A key and often misunderstood point is that increases in ICP are withstood remarkably well by the brain, as long as they progress relatively slowly. InpatientswithchronicelevationofCSF
pressure, such as those with pseudotumor cerebri, there is little evidence of brain dysfunction, even when CSF pressures reach 600 mm of water or greater. The chief problems induced by increased ICP are papilledema and headache, until the pressure gets high enough to impair cerebral blood flow.
Papilledema is due to the pressure disc. Similarly, the retinal veins within the eye are subject to intraocular pressure. They also leave through the optic disc and run along the optic nerve. The optic nerve in turn is surrounded by a dural and arachnoid sleeve, which contains CSF that communicates with the CSF in the subarachnoid space around the brain.5 The optic disk itself is composed of a dense fibrous network forming a cribriform (from the Latin for sieve) plate that acts as a pressure fitting, so that the optic nerve and retinal vein are exposed to intraocular pressure on one side of the disk and to ICP on the other side.
Normally, axonal transport proceeds unimpeded and the retinal veins show normal venous pulsations, as there is little, if any, pressure differential between the two compartments. As ICP rises above systemic venous pressure, retinal venous pulsations are damped or eliminated as an early feature of papilledema. The retinal veins become larger and more numerous appearing, because increased venous pressure causes smaller veins to become more noticeable on funduscopy.
Thus, the presence of retinal venous pulsations is a good but not invariable sign of normal ICP, and engorgement of retinal veins is a reliable early sign of increased ICP.6,7 A second consequence of increased ICP is that axoplasmic flow is impaired (as if a loose ligature had been tied around the nerve), and there is buildup of axoplasm on the retinal side of the disk. The swollen optic axons obscure the disk margins, beginning at the superior and inferior poles, then extending laterally and finally medially.8 The size of the optic disk increases, and this can be mapped as a larger
Structural Causes of Stupor and Coma 105
‘‘blind spot’’ in the visual field. Some patients even complain of a visual scotoma in this area.
If ICP is increased sufficiently, the ganglion cells begin to fail from the periphery of the retina in toward the macula. This results in a concentric loss of vision.
Because papilledema reflects the backpressure on the optic nerves from increased ICP, it is virtually always bilateral. A rare exception occurs when the optic nerve on one side is itself compressed by a mass lesion (such as an olfactory groove meningioma), thus resulting in optic atrophy in one eye and papilledema in the other eye (the Foster Kennedy syndrome). On the other hand, optic nerve injury at the level of the optic disk, either due to demyelinating disease or vascular infarct of the vasa nervorum (anterior ischemic optic neuropathy), can also block axonal transport and venous return, due to retrobulbar swelling of the optic nerve.9 The resulting papillitis can look identical to papilledema but is typically unilateral, or at least does not involve the optic nerves simultaneously. In addition, papillitis is usually accompanied by the relatively rapid onset of visual loss, particularly focal loss called a scotoma, so the clinical distinction is usually clear.
The origin of headache in patients with increased ICP is not understood. CSF normally leaves the subarachnoid compartment mainly by resorption at the arachnoid villi.10 These structures are located along the surface of the superior sagittal sinus, and they consist of invaginations of the arachnoid membrane into the wall of the sinus. CSF is taken up from the subarachnoid space by endocytosis into vesicles, the vesicles are transported across the arachnoid epithelial cells, and then their contents are released by exocytosis into the venous sinus. Imbalance in the process of secretion and resorption of CSF occurs in cases of CSFsecreting tumors as well as in pseudotumor cerebri. In both conditions, very high levels of CSF pressure, in excess of 600 mm of water, may be achieved, but rather little in the way of brain dysfunction occurs, other than headache. Experimental infusion of artificial CSF into the subarachnoid space, to pressures as high as 800 or even 1,000 mm of water, also does not cause cerebral dysfunction and, curiously, often does not cause headache.11,12 However, conditions that cause diffusely increased ICP such as pseudotumor cerebri usually do cause headache,13 suggesting
that they must cause some subtle distortion of pain receptors in the cerebral blood vessels or the meninges.14
On the other hand, when there is obstruction of the cerebral venous system, increased ICP is often associated with signs of brain dysfunction as well as severe headache. The headache is localized to the venous sinus that is obstructed (superior sagittal sinus headache is typically at the vertex of the skull, whereas lateral sinus headache is usually behind the ear on the affected side). The headache in these conditions is thought to be due to irritation and local distortion of the sinus itself. Brain dysfunction is produced by back-pressure on the draining veins that feed into the sinus, thus reducing the perfusion pressure of the adjacent areas of the brain, to the point of precipitating venous infarction (see page 154). Small capillaries may be damaged, producing local hemorrhage and focal or generalized seizures.
Superior sagittal sinus thrombosis produces parasagittal ischemia in the hemispheres, causing lower extremity paresis. Lateral sinus thrombosis typically causes infarction in the inferior lateral temporal lobe, which may produce little in the way of signs, other than seizures.
The most important mechanism by which diffusely raised ICP can cause symptoms is by impairment of the cerebral arterial supply. The brain usually compensates for the increased ICP by regulating its blood supply as described in Chapter 2. However, as ICP reaches and exceeds 600 mm of water, the back-pressure on cerebral perfusion reaches 45 to 50 mm Hg, which becomes a major hemodynamic challenge. Typically, this is seen in severe acute liver failure,15 with vasomotor paralysis following head injury, or occasionally in acute encephalitis. When perfusion pressure falls below the lowerlimit required for brain function, neurons fail to maintain their ionic gradients due to energy failure, resulting in additional swelling, which further increases ICP and results in a downward spiral of reduced perfusion and further brain infarction.
Decreased perfusion pressure can also occur when systemic blood pressure drops, such as when assuming a standing position. Some patients with increased ICP develop brief bilateral visual loss when they stand, called visual obscurations, presumably due to failure to autoregulate the posterior cerebral blood flow. Failure of perfusion pressure can also
occur focally (i.e., in a patient with an otherwise asymptomatic carotid occlusion who
develops symptoms in the ipsilateral carotid distribution on standing because of the resulting small drop in blood pressure). If the patient has bilateral chronic carotid occlusions, transient loss of consciousness may result.16
Patients with elevated ICP from mass lesions often suffer sudden rises in ICP precipitated by changes in posture, coughing, sneezing, or straining, or even during tracheal suctioning (plateau waves).17 The sudden rises in ICP can reduce cerebral perfusion and produce a variety of neurologic symptoms including confusion, stupor, and coma18 (Table 3–2). In general, the symptoms last only a few minutes and then resolve, leading some observers to confuse these with seizures.
Finally, the loss of compliance of the intracranial system to further increases in volume and the rate of change in ICP plays an important role in the response of the brain to increased ICP. Compliance is the change in pressure caused by an increase in volume. In a normal brain, increases in brain volume (e.g.,
due to a small intracerebral hemorrhage) can be compensated by displacement of an equal
volume of CSF from the compartment.
However, when a mass has increased in size to the point where there is little remaining CSF in the compartment, even a small further increase in volume can produce a large increase in compartmental pressure. This loss of compliance in cases where diffuse brain edema has caused a critical increase in ICP can lead to the development of plateau waves. These are large, sustained increases in ICP, which may approach the mean arterial blood pressure, and which occur at intervals as often as every 15 to 30 minutes.19,20 They are thought to be due to episodic arterial vasodilation, which is due to systemic vasomotor rhythms, but a sudden increase in vascular volume in a compartment with no compliance, even if very small, can dramatically increase ICP.21 These sudden increases in ICP can thus cause a wide range of neurologic paroxysmal symptoms (see Table 3–2). When pressure in neighboring compartments is lower, this imbalance can cause herniation (see be-
Table 3–2 Paroxysmal Symptoms That May Result From a Sudden
Increase in Intracranial Pressure
Impairment of consciousness Opisthotonus, trismus
Trancelike state Rigidity and tonic extension/flexion
Unreality/warmth of the arms and legs
Confusion, disorientation Bilateral extensor plantar responses Restlessness, agitation Sluggish/absent deep tendon reflexes Disorganized motor activity, carphologia Generalized muscular weakness Sense of suffocation, air hunger Facial twitching
Cardiovascular/respiratory disturbances Clonic movements of the arms and legs
Headache Facial/limb paresthesias
Pain in the neck and shoulders Rise in temperature
Nasal itch Nausea, vomiting
Blurring of vision, amaurosis Facial flushing Mydriasis, pupillary areflexia Pallor, cyanosis
Nystagmus Sweating
Oculomotor/abducens paresis Shivering and ‘‘goose flesh’’
Conjugate deviation of the eyes Thirst External ophthalmoplegia Salivation
Dysphagia, dysarthria Yawning, hiccoughing
Nuchal rigidity Urinary and fecal urgency/incontinence
Retroflexion of the neck Adapted from Ingvar.18
Structural Causes of Stupor and Coma 107 low).22
Conversely, when a patient shows early signs of herniation, it is often possible to reverse the situation by restoring a small margin of compliance to the compartment containing the mass lesion. Hyperventilation causes a fall in arterial pCO2, resulting in arterial and venous vasoconstriction. The small reduction in intracranial blood volume may reverse the herniation syndrome dramatically in just a few minutes.