Case 1 SF

• 41 y/o woman with no PMHx p/w blurry vision and headache worsening x few weeks. No meds, no toxic habits.

• PE: Afeb VSS. Bilateral lid swelling. • Neuro exam: MSE with mild cognitive

slowing and diminished attention, otherwise normal. CN: diminished VA with disc swelling b/l.

• Motor/sensory/cerebellar intact.

Other w/u

• LP: elevated opening pressure, CSF lymphocytic pleocytosis (60-80), prt 80

• Serum ACE: ~65

• CSF ACE: ~20

Clinical course

• Progressive cognitive decline, recurring bouts of aseptic meningitis with visual blurring partially responsive to IV steroids.

• Poor compliance pulse Cytoxan

• Later developed poor vision d/t glaucoma and b/l optic neuritis

• Panhypopituitarism

• Dementia

Case 2 RC

• 44 y/o man with hx of CVA and behavioral problems, p/w AMS and difficulty walking. Prior CVA admitted at Montefiore 2005, p/w . W/u revealed basal ganglia and cerebellar calcification on CT scan, acute R midbrain/thalamic infarct on MRI. Cause of stroke in young uncertain, however pt found to be ANA+.

• Meds:

• PE: Afeb VSS

Neuro: MSE: alert, Ox2, dim attention, STM 1/3.

CN: dysarthric, otherwise intact

Motor: increased tone in legs, full strength, mild incoordination on FTN,

DTRs: hyperactive

Gait: spastic/ataxic

Imaging

Other w/u

• ESR 120

• Creatinine 2-3 (prior baseline 1-1.5)

• ANA and dsDNA+

• Anti-cardiolipin Ab+

• MRI spinal cord: no significant abnl

• Cerebral angiogram: possibly slight medium vessel irregularity c/w vasculopathy

Clinical course

• IV steroids

• IVIG

• Mycophenolate

• Warfarin

• Worsening dementia and paraparesis

• D/c to SNF

CNS Inflammatory Disease

• Primary, recurrent demyelinating diseases: MS, Neuromyelitis Optica (NMO, Devic’s Dx)

• Mono-phasic demyelinating diseases: Acute disseminated encephalomyelitis (ADEM), acute hemorrhagic leukoencephalitis (AHLE), transverse myelitis (TM), optic neuritis (ON); often these are para-infectious

• CNS involvement with systemic (clinical or sub-clinical) auto-immune disease; includes primary and secondary CNS vasculitis

• Paraneoplastic dx• Immune reconstitution inflammatory syndrome (IRIS) • CNS infections (discussed in other lecture)

Systemic inflammatory conditions with frequent neurological manifestations

• SLE neuropsychiatric manifestations• Sjogren’s• Sarcoid• Anti-phospholipid Ab syndrome (1º or 2º)• Rheumatoid arthritis: PNS• Vasculitis: large or small vessel• Large: Giant cell arteritis: CN>CVA• Small: Wegener’s, polyarteritis nodosum: mononeuritis

multiplex > CN >>CNS • Paraneoplastic syndromes: cerebellar dx, limbic

encephalitis, PNS

Focal Clinical Presentation

• Focal CNS deficit (brain or brainstem): hemiparesis, hemisensory loss, hemiataxia, diplopia, vertigo, dysarthria

• Spinal cord syndrome: complete (motor/sensory/autonomic), anterior, posterior, Brown Sequard

• Cranial nerve: optic neuritis, trigeminal neuralgia, facial paresis

• Pseudo-peripheral: Lhermitte’s sign, paresthesias, pain

• Focal cognitive deficit: aphasia, apraxia, neglect

Neuropyschiatric SLE: 19 syndromes described

Joseph (2007) Neurology

NPSLE

• Neurological dx present in: ~50% (15-90%)• Presenting with neuro symptoms: 3-5%• NPSLE worsens prognosis• NPSLE can occur without systemic flare• Lab abnl: ESR elevated 50%, ANA+ 85%,

dsDNA+ 72%, anti-phospholipid Ab 30%, complement low during flare 44%, ribosomal P Ab and C3A frequently elevated prior to/during flare.

• APS associated with NPSLE, CVA, other focal dx

Neuro testing in NPSLE

• CSF abnl: 20-40% (lymphocytic pleocytosis, elevated prt, OCB each present in ~20%).

• EEG abnl: up to 80% abnl, mostly non-specific changes but some with epileptogenic focus.

• EMG/NCS: high% abnl in symptomatic PNS dx

Neuroimaging

• Brain MRI: abnl in 20-70%; most common findings are multifocal small white matter hyperintensities and atrophy; stroke in < 20%; lower % show basal ganglia calcification, reversible leukoencephalopathy syndrome (RPLS).

• SPECT: detects multifocal or patchy/diffuse perfusion deficits in 50-90%

• MR spectroscopy: abnl in ? 20-50%

MRI abnl in NPSLE ptsCsepany (2003) J Neurol

NPSLE RxSanna 2003

CNS LupusCsepany 2003

Lupus RPLSMagnano 2006

EMT with SLE, APS, complicated migraine with aphasia and RHP

Neurosarcoidosis

• Neurological manifestations in ~10% (~20% at autopsy).

• Rarely presents with neurologic syndrome %

• Very rarely limited to NS %

Joseph (2008) JNNP

Spencer (2004) Sem Arthritis Rheum

Laboratory findings in neurosarcoidosis

• CXR abnl: ~40-50% (30-80% range)

• Chest CT abnl: ~60-75% (? up to 90%)

• Gallium/PET scan abnl: 25-80%

• Serum ACE elevation: 25-75%

• CSF prt elevation: 50%

• CSF lymphocytic pleocytosis: 40%

• CSF OCB: 20-40%

Neurosarcoid MRI abnl

• Any abnl: up to 80%

• Leptomeningeal or parenchymal enhancement: 25-50%

• White matter lesions: 30-50%

Neurological manifestations of Sjogren’s syndrome

• Common disorder, affecting ~2-3% of adults.

• Neurological dx present in 5-60%.

• CNS and PNS dx both common.

• Neurological symptoms occur prior to diagnosis in 80-90% of patients.

• Sicca symptoms present in <50% at presentation.

PNS Sjogren’sMori (2005) Brain

MRI, path, and sweat testing in Sjogren’s sensory neuropathy (Mori 2005)

Lab abnl in Neuro-Sjogren’s

• SSA/SSB+: 45%

• Schirmer’s test abnl: 90%

• Salivary scintography abnl: 65%

• Lip bx abnl: 95%

References

• SLE: • Joseph (2008) JNNP• Sanna (2003) Lupus• Csepany et al (2003) J Neurol• Sjogren’s: • Mori (2005) Brain • Delalande (2004) Medicine• Soliotis (1999) Ann Rheum Dis• Sarcoid:• Joseph (2008) JNNP

• Joseph (2007) Practical neurology

• Spencer (2004) Sem Arthritis Rheum

NeurosarcoidSpenser 2004

CNS Sjogren’s