MS or Lyme or neither?

40 year old lady married + 4 children, born in Israel, with presumptive diagnosis of MS presenting with blurred vision of the right eye

2002

Admitted with right leg weakness

Myelopathic signs on examination

MRI revealed inflammatory lesion T7-8

LP: TP 501, no cells, OCB negative

Treated with steroids with marked improvement

No neurological symptoms until current presentation

At presentation mild sensory symptoms only

Current admission

3 days prior to admission, after slight bump to head, noticed blurred vision of R eye

Vision deteriorated over following 3 days with pain on eye movement

Past history

No other neurological problems

No other clinical features referable to auto-immune disease ( e.g. SLE, Bechets)

No history of miscarriage

Serological abnormalities ( to be discussed)

Had traveled to New England but no history of tick bite

Examination

General examination unremarkable

RAPD on the right

Fundoscopy normal

Remainder of examination normal with no evidence of myelopathy

Steroids started for presumptive “ MS exacerbation”

Laboratory investigation prior to admission

Immunology

ATG 87, 87 ( <100) 3.2003, 1.2004

ATPO 793, 538 ( <75)!! (TSH 3.56 - normal)

ANA +2 / 4 (2002) –ve x2 (2003,2004)

ENA +ve x1 (2002) –ve x2

ANCA –ve x2

Laboratory investigation prior to admission

Serology

CMV past infection

EBV past infection

VZV past infection

Toxoplasma neg

Brucella neg

VDRL neg

Brucella neg

Lyme +ve x2 ( 10.2003, 1.2004)

Brain MRI

Laboratory investigation during current admission

FBC, Bioch normal

ESR 18

LP: - Pressure 12 cm H 2 O

- TP 488, no cells, OCB negative

Anticardiolipin Ab’s negative

pANCA cANCA negative

ANA negative

TSH normal

Anti TPO 397 ( 0-35)

Anti TG normal

Homocysteine Pending

Course

Received high dose steroids

Day 4: Ceftriaxone added, steroids tapered

Day 5: improvement noted in vision

Day 6 am : - mild left hemiparesis noted, steroid dose incresed

Day 6 pm: witnessed tonic-clonic seizure. On examination, severe L hemiparesis

Brain CT unremarkable

Course cont.

Further seizures: Unresponsive to benzodiazepines phenytoin, phenobarbital (RSE)

Intubation, propofol IV

MRI: Right MCA infarct

Anticoagulant treatment commenced

Brain MRI after Seizure

Further Investigation

Angiograpghy - decreased perfusion in R MCA territory

TEE - no clot detected

Course cont.

Weaned from propofol and BZD’s

Extubated

Marked improvement of hemiparesis

Neurological features of chronic Lyme disease

CSF in Chronic Lyme

In early cases of neuroborreliosis, spinal fluid findings may still be negative.

In cases of chronic disease, only mild elevations of protein may persist.

In these circumstances, detection of B. burgdorferi DNA by PCR may be important to establish the diagnosis.

Serology

Both IgG and IgM responses can persist for over 10 years, even after successful antibiotic treatment

False positive ELISA results can be caused by other bacteria (e.g. Treponema denticulata ) or by a polyclonal B cell stimulation.

Positive serology alone is not sufficient to make the diagnosis

Cross-reactivities with syphilis tests do occur

Direct detection methods (PCR) diagnostic

Value of Serology

Proposed diagnostic criteria

clouding of consciousness with reduced wakefulness, attention, or cognitive function

no CSF evidence of bacterial or viral infection

high serum concentration (or titer) of antithyroid microsomal, antithyroid peroxidase, or antithyroglobulin antibodies

Thyroid function

MRI in Hashimoto Encephalopathy

Summary of Neurological Features

Stroke-like signs in 23 patients (27%)

seizures in 56 patients (66%)

status epilepticus (10 patients [12%])

course relapsing and remitting in 51 patients (60%).

CSF in Hashimoto Encephalopathy

65 patients (76%), the CSF contained 0 to 3 nucleated cells/mm3

In 3 patients (4%), it contained more than 100 cells/mm3

CSF protein concentration was high in 66 patients (78%), exceeding 0.01 g/dL in 18 patients (21%).

Imaging

11 had cerebral atrophy

13 had nonspecific subcortical focal white matter abnormality

8 had diffuse subcortical abnormality,

7 had focal cortical abnormality

1 had transient bilateral narrowing of a middle cerebral artery

Antiphospholipid syndrome

Can simulate MS

especially in patients with myelitis and optic neuritis

Especially in those without OCB’s

( Karussis et al, Annals of Neurology 1998 )

Associated with stroke in the young

However:

Anticardiolpin negative during current hospitalisation (steroids should not cause disappearance)

Lupus anticoagulant not checked prior to heparin treatment

MS

Clinical and MRI features fit

Against

OCB –ve twice

Stroke

( therefore other conditions must be excluded)

Out of 31 MS patients 5 (16%) had Anti TPO Ab’s Normal values: TPO-Ab 0–10 IU/mL;

CNS Vasculitis - GANS - PAN ( but no systemic features) GANS CSF and angiography normal MRI probably “ too severe” given mild clinical features prior to stroke No headache Clinical course typical of MS Stroke Optic nerve and spinal cord involvement rare Can simulate relapsing – remitting course of MS Against For

Is MS associated with alteration of platelet function? “ platelet aggregation and MS” Neu et al 1982 Acta neurologica Scand.