Lateralized Effect of Thalamic Deep Brain Stimulation Location on Verbal Abstraction.

BACKGROUND: Regionalized thalamic activity has been implicated in language function, and yet the effect of thalamic deep brain stimulation (DBS) on language-related clinical outcomes is underexplored. OBJECTIVE: The objective of this study was to determine if the location of stimulation within the thalamus correlates with changes in language-related neuropsychological outcomes following DBS for essential tremor. METHODS: Thirty patients with essential tremor underwent comprehensive neuropsychological evaluations before and after DBS surgery targeting the ventral intermediate nucleus of the thalamus. Changes in neuropsychological functions were evaluated. The relationships between language-related outcomes and stimulation location were assessed using both categorical and linear methods. Any significant results were further validated using linear discriminant analysis. RESULTS: Most neuropsychological functions remained unchanged at the group level. However, outcome on a measure of verbal abstraction was significantly dependent on stimulation location along the anterior-posterior axis within the left ventral lateral thalamus, with anterior stimulation associated with reduced verbal abstraction performance. This result was supported by linear discriminant analysis, which showed that stimulation locations with improved and reduced verbal abstraction function were best separated by a vector nearly parallel to the anterior-posterior axis. No stimulation location dependence was found for verbal abstraction outcome in the right thalamus or for outcomes of other language functions in either hemisphere. CONCLUSION: We demonstrate an effect of thalamic DBS on verbal abstraction as a function of left thalamic topography. This finding provides clinical evidence for the lateralization and regionalization of thalamic language function that may be relevant for understanding nonmotor effects of stimulation. © 2021 International Parkinson and Movement Disorder Society.

Association of Preoperative Visual Hallucinations With Cognitive Decline After Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: Deep brain stimulation (DBS) is effective for the motor symptoms of Parkinson's disease (PD). Although most patients benefit with minimal cognitive side effects, cognitive decline is a risk, and there is little available evidence to guide preoperative risk assessment. Visual illusions or visual hallucinations (VHs) and impulse-control behaviors (ICBs) are relatively common complications of PD and its treatment and may be a marker of more advanced disease, but their relationship with postoperative cognition has not been established. The authors aimed to determine whether any preoperative history of VHs or ICBs is associated with cognitive change after DBS. METHODS: Retrospective chart review identified 54 patients with PD who received DBS of the subthalamic nucleus or globus pallidus internus and who completed both pre- and postoperative neuropsychological testing. Linear regression models were used to assess whether any preoperative history of VHs or ICBs was associated with changes in attention, executive function, language, memory, or visuospatial cognitive domains while controlling for surgical target and duration between evaluations. RESULTS: The investigators found that a history of VHs was associated with declines in attention (b=-4.04, p=0.041) and executive function (b=-4.24, p=0.021). A history of ICBs was not associated with any significant changes. CONCLUSIONS: These results suggest that a history of VHs may increase risk of cognitive decline after DBS; thus, specific preoperative counseling and targeted remediation strategies for these patients may be indicated. In contrast, a history of ICBs does not appear to be associated with increased cognitive risk.

Anatomic ACL reconstruction reduces risk of post-traumatic osteoarthritis: a systematic review with minimum 10-year follow-up.

PURPOSE: To systematically review the literature for radiographic prevalence of osteoarthritis (OA) at a minimum of 10 years following anterior cruciate ligament (ACL) reconstruction (ACLR) with anatomic vs. non-anatomic techniques. It was hypothesized that the incidence of OA at long-term follow-up would be lower following anatomic compared to non-anatomic ACLR. METHODS: A systematic review was performed by searching PubMed, MEDLINE, EMBASE, and the Cochrane Library, for studies reporting OA prevalence by radiographic classification scales at a minimum of 10 years following ACLR with autograft. Studies were categorized as anatomic if they met or exceeded a score of 8 according the Anatomic ACL Reconstruction Scoring Checklist (AARSC), while those with a score less than 8 were categorized as non-anatomic/non-specified. Secondary outcomes included graft failure and measures of knee stability (KT-1000, Pivot Shift) and functional outcomes [Lysholm, Tegner, subjective and objective International Knee Documentation Committee (IKDC) scores]. OA prevalence on all radiographic scales was recorded and adapted to a normalized scale. RESULTS: Twenty-six studies were included, of which 5 achieved a score of 8 on the AARSC. Using a normalized OA classification scale, 87 of 375 patients (23.2%) had diagnosed OA at a mean follow-up of 15.3 years after anatomic ACLR and 744 of 1696 patients (43.9%) had OA at mean follow-up of 15.9 years after non-anatomic/non-specified ACLR. The AARSC scores were 9.2 ± 1.3 for anatomic ACLR and 5.1 ± 1.1 for non-anatomic/non-specified ACLR. Secondary outcomes were relatively similar between techniques but inconsistently reported. CONCLUSIONS: This study showed that anatomic ACLR, defined as an AARSC score ≥ 8, was associated with lower OA prevalence at long-term follow-up. Additional studies reporting long-term outcomes following anatomic ACLR are needed, as high-level studies of anatomic ACLR are lacking. The AARSC is a valuable resource in performing and evaluating anatomic ACLR. Anatomic ACLR, as defined by the AARSC, may reduce the long-term risk of post-traumatic OA following ACL injury to a greater extent than non-anatomic ACLR. LEVEL OF EVIDENCE: IV.

Hyperdirect connectivity of opercular speech network to the subthalamic nucleus.

How the basal ganglia participate in the uniquely human behavior of speech is poorly understood, despite their known role in modulating critical aspects of cognitive and motor behavior. The subthalamic nucleus (STN) is well positioned to facilitate basal ganglia functions critical for speech. Using electrocorticography in patients undergoing awake deep brain stimulation (DBS) surgery, evidence is reported for a left opercular hyperdirect pathway in humans via stimulating the STN and examining antidromic-evoked activity in the left temporal, parietal, and frontal opercular cortex. These high-resolution cortical and subcortical mapping data provide evidence for hyperdirect connectivity between the inferior frontal gyrus and the STN. In addition, evoked potential data are consistent with the presence of monosynaptic projections from areas of the opercular speech cortex that are primarily sensory, including the auditory cortex, to the STN. These connections may be unique to humans, evolving alongside the ability for speech.

Depression history modulates effects of subthalamic nucleus topography on neuropsychological outcomes of deep brain stimulation for Parkinson's disease.

Patients with psychiatric symptoms, such as depression, anxiety, and visual hallucinations, may be at increased risk for adverse effects following deep brain stimulation of the subthalamic nucleus for Parkinson's disease, but there have been relatively few studies of associations between locations of chronic stimulation and neuropsychological outcomes. We sought to determine whether psychiatric history modulates associations between stimulation location within the subthalamic nucleus and postoperative affective and cognitive changes. We retrospectively identified 42 patients with Parkinson's disease who received bilateral subthalamic nucleus deep brain stimulation and who completed both pre- and postoperative neuropsychological testing. Active stimulation contacts were localized in MNI space using Lead-DBS software. Linear discriminant analysis identified vectors maximizing variance in postoperative neuropsychological changes, and Pearson's correlations were used to assess for linear relationships. Stimulation location was associated with postoperative change for only 3 of the 18 neuropsychological measures. Variation along the superioinferior (z) axis was most influential. Constraining the analysis to patients with a history of depression revealed 10 measures significantly associated with active contact location, primarily related to location along the anterioposterior (y) axis and with worse outcomes associated with more anterior stimulation. Analysis of patients with a history of anxiety revealed 5 measures with location-associated changes without a predominant axis. History of visual hallucinations was not associated with significant findings. Our results suggest that a history of depression may influence the relationship between active contact location and neuropsychological outcomes following subthalamic nucleus deep brain stimulation. These patients may be more sensitive to off-target (nonmotor) stimulation.

Classification of Individual Finger Movements Using Intracortical Recordings in Human Motor Cortex.

BACKGROUND: Intracortical microelectrode arrays have enabled people with tetraplegia to use a brain-computer interface for reaching and grasping. In order to restore dexterous movements, it will be necessary to control individual fingers. OBJECTIVE: To predict which finger a participant with hand paralysis was attempting to move using intracortical data recorded from the motor cortex. METHODS: A 31-yr-old man with a C5/6 ASIA B spinal cord injury was implanted with 2 88-channel microelectrode arrays in left motor cortex. Across 3 d, the participant observed a virtual hand flex in each finger while neural firing rates were recorded. A 6-class linear discriminant analysis (LDA) classifier, with 10 × 10-fold cross-validation, was used to predict which finger movement was being performed (flexion/extension of all 5 digits and adduction/abduction of the thumb). RESULTS: The mean overall classification accuracy was 67% (range: 65%-76%, chance: 17%), which occurred at an average of 560 ms (range: 420-780 ms) after movement onset. Individually, thumb flexion and thumb adduction were classified with the highest accuracies at 92% and 93%, respectively. The index, middle, ring, and little achieved an accuracy of 65%, 59%, 43%, and 56%, respectively, and, when incorrectly classified, were typically marked as an adjacent finger. The classification accuracies were reflected in a low-dimensional projection of the neural data into LDA space, where the thumb-related movements were most separable from the finger movements. CONCLUSION: Classification of intention to move individual fingers was accurately predicted by intracortical recordings from a human participant with the thumb being particularly independent.

Anterior Sensorimotor Subthalamic Nucleus Stimulation Is Associated With Improved Voice Function.

BACKGROUND: Despite the impact of Parkinson disease (PD) on speech communication, there is no consensus regarding the effect of lead location on voice-related outcomes in subthalamic nucleus (STN) deep brain stimulation (DBS). OBJECTIVE: To determine the relationship of stimulation location to changes in cepstral analyses of voice following STN DBS. METHODS: Speech pathology evaluations were obtained from 14 PD subjects, before and after STN DBS, including audio-perceptual voice ratings (overall severity, loudness, hoarseness changes), measured indices of dysphonia (cepstral peak prominence and cepstral spectral index of dysphonia), and phonatory aerodynamics. The contact locations used for active stimulation at the time of postoperative voice evaluations were determined and assessed in relation to voice outcomes. RESULTS: Voice outcomes remained relatively unchanged on average. Stimulation locations in the anterior portion of the sensorimotor region of the left STN, however, were associated with improvements in voice severity scores, cepstral spectral index of dysphonia, shortness of breath, and phonatory airflow during connected speech. Posterior locations were associated with worsening of these outcomes. Variation in the medial-lateral or dorsal-ventral position on the left, and in any direction on the right, did not correlate with any voice outcome. CONCLUSION: Active contact placement within the anterior sensorimotor STN was associated with improved perceptual and acoustic-aerodynamic voice-related outcomes. These findings suggest an STN topography for improving airflow for speech, in turn improving how PD patients' voices sound.

Routine deep vein thrombosis screening after lung transplantation: Incidence and risk factors.

BACKGROUND: Deep vein thrombosis (DVT) remains a common complication following lung transplantation despite universal routine DVT screening. Moreover, many of the previously reported risk factors are incompletely defined. We sought to explore the influence of DVT screening and to more definitively assess predisposing risk factors. METHODS: A single-institution, retrospective, cohort study of 1141 patients undergoing lung transplantation from January 1, 2005, to December 31, 2014, was performed evaluating for the rate of DVT. Patients were given prophylactic subcutaneous heparin postoperatively. DVT events were noted if they occurred before 90 days after transplant. We compared DVT rates before and after 2008 when universal screening was implemented. We also evaluated the timing of DVT event and location (above the knee vs below the knee). DVTs were treated with standard anticoagulation therapy or an inferior cava filter when patients were unable to tolerate anticoagulation treatment. Univariable and multivariable models were used to identify risk factors for occurrence. A propensity match was performed to match groups across the eras, and a Cox regression was performed to identify differences in 1-year survival trajectory between cohorts. RESULTS: The rates of DVT before and after routine screening were 8.8% (36 DVT out of 412 transplants) and 17.3% (126 out of 729 transplants), respectively. These 2 rates were significantly different (P < .01); moreover, the observed DVT incidence per year was not significantly different across the 6 years after universal DVT screening was implemented (P > .90 for all comparisons). Observed DVT incidence at day 0 and day 14 were 3.8% and 3.8%, respectively, for the cohort before DVT protocols were established. Observed DVT incidence for the cohort after protocols were established at the same time points was 8.7% and 3.7%, respectively. Univariable analysis revealed that significant factors associated with a DVT include hypercholesterolemia (odds ratio [OR], 6.90; 95% confidence interval [CI], 1.82-26.13; P < .01), the number of days in the intensive care unit (OR, 1.03; 95% CI, 1.00-1.01; P < .01), and the length of stay in the hospital (OR, 1.01; 95% CI, 1.01-1.02; P < .01), whereas having quit smoking (vs never smoked) was associated with a decrease in DVT development (OR, 0.50; 95% CI, 0.33-0.75; P < .01). Multivariable analysis revealed 2 significant variables: hypercholesterolemia (OR, 8.13; 95% CI, 1.22-54.37; P = .03) and length of stay (OR, 1.03; 95% CI, 1.01-1.05; P < .01). There was a trend for better 1-year survival in the post-2008 era (Exp[ß], 1.49; P = .09). CONCLUSIONS: The rate of DVT diagnosis significantly increased after universal DVT screening was implemented. Furthermore, those patients undergoing lung transplantation with extended length of stay and hypercholesterolemia were prone to increased rates of DVT. There was a trend toward better 1-year survival in DVT-screened patients, suggesting DVT screening may result in beneficial outcomes.

Patient Education and Engagement Through Multimedia: A Prospective Pilot Study on Health Literacy in Patients with Cerebral Aneurysms.

BACKGROUND: Improving the comprehension and communication of patient education materials could augment patient participation in shared clinical decision making. Inadequate healthcare-oriented educational resources for patients with a newly diagnosed complex disease, such as a cerebral aneurysm, can lead to an insufficient understanding of their ailment. As such, we hypothesized that a PowerPoint-style educational intervention with grade-conscious (i.e., sixth grade level) written material accompanied by visual graphics would help improve patient health literacy and satisfaction. METHODS: A randomized prospective pilot study was conducted during a 1-year period in 2018. Preclinic encounter knowledge assessment surveys were administered to 52 patients with brain aneurysms (newly diagnosed or during follow-up) presenting for their neurosurgery outpatient clinic visit. The patients were assigned to 1 of 2 cohorts, with 26 each in the educational intervention group and control group, using a quasi-randomization method of alternating the assigned group for each successive patient. At the conclusion of their clinic encounter, all the patients completed a postclinic encounter knowledge assessment and satisfaction survey. Differences in covariates such as gender distribution, age, and family history of aneurysms were analyzed between the control and intervention groups. RESULTS: The overall study cohort had a high baseline knowledge about cerebral aneurysms with an average preclinic encounter score of 5.37 on the 7-question survey. The educational intervention resulted in an upward trend in the patient knowledge scores. No statistically significant difference was detected in the patient satisfaction scores between the intervention and control groups. However, most of the patients receiving the educational intervention reported that the educational material was easy to understand (95.7%), helpful (86.9%), and relevant (87%) to their clinic visit. CONCLUSION: Overall, in the present prospective study, the use of a multimedia-based educational intervention resulted in an upward trend in knowledge without a statistically significant difference in patient satisfaction scores compared with the control patients. To better measure the effectiveness of multimedia-based patient education interventions, future studies should account for the patients' baseline education level, preexisting educational resources available to study patients, socioeconomic factors, and emotional state.

Metastatic calcinosis cutis due to refractory hypercalcaemia responsive to denosumab in a patient with multiple sclerosis.

Metastatic calcinosis cutis results from abnormal calcium levels leading to the precipitation of insoluble calcium salts in the skin and subcutaneous tissue. Here, we present the case of a 67-year-old man with multiple sclerosis on chronic dexamethasone and concurrent supplementation of calcium and daily cholecalciferol presenting with painful calcified lesions. During initial presentation, corrected calcium was 13.8 mg/dL (reference range: 8.5-10.1 mg/dL), ionised calcium was 1.70 mg/dL (reference range: 1.13-1.32 mg/dL) and 25-hydroxyvitamin D was 41.6 ng/mL (reference range 30-100 ng/mL). Normocalcaemia was restored with the off-label use of denosumab, usually reserved for hypercalcaemia of malignancy and intractable osteoporosis. We discuss potential aetiologies of this patient's hypercalcaemia, calcinosis cutis diagnosis and management and the off-label use of denosumab.

Current Agents and Related Therapeutic Targets for Inflammation After Acute Traumatic Spinal Cord Injury.

BACKGROUND: The infliction of a traumatic spinal cord injury (SCI) propagates damage that occurs in 2 stages. The first phase of trauma develops from the initial mechanical insult. The second phase involves the degradation of nervous tissue but is likely not affected by the initial insult. Thus, therapeutic targets with a high specificity for these secondary injury processes have been of increasing interest. We reviewed the pathophysiologic cascades of inflammation after SCI and potential therapeutic targets. METHODS: The PubMed and EMBASE databases were queried using appropriate medical subject headings for studies involving tumor necrosis factor (TNF)-α), nuclear factor (NF)-κB, inducible nitric oxide synthase (iNOS), interleukin (IL)-1ß, and/or Fas ligand (FasL) targets. The relevant studies found were graded into 3 levels (i.e., A, B, C) according to the quality of evidence. RESULTS: We have summarized the basis of the neurological damage for TNF-α, NF-κB, iNOS, IL-1ß, and FasL after SCI. A total of 17 studies were rated, each of which had reported histological, biochemical, physiological, and behavioral outcomes according to the treatment that had focused on TNF-α, NF-κB, iNOS, IL-1ß, and FasL. CONCLUSION: The TNF-α, iNOS, NF-κB, IL-1ß, and FasL will become active within minutes after SCI. The adverse effects from the activity of these receptors include inflammation and other important neurological damage. Each of these targets can be modulated by specific agents with differing degrees of efficacy according to the reported data.

Area Under the Curve of Somatosensory Evoked Potentials Detects Spinal Cord Injury.

PURPOSE: Intraoperative neurophysiological monitoring using somatosensory evoked potentials has been linked to a reduction in the incidence of neurological deficits during corrective surgery. Nonetheless, quantitative assessments of somatosensory evoked potential waveforms are often difficult to evaluate, because they are affected by anesthesia, injury, and noise. Here, we discuss a novel method that integrates somatosensory evoked potential signals into a single metric by calculating the area under the curve (AUC). METHODOLOGY: Thirty-two Sprague-Dawley rats underwent a laminectomy procedure and were then randomly assigned to a control group or to receive a contusive spinal cord injury ranging from 100 to 200 kilodynes. Neurophysiological testing was completed at various points perioperatively and postoperatively. Somatosensory evoked potential traces obtained were processed and the AUC metric was calculated. RESULTS: The AUC significantly decreased to 11% of its baseline value after impact and remained at 25% baseline after 1 hour for the 200-kdyn cohort. Postimpact, AUC for the control versus the 150-kdyn and 200-kdyn groups, and the 150-kdyn versus 200-kdyn groups were significantly higher (P < 0.01, P < 0.001, and P < 0.05, respectively). Across days, the only significant parameter accounting for AUC variability was impact force, P < 0.0001 (subject parameters and number of days were not significant). CONCLUSIONS: The AUC metric can detect an iatrogenic contusive spinal cord injury immediately after its occurrence. Moreover, this metric can detect different iatrogenic injury impact force levels and identify injury in the postoperative period. The AUC integrates multiple Intraoperative neurophysiological monitoring measures into a single metric and thus has the potential to help clinicians and investigators evaluate spinal cord impact injury status.

The Effect of Prophylactic Hypothermia on Neurophysiological and Functional Measures in the Setting of Iatrogenic Spinal Cord Impact Injury.

BACKGROUND: Iatrogenic spinal cord injury (iSCI) during spinal corrective surgery can result in devastating complications, such as paraplegia or paraparesis. Perioperatively, iSCI often occurs as a direct injury during spinal cord instrumentation placement. Currently, treatment of iSCI remains limited to posttraumatic hypothermia, which has demonstrated some value in recent clinical trials. Here we report the outcomes of preinjury hypothermia initiated preprocedurally and maintained for a considerable time after iSCI. METHODS: Twenty-six female Sprague-Dawley rats were assigned at random to either a normothermic group (36 °C) or a hypothermic group (32 °C) and then underwent a laminectomy procedure at the T8 level. Each group was further divided at random to receive a 200-kdyn force contusive spinal cord injury or a sham impact. Hypothermic rats were then rewarmed after 2 hours of hypothermic treatment. Behavioral scores, temperature profiles, weights, and somatosensory evoked potentials were obtained at baseline and at specified time points after the procedure. RESULTS: The median survival was 42 days for the iSCI hypothermic group and 11 days for the iSCI normothermic group (hazard ratio, 3.82; 95% confidence interval, 1.52-9.57). The probability of survival was significantly higher in the iSCI hypothermic group compared with the iSCI normothermic group (χ2 = 4.18; P = 0.040). The hypothermic group exhibited a higher Basso, Beattie and Bresnahan (BBB) locomotor rating scale score (17 vs. 14; P < 0.01), lower normalized latencies (1.06 ± 0.16 seconds vs. 1.34 ± 0.17 seconds; P = 0.04), and higher peak-to-peak amplitudes (0.32 ± 0.10 µV vs. 0.12 ± 0.09 µV; P = 0.005). CONCLUSIONS: The use of prophylactic hypothermia before iSCI was significantly associated with an increased survival rate, higher BBB scores, and improved neurophysiological measures.

Outcomes in socioeconomically disadvantaged patients with spinal cord injury: a systematic review.

OBJECTIVEIndividuals with a spinal cord injury (SCI) in socioeconomically disadvantaged settings (e.g., rural or low income) have different outcomes than their counterparts; however, a contemporary literature review identifying and measuring these outcomes has not been published. Here, the authors' aim was to perform a systematic review and identify these parameters in the hope of providing tangible targets for future clinical research efforts.METHODSA systematic review was performed to find English-language articles published from 2007 to 2017 in the PubMed/MEDLINE, EMBASE, and SCOPUS databases. Studies evaluating any outcomes related to patients with an SCI and in a low-resource setting were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and a flowchart was created. Of the 403 articles found, 31 underwent complete review and 26 were eligible for study inclusion. According to the current study criteria, any case studies, studies in less developed countries, studies including and not separating other types of neurological disorders, studies not assessing the effects of a low-resource setting on outcomes in patients with SCI, and studies evaluating the causes of SCI in a low-resource setting were excluded.RESULTSIn SCI patients, a lower income was a predictor of death (OR 2.1, 95% CI 1.7-2.6, p = 0.0002). Moreover, secondary outcomes such as pain intensities (OR 3.32, 95% CI 2.21-4.49, p < 0.001), emergency room visits (11% more likely, p = 0.006), and pressure ulcer formation (OR 2.1, 95% CI 1.5-3.0, p < 0.001) were significantly higher in the lower income brackets. Rurality was also a factor and was significantly associated with increased emergency room visits (OR 1.5, 95% CI 1.1-2.1, p = 0.01) and lower outpatient service utilization (incidence rate ratio [IRR] 0.57, 95% CI 0.35-0.93, p < 0.05).CONCLUSIONSThe authors showed that individuals in a low-resource setting who have suffered an SCI have significantly different outcomes than their counterparts. These specific outcomes are promising targets for future research efforts that focus on improving health conditions among this population.

Fluctuaciones de la homeostasis del zinc relacionadas con estadios del crecimiento-desarrollo humano / Fluctuations of zinc homeostatics related to the human growth-development stages

Se conoce que el Factor de Crecimiento Insulino Dependiente I (IGF-I), disminuye su expresión en presencia de déficit plasmático de zinc. El objetivo de la presente revisión es relacionar fluctuaciones de la homeostasis del zinc con estadios del crecimiento-desarrollo humano. De la discusión de la data presentada se tiene que: el crecimiento‒desarrollo humano es un proceso con incidencias del calcio y del zinc, donde el déficit de zinc resulta un factor de alto riesgo para el nacimiento prematuro de infantes y de niños con baja talla; existen evidencias suficientes para inferir una asociación débil directa entre el incremento gradual de los niveles plasmáticos de zinc y calcio con el aumento de la edad durante la infancia y la adolescencia y de que la interacción de colaboración entre el calcio y el zinc en la osteogénesis, sufre una diferenciación de funciones en la osificación endocondral, y se transforma en una relación de competencia en la formación del esmalte dental; se manifiesta como tendencia un incremento del zinc plasmático con el aumento de la edad, con sesgos debidos al sobrepeso y la obesidad y a la fertilidad productiva de la mujer. Puede entonces considerarse finalmente que la homeóstasis del zinc plasmático, estabilizada en un intervalo de valores normales para un estadio dado, propicia el crecimiento‒desarrollo necesario y suficiente, siendo el envejecimiento un momento de involución en aquella tendencia de incremento de valores plasmáticos de zinc con la edad.

It is known that the Factor of Insulin Dependent Growth I (IGF-I), it diminishes their expression in presence of plasmatic deficit of zinc. The objective of the present revision is to relate fluctuations of the homeostasis of the zinc with stages of the human growth-development. Of the discussion of it dates it presented one has that: the human growth-development is a process with incidences of the calcium and of the zinc, where the deficit of zinc is a factor of high risk for the premature birth of infants and of children with drop carves; enough evidences exist to infer a direct weak association between the gradual increment of the plasmatic levels of zinc and calcium with the increase of the age during the childhood and the adolescence and that the interaction of collaboration between the calcium and the zinc in the osteogenesis, suffers a differentiation of functions in the enchondral ossification , and it becomes a competition relationship in the formation of the dental enamel ; it is manifested as tendency an increment of the plasmatic zinc with the increase of the age, with due biases to the overweight and the obesity and to the woman's productive fertility. Then it can be considered finally that the homeostasis of the plasmatic zinc, stabilized in an interval of normal values for a given stadium, favorable the necessary and enough growth-development being the aging an involution moment in that tendency of increment of plasmatic values of zinc with the age.