1. Group B February 1, 2019

2.   Consciousness  Definition  Causes of coma  Coma syndromes  Approach to the patient  Management  Prognosis  Coma-like states Outline 4/12/20192

3.   A clear state of awareness of self and the environment in which attention is focused on immediate matters  Determined by two main functions: 1.Arousal (level of consciousness) – the degree of the ability to interact with the environment 2.Awareness (content of consciousness) – depth and content of the aroused state  Attention – the ability to respond to particular types of stimuli; depends on awareness Consciousness 4/12/20193

4.   Altered level of consciousness  Altered content of consciousness  Both Altered level of consciousness 4/12/20194

5.   Concussion  Seizure  Syncope  Metabolic encephalopathy  Coma  Persistent vegetative state  Minimal consciousness state Altered level of consciousness 4/12/20195

6.   Dementia  Delusion  Confusion  Inattention Altered content of consciousness 4/12/20196

7.   Cerebral hemispheres  Diencephalon – hypothalamus and thalamus  Brainstem – ascending reticular system The consciousness system 4/12/20197

8. 8

9.  To maintain consciousness, at least one hemisphere, as well as the reticular activating system, must be functioning normally 4/12/20199

10.  If there is altered consciousness, where is the lesion? In other words… 4/12/201910

11.  Posterior fossa level  Lesions of the brainstem RAS  Supratentorial  Posterior hypothalamus bilaterally  Bilateral Interruption of the Ascending Projections at the level of the Thalamus  Diffuse or Bilateral Hemispheric Cortical Lesions 4/12/201911

12.   Clouding of consciousness - Impaired capacity to think clearly and remember current stimuli  Delirium - disturbed consciousness with motor restlessness, disorientation and hallucination  Drowsiness – easy arousal and the persistence of alertness for brief periods, stimulates light sleep  Stupor - higher degree of arousability in which the patient can be transiently awakened by vigorous stimuli, accompanied by motor behavior that leads to avoidance of uncomfortable or aggravating stimuli  Coma - deep sleeplike state from which the patient cannot be aroused Altered consciousness is a continuum … 4/12/201912

13.   Coma is a state of extended unconsciousness in which the patient is unarousable and shows little or no spontaneous movement and little or no alerting response to painful or noxious stimuli. Definition 4/12/201913

14.  1.Lesions that damage the RAS in the upper midbrain or its projections 2.Destruction of large portions of both cerebral hemispheres 3.Suppression of reticulocerebral function by drugs, toxins, or metabolic derangements such as hypoglycemia, anoxia, uremia, and hepatic failure Causes of coma 4/12/201914

15.   Herniation syndromes  Brainstem lesions  Metabolic coma  Toxic syndromes Coma syndromes 4/12/201915

16.   Herniation is displacement of brain tissue by an overlying or adjacent mass into a contiguous compartment that it normally does not occupy  Occurs with expanding mass lesion:  Intracerebral, subdural, or epidural hemorrhage  Large ischemic stroke  Abscess  Tumor  Obstructive hydrocephalus Herniation syndromes 4/12/201916

17. Types of brain herniation 4/12/201917

18.   Initial loss of consciousness is related to lateral rather than downward displacement  Horizontal shift of pineal gland  3-5 mm – drowsiness  6-8 mm – stupor  >9 mm – coma  Other signs will be seen  Increased intracranial pressure  Papilledema  Cushing’s triad (hypertension, bradycardia, irregular breathing) Cont’d 4/12/201918

19.   Further shifts in brain structures can lead to downward, transtentorial herniation deterioration can be precipitous.  Two variants are recognized:  Central herniation syndrome  Uncal herniation syndrome Cont’d 4/12/201919

20.   Impaction of the anterior medial temporal gyrus (the uncus) into the tentorial opening just anterior to and adjacent to the midbrain  Due to more laterally directed forces Uncal herniation syndrome 4/12/201920

21.   The uncus compresses the third cranial nerve as it traverses the subarachnoid space  Pupillary dilatation  Downward and outward eye deviation  coma due to compression of the midbrain against the opposite tentorial edge  opposite cerebral peduncle compressed against the tentorial edge, producing a Babinski sign and hemiparesis contralateral to the mass  Anterior and posterior cerebral artery compression – brain infarction  portions of the ventricular system may be entrapped – hydrocephalus Cont’d 4/12/201921

22.   symmetric downward movement of the thalamic structures through the tentorial opening with compression of the upper midbrain  Heralded by miotic pupils and drowsiness Central herniation syndrome 4/12/201922

23.   Both forms cause progressive compression of the brainstem producing an approximate sequence of neurologic signs that corresponds to each affected level.  Other forms of herniation:  Transfalcial herniation (displacement of the cingulate gyrus under the falx and across the midline)  Foraminal herniation (downward forcing of the cerebellar tonsils into the foramen magnum), which causes compression of the medulla, respiratory arrest, and death. Cont’d 4/12/201923

24.   Infarction or hemorrhage of the upper pons and/or midbrain  Osmotic demyelination syndrome (formerly called central pontine myelinolysis)  Brainstem encephalitis  Bilateral long tract involvement – flaccid quadriparesis or decerebrate posturing  Notably asymmetric or absent eye movements  Pupils are classically small  Ensure that these patients are not locked-in Brainstem lesions 4/12/201924

25.   Cardinal feature – symmetrical nature of the neurologic deficits  Except, hypo- and hyperglycemia - frequently associated with lateralized motor findings  Tremor  Asterixis  Multifocal myoclonus  Muscle tone usually decreased  Pupils may appear abnormal but almost always are symmetric and constrict with light.  Suppression of VORs and corneal reflex occur with very deep metabolic coma Metabolic coma 4/12/201925

26.   Postictal coma even in the absence of motor convulsions (nonconvulsive status epilepticus)  May be due to exhaustion of energy reserves or effects of locally toxic molecules that are the by-product of seizures.  EEG findings similar to that of metabolic encephalopathies Epileptic coma 4/12/201926

27.   Drug overdoses or poisonings often appear similar to metabolic coma, but may be associated with distinctive clinical features Toxic syndromes 4/12/201927

28. 4/12/2019 28

29. 4/12/2019 29

30.   Initial assessment  History  Physical examination  Workup Approach to the patient 4/12/201930

31.   Rapid initial assessment should be performed to correct immediate treat to life  ABC – rapidly assessed and critical intervention made as required  Airway - evaluate airway patency  Breathing - appropriate respiratory rate, adequate gas exchange, adequate and symmetrical breath sounds  Circulation - Check pulses, heart rate, blood pressure, perfusion Initial assessment 4/12/201931

32.   Cause of coma – may be immediately evident in some cases  Trauma  Cardiac arrest  Observed drug ingestion History 4/12/201932

33.   The circumstances and rapidity with which neurologic symptoms develop  The antecedent symptoms – confusion, weakness, headache, fever, seizures, dizziness, double vision or vomiting  The use of medications drugs or alcohol  Chronic liver, kidney, lung, heart or other medical disease Other important points 4/12/201933

34.   Vital signs – temperature, respiration, blood pressure  Funduscopic examination  Integumentary system General physical examination 4/12/201934

35.   Alcohol, barbiturate, sedative, phenothiazine intoxication  hypoglycemia  peripheral circulatory failure  extreme hypothyroidism  Hypothermia itself causes coma when the temperature is <31°C Hypothermia  systemic infection  bacterial meningitis  Encephalitis  heat stroke  neuroleptic malignant syndrome,  Malignant  following vigorous convulsions Fever Temperature 4/12/201935

36.   brainstem disorders Aberrant respiratory patterns  systemic acidosis  pneumonia  infiltration of the brain with lymphoma Tachypnea Respiration 4/12/201936

37.   alcohol or barbiturate intoxication  internal hemorrhage  myocardial infarction  Sepsis  profound hypothyroidism  Addisonian crisis Hypotension  hypertensive encephalopathy  cerebral hemorrhage  head injury Hypertension Blood pressure 4/12/201937

38.   Subarachnoid hemorrhage  Hypertensive encephalopathy  Increased intracranial pressure (ICP) Funduscopic examination 4/12/201938

39.   Cutaneous petechiae  thrombotic thrombocytopenic purpura  meningococcemia, or a  bleeding diathesis associated with an intracerebral hemorrhage.  Cyanosis and reddish or anemic skin coloration  underlying systemic disease  carbon monoxide Integumentary system 4/12/201939

40.   Level of consciousness  Uninterrupted observation – motor examination  Brainstem reflexes Neurologic examination 4/12/201940

41.   Needs some form of stimulation – auditory, visual and noxious  Stimulus of progressively increasing intensity should be used  Exact stimulus and patient’s response should be recorded  Differentiate between coma and locked-in syndrome Level of consciousness 4/12/201941

42.   The Glasgow coma scale  The four coma scale  The continuous performance test  The hand position test Scales used to assess level of consciousness 4/12/201942

43.   LIMITATIONS  Failure to assess other essential neurological parameters for patients who are :  Intubated  Facial trauma  Aphasia  Used widely to assess the initial severity of traumatic brain injury  Assesses three separate aspects of a patient's behavior :The stimulus required to :  Induce eye opening  The best motor response  The best verbal response  Simple and reproducible The Glasgow coma scale 4/12/201943

44. The Glasgow coma scale 4/12/201944

45. 45 DOMAINSCOREBEHAVIOR EYE RESPONSE 4Eyelids open or opened, tracking, or blinking to command 3Eyelids open but not tracking 2Eyelids closed but open to loud voice 1Eyelids closed but open to pain 0Eyelids remain closed with pain MOTOR RESPONSE 4Thumbs-up, fist, or peace sign 3Localizing to pain 2Flexion response to pain 1Extension response to pain 0No response to pain or generalized myoclonic status BRAIN STEM REFLEXES 4Pupil and corneal reflexes present 3One pupil wide and fixed 2Pupil OR corneal reflexes absent 1Pupil AND corneal reflexes absent 0Absent pupil, corneal, and cough reflex RESPIRATION 4Not intubated, regular breathing pattern 3Not intubated, Cheyne-Stokes breathing pattern 2Not intubated, irregular breathing 1Breathes above ventilator rate 0Breathes at ventilator rate or apnea FULL OUTLINE OF UNRESPONSIVENESS (FOUR) SCORE TESTING 4/12/2019

46.  46  The continuous performance test  Monitors LEVEL OF ALERTNESS Requires the patient to raise a hand every time he or she hears a certain letter sound in a standardized sentence spoken by the examiner  THE HAND POSITION TEST  Is a test of PRAXIS The patient must mimic three different hand positions demonstrated by the examiner Cont’d 4/12/2019

47.   Lack of restless movements on one side  An outturned leg Hemiplegia  Tossing about in the bed  Reaching up toward the face  crossing legs  Yawning  Swallowing  Coughing  Moaning reflect Drowsy state Motor examination 4/12/201947

48.   Multifocal myoclonus  particularly uremia, anoxia, drug intoxication (especially with lithium or haloperidol), or a prion disease  Bilateral asterixis  metabolic encephalopathy or drug intoxication. Metabolic disorders  Intermittent twitching movements of a foot, finger, or facial Seizures Cont’d 4/12/201948

49.   Bilateral damage rostral to the midbrain Decorticate posturing  Damage to motor tracts in the midbrain or caudal diencephalon Decerebrate posturing  Lesions in the pons Arm extension with flexed or flaccid legs These concepts have been adapted from animal work and cannot be applied with precision to coma in humans. In fact, acute and widespread disorders of any type, regardless of location, frequently cause limb extension, and almost all extensor posturing becomes predominantly flexor as time passes. 4/12/201949

50.   Essential to localization of the lesion  The examined reflexes are:  pupillary size and reaction to light  spontaneous and elicited eye movements  corneal responses  respiratory pattern  These reflexes are preserved in coma due to bilateral hemispheral disease Brainstem reflexes 4/12/201950

51.   Use a bright, diffuse light  If the room has bright lighting, it mutes the pupillary reflex  Reactive and round pupils of midsize (2.5–5 mm) essentially exclude midbrain damage, either primary or secondary to compression.  A response to light may be difficult to appreciate in pupils <2 mm in diameter Pupillary signs 4/12/201951

52.   Unilateral  compression or stretching of the third nerve from the effects of a cerebral mass above  Contralateral hemispherical mass (rarely)  Bilateral  severe midbrain damage, usually from compression by a supratentorial mass  ingestion of drugs with anticholinergic activity  use of mydriatic eye drops  direct ocular trauma Enlarged pupil 4/12/201952

53.   Unilateral  dysfunction of sympathetic efferents (posterior hypothalamus, tegmentum of the brainstem, cervical cord)  large cerebral hemorrhage that affects the thalamus  Bilateral  1–2.5 mm  metabolic encephalopathies  deep bilateral hemispheral lesions such as hydrocephalus or thalamic hemorrhage.  <1 mm  narcotic or barbiturate overdoses  extensive pontine hemorrhage Small pupil 4/12/201953

54.   eyes are first observed by elevating the lids and observing the resting position and spontaneous movements of the globes  Lid tone  tested by lifting the eyelids and noting their resistance to opening and the speed of closure  progressively reduced as unresponsiveness progresses  Horizontal divergence of the eyes at rest is normal in drowsiness. As coma deepens, the ocular axes may become parallel again Ocular movements 4/12/201954

55.   Conjugate horizontal roving in coma  The eyes look toward a hemispheral lesion and away from a brainstem lesion eyes turned down and inward in thalamic and upper midbrain injuries (most common – thalamic hemorrhage)  “Ocular bobbing” - brisk downward and slow upward movements of the eyes associated with loss of horizontal eye movements and is diagnostic of bilateral pontine damage, usually from thrombosis of the basilar artery.  “Ocular dipping” is a slower, arrhythmic downward movement followed by a faster upward movement in patients with normal reflex horizontal gaze; it usually indicates diffuse cortical anoxic damage. Spontaneous eye movement 4/12/201955

56.   elicited by moving the head from side to side or vertically and observing eye movements in the direction opposite to the head movement,  “doll’s eyes  reflex normally suppressed in the awake patient  If elicited  reduced cortical influence on the brainstem  intact brainstem pathways,  i.e. indicating that coma is caused by a lesion or dysfunction in the cerebral hemispheres Oculocephalic reflexes 4/12/201956

57.   irrigating the external auditory canal with cool water in order to induce convection currents in the labyrinths.  After a brief latency, the result is tonic deviation of both eyes to the side of cool-water irrigation and nystagmus in the opposite direction.  The loss of induced conjugate ocular movements indicates brainstem damage.  The presence of corrective nystagmus indicates that the frontal lobes are functioning and connected to the brainstem; thus catatonia or hysterical coma is likely. Oculovestibular response 4/12/201957

58.   touching the cornea with a wisp of cotton to illicit a brief bilateral lid closure  depends on the integrity of pontine pathways between the fifth (afferent) and both seventh (efferent) cranial nerves  a useful test of pontine function  disappear soon after reflex eye movements are paralyzed but before the pupils become unreactive to light  may be lost for a time on the side of an acute hemiplegia Corneal reflex 4/12/201958

59.   less localizing value in comparison to other brainstem signs.  Shallow, slow, but regular breathing  metabolic or drug depression.  Cheyne-Stokes respiration  bihemispheral damage or metabolic suppression  Rapid, deep (Kussmaul) breathing  metabolic acidosis, pontomesencephalic lesions  Agonal gasps  lower brainstem (medullary) damage  the terminal respiratory pattern of severe brain damage. Respiratory patterns 4/12/201959

60.   The goal of diagnostic testing in a patient in coma is to identify treatable conditions (infection, metabolic abnormalities, seizures, intoxications/overdose, surgical lesions)  Because neurologic recovery is often reliant on early treatment, testing must proceed rapidly in concert with the clinical evaluation Workup 4/12/201960

61.   Investigations almost always include laboratory testing and neuroimaging.  Some patients require lumbar puncture and electroencephalography (EEG).  Testing should be prioritized according to the clinical presentation. Cont’d 4/12/201961

62.   Screening tests for uncertain causes  Complete blood count  Serum electrolytes, calcium, magnesium, phosphate, glucose, urea, creatinine, liver function tests, lactate, and Osmolarity  Arterial blood gas  Prothrombin and partial thromboplastin time  Drug screen (usually done on urine and serum) Laboratory tests 4/12/201962

63.   In selected patients, when other conditions are suspected or if the cause of coma remains obscure, further laboratory testing is required:  Adrenal and thyroid function tests  Blood cultures  Blood smear: screen for TTP, DIC and antiphospholipid determination  Carboxyhemoglobin – CO poisoning suspected  Serum drug concentrations for specific drugs Cont’d 4/12/201963

64.   CT scan  Allows for quick assessment of intracranial structural changes  Test of choice for initial evaluation of coma patients  Very sensitive for structural causes of coma except for focal brainstem lesions Neuroimaging 4/12/201964

65.   MRI  Can better detect abnormalities in patients with  herpes simplex encephalitis  early ischemic strokes (especially involving the brainstem)  multiple small hemorrhages or white matter tract disruption associated with traumatic diffuse axonal injury  anoxic-ischemic damage from cardiac arrest  most disorders affecting the white matter Cont’d 4/12/201965

66.   However, MRI  Takes longer to perform than CT  Requires patient to be farther from monitoring personnel  Problematic for unstable patients  Therefore, in general CT is the test of choice for initial evaluation. Follow-up MRI is recommended when CT and other testing do not explain, or incompletely explain, the clinical picture. Cont’d 4/12/201966

67.   If CNS infection is suspected  First exclude intracranial mass with CT and get coagulation profile  If highly suspicious, start empirical therapy after taking the CSF sample without waiting for results  Useful to exclude subarachnoid hemorrhage when CT is normal and the diagnosis remains suspect  May be helpful in the diagnosis of less common infections, demyelinating, inflammatory, and neoplastic conditions Lumbar puncture 4/12/201967

68.   Used primarily to detect seizures – non convulsion seizures  Can confirm toxic metabolic encephalopathy  helps in determining the prognosis of cardiac arrest Electroencephalography (EEG) 4/12/201968

69.  1.Primary ABCs (oxygen supplementation and intubation if necessary), take vital signs, establish initial GCS score, measure arterial blood gas and send for blood and urine tests 2.Treat hypo- or hypertension. Monitor with 12 lead ECG 3.Give 25g dextrose and 100g thiamine while waiting or blood tests 4.Urgent treatment if herniation syndrome is evident or confirmed by CT – mannitol and hyperventilation 5.Lower fever with antipyretics or cooling blanket, start empiric antibiotic therapy Management 4/12/201969

70.  6.Treat only extreme hypothermia (<33°C), especially in cardiac arrest – hypothermia has neuroprotective role 7.Treat seizures with phenytoin or fosphenytoin 8.Definitive therapy on establishing the precise diagnosis Cont’d 4/12/201970

71.   Coma is a transitional state that rarely lasts more than several weeks, except in cases of ongoing sedative therapies or protracted sepsis.  Patients either recover or evolve into brain death or a persistent vegetative or minimally conscious state.  The prognosis depends on the underlying etiology, as well as the severity of the insult and other premorbid factors, including age Prognosis 4/12/201971

72. 4/12/201972

73.   Vegetative state  Minimally conscious state  Locked-in state  Akinetic mutism  Catatonia  Brain death Coma-like states (pseudocoma) 4/12/201973

74.  Vegetative state  an awake-appearing but nonresponsive state  eyelids may open, giving the appearance of wakefulness  Respiratory and autonomic functions are retained. Yawning, coughing, swallowing, and limb and head movements persist, may follow visually presented objects  in essence, an “awake coma.”- few if meaningful responses because they have retained wakefulness but lack awareness 744/12/2019

75.  75  Preserved hypothalamus and brainstem autonomic functions and preserved CN reflex  The prognosis for regaining mental faculties once the vegetative state has supervened for several months is very poor, and after a year, almost nil; hence the term persistent vegetative state  The vegetative state is deemed to be permanent 12 months after traumatic brain injury and 3 months after non-traumatic injury Cont’d 4/12/2019

76.  76  Closely related to vegetative state  Are able to 1.Follow simple commands 2.Gesture or verbally give yes or no response 3.Verbalize intelligibly 4.Perform movements or affective behaviors in relation to environmental stimuli  Arousal + Awareness(minimal)  Better prognosis than in vegetative state Minimally conscious state 4/12/2019

77.  77  Patients with acute lesions of the brainstem, particularly the pons(sparing the midbrain), may be unable to move or speak while retaining awareness.  retains voluntary vertical eye movements and lid elevation  pupils are normally reactive.  complete paralysis of the voluntary motor systems  Other causes of severe motor paralysis (eg, Guillain-Barre syndrome, botulism) may also cause a similar condition. Locked-in state 4/12/2019

78.  78  partially or fully awake state in which the patient is able to form impressions and think, as demonstrated by later recounting of events, but remains virtually immobile and mute.  lesions in the portions of the frontal lobes responsible for initiating movement.  Tone, reflexes, and postural reflexes usually remain intact.  Abulia -a milder form of akinetic mutism characterized by mental and physical slowness and diminished ability to initiate activity. It is also usually the result of damage to the frontal lobes and its connections Akinetic mutism 4/12/2019

79.  79  is a curious hypomobile and mute syndrome that occurs as part of a major psychosis, usually schizophrenia or major depression.  few voluntary or responsive movements, although they blink, swallow, and may not appear distressed.  These patients often resist passive eye opening, move to avoid noxious stimuli, turn the eyes towards the floor regardless of which side they are lying on, or have nonepileptic seizures.  Catatonia is distinguished from coma by the preserved ability to maintain trunk and limb postures, even the ability to sit or stand. Catatonia 4/12/2019

80.   Permanent absence of all brain activity, including brainstem function.  Irreversibly comatose and apneic  Absent brainstem function including loss of all CN function unlike patients in coma who have preserved brainstem function and some degree of respiratory drive Brain death 4/12/201980

81.  4/12/201981  Harrison`s Principles Of Internal Medicine 19th edition  Uptodate 21.6 References

82.  4/12/201982 Thank You!