Transcript ppt
30 y.o. ICU assistant • 2 Weeks prior to admission--fever, chills, myalgias along with bad headaches • St. Paul ER--diagnosed with UTI and started on Levaquin • 1 Week prior to admission seen in PHD ER and diagnosed with flu • On day of admission (9/6/03), found on floor unable to get up with shaking, and ?seizures Exam •Unresponsive. Eyes tended to deviate downward and to the right. Corneals intact. Followed no commands. On a respirator •Marked increased tone in the extremities, with flexion at the elbows and extension of the legs •DTR’s increased. Plantars flexor. •LP done: 34 WBC’s, mostly lymphs, protein 179, glucose 34 •Fungal antigens, cultures, PCR for herpes, etc. all negative in CSF •Initially started on Rocephin; had also been started on acyclovir •After MRI, started on 1gm solu medrol per day •No change in neuro exam and brain biopsy done on 9/10/03 •Biopsy initially read as meningitis and possible encephalitis, and even a diagnosis of vasculitis entertained. •No improvement and antibiotics discontinued and solu medrol tapered. •Then because of worsening changes on MRI, IV solu medrol increased again and given a course of IVIG around 10 days after admission •Never any improvement and after a few weeks, she remained unresponsive with posturing of the extremities and marked increased tone Brain Biopsy Findings Light microscopy: • perivascular chronic inflammation • Predominant white matter findings of macrophage infiltrate consistent with demyelination • chronic inflammation in leptomeninges • no granulomas, vasculitis or viral cytopathic changes • stains for bacteria, fungi, AFB, HSV, varicella, CMV, measles, adenovirus, EBV and bacilli associated with Whipple’s Disease negative Electron microscopy: • evidence of myelin breakdown • no viral organisms identified Differential Diagnosis • • • • Acute disseminated encephalomyelitis viral encephalitis subacute sclerosing panencephalitis PML (progressive multifocal leukoencephalopathy) • Whipple’s Disease • multiple sclerosis • metabolic leukodystrophy Viral Encephalitis • • • • • • neuronophagia with microglial nodules perivascular lymphocytes nonsuppurative leptomeningitis intranuclear inclusions predominantly gray matter parenchymal necrosis with macrophage infiltrate Subacute Sclerosing Panencephalitis • chronic progressive encephalitis past exposure to measles virus by several years • patchy demyelination, IN inclusions, gliosis Progressive Multifocal Leukoencephalopathy • caused by JC, polyoma virus • immunocompromised patients • demyelination, IN inclusions in oligodendrocytes Whipple’s Disease • chronic multisystem disorder • gram positive bacillus Tropheryma • heavy macrophage infiltrate in organs with PAS+ rods (small bowel, CNS) Multiple Sclerosis • chronic progressive demyelinating disorder • plaques of different ages • usually associated with persistent oligoclonal bands of immunoglobulins Metabolic Leukodystrophy • inherited metabolic disorders affecting white matter • usually infants, children • demyelination and macrophage accumulation Acute Disseminated Encephalomyelitis (ADEM) • Immune mediated inflammatory demyelinating encephalomyelitis • Usually preceded days to weeks before by an antecedent event such as viral illness or inoculation • Acute onset of fever, headache, and rapidly followed by meningeal signs, altered consciousness, and focal central neurological signs • Young adults and children most commonly affected Acute Necrotizing Hemorrhagic Encephalopathy (ANHE) • Similar to ADEM • Much more explosive in onset • Characterized by hemorrhage which can be extensive • Usually fatal Differential Diagnosis • Viral encephalitis as well as other infectious etiologies – The history of a period of relative well-being following a febrile illness suggests ADEM – In this case, the distribution of the abnormalities predominantly in the white matter would be unusual for viral encephalitis – Negative serologies and cultures would favor ADEM – Even biopsy may not always be conclusive • Vasculitis – Usually see multiple areas of infarction evident on diffusion weighted images and FLAIR – Diagnosis suggested by Agram and confirmed by biopsy Relationship to Multiple Sclerosis ADEM • Inciting antigenic stimulus • Monophasic illness though relapses in up to 20% • Alteration of consciousness common • Oligoclonal bands absent • 14/40 adult patients developed MS • 0/31, 10/25 children developed MS • • • • • Multiple Sclerosis No causal relationship to infection or inoculation Polyphasic with relapses and remittances or slow progression Alteration of consciousness rare and coma unheard of Oligoclonal bands present Fever/meningismus rare Optic Neuritis • Occurs in 90% of multiple sclerosis patients • 13-85% progress to multiple sclerosis. Predictors: – – – – More than 4 lesions on MRI of brain (85%) Presence of oligoclonal bands RR 5.2 HLA-DR2 RR 3.2 Unilateral optic neuritis more likely to progress to MS Transverse Myelitis • 1/3 of idiopathic give history of URI or flulike illness • Less than 10% progress to multiple sclerosis • Devic’s disease (neuromyelitis optica) Other Demyelinating Disease • Leukodystrophies • Progressive multifocal leukoencephalopathy – Immunocompromised individuals – JC virus or polyoma SV40 – Heavy involvment of U fibers evident on MRI Viral Infections • ADEM in 1/1000 measles infections – Mortality 25%; 25-40% of survivors permanent neurological impairment – Myoclonus common – Must be distinguished from SSPE • Rubella – 1/500 • Varicella-zoster – 1/10,000 – An acute cerebellar syndrome common • Mumps – Hemiplegia common • Others: herpes simplex, influenza, HIV, EB virus Bacterial Infections • Most commonly mycoplasma • Others: – – – – Streptococcus chlamydia legionella campylobcter Vaccines • Rabies--common in the past(1/400), almost nonexistent now with human diploid cell vaccine • DTP • Smallpox 1/4,000 • Measles 1-2/million • Japanese B encephalitis • Polio • Hepatitis B • Influenza Treatment • Methylprednisolone • IVIG • Plasmapharesis Prognosis • 40 adult patients – 14 developed MS – Of remaining 26: • 2 died • 9 had minor residual deficits and 3 modt. Deficits • 12 were completely recovered • 31 Children – 81% recovered completely – In the remaining 5 patients, only mild neurological sequelae – 4 had relapses