José León-Carrión

Consensus guidelines on screening for hypopituitarism following traumatic brain injury

Primary objective: The goal of this consensus statement is to increase awareness among endocrinologists and physicians treating patients with traumatic brain injury (TBI) of the incidence and risks of hypopituitarism among patients with TBI. Rationale: TBI poses significant risk to the pituitary gland, leading to elevated risks of diabetes, hypopituitarism and other endocrinopathies. Signs and symptoms associated with hypopituitarism often mimic the sequellae of TBI, although the severity of symptoms is not necessarily related to the severity of the injury. Patients with TBI-induced hypopituitarism may benefit both physically and psychologically from appropriate hormone replacement therapy (HRT). Participants at this unique consensus meeting attempted to define and spearhead an approach to increase awareness of the risks of TBI-induced endocrinopathies, in particular growth hormone deficiency (GHD), and to outline necessary and practical objectives for managing this condition. Recommendations: Systematic screening of pituitary function is recommended for all patients with moderate-to-severe TBI at risk of developing pituitary deficits. Patients with hypopituitarism benefit from appropriate hormonal replacement and prospects for rehabilitation of patients with TBI-induced hypopituitarism may be enhanced by appropriate HRT. Further exploration of this possibility requires: (1) active collaboration between divisions of endocrinology and rehabilitation at the local level to perform a screening of pituitary function in patients after TBI, (2) creation of a consultancy service by endocrine societies for use by rehabilitation centres, (3) development of continuing medical education (CME) programmes that can be offered as crossover training to the physicians who manage the care of patients with TBIs, (4) targeting of patient organizations with educational information for dissemination to patients and their families, (5) continued efforts to more clearly define the population at greatest risk of TBI-induced hypopituitarism and (6) monitor results of efficacy studies as they become available to evaluate whether and how much replacement therapy can improve the symptoms of individuals with TBI-induced hypopituitarism.

DEVELOPMENT OF THE INHIBITORY COMPONENT OF THE EXECUTIVE FUNCTIONS IN CHILDREN AND ADOLESCENTS

The development of inhibitory control, one component of the executive functions, during childhood and adolescence was the focus of the present study. A group of 99 participants between 6 and 17 years of age were studied using the Stroop test. Results suggest the existence of age-related differences both in response times and errors that follow a nonlinear relationship. Interference increased in the first age groups, declining from around 10 years till 17 years. Data also suggest that word reading plays an important role in the performance of the task. When reading is blocked, linear relationships between age and interference measures emerge, showing an increase in inhibitory functions during childhood and adolescence.

The locked-in syndrome: a syndrome looking for a therapy.

A review of the scientific literature on locked-in syndrome (LIS) is offered. The clinical features, diagnosis and prognosis of LIS are reviewed, and methods regarding the differential diagnosis of LIS with severe disorders of consciousness are considered. Effective treatment, physiotherapy, and methods of communication are reviewed. Although progress in the field of communication for patients with LIS is promising, it is concluded that there are new possibilities to be pursued and that a more positive outlook in the area of professional care of the patients, as well as more extensive imaginative research will facilitate new and positive strategies for this syndrome.

Theory of mind deficits in patients with acquired brain injury: A quantitative review

Impaired theory of mind (ToM) reasoning is considered an underlying cause of social cognition deficits in patients with acquired brain injury (ABI). However, the literature does not agree on the severity of ToM impairment in this clinical population, nor does it coincide on the proper tools for its assessment. In this paper, we use a meta-analytic approach to review 26 studies which compare the performance of ABI patients and healthy controls in four widely-used ToM tasks: first-order belief task, second order belief task, understanding indirect speech (IS) and social faux pas. Overall, patients show moderate to severe ToM impairment. The latter appears in faux pas (effect size=0.70) and understanding IS tasks (ES=0.87), while moderate impairment can be seen in second-order (ES=0.60) and first-order belief tasks (ES=0.52). The severity of ToM impairment was influenced by ratio of patients with frontal lobe lesion, ratio of patients with right hemisphere injury, type of belief task, and heterogeneity of the samples etiology. Our results provide important quantitative evidence on the severity of ToM deficits in the ABI population, while identifying variables that influence these deficits. Implications for basic and clinical neuropsychology are discussed.

Blows to the head during development can predispose to violent criminal behaviour: rehabilitation of consequences of head injury is a measure for crime prevention.

Criminal behaviour and violence may be the consequence of head injuries acquired during childhood and youth (gang fights, domestic violence, small blows to the head while driving, falls and so forth). In this study, a comparison was made of the school and head injury histories of violent and non-violent prisoners. It was found that the delinquent subjects in both groups had a history of academic difficulties. However, what differentiated the violent from the non-violent group was a history of having suffered head injuries that were never treated. Problems at school are not enough themselves to predict violent behaviour. A history of discrete neurological damage as a consequence to blows received to the head must also be present. The results suggest to the authors that the treatment of the cognitive, behavioural and emotional consequences of brain injury could be a measure for crime prevention. Measures both for prevention and rehabilitation are discussed.

Survey: The locked-in syndrome: a syndrome looking for a therapy

The locked-in syndrome (LIS) is a very severe condition caused by a primary vascular or traumatic injury to the brainstem, normally corresponding to a ventral pons lesion due to an obstruction of the basilar artery, and characterized by upper motor neuron quadriplegia, paralysis of lower cranial nerves, bilateral paresis of horizontal gaze and anarthria, and with preserved consciousness. Patients who have suffered this pontine lesion generally have preserved vertical eye movements and movement of the eyelids (blinking), this being their only means of responding to the outside world. A survey was conducted of 44 people diagnosed with LIS, all of them belonging to the Association of Locked-in Syndrome (ALIS) of France. Results of this survey showed that LIS was equally frequent in men and women (51.2% vs. 48.1%) and had occurred at any age between 22-77 years of age (normally between 41-52 years, the mean age being 46.79 years). The average time that transpired post-insult was 71.35 months. The principal cause of LIS was stroke (86.4%), with traumatic brain injury (TBI) being a distant second cause with an incidence of only 13.6%. The diagnosis of LIS was usually made around the middle of the second month after onset (mean of 78.76 days). The principal treatments, when present, were pharmacological and physiotherapy. However, 47.1% of the patients were not receiving treatment of any kind at the time of the survey. Neuropsychologically, 86% had a good attentional level, 97.6% were temporally oriented and 76.7% could read; 18.6% reported memory problems and 24% showed visual deficit (found mainly in patients with LIS originated by TBI); 47.5% reported a good mood state and 12.5% reported feeling depressed; 61.1% reported having sexual desire, but only 30% maintained sexual relations; 78% were capable of emitting sounds and 65.8% could communicate without technical aid; 73.2% enjoyed going out and 81% met with friends at least twice a month. Only 14.3% participated in social activities and 23.8% watched television regularly. Nearly 100% of the patients reported being sensitive to touch to any part of their bodies. This survey suggests diagnostics and rehabilitation procedures.

Epidemiology of Traumatic Brain Injury and Subarachnoid Hemorrhage

Incidence rates of traumatic brain injury are high in both industrialized and non-industrialized countries and have been estimated variously to be between 150–250 cases per 100,000 population per year. The estimated incidence rates for subarachnoid hemorrhage (SAH) are between 10 to 25 cases per 100,000 population per year. Seasonal variation in the occurrence of subarachnoid hemorrhage has been reported in studies from different countries, with significant seasonal variations and peak periods for aneurysmal SAH differing widely. A differential racial distribution for SAH has been found as well as a higher mortality rate for women than for men. The cognitive and behavioral consequences of TBI and SAH are significant and affect the quality of life of patients and their families. Recent publications have informed of hypopituitary deficits in patients sustaining TBI or SAH. It is not clear whether the cognitive deficits found in these patients are due to the consequences of the brain injury itself or are related to the hypopituitary deficits. There is a need for research distinguishing the differential cognitive and behavioral effects of the brain injury and the endocrinological deficits in these patients, and for developing adequate treatment.

Accuracy of the S100β protein as a marker of brain damage in traumatic brain injury.

Introduction: This study tested the hypothesis that S100β is a useful screening tool for detecting intracranial lesion (IL) in patients with a normal level of consciousness after traumatic brain injury (TBI). Methods: One hundred and forty-three post-TBI patients without a decrease in consciousness (GCS = 15) and with at least one neurological symptom (e.g. transitory loss of consciousness, amnesia, headache, dizziness or vomiting) were prospectively included. A blood sample was drawn at 6-hours post-TBI. A routine CT scan was obtained within 24 hours post-injury. Diagnostic properties of S100β for IL prediction in CT scan findings were tested using ROC-analysis. Results: A total of 15 patients (10.5%) had IL. Serum levels were significantly higher in these patients. Significant differences were found between S100β levels and CT scan findings (p = 0.007). ROC-analysis showed that S100β is a useful tool for detecting the presence of IL in CT scans (p = 0.007). In this series, the best cut-off for S100β is 0.130 µg L−1, with 100% sensitivity and 32.81% specificity. Conclusion: Within the first 6 hours post-TBI, serum S100β seems to be an effective biochemical indicator of IL in patients without a decrease in consciousness. These results indicate that higher S100β cut-off values substantially improve the clinical relevance of this protein.

Evidence of Cognitive and Neurophysiological Impairment in Patients with Untreated Naive Acromegaly

CONTEXT Recent studies have suggested that long-term exposure to high levels of GH and IGF-I affect brain and cognitive functions. However, very few human studies have challenged this hypothesis. OBJECTIVE The aim of this study is to explore whether GH/IGF-I excess in naive patients with acromegaly alters cognitive functions, particularly memory, and whether these alterations are accompanied by neurophysiological correlates. DESIGN We conducted a comprehensive neuropsychological and neurophysiological exam on 16 naive acromegaly patients and 16 strictly matched healthy controls. Comparative analyses were carried out on major neurocognitive domains (executive functions, visual/verbal memory, attention, visuoconstructive abilities, and verbal fluency) and on quantitative electroencephalogram and low-resolution brain electromagnetic tomography sources. Results were correlated with GH and IGF-I hormone concentrations. RESULTS Short- and long-term memory were the most severely impaired cognitive functions. Moreover, memory performance correlated negatively with GH and IGF-I concentrations. No association was detected between depression and memory impairment, and only a marginal association was found with quality of life. Finally, acromegaly patients showed power attenuation in fast frequency electroencephalogram bands, as well as decreased activity in prefrontal and middle temporal cortices, that was associated to cognitive performance. CONCLUSIONS Results provide evidence of cognitive and neurophysiological impairment, characterized by moderate-to-severe memory impairment and decreased neural activity in specific brain areas. High levels of GH and IGF-I in acromegaly patients could be the basis for these findings.

Cognitive deterioration due to GH deficiency in patients with traumatic brain injury: A preliminary report

Primary objective: To determine whether cognitive and behavioural disorders observed in TBI patients are due to hormonal deficits or to the brain injury itself. Research design: Transversal, between-group design. Methods and procedures: Studied 22 severe TBI patients (GCS < 8): 11 had isolated GH deficiency and 11 did not. Prepared detailed clinical reports on patients and performed physical examinations, standard biochemical and full blood count analysis. Patients underwent neuropsychological assessment and hormonal evaluation 6 months after TBI diagnosis. Results: TBI patients with GH deficiency show greater deficits in attention, executive functioning, memory and emotion than those without GH deficiency. Conclusions: Results show GH-related cognitive impairment in patients who develop GH deficiency after TBI and suggest that treatment of GH deficiency would improve cognition. The clinical importance of these findings should be established to better understand the nature, magnitude and meaning of GH-related cognitive impairment in patients who develop GH deficiency after TBI.