Does Lithium Prevent Alzheimer's Disease?

Lithium salts have a well-established role in the treatment of major affective disorders. More recently, experimental and clinical studies have provided evidence that lithium may also exert neuroprotective effects. In animal and cell culture models, lithium has been shown to increase neuronal viability through a combination of mechanisms that includes the inhibition of apoptosis, regulation of autophagy, increased mitochondrial function, and synthesis of neurotrophic factors. In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of anti-apoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor (BDNF), cortical thickening, increased grey matter density, and hippocampal enlargement. Recent studies addressing the inhibition of glycogen synthase kinase-3 beta (GSK3B) by lithium have further suggested the modification of biological cascades that pertain to the pathophysiology of Alzheimer's disease (AD). A recent placebo-controlled clinical trial in patients with amnestic mild cognitive impairment (MCI) showed that long-term lithium treatment may actually slow the progression of cognitive and functional deficits, and also attenuate Tau hyperphosphorylation in the MCI-AD continuum. Therefore, lithium treatment may yield disease-modifying effects in AD, both by the specific modification of its pathophysiology via inhibition of overactive GSK3B, and by the unspecific provision of neurotrophic and neuroprotective support. Although the clinical evidence available so far is promising, further experimentation and replication of the evidence in large scale clinical trials is still required to assess the benefit of lithium in the treatment or prevention of cognitive decline in the elderly.

Electric Ventilation: indications for and technical aspects of diaphragm pacing stimulation surgical implantation

Objective: Patients with high cervical spinal cord injury are usually dependent on mechanical ventilation support, which, albeit life saving, is associated with complications and decreased life expectancy because of respiratory infections. Diaphragm pacing stimulation (DPS), sometimes referred to as electric ventilation, induces inhalation by stimulating the inspiratory muscles. Our objective was to highlight the indications for and some aspects of the surgical technique employed in the laparoscopic insertion of the DPS electrodes, as well as to describe five cases of tetraplegic patients submitted to the technique. Methods: Patient selection involved transcutaneous phrenic nerve studies in order to determine whether the phrenic nerves were preserved. The surgical approach was traditional laparoscopy, with four ports. The initial step was electrical mapping in order to locate the "motor points" (the points at which stimulation would cause maximal contraction of the diaphragm). If the diaphragm mapping was successful, four electrodes were implanted into the abdominal surface of the diaphragm, two on each side, to stimulate the branches of the phrenic nerve. Results: Of the five patients, three could breathe using DPS alone for more than 24 h, one could do so for more than 6 h, and one could not do so at all. Conclusions: Although a longer follow-up period is needed in order to reach definitive conclusions, the initial results have been promising. At this writing, most of our patients have been able to remain ventilator-free for long periods of time.

Multiple Intravenous Administrations of Human Umbilical Cord Blood Cells Benefit in a Mouse Model of ALS

Background: A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (25x10(6) cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. However, this single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was therefore to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages. Methodology/Principal Findings: Mice received weekly intravenous injections of MNC hUCB or media. Symptomatic mice received 10(6) or 2.5x10(6) cells from 13 weeks of age. A third, pre-symptomatic, group received 10(6) cells from 9 weeks of age. Control groups were media-injected G93A and mice carrying the normal hSOD1 gene. Motor function tests and various assays determined cell effects. Administered cell distribution, motor neuron counts, and glial cell densities were analyzed in mouse spinal cords. Results showed that mice receiving 10(6) cells pre-symptomatically or 2.5x10(6) cells symptomatically significantly delayed functional deterioration, increased lifespan and had higher motor neuron counts than media mice. Astrocytes and microglia were significantly reduced in all cell-treated groups. Conclusions/Significance: These results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies.

Impaired blood-brain/spinal cord barrier in ALS patients

Vascular pathology, including blood-brain/spinal cord barrier (BBB/BSCB) alterations, has recently been recognized as a key factor possibly aggravating motor neuron damage, identifying a neurovascular disease signature for ALS. However, BBB/BSCB competence in sporadic ALS (SALS) is still undetermined. In this study, BBB/BSCB integrity in postmortem gray and white matter of medulla and spinal cord tissue from SALS patients and controls was investigated. Major findings include (1) endothelial cell damage and pericyte degeneration, (2) severe intra- and extracellular edema, (3) reduced CD31 and CD105 expressions in endothelium, (4) significant accumulation of perivascular collagen IV, and fibrin deposits (5) significantly increased microvascular density in lumbar spinal cord, (6) IgG microvascular leakage, (7) reduced tight junction and adhesion protein expressions. Microvascular barrier abnormalities determined in gray and white matter of the medulla, cervical, and lumbar spinal cord of SALS patients are novel findings. Pervasive barrier damage discovered in ALS may have implications for disease pathogenesis and progression, as well as for uncovering novel therapeutic targets. (C) 2012 Elsevier B.V. All rights reserved.

Motor Neuron Disease and Acquired Axonal Neuropathy Association in HIV Infection: Case Report and Update

Background: A possible viral etiology has been documented in the genesis of motor neuron disorders and acquired peripheral neuropathies, mainly due to the vulnerability of peripheral nerves and the anterior horn to certain viruses. In recent years, several reports show association of HIV infection with Amyotrophic Lateral Sclerosis Syndrome, Motor Neuron Diseases and peripheral neuropathies. Objective: To report a case of an association between Motor Neuron Disease and Acquired Axonal neuropathy in HIV infection, and describe the findings of neurological examination, cerebrospinal fluid, neuroimaging and electrophysiology. Methods: The patient underwent neurological examination. General medical examinations were performed, including, specific neuromuscular tests, analysis of cerebrospinal fluid, muscle biopsy and imaging studies. Results and Discussion: The initial clinical presentation of our case was marked by cramps and fasciculations with posterior distal paresis and atrophy in the left arm. We found electromyography tracings with deficits in the anterior horn of the spinal cord and peripheral nerves. Dysphagia and release of primitive reflexes were also identified. At the same time, the patient was informed to be HIV positive with high viral load. He received antiretroviral therapy, with load control but with no clinical remission. Conclusion: Motor Neuron disorders and peripheral neuropathy may occur in association with HIV infection. However, a causal relationship remains uncertain. It is noteworthy that the antiretroviral regimen may be implicated in some cases.

Diaphragmatic pacing stimulation in spinal cord injury: anesthetic and perioperative management

OBJECTIVE: The standard therapy for patients with high-level spinal cord injury is long-term mechanical ventilation through a tracheostomy. However, in some cases, this approach results in death or disability. The aim of this study is to highlight the anesthetics and perioperative aspects of patients undergoing insertion of a diaphragmatic pacemaker. METHODS: Five patients with quadriplegia following high cervical traumatic spinal cord injury and ventilator-dependent chronic respiratory failure were implanted with a laparoscopic diaphragmatic pacemaker after preoperative assessments of their phrenic nerve function and diaphragm contractility through transcutaneous nerve stimulation. ClinicalTrials.gov:NCT01385384. RESULTS: The diaphragmatic pacemaker placement was successful in all of the patients. Two patients presented with capnothorax during the perioperative period, which resolved without consequences. After six months, three patients achieved continuous use of the diaphragm pacing system, and one patient could be removed from mechanical ventilation for more than 4 hours per day. CONCLUSIONS: The implantation of a diaphragmatic phrenic system is a new and safe technique with potential to improve the quality of life of patients who are dependent on mechanical ventilation because of spinal cord injuries. Appropriate indication and adequate perioperative care are fundamental to achieving better results.

Chromatic discrimination losses in multiple sclerosis patients with and without optic neuritis using the Cambridge Colour Test

We assessed chromatic discrimination in multiple sclerosis (MS) patients both with (ON) and without (no ON) a history of optic neuritis using the Cambridge color test (CCT). Our goal was to determine the magnitude and chromatic axes of any color vision losses in both patient groups, and to evaluate age-related changes in chromatic discrimination in both patient groups compared to normals. Using the CCT, we measured chromatic discrimination along the protan, deutan and tritan axes in 35 patients with MS (17 ON eyes) and 74 age matched controls. Color thresholds for both patient groups were significantly higher than controls` along the protan and tritan axes (P < 0.001). In addition, the ON and no-ON groups differed significantly along all three-color axes (p < 0.001). MS patients presented a progressive color discrimination impairment with age (along the deutan and tritan axes) that was almost two times faster than controls, even in the absence of ON. These findings suggest that demyelinating diseases reduce sensitivity to color vision in both red-green and blue-yellow axes, implying impairment in both parvocellular and koniocellular visual pathways. The CCT is a useful tool to help characterize vision losses in MS and the relationship between these losses and degree of optic nerve involvement.

Moxonidine into the lateral parabrachial nucleus reduces renal and hormonal responses to cell dehydration

The deactivation of the inhibitory mechanisms with injections of moxonidine (alpha(2)-adrenoceptor/imidazoline receptor agonist) into the lateral parabrachial nucleus (LPBN) increases hypertonic NaCl intake by intra- or extracellular dehydrated rats. In the present study, we investigated the changes in the urinary sodium and volume, sodium balance, and plasma vasopressin and oxytocin in rats treated with intragastric (i.g.) 2 M NaCl load (2 ml/rat) combined with injections of moxonidine into the LPBN. Male Holtzman rats (n=5-12/group) with stainless steel cannulas implanted bilaterally into LPBN were used. Bilateral injections of moxonidine (0.5 nmol/0.2 mu l) into the LPBN decreased i.g. 2 M NaCIinduced diuresis (4.6 +/- 0.7 vs. vehicle: 7.4 +/- 0.6 ml/120 min) and natriuresis (1.65 +/- 0.29 vs. vehicle: 2.53 +/- 0.17 mEq/120 min), whereas the previous injection of the alpha(2)-adrenoceptor antagonist RX 821002 (10 nmol/0.2 mu l) into the LPBN abolished the effects of moxonidline. Moxonidine injected into the LPBN reduced i.g. 2 M NaCl-induced increase in plasma oxytocin and vasopressin (14.6 +/- 2.8 and 2.2 +/- 0.3 vs. vehicle: 25.7 +/- 7 and 4.3 +/- 0.7 pg/ml, respectively). Moxonidine injected into the LPBN combined with i.g. 2 M NaCl also increased 0.3 M NaCl intake (7.5 +/- 1.7 vs. vehicle: 0.5 +/- 0.2 mEq/2 h) and produced positive sodium balance (2.3 +/- 1.4 vs. vehicle: -1.2 +/- 0.4 mEq/2 h) in rats that had access to water and NaCl. The present results show that LPBN alpha(2)-adrenoceptor activation reduces renal and hormonal responses to intracellular dehydration and increases sodium and water intake, which facilitates sodium retention and body fluid volume expansion. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Feasibility of Intralaminar, Lateral Mass, or Pedicle Axis Vertebra Screws in Children Under 10 Years of Age: A Tomographic Study

BACKGROUND: There are several techniques for screw insertion in upper cervical spine surgery, and the use of the 3.5-mm screw is usually the standard. However, there is no consensus regarding the feasibility of using these screws in the pediatric population. OBJECTIVE: To determine the measurement of the lamina angle, lamina and pedicle length and thickness, and lateral mass length of the topographic axial view of the axis vertebra of 2- to 10-year-old children to guide the use of surgical screws. METHODS: Seventy-five computed tomography scans from 24- to 120-month-old patients were studied. Measurements were taken in an axial view of C2 and correlated with 2 age groups and both sexes. Statistical analysis was performed with the Student t test. RESULTS: In the 24- to 48-month age group, only 5.5% of the lamina and 8.3% of the pedicles had thicknesses < 3.5 mm. In the 49- to 120-month age group, there were no lamina thickness values < 3.5 mm, and 1.2% of pedicle thicknesses were < 3.5 mm. Both age groups had no lamina and pedicle lengths < 12 mm and no lateral mass lengths > 12 mm. CONCLUSION: In the majority of cases, the use of 3.5-mm lamina and pedicle screws in children is feasible. A base value of 45 degrees for the spinolaminar angle can be adopted as a reference for insertion of screws in the C2 lamina. This information can be particularly useful for decision making during preoperative planning for C1-C2 or craniocervical arthrodesis in children.

Systemic sclerosis sine scleroderma associated with antiphospholipid syndrome

The antiphospholipid syndrome (APS) can be primary, when it occurs alone, or secondary, when it is associated with another autoimmune disease, mainly systemic lupus erythematosus and rarely other autoimmune diseases. Cases described in literature (Medline 1966 to December 2009) associate the presence of antiphospholipid antibodies with the presence of APS and systemic sclerosis (SS). Currently, however, no cases of the SS variant sine scleroderma with APS have been described. In this study, the authors describe the case of a patient with APS characterised by thrombosis of the retinal veins, in May 2006, the presence of lupus anticoagulant and an anticardiolipin IgG antibody. In May 2007, this patient developed Raynaud's phenomenon, a lack of oesophageal motility and nailfold capillaroscopy with a scleroderma pattern. The patient was positive for the anti-centromere antibody but lacked any evidence of cutaneous thickening or involvement. In summary, the authors describe the first case of a patient with APS associated with SS sine scleroderma.

Effectiveness of Piezoelectric Surgery in Preparing the Lateral Window for Maxillary Sinus Augmentation in Patients with Sinus Anatomical Variations: A Case Series

Purpose: The present article sought to evaluate the effectiveness of a piezoelectric surgical unit for maxillary sinus augmentation surgeries in avoiding perforation of the sinus membrane and other possible procedural complications in patients with anatomical variations of the sinus. Materials and Methods: Twenty-five patients presenting sinus anatomical variations, who were indicated for a total of 40 sinus grafting procedures performed by the lateral window approach with a piezoelectric device, were analyzed. After 6 months of healing, implants were placed. Information collected included clinical and computed tomographic information on anatomical variations in the sinus bone walls, in the size of the sinus, and in the thickness of the sinus membrane. Occurrence of sinus membrane perforation and computed tomographic measurements of the amount of bone height gained with the grafting procedures were also recorded. Results: Only two patients presented a small perforation (less than 5 mm in diameter) of the sinus membrane, which occurred only after osteotomies of the lateral windows and did not compromise the surgical outcome. No implants were lost during a mean follow-up period of 19 months. Conclusion: The use of piezoelectric surgery allowed for the accomplishment of all rehabilitation treatments within the follow-up period of this study. INT J ORAL MAXILLOFAC IMPLANTS 2012;27:1211-1215

Use of a titanium device in lateral sinus floor elevation: an experimental study in monkeys

Aim: To evaluate the effect of a space-maintaining device fixed to the lateral wall of the maxillary sinus after the elevation of the sinus mucosa on bone filling of the sinus cavity. Material and methods: Immediately after the elevation of the maxillary sinus Schneiderian membrane accomplished through lateral antrostomy in four monkeys, a titanium device was affixed to the lateral sinus wall protruding into the sinus cavity to maintain the mucosa elevated without the use of grafting material. The healing of the tissue around the implants was evaluated after 3 and 6 months. Ground sections were prepared and analyzed histologically. Results: The void under the elevated sinus membrane, originally filled with the blood clot, was reduced after 3 as well as after 6 months of healing of about 56% and 40.5%, respectively. In seven out of eight cases, the devices had perforated the sinus mucosa. The formation of mineralized bone and bone marrow amounted to about 42% and 69% after 3 and 6 months, respectively. The connective tissue represented about 53% and 23% of the newly formed tissue after 3 and 6 months, respectively. Conclusions: New bone formation was found below the devices. However, shrinkage of the newly formed tissue was observed both after 3 and 6 months of healing. Hence, the space-maintaining function of the devices used in the present study has to be questioned.

Functional MMP-9 polymorphisms modulate plasma MMP-9 levels in multiple sclerosis patients

We have described that MMP-9 C- T-1562 and (CA)(n) polymorphisms contribute to multiple sclerosis (MS). Here, we evaluate whether plasma MMP-9 levels are related to disease severity, drug therapy resistance and polymorphisms. For sub-study 1, 36 patients with MS and 35 controls were recruited. For sub-study 2, 88 individuals (53 patients and 35 controls) were included in a cross-sectional analysis. MS patients presented higher MMP-9 activity (1.4 +/- 0.18 versus 0.93 +/- 0.18 A.U. for control, P<0.05). Drug-therapy resistant individuals exhibited increased MMP-9 activity (1.96 +/- 0.25 versus 1.21 +/- 0.09 A.U. for non-resistant patients). EDSS score was also related to MMP-9 levels. The CT + TT and HH genotypes had higher MMP-9 levels as compared to patients carrying the CC and LL Drug therapy resistance, disease severity. MMP-9 plasma activity and polymorphisms are associated with MS. (C) 2012 Elsevier B.V. All rights reserved.

Retinal nerve fiber evaluation in neuro-ophthalmic diseases of the anterior visual pathway

Retinal nerve fiber evaluation is important in the diagnosis and management of several diseases of the anterior visual pathway. In this report we review the clinical findings and the current techonologies avalilable to analyse the retinal nerve fiber layer. We furthermore review the main findings in several disease of the anterior visual pathways including inflammatory, ischemic, toxics, hereditary, compressive and traumatic optic neuropathies as well as lesion of the optic chiasm, optic tract and lateral geniculate body.