persistent vegetative state (medicine)



Overview

Definition

Vegetative state refers to a state in which the cerebral cortex loses its function while the brain stem retains its function, commonly known as “vegetative state”.

The patient retains the basic reflexes of the brainstem, such as breathing, heartbeat and sleep-wake cycle, and can swallow, cough, open eyes and other movements, but these behaviors are not purposeful and conscious. The patient is unable to perceive the external environment and has no internal needs such as thinking and emotions, and his state of being appears to be vegetative.

The current diagnostic criteria for vegetative state are not uniform. Some diagnostic criteria diagnose those who have been in a vegetative state for more than 1 month as persistent vegetative state; some diagnostic criteria are that the vegetative state lasts for more than 12 months (applicable to traumatic brain injury); however, most scholars believe that a vegetative state lasting for more than 3 months can be diagnosed as persistent vegetative state [1-3].

Persistent vegetative state does not mean that the patient never has the chance to wake up, and some patients can regain consciousness completely or partially after standardized treatment. Therefore, it is meaningful to provide long-term, active and standardized treatment for patients with persistent vegetative state.

Morbidity

Due to differences in diagnostic criteria, there are no authoritative morbidity data for persistent vegetative state in China.

A study in 2013 estimated that the number of patients with persistent vegetative state in China is 70,000-100,000, and the age of onset is concentrated in 20-40 years old, with more men than women [2].

Etiology

The etiologic causes of vegetative state include acute and chronic brain injury and brain lesions.

When these disorders result in loss of cortical function and preservation of brainstem function, the patient presents with a vegetative state that appears to be awake but has no conscious content.

Causes

Various acute and chronic brain injuries, and brain lesions can cause a vegetative state, with some of these patients converting to a persistent vegetative state [2].

Acute brain injury

Craniocerebral trauma

Most common, including cerebral contusion, intracranial hematoma, diffuse axonal injury, and gunshot wounds.

Non-traumatic injury

Hypoxic-ischemic encephalopathy due to various causes, such as cardiac respiratory arrest, drowning, gas (carbon monoxide) poisoning, and severe persistent hypotensive episodes.

Cerebrovascular accidents, such as cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, etc.

Infections and tumors of the central nervous system.

Chronic brain injury

Mainly includes neurodegenerative diseases, metabolic diseases.

Adults: common late-stage Alzheimer’s disease, Pick’s disease, Creutzfeldt-Jakob disease, Huntington’s disease, Parkinson’s disease and other diseases.

Children: common genetic and metabolic diseases, such as ganglioside storage disease, adrenoleukodystrophy, mitochondrial encephalopathy and other diseases; congenital developmental malformations, such as anencephaly, congenital hydrocephalus, cerebellar malformations and so on.

Pathogenesis

Patients in a persistent vegetative state have severe impairment of consciousness.

Conscious activity includes both level of consciousness and content of consciousness. The brainstem is mainly responsible for the level of consciousness, which refers to the waking state that alternates periodically with sleep. The cerebral cortex is responsible for the content of consciousness, including mental and psychological processes such as perception, thinking, memory, attention, intelligence, emotion and volitional activity.

Various sensory signals received by the human body need to pass through specific conduction pathways and the brainstem to reach the cerebral cortex. When there is extensive damage to the cerebral cortex and loss of the ability to produce conscious content, while the brainstem function remains relatively preserved, a state of seeming wakefulness but a complete lack of conscious content will occur.

Symptoms

Patients with persistent vegetative state can autonomously maintain vital signs such as respiration and heartbeat, can perform reflexive behaviors such as sucking, chewing and swallowing, and can show certain meaningless expressions, but are unable to communicate with the outside world and have no ability to think, and this condition lasts for more than 3 months.

Patients often suffer from bed-ridden related complications, such as pressure ulcers, deep vein thrombosis, pulmonary embolism, joint contractures, infections, etc., which can be life-threatening in severe cases.

Main Symptoms

Breathing, heartbeat, but should not be able to call out, unable to receive or express language, unable to communicate with the outside world.

Responds to visual, auditory, tactile, or injurious stimuli, but without sustained, repetitive, and purposeful random movements.

Can breathe spontaneously.

Can perform behaviors such as sucking, chewing, swallowing, and coughing.

Spontaneous eye opening or stimulated eye opening may occur, but the patient remains completely unconscious.

Meaningless crying, laughing, frowning and even yawning may occur.

Incontinence.

Female patients may still experience menstruation.

The above states persist for a long period of time and meet the diagnostic criteria for persistent vegetative state [1-3].

Complications

Patients with persistent vegetative state are bedridden for a long period of time and are therefore prone to the following complications [3-5].

Pressure sores

Manifested as redness, purplish, blisters and rupture of the pressure site.

Deep vein thrombosis and pulmonary embolism

The manifestation of limb swelling, local skin temperature is slightly high, and in severe cases, there may be distal necrosis of the limb.

The dislodgement of thrombus may cause pulmonary embolism, with life-threatening respiratory distress, cyanosis, cough and hemoptysis.

Joint contracture and deformity

Manifested by stiffness of the tissues around the joints, inability to move voluntarily, and deformity.

Infection

Lung, urinary tract and skin infections may occur due to patient’s aspiration, weak coughing, poor urination and inadequate cleaning.

Symptoms such as fever, cough, sputum, cloudy urine, rash and pustules are manifested.

Seek medical attention

Patients with persistent vegetative state can go to the Department of Neurology, Neurosurgery, and Rehabilitation Medicine.

Doctors will ask family members about the patient’s main symptoms, the onset of the disease, past medical history, as well as relevant examinations and treatments.

Department of Neurology

Neurology

Neurology is recommended for patients with prolonged coma and inability to communicate with the outside world.

Neurosurgery is recommended for patients with traumatic brain injury or brain tumors. Some neurosurgery centers have comprehensive treatment measures such as neuromodulation to promote awakening.

Department of Rehabilitation Medicine

Patients in a persistent vegetative state who are stabilized and undergoing rehabilitation should consult the Department of Rehabilitation Medicine.

Preparation for medical treatment

Preparation for medical consultation: registration, preparation of documents, and frequently asked questions

Tips for medical treatment

Family members should try to record the symptoms and changes in the patient’s condition so as to give more reference to the doctor.

Preparation Checklist

Symptom list

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

When and under what circumstances did the onset of symptoms occur? How long has it lasted?

Are there reflexes such as sucking, chewing, swallowing?

Does it respond to stimuli such as speech, pain, etc.?

Does the condition fluctuate?

List of medical history

Was there trauma, drowning, choking prior to the onset of illness?

Were there any symptoms such as fever, headache, vomiting, seizures, palpitations, dyspnea, etc. before the onset of the illness?

What was the patient’s previous health status? This includes chronic diseases involving the brain, heart, liver, lungs, kidneys, and other organs.

What are the patient’s medications, have they taken sedative sleeping pills and antipsychotic drugs?

Has the patient been exposed to toxic substances such as carbon monoxide and cyanide?

Checklist

Examination results in the last six months, which can be brought to the doctor’s office

Cranial CT, cranial magnetic resonance imaging, EEG, evoked potentials, etc.

Medication list

Medication use in the last 3 months, if available in boxes or packages, you may bring them to the doctor’s office

Amantadine, baclofen, levodopa, modafinil, bromocriptine, etc.

Diagnosis

The diagnosis of persistent vegetative state is mainly based on clinical manifestations, which need to strictly meet the diagnostic criteria. Auxiliary examinations, such as imaging and neurophysiological examinations, play a role in assisting diagnosis, evaluating the efficacy of treatment and prognosis judgment [5-8].

The persistent vegetative state should be differentiated from brain death, atresia syndrome and minimal consciousness.

Diagnostic basis

Medical history

Patients may have a history of acute or chronic brain injury, including traumatic brain disease, cerebrovascular disease, neurodegenerative disease, metabolic disease, and developmental malformation of the brain.

Clinical manifestations

Symptoms

Persistent manifestations include inability to communicate with the outside world, response to stimuli, and ability to perform behaviors such as sucking, chewing, swallowing, coughing, etc., but no awareness of oneself and the external environment.

Physical signs

Mainly include temperature, respiration, blood pressure, pulse and other general conditions. In addition to a comprehensive and systematic physical examination, focus on neurological examination.

Check the head: whether there are traumas, fractures, signs of surgery.

Check the eyes: whether the pupils are dilated or narrowed, how is the reflex to light; whether the position of the eyeball is abnormal; whether the corneal reflex exists; whether there is optic papillary edema, retinal hemorrhage or exudate at the bottom of the eye.

Neurologic reflexes: mainly check whether deep reflexes and superficial reflexes are present, whether the right and left sides are symmetrical; whether pathological reflexes are present.

Laboratory tests

Blood routine: It is valuable for the diagnosis of anemia and infection.

Blood biochemical examination: blood glucose is an important indicator for confirming the diagnosis of diabetic coma; blood ammonia and liver function test can help the diagnosis of hepatic encephalopathy; renal function test is an indicator for determining renal encephalopathy; electrolyte test can be used to diagnose electrolyte disorders.

Thyroid function test: helps to confirm the diagnosis of thyroid encephalopathy.

Blood gas analysis: used to diagnose consciousness disorder caused by acid-base metabolism imbalance.

Toxic substance testing: special testing for various toxic substances such as organophosphorus pesticides and alcohol can assist in determining the cause of poisoning.

Cerebrospinal fluid examination

Detecting the composition of cerebrospinal fluid by lumbar puncture is necessary for the diagnosis of intracranial infection and atypical subarachnoid hemorrhage.

It can also detect intracranial pressure, which is important for the diagnosis of abnormal intracranial pressure, hydrocephalus and other diseases.

Precautions: Keep the local skin clean and dry after the examination to prevent infection at the puncture site.

Imaging

Cranial magnetic resonance imaging (MRI) and CT examination

It can clearly show the structure of the intracranium, and can clearly show intracranial hemorrhage, ischemia, infarction, demyelination, edema, tumors, abscesses, parasites and other lesions, which is very important for the diagnosis of the cause of the disease.

Precautions: metal objects should be removed from the body during the examination, such as metal jewelry, clothing with metal button fittings; people with dentures, cardiac stents and other metal implants in the body should consult the doctor whether MRI examination can be performed.

Neurophysiological examination

Electroencephalogram (EEG)

The patient’s condition can be assessed by observing the amplitude and rhythm of the EEG waves and their responsiveness to external conditioned stimuli (pain, sound, light, etc.).

The sleep-wake cycle can be observed on the EEG.

Wake EEG: shows focal or diffuse sustained theta or delta slow waves with intermittent delta rhythms; decreased amplitude, sometimes down to the isoelectric line; epileptiform discharges such as focal spike waves may also be present.

Sleep EEG: diffuse low-voltage slow waves.

Evoked potentials

Includes visual evoked, auditory evoked and somatosensory evoked potentials.

Helpful in assessing the integrity of the patient’s consciousness-related conduction pathways.

Diagnostic Criteria

The clinical diagnostic criteria for persistent vegetative state in China are mainly based on the Diagnostic Criteria and Clinical Efficacy Rating Scale for Persistent Vegetative State (China Nanjing Standard 2011 Revision) [3].

Diagnostic criteria for persistent vegetative state

Loss of cognitive function, unconscious activity, inability to carry out instructions.

The ability to open the eyes automatically or under stimulation.

Sleep-wake cycle.

Purposeless eye-tracking movements.

Inability to understand and express language.

Maintains voluntary respiration and blood pressure.

Subthalamic and brainstem functions are largely preserved.

Diagnosis of persistent vegetative state

A persistent vegetative state is diagnosed if the vegetative state is more than 3 months old.

Differential diagnosis

The persistent vegetative state needs to be differentiated from brain death, prolonged atresia syndrome, and minimal consciousness [6-9].

Brain death

Brain death is an irreversible loss of total brain function in which the patient is unable to autonomously maintain basic life functions.

The patient has no voluntary respiration, blood pressure, or heart rate and must be maintained with the aid of an artificial respirator, and all brain reflexes are absent.

Atresia syndrome

Loss of all motor functions due to bilateral lesions at the base of the pontine bridges and damage to the corticobulbar and corticospinal tracts on the ventral side of the brainstem.

The patient is conscious, has no impairment in language comprehension but is unable to communicate, cannot turn his eyes to either side, is quadriplegic, and can only establish contact with his surroundings by blinking or vertical eye movements schematically.

Minimal Consciousness

The patient is in a state between wakefulness and coma, retaining some degree of awareness and attention to the outside world and to himself/herself, and this degree is small but clear.

For example, if an object is moved in front of the patient’s eyes while the patient’s eyes are open, the patient’s eyeballs may follow the movement. Occasionally, the patient can follow instructions to perform simple movements such as hooking a finger or opening or closing the eyes.

Treatment

Aims of treatment: to stabilize life, improve the state of consciousness, and prevent or treat complications.

Treatment principle: To promote recovery through a combination of drugs, rehabilitation, hyperbaric oxygen and neuromodulation.

Supportive treatment

Maintain the patient’s respiration and blood circulation stable, open the airway, ventilator-assisted respiration, and maintain blood pressure, etc. as required by the condition.

Maintain electrolyte and acid-base balance, and maintain the balance of in and out.

Prevent lower extremity venous thrombosis, pressure ulcers, stress ulcers, joint contractures and other complications.

Depending on the nutritional status of the patient, give enteral nutritional support with sufficient calories to avoid malnutrition.

Drug treatment

Wakefulness promotion therapy

There is insufficient evidence to support the use of drugs to improve the level of consciousness in patients with persistent vegetative state.

Some drugs that help to improve cognition, cerebral blood circulation, and nutrient nerves, as well as Chinese medicines that open the mind and wake up the brain, can be tried, but their efficacy needs to be further confirmed [8-10].

Common types of drugs include ganglioside, cytarabine, cerebral protein hydrolysate, memantine, amantadine, bromocriptine, naloxone, Angong Niu Huang Wan, and Wake-up Brain Jing.

Prevention and treatment of complications

Anti-spasmodic drugs: For patients who develop severe limb spasms, anti-spasmodic drugs such as baclofen and tizanidine can be used for treatment.

Anti-infective drugs: for patients with lung infection and urinary tract infection, ceftriaxone, cefotaxime, penicillin, ampicillin, chloramphenicol, vancomycin and other treatments can be selected according to the drug sensitivity test.

Venous thrombosis: for patients who develop lower limb venous thrombosis, they can be treated by drugs such as rivaroxaban and low molecular heparin.

Hyperbaric oxygen therapy

Hyperbaric oxygen therapy is to let patients inhale high pressure and high concentration of oxygen in a closed pressurized device, which can improve the oxygen tension of brain tissue, promote the excitability of the brainstem reticularis superior system, and promote the opening of collateral circulation.

It helps the patient’s nerve repair and improve cognition.

Doctors will choose different treatment pressures, oxygen inhalation methods and courses according to patients’ specific conditions.

Neuromodulation Therapy

Neuromodulation therapy is a therapeutic method of targeting electromagnetic stimulation or chemical stimulants delivered to specific parts of the nervous system through specific equipment in order to change nerve activity.

In recent years there has been great progress in the research of treatment mechanism and enhancement of therapeutic effect, which helps to study the repair mechanism of brain network and helps to promote the recovery of patients’ consciousness [1-3].

Non-invasive neuromodulation therapy

It mainly includes repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and median nerve electrical stimulation.

Patients should be prioritized to receive conventional rehabilitation to promote awakening treatment on the basis of additional neuromodulation therapy.

Invasive Neuromodulation Therapy

The main treatment modalities include deep brain electrical stimulation, spinal cord electrical stimulation, cortical electrical stimulation, and vagus nerve electrical stimulation [10-11].

Neuromodulation surgery is generally used as a complementary means to conventional treatment.

Rehabilitation therapy

Rehabilitation therapy is crucial in the long-term treatment of patients, helping to promote the recovery of consciousness, maintain the functional status of the patient’s organism, and reduce the occurrence of complications [3-6].

Rehabilitation of motor dysfunction

Limb function training

Rehabilitation therapists will perform massage and passive limb activities on patients.

It prevents disuse atrophy of muscles, bones and skin in patients with persistent vegetative state, improves muscle tone and also helps to maintain joint mobility.

Standing training

When the disease is stable, the patient can be helped by family members, passive sitting training or fixed in the starting bed to different angles of standing training, the angle gradually increased.

Rehabilitation of swallowing function

Swallowing function training can prevent disuse atrophy of swallowing organs, reduce the occurrence of aspiration pneumonia and malnutrition.

Sensory stimulation of the head and neck, oral cavity and pharyngeal skin and mucosa, and passive movement and relaxation of the relevant muscles are mainly carried out, and dysphagia therapeutic instrument can also be used for treatment.

Stimulation therapy

According to the patient’s pre-morbid hobbies and habits, multi-sensory stimulation such as sound, odor, touch, taste, etc., which the patient likes or hates, is given to promote the connection between the patient’s cerebral cortex and subcortex.

Music therapy

Music has a broader activation effect on the cerebral cortex, and playing the patient’s favorite music will help him/her recover consciousness.

Traditional Chinese Medicine (TCM)

Acupuncture and moxibustion can be used under the guidance of a doctor to identify and treat the symptoms. Acupuncture has the effect of waking up the brain and improving blood circulation in the brain, such as stimulating acupoints such as Baihui, Si Shencong and Shenting.

Prognosis

The overall prognosis for persistent vegetative state is poor, with a low chance of regaining consciousness.

Children, traumatic brain injury and those who have entered the vegetative state for a shorter period of time have a higher chance of recovery.

Cure

Patients in a persistent vegetative state have a chance of awakening, but recovery is more difficult.

The likelihood of recovery of consciousness in patients with persistent vegetative state is related to age, cause and duration of the disease.

Age: Children usually have a better prognosis than adults.

Etiology: Trauma patients have a better prognosis than non-trauma patients.

Duration: The longer the duration of the persistent vegetative state, the less likely recovery is.

Hazards.

Persistent vegetative state often requires a long treatment period, many complications, high treatment cost, and requires long-term accompanying by family members, which brings a huge burden to the family and the society.

Daily care

Daily care for patients with persistent vegetative state includes regular expectoration, keeping clean, wearing soft clothes, turning regularly and skin cleaning. In addition, family members need to adjust their mindset and actively seek support.

Avoiding head trauma, active treatment of brain diseases and regular medical check-ups can help reduce the risk of the disease.

Daily management

Help the patient to pat the back and expel sputum at regular intervals to keep the mouth and airways clean and clear.

Pillow towels, bed sheets, duvet covers and diapers should be kept clean and dry and changed regularly.

Wear soft, loose, easy to put on and take off cotton clothes.

Help the patient to turn over at least every 2 hours, and foam wedges and pillows may be used for positional placement.

Cleanse the skin daily with lukewarm water, do not use harsh cleansers, pat gently and avoid rubbing.

Patients in a persistent vegetative state are usually seriously ill, have a long course of illness, and spend a lot of money on treatment. Family members should try to adjust their own state of mind while caring for the patient, and obtain support and help from other relatives, friends and social forces as much as possible.

Disease monitoring

If symptoms worsen during treatment or new symptoms appear, consult a doctor promptly.

Observe whether there are any changes in the patient’s language expression and body movement.

When helping the patient to turn over, family members should pay attention to observing his/her skin condition, such as whether there are any skin erythema, ulcers, blisters, etc. on the protruding parts of the bones.

Prevention

There is no method that can effectively prevent persistent vegetative state, but the following measures can be taken to reduce the risk of the disease [1-3].

Avoid head trauma.

Actively treat Alzheimer’s disease, multiple cerebral infarction, Parkinson’s disease, ganglioside storage disease, adrenoleukodystrophy and other diseases.

Regular physical examination, found abnormalities should be timely consultation and treatment.