It might seem as if it came straight out of a movie: a comatose patient suddenly moves his hand in a purposeful manner, trying to grab the bed rail or even your hand. There are times when a neurologist may be called to evaluate such a patient with limb movements that may seem rhythmic, chaotic, sudden, or purposeful, or even eyes that may be moving from side to side as if scanning the surroundings. For some, this concept may seem enigmatic or even raise doubts that the patient is in a coma. Although the novice may find such a consultation intellectually perplexing, the experienced neurologist encounters this routinely. Typically, the neurologist is asked to investigate because of clinical concerns of a seizure. While evaluating these patients, the clinician also must be able to distinguish between the different states of consciousness that may mimic coma, such as akinetic mutism, locked-in state, coma vigil, vegetative state, and even psychogenic unresponsiveness. This chapter will provide a review of different types of nonepileptic movements in coma patients.

There is a strong correlation between etiology, neuroanatomy, pathophysiology, and phenomenology in the production of nonepileptic movements in coma. It is because of this complexity that this chapter is outlined in two different forms. The initial part of the chapter follows the phenomenological view, and the latter part follows an etiologic approach.

To fully appreciate the variety of movements associated with the comatose state, an understanding of the anatomical basis of consciousness is necessary. The interactions between the ascending reticular activating system (ARAS) and the cerebral cortex enable consciousness. In 1949, Moruzzi described a distinct lesion to the ARAS that could induce a state of coma with persistent sleep patterns on electroencephalographic (EEG) studies, despite application of a noxious stimulus.¹The ARAS projects from the paramedian tegmental rostral half of the pons up through the midbrain, to the dorsal hypothalamus, and into the thalamic reticular formation.² The thalamus is rich in cholinergic, noradrenergic, and serotoninergic neurotransmitters, which play an important functional role within the reticular system and therefore with coma.³ When bilateral thalami are lesioned, their delicate neurochemical homeostasis is perturbed, resulting in neuronal dysfunction and a comatose state.⁴ Direct damage to these structures, or inhibition of their cortical inputs, results in impaired consciousness. The source of damage and inhibition is generally divided into two categories: metabolic and structural.

The metabolic comas are considered to be encephalopathic in nature. Abnormal movements such as tremor, asterixis, and myoclonus are commonly associated with metabolic encephalopathies.² Primary encephalopathies are intrinsic disorders affecting glial or neuronal metabolism. Secondary encephalopathies are extrinsic to the metabolism of the central nervous system (CNS) and result from impaired metabolism and intoxication of other systemic organ systems. Ischemic encephalopathy is characterized by severe changes in cerebral blood flow. During sleep and wakefulness, the cerebral metabolic rate of oxygen (CMRO₂) remains constant in individuals with normal brain function and intact autoregulation.^5,6 When the CMRO₂ falls below 2 cc of oxygen per 100 g of brain tissue per minute, patients will experience severely impaired alertness.⁷

According to Brazis PW, movements in light coma can range from motionless to wildly thrashing.² When examining the patient, one must distinguish between stimulus-induced (reflex) and spontaneous (automatisms) movements. The motor responses can be further divided into three types: appropriate, inappropriate, and absent. Appropriate responses are found when the corticospinal tracts (partial or complete) are intact, such as in psychogenic unresponsiveness. Inappropriate responses are decorticate posturing, decerebrate posturing, and decerebrate posturing of the upper limbs with lower limb flexing.⁸ Decorticate posturing tends to occur when the lesion is above the midbrain’s red nucleus. In decerebrate posturing, the lesion is below the red nucleus, leaving the vestibular nuclei and reticulospinal tracts unchecked by more rostral input. This uninhibited stimulation of the vestibular nuclei causes an increase in extensor tone to the vestibulospinal tracts.²

The basal ganglia play an important role not only in movement but also in alertness.⁹ The basal ganglia are known to have two principal neurotransmitters: dopamine and glutamate. The dopaminergic systems are divided into three pathways: striatonigral, mesocortical, and mesolimbic.¹⁰ Lesions to any of these three systems can cause abnormal limb movements, and when the ARAS, thalamus, or diffuse cortical involvement has occurred, patients can present in a comalike state with involuntary limb movements. Orofacial dyskinesias can occur from striatonigral lesions. These abnormal movements are considered involuntary facial, lip, and tongue movements that occur spontaneously.¹¹ The etiologies of such dyskinesias are multiple, but when the lesion involves the thalamus or ARAS, the patient may be in a coma. In a comatose patient with orofacial dyskinesias, it is of utmost importance to obtain an EEG to rule out a seizure.

Because there tends to be a blurry line between coma and brain death, practitioners often have difficulty in distinguishing between the two when a brain-dead person is moving. Most of the common movements occur within the first 24 hours after brain death is declared, but they can also be seen as long as 72 hours after brain death. Lazarus sign, limb elevation, hugging-like motion, head turning, facial myokymia, eyelid opening, spinal myoclonus, and undulating toe, finger, and toe jerking are some of the most commonly reported movements. Of these movements, undulating toe, finger, and toe jerking is considered the most common sign.^12,13 Just prior to brain death, steplike movements can be seen secondary to brain disinhibition. When there is a question as to the source of movement, evoked potentials (somatosensory [SSEP] and brainstem auditory [BAEP]) can provide definitive help by evaluating the functional integrity of the central cerebrum.¹⁴

Eyelid opening apraxia is the inability to raise one’s eyelids voluntarily in the absence of ptosis or blepharospasm. This can make the patient appear comatose. Depending on the extent of the lesion, the patient will move his or her limbs purposefully, like a comatose patient having involuntary movements. Nondominant or bilateral hemispheric lesions can cause eyelid apraxia.¹⁵ Other lesions that can cause eyelid apraxia and coma may be in the subthalamic nucleus or putamen. Eyelid apraxia and a comalike stage also may occur in the later stages of amyotrophic lateral sclerosis, parkinsonism-dementia complex, progressive supranuclear palsy, neuroacanthocystosis, Huntington disease, Parkinson disease, and multisystem atrophy-autonomic subtype (formerly Shy-Drager syndrome).^16–19

The interconnections among the basal ganglia, supplementary motor cortex, and ventrolateral thalamus result in production of movement. Excess activity in the globus pallidus internus and subthalamic nucleus can bring about bradykinesia.²⁰ Although bradykinesia is most commonly recognized in Parkinson disease, it can occur in patients who have thalamic or basal ganglia lesions. The paucity of movement can be mistaken for arrest of motor activity seen during complex partial seizures, especially when unilateral and at rest. According to Lee and Stein, tremororiginates from disinhibition of the thalamic pacemaker cells that typically discharge rhythmically at 5 to 6 Hz.²¹ When metabolic encephalopathy is the cause of tremor, it tends to be coarse and irregular and has a rate of 8 to 10 Hz. Often, this tremor may be thought of as a seizure, especially if it has a characteristic rhythmicity. Tremor can be found in different parts of the body, such as the face, tongue, and limbs. Most commonly, the hands are affected.⁷ The tremor severity has been shown to correlate with the degree of decreased homovanyllic acid concentration in the pallidum.²²

Rigidity is believed to be caused by hyperactive fusimotor activity of alpha, beta, and gamma motor neurons.²⁰ Involuntary contractions, known as a Westphal phenomenon, can be caused by excessive supraspinal drive on normal spine mechanisms.²³ Involuntary movements can also be caused by chronic use of indirect-acting dopamine agonists.²⁴ Choreiform movements are involuntary, rhythmic, dancing-like limb movements. Deterioration of the dopaminoceptive cells in the striatum is known to cause choreiform movements. Involuntary limb movements can also result from a lesion of the subthalamic nucleus.²⁰ Dopamine receptor antagonists can be used for the management of these choreiform movements.²⁵

Myoclonus is manifested as sudden, nonrhythmic involuntary movements that may affect single or bilateral limbs. It has a broad range of etiologies, including vascular, infectious, drug-induced, and metabolic causes,²⁶ but is commonly seen in uremic patients. Multifocal myoclonus is generally seen in severe stages of toxic-metabolic encephalopathy in which the patient is stuporous or comatose.⁷ Multifocal myoclonus is characterized as nonrhythmic, sudden, unilateral movements, which then spread to the contralateral side of the body as the etiologic disorder progressively evolves. Frequently, proximal muscles are involved. Posterior thalamic lesions can result in a specific form of myoclonus associated with dystonic movements.²⁷

Asterixis is a coarse, involuntary tremor commonly resulting from systemic organ failure and resultant impairment in cerebral metabolism. The etiology can range from toxic metabolic causes to structural thalamic lesions. Asterixis was first described in hepatic coma.²⁸ Although asterixis tends to subside with worsening levels of consciousness, it can still be demonstrated by dorsiflexion of the wrist during examination.²⁹ EEG in both myoclonus and asterixis may show triphasic waves, particularly when the etiology is toxic-metabolic (Figure 29-1).

A tremendous diversity of eye movements can be found in comatose patients. The overwhelming variety and subtlety of these movements can create misunderstandings in their interpretation and anatomical localization. Considering the numerous types of abnormal ocular movements, this section will focus on those commonly seen in comatose patients that can be mistaken as epileptic. Most abnormalities of ocular movement are attributable to discrete or functional lesions of the rostral midbrain. The two specific regions of interest are the ocular motor nerve and the rostral interstitial medial longitudinal fasciculus (riMLF). Although thalamic lesions are not known to cause abnormal ocular movements (i.e., vertical gaze palsies), extension of these lesions from the thalamus routinely involves the upper midbrain.³⁰ Elevated intracranial pressure due to hydrocephalus or a midbrain lesion can give rise to Parinaud phenomenon (Figures 29-2 and 29-3). This phenomenon is manifested by tonic eye deviation in a down and inward pattern with accompanying convergence retraction nystagmus and eyelid retraction.³¹ Blepharospasm, which can mimic subtle eye movements suggestive of nonconvulsive seizures, occurs with diencephalic lesions.³²

Involuntary eye movements that pan from one extreme of the horizontal plane to the other are referred to as ocular roving. These movements take ~2.5 to 8.0 seconds for each oscillating cycle. Lack of cortical inhibition to the paramedian pontine reticular formation (PPRF) will result in ocular roving. This tends to occur after diffuse bihemispheric damage with an intact brainstem.^33–35 Nystagmus jerking of a single eye, in a vertical, rotatory, or horizontal direction, can occur with pontine lesions.² Repetitive divergence is a synchronously slow divergence of both eyes outward with a rapid return to the midposition. Metabolic encephalopathies, especially hepatic, can cause such a synchronously cyclic horizontal divergence.³⁷

Ocular bobbing is a rapid, intermittent, conjugate, bilateral downward movement of the eyes with a slow return to the midposition.³⁸ There are two types of ocular bobbing: typical and atypical. Typical ocular bobbing is somewhat specific, though not pathognomonic, of acute pontine lesions and is associated with impaired lateral gaze (Figure 29–4). The atypical type is less localizable and marked by retention of horizontal gaze function.³⁹ Inverse ocular bobbing manifests itself as slowly moving eyes downward, then returning rapidly to the midposition. It may occur after prolonged status epilepticus or anoxic coma.^40–42 Considering the brainstem is usually intact in these scenarios, it likely is reflective of diffuse brain dysfunction.²

Converse ocular bobbing is a slow upward ocular movement that then returns rapidly to the midposition.⁴³ This type of ocular bobbing is poorly localizable but has been described in pontine infarctions⁴⁴ and both viral and metabolic encephalopathies.⁴⁵ Reverse ocular bobbing is an upward, rapid eye movement with a slow return to the midposition.⁴³ Drug-induced reverse ocular bobbing has been described with benzodiazepine and phenothiazine poisoning.⁴⁶ Pontine hemorrhage, viral encephalitis, and metabolic encephalopathy have also been linked with this phenomenon.^44,45,47

In vertical ocular myoclonus, the eyes tend to move vertically and are pendular in nature. This is seen in coma or locked-in state (deefferent state) resulting from pontine lesions. Usually associated with palatal myoclonus, in vertical ocular myoclonus, the eyes tend to oscillate at a frequency of 2 Hz, are in isolation, and move in a to-and-fro pattern. Because of this, the term myoclonus is misleading.⁴⁸ Ocular myoclonus shares a mechanistic link with palatal myoclonus and therefore may occur concomitantly.⁴⁹ This association is understandably referred to as oculopalatal myoclonus.⁵⁰

A commonly associated localization is the dentatorubral-olivary pathway (Guillain-Mollaret triangle).⁴³

In oculogyric crisis, the eyes move up and laterally in a spastic, episodic, and conjugate manner. Rarely, they move downward and laterally. This disorder was once commonly seen in postencephalitic parkinsonism, but now it is more prominently seen as a side effect of neuroleptic medications. Other disorders that can be associated with oculogyric crisis are encephalitis (lethargica and brainstem), traumatic brain injury, bilateral putamenal hemorrhage, and third ventricular gliomas.^27,43 Refractory nystagmus, first described by Koeber in 1903, is a simultaneous co-contraction of all six extraocular muscles that manifests as irregular ocular jerks that retract the globe back into the orbit.^51,52 The lesion tends to be localizable to the mesencephalon.⁵³ Table 29-1 shows some spontaneous ocular movements seen in coma patients.

Vascular Etiologies

Abnormal movements are often a result of impairment in neuronal pathways responsible for execution of normal movements. Such dysfunctions result from a variety of causes, but perhaps no cause is more common than vascular lesions. Vascular lesions may take the form of ischemic infarction, either related to a primary stroke or secondary to edema, vascular spasm, or impaired perfusion. Hemorrhage may result from aneurysmal rupture, vascular malformations, or inflammation and fragility of vessel walls. Although an exhaustive description detailing all of the possible vascular causes of stroke is beyond the scope of this chapter, an appreciation of the vascular supplies of the deep subcortical regions of the brain is necessary. Common abnormal movements with their anatomical localization and vascular territories are listed in Table 29-2.