Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
There is limited evidence that the hypnotic drug zolpidem has an effect. The results of the few scientific studies that have been published so far on the effectiveness of zolpidem have been contradictory.
Currently no treatment for vegetative state exists that would satisfy the efficacy criteria of evidence-based medicine. Several methods have been proposed which can roughly be subdivided into four categories: pharmacological methods, surgery, physical therapy, and various stimulation techniques. Pharmacological therapy mainly uses activating substances such as tricyclic antidepressants or methylphenidate. Mixed results have been reported using dopaminergic drugs such as amantadine and bromocriptine and stimulants such as dextroamphetamine. Surgical methods such as deep brain stimulation are used less frequently due to the invasiveness of the procedures. Stimulation techniques include sensory stimulation, sensory regulation, music and musicokinetic therapy, social-tactile interaction, and cortical stimulation.
The treatment hospitals use on comatose patients depends on both the severity and cause of the comatose state. Although the best treatment for comatose patients remains unknown, hospitals usually place comatose patients in an Intensive Care Unit (ICU) immediately. Attention must first be directed to maintaining the patient's respiration and circulation, using intubation and ventilation, administration of intravenous fluids or blood and other supportive care as needed. Once a patient is stable and no longer in immediate danger, the medical staff may concentrate on maintaining the health of patient’s physical state. The concentration is directed to preventing infections such as pneumonias, bedsores (decubitus ulcers), and providing balanced nutrition. Infections may appear from the patient not being able to move around, and being confined to the bed. The nursing staff moves the patient every 2–3 hours from side to side and depending on the state of consciousness sometimes to a chair. The goal is to move the patient as much as possible to try to avoid bedsores, atelectasis and pneumonia. Pneumonia can occur from the person’s inability to swallow leading to aspiration, lack of gag reflex or from feeding tube, (aspiration pneumonia). Physical therapy may also be used to prevent contractures and orthopedic deformities that would limit recovery for those patients who awaken from coma.
A person in a coma may become restless, or seize and need special care to prevent them from hurting themselves. Medicine may be given to calm such individuals. Patients who are restless may also try to pull on tubes or dressings so soft cloth wrist restraints may be put on. Side rails on the bed should be kept up to prevent the patient from falling.
Methods to wake comatose patients include reversing the cause of the coma (i.e., glucose shock if low sugar), giving medication to stop brain swelling, or inducing hypothermia. Inducing hypothermia on comatose patients provides one of the main treatments for patients after suffering from cardiac arrest. In this treatment, medical personnel expose patients to “external or intravascular cooling” at 32-34 °C for 24 hours; this treatment cools patients down about 2-3 °C less than normal body temperature. In 2002, Baldursdottir and her coworkers found that in the hospital, more comatose patients survived after induced hypothermia than patients that remained at normal body temperature. For this reason, the hospital chose to continue the induced hypothermia technique for all of its comatose patients that suffered from cardiac arrest.
Coma has a wide variety of emotional reactions from the family members of the affected patients, as well as the primary care givers taking care of the patients. Common reactions, such as desperation, anger, frustration, and denial are possible. The focus of the patient care should be on creating an amicable relationship with the family members or dependents of a comatose patient as well as creating a rapport with the medical staff.
There is currently no definitive evidence that support altering the course of the recovery of minimally conscious state. There are currently multiple clinical trials underway investigating potential treatments.
In one case study, stimulation of thalamus using deep brain stimulation (DBS) led to some behavioral improvements. The patient was a 38-year-old male who had remained in minimally conscious state following a severe traumatic brain injury. He had been unresponsive to consistent command following or communication ability and had remained non-verbal over two years in inpatient rehabilitation. fMRI scans showed preservation of a large-scale, bi-hemispheric cerebral language network, which indicates that possibility for further recovery may exist. Positron emission tomography showed that the patient's global cerebral metabolism levels were markedly reduced. He had DBS electrodes implanted bilaterally within his central thalamus. More specifically, the DBS electrodes targeted the anterior intralaminar nuclei of thalamus and adjacent paralaminar regions of thalamic association nuclei. Both electrodes were positioned within the central lateral nucleus, the paralaminar regions of the median dorsalis, and the posterior-medial aspect of the centromedian/parafasicularis nucleus complex. This allowed maximum coverage of the thalamic bodies. A DBS stimulation was conducted such that the patient was exposed to various patterns of stimulation to help identify optimal behavioral responses. Approximately 140 days after the stimulation began, qualitative changes in behavior emerged. There were longer periods of eye opening and increased responses to command stimuli as well as higher scores on the JFK coma recovery scale (CRS). Functional object use and intelligible verbalization was also observed. The observed improvements in arousal level, motor control, and consistency of behavior could be a result of direct activation of frontal cortical and basal ganglia systems that were innervated by neurons within the thalamic association nuclei. These neurons act as a key communication relay and form a pathway between the brainstem arousal systems and frontal lobe regions. This pathway is crucial for many executive functions such as working memory, effort regulation, selective attention, and focus.
In another case study of a 50-year-old woman who had symptoms consistent with MCS, administration of zolpidem, a sedative hypnotic drug improved the patient's condition significantly. Without treatment, the patient showed signs of mutism, athetoid movements of the extremities, and complete dependence for all personal care. 45 minutes after 5 to 10 mg of zolpidem was administered, the patient ceased the athetoid movements, regained speaking ability, and was able to self-feed. The effect lasted 3–4 hours from which she returned to the former state. The effects were repeated on a daily basis. PET scans showed that after zolpidem was administered, there was a marked increase in blood flow to areas of the brain adjacent to or distant from damaged tissues. In this case, these areas were the ipsilateral cerebral hemispheres and the cerebellum. These areas are thought to have been inhibited by the site of injury through a GABA-mediated mechanism and the inhibition was modified by zolpidem which is a GABA agonist. The fact that zolpidem is a sedative drug that induces sleep in normal people but causes arousal in a MCS patient is paradoxical. The mechanisms to why this effect occurs is not entirely clear.
There is recent evidence that transcranial direct current stimulation (tDCS), a technique that supplies a small electric current in the brain with non-invasive electrodes, may improve the clinical state of patients with MCS. In one study with 10 patients with disorders of consciousness (7 in VS, 3 in MCS), tDCS was applied for 20 minutes every day for 10 days, and showed clinical improvement in all 3 patients who were in MCS, but not in those with VS. These results remained at 12-month follow-up. Two of the patients in MCS that had their brain insult less that 12 months recovered consciousness in the following months. One of these patients received a second round of tDCS treatment 4 months after his initial treatment, and showed further recovery and emerged into consciousness, with no change of clinical status between the two treatments. Moreover, in a sham-controlled, double-blind crossover study, the immediate effects of a single session of tDCS were shown to transiently improve the clinical status of 13 out of 30 patients with MCS, but not in those with VS
Behavioral treatment can be effective in some cases. Sedative hypnotics may also help relieve the symptoms. Additionally, education about normal patterns of the sleep-wake cycle may alleviate anxiety in some patients. For patients with severe depression resulting from the fear of having insomnia, electroconvulsive therapy appears to be a safe and effective treatment.
Oneirophrenic patients are resistant to insulin and when injected with glucose, these patients take 30 to 50% longer to return to normal glycemia. The meaning of this finding is not known, but it has been hypothesized that it may be due to an insulin antagonist present in the blood during psychosis. However, There is currently no known treatment for oneiophrenia.
The condition may worsen as a result of persistent attempts to treat the symptoms through conventional methods of dealing with insomnia. The prescription of hypnotics or stimulants may lead to drug dependency as a complication.
Nonetheless, chronic SSM may increase risk for depression, anxiety, and substance abuse. It has also been noted that patients with this condition may sometimes opt to take medications over other treatments "for the wrong reasons (e.g. because of euphoriant properties)."
The DSM-IV-TR states that the fugue may have a duration from days to months, and recovery is usually rapid. However, some cases may be refractory. An individual usually has only one episode.
Neither a standard treatment nor a cure is available. Stimulation of muscle reflexes with electrodes (NMES) has been known to help patients regain some muscle function. Other courses of treatment are often symptomatic. Assistive computer interface technologies, such as Dasher, or OptiKey, combined with eye tracking, may be used to help a LIS survivor communicate with their environment in a better way.
Treatments using intravenous magnesium sulfate have shown to reduce the symptoms of akinetic mutism. In one case, a 59-year-old woman was administered intravenous magnesium sulfate in an attempt to resolve her akinetic mutism. The patient was given 500 mg of magnesium every eight hours, and improvement was seen after 24 hours. She became more verbal and attentive, and treatment was increased to 1000 mg every eight hours as conditions continued to improve.
Treatment of mixed states is typically based upon administration of mood stabilizing medication, which may include anticonvulsants such as valproic acid; atypical antipsychotics such as olanzapine, aripiprazole, and ziprasidone; or first-generation antipsychotics such as haloperidol. There is question of lithium's efficacy for treatment of mixed states due to conflicting conclusions drawn from various trials and research. Mood stabilizers work to reduce the manic symptoms associated with the mixed state, but they are not considered particularly effective for improving concurrent depressive symptoms.
Before beginning treatment for mania, careful differential diagnosis must be performed to rule out secondary causes.
The acute treatment of a manic episode of bipolar disorder involves the utilization of either a mood stabilizer (valproate, lithium, or carbamazepine) or an atypical antipsychotic (olanzapine, quetiapine, risperidone, or aripiprazole). Although hypomanic episodes may respond to a mood stabilizer alone, full-blown episodes are treated with an atypical antipsychotic (often in conjunction with a mood stabilizer, as these tend to produce the most rapid improvement).
When the manic behaviours have gone, long-term treatment then focuses on prophylactic treatment to try to stabilize the patient's mood, typically through a combination of pharmacotherapy and psychotherapy. The likelihood of having a relapse is very high for those who have experienced two or more episodes of mania or depression. While medication for bipolar disorder is important to manage symptoms of mania and depression, studies show relying on medications alone is not the most effective method of treatment. Medication is most effective when used in combination with other bipolar disorder treatments, including psychotherapy, self-help coping strategies, and healthy lifestyle choices.
Lithium is the classic mood stabilizer to prevent further manic and depressive episodes. A systematic review found that long term lithium treatment substantially reduces the risk of bipolar manic relapse, by 42%. Anticonvulsants such as valproate, oxcarbazepine and carbamazepine are also used for prophylaxis. More recent drug solutions include lamotrigine, which is another anticonvulsant. Clonazepam (Klonopin) is also used. Sometimes atypical antipsychotics are used in combination with the previous mentioned medications as well, including olanzapine (Zyprexa) which helps treat hallucinations or delusions, Asenapine (Saphris, Sycrest), aripiprazole (Abilify), risperidone, ziprasidone, and clozapine which is often used for people who do not respond to lithium or anticonvulsants.
Verapamil, a calcium-channel blocker, is useful in the treatment of hypomania and in those cases where lithium and mood stabilizers are contraindicated or ineffective. Verapamil is effective for both short-term and long-term treatment.
Antidepressant monotherapy is not recommended for the treatment of depression in patients with bipolar disorders I or II, and no benefit has been demonstrated by combining antidepressants with mood stabilizers in these patients.
Currently no effective treatment exists for kernicterus. Future therapies may include neuroregeneration. A handful of patients have undergone deep brain stimulation, and experienced some benefit. Drugs such as baclofen, clonazepam, and artane are often used to manage movement disorders associated with kernicterus. Proton pump inhibitors are also used to help with reflux. Cochlear implants and hearing aids have also been known to improve the hearing loss that can come with kernicterus (auditory neuropathy - ANSD).
Disorders of consciousness are medical conditions that inhibit consciousness. Some define disorders of consciousness as any change from complete self-awareness to inhibited or absent self-awareness and arousal. This category generally includes minimally conscious state and persistent vegetative state, but sometimes also includes the less severe locked-in syndrome and more severe but rare chronic coma. Differential diagnosis of these disorders is an active area of biomedical research. Finally, brain death results in an irreversible disruption of consciousness. While other conditions may cause a moderate deterioration (e.g., dementia and delirium) or transient interruption (e.g., grand mal and petit mal seizures) of consciousness, they are not included in this category.
If not stimulated externally, a patient with stupor will be in a sleepy state most of the time. In some extreme cases of severe depressive disorders the patient can become motionless, lose their appetite and become mute. Short periods of restricted responsivity can be achieved by intense stimulation (e.g. pain, bright light, loud noise, shock).
Since hypermetabolism itself is a symptom and not an independent disease, treatment first and foremost requires attention to the underlying disease. Usually once the underlying cause is remedied, the symptoms will subside. The duration of symptoms depends upon the severity of the illness or trauma. Although hypermetabolism is a potentially dangerous condition that usually signals an underlying issue, it is one of the body’s strongest defenses against illness and injury.
Disorders of consciousness present a variety of ethical concerns.
Most obvious is the lack of consent in any treatment decisions. Patients in PVS or MCS are not able to decide for the possibility of withdrawal of life-support. It is also a general question whether they should receive life-sustaining therapy and, if so, for how long? The problems regarding a patient's consent also account for neuroimaging studies. Without patient's consent, such studies are perceived as unethical.
Additionally only few patients have created advance directives before losing decision-making capacity.
Typically approval must be obtained from family or legal representatives depending on governmental and hospital guidelines.
But even with the consent of representatives, researchers have been refused grants, ethics committee approval and publication.
Social issues arise from the enormous costs that are caused by people with disorders of consciousness. Especially chronic comatose and vegetative patients, when recovery is highly unlikely and treatment in the ICU is considered futile by clinicians.
In addition to the aforementioned problems, the question rises why medical resources were being used not for the broader public good but for patients who seemed to have only little to gain from them.
Still research is everything but sure about the irreversibility of these conditions. Some studies demonstrated that some patients suffering from disorders of consciousness may be aware despite clinical unresponsiveness. These recent findings could have a major impact on ethical and social issues.
As seen in the case of Elsie Nicks, the puncture or removal of a cyst causing akinetic mutism can relieve symptoms almost immediately. However, if the cyst fills up again, the symptoms can reappear.
Stupor (from Latin "stupere", "be stunned or amazed") is the lack of critical mental function and a level of consciousness wherein a sufferer is almost entirely unresponsive and only responds to base stimuli such as pain. Those in a stuporous state are rigid, mute and only appear to be conscious, as the eyes are open and follow surrounding objects. The word derives from the Latin "" ("numbness, insensibility"). Being characterized by impairments to reactions to external stimuli, it usually appears in infectious diseases, complicated toxic states (e.g. heavy metals), severe hypothermia, mental illnesses (e.g. schizophrenia, severe clinical depression), epilepsy, vascular illnesses (e.g. hypertensive encephalopathy), shock (e.g. learning of a death or surviving a car crash), neoplasms (e.g. brain tumors), vitamin D deficiency and other maladies.
One of the defining characteristics of minimally conscious state is the more continuous improvement and significantly more favorable outcomes post injury when compared with vegetative state. One study looked at 100 patients with severe brain injury. At the beginning of the study, all the patients were unable to follow commands consistently or communicate reliably. These patients were diagnosed with either MCS or vegetative state based on performance on the JFK Coma Recovery Scale and the diagnostic criteria for MCS as recommended by the Aspen Consensus Conference Work-group. Both patient groups were further separated into those that suffered from traumatic brain injury and those that suffered from non-traumatic brain injures (anoxia, tumor, hydrocephalus, infection). The patients were assessed multiple times over a period of 12 months post injury using the Disability Rating Scale (DRS) which ranges from a score of 30=dead to 0=no disabilities. The results show that the DRS scores for the MCS subgroups showed the most improvement and predicted the most favorable outcomes 12 months post injury. Amongst those diagnosed with MCS, DRS scores were significantly lower for those with non-traumatic brain injuries in comparison to the vegetative state patients with traumatic brain injury. DRS scores were also significantly lower for the MCS non-traumatic brain injury group compared to the MCS traumatic brain injury group. Pairwise comparisons showed that DRS scores were significantly higher for those that suffered from non-tramuatic brain injuries than those with traumatic brain injuries. For the patients in vegetative states there were no significant differences between patients with non-traumatic brain injury and those with traumatic brain injuries. Out of the 100 patients studied, 3 patients fully recovered (had a DRS score of 0). These 3 patients were diagnosed with MCS and had suffered from traumatic brain injuries.
In summary, those with minimally conscious state and non-traumatic brain injuries will not progress as well as those with traumatic brain injuries while those in vegetative states have an all around lower to minimal chance of recovery.
Because of the major differences in prognosis described in this study, this makes it crucial that MCS be diagnosed correctly. Incorrectly diagnosing MCS as vegetative state may lead to serious repercussions related to clinical management.
It is important for MADD patients to maintain strength and fitness without exercising or working to exhaustion. Learning this balance may be more difficult than normally, as muscle pain and fatigue may be perceived differently from normal individuals.
Symptomatic relief from the effects of MADD may sometimes be achieved by administering ribose orally at a dose of approximately 10 grams per 100 pounds (0.2 g/kg) of body weight per day, and exercise modulation as appropriate. Taken hourly, ribose provides a direct but limited source of energy for the cells. Patients with myoadenylate deaminase deficiency do not retain ribose during heavy exercise, so supplementation may be required to rebuild levels of ATP.
Creatine monohydrate could also be helpful for AMPD patients, as it provides an alternative source of energy for anaerobic muscle tissue and was found to be helpful in the treatment of other, unrelated muscular myopathies.
It is extremely rare for any significant motor function to return. The majority of locked-in syndrome patients do not regain motor control, but devices are available to help patients communicate. However, some people with the condition continue to live much longer, while in exceptional cases, like that of Kerry Pink and Kate Allatt, a full spontaneous recovery may be achieved.
With due regard for the cause of the coma, and the rapidity of its onset, testing for the purpose of diagnosing death on brainstem death grounds may be delayed beyond the stage where brainstem reflexes may be absent only temporarily – because the cerebral blood flow is inadequate to support synaptic function although there is still sufficient blood flow to keep brain cells alive and capable of recovery. There has recently been renewed interest in the possibility of neuronal protection during this phase by use of moderate hypothermia and by correction of the neuroendocrine abnormalities commonly seen in this early stage.
Published studies of patients meeting the criteria for brainstem death or whole brain death – the American standard which includes brainstem death diagnosed by similar means – record that even if ventilation is continued after diagnosis, the heart stops beating within only a few hours or days. However, there have been some very long-term survivals and it is noteworthy that expert management can maintain the bodily functions of pregnant brain dead women for long enough to bring them to term.
The management of patients pronounced dead on meeting the brainstem death criteria depends upon the reason for diagnosing death on that basis. If the intent is to take organs from the body for transplantation, the ventilator is reconnected and life-support measures are continued, perhaps intensified, with the addition of procedures designed to protect the wanted organs until they can be removed. Otherwise, the ventilator is left disconnected on confirmation of the lack of respiratory centre response.
Hyperprosexia, and paraprosexia are closely related medical and neuro-psychiatric phenomena associated with attention and concentration. They typically occur in patients suffering traumatic brain injuries.
- "Aprosexia" is an abnormal inability to pay attention, characterized by a near-complete indifference to everything.
- "Hyperprosexia" is the abnormal state in which a person concentrates on one thing to the exclusion of everything else.
- "Paraprosexia" is the inability to pay attention to any one thing (a state of constant distraction).