Differential Diagnosis Made Easy

General Approach

Differential diagnosis in cerebrovascular disease can be divided into ischemic and hemorrhagic disorders. After establishing that a condition is cerebrovascular and determining whether it is ischemic or hemorrhagic (see pp. 3-4), the clinician must try to identify the underlying pathophysiologic mechanism for the condition. This step constitutes the bulk of the differential diagnosis in cerebrovascular disease and facilitates optimal treatment. Although the underlying mechanism cannot be identified with certainty in many cases (as much as 30%), the number of such cases can be minimized by following a systematic approach to classification and differential diagnosis.

ISCHEMIC CEREBROVASCULAR DISORDERS

Ischemic cerebrovascular disorders are often classified according to temporal profile, including transient ischemic attack (historically defined as resolution of symptoms within the first 24 hours; for new definition, see Chapter 12) and ischemic stroke (historically defined as symptoms that last longer than 24 hours). The term “reversible ischemic neurologic deficit” (previously used for ischemic stroke with resolution of symptoms after 24 hours but within 3 weeks) is no longer used, and progressive ischemic stroke varies in duration (progressive deficit, often for as long as 24-72 hours). The classification does not help to define pathophysiologic mechanisms, because each of the temporal profiles may be associated with any of the various underlying mechanisms for cerebral ischemic events.

An easy method for categorizing all ischemic conditions, which relates to the underlying pathophysiology, is to classify the mechanisms into four main groups, proceeding from proximal to distal in the arterial system: (1) cardiac disease, (2) large vessel disease (craniocervical occlusive disease), (3) small vessel disease (intracranial occlusive disease), and (4) hematologic disease (Table 8-1).

Traditional clinical and radiologic features that are considered to differentiate cardioembolic events from cerebral ischemic events of other causes have lower predictive value than previously reported. These features may be suggestive of cardioembolic cause, but the clinician must acknowledge that overlap exists. Abrupt onset of maximal neurologic deficit and hemorrhagic transformation, particularly at a subcortical site, may indicate a proximal embolic source. Suggestive clinical syndromes include cortical events, isolated Wernicke’s aphasia, isolated Broca’s aphasia, posterior cerebral artery ischemia with homonymous hemianopia, and top of the basilar syndrome. The findings of seizures and headache are of little use in differentiating mechanism.

TABLE 8-1 Four Major Groups of Diseases Associated with Ischemic Cerebrovascular Disorders

Cardiac disorders	Valve-related emboli: rheumatic heart disease, calcific aortic stenosis, cardiac surgery, prosthetic heart valve, infective endocarditis, nonbacterial thrombotic endocarditis
	Intracardiac thrombus or tumor: left atrial thrombus, left ventricular thrombus, recent myocardial infarction, congestive heart failure, cardiomyopathy, atrial myxoma, cardiac papillary fibroelastoma
	Rhythm disturbances: atrial fibrillation, atrial flutter, sick sinus syndrome, other major rhythm disturbances
	Systemic venous thrombi with right-to-left cardiac shunt: interatrial septal defect, patent foramen ovale, interventricular septal defect, pulmonary vein thrombosis, pulmonary arteriovenous malformation
Large vessel diseases (craniocervical or aortic arch)	Atherosclerosis: cervical arteries, major intracranial arteries, and aortic arch
	Fibromuscular dysplasia: the internal carotid arteries above the carotid bifurcation or vertebral arteries
	Dissection: carotid or vertebral dissection: traumatic, spontaneous, or caused by fibromuscular dysplasia; aortic dissection: traumatic, spontaneous
	Takayasu’s disease (see also noninfectious arteritis, below)
	Other: vasospasm (migraine), moyamoya disease, homocystinuria, Fabry’s disease, pseudoxanthoma elasticum
Small vessel diseases (intracranial occlusive diseases)	Hypertension Infectious arteritis caused by bacterial; fungal; tuberculous meningitis; or other infective processes of central nervous system, such as tertiary syphilis, malaria, Lyme disease, rickettsial diseases, mucormycosis, aspergillosis, trichinosis or schistosomiasis, herpes zoster, basal meningitis (Cryptococcus, Histoplasma, Coccidioides) Noninfectious arteritis: primary central nervous system vasculitis (primary angiitis of the central nervous system), systemic lupus erythematosus; polyarteritis nodosa; temporal arteritis; drug use and abuse, including cocaine, heroin, methamphetamine, phencyclidine, and LSD; irradiation arteritis; Wegener’s granulomatosis; sarcoidosis; Behçet’s disease Other: reversible cerebral vasoconstriction syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
Hematologic diseases	Polycythemia, thrombocythemia, thrombotic thrombocytopenic purpura, sickle cell disease, dysproteinemia, leukemia, disseminated intravascular coagulation, antiphospholipid antibody syndromes (lupus anticoagulant, anticardiolipin antibodies), protein C and protein S deficiency, resistance to activated protein C, antithrombin III deficiency, prothrombin gene mutation, factor V Leiden deficiency, elevated homocysteine level
LSD = lysergic acid diethylamide.