Back pain, ophthalmoplegia, and more…

Back pain, ophthalmoplegia, and more… Dr MJ Thurtell1,2 Dr PJ Ho2 Dr GM Halmagyi2 1University

Hospitals Case Medical Center, Cleveland OH 2Royal Prince Alfred Hospital, Sydney NSW, Australia

Case Description • Presenting Complaint: – 73-year-old Caucasian male – Back pain

• Past Medical History: – Hypertension – Dyslipidemia – Ischemic heart disease – Sciatica

Case Description • History of Presenting Illness: – Presented to primary care physician with: • Several week history of dull lumbar back pain

– Denied: • • • • • •

Lower limb weakness Appendicular or gait ataxia Sensory disturbance Sphincter disturbance Antecedent illness Constitutional symptoms (e.g. fever, sweats, loss of weight, anorexia, etc)

Case Description • History of Presenting Illness: – Examination: • Vital signs WNL • Long-standing foot drop, no new neurologic signs

– Investigations: • CT lumbosacral spine reportedly showed minor degenerative changes

– Provisional diagnosis: • Musculoskeletal back pain

– Treatment: • Analgesia

Case Description • History of Presenting Illness: – Represented 2 weeks later with: • Diplopia • Right-sided ptosis • Persistent lumbar back pain

– Examination by general ophthalmologist: • Incomplete right third nerve palsy • Pupillary involvement?

– Investigations: • Urgent CT brain with contrast and CT angiography unremarkable

Case Description • History of Presenting Illness: – Over the next 2 days, developed: • Sensory disturbance in limbs • Appendicular and gait ataxia • Limb weakness

– Examination on admission to hospital: • Complex ophthalmoplegia • Flaccid quadriparesis • Areflexia

– Progress: • Increasing respiratory failure Æ intubated/ventilated

Case Description • Examination following transfer (Friday PM): – Vital signs: • Tachycardia • Fever (103.1ºF)

– General examination: • • • • •

Intubated/ventilated, decreased AE at lung bases No meningismus No rash No focus of infection General examination (cardiovascular, respiratory, gastrointestinal, endocrine, etc) unremarkable

Case Description • Examination following transfer (Friday PM): – Neurologic examination: • Alert, following commands • Complex ophthalmoplegia, very restricted range of movement in all directions (could not be overcome with VOR), asymmetric ptosis (R>L). No Cogan lid twitch or any other signs suggestive of fatigability. • Miotic (2mm) pupils, with normal reaction to light. • Facial diplegia • Flaccid quadriparesis • Areflexia • Minor peripheral sensory loss

Any thoughts, what would you do next? 1. Nerve conduction studies and electromyography 2. Anti-GQ1b 3. Serum botulinum titers & give antitoxin 4. Lumbar Puncture 5. Antineuronal antibody panel

44%

22% 16% 11% 7%

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Case Description • Investigations: – Cerebrospinal fluid examination: • Biochemistry: – Protein 0.61g/L – Glucose normal

• Cell count: – Red cell count 90,000 × 106/L – White cell count 20 × 106/L

• Microscopy: – No organisms on Gram stain – No abnormal cells on cytology

• Culture: – No growth

Case Description • Investigations: – Nerve conduction studies: • Decreased motor conduction velocities • Low amplitude sensory nerve action potentials • F-waves: – Prolonged latencies, UL (LUL>RUL) > LL – Impersistent, UL (LUL>RUL) > LL

– Septic screen: • Chest x-ray: – Bibasal collapse/consolidation

• Blood/urine/sputum cultures: – No growth

Provisional Diagnosis? Acute Inflammatory Demyelinating Polyneuropathy – overlap syndrome? Ventilator-Associated Pneumonia

Case Description • Management: – Intravenous Immunoglobulin (0.4g/kg/day) – Broad-spectrum antibiotics – Ongoing supportive care

• Progress: – Slight improvement after 2 days of treatment – Fever persisted (assumed to be from resolving ventilator-associated pneumonia)

Any further investigations?

Axial T2-weighted MRI

Axial T1-weighted MRI with contrast

Coronal fluid-attenuated inversion recovery (FLAIR)

Coronal T1-weighted MRI with contrast

Sagittal T1-weighted MRI with contrast

Coronal T1-weighted MRI with contrast

Axial T2-weighted MRI

Axial T1-weighted MRI with contrast

Given the history, which would seem to be the most likely cause? 1. Chronic bacterial meningitis 2. Fungal meningitis 3. Idiopathic hypertrophic pachymeningitis 4. Carcinomatous meningitis 5. Lymphoma 6. Neuro-sarcoidosis

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30%

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Any further investigations? Clues: 1. Rapidly falling platelet count 2. Abnormality noted on blood film

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Blood Film (H&E)

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Blood Marrow Trephine (H&E)

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Blood Marrow Trephine (H&E)

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Blood Marrow Aspirate (H&E)

Case Description • Investigations: – Immunohistochemistry: • • • • • • • • • • •

CD10 +++ CD20 +++ CD70a +++ Kappa (light chains) and surface Ig + Ki67 + on 70% of tumor cells CD1a – CD3 some small cells weakly + CD5 – TdT – Myeloperoxidase – Cytokeratin –

Full Body FDG Positron Emission Tomography (FDG-PET)

Case Description • Management: – High-dose dexamethasone – “CHOP” regimen of chemotherapy – Intrathecal methotrexate

• Progress: – Rapid clinical and radiological improvement, with complete hematologic remission – Months later, developed central line infection Æ infective endocarditis Æ septic embolus causing “top of basilar syndrome” Æ died

Final Diagnosis? Diffuse Large B-Cell Lymphoma with CNS Involvement Mimicking Acute Inflammatory Demyelinating Polyneuropathy (AIDP)

Case Discussion • AIDP presenting with ophthalmoplegia: – May rarely occur in the ophthalmoplegic-variant of Guillain-Barre syndrome (GBS), which has a ‘descending’ rather than ‘ascending’ onset. [ter Bruggen et al. Muscle & Nerve 1998; 21: 239-242]

– May occur in Miller-Fisher syndrome (MFS), although progression to flaccid quadriparesis is rare in MFS. [Lo. Muscle & Nerve 2007; 36: 615-627] – Quadriparesis may occur if there is overlap of MFS with Bickerstaff’s brainstem encephalitis. [Odaka et al. Brain 2003; 126: 2279-2290; Winer. JNNP 2001; 71: 433-435]

Case Discussion • Lymphoma/leukemia and AIDP-picture: – Most prior cases have occurred following the initiation of treatment: • secondary to neurotoxicity from treatment, or • paraneoplastic phenomenon

– In rare cases, neoplastic cells shown to be infiltrating nerve roots or peripheral nerves. [Boiron et al. Leuk Lymphoma 1993; 10: 489-491]

– Few cases of ophthalmoplegic AIDP-picture found to be due to extradural/CNS lymphoma or leukemic deposits. [Toren et al. Med Pediatr Oncol 1994; 23: 372-375]

Case Discussion • The struggles/dilemmas in this case: – Presented with features suggestive of AIDP, although not typical of either GBS or MFS. – CSF findings and nerve conduction studies supported a diagnosis of AIDP. – The correct diagnosis of diffuse large B-cell lymphoma was only made after imaging and hematologic studies suggested an alternative diagnosis. – Apart from fever at the time of transfer, there were no other features to suggest lymphoma.

Take-Home Message Lymphoma may present with symptoms and signs that mimic an acute inflammatory demyelinating polyneuropathy such as GBS