Minocycline Synergizes with N-Acetylcysteine and Improves Cognition and Memory Following Traumatic Brain Injury in Rats

Background: There are no drugs presently available to treat traumatic brain injury (TBI). A variety of single drugs have failed clinical trials suggesting a role for drug combinations. Drug combinations acting synergistically often provide the greatest combination of potency and safety. The drugs examined (minocycline (MINO), N-acetylcysteine (NAC), simvastatin, cyclosporine A, and progesterone) had FDA-approval for uses other than TBI and limited brain injury in experimental TBI models. Methodology/Principal Findings: Drugs were dosed one hour after injury using the controlled cortical impact (CCI) TBI model in adult rats. One week later, drugs were tested for efficacy and drug combinations tested for synergy on a hierarchy of behavioral tests that included active place avoidance testing. As monotherapy, only MINO improved acquisition of the massed version of active place avoidance that required memory lasting less than two hours. MINO-treated animals, however, were impaired during the spaced version of the same avoidance task that required 24-hour memory retention. Coadministration of NAC with MINO synergistically improved spaced learning. Examination of brain histology 2 weeks after injury suggested that MINO plus NAC preserved white, but not grey matter, since lesion volume was unaffected, yet myelin loss was attenuated. When dosed 3 hours before injury, MINO plus NAC as single drugs had no effect on interleukin-1 formation; together they synergistically lowered interleukin-1 levels. This effect on interleukin-1 was not observed when th

Long-term outcomes five years after selective dorsal rhizotomy

<p>Abstract</p> <p>Background</p> <p>Selective dorsal rhizotomy (SDR) is a well accepted neurosurgical procedure performed for the relief of spasticity interfering with motor function in children with spastic cerebral palsy (CP). The goal is to improve function, but long-term outcome studies are rare. The aims of this study were to evaluate long-term functional outcomes, safety and side effects during five postoperative years in all children with diplegia undergoing SDR combined with physiotherapy.</p> <p>Methods</p> <p>This study group consisted of 35 children, consecutively operated, with spastic diplegia, of which 26 were Gross Motor Function Classification System (GMFCS) levels III–V. Mean age was 4.5 years (range 2.5–6.6). They were all assessed by the same multidisciplinary team at pre- and at 6, 12, 18 months, 3 and 5 years postoperatively. Clinical and demographic data, complications and number of rootlets cut were prospectively registered. Deep tendon reflexes and muscle tone were examined, the latter graded with the modified Ashworth scale. Passive range of motion (PROM) was measured with a goniometer. Motor function was classified according to the GMFCS and measured with the Gross Motor Function Measure (GMFM-88) and derived into GMFM-66. Parent's opinions about the children's performance of skills and activities and the amount of caregiver assistance were measured with Pediatric Evaluation Disability Inventory (PEDI).</p> <p>Results</p> <p>The mean proportion of rootlets cut in S2-L2 was 40%. Muscle tone was immediately reduced in adductors, hamstrings and dorsiflexors (p < 0.001) with no recurrence of spasticity over the 5 years. For GMFCS-subgroups I–II, III and IV–V significant improvements during the five years were seen in PROM for hip abduction, popliteal angle and ankle dorsiflexion (p = 0.001), capacity of gross motor function (GMFM) (p = 0.001), performance of functional skills and independence in self-care and mobility (PEDI) (p = 0.001).</p> <p>Conclusion</p> <p>SDR is a safe and effective method for reducing spasticity permanently without major negative side effects. In combination with physiotherapy, in a group of carefully selected and systematically followed young children with spastic diplegia, it provides lasting functional benefits over a period of at least five years postoperatively.</p

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children &lt;18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p&lt;0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p&lt;0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p&lt;0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

TETHERED CORD IN THE ADULT MIMICKING THE LUMBAR DISC SYNDROME - REPORT OF 2 CASES

Two adult patients with tethered cords whose symptoms mimicked those of lumbosacral intervertebral disc herniation are reported. Neither one of the patients had cutaneous stigmata, and one had normal plain x-ray examination of the spine. Magnetic resonace imaging in both patients demonstrated tethering of the cord. Untethering of the cord resulted in disappearance of the symptoms in both patients. These unusual cases suggest that tethering of the cord must be included in the differential diagnosis of the herniated lumbar intervertebral disc syndrome

Spontaneous Rhinorrhea mimicking sinusitis

Spotaneous or non-traumatic cerebrospinal fluid rhinorrhea is an uncommon condition and may present a diagnostic challenge to clinicians. This condition is often being misdiagnosed for allergic rhintis or chronic sinusitis since the precipitating cause is not readily apperent in most patients. The mechanism of rhinorrhea is stil not completely clarified. We describe a case of this condition occuring in association with allergic rhinitis and sinusitis. A 52 year-old, obese female patient presented with two weeks history of bilateral clear nasal discharge and postural headache. Sample of nasal discharge tested for glucose and protein. The result was that the collection fluid was cerebrospinal fluid. The origin of cerebrospinal fluid fistula could not be identified despite the diagnostic tests

A Comparative-Study of Brain-Stem Auditory Evoked-Potentials and Blink Reflexes In Posterior-Fossa Tumor Patients

WOS: A1988Q731700003PubMed ID: 318372