Frostbite is tissue damage caused by freezing temperatures and constitutes an important cause of morbidity in cold climate zones and high altitude. The direct effects of sub-zero temperatures lead to tissue freezing, electrolyte shifts and pH alterations, microvascular damage, and eventually to cell death. Upon rewarming, inflammatory reperfusion injury and thrombosis may lead to further tissue damage. Several studies and various case reports show that many patients suffer from long-term sequelae such as vasomotor disturbances (associated with susceptibility to refreezing), and neuropathic and nociceptive pain, as well as damage to skeletal structures. There are still many uncertainties regarding the pathophysiology of these sequelae. It has been shown that the transient receptor potential channel (TRP) family plays a role in cold allodynia. Botulinum Toxin type A (BTX-A) injections have been reported to be beneficial in vasomotor and neuropathic disturbances secondary to frostbite. Epidural sympathetic block has been used for short-term treatment of frostbite induced chronic pain. Furthermore, amitriptyline, gabapentinoids, and duloxetine may have some benefits. Frostbite arthritis clinically resembles regular osteoarthritis. In children there is a risk of epiphyseal cartilage damage leading to bone deformities. Despite some promising therapeutic concepts, the scarcity of data on frostbite long-term sequelae in the literature indicates the need of more in-depth studies of this pathology in all its aspects.

Several aspects of cognition can be affected after cold exposure, but contradictory results have been reported regarding affected cognitive domains. The aim of the current systematic review was to evaluate the effects of specific cold exposure on cognitive performance in healthy subjects. A systematic search was performed using MEDLINE (through PubMed), EMBASE (Scopus) and PsycINFO databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were healthy subjects exposed to a cold environment (either simulated or not) and cognitive performance related to cold exposure with an experimental design. The literature search identified 18 studies, eight studies investigated the effect of cold air exposure and ten the effect of cold water immersion on cognitive performance of healthy subjects. There were several differences among the studies (environmental temperature reached, time of exposure, timing, and type of cognitive test administration). Cold exposure induced in most of the experimental settings (15 of 18) an impairment of CP even before accidental hypothermia was established. The most investigated and affected cognitive domains were attention and processing speed, executive function, and memory. Gender differences and effects of repeated exposure and possible acclimation on cognitive performance need further studies to be confirmed.

Cognitive function impairment due to high altitude exposure has been reported with some contradictory results regarding the possible selective cognitive domain involvement. We prospectively evaluated in 36 lowlanders, exposed for 3 consecutive days to an altitude of 3,269 m, specific cognitive abilities (attention, processing speed, and decision-making) required to safely explore the mountains, as well as to work at altitude. We simultaneously monitored the physiological parameters. Our study provides evidence of a reduced processing speed in lowlanders when exposed to altitude in the first 24 h. There was a fairly quick recovery since this impairment was no more detectable after 36 h of exposure. There were no clinically relevant effects on decision-making, while psychomotor vigilance was unaffected at altitude except for individuals with poor sleep. Significant changes were seen in physiological parameters (increased heart rate and reduced peripheral oxygen saturation). Our results may have practical implications, suggesting that individuals should practice prudence with higher ascent when performing risky activities in the first 24–36 h, even at altitudes below 3,500 m, due to an impairment of the cognitive performance that could worsen and lead to accidents.

Background: Several neurological conditions might worsen with the exposure to high altitude (HA). The aim of this review was to summarize the available knowledge on the neurological HA illnesses and the risk for people with neurological disorders to attend HA locations. Methods: A search of literature was conducted for several neurological disorders in PubMed and other databases since 1970. The neurological conditions searched were migraine, different cerebrovascular disease, intracranial space occupying mass, multiple sclerosis, peripheral neuropathies, neuromuscular disorders, epileptic seizures, delirium, dementia, and Parkinson’s disease (PD). Results: Attempts were made to classify the risk posed by each condition and to provide recommendations regarding medical evaluation and advice for or against traveling to altitude. Individual cases should be advised after careful examination and risk evaluation performed either in an outpatient mountain medicine service or by a physician with knowledge of HA risks. Preliminary diagnostic methods and anticipation of neurological complications are needed. Conclusions: Our recommendations suggest absolute contraindications to HA exposure for the following neurological conditions: (1) Unstable conditions–such as recent strokes, (2) Diabetic neuropathy, (3) Transient ischemic attack in the last month, (4) Brain tumors, and 5. Neuromuscular disorders with a decrease of forced vital capacity >60%. We consider the following relative contraindications where decision has to be made case by case: (1) Epilepsy based on recurrence of seizure and stabilization with the therapy, (2) PD (± obstructive sleep apnea syndrome-OSAS), (3) Mild Cognitive Impairment (± OSAS), and (4) Patent foramen ovale and migraine have to be considered risk factors for acute mountain sickness.

Objective: To evaluate, under replicable, blinded and standardised conditions, the effect of acute exposure to hypobaric hypoxia (HH) (equivalent to 200 or 3000 or 5000 m above sea level (asl)) on selected cognitive domains and physiological parameters in personnel of helicopter emergency medical service (HEMS). Methods: We conducted a randomized clinical trial using a single-blind crossover design in an environmental chamber ( terraXcube ) to induce HH in 48 HEMS personnel. Participants performed cognitive tests (CT) before the ascent, after 5 min at altitude, and after simulated cardiopulmonary resuscitation (SCR). CT evaluated: sustained attention using the psychomotor vigilance test (PVT) that included measurement of reaction time (RT); risky decision making using the balloon analogue risk task (BART), and attention and speed of processing using the digit symbol substitution test (DSST). CT performance was subjectively rated with a visual analogue scale (VAS). Physiological data were recorded with a physiological monitoring system. Data were analysed using a linear mixed model and correlation analysis. Results: Mean reaction time was significantly slower ( p = 0.002) at HH (5000 m asl), but there were no independent effects of HH on the other parameters of the PVT, BART or DSST. Participants did not detect subjectively the slower RT at altitude since VAS performance results showed a positive correlation with mean RT ( p = 0.009). DSST results significantly improved ( p = 0.001) after SCR. Conclusion: Acute exposure of HEMS personnel to HH induced a slower RT but no changes in any other investigated measures of cognition. The reduced RT was not detected subjectively by the participants. Trial number 3489044136, ClinicalTrials.gov trial registration.