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