Case Discussion m/w), word finding difficulties, cognitively slower, - - PowerPoint PPT Presentation

2/9/2017 1

Case Discussion

Jeffrey M. Gelfand, MD, MAS, FAAN

UCSF MS and Neuroinflammation Center

Recent Advances in Neurology - 2017

Case History

70 yo right-handed man

• Trouble reading & distinguishing letters (i.e. b/p or

m/w), word finding difficulties, cognitively slower, progressed over days

• Right superior homonymous quadrantanopsia,

progressed over days

• Fatigue

FLAIR T1 Post-Gadolinium Ill-defined, peripherally enhancing solitary lesion in the left occipital lobe with subtle mass effect and surrounding vasogenic edema. No abnormal diffusion or susceptibility or intrinsic T1. No other brain or spine lesions.

Case History - 2

Past Medical History

• PE and mild anemia -> dx 1 year prior with

Smoldering Multiple Myeloma

• SPEP with monoclonal gammopathy
• 20-30% plasma cells on bone marrow
• High risk cytogenetic profile
• Heme-onc monitoring, not routinely treated
• Hypertension

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Key Diagnostics

LABS

• SPEP with monoclonal gammopathy, IgG 1900 (normal <1760)
• Elevated free lamda light chains (222, normal <26), LDH normal
• HIV negative, RPR NR, HTLV neg
• NMO (AQP4) IgG neg; ANA neg

BODY IMAGING

• CT Chest/Abd/Pelvis: No malignancy
• FDG-PET: Brain lesion is hypermetabolic, no other FDG-avid disease

CSF EXAM Opening Pressure: 14 cm 2 WBC (53%L, 47% Monos, no eos, no polys) 0 RBC Protein 54 (mildly elevated) Glucose 72 (serum 120) IgG index 0.5 1 unique oligoclonal band Cytology/Flow cytometry: Benign JCV PCR negative

Stereotactic Brain Biopsy

“Macrophage-rich demyelinating lesion”

Foamy macrophages and scattered reactive astrocytes, some of which have mildly enlarged and hyperchromatic nuclei. Complete loss of myelin, with relative preservation of axons Many macrophages, no B lymphocytes, small mature perivascular T lymphocytes, no malignancy Negative for polyoma virus (i.e. negative for PML)

Tumefactive Demyelinating Lesions (TDLs)

Solid

Incomplete Rim Nodular Patchy Cystic Balo-Like

Tremblay, Villanueva-Meyer, Cha, Tihan and Gelfand, et. al. In preparation

TDLs: Atypical inflammatory- demyelinating lesions >2 cm

• 1-2/1000 cases of MS; also

associated with “ADEM”, NMO, HIV, connective tissue disease or as a stand-alone diagnosis Relapse risk highly variable in literature; esp high if

• therwise have MS

Of 31 biopsy-confirmed cases at UCSF, 2 were malignant diagnoses (glioma, lymphoma). Up to 50% with f/u relapsed, 3 with recurrent TDLs. FLAIR T1 Post Gadolinium REPEAT MRI SIX WEEKS LATER, improved, no new lesions, resolution of abnormal enhancement Treated with oral glucocorticoids, down to 0.5 mg/day dexamethasone. Language much improved. Prominent right homonymous hemianopsia. No new symptoms.

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What is the diagnosis?

Solitary Tumefactive Demyelinating Lesion – but why?

• ?Clinically Isolated Syndrome (i.e. MS disease spectrum)?
• ?“Paraneoplastic” Disorder, secondary to smoldering myeloma?
• ?Malignancy
• ?Infection

What is the treatment?

• ?Watch and wait
• ?Repeat biopsy
• ?MS Disease Modifying Therapy
• ?Other immunosuppressive therapy
• ?Antibiotics
• 8 months later -> Localization-related Seizures (flashing green

lights right visual field, aphasia, confusion, then generalized tonic-clonic)

• MRI stable (no new or active lesions)
• EEG: Left temporal slowing, intermittent epileptiform

discharges midtemporal region

• Repeat CSF bland -> 1WBC (81% L, 16% M), 20 RBC, protein

64, glucose 67 (serum 130), IgG Index 0.5, matched bands but no unique oligoclonal bands, cytology/flow cytometry benign

Follow-up

10 months later: Subacute Ataxia, Vertigo. MRI new right cerebellar peduncular lesion extending adjacent to the 4th ventricle. Enhancing. Demyelinating etiology favored. LABS

• SPEP with monoclonal gammopathy, IgG 1900 ->3310
• Bone Marrow with 30-40% plasma cells, lambda monotypic with atypia and

plasma cell aggregates

• LDH normal, ESR normal, ANA neg

BODY IMAGING

• CT Chest/Abd/Pelvis: Segmental Pulmonary Emboli, no malignancy
• FDG-PET: Unremarkable
• MRI Total Spine: Diffuse heterogenous bone marrow signal with mottled
• enhancement. New endplate compression fractures (T8-12)

CSF EXAM:

• 9 WBC (90%L), protein 54, glucose 60, IgG index 0.6, matched bands, benign

cytology and flow cytometry

1) Transformed to Multiple Myeloma (Stage 2): treatment initiated 2) Relapsing-Remitting Demyelinating Disease – ?MS, paraneoplastic, coincidental? Temporally correlated with transition from smoldering to relapsing myeloma. No further CNS inflammatory activity on myeloma therapy.