Diagnosing CNS Vasculitis the Case Against Empiric Treatment
Total Page：16
File Type：pdf, Size：1020Kb
CASE REPORT/CASE SERIES Diagnosing CNS Vasculitis The Case Against Empiric Treatment Elisabeth B. Marsh, MD, Steven R. Zeiler, MD, PhD, Michael Levy, MD, PhD, Rafael H. Llinas, MD, and Victor C. Urrutia, MD and/or hemorrhage, CNS vasculitis is often included on the Introduction: Primary central nervous system vasculitis (PCNSV) is a differential diagnosis of stroke. rare inflammatory arteriopathy confined to the brain, spinal cord, and A major diagnostic challenge is the similarity between leptomeninges. Because of its nonspecific presentation and difficulties CNS vasculitis and other more common disease mimics. Intra- in making a positive diagnosis, empiric treatment is often instituted. cranial atherosclerosis and reversible cerebral vasoconstriction Case Series: We report a case series of 5 patients who were admitted syndrome (RCVS) are far more common disorders6,7 and often or transferred to the Johns Hopkins Hospital with a clinical history and misdiagnosed, as we illustrate below. Other mimics include magnetic resonance imaging findings suggestive of PCNSV. Four pa- CNS lymphoma, neurosarcoidosis, multiple sclerosis, fibro- tients had received at least 1 course of immunosuppression with high- muscular dysplasia, hypercoaguable states (ie, antiphospholipid dose intravenous (IV) corticosteroids and/or a corticosteroid-sparing antibody syndrome), amyloid angiopathy, and malignancy.8–12 agent. Each underwent an extensive workup including 4-vessel cere- CNS infections and changes secondary to drug exposure and bral angiography and, in the majority of cases, brain biopsy to evaluate for mimics of PCNSV. In each of the 5 cases, an alternative diagnosis radiation can also have similar clinical presentations and was found. imaging findings. The frequency of their occurrence is sig- nificantly higher than CNS vasculitis.4 Conclusions: We propose a cautious, multistep approach to the di- Although CNS vasculitis requires expeditious diagnosis agnosis of PCNSV, which takes into account more common diagnoses and treatment, the empiric use of immunosuppressive agents to and avoids the pitfalls of empiric treatment. treat suspected cases also poses risk. The typical treatment is Key Words: stroke, arteriopathy, vasculitis, cerebral angiogram, an initial pulse of high-dose corticosteroids followed by a immunosuppression prolonged taper, and/or a corticosteroid-sparing agent. Long- term corticosteroid use is associated with weight gain, hyper- (The Neurologist 2012;18:233–238) tension, dyslipidemia, peptic ulcer disease, diabetes, and avascular necrosis.13 Chronic immunosuppression can lead to increased risk of infection or malignancy.13 Furthermore, rimary central nervous system vasculitis (PCNSV) is a rare empiric corticosteroid administration may result in falsely Pinflammatory arteriopathy confined to the brain, spinal negative serologic and imaging markers (eg, enhancement), cord, and leptomeninges. Diagnostic criteria include newly thereby obscuring the correct diagnosis. acquired neurological deficits, unexplained by another central Brain biopsy, along with serologic/CSF studies and nervous system (CNS) or systemic process, in the presence of a imaging, are critical in the evaluation of patients with sus- highly suggestive angiogram and/or biopsy.1,2 There are few pected CNS vasculitis. They are particularly useful in the di- cases each year 3 making further characterization and correct agnosis of more common disease mimics.14 In the past, the risk diagnosis difficult. of brain biopsy, coupled with poor diagnostic yield, out- True PCNSV is devastating. It is typically insidious in weighed its benefit as a diagnostic tool. Patients with suspected onset and progressive, presenting around the fourth decade of CNS vasculitis were instead placed on a trial of corticosteroids. life.4 Classically, patients report progressive headache and However, with advancements in neurosurgical techniques, the encephalopathy.5 They have multiple radiographic lesions in complication rate for a routine brain biopsy has been sig- varying vascular distributions on neuroimaging that can be nificantly reduced,15 and more sophisticated neuroimaging both ischemic and hemorrhagic in nature. Tertiary referral techniques now allow the surgeon to biopsy tissue directly centers regularly evaluate patients with atypical presentations from an affected area. in whom the diagnosis of “CNS vasculitis” is entertained. We report a small case series of patients empirically Because of this, and that the most common symptoms of treated for suspected CNS vasculitis, who were found to have vasculitis are relatively nonspecific, the average time to diag- other diseases by biopsy or autopsy (see Table 1 for an over- nosis can be several months.4 Given the presence of ischemia view of patient characteristics). CASE 1 A 66-year-old woman with a history of hypertension and hy- From the Department of Neurology, Johns Hopkins University, Baltimore, percholesterolemia was transferred to Johns Hopkins Hospital with MD. left-sided weakness and altered mental status after magnetic resonance The authors declare no conflict of interest. imaging (MRI) revealed multiple acute infarcts in the cerebellar Reprints: Victor C. Urrutia, MD, Department of Neurology, Johns Hopkins hemispheres bilaterally and magnetic resonance angiogram (MRA) University School of Medicine, 601 N. Caroline St., suite 5073A, Baltimore, MD 21287. E-mail: [email protected]. demonstrated stenosis of the bilateral carotid arteries, vertebral ar- Copyright r 2012 by Lippincott Williams & Wilkins teries, and right middle cerebral artery/anterior cerebral arteries. She ISSN: 1074-7931/12/1804-0233 was treated empirically with high-dose IV methylprednisolone and DOI: 10.1097/NRL.0b013e31825c6d23 cyclophosphamide for presumed CNS vasculitis before transfer. The Neurologist Volume 18, Number 4, July 2012 www.theneurologist.org | 233 Marsh et al The Neurologist Volume 18, Number 4, July 2012 TABLE 1. Patient Characteristics Presenting Case Symptoms MRI Findings Angiogram Results Immunosuppression Final Diagnosis 1 First: Visual deficits First: Acute right occipital and First: Stricture of the right 2 courses of high-dose Atherosclerosis Second: Left-sided cerebellar strokes vertebral artery IV weakness, altered Second: Multiple acute infarcts in Second: Multifocal vascular methylprednisolone mental status the bilateral cerebellar stenoses of the proximal Cyclophosphamide hemispheres with stenosis of vessels with sparing of the multiple large arteries cortical vessels 2 First: Left-sided First: Multiple bilateral T2/ Diffuse intracranial 2-5 d courses of high- Arteriolosclerosis numbness, altered FLAIR hyperintensities vasculopathy dose IV mental status Second: New bilateral methylprednisolone Second: Right-sided hyperintensities involving deep Steroid taper weakness, altered gray and white matter mental status, Third: Worsening bilateral vertigo lesions Third: Headache, loss of vision 3 First: Bilateral First: FLAIR abnormalities of Subtle multifocal distal small 2-5 d courses of high- Diffuse large hearing loss, word Heschl gyri and left temporal vessel caliber changes dose IV B-cell finding difficulty lobe, susceptibility artifact and bilaterally methylprednisolone lymphoma Second: Worsening diffusion restriction in the Mycophenolate mofetil symptoms with central pons and right occipital Steroid taper altered mental lobe status Second: Bitemporal lobe enhancement Third: New bilateral FLAIR hyperintensities with hemorrhage 4 First: Headache, First: Left frontal intracranial Normal:No vasculopathy or Cerebral amyloid confusion, hemorrhage aneurysm angiopathy memory problems Second: SAH Second: Worsening Third: Progression of hemorrhage cognition Fourth: Right frontal SAH Third: Headache 5 First: Headache First: Diffuse gyral enhancement Multifocal areas of alternating High-dose IV Reversible Second: Right-sided Second: Left posterior parietal dilatation and constriction methylprednisolone cerebral hemiparesis, lobe infarct Cyclophosphamide vasoconstric- expressive Third: Right occipital lobe infarct tion syndrome aphasia Five similar presentations concerning for central nervous system vasculitis. Four alternative diagnoses found. MRI indicates magnetic resonance imaging; SAH, subarachnoid hemorrhage. Five months earlier she had been diagnosed with polymyalgia diagnosed clinically with a stroke. When symptoms progressed 2 months rheumatica after presenting with joint pain and an elevated eryth- later, he was reevaluated and diagnosed with acute disseminated ence- rosedimentation rate (ESR) (90 mm/h). After 3 months she developed phalomyelitis given multiple areas of T2/FLAIR hyperintensity on MRI. visual deficits and an MRI showed acute right occipital and cerebellar He improved with high-dose IV methylprednisolone, but 3 months later strokes. A temporal artery biopsy was obtained to evaluate for giant presented with a new episode of right-sided weakness, altered mental cell arteritis which was negative. A cerebral angiogram revealed status, vertigo, and imbalance. A repeat MRI of the brain revealed new a stricture of the right vertebral artery “suggestive of vasculitis.” bilateral hyperintensities involving the periventricular white matter, A rheumatologic workup was negative. She was treated with clopi- thalami, brainstem, and left cerebellum; minimal gyriform enhancement; dogrel and IV methylprednisolone for 3 days. and no restricted diffusion or mass effect. Evaluation for infection, Once she was transferred to Johns Hopkins Hospital,