Clinical manifestations

Presentation and course

The clinical symptoms of decompression sickness develop rapidly and appear during or immediately after the ascent. They usually occur within three hours of surfacing, but may, in some cases, take as long as 24 to 36 hours to manifest. They are mainly seen in persons who have experienced pressures greater than 2 atmospheres absolute. The clinical manifestations can be divided into type 1 and type 2. Type 1 decompression sickness, characterized by limb and joint pain (bends), is the mildest form. Type 2 is constituted by systemic symptoms or signs. Neurologic (hits), pulmonary (the chokes), and cardiac manifestations may occur.

Cutis marmorata, a cutaneous manifestation of decompression sickness with rash and pruritus, may precede illness involving the central nervous system (24). Occasionally, cutis marmorata is accompanied by other manifestations such as visual distortions, vertigo, or mild cerebral dysfunction. According to one hypothesis, the pathogenesis of these neurologic manifestations is embolization of the brain stem with gas bubbles, resulting in disturbance of the regulation of skin blood vessel dilation and constriction by the autonomic nervous system (15). Cutis marmorata skin should no longer be considered a mild, innocuous manifestation but rather a serious, neurologic form of decompression sickness and should be treated accordingly.

This review concerns only the neurologic manifestations of decompression sickness due to disturbances of the cerebral hemispheres and the spinal cord.

The most common neurologic manifestation of decompression sickness is caused by involvement of the spinal cord. It has been called "hits" by divers. Symptoms of medullar involvement usually appear early, most often within three minutes of surfacing. They are characterized by weakness of the legs with walking difficulties, paresthesias and numbness of the legs, and bladder dysfunction. The severity of the "hits" varies from bilateral numbness only to paraplegia or even tetraplegia. In most cases, the level of the lesion is around the sixth to eighth thoracic segment, which is the part most susceptible to ischemia. The level may, however, vary from C4 and down to L1.

Spinal cord decompression sickness presenting as complete Brown-Sequard syndrome with MRI signal abnormalities corresponding to an infarction in the posterior spinal artery territory has been reported to improve considerably following hyperbaric oxygen therapy (31). Six further cases of this syndrome with decompression sickness have been described in the literature, and the diagnosis is mainly based on clinical findings rather than MRI (42).

The severity of the medullar lesion varies considerably. Fortunately, in many cases, the symptoms gradually disappear, leaving the patient asymptomatic, although slight reflex abnormalities may persist as evidence of earlier damage. Others may develop paralysis of both legs. Although no evidence of neurologic damage is found in some cases who recover from decompression sickness, medullary demyelination may occur in persons who have suffered from decompression sickness previously and are asymptomatic.

Other neurologic syndromes may also occur. Some divers develop evidence of acute cerebral hemisphere dysfunction, such as hemiparesis, aphasia, or hemianopsia. Memory loss, convulsions, and even coma can occur.

Anton syndrome (visual anosognosia due to cortical blindness) has been reported as a manifestation of decompression illness in a scuba diver with patent foramen ovale (01). This resolved after treatment with repeated recompression.

Benign paroxysmal positional vertigo may be due to semicircular canal nitrogen bubble formation. Inner ear decompression sickness has been reported to manifest as vertigo and additional hearing loss (27).

Deep-diving. Diving conducted at depths of more than 50 m of seawater is designated deep-diving. Breathing air is not possible at those depths due to the toxic effect of the high partial pressure of nitrogen. Therefore, a mixture of helium and oxygen (heliox) is used as a breathing gas. Diving with heliox to depths greater than 150 m produces signs and symptoms of the high-pressure neurologic syndrome. The syndrome includes tremor in the upper extremities, impaired memory, dizziness, nausea, and in severe cases, myoclonic jerks and even unconsciousness. High pressure neurologic syndrome is accompanied by EEG changes with an increased amount of 2- to 7-Hz slow activity (18).

Deep-diving requires a prolonged period of compression and a decompression period extended over several days. Even after uncomplicated deep dives, transitory focal neurologic changes have been reported. It is not known whether these represent an unmasking of prior decompression sickness-caused lesions or are evidence of new lesions.

Prognosis and complications

Long-term follow-up of 30 divers treated with hyperbaric oxygen for decompression sickness in 2009 and 2010 revealed that a quarter had long-term residual symptoms (Svendsen et al 2016). In decompression sickness with spinal cord involvement, the improvement in MRI findings is not associated with improved clinical status, suggesting that delayed damage subsequent to initial spinal cord lesions may affect the clinical course (44). MRI could be helpful in predicting clinical outcome of decompression sickness with spinal cord involvement. The presence of lesions causing medullary compression along with back pain after surfacing indicates increased likelihood of severe myelopathy with incomplete recovery (12). Initial motor impairment, further aggravation during transfer to the hyperbaric facility, and development of sphincter dysfunction are indicators of poor prognosis, regardless of the treatment (30).

A population-based study has shown that patients who suffer from decompression sickness have a 3.8-fold risk of developing psychiatric disorders, and a 5.7-fold risk of developing sleep disorders (41).

Dysbaric osteonecrosis (aseptic bone necrosis) can occur after repeated hyperbaric exposures. It is an occupational hazard for commercial and navy divers but is also seen in sport divers. It is most common in the head of the femur, and the symptoms may appear many months after decompression (19).

According to a study on military divers with decompression sickness, the main independent risk factor associated with a poor outcome is the severity of neurologic manifestations at onset, and recovery is not significantly improved by prompt administration of recompression treatment (04).

A prospective study on divers with neurologic decompression sickness at a hyperbaric facility showed that those who presented more than 17 hours after surfacing were likely to have more intense symptoms than those who presented earlier for treatment (33). Neither had more hyperbaric oxygen treatment or worse outcome related to the delay, but the amount of oxygen that had to be administered in total during the whole course of treatment was lower in cases that responded better.

Therapeutic response in patients with inner ear decompression sickness remains poor, and incomplete recovery was found in 68% of the patients that were followed (14). Time to recompression did not seem to influence the clinical outcome in these cases. Treatment with 100% oxygen followed by recompression in a hyperbaric chamber will prevent long-term effects in most cases, but permanent injury is still possible.

Clinical vignette

A 56-year-old man with extensive experience in scuba diving was diving to a ship wreck at a depth of 60 meters, when he was trapped in a tangle of steel structures and had to work heavily to get loose. During this exercise, he was short of oxygen and had to ascend quicker than allowed with an uncontrolled ascent from 15 meters. He received oxygen onshore, dived again, but noted pain in the stomach, ascended, and was brought to hospital. It took approximately two hours until he received hyperbaric oxygen treatment. He was able to walk into the pressure chamber but became increasingly weak in both legs and developed a transversal spinal cord syndrome with paralysis of both legs and complete analgesia below Th11 level.

Biological basis

Etiology and pathogenesis

Etiology. When a diver breathes air under increased pressure, the nitrogen concentration in the tissues will increase. As the diver returns to the surface, the gas tension in the tissue may exceed the ambient pressure. This results in the liberation of free gas from the tissues. Gas bubbles are formed in the tissues and thereafter in the venous circulation. Aviators and astronauts are at risk of decompression sickness when the ambient pressure reductions exceed a critical threshold. Cases of decompression sickness have been reported in an Air Force training facility during reduction of pressure in a chamber to simulate altitudes between 25,000 and 35,000 feet (7,500 and 10,668 meters), and some of these had neurologic manifestations (05). According to a retrospective study, the number of altitude decompression sickness incidents with central nervous system manifestations in U-2 pilots of the U.S. Air Force increased during 2002-2009 as compared to the preceding 47 years (22). One of the probable causes was longer, more frequent high-altitude exposure. A review of decompression sickness cases associated with the NASA altitude physiological training program at Johnson Space Center indicated a prevalence rate of 1.16 cases per 1000 exposures with significant heterogeneity across studies (08). Denitrogenation time, exposure pressure, and exposure time were associated with probability of decompression sickness in the meta-regression model.

Decompression illness is one of the most likely adverse effects in pilots of supersonic, high-altitude aircraft, and they may require hyperbaric oxygen treatment before resuming active duty (35). An F/A-18D pilot, who presented with neurologic symptoms following loss of cabin pressure at altitude, required multiple hyperbaric oxygen treatments over several days due to recurrence of symptoms on resumption of flying.

Extravascular bubbles in the white matter of the spinal cord may cause axon disruption and pressure-induced ischemia (19). If a cardiac right-to-left shunt is present, there is an additional risk for the occurrence of diving-related cerebral decompression illness.

Predisposing factors. An experimental study in rats has shown that pre-treatment with sildenafil, a phosphodiesterase-5 blocker used for treatment of erectile dysfunction, promotes the onset and severity of neurologic decompression sickness (03). This effect could be related to vasodilation with increased cerebral blood flow.

Shortness of breath after heavy exercise during the dive, dehydration, and dive depths exceeding 30 msw are relative risk factors for decompression sickness (39). Persons with a patent foramen ovale and a cardiac right-to-left shunt have an increased risk of developing neurologic complications even after recreational scuba diving in shallow water. Whether cigarette smoking increases the risk of developing decompression sickness has been debated.

Yo-yo diving, defined as a series of short-duration dives alternating with similar periods of time on the surface, was previously considered to reduce bubble formation and risk of decompression illness based on studies in rats. Now there is a concern about the increased risk of neurologic decompression sickness in yo-yo divers. This has been confirmed by detection of gas bubbles in the left ventricle with neuronal cell injury in the spinal cord after the 4-peep dives in a pig model (34).

Hypovolemia while diving is a predisposing factor for decompression illness. A patient who presented with neurologic symptoms and hypovolemic shock after two risky dives was found to have multiple cerebral and pulmonary thromboembolisms on MRI (26). Early hyperbaric oxygen therapy reduced the neurologic deficits, and cardiopulmonary as well as renal function normalized after volume expansion.

Pathophysiology. Decompression sickness is caused by a rapid reduction of the environmental pressure that is sufficient to cause formation of bubbles from inert gases in the body tissue. Gas bubbles are present in venous blood after ascent from water depths as shallow as three meters. Free gas does not invariably lead to decompression sickness because the lungs represent a competent filter. Most bubbles will be filtered out by the pulmonary capillaries and do not enter the arterial circulation. However, divers with patent foramen ovale are more liable to develop decompression sickness than divers without patent foramen. Such shunts are present in about 10% to 30% of the general population. In another study, shunting was not associated with the increased incidence of cervical spinal cord decompression sickness, whereas a significant relationship between large right-to-left shunts due to foramen ovale and spinal cord decompression sickness with thoracolumbar involvement was demonstrated (11).

The symptoms of decompression sickness resemble those of thromboembolic cerebrovascular sickness, except that decompression sickness more often affects the spinal cord. Due to retrograde migration of bubbles from the vena cava, bubbles may accumulate in the epidural vertebral venous plexus. This is a valveless system that facilitates further growth of bubbles leading to venous stasis and eventually to spinal infarction. In those with patent foramen ovale, bubbles may block the anterior spinal artery, which may lead to weakness in both lower extremities (43).

One study has reported a high prevalence of patent foramen ovale in divers suffering from inner ear decompression sickness manifested by vestibular and cochlear symptoms following dives while breathing helium-based mixtures (17). One explanation is that the inner ear has a slower gas washout than the brain, which makes it more vulnerable to deleterious effects of any bubbles that cross a persistent foramen ovale.

Pathology. In a few reported autopsies of unaffected divers, degeneration and vasculopathy have been found in the brains and spinal cords resembling the abnormalities found after decompression illness. Small bubbles behaving like emboli may not cause infarction but disturb the blood-brain barrier, inducing a “perivenous syndrome” with areas of demyelination resembling those in multiple sclerosis (20).

In a study, neurologic decompression sickness in high-altitude pilots was associated with a significant increase in MRI hyperintense white matter lesion volume, especially in the insula, and this was attributed to hypobaric exposure rather than hypoxia as all pilots were maintained on 100% oxygen throughout the flight (32). Prediction of the probability of developing hypobaric decompression sickness on exposure of pilots to extreme altitudes, based on analysis of the U.S. Air Force Research Laboratory Altitude Decompression Sickness Research Database, shows that decompression dose, male gender, and high exercise intensity are important contributors (07). The modeled decompression dose is increased by higher tissue ratio or bubble growth index.

Epidemiology

Decompression sickness is more common among sport divers than among professional divers. There are about three million certified sport divers in the United States and about one million in Europe, but no data are available on how often they develop decompression sickness. Incidental MRI changes have been observed in scuba divers without any clinical manifestations of decompression sickness. One survey has shown that vestibular symptoms are more prevalent in retired divers than in controls: 28% have dizziness, 14% have vertigo, and 25% have unsteady gait (16). The high exposure to decompression sickness is probably an important factor in the etiology of these symptoms. A retrospective study of the incidence and characteristics of decompression sickness in Denmark for the period of 1999 to 2013 revealed 205 cases, which is a more than 10-fold increase since the period 1966 to 1980 (Svendsen et al 2016). The most frequent symptoms in this series were paresthesia (50%), pain (42%), and vertigo (40%).

Prevention

Decompression sickness can be prevented when care is taken during ascent to normal pressure. Both the navy and commercial diving companies have detailed decompression tables. To prevent the excess formation of bubbles leading to decompression sickness, divers should limit their ascent rate to about 10 meters (33 ft) per minute as recommended by popular decompression models.

Pre-dive conditioning measures such as endurance exercise in a warm environment, oral hydration, and normobaric oxygen breathing can reduce the risk of decompression sickness in scuba divers by up-regulation of cytoprotective proteins and reduction of bubbles formation (10). In a rat model of decompression sickness, preconditioning by inhalation of a mixture of 79% helium and 21% oxygen for five minutes interspersed with five minutes of air breathing resulted in a significantly decreased incidence of decompression sickness with a decrease in platelet count, abnormal somatosensory evoked potential waves, and histological spinal lesions (45). Because helium-oxygen mixtures are already being used in divers, human application of this preventive measure is feasible.

In divers with a history of major neurologic decompression symptoms without evident cause, transesophageal echocardiography must be performed to exclude patent foramen ovale. Whether all divers should be screened for patent foramen ovale is an ongoing discussion. If a cardiac right-to-left shunt is present, divers with a history of decompression sickness should stop diving. Different decompression tables for such divers need to be developed.

Differential diagnosis

The symptoms of decompression sickness resemble those of thromboembolic cerebrovascular disease, but decompression sickness more commonly affects the spinal cord. However, the diagnosis of decompression sickness is not difficult when the symptoms appear during diving operations or rapid decompression. It should be remembered, however, that symptoms occurring during diving are not necessarily related to variations in the environmental pressure. Cases of factitious decompression sickness have been reported as some persons feign the symptoms in order to receive care and attention despite the lack of an underlying illness (25).

Another condition to consider in differential diagnosis is high-pressure neurologic syndrome, which can occur in deep-sea diving beyond a depth of 100 meters. This syndrome is characterized by tremor, convulsions, cognitive disturbances, and characteristic EEG changes such as frontal midline theta activity.

Unusual presentation of a case with mixed signs and symptoms of cervical myelopathy and type 2 neurologic decompression sickness presented a diagnostic dilemma that required the use cervical spine MRI, which revealed the presence of tiny hypointensities and edema within the spinal cord corresponding to the clinical findings (29). The diagnosis of decompression sickness was confirmed by recovery with residual neurologic deficits following hyperbaric oxygen therapy.

Diagnostic workup

The diagnosis of decompression sickness is based on history and clinical features. If a person has been diving to less than 10 m or has been exposed to pressures lower than 2 atmospheres absolute, it is unlikely that the symptoms are caused by decompression sickness.

A neurologic examination should be performed in cases with type 2 decompression sickness.

Routine blood examination should include serum albumin measurement. Hypoalbuminemia at initial presentation due to capillary leak, although rare, accurately predicts the neurologic manifestations of decompression sickness in scuba divers (13). However, serum albumin as a biomarker of type 2 decompression syndrome has not been validated yet for prognosis or as a guide to albumin infusion as treatment.

When spinal symptoms dominate, CSF examination and MRI of the spinal cord should be performed, which may reveal demyelination. MRI may also show dorsal white matter lesions typical of venous infarction. EEG and cerebral MRI are indicated with cerebral symptomatology. Functional MRI has revealed acute subcortical lesions and hyperintense white matter lesions in U-2 pilots with neurologic decompression sickness, although clinical correlations have not been established (23).

Ultrasonic monitoring of bubbles during decompression has not been shown to be helpful in prediction of neurologic sequelae of decompression sickness. Detection of marrow bubbles with MRI after musculoskeletal decompression sickness, however, can be predictive of subsequent dysbaric osteonecrosis (Stéphant et al 2008). Bone necrosis due to decompression can be detected on x-rays.

Retinal fluorescein angiography has demonstrated vasculopathy in divers with no history of decompression sickness.

There is increasing evidence from studies using different techniques for examination that divers with a history of decompression sickness have evidence of subclinical damage. Hexamethyl propylene amine oxime single-photon computed tomography has shown that diving may lead to subclinical nervous tissue damage. Neuropsychological testing can detect cognitive impairment also in the absence of neurologic signs.

Management

Recompression and hyperbaric oxygen. The treatment of decompression sickness is, first and foremost, recompression. The aim of the treatment is to reduce bubble growth, promote the clearance of gas, and counteract ischemia and hypoxia in the affected tissues. Therefore, it is extremely important that the treatment is initiated before the changes have become irreversible. In a retrospective study hyperbaric oxygen therapy, administered within 24 hours of onset of type 1 decompression syndrome, was associated with rapid relief of symptoms after a single treatment (28). In this study, seasoned military divers showed a faster response after recompression with fewer residual symptoms in comparison with commercial and recreational divers.

The treatment is performed in a hyperbaric chamber following various hyperbaric oxygen protocols (19). The role of oxygen treatment is well documented and is employed by most physicians who treat divers. The use of helium and oxygen as an alternative to air has been put forward, and the results indicate that helium-oxygen recompression therapy may give better results than air-oxygen tables in the treatment of type 2 decompression sickness. Oxygen provided under hyperbaric conditions has been shown to be effective in the restoration and preservation of neurologic function in the “perivenous' syndrome” associated with decompression sickness in both animal and clinical studies (20).

A patient with high-altitude decompression sickness made complete recovery following treatment with hyperbaric oxygen, recompression, and extracorporeal oxygenation (36).

Supporting drug therapy. Not all divers with spinal cord decompression sickness improve with recompression. If paresis is severe and develops immediately after surfacing, this may indicate that the lesion has been complicated with a hemorrhage into the medulla. In such situations, recompression treatment should be supported by conventional drug therapy for spinal cord injury. The use of high-dose steroids in decompression sickness is controversial. Aspirin is used frequently for treatment of decompression sickness, but its efficacy has not been established by controlled studies. Fluoxetine, an antidepressant with antiinflammatory properties, decreases the incidence of experimental decompression sickness in mice and improves motor recovery by limiting the inflammation process as evidenced by the reduction of circulating IL-6, a biomarker of systemic inflammation (02). Use of statins, which are approved for treatment of hypercholesterolemia, may be considered. Statin-mediated lipid reduction may reduce bubble generation via alterations in plasma rheology and surface tension. Use of nitric oxide-donor medications such as isosorbide mononitrate and nitroglycerin should be investigated for the treatment of decompression sickness. Intravenous perfluorocarbon emulsions, which are halogen substituted carbon non-polar oils with resultant enhanced oxygen solubility, have been investigated as oxygen therapeutics as well for the enhancement of other gas movements within the body. Use of intravenous perfluorocarbon has been investigated for the treatment of decompression sickness. Results of an animal experimental study indicate that improved oxygenation partly explains therapeutic effects of perfluorocarbons in decompression syndrome (37). One concern is that perfluorocarbon may further decrease platelet count, which is already low in decompression syndrome because of platelet activation. In a swine model of decompression sickness, treatment with Oxycyte, a perfluorocarbon, did not impact platelet numbers and whole blood clotting by thromboelastometry, or result in bleeding (09). This topic requires further investigation.

Special considerations

Pregnancy

Information on pregnancy outcomes in humans is limited, with inconsistent data on diving and birth defects, spontaneous abortions, and stillbirth. The safest choice during pregnancy is to avoid diving (06). The fetus is not protected from decompression problems and is at risk of congenital malformations and gas embolism. However, if a pregnant woman develops decompression sickness, hyperbaric oxygen treatment can be considered. Such treatments have been carried out safely in pregnant women for other indications and are considered safe for the fetus in later months of pregnancy, but experimental evidence raises the possibility of congenital malformations in early stages of pregnancy.

Anesthesia

If surgical treatment is indicated for patients involved in a diving accident, anesthetic care can be delivered at increased pressure. The clinical performance of the personnel may, however, be influenced by the rapid compression that will be necessary. Inert gas narcosis can be observed at pressures of 2 absolute atmospheric pressure and greater (19).

There are no special anesthetic problems related to neurologic complications in decompression sickness.