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BL Hand Muscle Wasting — Does Everything on This Diagram Cause It?

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LEFT BRANCH: UMN Signs (+) → Mixed UMN + LMN

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RIGHT BRANCH: Pure LMN Type

Anterior Horn Cell

Root (C8–T1 Radiculopathy)

Plexus

Peripheral Nerve

Muscle

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Bottom Left: Disuse Atrophy → RA

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Summary

1. Typically unilateral (unless bilateral disease): Pancoast tumour, lower trunk plexopathy, TOS, C8–T1 radiculopathy, ulnar neuropathy
2. Characteristically unilateral/asymmetric: Hirayama disease, MMN (multifocal motor neuropathy)
3. Bilateral but primarily proximal (hand wasting not a main feature): LGMD

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History to Ask — Structured Approach

🔴 The Working Diagnosis: Paraneoplastic Cerebellar Degeneration (PCD)

"Paraneoplastic cerebellar degeneration associated with breast and gynecologic (ovaries, uterus) carcinomas — anti-Yo, anti-Ri antibodies" — Localization in Clinical Neurology, 8e

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1. History of Presenting Illness — Cerebellar Symptoms

• Onset and progression — subacute onset over weeks to months is a red flag for PCD (vs. slow years-long course of hereditary ataxia)
• Sequence — which came first: gait unsteadiness, limb ataxia, slurred speech, double vision, oscillopsia?
• Any nystagmus / oscillopsia noticed?
• Dysphagia or dysphonia — brainstem involvement (paraneoplastic encephalomyelitis overlap)
• Cognitive changes / memory problems — limbic encephalitis component?
• Sensory symptoms in limbs — sensory neuronopathy (anti-Hu)
• Autonomic symptoms — postural dizziness, constipation, gastroparesis (anti-Hu PEM)

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2. Gynecological / Oncological History ← Most Critical in a 60F

• Last Pap smear / cervical screening — when was it done?
• Postmenopausal bleeding — endometrial/uterine carcinoma
• Breast lump, nipple discharge, last mammogram — breast cancer (anti-Yo)
• Ovarian symptoms — bloating, early satiety, pelvic fullness (ovarian carcinoma)
• Family history of breast, ovarian, or colorectal cancer (BRCA risk)

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3. Weight Loss Characterisation

• Duration — how long for 10 kg loss?
• Associated anorexia vs. normal appetite (anorexia + weight loss = malignancy)
• Night sweats — lymphoma (Hodgkin's → anti-Tr cerebellar degeneration)
• Dysphagia / odynophagia — oesophageal/gastric malignancy
• Haemoptysis / chronic cough / smoker — SCLC (anti-Hu)
• Change in bowel habits, rectal bleeding — colorectal cancer

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4. Smoking & Substance History

• Smoking pack-years — SCLC most associated with PCD via anti-Hu; also risk for paraneoplastic encephalomyelitis
• Alcohol — chronic alcohol use is a major non-paraneoplastic cause of cerebellar degeneration (vermis predominant, but can be pancerebellar)
• Alcohol quantity and duration — vermis atrophy, thiamine deficiency (Wernicke's)

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5. Medication & Toxic History

• Phenytoin — classic cause of cerebellar atrophy/toxicity
• Chemotherapy (prior cancer treatment) — cytarabine, 5-FU, methotrexate can cause cerebellar syndrome
• Lithium toxicity
• Heavy metals — mercury, lead

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6. Family History

• Hereditary ataxias (SCA — spinocerebellar ataxia types): onset at 60 is late but possible for SCA3/SCA6
• Family history of ataxia, Parkinson's, tremor

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7. Past Medical History

• Prior malignancy (even if "cured" — recurrence can present with PCD, including Hodgkin's)
• Hypothyroidism — cause of cerebellar syndrome (ask about fatigue, cold intolerance, constipation)
• Coeliac disease — ask about chronic diarrhoea, bloating (gluten ataxia)
• Diabetes — non-ketotic hyperglycaemia can cause cerebellar signs; also peripheral neuropathy
• Autoimmune disease — SLE, Sjögren's (anti-Ro antibodies linked to cerebellar ataxia)

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8. Systems Review

• Rash — dermatitis herpetiformis (gluten ataxia), or paraneoplastic
• Uveitis / vision changes
• Myoclonus / jerks — opsoclonus-myoclonus (anti-Ri, breast/gynaecological)
• Psychiatric symptoms — depression, anxiety, personality change (limbic involvement)

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Bottom Line for Exam

1. Gynaecological cancer (ovary/uterus → anti-Yo) — most likely in this demographic
2. Breast cancer screening history
3. Smoking/SCLC (anti-Hu)
4. Lymphoma (night sweats, nodes → anti-Tr)
5. Alcohol (non-paraneoplastic cause to exclude)
6. Subacute onset (weeks–months) — confirms paraneoplastic pattern vs. hereditary (years)

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Temporal Lobe Hyperintensity on MRI — Differentials & Approach

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DIFFERENTIALS

🔴 Category 1: Infectious / Inflammatory

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🟠 Category 2: Autoimmune / Paraneoplastic Limbic Encephalitis

"Typical MRI findings include unilateral or bilateral mesial temporal lobe abnormalities best seen on T2-weighted and FLAIR images. The temporal-limbic regions may be hypointense on T1 and rarely enhance with contrast." — Bradley & Daroff's Neurology

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🟡 Category 3: Vascular

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🟢 Category 4: Tumour

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🔵 Category 5: Metabolic / Toxic / Genetic

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APPROACH

Step 1 — Characterise the MRI Signal

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Step 2 — Clinical Context (History + Exam)

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Step 3 — Investigations

• FBC, CRP, ESR
• Electrolytes (hyponatraemia → LGI1)
• Serum autoimmune encephalitis panel: Anti-NMDAR, LGI1, CASPR2, AMPAR, GABA-B, Hu, Ma2
• Paraneoplastic screen (Anti-Hu, Yo, Ri)
• Lactic acid (MELAS)
• Thyroid (Hashimoto encephalopathy)

• Opening pressure, cells, protein, glucose
• HSV PCR ← start empirical aciclovir BEFORE result
• VZV, EBV, HHV-6, CMV PCR
• Oligoclonal bands
• CSF autoimmune antibodies (more sensitive than serum for some)
• Cytology (if malignancy suspected)

• Temporal lobe epileptiform activity supports limbic encephalitis or TLE
• Periodic lateralising discharges (PLEDs) → HSE

• MRI with contrast — enhancement pattern
• MR spectroscopy — if tumour vs. inflammation unclear
• PET/CT whole body — if autoimmune/paraneoplastic (find hidden primary)
• CT chest/abdomen/pelvis — tumour screen

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Step 4 — Management Principle

Temporal lobe hyperintensity → fever/acute onset?
        ↓ YES → Start IV Aciclovir immediately (HSE treatment)
        ↓ NO → Subacute? → Autoimmune workup + paraneoplastic screen
                        → Seizures only? → Consider status/postictal change
                        → Structural/chronic? → Tumour / hippocampal sclerosis workup

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CSF Findings: HSE vs Limbic Encephalitis

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Key Differentiating Points

1. RBCs in CSF — the single most useful bedside discriminator

"Up to 500 red cells/mm³ are common [in HSE], and the CSF protein content is usually elevated." — Plum & Posner's Diagnosis & Treatment of Stupor and Coma

2. Pleocytosis is variable in both — but more marked in HSE

• HSE: typically 50–200 WBC/µL, can be up to 1,000
• Limbic encephalitis: mild or absent — the CSF can be entirely normal in up to 50% of autoimmune cases

"CSF often demonstrates findings consistent with inflammation (protein >50 mg/dL or lymphocytic pleocytosis >5 cells/µL) but can be normal." — Washington Manual of Medical Therapeutics

3. HSV PCR — definitive test, but timing matters

• Sensitivity 96%, specificity 99% when tested at 48–72 hrs after symptom onset
• Can be falsely negative in the first 24–48 hours — a negative early PCR does NOT rule out HSE
• If strong clinical suspicion + negative PCR < 72 hrs → repeat LP at 72–96 hrs
• Never stop aciclovir based on a single negative early PCR

4. Antibody testing in CSF vs serum

• For autoimmune encephalitis, CSF antibodies are more sensitive than serum for some (e.g., anti-NMDAR)
• Must be sent specifically; not part of routine CSF biochemistry
• Some antibodies (Anti-LGI1, CASPR2) are more reliably detected in serum than CSF

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Practical Algorithm

CSF Result
    │
    ├─ RBCs present + lymphocytic pleocytosis + elevated protein
    │        → HSE most likely → CONTINUE aciclovir, await PCR
    │
    ├─ Lymphocytic pleocytosis, NO RBCs, normal glucose
    │        → HSE still possible (early) OR autoimmune
    │        → Send HSV PCR + autoimmune antibody panel
    │
    └─ Completely NORMAL CSF
             → Does NOT exclude autoimmune limbic encephalitis
             → Does make HSE less likely (but not impossible early)
             → Send serum + CSF antibody panel

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Important Caveat — Post-HSE Autoimmune Encephalitis

"Late autoimmune encephalitis can occur 1 to 7 weeks after herpes simplex encephalitis, associated with NMDA-receptor antibodies in the spinal fluid." — Goldman-Cecil Medicine

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MRI Images: HSE vs Limbic Encephalitis

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🔴 Herpes Simplex Encephalitis (HSE)

• A & B (Case 1): Axial + coronal FLAIR — hyperintense signal in the left medial temporal lobe and insula (arrows), with cortical swelling. Classic HSE territory.
• C (Case 2): T1 non-contrast — swollen left temporal lobe with faint cortical hyperintensity indicating haemorrhage (black arrows).
• D: T1 post-contrast — gyriform enhancement (white arrows) — a pattern highly suggestive of HSE.

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• (A) FLAIR: massive bilateral temporal lobe hyperintensity — confluent and asymmetric, consistent with fulminant HSE. Note the left temporal lobe is more severely affected.
• (B) Post-contrast T1: bilateral enhancement pattern with associated swelling.

Key radiological hallmarks of HSE: medial temporal + insula + cingulate + orbitofrontal involvement; haemorrhagic component; gyriform enhancement; grey matter > white matter.

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🟠 Autoimmune / Limbic Encephalitis

• A — Limbic Encephalitis (anti-Hu, Ma2, AMPAR, GABA-B, LGI1, Caspr2): Bilateral medial temporal lobe FLAIR hyperintensity — confined, symmetric, no haemorrhage, no gyriform enhancement. Clean signal restricted to hippocampus/amygdala.
• B — Anti-NMDAR encephalitis: Often normal MRI or only mild, subtle FLAIR changes — despite severe clinical syndrome.
• C — Anti-GABA-B encephalitis: Multiple cortical-subcortical FLAIR changes, more widespread than classic limbic encephalitis.
• D — MOG-antibody encephalitis (paediatric): Extensive cortical T2 signal, diffuse cortical involvement.

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Side-by-Side Differentiating Features on MRI

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Memory Hook

HSE = Haemorrhage + Swelling + Enhancement (gyriform) + Insula involved
Limbic Encephalitis = Limited to mesial temporal, Enhancement absent, Bilateral and symmetric