal/23301619/homepage/mdc312551-sup-v001_1.htm. BACKGROUND: Spinocerebellar ataxia type 12 (SCA12) is a rare form of an autosomal-dominant ataxic disorder associated with an expansion of CAG repeat length. Here, we present a large case series of patients with SCA12 and describe a wide range of typical and rare symptoms. METHODS: Twenty-one consecutive patients with genetically proven SCA12 underwent detailed neurological examination. We assessed clinical characteristics using validated rating scales for evaluating motor features in SCA. Nonmotor symptoms and quality of life were assessed using appropriate, validated scales. Correlations of CAG repeat length with both severity score and age of onset were explored. RESULTS: The mean age of onset was 51 years, and most patients were descendants of a single, endogamous Indian community (Agarwal). Tremor was the most common initial presenting symptom (90%). Hand dystonia was present in 14 of 21 patients, and most patients in the cohort presented with gait disturbance. Neuropsychiatric manifestations were common coexisting features. The CAG repeat length was significantly correlated (r = -0.760; P = 0.0001) with early age of onset, but not with disease severity. Tremor affected the quality of life in 18 of 21 patients, because they had difficulty in handling liquids. CONCLUSIONS: Tremor was the most common, nonataxic symptom at initial presentation in patients with SCA12. Proximal upper limb tremor, typically with high amplitude and low frequency, can raise a strong diagnostic suspicion. Associated hand dystonia was a common coexisting motor feature. Various nonmotor features were also observed in several cases which require therapeutic attention.

Levosulpiride-induced Movement Disorders.

We reported a series of patients who presented with LSP-induced movement disorders specifically, dyskinetic movements. We have presented one case of LSP-induced parkinsonism and summarized ten cases of LSP-induced dyskinesia. The causality of the adverse drug reaction was assessed systematically using a validated rating system, and we extensively qualified the clinical presentation of each case of dyskinesia using a clinical rating scale. We described an unusual case of acute onset LSP-induced parkinsonism in a 56-year-aged female. The mean age of ten patients of LSP-induced dyskinesia was 65.3 years (standard deviation 10.4), and 25% of patients were female. They were consuming suspected medication for a median duration of 13 months (range 1-60 months). We noted LSP-induced dyskinesia was challenging to treat as its resolution is often incomplete even with adequate treatment.