S5 E17: Serendipity

Do you believe in coincidence? How about serendipity?

Today the group is joined by Internal Medicine PGY-2 Dr. Alastair Williams who presents a case that brings everyone to a stand still. Is it possible to solve a case if you’re unable to connect the dots? Have a listen to see if you can make the diagnosis!

ID –

39yo previously healthy male presented with 2mo hx worsening leg weakness and tingling in feet

HPI –
Noticed increasing difficulties hiking and doing normal activities

PMHx –
Depression
Anxiety
Chronic lymphedema in lower legs
Hx of inguinal repair
Recurrent HPV infections of hands and feet

Medications –
Escitalopram
Lorazepam

Social Hx –
Caucasian
Born and raised in Canada
No IV drug use
Previously used cocaine recreationally, high risk alcohol use previously but now abstinent, smokes cannabis daily
Never travelled out of North America
Previously worked as a painter and resurfacer

Physical exam

Neurologic exam
- Normal cranial nerves
- Mild weakness right finger abductors and bilateral finger flexors
- Bilateral Hoffman sign
- Normal upper extremity tone and sensation
- Normal lower extremity power
- Lack of pinprick up to inguinal areas
- Impaired vibration of great toes
- Brisk upper and lower extremity reflexes
- Bilateral Babinski sign
- Difficulty with tandem gait
- Positive Rhomberg
Head and neck, cardiac, respiratory, abdominal exams are normal

Initial Investigations

Investigations
- Blood
  - WBC 2.2 × 10⁹/L (normal 3.5-10.5 x 10⁹/L)
  - Neutrophils 1.5 × 10⁹/L (normal 2.0-7.5 x 10⁹/L)
  - Lymphocytes 0.5 (normal 0.8-3.5 x 10⁹/L)
  - Monocytes undetectable
  - Normal eosinophil and basophil counts
  - Hgb 153 g/L (normal 125-170 g/L)
  - Plt 174 × 10⁹/L (normal 130-380 x 10⁹/L)
  - Normal coagulation studies
  - Normal lytes and extended lytes
  - ALP 120 (normal 50-136 IU/L)
  - GGT 85 (15.0-85.0 IU/L)
  - Bili 26 (3-17 µmol/L)
  - Normal LDH, ALT, AST, albumin

More information

Investigations
- Imaging
  - MRI whole spine
    - Linear band of high signal in dorsal aspect of the cervical cord from C1-C6
    - Abnormal signal in right lateral aspect of cervical cord
    - Cervical spinal canal normal, no disc herniation or masses
    - High signal in right lateral aspect of thoracic cord
    - Focal disc or osteophyte at T3 level without significant cord compression
    - Diffuse disc bulging at L4 and L5 without cord compression
    - Otherwise unremarkable
    - No enhancements in cord on contrast-enhanced study
  - MRI brain
    - Ill-defined patchy T2 flare in bilateral pons and midbrain
    - Hyperintense T2 flare focus in frontal lobes
    - No mass or enhancing lesions
- Lumbar puncture
  - No nucleated cells
  - Glucose 3.1 mmol/L (normal 2.77-4.44 mmol/L)
  - Protein 1.18 g/L (0.15-0.6 g/L)
  - No xanthochromia
  - Cytology negative for malignant cells but showed rare small mature lymphocytes
  - Oligoclonal bands present in both CSF and serum not supporting diagnosis of multiple sclerois
  - Culture negative for bacteria, fungi, mycobacteria
  - TB PCR negatives
  - Crypotoccocal antigen negative
- Blood
  - Infectious
    - VDRL, HIV negative
    - Crypotoccocal antigen negative
    - HTLV-1 and HTLV-2 antibody negative
  - Autoimmune
    - ANA positive 1:80
    - Rheumatoid factor 34.3 kIU/L (normal ≤ 20 kIU/L)
    - ENA negative
    - C3/C4 negative
    - MPO/PR3 negative
    - IgG, IgA, IgM elevated
    - SPEP – Polyclonal hypergammaglobulinemia
    - UPEP – Trace proteinuria, primarily albumin
  - Endocrine
    - TSH and cortisol normal
  - Normal vitamin B12 level
  - Bone marrow biopsy
    - Both erythropoiesis and granulopoiesis unremarkable in number, maturation, and morphology
    - Slight excess of mature plasma cells
    - No excess lymphocytes or blasts and no metastatic cells
    - 1+/4 iron stores
    - Core biopsy 25% cellularity decreased for age
    - Trilineage hematopoiesis present and unremarkable in morphology

More information

Physical examination
- Neurological examination
  - New spasticity
  - More pronounced global hyperreflexia
  - 4/5 strength bilaterally in lower extremities
Investigations
- Imaging
  - MRI brain and whole spine
    - Unchanged T2 flare hyperintensities in cervical/thoracic spinal cord, pons, and midbrains
  - PET
    - No FDG-avid lesions
- Blood
  - Infectious
  - Toxins
    - Negative heavy metal testing
  - Chemistry
    - IgG testing negative
    - Hepatitis serologies negative
    - Porphyria testing negative
    - tTG-IgA negative
    - Liver enzymes normalized
    - Normal kidney function

More information

Investigations
- Upper endoscopy
  - H. pylori induced lymphocytic gastritis
- Lower endoscopy
  - No abnormalities
- Skin biopsy
  - Panniculitis
  - No organisms isolated
- Blood
  - WBC 1.5 × 10⁹/L (normal 3.5-10.5 x 10⁹/L) -> 5.6 × 10⁹/L
  - Neutrophils 4.0 × 10⁹/L (normal 2.0-7.5 x 10⁹/L)
  - Lymphocytes 1.4 × 10⁹/L (normal 0.8-3.5 x 10⁹/L)
  - Monocytes 0.2 × 10⁹/L (normal 0.1–1.0 × 10⁹/L)
  - Eosinophils and basophils undetectable
Physical examination
- Neurological exam
  - Normal cranial nerves
  - Lower extremity increased tone
  - Normal hip flexor power
  - Dorsiflexors 4/5 strength bilaterally
  - Few beats of clonus at ankle
  - Wide-based gait
  - Brisk reflexes
  - Sensory level at inguinal region
  - Mild dysmetria in both upper and lower extremity

More information

Investigations
- Imaging
  - MRI brain and whole spine
    - Patchy confluent areas of increased T2 signal in periventricular white matter
    - Confluent bilateral midbrain and pontine T2 signal similar to previous
    - No abnormalities involving orbits
    - Subtle increased T2 signal in dorsal aspect of thoracic spinal cord from T3-T6 similar to previous

More information

Physical examination
- Neurological exam
  - Increased upper and lower extremity tone and spasticity
  - 3/5 power in lower extremities
  - Diminished light touch and pinprick up to lower chest wall
  - Broad based and spastic gait
  - Could not perform tandem gait
  - Impaired finger-to-nose and heel-to-shin
Investigations
- Blood
  - WBC 1.5 × 10⁹/L (normal 3.5-10.5 x 10⁹/L)
  - Neutrophils 0.6 × 10⁹/L (normal 2.0-7.5 x 10⁹/L)
  - Lymphocytes 0.8 × 10⁹/L (normal 0.8-3.5 x 10⁹/L)
  - Hgb 134 g/L (normal 125-170 g/L)
  - Platelets normal
  - Monocytes, eosinophils and basophils undetectable
  - Normal blood chemistries and liver function tests
  - CRP 2.9
- Rheumatologic
  - ANA 1:80
  - Lupus autoantibody profile negative
  - CK normal
  - Anti-smooth muscle antibody negative
  - GAD65 antibody negative
  - Myelin-associated glycoprotein antibody negative
  - Anti-GM1 IgM positive from neurologic disease profile on serum
  - Anti-aquaporin-4 negative
  - Anti-MOG negative
- CSF
  - Negative for all tested autoantibodies

More information

Investigations
- Bone marrow biopsy
  - Occaisional dysplastic megakaryocytes and disintegrated nuclei and high nuclear-to-cytoplasmic ratio
  - Megaloblastic erythropoiesis
  - Mature neutrophils show dysplastic features
  - Blasts are 7% of differential
  - Potentially in keeping with myelodysplastic syndrome with excess blasts
- Next-gen sequencing panel and whole exome sequencing
  - GATA2 gene mutation

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