Disorders of consciousness

Physiological basis of consciousness and alteration of consciousness

Consciousness has two components:

a. Arousal or wakefulness and loss of arousal is the most important cause of alteration of level of consciousness in clinical practice.

b. Content reflecting the quality and coherence of thought and behavior reflecting the sum of cognitive and affective function.

—Perception – Awareness of self and environment (Sensory integration)

—Reaction – Meaningful responsiveness of behavior (Motor response)

Arousal is predominantly a function of the ascending reticular activating system (ARAS), located in pons and midbrain and the axons ascend in the central tegmental tract. ARAS receives collaterals from somatic and special sensory systems and projects to the reticular nucleus of thalamus and to hypothalamus (which projects to limbic cortex and basal forebrain), in addition, the midline raphe nuclei and locus ceruleus project diffusely to cerebral cortex.

Awareness of content is a direct function of the cerebral hemispheres and the projections to them from thalamus, hypothalamus and brainstem.

Different states

Consciousness is the quality or state of being aware especially of something within oneself, or the state or fact of being conscious of an external object, state, or fact, c. awareness; especially:  concern for some social or political cause.

Unconsciousness as a result of brain injury rarely lasts more than 2–4 weeks. Based on this observation it is logical to classify disorders of consciousness into two broad categories: A. acutely altered states of consciousness and B. chronically altered states of consciousness.

Causes

This disturbance can be caused by lesions in the ascending reticular activating system or both hemispheres or by lesions outside this structures but capable of affect their normal function causes alteration of consciousness.

Axis I – anatomical localization

Supratentorial lesions

Rhinencephalic and subcortical destructive lesions

Thalamic infarcts

Supratentorial mass lesions

Hemorrhage

Intracerebral

Hypertensive

Vascular anomaly

Other

Epidural

Subdural

Pituitary apoplexy

Infarction

Arterial occlusions

Thrombotic

Embolic

Venous occlusions

Tumors

Primary

Metastatic

Abscess

Intracerebral

Subdural

Closed head injury

Subtentorial lesions

Compressive lesions

Cerebellar hemorrhage

Posterior fossa subdural or extradural hemorrhage

Cerebellar infarct

Cerebellar tumor

Cerebellar abscess

Basilar aneurysm

Destructive or ischemic lesions

Pontine hemorrhage

Brainstem infarct

Basilar migraine

Brainstem demyelination

Diffuse and/or metabolic brain dysfunction

Diffuse intrinsic disorders of brain

Encephalitis or encephalomyelitis

Subarachnoid hemorrhage

Concussion, nonconvulsive seizures, and postictal states

Primary neuronal disorders

Extrinsic and metabolic disorders

Anoxia or ischemia

Hypoglycemia

Nutritional

Hepatic encephalopathy

Uremia and dialysis

Pulmonary disease

Endocrine disorders (including diabetes)

Remote effects of cancer

Drug poisons

Ionic and acid-base disorders

Temperature regulation

Mixed or nonspecific metabolic coma

Psychiatric coma

Summary of anatomical Localization

Axis II – clinical syndrome

1. Diseases that cause no focal or lateralizing neurologic signs, usually with normal brainstem functions; CT scan and cellular content of the CSF are normal
   1. Intoxications: alcohol, sedative drugs, opiates, etc.
   2. Metabolic disturbances: anoxia, hyponatremia, hypernatremia, hypercalcemia, diabetic acidosis, nonketotic hyperosmolar hyperglycemia, hypoglycemia, uremia, hepatic coma, hypercarbia, addisonian crisis, hypo- and hyperthyroid states, profound nutritional deficiency
   3. Severe systemic infections: pneumonia, septicemia, typhoid fever, malaria, Waterhouse-Friderichsen syndrome
   4. Shock from any cause
   5. Postseizure states, status epilepticus, subclinical epilepsy
   6. Hypertensive encephalopathy, eclampsia
   7. Severe hyperthermia, hypothermia
   8. Concussion
   9. Acute hydrocephalus
2. Diseases that cause meningeal irritation with or without fever, and with an excess of WBCs or RBCs in the CSF, usually without focal or lateralizing cerebral or brainstem signs; CT or MRI shows no mass lesion
   1. Subarachnoid hemorrhage from ruptured aneurysm, arteriovenous malformation, trauma
   2. Acute bacterial meningitis
   3. Viral encephalitis
   4. Miscellaneous: Fat embolism, cholesterol embolism, carcinomatous and lymphomatous meningitis, etc.
3. Diseases that cause focal brainstem or lateralizing cerebral signs, with or without changes in the CSF; CT and MRI are abnormal
   1. Hemispheral hemorrhage (basal ganglionic, thalamic) or infarction (large middle cerebral artery territory) with secondary brainstem compression
   2. Brainstem infarction due to basilar artery thrombosis or embolism
   3. Brain abscess, subdural empyema
   4. Epidural and subdural hemorrhage, brain contusion
   5. Brain tumor with surrounding edema
   6. Cerebellar and pontine hemorrhage and infarction
   7. Widespread traumatic brain injury
   8. Metabolic coma (see above) with preexisting focal damage
   9. Miscellaneous: cortical vein thrombosis, herpes simplex encephalitis, multiple cerebral emboli due to bacterial endocarditis, acute hemorrhagic leukoencephalitis, acute disseminated (postinfectious) encephalomyelitis, thrombotic thrombocytopenic purpura, cerebral vasculitis, gliomatosis cerebri, pituitary apoplexy, intravascular lymphoma, etc.

Axis III – etiology

1. 1. Vascular
      1. Ischemic stroke
         1. bihemispheric,
         2. diencephalic,
         3. upper brainstem
         4. Cerebral venous thrombosis
      2. Hemorrhage
         1. subarachnoid,
         2. intraparenchymal,
         3. subdural,
         4. epidural
         5. Pituitary apoplexy
         6. Hypertensive encephalopathy
      3. Infections
         1. Cerebral abscess
         2. Subdural empyema
         3. Viral encephalitis
         4. Malaria
         5. Typhoid fever
         6. Sepsis
         7. Syphilis
         8. Postinfectious encephalomyelitis
      4. Inflammatory
         1. Acute demyelinating encephalomyelitis
         2. Multiple sclerosis (fulminant)
         3. Multifocal leukoencephalopathy
      5. Neoplastic
         1. Any neoplasm—bihemispheric,
         2. unilateral hemisphere with midline shift and herniation,
         3. diencephalic, upper brainstem, associated with hydrocephalus
         4. Paraneoplastic Limbic encephalitis
      6. Metabolic
         1. Addisonian crisis
         2. Diabetic ketoacidosis
         3. Dialysis encephalopathy
         4. Hepatic encephalopathy
         5. Hyper- or hypocalcemia Hypermagnesemia
         6. Hyper- or hypoglycemia
         7. Hypercapnia
         8. Hyper- or hyponatremia
         9. Hypothyroid
         10. Hyper- or hypothermia
         11. Lactic acidosis and mitochondrial disease
         12. Diffuse hypoxia
         13. Porphyria
         14. Uremia
         15. Wernicke's encephalopathy
      7. Toxins
         1. Carbon monoxide
         2. Cyanide
         3. Ethylene glycol
         4. Lead
         5. Methanol
      8. Medications, Drugs
         1. Alcohol
         2. Anticholinergics
         3. Barbiturates
         4. Lithium
         5. Opiates
         6. Psychotropics
         7. Benzodiazepines
      9. Others
         1. Status epilepticus
         2. Hydrocephalus
         3. Trauma
         4. Reye's syndrome
      10. Mimics
          1. Locked-in syndrome
          2. Catatonia
          3. Conversion reaction
          4. Neuromuscular weakness
          5. Guillain–Barré syndrome
          6. Myasthenia gravis

Emergency management

Disorders of consciousness leading to acute confessional states and comas are one of the most common (3–5%) neurological emergencies in any clinical practice over last century. A large proportion of comatose patients recover, but untreated coma may lead to further brain damage, anf to reach the final diagnosis depends on systematic approach.

Primary objective:

To stabilize, evaluate, and treat the comatose patient in the emergent setting by:

1. Secure airway
2. Establish Adequacy of Ventilation
3. Establish Adequacy of Circulation
4. Insert Intravenous cannula
5. Draw blood for laboratory studies
6. Treat immediately reversible causes of coma
   1. Hypoglycemia – 25g of glucose I.V
   2. Opiate overdose – Naloxe 2 mg I.V
   3. Wernicke's encephalopathy – Thiamine 100 mg I.V
7. Treat seizures
8. Evaluation as to whether there is significant increased ICP or mass lesions. Treatment of ICP to temporize until surgical intervention is possible.
9. Send for CT scan brain once general patient is stabilized to find the structural cause of alteration of consciousness.

Secondary objectives

To understand and recognize the cause of coma.

Psychogenic coma

Holds eye tight, resist opening

Fixed stare, quick blink

Normal pupil

Normal oculocephalic

Normal oculovestibular

Normal posture, breathing, bp,pulse

Supratentorial mass lesions

Initiating signs usually of focal cerebral dysfunction

Signs of dysfunction progress rostral to caudal

Neurologic signs at any given time point to one anatomic area – diencephalon, midbrain, brainstem

Motor signs are often asymmetrical

Subtentorial mass lesions

History of preceding brainstem dysfunction or sudden onset of coma

Localizing brainstem signs precede or accompany onset of coma and always include oculovestibular abnormality

Cranial nerve palsies usually present

"Bizarre" respiratory patterns common, usually present at onset of coma

Herniation syndromes

Confusional state → coma, fluctuation

No focal neurological sign

No neck stiffness

Normal brainstem reflexes

Coarse tremor 8–10 Hz

Multifocal myoclonus

Asterixis

Generalized/periodic myoclonus

History

Circumstances and temporal profile of the onset of coma

Details of preceding neurological

Symptoms headache, weakness seizure

Any fall

Use of drug and alcohol

Previous medical illness liver, kidney

Previous psychiatric illness

Yawning

—Poor localizing value

—Posterior fossa expanding lesion

—Medial temporal, third ventricular Hiccup

—Medullary lesion in the region of Third ventricle

Vomiting

—Lateral reticular formation of the medulla

—Projectile (usually nausea)

—Medulloblastoma ependymoma

—Raised Intracranial Pressure → compression of medulla

—Basal meningitis

—Intraventricular hemorrhage → irritating fourth ventricle

—Lateral medullary infarct (vestibular)

Physical examination

Emergent examination

1. The level of consciousness
2. The pattern of breathing
3. Circulation – blood pressure and pulse
4. The size and reactivity of the pupils
5. The eye movements and oculovestibular responses
6. The skeletal motor responses.

The level of consciousness

Glasgow coma scale (GCS) is the best way to objectively document level of consciousness in emergency and ICU.

The pattern of breathing

Forebrain

1. —Post hyperventilation apnea
2. —Cheyne stoke respiration¢Forebrain
3. —Post hyperventilation apnea
4. —Cheyne stoke respiration

Hypothalamus midbrain

1. —Central neurogenic hyperventilation

Basis pontis

1. —Pseudobulbar paralysis of voluntary center

Lower pontine tegmentum

1. —Apneustic breathing
2. —Cluster breathing
3. —Short cycle periodic breathing
4. —Ataxic breathing

Medulla

1. —Ataxic breathing
2. —Slow regular respiration
3. —Gasping

Respiration altered in

—Acid-base derangements

—Hypoxia

—Cardiac influences

Circulation

Kocher–Cushing response – rise in BP → bradycardia due to rise in ICP → compression of floor of the iv ventricle → fall in BP and tachycardia. Usually terminal event due to medullary failure.

Elevation of blood pressure can indicate

1. Long-standing hypertension, which predisposes to intracerebral hemorrhage or stroke.
2. Hypertensive encephalopathy
3. May be a consequence of the process causing the coma (intracerebral or subarachnoid hemorrhage)

Pupil

1. 1. Bilateral dilated pupils – Are greater than 7 mm in diameter and do not react to light stimulation. Are seen in:
      1. Transtentorial herniation of both medial temporal lobes
      2. Anticholinergic or Sympathomimetic drug intoxication
   2. Bilateral pinpoint pupils – Have 1–1.5 mm in diameter and are seen in:
      1. Morphine poisoning
      2. Pontine hemorrhage
      3. neurosyphilis
      4. Organophosphates poisoning
      5. Miotic eyes drops
   3. Asymmetric pupils (anisocoria) – With a difference of 1 mm or less in diameter and a normal constriction response to light is a normal finding in 20% of the population. If the dilated pupil do not react to light or do it slowly, it usually indicates a rapidly expanding lesion on the ipsilateral side as in subdural or middle meningeal hemorrhage or brian tumor, that is compressing the midbrain or oculomotor nerve directly or by mass effect.
   4. Fixed midsized pupils – Are about 5 mm in diameter, do not react to light and are the result of midbrain lesion.

Pupil Summary

Metabolic: Small reacting

Diencephalic: Small reacting

Tectal (Midbrain): Large fixed hippus

3rd Nerve Uncle herniation: Large fixed

Midbrain; Midsize not reacting

Pons: Small pinpoint

Opiate Pinpoint

Organophosphorus Small

Atropine Wide dilated

The eye movements

Extraocular Movements – In the comatose patient eye movements are tested by stimulating the vestibular system by the oculocephalic reflex(doll's head maneuver) which consists of passive head rotation or by the oculovestibular reflex(cold-water calorics test) which uses ice-water irrigation against the tympanic membrane.

Normal – The presence of full reflex eye movements (full conjugate horizontal eye movement during the doll's head maneuver and tonic conjugate movement of both eyes to the side of the ice-water irrigation during caloric test) attests to the integrity of the brain stem from the pontine to the midbrain level.

Abnormal:

1. Impaired unilateral adduction – Indicates lesions of the oculomotor nerve or midbrain lesions involving the oculomotor nucleus.
2. Downward deviation of one or both eyes – is suggestive of sedative drug intoxication.
3. No response – Complete absence of response on oculovestibular testing implies either a structural lesion of the brain stem at the level of the pons or a metabolic disorder with a particular predilection for brain stem involvement(sedative drug intoxication).
4. —Moving: Roving, dipping, bobbing are signs of pontine lesion with Ipsilateral 6th, —Ipsilateral gaze palsy, —One and half syndrome, —Bilateral gaze palsy, —Ocular bobbing, —MLF (median longitudinal fasciculus) syndrome

Eye movement Summary

Symmetric responses seen with metabolic or structural causes

Asymmetric responses seen with structural causes

The hemispheres (smart) are responsible for:

—Inhibiting Doll's eyes

—Fast component of nystagmus

The brain stem (dumb) is responsible for:

—Allowing Doll's eyes

Slow component of nystagmus

Motor response

Assess tone, presence of asterixis

Response to painful stimuli

—none

—abnormal flexor

—abnormal extensor

—normal localization/withdrawal

Symmetric responses seen with metabolic or structural causes

Asymmetric responses seen with structural causes

Posture

1. Cerebral hemisphere: —Decorticate posture
2. Diencephalon supratentorial:—Diagonal posture
3. Upper brain stem: —Decerebrate posture
4. Pontine: —Abnormal ext arm, —Weak flexion leg
5. Medullary: —Flaccidity

Detailed examination

General physical examination

Evidence of external injury

Colour of skin and mucosa

Odour of breath

Posture – Look for muscle jerks or tremors. Inspect the respiratory movements for tachypnea, bradypneia, Cheyne-Stokes breathing and Kussmaul breathing.

Color – Look for pallor, icterus, the cherry-red color of carbon monoxide hemoglobin and the cyanosis of methemoglobinemia.

Facial muscles – Look for asymmetry of the face which may indicate hemiplegia

Oral cavity – Look for lacerations in the tongue which may indicate biting during a convulsive seizure. Smell the breath for alcohol or ammonia.

Ears – Look for pus

Neck – Test for nuchal rigidity, Brudzinski sign, Kernig sign, for evidence of meningeal irritation.

Temperature

1. Hypothermia – can occur in ethanol or sedative drug intoxication, Wernicke's encephalopathy, hepatic encephalopathy, and Myxedema.
2. Hyperthermia – can occur in status epilepticus, pontine hemorrhage, heat stroke, malignant hyperthermia and anticholinergic intoxication.

Signs of trauma:

1. Battle's sign (swelling and discoloration overlying the mastoid bone behind the ear)
2. Raccoon eyes (Periorbital ecchymosis)
3. Cerebrospinal fluid rhinorrhea or otorrhea
4. Skull fractures

Systemic examination

Neurologic examination

Systematic assessment of brainstem function via reflexes

Cranial Nerve Exam

—Pupillary light response (CN 2-3)

—Occulocephalic/calorics (CN 3,4,6,8)

—Corneal reflex (CN 5,7)

—Gag refelx (CN 9,10)

Funduscopy

Look for papilledema or retinal hemorrhage which may indicate chronic or acute hypertension or an elevation in intracranial pressure.

Subhyaloid hemorrhages in an adult suggest subarachnoid hemorrhage.

Heart lung

Abdomen

Investigation

Complete blood count, MP, B.sugar

Blood urea, s. creatinine, s.electrolyte

Blood gases, ALT, AST

CSF examination

CT scan/ MRI

X-ray chest, ECG

ECG changes in coma (SAH, ICH, INFARCT)

—Tall T, prolonged QT

—Q wave with st depression

—SVT, AF, AFL

—Sinus bradycardia,arrest, nodal rhythm

—A-V block or dissociation

PVc's, VFL, VF

Treatment

The emergency management of comatose patient is the first part of the treatment. It is necessary to stabilize the patient and to permit further evaluation. The continuation of treatment depends on the etiology of the coma and can vary from medical therapy to neurosurgical intervention.

Subsequent management

Eye, mouth, skin

Fluid electrolyte, feeding

Respiration, circulation

Urine, bowel

Stimulation

Infection control

Prognosis

The most important aspect of evaluation of the comatose patient is to decide whether unconsciousness is the result of a structural brain lesion or a diffuse encephalopathy caused by metabolic disturbance, meningitis or seizures, because they need different therapies. Structural brain lesions may need neurosurgical intervention while diffuse encephalopathy may require only medical treatment. Another important part of medical evaluating includes forecasting the outcome of illness, since vigorous treatment may be followed by an unwanted outcome.

Methodological problems

Metabolic studies are useful, but they are not able identify neural activity within a specific region to specific cognitive processes. Functionality can only be identified at the most general level: Metabolism in cortical and subcortial regionas that may contribute to cognitive processes.

At present, there is no established relation between cerebral metabolic rates of glucose or oxygen as meaured by PET and patient outcome. The decrease of cerebral metabolism occurs also when patients are treated with anaesthetics to the point of unresponsiveness. Lowest value (28% of normal range) have been reported during propofol anaesthesia. Also deep sleep represents a phase of decreased metabolism (down to 40% of the normal range) In general, quantitative PET studies and the assessment of cerebral metabolic rates depends on many assumptions. PET for example requires a correction factor, the lumped constant, which is stable in healthy brains. There are reports, that a global decrease of this constant emerges after a traumatic brain injury. But not only the correction factors change due to TBI. Another issue is the possibility of anaerobic glycolysis that could occur after TBI. In such a case the glucose levels measured by the PET are not tightly connected to the oxygen consumption of the patient's brain. Third point regarding PET scans is the overall measurement per unit volume of brain tissue. The imaging can be affected by the inclusion of metabolically inactive spaces e.g. cerebrospinal fluidin the case of gross hydrocephalus, which artificially lowers the calculated metabolism. Also the issue of radiation exposure must be considered in patients with already severely damaged brains and preclude longitudinal or follow-up studies.

Ethical issues

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 irreverebility of these conditions. Some studies demonstrated that some patients suffering from disorders of consciousness may be aware despite clinical unresponsivesness. These recent findings could have a major impact on ethical and social issues.