Neurology_Adams

Neurology_Adams. Quite often in clinical practice, cerebral angiography, MRI, MRA, or CT performed for an unrelated reason discloses the presence of an unruptured saccular aneurysm. Or, a second or third aneurysm is found during the angiogram to assess a ruptured one. There is now a reasonably sound body of information about the natural history of these lesions. Wiebers and colleagues (1987) observed 65 patients with one or more unruptured aneurysms for 5 years or longer after their detection. The only feature of significance relative to rupture was aneurysmal size. Of the 44 aneurysms smaller than 10 mm in diameter, none had ruptured, whereas 8 of 29 aneurysms 1 cm or larger eventually did so, with a fatal outcome in 7 cases. Two large studies have attempted to refine these statistical data. In the older Cooperative Study of Intracranial Aneurysms, none of the aneurysms less than 7-mm diameter “had further trouble.” A more recent and sizable cooperative study that included 4,060 patients and gathered


Neurology_Adams

Neurology_Adams. Cooperative Study of Intracranial Aneurysms, none of the aneurysms less than 7-mm diameter “had further trouble.” A more recent and sizable cooperative study that included 4,060 patients and gathered data prospectively for 5 years, conducted by the International Study of Unruptured Intracranial Aneurysms Investigators, found an extremely low rate of rupture, approximately 0.1 percent yearly, for aneurysms smaller than 7 mm in diameter, an annual risk of 0.5 percent for aneurysms between 7 and 10 mm, and a risk ranging from 0.6 to 3.5 percent for lesions between 13 and 24 mm (depending on location). The risk ranged up to 10 percent for aneurysms greater than 25-mm diameter. The yearly rates for rupture were higher in all categories if there had been prior bleeding from another site. The location of the lesion also had great bearing on the risk of rupture, as did increasing age; notably, vertebrobasilar and posterior cerebral aneurysms bled at a rate many times higher than the others.


Neurology_Adams

Neurology_Adams. of the lesion also had great bearing on the risk of rupture, as did increasing age; notably, vertebrobasilar and posterior cerebral aneurysms bled at a rate many times higher than the others. Such data aids in comparing the risk of surgery and endovascular treatment, which, for example, exceed the risk of bleeding within 5 years for small aneurysms located in the carotid circulation. In almost all other circumstances, there is overall benefit to obliterating the unruptured aneurysm.


Neurology_Adams

Neurology_Adams. A special problem pertains to clots within an aneurysm that cause transient ischemic attacks or small strokes in the vascular territory distal to the site. The frequency of this complication is not clear and it occurs at times without evident intraluminal clot on an angiogram.


Neurology_Adams

Neurology_Adams. These are considered to be congenital anomalies even when there is considerable atherosclerosis in their walls. They may become enormous in size, by definition greater than 2.5 cm in diameter, but sometimes twice or more as large. Most are located on a carotid, basilar, anterior, or middle cerebral artery, but also are found on the vertebral artery (Fig. 33-29). They grow slowly by accretion of blood clot within their lumens or by the organization of surface blood clots from small leaks. At a certain point they may compress adjacent structures, for example, those in the cavernous sinus, optic nerve, or lower cranial nerves. The giant fusiform aneurysm of the midbasilar artery, with signs of brainstem ischemia and lower cranial-nerve palsies, is a relatively common form. Clotting within the aneurysm may cause ischemic infarction in its territory of supply, as mentioned in the case of berry aneurysms. Giant aneurysms may also rupture and cause subarachnoid hemorrhage, but not nearly as


Neurology_Adams

Neurology_Adams. aneurysm may cause ischemic infarction in its territory of supply, as mentioned in the case of berry aneurysms. Giant aneurysms may also rupture and cause subarachnoid hemorrhage, but not nearly as often as saccular aneurysms. These clinical observations were confirmed by the International Study, referred to above.


Neurology_Adams

Neurology_Adams. Treatment of saccular aneurysms is surgical if the lesion is symptomatic and it is accessible; endovascular techniques have been employed if the lesion is in the vertebral or midbasilar artery. Obliteration of the lumen, coupled with vascular bypass procedures, has been successful in the hands of cerebrovascular neurosurgeons, but the morbidity is high. Some giant aneurysms can be ligated at their necks, others by trapping or by the use of an intravascular detachable balloon. Drake summarized his surgical experience in the treatment of 174 such cases in past years. Some fusiform aneurysms have been wrapped in muslin or similar material with mixed results. We have followed one such patient who had been operated on by T. Sundt more than 35 years ago. Recent attempts at stabilizing the expansion of the aneurysm by deploying an intravascular stent are under study.


Neurology_Adams

Neurology_Adams. The term mycotic aneurysm designates an aneurysm caused by a localized bacterial or fungal inflammation of an artery. (Osler introduced the misnomer mycotic aneurysm to describe an infectious process in the wall of a vessel.) With the introduction of antibiotics, mycotic aneurysms have become less frequent, but they are still being seen in patients with bacterial endocarditis and in intravenous drug abusers. Peripheral arteries are involved more often than intracranial ones; about two-thirds of the latter are associated with bacterial endocarditis caused by streptococcal infections. In recent years, the number of mycotic aneurysms caused by staphylococcal infections and acute endocarditis has increased. The usual pathogenic sequence is an embolic occlusion of a small artery, which may announce itself clinically by an ischemic stroke with white blood cells in the CSF. Later, or sometimes as the first manifestation, the weakened vessel wall ruptures and causes a subarachnoid or brain


Neurology_Adams

Neurology_Adams. itself clinically by an ischemic stroke with white blood cells in the CSF. Later, or sometimes as the first manifestation, the weakened vessel wall ruptures and causes a subarachnoid or brain hemorrhage. An important point is that the aneurysm may appear within days of seeding of the vessel and rupture at any time, although the rates of rupture with subarachnoid hemorrhage are low.


Neurology_Adams

Neurology_Adams. The mycotic aneurysm may appear on only one artery or several arteries, and the hemorrhage, if it has happened, may recur. A consensus regarding the treatment of mycotic aneurysm has not been reached. The underlying endocarditis or bacteremia mandates appropriate antibiotic therapy and, in at least 30 percent of cases, healing of the aneurysm can be observed in successive arteriograms with this approach alone. Antibiotic or antifungal treatment is usually continued for at least 6 weeks. Some neurosurgeons favor excising an accessible aneurysm if it is solitary and the systemic infection is under control. Many mycotic aneurysms do not bleed, and in our view medical therapy takes precedence over surgical therapy.


Neurology_Adams

Neurology_Adams. The finding of blood over a convexity of the cerebral hemisphere, usually discovered because of an evaluation for sudden headache, has become a relatively common occurrence. The causes for this bleeding are numerous, the most obvious being cranial trauma but a diversity of processes may be responsible including cerebral amyloid angiopathy, reversible cerebral vasoconstriction syndrome, cortical vein thrombosis, the use of cocaine, cavernous angioma, dural arteriovenous fistula, and posterior reversible leukoencephalopathy. It is interesting to note that this list largely overlaps with the causes of “thunderclap headache,” discussed earlier and in Chap. 9. Of course, in the appropriate clinical circumstances, ruptured aneurysm and mycotic aneurysm are still concerns. In a survey conducted by Kumar and associates, it was suggested that younger patients present with abrupt headache and older ones, with TIA-like symptoms and imaging findings that were consistent with cerebral amyloid


Neurology_Adams

Neurology_Adams. by Kumar and associates, it was suggested that younger patients present with abrupt headache and older ones, with TIA-like symptoms and imaging findings that were consistent with cerebral amyloid angiopathy. Further notable is the later occurrence of meningeal hemosideriosis as a result of these lesions, particularly with amyloid angiopathy (see Linn and colleagues).


Neurology_Adams

Neurology_Adams. An arteriovenous malformation (AVM) consists of a tangle of dilated vessels that form an abnormal communication between the arterial and venous systems. These are developmental abnormalities that represent persistence of an embryonic pattern of blood vessels and not a neoplasm, but the constituent vessels may proliferate and enlarge with the passage of time. Venous malformations, consisting purely of distended veins deep in the white matter, are a separate entity; they may be the cause of seizures and headaches but less often, of hemorrhage. When a small hemorrhage occurs, it is usually the result of an associated malformation of the so-called cavernous type; these are small hamartomatous lesions of multiple juxtaposed endothelium-lined cavities without interposed neural tissue. These are discussed further on.


Neurology_Adams

Neurology_Adams. True vascular malformations vary in size from a small blemish a few millimeters in diameter lying in the cortex or white matter to a huge mass of tortuous channels constituting an atrioventricular (AV) shunt of sufficient magnitude to raise cardiac output. Hypertrophic dilated arterial feeders can be seen approaching the main lesion and to break up into a network of thin-walled blood vessels that connect directly with draining veins. The latter often form greatly dilated, pulsating channels, carrying away arterial blood. The blood vessels interposed between arteries and veins are abnormally thin and do not have the structure of normal arteries or veins. AVMs occur in all parts of the cerebrum, brainstem, and cerebellum (and spinal cord), but the larger ones are more frequently found in the central part of a cerebral hemisphere, commonly forming a wedge-shaped lesion extending from the cortex to the ventricle. Some lie on the dural surface of the brain or spinal cord, but these more


Neurology_Adams

Neurology_Adams. the central part of a cerebral hemisphere, commonly forming a wedge-shaped lesion extending from the cortex to the ventricle. Some lie on the dural surface of the brain or spinal cord, but these more often turn out to be direct arteriovenous fistulas, as discussed further on.


Neurology_Adams

Neurology_Adams. When hemorrhage occurs from an AVM, it is typically in the form of an intracerebral lesion causing a hemiparesis, hemiplegia, and so forth, or even death. Blood may enter the subarachnoid space, producing a picture almost identical to that of a ruptured saccular aneurysm, but generally less severe. AVMs are about one-tenth as common as saccular aneurysms and about equally frequent in males and females. The two lesions—AVM and saccular aneurysm (on the main feeding artery of the AVM)—are associated in approximately 5 percent of cases; the conjunction increases with the size of the AVM and the age of the patient (Miyasaka et al). AVMs rarely occur in more than one member of a family in the same generation or successive ones. For a review of the embryologic theories of formation of AVMs, the reader is directed to the article by Fleetwood and Steinberg. However, Nikolaev and colleagues found somatic (not germline) mutations in KRAS in endothelial cells within the malformation in about


Neurology_Adams

Neurology_Adams. the reader is directed to the article by Fleetwood and Steinberg. However, Nikolaev and colleagues found somatic (not germline) mutations in KRAS in endothelial cells within the malformation in about half of their patient’s specimens and some evidence of upregulation of angiogenesis as a result.


Neurology_Adams

Neurology_Adams. Bleeding or seizures are the main modes of presentation. Most AVMs are clinically silent for a long time. Although the lesion is present from birth, onset of symptoms is most common between 10 and 30 years of age; occasionally it is delayed to age 50 or even beyond. In almost half of patients, the first clinical manifestation is a cerebral subarachnoid hemorrhage; in 30 percent, a seizure is the first and only manifestation; and in 20 percent, the only symptom is headache. Progressive hemiparesis or other focal neurologic deficit is present in approximately 10 percent of patients. The first hemorrhage may be fatal, but in more than 90 percent of cases the bleeding stops and the patient survives. Most often there are no symptoms before rupture. Chronic, recurrent headache may be a complaint; usually it is of a nondescript type but a classic migraine with or without neurologic accompaniment occurs in approximately 10 percent of patients—probably with greater frequency than it does in


Neurology_Adams

Neurology_Adams. usually it is of a nondescript type but a classic migraine with or without neurologic accompaniment occurs in approximately 10 percent of patients—probably with greater frequency than it does in the general population. Most of the malformations associated with migraine-like headaches lie in the parietooccipital region of one cerebral hemisphere, and about two-thirds of such patients have a family history of migraine.


Neurology_Adams

Neurology_Adams. Huge AVMs may produce a slowly progressive neurologic deficit because of compression of neighboring structures by the enlarging mass of vessels and by shunting of blood through greatly dilated vascular channels. It has also been proposed that an “intracerebral steal” can result in hypoperfusion of the surrounding brain (Homan et al). When the vein of Galen is enlarged as a result of drainage from an adjacent AVM, hydrocephalus may result, particularly in children. With moderate size and large lesions, one or both carotid arteries frequently pulsate unusually forcefully in the neck. A systolic bruit heard over the carotid in the neck or over the mastoid process or the eyeballs in a young adult is suggestive of an AVM. However, such bruits have been heard in fewer than 25 percent of our patients. Exercise such as repeated squatting that increases the pulse pressure may bring out a bruit if none is present at rest. There is no relation of the existence of an AVM, or its rupture, to


Neurology_Adams

Neurology_Adams. patients. Exercise such as repeated squatting that increases the pulse pressure may bring out a bruit if none is present at rest. There is no relation of the existence of an AVM, or its rupture, to chronic hypertension (the same pertains to cerebral aneurysms).


Neurology_Adams

Neurology_Adams. Inspection of the eye grounds will rarely disclose a retinal vascular malformation that is coextensive with a similar lesion of the optic nerve and basal portions of the brain. Cutaneous, orbital, and nasopharyngeal AVMs may occasionally be found in relation to a cerebral lesion. Skull films rarely show crescentic linear calcifications in the larger malformations.


Neurology_Adams

Neurology_Adams. The size, location, and venous drainage characteristics of a cerebral AVM for surgical planning, Spetzler and Martin devised a widely used grading scale. The summed score gives guidance as to the difficulty in surgical removal and has a less certain relationship to the clinical behavior of the lesion. Lesions 1 to 3 mm are considered small, and give 1 point; 3 to 6 mm are medium sized and 2 points; over 6 mm are large and assigned 3 points; location in an eloquent site gives 1 point and venous drainage to the deep veins gives another point (the summed score is between 1 and 5). The use of this scale to plan treatment is discussed in the next section.


Neurology_Adams

Neurology_Adams. It is estimated that the risk of bleeding from a known AVM is approximately 3 percent per year but the rate varies with the location of the lesion and whether there has been bleeding in the past. Features that have been related to risk of bleeding in some series have been a deep or brainstem location of the AVM or deep venous drainage channels, and a previous hemorrhage summarized by Stapf and colleagues. The natural history of AVMs has been studied by Ondra and colleagues, who presented a large and comprehensive series of untreated malformations in Finland over a 30-year period, and another similar series has been reported by Crawford and coworkers in Great Britain. As commented, the rate of rebleeding in most series has been 2 to 4 percent per year over decades but may be as high as 6 to 9 percent in the year after a first hemorrhage. In a series of 1,000 patients referred mainly for proton-beam radiation of an AVM and studied by our colleague


Neurology_Adams

Neurology_Adams. R.D. Adams, 464 had a hemorrhage as the first manifestation and 218 had a seizure (mainly with frontal and frontoparietal lesions). In those few AVMs that came to attention as a result of a progressive neurologic deficit, most were situated in the posterior fossa or axially in the cerebrum. The combination of a prolonged history of headaches, seizures, and a progressive deficit in Adams’ series almost always indicated a large malformation. The matter of an increased risk of AVM rupture during pregnancy has been disputed. The weight of evidence suggests that the risk is not greatly raised by pregnancy alone.


Neurology_Adams

Neurology_Adams. Fully 90 percent of AVMs are disclosed by CT if performed with contrast infusion, and an even larger number by MRI (Fig. 33-30). Magnetic-susceptibility MRI shows small areas of previous bleeding around AVMs. Arteriography is usually necessary to establish the diagnosis with certainty and will demonstrate AVMs larger than 5 mm in diameter; MRI may fail to reveal smaller lesions. Another value of arteriography, particularly if performed with rapid sequential and delayed images is to define all of the feeding arteries, the presence of an associated aneurysm and the channels of venous drainage, all of which inform the expectations of future bleeding and the most advisable methods of obliterating the lesion. The decision to obtain imaging to detect an AVM in cases of typical cerebral hemorrhage of the type discussed in earlier sections is based on factors such as young age (childhood and adolescence onset is particularly suggestive), a history of an unusual unilateral headache syndrome, a


Neurology_Adams

Neurology_Adams. of the type discussed in earlier sections is based on factors such as young age (childhood and adolescence onset is particularly suggestive), a history of an unusual unilateral headache syndrome, a focal seizure disorder, the absence of other apparent cause (e.g., coagulopathy, chronic hypertension, metastatic tumor), but most of all, recurrent bleeding in one location of the brain.


Neurology_Adams

Neurology_Adams. There has been considerable controversy regarding the best mode of treatment: surgical excision, stereotactic radiosurgery, endovascular embolization (or a combination of these), or no treatment. The complexity of these choices is discussed in the review by Solomon and Connolly. The only adequate randomized trial, ARUBA, reported by Mohr and colleagues (2014), comparing intervention of any kind to expectant management found that death or stroke occurred in 10 percent in the expectant management group compared to 31 percent in the group that had intervention. The main criticisms have been the short follow up of 33 months and the lack of assignment by risk of rebleeding or suitability for surgery or another type of treatment. This has engendered considerable controversy and criticism but must be taken into account when advising patients. In a meta-analysis of 13,698 patients, approximately 7 percent with surgical resection and 5 percent after stereotactic radiosurgery were left with


Neurology_Adams

Neurology_Adams. must be taken into account when advising patients. In a meta-analysis of 13,698 patients, approximately 7 percent with surgical resection and 5 percent after stereotactic radiosurgery were left with neurological deficits (van Beijnum et al).


Neurology_Adams

Neurology_Adams. The Spetzler-Martin Scale, which uses a point scale for size (1 to 3), location (eloquent vs non-eloquent) and venous drainage (deep vs superficial) has been used to give guidance as to the surgical difficulty and surgical risk. Grades IV and V, generally representing large deep lesions, are generally not resected; grade III lesions, typically mid or large sized lesions, may be approached surgically but often with preceding interventional embolization of parts of the lesion. Some 20 to 40 percent of AVMs are amenable to block dissection, with an operative mortality rate of 2 to 5 percent and a morbidity of 5 to 10 percent. For inaccessible lesions, attempts have been made to obliterate the malformed vessels by ligation of feeding arteries or by the use of endovascular embolization with liquid adhesives or particulate material that is injected via a balloon catheter that has been navigated into a feeding vessel. Complete obliteration of large AVMs is usually not possible by these


Neurology_Adams

Neurology_Adams. liquid adhesives or particulate material that is injected via a balloon catheter that has been navigated into a feeding vessel. Complete obliteration of large AVMs is usually not possible by these methods but they are effective in reducing the size of the AVM prior to surgery.


Neurology_Adams

Neurology_Adams. Several modes of radiosurgery are used to decrease the size of the lesion, albeit with a substantial delay. This approach is utilized most often with AVMs of 3 cm or smaller located in an area of the brain in which resection would be likely to produce a serious neurologic disability. Kjellberg and Chapman pioneered the treatment of AVMs using a single dose of subnecrotizing stereotactically directed proton radiation. The technique of stereotactic radiosurgery has been adopted using photon radiation sources, such as a linear accelerator, gamma radiation (Karlsson et al) and other modes of focused x-ray radiation as accepted alternatives to operative treatment of small lesions or those situated in deep regions, including the brainstem, the thalamus, or in “eloquent” areas of the cortex. The main drawback to radiosurgery is that obliteration of AVMs occurs in a delayed manner, usually with a latency of at least 18 to 24 months after treatment, during which the patient is unprotected from


Neurology_Adams

Neurology_Adams. main drawback to radiosurgery is that obliteration of AVMs occurs in a delayed manner, usually with a latency of at least 18 to 24 months after treatment, during which the patient is unprotected from rebleeding. The likelihood of successful radiotherapy treatment and the nature of the risks depend on the location and size of the AVM and the radiation dose delivered. After 2 years, 75 to 80 percent of AVMs smaller than 2.5 cm in diameter have been obliterated. Even for those AVMs that have not been totally eliminated, the radiation effect appears to confer some long-term protection from bleeding. Of the larger ones, a majority shrink or appear less dense. A proportion of larger AVMs that are initially obliterated will later recanalize, and many of these will subsequently bleed. Among more than 250 patients whose AVMs disappeared following proton-beam therapy, there has been no recurrence of hemorrhage for up to 10 years (Chapman, personal communication). The results of treatment with


Neurology_Adams

Neurology_Adams. than 250 patients whose AVMs disappeared following proton-beam therapy, there has been no recurrence of hemorrhage for up to 10 years (Chapman, personal communication). The results of treatment with focused radiation have been about the same. In one study, the risk of hemorrhage was reduced by 54 percent between the time of radiation and obliteration of the malformation and by 88 percent thereafter (Maruyama et al).


Neurology_Adams

Neurology_Adams. Two types of complications of radiation occur at a combined rate of approximately 2 to 4 percent. The first is delayed radiation necrosis, which is predictable based on the radiation dose, and the second is venous congestion that occurs several weeks or months after treatment. The latter is indicative of the desired effect of thrombosis of the malformation. Both may cause local symptoms for weeks or months. Radiation necrosis may be reduced by the administration of corticosteroids but the vascular problem generally is not helped.


Neurology_Adams

Neurology_Adams. The treatment of AVMs by endovascular techniques is increasingly being used but has not been fully evaluated. Nearly every AVM has several feeding arteries, some not reachable by a catheter, and some part of the AVM may remain after treatment. In most series, 25 percent or more of AVMs, mostly of small and medium size, have been completely obliterated, with a mortality rate below 3 percent and morbidity of 5 to 7 percent, both of which compare favorably with surgical outcomes. These techniques are particularly suited to lesions of a combined AVM and an aneurysm on the feeding vessel.


Neurology_Adams

Neurology_Adams. In the past several years, combined therapy that begins with endovascular reduction of the lesion and is followed by either surgery or radiation has been viewed favorably. Using this approach, more than 90 percent of lesions can be obliterated with a very low rebleeding rate over several years. It is clear that the plan for each patient must be individualized based on the size, location, nature of feeding vessels, the presence of other vascular lesions (aneurysm or additional AVM), and the age of the patient. Another strategy for otherwise untreatable grade IV and V lesions has been to stage radiosurgery in order to reduce parts of the lesions sequentially as described by Sirin and colleagues. Even then, there will be differences of opinion based on local resources and experience.


Neurology_Adams

Neurology_Adams. Finally, if the primary problem is recurrent seizure, eliminating the malformation often achieves reduction or cessation of seizures in a high proportion of cases but some observational series suggest otherwise. In the interval, antiepileptic drugs are required and may be needed for a period of years after obliteration.


Neurology_Adams

Neurology_Adams. These curious vascular abnormalities, occurring in both the cranial and spinal dura, have different presentations at each site. The spinal form, more common in general experience, is discussed with other diseases of the spinal cord in Chap. 42. The cranial type is being detected with increasing frequency as refinements continue to be made in imaging of the cerebral vessels, but its incidence and pathogenesis are not fully known. The defining features are radiologic—a nidus of abnormal arteries and veins with arteriovenous shunting contained entirely within the leaflets of the dura. The lesion is usually fed by dural arterial vessels derived from the internal cranial circulation and often, more prolifically, from the external cranial circulation (external carotid artery and muscular branches of the vertebral artery). Venous drainage of these lesions is often complex and is largely directed to the dural venous sinuses (Fig. 33-31). The rapid transit of injected angiographic dye through


Neurology_Adams

Neurology_Adams. of the vertebral artery). Venous drainage of these lesions is often complex and is largely directed to the dural venous sinuses (Fig. 33-31). The rapid transit of injected angiographic dye through dural fistulas accounts for the early opacification of the draining venous structures. In the case of high-flow connections, this may not be seen unless images are taken almost immediately after the injection. A number of potential feeding vessels must be individually opacified to demonstrate all the conduits into the lesion. On CT and MRI, the fistula is sometimes detected as a thickening or enhancement of a region of dura, generally close to a large dural venous sinus. In other cases, the dilated draining vessels may be seen only with the injection of dye or gadolinium. Probably, many are not detected by either of these techniques.


Neurology_Adams

Neurology_Adams. Several classification systems have been developed that are based on the nature and direction of the drainage of the lesion. There are some associations between the nature of these drainage patters, as summarized by the classification systems, and clinical presentation.


Neurology_Adams

Neurology_Adams. The origin of these vascular lesions has not been settled—several mechanisms may be involved. Most evidence suggests that at least some of them, unlike conventional cerebral AVMs and aneurysms, are not developmental in origin. The best-defined examples of acquired fistulas are those that arise adjacent to a venous sinus thrombosis or in association with a vascular atresia, most often of the transverse sigmoid sinus or adjacent to the cavernous sinus. However, it is not always clear whether the abnormality of the venous sinus is the cause or the result of the dural fistula. In a number of cases, a dural fistula has appeared after a forceful head injury, often in a region remote from the site of impact. Another small group that is more clearly developmental is associated with the Klippel-Trenaunay or Osler-Weber-Rendu syndromes, diseases in which a conjunction with AVMs is well known. (In the first of these, they may also be an associated enlargement of the limb containing the


Neurology_Adams

Neurology_Adams. or Osler-Weber-Rendu syndromes, diseases in which a conjunction with AVMs is well known. (In the first of these, they may also be an associated enlargement of the limb containing the malformation.) Usually, these causes can be excluded by physical examination and an absence of family history and the largest group remains idiopathic.


Neurology_Adams

Neurology_Adams. A major obstacle to understanding of dural fistula is the varied ways in which this lesion presents itself clinically. Most commonly, there is a fluctuating ischemic-like deficit appropriate to the cerebral or spinal location underlying the lesion or at some distance from it in the case of spinal lesions. The spinal presentations are complex and discussed in Chap. 42. Subdural hemorrhage is an infrequent but dramatic mode of presentation, sometimes creating a large and fatal clot; another syndrome is a cerebral–subarachnoid hemorrhage, although this occurs with not nearly the same frequency or severity as bleeding from brain AVMs. Indeed, the risk of bleeding from dural fistulas and the evolution of these lesions is far less precisely known than it is for cerebral AVMs. It appears that the dural lesions most at risk of bleeding are those located in the anterior cranial fossa and those at the tentorial incisura. Seizures are uncommon. Yet another special syndrome linked to dural AVMs,


Neurology_Adams

Neurology_Adams. dural lesions most at risk of bleeding are those located in the anterior cranial fossa and those at the tentorial incisura. Seizures are uncommon. Yet another special syndrome linked to dural AVMs, although it may occur also with high-flow cerebral malformations, is of headache, vomiting, and papilledema—namely, pseudotumor cerebri (see Chap. 29). A rare syndrome is that of thalamic venous congestion causing a dementing syndrome. Whether the increased intracranial pressure is the cause or the result of the fistula is unsettled, but relief of venous insufficiency may result in regression of fistulae. A cranial bruit, audible to either the examiner or patient, is infrequent with fistula but may be sought. In small children, the high-flow lesions may shunt so much blood as to cause congestive heart failure, similar to arteriovenous malformations of the vein of Galen.


Neurology_Adams

Neurology_Adams. Treatment is by surgical extirpation or endovascular embolization, at times a painstaking procedure because of the multitude of potential feeding vessels. Surgery seems preferable for the smaller lesions and embolization for larger and inaccessible ones. Slowed flow in a venous sinus that is draining a malformation risks venous thrombosis but the advisability of anticoagulation in this circumstance remains uncertain.


Neurology_Adams

Neurology_Adams. Vascular malformations composed mainly of clusters of thin-walled veins without important arterial feeders and with little or no intervening nervous tissue make up a significant group, some 7 to 8 percent of cerebral AVMs. Conventional subdivisions of this group into cavernous, venous, and telangiectatic types have not proven useful. Most clinicians roughly designated them all as cavernous malformations and several attributes set them apart from other vascular malformations. Their tendency to bleed is probably no less than that of the more common AVMs but far more often, the hemorrhages are small and clinically silent. The incidence of bleeding is uncertain but is estimated to be less than 1 percent per year per lesion but quite often they are multiple lesions so that the cumulative risk in any one patient is higher. Flemming and colleagues, in a survey of 292 patients followed for an average of almost 10 years, gave the rate as 0.3 percent annually for asymptomatic lesions and found


Neurology_Adams

Neurology_Adams. in any one patient is higher. Flemming and colleagues, in a survey of 292 patients followed for an average of almost 10 years, gave the rate as 0.3 percent annually for asymptomatic lesions and found that individuals who had a previous episode of bleeding or had more than one lesion were 2.5 times more likely to have another hemorrhage. Of course, the location of the bleeding, especially if in the brainstem, can have major clinical consequences.


Neurology_Adams

Neurology_Adams. As mentioned, approximately 10 percent of these lesions are multiple and 5 percent are familial. In one family we followed, there were 29 affected members in three generations and inheritance followed an autosomal dominant pattern. At the present, several genes have been identified, particularly KRIT1, as possibly causative in individual families. One interesting characteristic of this group, as pointed out by Labauge and colleagues, is the appearance over time of new lesions in one-third of patients. The followup of some of our patients has affirmed this. The diagnosis is based on clinical manifestations and MRI, which discloses a cluster of vessels surrounded by a zone of hypodense ferritin in the T1-weighted images (Fig. 33-32), the product of previous small episodes of bleeding. An uncertain number is associated with adjacent deep venous anomaly visualized by imaging studies and these are discussed in a separate section below.


Neurology_Adams

Neurology_Adams. About one-half of all cavernous angiomas lie in the brainstem, and in the past (before the availability of MRI), many of them were misdiagnosed as multiple sclerosis because of the stepwise accumulation of neurologic deficits with each hemorrhage. A large series of cavernous malformations of the brainstem, most in the pons, has been described by Porter and colleagues. They describe a higher rate of bleeding than had been reported for similar malformations in the cerebral hemispheres, frequent adjacent venous anomalies, and good results from surgical ablation. They estimated the rate of bleeding to be 5 percent per year and the rate of rebleeding, close to 30 percent per year.


Neurology_Adams

Neurology_Adams. Treatment Cavernous angiomas on the surface of the brain, within reach of the neurosurgeon, even those in the brainstem, can be plucked out like blackberries, with low morbidity and mortality. Kjellberg and colleagues treated 89 deeply situated cavernous angiomas with low-dose proton radiation, but our impression is that these vascular malformations, like hemangioblastomas, respond poorly to radiation and are not amenable to treatment by endovascular techniques. Lesions that cause recurrent bleeding and are surgically accessible with little risk are often removed but incidentally discovered angiomas, even if they have caused a small hemorrhage, and those that are inaccessible may be left alone. Although this conservative approach is usually taken, there are not adequate data on the rate and risk of bleeding to determine the proper course of action.


Neurology_Adams

Neurology_Adams. This is perhaps the most common cerebral vascular malformation, estimated to occur in almost 3 percent of large autopsy series. As with cavernous angiomas, these lesions are frequently detected as asymptomatic problems in brain imaging. The defining characteristics are of a caput medusa draining into a small collecting vein. The draining vein itself is often visualized most easily and fills with contrast concurrently with normal cerebral (Fig. 33-33). As mentioned earlier, up to 40 percent of cavernous malformations (probably fewer) have an associated deep venous anomaly. Although the risks of stroke in relation to one of these anomalies is low, less than 1 percent per year, small hemorrhage or infarction surrounding a deep venous anomaly may result from acute thrombosis in a collecting vein. A summary of the clinical and imaging features of venous anomalies is given by Ruiz and colleagues. They reviewed the interesting cases reported in the literature in which the anomaly has


Neurology_Adams

Neurology_Adams. vein. A summary of the clinical and imaging features of venous anomalies is given by Ruiz and colleagues. They reviewed the interesting cases reported in the literature in which the anomaly has thrombosed, and discuss the possible pathophysiologic relationship between the vein and the development of a cavernous malformation.


Neurology_Adams

Neurology_Adams. The management of developmental venous anomalies has not been clarified although numerous forms of surgery, embolization, or focused radiation, have been used depending on the nature of an associated lesion such as cavernous malformation, and the occurrence of repeated bleeding. In general, incidentally discovered lesions are simply followed with imaging at reasonable intervals. Other Causes of Intracranial Bleeding and Multiple Cerebral Hemorrhages


Neurology_Adams

Neurology_Adams. Other Causes of Intracranial Bleeding and Multiple Cerebral Hemorrhages Next in frequency to hypertension, anticoagulant therapy is currently the most common cause of cerebral hemorrhage. The hemorrhages that develop, although sometimes situated in the sites of predilection of hypertensive hemorrhage, are more likely to occur elsewhere, mainly in the lobes of the brain. The reversal of anticoagulant or antiplatelet agents is discussed in an earlier section on “Treatment of Cerebral Hemorrhage.” When bleeding is associated with aspirin therapy or other agents that affect platelet function, fresh platelet infusion, often in massive amounts, may be used to control the hemorrhage; however, their effectiveness in management of cerebral hemorrhage has been questioned.


Neurology_Adams

Neurology_Adams. In the elderly, amyloid angiopathy appears to be a major cause of lobar bleeding, but more characteristic are small, multiple, and successive areas of bleeding. Several of our patients who later proved to have amyloid angiopathy had minor head injuries in the weeks before hemorrhage. The subject is discussed in a later section and the characteristic multiple spot hemorrhages are shown in Fig. 33-34.


Neurology_Adams

Neurology_Adams. Several primary hematologic disorders are also complicated by hemorrhage into the brain. The most frequent of these are leukemia, aplastic anemia, and thrombocytopenia of various causes. Often they give rise to multiple intracranial hemorrhages, some in the subdural and subarachnoid spaces. As a rule, this complication signals a fatal outcome. Other, less-common causes of intracerebral bleeding are advanced liver disease, uremia that is being treated with dialysis, and lymphoma. Usually several factors are operative in these hematologic cases: reduction in prothrombin or other clotting elements (fibrinogen, factor V), bone marrow suppression by antineoplastic drugs, and disseminated intravascular coagulation. Any part of the brain may be involved, and the hemorrhagic lesions are usually multiple. Frequently there is also evidence of abnormal bleeding elsewhere (skin, mucous membranes, kidneys) by the time cerebral hemorrhage occurs. Plasma exchange, used in the treatment of myasthenia


Neurology_Adams

Neurology_Adams. Frequently there is also evidence of abnormal bleeding elsewhere (skin, mucous membranes, kidneys) by the time cerebral hemorrhage occurs. Plasma exchange, used in the treatment of myasthenia gravis and Guillain-Barré disease, lowers the serum fibrinogen to a marked degree, but we have not observed a single instance of intracerebral hemorrhage in more than 500 patients treated in this way.


Neurology_Adams

Neurology_Adams. Occasionally the origin of intracranial hemorrhage cannot be determined clinically or pathologically. In some postmortem cases, a careful microscopic search discloses a small arteriovenous malformation; this is the basis for suspecting that an overlooked lesion of this type may be the cause of cerebral hemorrhage in other cases. Primary intraventricular hemorrhage, a rare event in adults, can sometimes be traced to a vascular malformation or neoplasm of the choroid plexus or one of the choroidal arteries; more often, such a hemorrhage is the result of periventricular bleeding often from a medial thalamic hemorrhage, in which blood enters the ventricle without producing a large parenchymal clot.


Neurology_Adams

Neurology_Adams. Hemorrhage into primary and secondary brain tumors is not rare. When this is the first clinical manifestation of the neoplasm, diagnosis may be difficult. Choriocarcinoma, melanoma, renal cell and bronchogenic carcinoma, pituitary adenoma, thyroid cancer, glioblastoma multiforme, intravascular lymphoma, carcinoid, and medulloblastoma may present in this way, but bleeding is most characteristic of the first three types. Careful inquiry will usually disclose that neurologic symptoms compatible with intracranial tumor growth had preceded the onset of hemorrhage or the primary neoplasm had been revealed previously. Needless to say, a thorough search should be made in these circumstances for evidence of intracranial tumor or of secondary tumor deposits in other organs, particularly the lungs.


Neurology_Adams

Neurology_Adams. A number of disparate diseases may result in a multitude of simultaneous or at least temporally clustered cerebral hemorrhages. Among the most common causes are cerebrovascular amyloidosis (amyloid angiopathy) as mentioned earlier and shown in Fig. 33-34, those related to hematologic and clotting disease, particularly ones that progress rapidly, such as leukemia, but almost any coagulopathy, including those brought on by the administration of medications. The most overwhelming examples in our experience have occurred in the hours after injecting tPA for acute stroke. Serious cranial injury itself may produce a passel of scattered contusions, some of which have the appearance of ball hemorrhages, but most are recognized to be along force lines (see Chap. 34). Occlusion of cerebral veins, particularly of the superior sagittal sinus, causes several biparietal hemorrhages.


Neurology_Adams

Neurology_Adams. Multiple small hemorrhages, brain “microbleeds,” are most commonly considered to be the result of vascular amyloid as discussed in the next section, but may also be associated with chronic hypertension according to Cordonnier and colleagues, but we have been unable to confirm this latter view from our own material. Often, these dozens of small areas of residual blood products or acute hemorrhages do not cause symptoms and are revealed on MRI that is performed for other reasons with gradient-echo and other susceptibility sequences (Fig. 33-34). Certainly, other forms of cerebrovascular disease are found disproportionately in these patients and several series suggest that they represent a risk for future bleeding or ischemic stroke, including lacunes. Multiple cavernous angiomas, the earlier-described amyloid angiopathy, CADASIL, bacterial endocarditis, moyamoya, and mutations that affect blood vessel integrity may also be implicated but the cause in any individual case often remains


Neurology_Adams

Neurology_Adams. amyloid angiopathy, CADASIL, bacterial endocarditis, moyamoya, and mutations that affect blood vessel integrity may also be implicated but the cause in any individual case often remains uncertain.


Neurology_Adams

Neurology_Adams. The pathologic entity called brain purpura (pericapillary encephalorrhagia), incorrectly referred to as “hemorrhagic encephalitis,” consists of multiple petechial hemorrhages scattered throughout the white matter of the brain. The clinical picture is that of a diffuse encephalopathy, but diagnosis is essentially a pathologic one. Blood does not appear in the CSF, and the condition should not be confused with a stroke. The pathologic appearance is highly characteristic. The lesions in brain purpura are small, 0.1 to 2.0 mm in diameter, and are confined to the white matter, particularly the corpus callosum, centrum ovale, and middle cerebellar peduncles. Each lesion is situated around a small blood vessel, usually a capillary. In this para-adventitial area, both the myelin and axis cylinders are destroyed, and the lesion is usually though not always hemorrhagic. Fibrin exudation, perivascular and meningeal infiltrates of inflammatory cells, and widespread necrosis of tissue are not


Neurology_Adams

Neurology_Adams. are destroyed, and the lesion is usually though not always hemorrhagic. Fibrin exudation, perivascular and meningeal infiltrates of inflammatory cells, and widespread necrosis of tissue are not observed. In these respects, brain purpura differs fundamentally from acute necrotizing hemorrhagic leukoencephalitis. Usually the patient becomes stuporous and comatose without focal neurologic signs.


Neurology_Adams

Neurology_Adams. The etiology of brain purpura is quite obscure and there may be several causes. It may complicate viral pneumonia, uremia, promyelocytic leukemia, arsenical intoxication, and, rarely, metabolic encephalopathy and sepsis, or there may be no associated disease. Amyloid angiopathy and an uncharacterized cerebral small vessel disease also have caused this picture of a multiplicity of small hemorrhages. Primary or secondary thrombotic thrombocytopenic purpura (TTP) may be the final common pattern for this entity. A degree of brain hemorrhage is to be expected in acute hemorrhagic leukoencephalitis (Hurst type), which represents an extreme form of acute disseminated encephalomyelitis (see Chap. 35), and in herpes encephalitis (see Chap. 32). The other rare types of hemorrhages, listed in Table 33-8, are self-explanatory.


Neurology_Adams

Neurology_Adams. Hemorrhages of intraspinal origin, all of them rare, may be the result of trauma, AVM (the usual cause of nontraumatic hematomyelia), dural AV fistula, anterior spinal artery aneurysms, or bleeding into tumors such as hemangioblastoma. Spinal subarachnoid hemorrhage from an AVM may simulate an intracranial subarachnoid hemorrhage, causing a stiff neck, headache, and even subhyaloid hemorrhages. Subarachnoid hemorrhage in which interscapular or neck pain predominates should raise the suspicion of an aneurysm of the anterior spinal artery or of a spinal AVM or cavernous angioma. Angiographic study of the radicular spinal vessels and the origins of the anterior spinal arteries from the vertebral arteries may disclose the source of bleeding. Extradural and subdural spinal extravasations may be spontaneous (sometimes in relation to rheumatoid arthritis) but are far more often a result of trauma, anticoagulants, or both. Extradural spinal hemorrhage causes the rapid evolution of paraplegia


Neurology_Adams

Neurology_Adams. spontaneous (sometimes in relation to rheumatoid arthritis) but are far more often a result of trauma, anticoagulants, or both. Extradural spinal hemorrhage causes the rapid evolution of paraplegia or quadriplegia; diagnosis must be prompt if function is to be salvaged by surgical drainage of the hematoma. These entities are discussed further in Chap. 42.


Neurology_Adams

Neurology_Adams. This angiopathy consists of the deposition of amyloid in the media and adventitia of small vessels, predominantly in the meninges, cortex, and cortical penetrating vessels. The incidence at autopsy of vascular amyloid deposition in the brain is related to the age of the population studied; rates of 12 percent are cited in patients older than 85 years of age (the same changes are present in more than 25 percent of individuals with Alzheimer disease, but the nature of the amyloid [Aβ40 in the pure cerebrovascular form] is different in the two conditions). The result of this deposition is several large or numerous small cerebral hemorrhages of various ages. There is a propensity for hemorrhages in the posterior parts of the brain. An association has been found with the homozygous APOE ε4/ε4 genotype by Greenberg and colleagues (1995) but others have found an association with the E2 allele. As alluded to in earlier sections on cerebral hemorrhage, cerebral amyloid angiopathy is a cause of


Neurology_Adams

Neurology_Adams. by Greenberg and colleagues (1995) but others have found an association with the E2 allele. As alluded to in earlier sections on cerebral hemorrhage, cerebral amyloid angiopathy is a cause of otherwise unexplained single of multiple cerebral hemorrhage in older people.


Neurology_Adams

Neurology_Adams. Hemosiderin deposition resulting from multiple small and larger hemorrhages are best visualized with gradient- echo or susceptibility-weighted MRI sequences; they appear as focal spots of abnormal hypointensity on both sequences (Fig. 33-34). Tiny hemorrhages may only be visualized on these sequences and not seen on T1 or T2 MRI sequences, or on CT. The location of the hemorrhages in cerebral amyloid angiopathy, subcortical, frequently posteriorly in the brain, and sometimes subpial, imparts a distinctive imaging pattern that is characteristic of this disease, and quite unlike the pattern of small hemorrhages in the basal ganglia, thalamus, and pons that accumulate in hypertensive disease. In addition to the focal microhemorrhages seen in cerebral amyloid angiopathy, there is frequently cortical gyriform hemosiderosis, reflecting leakage of blood products associated with pial or subpial hemorrhages.


Neurology_Adams

Neurology_Adams. The biology of cerebrovascular amyloid has been summarized by Viswanathan and Greenberg. In our own material, only severe impregnation of vessels with amyloid and fibrinoid change in the vessel wall were associated with hemorrhage (Vonsattel et al). Contrary to previous pronouncements, there is probably no greater risk in evacuating these clots surgically than in the case of other cerebral hemorrhages, but most of them are of a size that allows conservative management and evidence is lacking that surgery improves outcome as discussed earlier.


Neurology_Adams

Neurology_Adams. Reports have emphasized multiple TIA-like syndromes, some with migrainous features such as spreading sensory symptoms that may be the most identifiable but not uniformly present characteristic of the process. They are not consistently related to visible ischemic lesions and may be associated with microhemorrhages and with diffuse white matter changes. In some cases, there is a fairly rapid progression to dementia but that is more characteristic of the inflammatory type of cerebrovascular amyloid discussed just below.


Neurology_Adams

Neurology_Adams. Our colleague S.M. Greenberg (1993) and others have emphasized certain clinical features associated with an inflammatory type of cerebrovascular amyloidosis (see Kinnecom et al and Eng et al), which is referred to as cerebral amyloid angiopathy-related inflammation. Included in the clinical picture are encephalopathy, seizures, headache, and focal cerebral symptoms such as aphasia. The MRI appearance is of large subcortical and cortical patches of abnormal T2 hyperintensity suggestive of cerebral edema. The findings are similar to the mainly white matter encephalitis that was found in some patients with Alzheimer disease who were treated with a monoclonal antibody directed against a-beta amyloid. This disease subtype has a significantly younger age at presentation compared to cerebral amyloid angiopathy and is strongly associated with the APOE ε4/ε4 genotype. It is treated with a course of high-dose corticosteroids or other forms of immunosuppression and some improvement is to be


Neurology_Adams

Neurology_Adams. amyloid angiopathy and is strongly associated with the APOE ε4/ε4 genotype. It is treated with a course of high-dose corticosteroids or other forms of immunosuppression and some improvement is to be expected though outcomes may be unfavorable.


Neurology_Adams

Neurology_Adams. An apparently separate granulomatous or nongranulomatous angiitis has been reported, mainly as a pathologic entity but its clinical characteristics are similar to the inflammatory type. The relationship of this entity to primary granulomatous angiitis of the central nervous system is unclear. There is a separate familial amyloidotic condition of diffuse white matter degeneration with dementia, associated in some families with calcification in the occipital lobes, and the aforementioned mutations in the COL4A gene cause a disruption of the small vessel wall that can cause small cerebral hemorrhages that are similar to those of typical cerebrovascular amyloid.


Neurology_Adams

Neurology_Adams. Hypertensive encephalopathy is the term applied to a relatively rapidly evolving syndrome of severe hypertension, usually systolic pressure above 195 mm Hg, in association with headache, nausea and vomiting, visual disturbances, confusion, and—in advanced cases—stupor and coma. Multiple seizures may occur and may be more marked on one side of the body. In special circumstances, the absolute level of blood pressure seems less pertinent that is a rapid rise in pressure as occurs in eclampsia and with exposure to certain drugs. The neurologic syndrome is usually dominated by symptoms referable to the occipital and adjacent parietal region. There may be visual field deficits, hallucinations, Balint syndrome, and cortical blindness. An indistinguishable syndrome with similar imaging characteristics also occurs with the use of a variety of mainly cancer chemotherapeutic agents as discussed in Chap. 41 and Table 41-1. Papilledema and retinal hemorrhages are frequent accompaniments and it was


Neurology_Adams

Neurology_Adams. also occurs with the use of a variety of mainly cancer chemotherapeutic agents as discussed in Chap. 41 and Table 41-1. Papilledema and retinal hemorrhages are frequent accompaniments and it was stated at one time that the diagnosis should not be made without those findings.


Neurology_Adams

Neurology_Adams. Diffuse cerebral disturbance may be accompanied by focal or lateralizing neurologic signs, either transitory or lasting, which may suggest cerebral hemorrhage or infarction, that is, the more common cerebrovascular complications of severe chronic hypertension. A clustering of multiple microinfarcts and petechial hemorrhages (the basic neuropathologic changes in hypertensive encephalopathy) in one region may occasionally result in a mild hemiparesis, aphasic disorder, or rapid failure or the above-noted distortion of vision.


Neurology_Adams

Neurology_Adams. In instances of typical accelerated hypertension, by the time the neurologic manifestations appear, the hypertension has usually reached the malignant stage, with diastolic pressures above 125 mm Hg, retinal hemorrhages, exudates, papilledema, and evidence of renal and cardiac disease. However, instances of encephalopathy at lower pressures are common, especially if the rise in pressure has been abrupt (see below). If the rate of elevation is high enough, the syndrome may be seen with blood pressure considered to be close to the normal range. Presumably, these circumstances have to do with a change in the permeability of cerebral vessels that is part of the process in special cases such as eclampsia and the hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome that are mentioned further on. The term hypertensive encephalopathy should probably be reserved for the above syndrome and should not be used to refer to chronic recurrent headaches, dizziness, epileptic


Neurology_Adams

Neurology_Adams. are mentioned further on. The term hypertensive encephalopathy should probably be reserved for the above syndrome and should not be used to refer to chronic recurrent headaches, dizziness, epileptic seizures, TIAs, or strokes, which may occur in association with elevated blood pressure.


Neurology_Adams

Neurology_Adams. Encephalopathy may complicate extreme hypertension from any cause (renal disease, renal artery stenosis, acute glomerulonephritis, acute toxemia, pheochromocytoma, Cushing syndrome), cocaine, or administration of drugs such as aminophylline or phenylephrine, but it occurs most often in patients with rapidly worsening “essential” hypertension. In eclampsia, which from a neurologic perspective may be considered a special form of hypertensive encephalopathy, and in acute renal disease, particularly in children, encephalopathic symptoms may develop at blood pressure levels considerably lower than those of hypertensive encephalopathy of “essential” type. Eclamptic retinal and cerebral lesions are the same as those that complicate malignant nephrosclerosis; in both there is also failure of autoregulation of the cerebral arterioles. A discussion of eclamptic seizures can be found in the section on that subject in Chap. 15.


Neurology_Adams

Neurology_Adams. Hypertensive encephalopathy is marked by changes already alluded to on CT and MRI. The findings are of large areas of white matter signal change of edema, but their tendency to normalize over several weeks is remarkable. As summarized by Hauser and coworkers, the main feature is a bilateral increase in T2 signal intensity in the white matter on MRI and a corresponding reduced density on CT, usually concentrated in the posterior part of the hemispheres (see Fig. 33-35). Thus the condition is one of the causes of reversible posterior leukoencephalopathy. These imaging characteristics are a result of an accumulation of fluid, but—unlike the edema in trauma, neoplasm, or stroke—there is little or no mass effect and the water does not tend to course along white matter tracts such as the corpus callosum. In addition, scattered cortical lesions may occur in a watershed vascular distribution and probably correspond to small infarctions. These same findings in the white matter and cortex occur


Neurology_Adams

Neurology_Adams. callosum. In addition, scattered cortical lesions may occur in a watershed vascular distribution and probably correspond to small infarctions. These same findings in the white matter and cortex occur in eclampsia and have been seen in cases of diffuse vasospasm caused by sympathomimetic and serotonergic drugs, discussed further on.


Neurology_Adams

Neurology_Adams. Many cases are also accompanied by focal or diffuse reduction in the caliber of cerebral vessels, especially those on the surface of the cerebral convexities, a configuration that characterizes reversible vasoconstriction syndrome discussed below. Hypertensive encephalopathy or eclampsia may cause additional localized subarachnoid hemorrhage. Most such cases are not caused by the rupture of an intracranial aneurysm and are not as overwhelming as in aneurysmal hemorrhage; indeed, the headache associated with reversible cerebral vasoconstriction syndrome tends to be milder than with aneurysmal rupture and it may be absent. The bleeding, if it occurs, is mainly a feature that is appreciated on MRI examination, as described by Shah. The mechanism is obscure.


Neurology_Adams

Neurology_Adams. In many, but not all, cases, the CSF pressure and protein values are elevated; the latter to more than 100 mg/dL, but there is no cellular reaction. Except to exclude primary subarachnoid hemorrhage, lumbar puncture is not needed to establish the diagnosis. Neuropathologic examination reveals a rather normal-looking brain, but in some cases cerebral swelling, hemorrhages of various sizes, or both will be found. In extreme instances, a cerebellar pressure cone reflects an increased volume of tissue and increased pressure in the posterior fossa; lumbar puncture appears to have only rarely precipitated fatalities. Microscopically there are widespread minute infarcts in the brain, the result of fibrinoid necrosis of the walls of arterioles and capillaries and occlusion of their lumens by fibrin thrombi (Chester et al). This is often associated with zones of cerebral edema. Similar vascular changes are found in other organs, particularly in the retinae and kidneys.


Neurology_Adams

Neurology_Adams. Volhard originally attributed the symptoms of hypertensive encephalopathy to vasospasm. This notion was reinforced by Byrom, who demonstrated, in rats, a segmental constriction and dilatation of cerebral and retinal arterioles in response to severe hypertension. However, the observations of Byrom and of others indicate that overdistention of the arterioles (which have lost their adaptive capacity), rather than excessive constriction, may be responsible for the necrosis of the vessel wall (see reviews of Auer and of Chester et al). The brain edema is the result of active exocytosis of water rather than simply a passive leak from vessels subjected to high pressures. In toxemia or eclampsia, rising levels of the antiangiogenic proteins endoglin, vascular endothelial growth factor, and placental growth factor had been postulated to play a role (Levine et al, 2006) but this has not been fully corroborated. The net result is of various forms of endothelial dysfunction, including presumably,


Neurology_Adams

Neurology_Adams. growth factor had been postulated to play a role (Levine et al, 2006) but this has not been fully corroborated. The net result is of various forms of endothelial dysfunction, including presumably, in the brain.


Neurology_Adams

Neurology_Adams. We have been impressed that the distribution of lesions on the MRI differs between eclamptic and older hypertensive patients, suggesting some difference in pathophysiology, or perhaps simply that chronic hypertension in the latter group predisposes to the occipital lesions. The forms of PRES that are induced by chemotherapeutic and other agents are more complex and are discussed in Chap. 41. A few eclamptic women will develop hemolysis, hepatic failure, and thrombocytopenia—HELLP syndrome—an illness that has similarities to TTP and the hemolytic uremic syndrome (HUS). The interplay between eclampsia and HELLP syndrome in relation to cerebral lesions is complex and not fully understood.


Neurology_Adams

Neurology_Adams. In the past, when effective treatment was not available, the outcome was often fatal. Lowering of the blood pressure with antihypertensive drugs may reverse the picture in a day or two. The same can be accomplished by administering magnesium sulfate in the eclamptic woman. However, antihypertensive drugs must be used cautiously; a safe target is a pressure of 150/100 mm Hg or a 20 percent reduction in mean pressure. One may use intravenous sodium nitroprusside, 0.5 to 0.8 mg/kg/min; a calcium channel blocker such as nifedipine, 10 to 20 mg sublingually; or intravenous beta-adrenergic blockers (labetalol, 20 to 40 mg intravenously followed by an infusion at 2 mg/min, or esmolol are favored). Longer-acting antihypertensive agents, such as ACE inhibitors and calcium channel blockers, must follow these. If there is already evidence of brain edema and increased intracranial pressure, dexamethasone, 4 to 6 mg every 6 h, is sometimes added, but its effect, and the use of hyperosmolar


Neurology_Adams

Neurology_Adams. must follow these. If there is already evidence of brain edema and increased intracranial pressure, dexamethasone, 4 to 6 mg every 6 h, is sometimes added, but its effect, and the use of hyperosmolar therapy, have not been studied systematically; our clinical impression is that they have little effect.


Neurology_Adams

Neurology_Adams. A widespread multifocal or diffuse reduction in the caliber of the cerebral vessels and their branches constitutes a special syndrome of several causes. Vasospasm is, of course, a well-known complication of subarachnoid hemorrhage as described earlier. But the process under discussion has different characteristics. Some degree of attenuation of large cerebral vessels is observed in hypertensive encephalopathy and eclampsia as noted above, but a more diffuse and sustained reduction in vascular caliber can result from various causes summarized in Table 33-10. The main characteristics are severe headache, usually of the “thunderclap” variety as described in Chap. 9, and less prominently or frequently, fluctuating but sudden onset focal neurologic signs, seizures, or confusion that may progress to multifocal cerebral infarction, almost exclusively in the cerebral hemispheres. Women are affected more often than men. The identifying feature pointed out by Call et al is a striking widespread


Neurology_Adams

Neurology_Adams. to multifocal cerebral infarction, almost exclusively in the cerebral hemispheres. Women are affected more often than men. The identifying feature pointed out by Call et al is a striking widespread segmental vasospasm of cerebral vessels. The middle cerebral artery and its branches are mainly affected; the angiographic appearance may be mistaken for arteritis (Fig. 33-36).


Neurology_Adams

Neurology_Adams. There may be an associated posterior leukoencephalopathy or focal brain edema that is similar to the imaging appearance in hypertensive encephalopathy discussed just above. Sometimes the headache is minimal and the attenuation of vessels is found in imaging performed for other reasons. As in hypertensive encephalopathy, the spinal fluid, except perhaps for elevated pressure and occasionally red blood cells in quantities less than seen in rupture of berry aneurysm, is normal. The patients we have seen with RCVS, after several days or weeks of dramatically fluctuating focal neurologic symptoms and disabling headache, have recovered completely or nearly so, but several have had small strokes. The longest recovery in our patients has taken 12 weeks in an idiopathic case. The syndrome is said to recur but two of our patients have had more than one attack, spaced years apart.


Neurology_Adams

Neurology_Adams. Many of our patients have had a history of migraine and the syndrome is often initially mistaken for a migraine attack. Series collected by others give an incidence of migraine of approximately 25 percent. This type of vasculopathy is produced by sympathomimetic drugs alone, such as ephedra in health food supplements, phenylpropanolamine, pseudoephedrine, methamphetamine, and cocaine, but there are few well-studied cases.


Neurology_Adams

Neurology_Adams. The cerebrovascular problems resulting from cocaine use are quite varied. Seizures and death may occur as a result of a syndrome of delirium and extreme hyperthermia. More pertinent to this chapter are the strokes that arise during and just after cocaine use. Here, as emphasized by Levine and colleagues (1991) many years ago, a distinction should be made between the complications of cocaine hydrochloride (the usual form of ingestible cocaine) and the alkaloid form, or “crack cocaine.” The former, when injected intravenously more so than when used intranasally, is prone to cause cerebral hemorrhage as a result of acute hypertension, similar to the bleeding that may be precipitated by other sympathomimetic drugs such as amphetamine and phenylpropanolamine. Both subarachnoid and intracerebral hemorrhage may result. Or, the features of hypertensive encephalopathy are precipitated, including changes in the posterior white matter of the cerebral hemispheres that are so striking on imaging


Neurology_Adams

Neurology_Adams. hemorrhage may result. Or, the features of hypertensive encephalopathy are precipitated, including changes in the posterior white matter of the cerebral hemispheres that are so striking on imaging studies (PRES, as discussed earlier). The strokes with crack cocaine, however, are more often ischemic, typically involving the territory of a large vessel. Some ambiguity attends the vasculopathy induced by crack cocaine, cocaine hydrochloride, and the amphetamines, particularly the first of these. There are undoubted instances of a true cerebral inflammatory vasculitis, perhaps of a hypersensitivity type such as those reported with biopsy verification by Krendel and colleagues, by Merkel and associates, and by others.


Neurology_Adams

Neurology_Adams. What is confusing about many of these cases is the normal angiographic appearance in many instances and large vessel occlusions in others, in contrast to the pathologic changes, which are concentrated in small cortical vessels. Many cases seem to be of an entirely different type, displaying long segments of vascular attenuation in the angiogram and no evidence of an inflammatory process in biopsy or autopsy material. The correct treatment, aside from lowering the blood pressure, is uncertain. A similar apparently vasospastic disorder is emerging from the use of high-potency cannabinoids (e.g., K-2, “spice”), including strokes.


Neurology_Adams

Neurology_Adams. Singhal and colleagues and others have brought to attention that serotonergic drugs may produce reversible multifocal vasospasm, severe headache, and stroke. One of their patients was using the antimigraine medicine sumatriptan; others were using serotonin reuptake inhibitor antidepressants and, in addition, had taken over-the-counter cold remedies that included pseudoephedrine and dextromethorphan; we are aware of other similar cases. These authors proposed that in these cases a “serotonin syndrome” had occurred, similar to what has been seen with overdoses of this class of antidepressants. A drug-induced vasculitis, typical of the ingestion of sympathomimetic compounds, is difficult to distinguish from a more common state of focal or diffuse vasospasm that may also be induced by these same agents. The nature of this process is indeterminate but may be related to the deposition of circulating immune complexes in the walls of cerebral vessels.


Neurology_Adams

Neurology_Adams. Whether there is an increased incidence of arteriovenous malformation and cerebral aneurysm in patients who have cerebral hemorrhages after ingestion of cocaine, as suggested in several articles, is uncertain but this, in any case, suggests that sympathomimetic drugs can precipitate hemorrhage from an underlying developmental vascular lesion (Fessler et al). Crack cocaine may also cause a choreiform disorder (“crack dancing”), not unlike that associated with antiphospholipid antibody but generalized rather than focal (see further on); usually there are small infarctions in the basal ganglia, but an immune mechanism has also been suggested.


Neurology_Adams

Neurology_Adams. The nature of diffuse vasospasm when there is no hyperadrenergic precipitant, trauma, or arterial dissection, is unknown. This was the process noted by Call et al. A relationship to hypertensive encephalopathy or to delayed postpartum eclampsia has been suggested because of the aforementioned widespread cerebral vasospasm that may be seen in eclamptic women, even those with marginally elevated blood pressures. Two of our patients have been in the postpartum period and other such patients have been described in the first 3 weeks after delivery. In an autopsy studied case, Kheir and coworkers found, in addition to fatal cerebral edema, a range of vascular cerebral parenchymal changes, mostly fibrinoid necrosis, perivascular hemorrhage, and exudates, all features found in hypertensive encephalopathy.


Neurology_Adams

Neurology_Adams. Treatment, alluded to above, has been difficult to establish. Systemic administration of calcium channel blockers or magnesium has given mixed results but is often used. Some groups have resorted to intrarterial injection of these agents. Stellate sympathetic block has been tried. Systemic glucocorticoids have been tried but retrospective one single center series suggested they may be detrimental (Singhal and Topcuoglu). A review of the subject is given by Ducros. The relationship of this process to a true vasculitis of cerebral vessels, most often from drug exposure, is uncertain and discussed separately below under “Arteritis Symptomatic of Underlying Systemic Disease and Sympathomimetic Drug Ingestion.”


Neurology_Adams

Neurology_Adams. Inflammatory diseases of the blood vessels that are of infectious origin and their effects upon the nervous system are considered in detail in Chap. 31. There it was pointed out that meningovascular syphilis, tuberculous meningitis, fungal meningitis, and the subacute (untreated or partially treated) forms of bacterial meningitis may be accompanied by inflammatory changes in the walls of vessels that pass through the subarachnoid space and result in occlusion of the arteries or veins. For example, a small deep stroke is the first clinical sign of chronic basilar meningitis, but more often it develops well after the meningeal symptoms are established. The nature of the cerebral vasculitis that may rarely accompany HIV is unclear. Independent of this possible mechanism, an increasing incidence of stroke in patients with HIV has drawn considerable attention, for example, the epidemiologic survey by Ovbiagele and Nath has indicated a 60 percent increase in hospitalizations for stroke in


Neurology_Adams

Neurology_Adams. of stroke in patients with HIV has drawn considerable attention, for example, the epidemiologic survey by Ovbiagele and Nath has indicated a 60 percent increase in hospitalizations for stroke in HIV patients over a recent decade. However, the autopsy study carried out by Connor and coworkers emphasized that the causes of stroke were of the mundane types seen in others and, while some nondescript vasculopathy was seen in small vessels, this was not related to vasculitis.


Neurology_Adams

Neurology_Adams. Typhus, schistosomiasis, mucormycosis, aspergillosis, malaria, and trichinosis are infrequent causes of inflammatory arterial disease, which, unlike the above-mentioned infections, are not secondary to meningeal infections. In typhus and other rickettsial diseases, capillary and arteriolar changes and perivascular inflammatory cells are found in the brain; presumably they are responsible for the seizures, acute psychoses, cerebellar syndromes, and coma characterizing the neurologic disorder in these diseases. The internal carotid artery may be secondarily occluded in diabetic patients as part of the orbital and cavernous sinus infections with mucormycosis. In trichinosis, the cause of the cerebral symptoms has not been clearly established. Parasites have been found in the brain; in one of our patients the cerebral lesions were produced by bland emboli arising in the heart and related to a severe myocarditis. In cerebral malaria, convulsions, coma, and, sometimes, focal symptoms appear


Neurology_Adams

Neurology_Adams. our patients the cerebral lesions were produced by bland emboli arising in the heart and related to a severe myocarditis. In cerebral malaria, convulsions, coma, and, sometimes, focal symptoms appear to be due to the blockage of capillaries and precapillaries by masses of parasitized red blood corpuscles. Schistosomiasis may invade cerebral or spinal arteries.


Neurology_Adams

Neurology_Adams. In a separate category is the embolic bacterial embolus to various sized vessels in the cerebrum that causes a focal, sometimes necrotizing, vasculitis from within the vessel. Infarction, local hemorrhage, and mycotic aneurysms may result. In the past, bacterial endocarditis was the main cause but other various causes of bacteremia now predominate. These diseases are discussed further in Chap. 31. Noninfectious Inflammatory Diseases of Cranial Arteries Included under this heading is a diverse group of arteritides that have little in common except their tendency to involve the cerebral vasculature in a multifocal manner. One group involves the larger caliber vessels and includes the giant cell arteritides—extracranial (temporal) arteritis; granulomatous arteritis of the brain; and aortic branch arteritis, one form of which is known as Takayasu disease. A special case is infiltration of the vessels by lymphoma cells; intravascular lymphoma, considered below.


Neurology_Adams

Neurology_Adams. A second group that affects the mediumand smaller-sized vessels includes polyarteritis nodosa, the Churg-Strauss type of arteritis, Wegener granulomatosis, systemic lupus erythematosus, Behçet disease, hypersensitivity angiitis, Kohlmeier-Degos disease, and the small vessel disorder of Susac syndrome. Immunologic studies show that in most of these processes there is an abnormal deposit of complement-fixing immune complex on the endothelium, leading to inflammation, vascular occlusion, or rupture with small hemorrhage. The initial inflammatory event is thought in some cases to be evoked by a virus, bacterium, or drug, but these are rarely proven in any one case. It is postulated by some immunologists that in the granulomatous arteritides, a different mechanism is operative—that an exogenous antigen induces antibodies that attach to the primary target (the vessel wall) as immune complexes, damage it, and attract lymphocytes and mononuclear cells. The giant cells form around remnants of


Neurology_Adams

Neurology_Adams. antigen induces antibodies that attach to the primary target (the vessel wall) as immune complexes, damage it, and attract lymphocytes and mononuclear cells. The giant cells form around remnants of the vessel wall. Wegener granulomatosis may fit this model. An acute necrotizing cerebral angiitis sometimes complicates ulcerative colitis and responds to treatment with prednisone and cyclophosphamide; it may also belong in this category. Mixed essential cryoglobulinemia, a vasculitic disorder that more often affects the peripheral than the central nervous system, may nonetheless produce an encephalopathy.


Neurology_Adams

Neurology_Adams. Another entirely different type of small vessel arteritis occurs as a hypersensitivity phenomenon. Often it is associated with an allergic skin lesion (Stevens-Johnson vasculopathy or a leukocytoclastic vasculitis). The clinical picture does not resemble that of polyarteritis nodosa, but the central or peripheral nervous system is affected in rare instances. The response to corticosteroids is excellent. The special case of intravascular lymphoma, which simulates a cerebral vasculitis, is discussed in Chap. 30. Temporal Arteritis (Giant Cell Arteritis, Cranial Arteritis) (See Also Chap. 9)


Neurology_Adams

Neurology_Adams. Temporal Arteritis (Giant Cell Arteritis, Cranial Arteritis) (See Also Chap. 9) In this disease, which is common among older persons, arteries of the external carotid system, particularly the temporal branches, are the sites of a subacute granulomatous inflammatory exudate consisting of lymphocytes and other mononuclear cells, neutrophilic leukocytes, and giant cells. The most severely affected parts of the artery usually become thrombosed. The sedimentation rate is characteristically elevated above 80 mm/h and sometimes exceeds 120 mm/h, but a small number of cases occur with values below 50 mm/h. The disease is included in this chapter because it uncommonly affects the extracranial internal and vertebral arteries and may result in stroke on the basis of ischemic occlusion or secondary embolus. However, significant inflammatory involvement of intracranial arteries from temporal arteritis is uncommon, perhaps because of a relative lack of elastic tissue.


Neurology_Adams

Neurology_Adams. Regional or bilateral headache or head pain is the chief complaint, and there may be severe pain, aching, and stiffness in the proximal muscles of the limbs associated with the markedly elevated sedimentation rate. Thus the clinical picture overlaps that of polymyalgia rheumatica as discussed in Chap. 9. Occlusion of branches of the ophthalmic artery (mainly those to the posterior ciliary artery and the choroidal circulation that supply the anterior optic nerve) results in blindness in one or both eyes, is the most feared complication, often unpredictably. This is one of the main forms of anterior ischemic optic neuropathy discussed in Chap. 12. In a few cases, blindness is preceded by transient visual loss, thereby simulating a TIA (transient monocular blindness). Other symptoms include jaw claudication due to ischemia of the masseter muscles. Occasionally the arteries of the oculomotor nerves are also involved, causing various ophthalmoplegias.


Neurology_Adams

Neurology_Adams. The administration of prednisone, 50 to 75 mg/d, provides striking relief of the headache and polymyalgic symptoms within days and sometimes within hours, and also prevents blindness. The medication must be given in gradually diminishing doses for at least several months or longer, guided by the symptoms and the sedimentation rate. The latter begins to drop within days but seldom falls below 25 mm/h. These issues are discussed in greater detail in Chap. 9.


Neurology_Adams

Neurology_Adams. Scattered examples of smalland medium-sized vessel giant cell arteritis of undetermined etiology in which only brain vessels are affected have come to medical attention over the years. The clinical aspects have taken diverse forms, sometimes presenting as low-grade, nonfebrile meningitis with sterile CSF followed by infarction of one or several parts of the cerebrum or cerebellum. In other cases, it has evolved over a period of weeks, with strokes or an unusual dementia. Headaches (variable in our experience but sometimes severe), focal cerebral or cerebellar signs of gradual (occasionally stroke-like) evolution, confusion with memory loss, pleocytosis and elevated CSF protein, and papilledema as a result of increased intracranial pressure (in about half of reported cases but far fewer in our experience) constitute the most frequently encountered syndromes. The symptoms usually persist for several months. In contrast to temporal arteritis, the sedimentation rate is generally normal or


Neurology_Adams

Neurology_Adams. our experience) constitute the most frequently encountered syndromes. The symptoms usually persist for several months. In contrast to temporal arteritis, the sedimentation rate is generally normal or only slightly elevated. An extensive early report given by Kolodny and colleagues still serves as a useful reference.


Neurology_Adams

Neurology_Adams. In about half the patients can the diagnosis be made by angiography, which demonstrates an irregular narrowing and in some cases blunt ending of several medium-sized cerebral arteries (Fig. 33-37). CT and MRI show multiple irregular white matter and cortical changes and small cortical lesions; sometimes these cannot be differentiated from a tumor or demyelinative or infectious process. If the white matter abnormalities become confluent, the radiologic appearance simulates Binswanger disease. The diagnosis is inferred from the imaging and CSF examination but made often by a brain biopsy, which includes a sample of the meninges with vessels, but even with tissue sampling, about half of suspected cases show the typical histopathologic changes. It is not unusual, however, for patients with normal angiograms to have the typical arteritic findings on biopsy. Tissue excised during an operation (or brain biopsy) for a suspected brain tumor, lymphoma, or white matter disease has revealed the


Neurology_Adams

Neurology_Adams. angiograms to have the typical arteritic findings on biopsy. Tissue excised during an operation (or brain biopsy) for a suspected brain tumor, lymphoma, or white matter disease has revealed the characteristic vasculitis in some of our patients; in others, the diagnosis has been made only at autopsy, the findings coming as a distinct surprise.


Neurology_Adams

Neurology_Adams. The affected vessels are mainly in the 100to 500-mm-diameter arteries and arterioles and are surrounded and infiltrated by lymphocytes, plasma cells, and other mononuclear cells; giant cells are distributed in small numbers in the media, adventitia, or perivascular connective tissue. Infarction of brain tissue can be traced to widespread thrombosis in these vessels. The meninges are variably infiltrated with inflammatory cells. Sometimes only a part of the brain has been clinically affected—in one of our cases the cerebellum, in another, one frontal lobe and the opposite parietal lobe.


Neurology_Adams

Neurology_Adams. Among the most important considerations in this disease is the cerebral arteritis caused by varicella zoster virus of the ophthalmic division of the trigeminal nerve; it simulates in imaging appearance granulomatous arteritis and giant cell arteritis. On occasion, intravascular lymphoma may present a similar picture and sympathomimetic agents, as mentioned earlier, cause a vasculopathy with segmental narrowing of cerebral vessels that has many similarities. The clinical and radiologic appearance of brain arteritis also raises the question of sarcoidosis, which is sometimes limited to the nervous system, of CADASIL, antiphospholipid antibody syndrome, or of the polyarteritis (allergic granulomatous angiitis) described by Churg and Strauss. Unlike some of these diseases, however, the lungs and other organs are spared; there is no systemic eosinophilia, increase in sedimentation rate or antineutrophil cytoplasmic antibodies (ANCA), or anemia.


Neurology_Adams

Neurology_Adams. Some patients with isolated angiitis of nervous system presenting as an aseptic meningitis and multiple cerebral infarcts have responded to corticosteroid and cyclophosphamide therapy (Moore, 1994), and we have used this combined approach from the time the diagnosis is established. The severity and configurations of the process are so variable that judging the effects of treatment is difficult, but our untreated patients have uniformly deteriorated or died without treatment.


Neurology_Adams

Neurology_Adams. This is a nonspecific inflammatory chronic arteritis involving the aorta and the large arteries arising from its arch. It is similar in some ways to giant cell arteritis except for its propensity to involve the proximal rather than the distal branches of the aorta. The name of the disorder comes from Takayasu’s 1908 article. Most of the patients have been young Asian women, but there are numerous reports from the United States, Latin America, and Europe. The etiology has never been ascertained but an autoimmune mechanism is suspected.


Neurology_Adams

Neurology_Adams. Constitutional symptoms such as malaise, fever, anorexia, weight loss, and night sweats usually introduce the illness. The erythrocyte sedimentation rate is elevated in the early and active stages. Later there is evidence of occlusion of the brachiocephalic, subclavian, carotid, vertebral, and other arteries that may be asymptomatic or cause neurologic ischemic symptoms. The affected arteries no longer pulsate, hence the descriptive term pulseless disease. When renal arteries are involved, hypertension results, and there may be coronary occlusion, which may be fatal. Involvement of the pulmonary artery may lead to pulmonary hypertension. Coolness of the hands and weak radial pulses are common indicators of the disease and headaches are frequent. Blurring of vision, especially upon physical activity or fever, dizziness, and hemiparetic and hemisensory syndromes are the usual neurologic manifestations (Lupi-Herrera et al). The frequency of posturally induced neurologic symptoms has been


Neurology_Adams

Neurology_Adams. activity or fever, dizziness, and hemiparetic and hemisensory syndromes are the usual neurologic manifestations (Lupi-Herrera et al). The frequency of posturally induced neurologic symptoms has been emphasized, as well as the relative infrequency of major strokes despite multiple TIA-like spells. The inflamed vessels in the thorax are revealed by radionuclide scans using gallium. Pathologic studies disclose a periarteritis of the large vessels, often with giant cells and reparative fibrosis.


Neurology_Adams

Neurology_Adams. Many of the patients die in 3 to 5 years. According to Ishikawa and colleagues, the administration of corticosteroids in the acute inflammatory stage of the disease improves the prognosis. Reconstructive vascular surgery has helped some of the patients in the later stages of the disease.


Neurology_Adams

Neurology_Adams. The inflammatory necrosis of arteries and arterioles throughout the body in this disease rarely affects the central (in contrast to frequent involvement of the peripheral) nervous system. The lungs are usually spared, which is the basis of distinguishing polyarteritis vasculitis from the Churg-Strauss granulomatous angiitis. It has been estimated that the brain is involved in fewer than 5 percent of cases of either of these processes and takes the form of one or more microinfarcts; macroscopic infarction is a rarity. The clinical manifestations vary and have included headache, confusion and fluctuating cognitive disorders, convulsions, hemiplegia, and brainstem signs. We have also observed one instance of acute spinal cord lesions. Brain hemorrhage is rare and usually occurs in a setting of extreme renal hypertension. Both of these diseases assume greater importance in the field of vasculitic neuropathy as discussed in Chap. 43.


Neurology_Adams

Neurology_Adams. This is a rare systemic disease of unknown cause, affecting adults as a rule and favoring males slightly. A subacutely evolving vasculitis with necrotizing granulomas of the upper and lower respiratory tracts followed by necrotizing glomerulonephritis are its main features. Neurologic complications come later in one-third to one-half of cases and take two forms: (1) a peripheral neuropathy either in a pattern of polyneuropathy or, far more frequently, in a pattern of mononeuropathy multiplex (see discussion in Chap. 43), and (2) multiple cranial neuropathies as a result of direct extension of the nasal and sinus granulomas into adjacent upper cranial nerves and from adjacent to pharyngeal lesions to the lower cranial nerves (see


Neurology_Adams

Neurology_Adams. Chap. 44). We have seen this disease produce the syndrome of episodic hemicrania, with periorbital ecchymosis. The basilar parts of the skull may be eroded, with spread of granuloma to the cranial cavity and more remote parts. A description is included here because cerebrovascular events, seizures, and cerebritis are less common but well-described neurologic complications. Spastic paraparesis, temporal arteritis, Horner syndrome, and papilledema have been observed but are rare (see Nishino et al). The orbits are involved in 20 percent of patients and lesions here simulate the clinical and radiologic appearance of orbital pseudotumor, cellulitis, or lymphoma. Pulmonary granulomas, usually asymptomatic but evident on a chest CT, are also common.


Neurology_Adams

Neurology_Adams. The vasculitis implicates both small arteries and veins. There is a fibrinoid necrosis of their walls and an infiltration by neutrophils and histiocytes. The sedimentation rate is elevated, as are the rheumatoid and antiglobulin factors. The presence in the blood of cytoplasmic antineutrophil cytoplasmic antibodies (cANCA) has been found to be relatively specific and sensitive for Wegener disease but it may also be present in intravascular lymphoma.


Neurology_Adams

Neurology_Adams. A degree of therapeutic success in this formerly fatal disease has been achieved by the use of cyclophosphamide, chlorambucil, rituximab, or azathioprine. Cyclophosphamide in oral doses of 1 to 2 mg/kg per day has ameliorated 90 to 95 percent of the cases. Methotrexate, azathioprine, and rituximab have been used infrequently studied systematically. An exception is the trial conducted by Guillevin and colleagues, in which rituximab was found to be superior to azathioprine in reducing relapses after patients with ANCA positive vasculitis had attained remission with cyclophosphamide and glucocorticoids. Approximately 40 percent of their patients had neurologic features. The literature can be consulted for doses and anecdotal effectiveness as applied to the neurologic aspects. In acute cases, rapidly acting steroids— prednisone, 50 to 75 mg/d—is usually given in conjunction with the immunosuppressant drug(s).


Neurology_Adams

Neurology_Adams. Involvement of the nervous system is an important aspect of this disease but referable syndromes are quite disparate. In the pathologic and clinical series reported by Johnson and Richardson, the central nervous system (CNS) was affected in 75 percent of cases, but our recent experience has suggested a lower frequency of clinical manifestations, especially if minor neurologic aspects such as headache are excluded. Disturbances of mental function—including alteration of consciousness, seizures, and signs referable to cranial nerves—are the usual neurologic manifestations; most often they develop in the late stages of the disease, but they may occur early and may be mild and transient. Hemiparesis, paraparesis, aphasia, homonymous hemianopia, movement disorders (chorea), and derangements of hypothalamic function occur but have been infrequent in our experience. Larger infarcts are usually traceable to emboli from Libman-Sacks (a form of nonbacterial thrombotic) endocarditis.


Neurology_Adams

Neurology_Adams. In some instances, the CNS manifestations resemble multiple sclerosis, especially when there is an optic neuritis or myelopathy. Two manifestations that should be noted are of “longitudinally extensive myelopathy” that simulates Devic disease, and of white matter changes in the cerebral hemispheres with varied clinical manifestations, (“Sjogren sclerosis,” or “lupus sclerosis”). These are discussed in Chap. 35 with multiple sclerosis and diseases that simulate it. The presence of serum antinuclear antibodies is of help in the differentiation of lupus erythematosus but in itself does not establish the diagnosis. Antibodies to double-stranded DNA (anti-dsDNA) are a sensitive indicator of the disease. The CSF is normal or shows only a mild lymphocytic pleocytosis and slight increase in protein content, although in some patients—primarily those with peripheral neuropathy and myelopathy—the protein content may be greatly increased.


Neurology_Adams

Neurology_Adams. Some of the neurologic manifestations can be accounted for by widespread microinfarcts in the cerebral cortex and brainstem; these, in turn, are related to destructive and proliferative changes in arterioles and capillaries. The acute lesion is subtle; it is not a typical fibrinoid necrosis of the vessel wall, like that in hypertensive encephalopathy, and there is no cellular infiltration. Attachment of immune complexes to the endothelium is the postulated mechanism of vascular injury. Thus, the changes do not represent a vasculitis in the strict sense of the word. However, there is also an immune component to some of the white matter and cord lesions that do not require implicating a vasculopathy (see Chap. 35).


Neurology_Adams

Neurology_Adams. It is not entirely clear to us what proportion of the cerebrovascular features of lupus might be explained on the basis of the coagulation disorder or Libman-Sacks (non-bacterial thrombotic) endocarditis. Other neurologic manifestations are related to hypertension, which frequently accompanies the disease and may precipitate cerebral hemorrhage; to endocarditis, which may give rise to cerebral embolism; to thrombotic thrombocytopenic purpura, which commonly complicates the terminal phase of the disease (Devinsky et al); and to treatment with corticosteroids, which may precipitate or accentuate muscle weakness, seizures, and psychosis. In other cases, steroids appear to improve these neurologic manifestations. A similar set of neurologic problems arises in relation to the antiphospholipid antibody syndrome, which may be a feature of lupus or arise independently (see “Antiphospholipid Antibody (Hughes) Syndrome”) and a special syndrome of chorea occurs with few other systemic


Neurology_Adams

Neurology_Adams. antibody syndrome, which may be a feature of lupus or arise independently (see “Antiphospholipid Antibody (Hughes) Syndrome”) and a special syndrome of chorea occurs with few other systemic manifestations of lupus, presumably on an autoimmune basis.


Neurology_Adams

Neurology_Adams. This is yet another poorly understood form of vasculitis, consisting of a microangiopathy affecting mainly the brain and retina (Susac and colleagues, 1979). Psychiatric symptoms, headache, dementia, sensorineural deafness, vertigo, and impairments of vision are the clinical manifestations. These are generally young patients, more often women and present with an incomplete syndrome, without one or more of the core features of deafness or branch retinal artery occlusion or encephalopathy. Funduscopy shows multiple retinal artery branch occlusions and retinal angiography shows multiple additional infarctions and evidence of diffuse vascular leakage from endothelial injury. The MRI may show characteristic white matter lesions, particularly in the central portion of the corpus callosum (Fig. 33-38) (see Susac and colleagues, 2003). Antibodies to endothelial cells have been identified by Magro and colleagues in many of their cases. The patients seem to respond to steroid therapy and most


Neurology_Adams

Neurology_Adams. 33-38) (see Susac and colleagues, 2003). Antibodies to endothelial cells have been identified by Magro and colleagues in many of their cases. The patients seem to respond to steroid therapy and most cases are singular and do not relapse but there are exceptions.