Cyclosporine A plus low-dose steroid treatment in COVID-19 improves clinical outcomes in patients with moderate to severe disease: A pilot study.

BACKGROUND: COVID-19 pandemic causes high global morbidity and mortality and better medical treatments to reduce mortality are needed. OBJECTIVE: To determine the added benefit of cyclosporine A (CsA), to low-dose steroid treatment, in patients with COVID-19. METHODS: Open-label, non randomized pilot study of patients with confirmed infection of SARS-CoV-2 hospitalized from April to May 2020 at a single centre in Puebla, Mexico. Patients were assigned to receive either steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days. RESULTS: A total of 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ± 13.3; 69% men), and 104 steroids alone (age 54.06 ± 13.8; 61% men). All patients received clarithromycin, enoxaparin and methylprednisolone or prednisone up to 10 days. Patient's death was associated with hypertension (RR = 3.5) and diabetes (RR = 2.3). Mortality was 22 and 35% for CsA and control groups (P = 0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (P = 0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, P = 0.001, log-rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39-3.34, 95%CI, P = 0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35-2.83, 95%CI, P = 0.0003) for all patients. CONCLUSION: CsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.

Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets.

STUDY DESIGN: This is a narrative review of the literature. OBJECTIVES: This review aims to be useful in identifying therapeutic targets. It focuses on the molecular and biochemical neuroplasticity changes that occur in the somatosensory system, including ascending and descending pathways, during the development of neuropathic pain. Furthermore, it highlights the latest experimental strategies, based on the changes reported in the damaged nociceptive neurons during neuropathic pain states. SETTING: This study was conducted in Girona, Catalonia, Spain. METHODS: A MEDLINE search was performed using the following terms: descending pain pathways; ascending pain pathways; central sensitization; molecular pain; and neuropathic pain pharmacological treatment. RESULTS AND CONCLUSION: Neuropathic pain triggered by traumatic lesions leads to sensitization and hyperexcitability of nociceptors and projection neurons of the dorsal horn, a strengthening in the descendent excitatory pathway and an inhibition of the descending inhibitory pathway of pain. These functional events are associated with molecular plastic changes such as overexpression of voltage-gated ion channels, algogen-sensitive receptors and synthesis of several neurotransmitters. Molecular studies on the plastic changes in the nociceptive somatosensory system enable the development of new pharmacological treatments against neuropathic pain, with higher specificity and effectiveness than classical drug treatments. Although research efforts have already focused on these aspects, additional research may be necessary to further explore the potential therapeutic targets in neuropathic pain involved in the neuroplasticity changes of neuropathological pathways from the injured somatosensory system.

Schwann cell targeting via intrasciatic injection of AAV8 as gene therapy strategy for peripheral nerve regeneration.

Efficient transduction of the peripheral nervous system (PNS) is required for gene therapy of acquired and inherited neuropathies, neuromuscular diseases and for pain treatment. We have characterized the tropism and transduction efficiency of different adeno-associated vectors (AAV) pseudotypes after sciatic nerve injection in the mouse. Among the pseudotypes tested, AAV2/1 transduced both Schwann cells and neurons, AAV2/2 infected only sensory neurons and AAV2/8 preferentially transduced Schwann cells. AAV2/8 expression in the sciatic nerve was detected up to 10 weeks after administration, the latest time point analyzed. The injected mice developed neutralizing antibodies against all AAVs tested; the titers were higher against AAV2/1 than AAV2/2 and were the lowest for AAV2/8, correlating with a higher transgene expression overtime. AAV2/8 coding for ciliary neurotrophic factor (CNTF) led to an upregulation of P0 and PMP22 myelin proteins, four weeks after transduction of injured sciatic nerves. Importantly, CNTF-transduced mice showed a significant increase in both GAP43 expression in sensory neurons, a marker of axonal regeneration, and the compound muscle action potential. These results prove the utility of AAV8 as a gene therapy vector for Schwann cells to treat myelin disorders or to improve nerve regeneration.

[Treatment of neuropathic pain in neurology units. The PREVADOL study]. / Tratamiento del dolor neuropático en las consultas de neurología. Estudio PREVADOL.

INTRODUCTION: Neuropathic pain (NPP) is defined as a pain started or caused by an injury to or dysfunction of the nervous system. Its treatment is different to that of nociceptive pain since it does not respond to conventional analgesics or non-steroidal antiinflammatory drugs. AIM: To describe the treatment being received by patients with NPP in the daily clinical practice of the specialist in neurology. PATIENTS AND METHODS: An observational, epidemiological, cross-sectional study was conducted in 36 neurology units (24 extra-hospital and 12 belonging to hospitals). We collected the clinical data and the treatment administered to the first 20 patients with NPP to visit the neurology units over a period of 20 consecutive working days. RESULTS: Data were collected for a total of 451 patients with NPP. The pharmacological groups most frequently used in patients with NPP attended in neurology units are antiepileptics (71%) and antidepressants (15%). Of these patients, 60% were being treated with a single drug (an antiepileptic agent in 84.5% of cases; antidepressants in 10.3%). Two pharmacological treatments were being received by 23.7%, and 2.3% of patients were given treatment involving three or more pharmacological agents. A total of 30% received non-pharmacological treatments, especially physiotherapy (50.4%). CONCLUSIONS: Most patients with NPP attended in neurology units follow first-order pharmacological treatments (antiepileptics or antidepressants). Over half the patients are controlled with monotherapy, usually with an antiepileptic agent. Non-pharmacological treatments (especially physiotherapy) are used in a third of the patients.

Epigallocatechin-3-gallate treatment reduces thermal hyperalgesia after spinal cord injury by down-regulating RhoA expression in mice.

BACKGROUND: (-)-Epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent found in green tea. It has been reported that may be a natural agent for reducing thermal and mechanical pain after nervous system injuries. However, the molecular pathways implicated in these beneficial effects have not been completely elucidated. This study aimed to assess the EGCG treatment effects on thermal hyperalgesia, spinal cord gliosis and modulation of Ras homologue gene family member A (RhoA), fatty acid synthase (FASN) and tumour necrosis factor alpha (TNF-α) expression after spinal cord contusion in mice. METHODS: Animals were subjected to a spinal cord contusion. Thirty minutes after contusion and daily during the first week post-surgery, animals were treated with EGCG or dimethyl sulfoxide-saline (DMSO-saline). At 7 and 14 days post-operation, motor recovery was evaluated using the Basso Mouse Scale, and nociceptive response was evaluated using the Hargreaves test. Furthermore, at 14 days, the expression of RhoA, FASN and TNF-α proteins was quantified in the lesion site of spinal cord by Western blot technique. Finally, spinal cord samples were processed by immunohistochemical techniques for observing astrocytes, microglia and afferent nerve fibres. RESULTS: At short time, EGCG treatment reduced significantly thermal hyperalgesia but had no effect on locomotor recovery in spinal cord injured mice. Furthermore, EGCG treatment down-regulated the RhoA, FASN and TNF-α proteins expression, and decreased astro- and microglia reactivity in spinal cord. CONCLUSION: These findings suggest that at short time EGCG treatment reduces thermal hyperalgesia and gliosis via FASN and RhoA pathway, causing a decrease in cytokines in spinal cord.

Antibiotic prophylaxis during prolonged clean neurosurgery. Results of a randomized double-blind study using oxacillin.

The efficacy of oxacillin as a prophylaxis for infection was analyzed in a 27-month randomized double-blind study of 400 patients who had undergone clean neurosurgical interventions lasting longer than 2 hours. Four neurosurgeons took part in the study and 356 patients were eligible for final analysis. Among the 171 patients treated with oxacillin, there was one case of infection (0.6%), compared to nine (4.9%) of the 185 patients given a placebo. The difference between the two groups was statistically significant (p = 0.0398). This study, together with others (randomized or not), clearly demonstrates the efficacy of antibiotic prophylaxis in prolonged clean neurosurgery.

[A program of quality improvement in transfusion safety. Experience at Saint-Camille Hospital]. / Programme d'amélioration de la qualité en sécurité transfusionnelle. L'expérience de l'hôpital Saint-Camille.

A program of quality improvement of blood transfusion safety was carried out in St Camille Hospital after a call for tenders had been jointly issued by the French Ministry of Health and the French Agency for Medical Evaluation (ANDEM). The blood transfusion process was analysed and a diagnosis of the situation was performed. Improvement actions were then undertaken to control the blood transfusion process. They consisted in education programs, elaboration of procedures and documents such as a transfusion record and a transfusion manual. The effectiveness of the actions was measured using indicators. Such a quality improvement approach revealed to be a good method to manage the blood transfusion process and to improve safety. However, it requires people's involvement in the project, and rigorous project management.

[Analysis of failures of spinal anesthesia as a function of practice development in a university hospital]. / Analyse des échecs de la rachianesthésie en fonction de l'évolution de la pratique d'un hôpital universitaire.

This study is a retrospective analysis of 303 consecutive spinal anaesthesia performed in orthopaedic patients of a University Hospital between January and December 1990. Failure of spinal anaesthesia was defined as the requirement for general anaesthesia to perform surgery. The parameters studied as possible risk factors of failure were patients demographics, local anaesthetic agents and solutions and techniques of spinal anaesthesia (single injection versus continuous spinal anaesthesia). Failures were related to inadequate or incomplete extension of sensory blockade or to difficulties to perform spinal injection. Continuous spinal anaesthesia was performed in 209 patients mostly with 0.5% isobaric bupivacaine, while 94 patients received a single injection of either hyperbaric 0.5% tetracaine with adrenaline or 0.5% bupivacaine or 5% lidocaine. Failures occurred in 6.3% of the cases but were significantly less frequent with continuous spinal anaesthesia (4.8%) than with the conventional technique (9.6%). The incidence of failure was higher with hyperbaric tetracaine (11.1%) confirming its poor reliability. Inadequate extension of the anaesthetic block was the main cause of failure whatever the spinal anaesthetic technique. These results point out the reliability of continuous spinal anaesthesia but problems may occasionally occur due to spinal catheter misplacement.

[Plexus nerve blocks for postoperative analgesia after orthopedic surgery of the lower limbs]. / Blocs nerveux tronculaires à visée analgésique après chirurgie orthopédique des membres inférieurs.

In our institution, plexus nerves blocks have been performed in seventy patients after lower limb surgery. The technique is considered as simple and reliable. The administration of a 0.375 per cent bupivacaine epinephrine containing solution allows to obtain analgesia longer than 15 hours in 45 p. 100 of the patients, devoided of side effects. Lower limb plexus nerves blocks appear as an efficient technique for postoperative analgesia following orthopaedic surgery.

[Sphincter function disorders. physiopathology and neurophysiological study]. / Trastornos de la funcion esfinteriana. Fisiopatología y estudio neurofisiológico.

Miction and defecation disturbances are very frequent in the general population and far more so among neurological patients. It is essential to know the physiopathology of these disorders in clinical practice. The neurological control of these functions is carried out by automatisms that are regulated in the nuclei of the brain stem through somatic and vegetative peripheral structures that act simultaneously. The cortical, hypothalamic and reticular levels play a part in the activation or inhibition of the pontine nuclei. Continence depends on the integrity of the anatomical structures and the sensory, pressure and mechanical systems that enable the automatisms to develop. Neurological examination must be combined with studies conducted by other specialists on patients in which no neurological illness is known, but who have this kind of dysfunction. Adding a neurophysiological examination allows us to complete the clinical study and to check objectively for the existence of external anal sphincter denervation or disorders involving the exteroceptive reflexes of the sacrum. The recent appearance of techniques for treating incontinence that make use of the repeated and continuous stimulation of the sacral roots has revolutionised the way these patients are treated and calls for greater involvement of neurologists in dealing with these problems.

[Truncal blocks of the lower limb]. / Blocs tronculaires du membre inférieur.

Plexus nerve blocks of the lower limb have been described for many years but were seldom used until recently. Postoperative analgesia is one of the main indications of these blocks. The blockade of both lumbar and sciatic plexuses is required for most of the surgical procedures performed on the proximal part of the lower limb. Nerve stimulators account for less difficulties to perform such blocks and results are more reliable. Several pharmacokinetic studies have documented that toxic thresholds of plasma concentrations of local anaesthetics are not reached with the doses commonly injected. Many different techniques and landmarks have been described providing several alternatives to perform these blocks according to the type and the localisation of the surgical procedure. Extensive indications are reported for day case surgery or patients at risk.

[Epidemiological study of prevalence, incidence and neuropathic pain characterization in neurology units. PREVADOL study]. / Estudio de prevalencia, incidencia y caracterización del dolor neuropático en consultas de neurología. Estudio PREVADOL.

INTRODUCTION: Neuropathic pain is defined as a pain initiated or caused by a lesion or dysfunction in the nervous system. The objectives of the study were to estimate the prevalence and incidence of neuropathic pain in hospital neurology units and primary care centres, to characterize the clinical profile of the patient with neuropathic pain and to know the most frequent treatments in the pharmacological management of this type of pain. METHODS: Observational, cross-sectional epidemiological survey carried out in 36 Neurology Units of the national territory (24 primary care centres and 12 hospitals). During 20 consecutive days neurologists collected the diagnoses of all the attended patients by any reason, up to 30 patients/day. In parallel the 20 first consecutive patients with neuropathic pain were chosen for their characterization in depth by means of a specific questionnaire. RESULTS: A total of 12,688 patients were attended and a total of 13,555 diagnoses were collected through 713 consultation days. The most frequent diagnosis was migraine/cephalea, with a prevalence of 23.40% (95% CI: 22.66%-24.14%). Neuropathic pain represented the eighth more frequent diagnosis, with a prevalence in neurology units of 3.88% (95% CI: 3.54%- 4.22%). The prevalence of neuropathic pain was 2.92% in primary care centres and 6.09% in hospital units (p < 0.01). The daily incidence of new neuropathic pain cases was 1.24% (95% CI: 1.05%-1.53%); 1.14% in primary care neurology centres and 1.45% in hospital units. CONCLUSIONS: The data obtained indicate that neuropathic pain is the eighth more frequent diagnosis in the neurology units. Medical assistance request by neuropathic pain is higher in the hospital units.

[Clinical analysis of musicians' focal hand dystonia. Review of 86 cases]. / Análisis clínico de la distonía focal en los músicos. Revisión de 86 casos.

INTRODUCTION: Focal hand dystonia in musicians due to its rareness and specificity. It has been insufficiently described thus remaining a largely unknown condition. OBJECTIVE: To describe the clinical characteristics of musician's focal dystonia. METHODS AND RESULTS: We analyzed 658 musicians' cases seen during the past 4 years in a medical center for performing artists. Of the musicians treated, 86 (13 %) suffered from focal dystonia, 42 % were guitarists, 21% pianists and 6% violinists. Men were more affected than women (7:1). Sufferers reported longer practice times (4.8 hours per day) and were older (33.6 years). In comparison, other pathologies were seen when musicians were younger (26.5 years) and played no more than 3.5 hours per day. CONCLUSIONS: Focal dystonia in musicians appear to be the consequence of a long history of intense and repetitive manual work while playing music added to other factors, as for example, gender.

[Electroneurographic parameters in cubital neuropathy of the elbow]. / Diferentes parámetros electroneurográficos en la neuropatía cubital en el codo. Interés de la conducción sensitiva antidrómica.

Using conventional techniques with cutaneous electrodes, 14 parameters of antidromic, motor and mixed segmentary sensory conduction of the cubital nerve were assessed in the first 45 patients presenting to us with some form of electroneurographic abnormality. Changes suggestive of axonal degeneration due to a decrease in amplitude or conduction velocity of the distal segment were found in 17. The remaining 28 patients showed only signs of change in conduction velocity at the elbow and could be classified according to electroneurographic degrees of progressive abnormality. Changes in antidromic sensory conduction are early and constant, constituting the parameter of choice for detection of slight compressive neuropathy.

[Physiopathology of meningeal hemorrhage caused by aneurysmal rupture: extracerebral aspects]. / Physiopathologie de l'hémorragie méningée par rupture anévrysmale: aspects extra-cérébraux.

Subarachnoid hemorrhage induces a lot of extracerebral disturbances such as: systemic hypertension, electrocardiographic abnormalities both morphological, rhythmic and subendocardial damages; those events have been interpreted as overactivity of the sympathetic nervous system. In biochemical changes, hyponatremia early recognized was referred during a long time to a syndrome of inappropriate secretion of antidiuretic hormone. Hyponatremia is now referred to a cerebral salt-wasting. Hypovolemia often observed supports the use of volemic expansion in the prevention and treatment of ischemic complications associated with ruptured intracranial aneurysms. The hypothalamus which lies in close anatomical proximity to the circle of Willis may be directly influenced by the rupture of a cerebral aneurysm. So, hypothalamic dysfunction may affect pituitary adrenal function sympathetic and parasympathetic activities. The knowledge of all these disturbances, and their mechanisms supports the current strategies for the management of aneurysmal subarachnoid hemorrhage.

[Nitrous oxide in neurosurgery]. / Protoxyde d'azote en neurochirurgie.

Nitrous oxide (N2O) is far from inert in terms of its cerebral effects. It can increase the cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen in animals and in man. In poor risks patients, the N2O may increase the intracranial pressure (ICP) but these effects are blocked by hyperventilation, benzodiazepines, barbiturates and narcotics. N2O is not epileptogenic but modifies evoked potentials. Because of its greater solubility than Nitrogen it can increase ICP, in case of pneumoencephalus and the size and consequences of gazous embolism. In neurosurgical patients, nitrous oxide should be used cautiously in regards of its neurological effects.

[The role of surgery and low molecular weight heparin in the treatment of cerebral venous thrombosis. Apropos of 2 cases]. / Place de la chirurgie et des héparines de bas poids moléculaire dans le traitement des thromboses veineuses cérébrales. A propos de 2 cas.

For one case of thrombosis of sinus sagittalis superior joint haemorrhagic cerebral softening necessitates surgical draining of haemorrhagic focus grown to a true intracranial haematoma; for the another case direct low molecular weight heparin treatment obtained a mere evolution. Authors are of the opinion that early low molecular weight heparin treatment is able to avoid massive haemorrhage.

[Congenital neuromyotonia. Retrospective study of 4 cases]. / Neuromiotonía congénita. Estudio retrospectivo de cuatro casos.

BACKGROUND: Fasciculation, double discharge, myokymia and neuromyotonia are different kinds of involuntary muscular activity that originate in ectopic discharges of the motor axons. Electrophysiological studies are needed in all cases for the diagnosis. Non rigorous electrophysiological studies in some cases is the cause of the historically unclear nosological delimitation of the neuromyotonic syndromes. OBJECTIVE: To report the clinical picture and electrophysiological findings in patients with congenital neuromyotonia. PATIENTS AND METHODS: Four patients with congenital neuromyotonia were studied. Electrophysiological exam included nerve conduction measurements, study of the after-discharges and conventional EMG. Spontaneous discharges were displayed after applying a low pass filter, signal trigger and delay line. RESULTS: In one case positive motor features predominate (continuous muscle fiber activity). On the contrary, two cases, showed neuropathic deficitary signs with a Charcot-Marie-Tooth type II disease phenotype; neuromyotonia was, in both cases, an electrophysiological feature. In the last patient, motor signs were limited to the facial muscles but electrophysiological study discovered generalized neuromyotonia. Treatment with carbamazepine or oxcarbazepine was useful in the four cases. CONCLUSION: Congenital neuromyotonia is a clinically heterogeneous syndrome with uniform electrophysiological features that permit its qualification.