case studies ms diagnosis giovannoni ens june 2013

Case study (1)

pitfalls in MS diagnosis

Gavin Giovannoni

Institute of Cell and Molecular Science

Barts and The London School of Medicine and Dentistry

Misdiagnoses • PPMS – spinal cord meningioma (MRI)

• SPMS – thoracic disc

• PPMS – HTLV1 myelopathy (Serology)

• RRMS / PMS – Paraneoplastic (PET, biopsy)

• RRMS / MADEM – CNS B cell lymphoma (Biopsy)

• RRMS – migraine / hypertensive small vessel disease

• RRMS – neurovascular syphilis (LP & serology)

• RRMS – MUS / somatisation disorder

• RRMS – NMO

• RRMS – swayback disease

• CIS – CRION

• RRMS - ADEM

• MS – Friedrich’s ataxia

• MS – chronic fatigue syndrome

• Neurosarcoidosis – RRMS (uveitis)

• SLE / Primary APLS - RRM

• Vasculitis - RRMS

• ADEM / MADEM – RRMS

• NMO - RRMS

34-yr old right handed male

• December ‘99 tingling tips of great toes

• April 2000 found to anaemic as a screen during blood donation

• Mild anaemia Hb 11 g/dL, normachromic normocytic anaemia

• VB12 and folate low normal

• Sensory symptoms gradually progressed to involve feet

• Referred to neurosurgeon

• Abnormal MRI

• Referred him to a neurologist

Diagnosis

• Subacute combined degeneration of spinal cord • vB12 supplementation

• No improvement

• Referred to haematologists • Bone marrow showed dysplastic marrow (non-specific)

• VEP’s • Bilaterally delayed (P100 ~ 125msecs)

? Multiple sclerosis

Jan 2002

• Myelopathy – sensory ataxia mild pyramidal signs.

• Optic neuropathy – VA 6/9 & 6/12, abnormal colour vision and pale discs

• Neuropathy – glove and stocking sensory loss with depressed ankle jerks

• FH (adopted)

• Non-smoker, Alcohol 14-21u/week

• Banker working in the city, married, two children

• MRI – C spine signal change had become more extensive

Jan 2002 • Bloods – Hb 8.9 g/dl (microcytic), neutrophils 1.2, platelets 95 • TFTs, U&E, LFTs, ESR, CRP, ANF, vB12, folate, HTLV-1&2, vE, lactate,

pyruvate normal or negative. • Transcobalamin 1, homocysteine and urinary malonic acids normal. • Plasma and urine organic acid profile were normal. • White cell enzymes normal • Iron 3.6 (low), TIBC 90 (45-70), Fe-binding sat. 4% (45-70), ferritin 151

(normal) – important result. • CSF – normal • VEP’s delayed • SEPs abnormal • NCS – absent SNAPs normal motor conduction studies – severe

sensory neuronopathy

Clinical phenotype

• Optic neuropathy – demyelinating

• Myelopathy – motor & sensory

• Sensory Neuronopathy

• Bone marrow dysplasia

• Fe block – unable to mobilise Fe from peripheral stores.

Diagnostic results

• Serum copper = 0.7 umol/L)

• Caeruloplasmin <0.02

• Serum zinc 32.4 umol/L (11-18umol/L)

• Penicillamine challenge – normnal urinary copper excretion

• Zinc toxicity with secondary copper deficiency

Case study (2)

MS mimics or not

Gavin Giovannoni

Institute of Cell and Molecular Science

Barts and The London School of Medicine and Dentistry

• 34-yr old afro Caribbean female presented

with episode of acute myelitis with

quadraparesis

• 3 months later episode of typical left acute

optic neuritis with with 6/60 vision

• MRI brain 2 non-specific white matter lesions

? Multiple Sclerosis

• 34-yr old afro Caribbean female presented with episode of acute myelitis with quadraparesis

• Longitudinally extensive spinal lesion (>3 vertebral segments)

• active CSF with 75 lymphocytes

• -ve OCBs

• MRI brain 2 non-specific white matter lesions

• Poor recovery of next 3 months

• 3 month later episode of typical left acute optic neuritis with with 6/60 vision

• Poor recovery 6/24 after 12 months

• 24 months later Coomb’s positive haemolytic anaemia

• Positive ANF titre of 1:320

• Positive anti-dsDNA