older male with headaches and confusion
DESCRIPTION
Older male with headaches and confusion. History. Middle -aged, right handed Caucasian male no home medications, no PMH Three week history of low grade fever and frontal headache Diagnosed by PCP as sinus infection and given antibiotics With no improvement admitted to OSH - PowerPoint PPT PresentationTRANSCRIPT
Older male with
headaches and confusion
History
• Middle-aged, right handed Caucasian male no home medications, no PMH
• Three week history of low grade fever and frontal headache
• Diagnosed by PCP as sinus infection and given antibiotics • With no improvement admitted to OSH
– LP: 73 WBC (73% L), 11 RBC, 44 protein. Viral testing and cultures were negative. Discharged home one day later ama as he felt better
• Readmitted 5 days later for somnolence and confusion. • CT head: two new low density lesions. MRI: multiple
acute infarcts in various distributions• Remote hx of pilonidal cyst removal, smokes 1ppd, no sick
contacts
Further work up at KU
• Infectious– West Nile CSF IgM/IgG,
Cryptococcal antigen, Influenza, Monospot, Enterovirus PCR, Hepatitis screen, HIV, VZV, HSV 1/2, Syphilis antibody, bacterial, fungal, viral cultures, T spot
• Autoimmune– Rheumatoid factor, C3/C4, ACE,
C-ANCA, P-ANCA, anti-double strand, myeloperoxidase, Serine protease, anti SSA, SSB, ANA screen
• Hypercoagable – Factor V Leiden in one allele
(heterozygous)
– Cardiolipin, protein C & S, antithrombin III, factor 2 mutation
• LdL 89, A1C 5.6% • Sed Rate 15, CRP 0.05• Two LPs with WBC 21-
29, protein 41-49• Paraneoplastic panel
negative• No oligoclonal bands,
CSF ACE <4, CSF IgG was normal
• CSF flow cytometry was negative x2
Imaging
• Radiology– IR Arteriogram
• Smooth vessels, no evidence of vasculitis
– MRI Brain w/wo gadolinium • Patchy areas of subacute ischemia
– PET scan • Normal
– Transesophageal echocardiogram• unremarkable
– CT chest • RLL pulmonary artery clot
• Factor V Leiden heterozygous positive 5-10 fold increase in venous thrombosis
• Ophthalmology found right eye papilledema but no known cause
• Discharged home after five days on coumadin, strokes thought likely to be due to FVL, smoking, athereosclerosis
Re-admission
• Re-admitted 2 weeks later with new onset imbalance and left arm and leg weakness
• Found to have new acute infarcts • Mental status detoriated and transient episodes of
hemiplegia upon awakening • Episodes of unresponsiveness, rigid, hypertension,
tachycardia and fever. Transferred to ICU and intubated
• Started on AEDs and VEEG monitoring. No epileptiform discharges. Thought to have autonomic storming
• Eventually had tracheostomy and percutaneous enteral feeding tube placed
• Repeat Imaging
• Where?• What?
• Brain biopsy“Although the changes are not specific or diagnostic of a
particular disorder, and while the current biopsy does not contain an infarct, the vascular changes observed
would be compatible with a vascular-ischemic disorder, such as vasculitis, a leading clinicoradiological
impression. A neoplastic process is not recognized."
• Pt started on high dose IV steroids, cytoxan• Propanolol for storming• Mental status plateaued • Discharged to L-TACH 6 weeks after admission
CNS VASCULITIS
CNS Vasculitis aka Primary Angiitis of the CNS (PACNS)
• Inflammation of small and medium sized arteries only in CNS causing CNS dysfunction– Unexplained neurologic or psychiatric deficit – Classic angiographic or histopathologic features– No evidence of systemic vasculitis
• Difficult to diagnose and study– Rarity – about 500 cases reported since 1959 – Nonspecific and various presentations– No useful animal models
Pathology
• Pathologic findings include Langerhans or foreign body giant cells, necrotizing vasculitis or lymphocytic vasculitis
• Inflammation causes vessels to become narrowed, occluded and thrombosed
• More likely to affect blood vessels in cerebral cortex and leptomeninges more than subcortical regions
• Cause is unknown– Infection Mycoplasma gallisepticum, VZV, WNV,
HIV have been proposed
Clinical Manifestations
• Suspected when in patients with recurrent strokes with no identifiable cause or other CNS dysfunction with no cause
• Male 2:1 predominance • Mean age is 42 but can occur at any age• Series of 116 patients presented with
– 83% had decreased cognition, 56% headache, 30% seizure, 14% stroke, 12% cerebral hemorrhage
• Strokes/TIAs occur in 30-50% of patients
Differential
• Reversible cerebral vasoconstriction syndrome (Call-Fleming)• Systemic vasculitis involving the brain
– Behcet’s, polyarteritis nodosa, Wegener’s, Churg-Strauss, cryoglobulinemic vasculitis
• Connective tissue diseases– SLE, NAIM, rheumatoid vasculitis, antiphospholipid syndrome
• Infections– Varicella zoster, HIV, hepatitis C, CMV,
• Atherosclerotic disease – – Premature intracranial, Chronic hypertension
• Demyelinating- MS, ADEM, PML• Embolic disease
– cardiogenic
• Malignancy – Intravascular lymphoma
• Miscellanous – PRES, sarcoidosis, Susac, CADASIL, MELAS, moyamoya
Testing
• ESR and CRP- usually normal• Complete infectious and rheumatologic
work up• Drugs of abuse screen- cocaine• CSF- abnormal in 80-90% of patients but
no specific abnormalities– Elevated protein and wbc – important to rule out other diseases
Imaging
• MRI – used frequently in work up to assess for stroke, leptomeningeal enchancement, follow progress of lesions
• Angiography: ectasia and stenosis “beading” usually in small arteries with involvement of several sites. – Also has multiple occlusions with sharp cutoffs and
circumferential or eccentric vessel irregularities – Two series of patients found sensitivity of 60%.
Cannot use negative exam to rule out • Vessels usually beyond resolution of exam
Differential Diagnosis of vascular constriction and ectasia/beading
VasospasmInfectionEmboliAthereosclerosisHypercoaguable state
Biopsy
• Gold standard• Sampling of leptomeninges and
underlying cortex• One case series found 25% false negative • Positive – still need to stain for organisms
Treatment
• Initial- with infection excluded– Glucocorticoids- no trials on route, dose or
length of treatment
• Biopsy confirmed– Glucocorticoids – Cyclophosphamide- 600-750mg/m2 qmonth for
three to sixth months – Once in remission for 3-6 months switch to
alternative agents MMF, Azathioprine and MTX
– Serial MRIs
Conclusion
• PACNS is a difficult disease to identify and treat
• Should be entertained in patients who have new onset neurologic deficits and multifocal strokes with no other apparent cause
• Diagnosis is arrived at by exclusion of other causes and a combination of clinical history, CSF findings, radiologic and pathologic findings