Review of Amyotrophic Lateral Sclerosis, Parkinson's and Alzheimer's diseases helps further define pathology of the novel paradigm for Alzheimer's with heavy metals as primary disease cause.

Pathologies of neurological diseases are increasingly recognized to have common structural and molecular events that can fit, sometimes loosely, into a central pathological theme. A better understanding of the genetic, proteomic and metabolic similarities between three common neurodegenerative diseases - Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) - and how these similarities relate to their unique pathological features may shed more light on the underlying pathology of each. These are complex multigenic neuroinflammatory diseases caused by a combined action by multiple genetic mutations, lifestyle factors and environmental elements including a proposed contribution by transition metals. This comprehensive dynamic makes disease decoding and treatment difficult. One case of ALS, for example, can manifest from a very different pool of genetic mutations than another. In the case of ALS multiple genes in addition to SOD1 are implicated in the pathogenesis of both sporadic and familial variants of the disease. These genes play different roles in the processing and trafficking of signalling, metabolic and structural proteins. However, many of these genetic mutations or the cellular machinery they regulate can play a role in one form or another in PD and AD as well. In addition, the more recent understanding of how TREM-2 mutations factor into inflammatory response has shed new light on how chronic inflammatory activity can escalate to uncontrolled systemic levels in a variety of inflammatory diseases from neurodegenerative, auto-inflammatory and autoimmune diseases. TREM-2 mutations represent yet another complicating element in these multigenic disease pathologies. This review takes us one step back to discuss basic pathological features of these neurodegenerative diseases known to us for some time. However, the objective is to discuss the possibility of related or linked mechanisms that may exist through these basic disease hallmarks that we often classify as absolute signatures of one disease. These new perspectives will be discussed in the context of a new paradigm for Alzheimer's disease that implicates heavy metals as a primary cause. Plausible links between these distinctly different pathologies are presented showing intersections of their distinct pathologies that hinge on metal interactions.

Thallium intoxication. Case Report.

We report a rare case of serious voluntary intoxication by laboratory thallium monobromate combined with alcohol intake by a 24-years old man. The diagnosis of thallium intoxication was based on history, nonspecific but typical clinical symptoms including gastrointestinal complaints, painful polyneuropathy, alopecia, and confirmed by the finding of increased thallium concentration in the urine. The treatment, performed at the due time, consisted of decontamination of the stomach by irrigation, administration of active charcoal and Prussian blue, correction of water and mineral dysbalance, symptomatic treatment, and led to complete recovery.

Ammonia encephalopathy and awake craniotomy for brain language mapping: Cause of failed awake craniotomy / Encefalopatía por amonio y cirugía con el paciente despierto para mapeo del lenguaje; causa de fracaso de craneotomía despierta

We report the case of an aborted awake craniotomy for a left frontotemporoinsular glioma due to ammonia encephalopathy on a patient taking Levetiracetam, valproic acid and clobazam. This awake mapping surgery was scheduled as a second-stage procedure following partial resection eight days earlier under general anesthesia. We planned to perform the surgery with local anesthesia and sedation with remifentanil and propofol. After removal of the bone flap all sedation was stopped and we noticed slow mentation and excessive drowsiness prompting us to stop and control the airway and proceed with general anesthesia. There were no post-operative complications but the patient continued to exhibit bradypsychia and hand tremor. His ammonia level was found to be elevated and was treated with an infusion of l -carnitine after discontinuation of the valproic acid with vast improvement. Ammonia encephalopathy should be considered in patients treated with valproic acid and mental status changes who require an awake craniotomy with patient collaboration (AU)

Se presenta el caso de un paciente con un glioma insulofrontotemporal izquierdo, tratado con levetiracetam, valproato y clobazam. Se realizó una primera cirugía bajo anestesia general para la exéresis del lóbulo temporal tumoral, y 8 días después se sometió a una cirugía con el paciente despierto para mapeo del lenguaje, bajo sedación consciente con remifentanilo y anestesia local. A la llegada a quirófano, el paciente se encontraba cansado y con cierta bradipsiquia; tras parar la infusión de remifentanilo, y antes de abrir la duramadre, el paciente presentó una disminución del nivel de consciencia con privación respiratoria que requirió intubación endotraqueal y la finalización de la cirugía. En el periodo posoperatorio se apreció bradipsiquia moderada, cansancio y temblor de manos. Fueron detectados niveles altos de amonio en sangre, y la clínica mejoró tras la administración de L-carnitina y la suspensión del valproato. La encefalopatía por amonio, aunque con mínima sintomatología, debería ser considerada en pacientes tratados con valproato que van a ser sometidos a una cirugía bajo sedación, donde se requiere que el paciente colabore (AU)

Heavy metals exposure and hearing loss in US adolescents.

INTRODUCTION: Hearing loss is common and, in young persons, can compromise social development and educational achievement. Exposure to heavy metals has been proposed as an important risk factor for hearing loss. METHODS: We evaluated the cross-sectional associations between blood lead, blood mercury, and urinary cadmium and arsenic levels and audiometrically determined hearing loss in participants aged 12 to 19 years in the 2005-2008 National Health and Nutrition Examination Survey after accounting for the complex survey design. There were 2535 individuals available for analysis of blood lead and mercury levels, 878 for urinary cadmium levels, and 875 for urinary arsenic levels. Multivariate logistic regression was used to calculate adjusted odds ratios (ORs) and 95% CIs. RESULTS: A blood lead level greater than or equal to 2 µg/dL (to convert to micromoles per liter, multiply by 0.0483) compared with less than 1 µg/dL was associated with increased odds of high-frequency hearing loss (OR, 2.22; 95% CI, 1.39-3.56). Individuals in the highest quartile of urinary cadmium levels had significantly higher odds of low-frequency hearing loss than those in the lowest quartile (OR, 3.08; 95% CI, 1.02-9.25). There was no overall association between quartiles of blood mercury or urinary arsenic levels and hearing loss. CONCLUSION: Blood lead levels well below the current recommended action level are associated with substantially increased odds of high-frequency hearing loss.

[Clinical and epidemiological peculiarities of multiple sclerosis in patients with different level of essential and toxic chemicals in blood serum].

Multiple sclerosis as it seen presently is a disease determined by the interaction of genetic and environmental factors. Risk factors are some chronic infections and living in ecological hazard areas. In this aspect, the authors review a role of metals which remains unclear so far. The paper presents the data on the effects of zinc, cadmium, lead and copper on the multiple sclerosis course.

Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: part B - behavioral results.

BACKGROUND: This study investigated the effects of oral dimercapto succinic acid (DMSA) therapy on the behavioural symptoms of children with autism spectrum disorders (ASD) ages 3-8 years. METHODS: Phase 1 involved 65 children with ASD who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo. RESULTS: The groups receiving one round and seven rounds of DMSA had significant improvements on all the assessment measures. For the seven round group, the degree of improvement on the assessment measures could be partially explained by a regression analysis based on excretion of toxic metals and changes in glutathione (adjusted R2 of 0.28-0.75, p < 0.02 in all cases). One round of DMSA had nearly the same benefit as seven rounds. The assessment measures correlated reasonably with one another at the beginning of the study (r = 0.60-0.87) and even better at the end of the study (r = 0.63-0.94). CONCLUSION: Overall, both one and seven rounds of DMSA therapy seems to be reasonably safe in children with ASD who have high urinary excretion of toxic metals, and possibly helpful in reducing some of the symptoms of autism in those children.

An uncommon cause of lower limb weakness.

We describe a case of a severely mentally disabled patient diagnosed as suffering from Guillain-Barré syndrome and treated with repeated plasma exchange. However, the abrupt onset of a cardiovascular collapse prompted a more in-depth diagnostic workup which demonstrated that the neurologic symptoms were likely to be ascribed to poisoning with heavy metals from a large number of ingested coins and other metallic items.