The Localization of Lesions Causing Coma

1. The Localization of Lesions Causing Coma Dr. Mohammed Alanazy

2. Outline • Coma, Akinetic Mutism, and Locked-In Syndrome • Anatomic Substrate of Alertness • Signs with Localizing Value in Coma • Respiratory Patterns • Temperature Changes • The Pupils • Eye Movements • Motor Activity of the Body and Limbs • Clinical Presentations of Coma-Inducing Lesions Depending on their Location • Metabolic Encephalopathy (Diffuse Brain Dysfunction) • Supratentorial Structural Lesions • Subtentorial Structural Lesions • Psychogenic Unresponsiveness

3. Coma, Akinetic Mutism, and Locked-In Syndrome • Akinetic mutism: refers to a state in which the patient, although seemingly awake, remains silent and motionless. Only the eyes dart in the direction of moving objects, such as the examiner approaching the patient's bed. The examiner, attempting to converse with a patient in this state, gets the distinct impression of failing to draw the patient's attention and interest. Despite the lack of movement, there are few signs indicative of damage to the descending motor pathways. • frontal release signs, may be present..

4. If a history is available, akinetic mutism can be usually distinguished from psychogenic (often catatonic) unresponsiveness. • Signs of frontal release or corticospinal tract damage favor the diagnosis of akinetic mutism. • In the catatonic patient, the EEG is normal (often desynchronized, with low-voltage fast activity), but in the patient with akinetic mutism the EEG often shows slow-wave abnormalities.

5. Localization: • bilateral frontal region (anterior cingulate gyri), • the diencephalo-mesencephalic reticular formation, • the globus pallidus, or • the hypothalamus . • Common causes : • anoxia, head trauma, cerebral infarction, severe acute hydrocephalus, and direct compression by tumors , air embolism or end-stage degenerative or infectious brain disorders, such as Creutzfeldt-Jakob disease • Metabolic or ictal disorders : transient disorder of alertness similar to akinetic mutism • A syndrome of transient mutism and relative akinesia may occur a few days after midline cerebellar or fourth ventricular surgery • Hyperkinetic mutism, with continuous bilateral ballism and dystonia, has been described in a diabetic with multiple subcortical and cortical infarcts

6. Vegetative state • a chronic neurologic condition characterized by lack of awareness of self and external stimuli • accompanied by sleep-wake cycles, • preservation of vital vegetative functions, such as cardiac function, respiration, and maintenance of blood pressure. • no evidence of sustained, reproducible, purposeful, or voluntary behavioral responses to visual, auditory, tactile, or noxious stimuli • show no evidence of language comprehension or expression • have bowel and bladder incontinence • variably preserved cranial nerve and spinal reflexes.

7. Persistent vegetative state is defined as a vegetative state lasting for at least 1 month • Recovery of consciousness from a posttraumatic persistent vegetative state is unlikely after 12 months in adults and children. • Recovery from a nontraumatic persistent vegetative state after 3 months is exceedingly rare in both adults and children.

8. locked-in syndrome • the patient is mute and motionless (de-efferented) but remains awake, alert, aware of self, and capable of perceiving sensory stimuli. • Horizontal eye movements are often impaired due to the involvement of the PPRF • vertical eye movements or eyelid movements are preserved . • The EEG reflects the patient's state of wakefulness. • Localization: • lesions involve the descending motor pathways bilaterally in the basis pontis but spare the more dorsal reticular formation • Bilateral ventral midbrain lesions • Causes: • basilar artery thrombosis with ventral pontine infarction • pontine hemorrhage • tumor • central pontine myelinolysis (osmotic demyelination syndrome) • tentorial herniation • Guillain-Barre syndrome or myasthenia gravis may rarely cause this syndrome.

10. Outline • Coma, Akinetic Mutism, and Locked-In Syndrome • Anatomic Substrate of Alertness • Signs with Localizing Value in Coma • Respiratory Patterns • Temperature Changes • The Pupils • Eye Movements • Motor Activity of the Body and Limbs • Clinical Presentations of Coma-Inducing Lesions Depending on their Location • Metabolic Encephalopathy (Diffuse Brain Dysfunction) • Supratentorial Structural Lesions • Subtentorial Structural Lesions • Psychogenic Unresponsiveness

11. Anatomic Substrate of Alertness • the maintenance of consciousness depends on interaction between the ascending reticular activating system (ARAS) and the cerebral hemispheres

12. the ARAS lies in the paramedian tegmental region of the posterior portion of the pons and midbrain . It is a complex polysynaptic fiber system that extends from the superior half of the pons through the midbrain to the posterior portion of the hypothalamus and to the thalamic reticular formation The thalamus is the source of diffuse thalamocortical projections that regulate and coordinate cortical activity Sedative drugs act, at least in part, by interfering with the synaptic network of the ARAS, which is played on by sensory stimuli.

13. Bilateral cerebral hemispheric lesions may cause transient coma, particularly when they involve the mesial frontal region. • Large unilateral lesions of the dominant hemisphere may occasionally cause transient unresponsiveness, even in the absence of a mass effect . • posterior hypothalamic lesions induce prolonged hypersomnia. • Acute bilateral damage of the paraventricular thalamic nuclei is attended by transient unresponsiveness, followed, when the lesions are large, by severe amnestic dementia .

15. Outline • Coma, Akinetic Mutism, and Locked-In Syndrome • Anatomic Substrate of Alertness • Signs with Localizing Value in Coma • Respiratory Patterns • Temperature Changes • The Pupils • Eye Movements • Motor Activity of the Body and Limbs • Clinical Presentations of Coma-Inducing Lesions Depending on their Location • Metabolic Encephalopathy (Diffuse Brain Dysfunction) • Supratentorial Structural Lesions • Subtentorial Structural Lesions • Psychogenic Unresponsiveness

16. Cheyne-Stokes respiration denotes a cyclic pattern of alternating hyperpnea and apnea. a bilateral hemispheric or diencephalic insult may indicate incipient transtentorial herniation CHF,COPD,OSA,Uremia. Hyperventilation injury in the pontine or midbrain tegmentum; respiratory failure, hemodynamic shock, fever, sepsis, metabolic disarray, and psychiatric disease. Apneustic breathing prolonged pause at the end of inspiration lateral tegmentum of the lower half of the pons. Cluster breathing Periodic respirations that are irregular in frequency and amplitude with variable pauses between clusters of breaths lower pontine tegmental lesion Ataxic breathing is irregular in both rate and tidal volume suggests damage to the medulla. Respiratory Patterns

17. Temperature Changes • caused by hypothalamic dysfunction • Neurogenic hyperthermia has also been described with pontine tegmental lesions

18. The Pupils • Sleep or bilateral diencephalic dysfunction (metabolic coma) is accompanied by small pupils that react well to light (diencephalic pupils). • Unilateral hypothalamic damage induces miosis and anhidrosis on the side of the body ipsilateral to the lesion. • Midbrain lesions • Tectal or pretectal lesions affecting the posterior commissure • abolish the light reflex, • the pupils are midsized or slightly large, • may show spontaneous oscillations in size (hippus) and become larger when the neck is pinched (ciliospinal reflex). • Tegmental lesions, which involve the third nerve nucleus, nonuniform paresis or paralysis of the pupil sphincter may cause irregular constriction of the sphincter of the iris, with a resultant pear-shaped pupil or displacement of the pupil to one side (midbrain corectopia) . The pupils, often unequal, tend to be midsized and lack light or ciliospinal responses.

19. Pontine tegmental lesions cause small pupils due to interruption of the descending sympathetic pathways. • Lateral pontine, lateral medullary, and ventrolateral cervical cord lesions produce an ipsilateral Horner syndrome. • Oculomotor nerve compression by uncal herniation affect pupillary function earlier and more noticeably than the extrinsic eye movements . The light reflex is sluggish or absent, and, the pupil becomes widely dilated owing to sparing of the sympathetic pathways (Hutchinson's pupil). • Posterior communicating artery aneurysms can compress the third nerve and a massive subarachnoid hemorrhage may result in coma. Fixed pupils are not necessarily a sign of irreversible coma. In a series of 40 patients with fixed pupils, 25% of them made a functional recovery . None of these patients recovered after more than 6 hours with fixed pupils.

22. Eye Movements • Roving eye movements • the eyelids are closed, and the eyes, slightly divergent, drift slowly from side to side • the brainstem is intact • cannot be voluntarily executed and are therefore incompatible with the diagnosis of pseudocoma. In metabolic coma, the pupils may still react when eye movements cannot be elicited. • eyes-open coma • The eyelids may remain tonically retracted because of failure of levator inhibition in some cases of pontine infarction.

25. Short-cycle periodic alternating gaze (ping-pong gaze), • roving of the eyes from one extreme of horizontal gaze to the other and back, with each oscillating cycle taking 2.5 to 8 seconds • This finding usually indicates bilateral cerebral damage (e.g., bilateral cerebral infarcts) with an intact brainstem, but it has also been described with posterior fossa hemorrhage, basal ganglia infarcts, hydrocephalus, …. • This disorder of ocular motility had no prognostic value .

26. Repetitive divergence • the eyes are in midposition or slightly divergent at rest. They then slowly deviate out, become fully deviated for a brief period, and then rapidly return to the primary position before repeating the cycle. These motions are synchronous in both eyes. • is rarely seen in patients with coma from metabolic encephalopathy (e.g., hepatic encephalopathy)

27. Nystagmoid jerking of a single eye, in a vertical, horizontal, or rotatory fashion, may occur with mid- to lower pontine damage. • status epilepticus without appendicular motor manifestations, due to anoxia, may result in brisk, small-amplitude, mainly vertical (occasionally horizontal) eye movements detectable by passive lid elevation

28. Ocular bobbing • intermittent, often conjugate, brisk, bilateral downward movement of the eyes with slow return to midposition • pontine lesions • extra-axial posterior fossa masses • diffuse encephalitis • Creutzfeldt-Jakob disease • toxic-metabolic encephalopathies (e.g., acute organophosphate poisoning) • Typical ocular bobbing, • associated with preserved horizontal eye movements, • specific but not pathognomonic of acute pontine injury, • Atypical ocular bobbing, • associated with absent horizontal eye movements, non-localizing • Monocular bobbing (paretic bobbing), may occur if there is a coexistent unilateral fascicular oculomotor nerve palsy

29. Inverse ocular bobbing (ocular dipping ) • consists of a slow-downward eye movement with fast return to midposition • occur in anoxic coma or after prolonged status epilepticus • It probably reflects diffuse brain dysfunction rather than a single structural lesion • brainstem horizontal gaze reflexes are usually intact.

30. Reverse ocular bobbing • fast-upward eye movement with a slow return to midposition, • occur in patients with metabolic encephalopathy, viral encephalitis, or pontine hemorrhage . • Reverse ocular dipping • slow-upward eye movements followed by fast return to midposition • metabolic or viral encephalopathy (i.e., diffuse cerebral dysfunction) . • pontine infarction (the patient had a one-and-a-half syndrome)

31. Pretectal pseudobobbing • has been described with acute hydrocephalus. • arrhythmic, repetitive downward and inward (V pattern) eye movements at a rate ranging from 1 per 3 seconds to 2 per second and an amplitude of 1/5 to 1/2 of the full voluntary range. • These movements may be mistaken for ocular bobbing, but their V pattern, their faster rate, and their pretectal rather than pontine-associated signs distinguished them from true pontine bobbing. • may have abnormal pupillary light reactions, intact horizontal eye movements, openand often retracted eyelids, a blink frequently preceding each eye movement, and a mute or stuporous rather than a comatose state.

32. Vertical ocular myoclonus • pendular, vertical isolated movements of the eyes noted • patients either locked-in or comatose after severe pontine strokes • other rhythmic body movements at a similar frequency occur after a 6-week to 9-month delay. • associated with palatal myoclonus (palatal tremor), with which they share a common mechanism

34. Abnormalities of Lateral Gaze • Conjugate Gaze When both eyes remain deviated toward the same side in a comatose patient, • Hemispheric lesion, the eyes look toward the lesion (away from the hemiparetic side) • A seizure originating in the frontal or occipital lobes may cause deviation of the eyes and head away from the lesion.

35. wrong-way eyes • forced deviation of the eyes to the side contralateral to the lesion • Thalamic and, rarely, basal ganglionic lesions, almost always hemorrhagic, • Very rarely, frontal-perisylvian lesions • Unilateral lesions affecting the tegmentum of the lower pons cause a horizontal gaze palsy toward the side of the lesion so that the eyes look toward the hemiparetic side. • Neither the oculocephalic maneuver nor caloric testing overcomes a pontine gaze palsy. • Coma due to toxic substances is often accompanied by impaired conjugate eye movements, horizontal as well as vertical ( Wernicke's encephalopathy)

36. Disconjugate Gaze • Isolated failure of ocular adduction, in the absence of pupillary changes and with normal vertical eye movements (elicited by oculocephalic or oculovestibular reflexes), • a lesion of the MLF in the upper pons ipsilateral to the eye that fails to adduct. • MLF involvement is commonly bilateral in comatose patients. • Latent strabismus may become apparent when the level of alertness is mildly impaired but disappears in deep coma.

37. Abnormalities of Vertical Gaze • Disconjugate vertical gaze in the resting position (skew deviation) • the brainstem, with increased intracranial pressure, or with hepatic coma • bilateral midbrain tectal damage: paresis of upward gaze • thalamic hemorrhage Tonic downward deviation of the eyes, often accompanied by convergence, (pressure on the dorsal mesencephalon) . • Sustained upgaze has been reported with severe anoxic encephalopathy and with phenothiazine intoxication.

38. Downward gaze is preferentially affected by bilateral lesions of the superomedial perirubral region • Large midbrain tegmental lesions abolish vertical gaze.

39. Corneal Reflex • The corneal reflex has a higher threshold in comatose patients. • decreased corneal sensitivity • cranial nerve V lesions, ipsilateral lateral pontomedullary lesions, or contralateral parietal lesions • impaired eye closure (as with cranial nerve VII lesions and low pontine lesions). • the stimulus may induce deviation of the jaw to the opposite side (corneopterygoid reflex), • given an intact upper pons and midbrain, the eyes may roll upward (Bell's phenomenon)

40. Motor Activity of the Body and Limbs • Rarely is a metabolic coma (notably hypoglycemic) accompanied by hemiparesis • decorticate and decerebrate rigidity, are often produced by metabolic disorders

41. Abnormal extension of the arms with weak flexion of the legs usually indicates damage of the pontine tegmentum With even lower lesions involving the medulla, total flaccidity ensues. Flaccidity in a critically ill patient can also be produced by a polyneuropathy/ myopathy Extensor (“decerebrate”) posturing adduction, extension,and pronation of the upper extremities and extension of the lower extremities; It is indicative of injury to the caudal diencephalon, midbrain, or pons Severe metabolic (e.g., anoxic) disorders • Flexor (“decorticate”) posturing • Flexion and adduction of arms and wrists with • extension of lower extremities; • it suggests hemispheric or thalamic damage, with sparing of structures below the diencephalons

42. Outline • Coma, Akinetic Mutism, and Locked-In Syndrome • Anatomic Substrate of Alertness • Signs with Localizing Value in Coma • Respiratory Patterns • Temperature Changes • The Pupils • Eye Movements • Motor Activity of the Body and Limbs • Clinical Presentations of Coma-Inducing Lesions Depending on their Location • Metabolic Encephalopathy (Diffuse Brain Dysfunction) • Supratentorial Structural Lesions • Subtentorial Structural Lesions • Psychogenic Unresponsiveness

43. Metabolic Encephalopathy (Diffuse Brain Dysfunction) • carbon monoxide poisoning causes pallidal necrosis in addition to the widespread cortical damage • Functions subserved by complex polysynaptic pathways are affected earlier by metabolic disturbances than those mediated by a few neurons. • Therefore, higher cortical functions and attention succumb early to metabolic insults, whereas the pupillary light reflex remains

44. Asymmetric motor findings speak against the diagnosis of metabolic encephalopathy • Exceptions: • downward deviation of the eyes may be occasionally associated with hepatic encephalopathy • hemiparesis with hypoglycemia. • ethylene glycol, produce focal brain injuries with the corresponding neurologic localizing findings • Focal seizures are common in metabolic encephalopathies, particularly those coursing with the breakdown of the blood-brain barrier, such as eclampsia, malignant hypertension, and acute intermittent porphyria

45. Toxic-metabolic disorders often induce abnormal movements (tremor, asterixis, myoclonus, and seizures) that seldom accompany focal structural lesions of the brain.

46. Unilateral asterixis may appear when a toxic encephalopathy coexists with a structural lesion in: • contralateral to lesions of the mesencephalon, ventrolateralthalamus, primary motor cortex, or parietal lobe • ipsilateral to lesions of the pons or medulla • Episodes of lapses of postural control by the reticular formation may be responsible for midbrain asterixis. • Occasionally, bilateral asterixis may occur with bilateral lesions of the midpons or with bilateral mesencephalic lesions.

47. Multifocal myoclonus • sudden, nonrhythmic twitching that affects first one muscle, then another, without any specific pattern except a tendency to involve the facial and proximal limb musculature. • The causes : • uremic • hyperosmolar-hyperglycemic encephalopathy, • carbon dioxide narcosis, • a large dose of intravenous penicillin

48. Generalized myoclonus, • mainly involves the axial musculature, which contracts suddenly, making the patient jump with a certain periodicity • It may also appear as irregular brief jerks in both face and limbs. • The myoclonus is often stimulus sensitive • is most prominent in the first postresuscitation day and tends to abate spontaneously in subsequent days. • The patients often have a burst-suppression pattern on EEGs and cerebral edema or infarcts on CT scan or MRI. • Severe anoxic cortical and brainstem damage are the most common pathologic correlates of generalized myoclonus (also called myoclonic status), which carries a poor prognosis

49. Supratentorial Structural Lesions • Lateral Herniation