MRI Bilateral Temporal + Cerebellar Hyperintensities with Progressive Cerebellar Symptoms (2-Year History)

Most Likely Diagnoses (Top Differential)

1. 🥇 Autoimmune / Paraneoplastic Limbic Encephalitis + Cerebellar Degeneration

2. Limbic Encephalitis (Non-Paraneoplastic or Paraneoplastic)

3. Anti-GAD Cerebellar Ataxia + Temporal Involvement

• Insidious, slowly progressive over years
• Women predominate (80–90%)
• Can overlap with stiff person syndrome or limbic encephalitis
• MRI: cerebellar atrophy ± T2 changes; temporal involvement reported
• Responds partially to IVIG + corticosteroids (35% improvement) — Bradley and Daroff's Neurology in Clinical Practice

4. Bickerstaff Brainstem Encephalitis (BBE)

• Progressive ophthalmoplegia + ataxia + altered consciousness
• T2 hyperintensity in brainstem, cerebellum, thalamus, subcortical white matter — temporal involvement less typical
• Anti-GQ1b antibodies positive in most cases
• Usually more acute; 2-year progression is atypical unless undertreated — Bradley and Daroff's Neurology in Clinical Practice

5. CLIPPERS (Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids)

• Subacute gait ataxia + diplopia + dysarthria
• MRI: pontocerebellar perivascular enhancement ("peppercorn pattern")
• Can be progressive; steroid-responsive
• Temporal involvement less characteristic

6. Mitochondrial Disease (MELAS / POLG-ataxia)

7. Neurosarcoidosis

• Chronic inflammatory granulomatous disease
• Cerebellar FLAIR hyperintensity → atrophy in chronic cases
• Brain/meningeal biopsy shows non-caseating granulomas
• Temporal involvement possible with leptomeningeal spread — Bradley and Daroff's Neurology in Clinical Practice

8. Prion Disease (Creutzfeldt-Jakob Disease — sCJD)

• Rapid progressive cerebellar + cortical involvement
• DWI > T2/FLAIR: cortical ribboning + basal ganglia, thalamic signal
• CSF: elevated 14-3-3 protein, tau; RT-QuIC positive
• Typically faster course than 2 years (weeks–months), but MM2 variant can be slower

9. Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)

• Older males (premutation carriers, FMR1 gene)
• MRI: middle cerebellar peduncle (MCP) hyperintensities + deep cerebral white matter; temporal occasionally involved
• Action tremor + cerebellar ataxia + cognitive decline

10. CADASIL / CARASIL

• Hereditary small vessel disease (NOTCH3 mutation / HTRA1)
• Bilateral white matter hyperintensities including temporal pole (Fazekas pattern — temporal pole involvement is a hallmark of CADASIL)
• Progressive cognitive decline, strokes, pseudobulbar palsy, migraine
• Cerebellar involvement possible with posterior fossa lacunes

Diagnostic Approach

STEP 1 — MRI Review
├── Confirm: Bilateral medial temporal T2/FLAIR hyperintensity?
├── Cerebellar: atrophy, white matter signal, MCP sign?
├── DWI: restricted diffusion? (CJD, stroke)
├── Enhancement pattern: perivascular (CLIPPERS), nodular, leptomeningeal?
└── Temporal pole involvement (CADASIL)?

STEP 2 — Blood Tests
├── Paraneoplastic panel: Anti-Hu, Anti-Yo, Anti-Ri, Anti-CV2, Anti-Ma2, Anti-VGCC
├── Autoimmune encephalitis: Anti-LGI1, Anti-CASPR2, Anti-NMDAR, Anti-GABA-B
├── Anti-GAD65 (high titre)
├── Thyroid antibodies (anti-TPO, anti-TG) → Hashimoto encephalopathy
├── Anti-gliadin, anti-TG6, anti-tTG → Gluten ataxia / celiac
├── ANA, dsDNA, ANCA, ACE → Lupus, vasculitis, sarcoidosis
├── Mitochondrial: lactate, pyruvate, genetic testing (POLG, MTTL1)
├── FMR1 premutation screen (males, family history)
└── HIV, RPR/VDRL, Lyme serology

STEP 3 — CSF Analysis
├── Cell count, protein, glucose, IgG index, oligoclonal bands
├── Paraneoplastic + autoimmune antibody panel (CSF more sensitive for some)
├── 14-3-3 protein, total tau, RT-QuIC (if CJD suspected)
├── Culture, PCR (HSV, EBV, JCV, VZV, CMV)
└── Cytology + flow cytometry (CNS lymphoma)

STEP 4 — Oncology Screening
├── CT chest/abdomen/pelvis (lung, ovarian, breast cancer)
├── PET-CT if CT negative and paraneoplastic suspected
└── Testicular ultrasound in young males

STEP 5 — Tissue / Special
├── Muscle biopsy with COX/SDH stain if mitochondrial suspected
├── Skin biopsy for CADASIL (NOTCH3 electron microscopy)
└── Brain biopsy if all else negative and steroid trial fails

Key Teaching Point

• Chronic autoimmune/paraneoplastic (anti-Hu, anti-GAD, anti-CASPR2)
• Metabolic/genetic (MELAS, POLG, CADASIL)
• A treatable autoimmune cause that has been missed

• Bradley and Daroff's Neurology in Clinical Practice — Acquired Causes of Ataxia; Paraneoplastic Cerebellar Degenerations; Anti-GAD Ataxia; Bickerstaff Encephalitis; CLIPPERS; Neurosarcoidosis
• Fishman's Pulmonary Diseases — Paraneoplastic Neurological Syndromes in SCLC
• Recent reviews: Mitoma & Manto (2024) — J Neurol PMID 39052041; Abbatemarco et al. (2024) — Handb Clin Neurol PMID 38494276 (paraneoplastic cerebellar and brainstem disorders)

Beevor's Sign

Note: The correct spelling is Beevor's sign (named after British neurologist Charles Edward Beevor, 1854–1908). "Beaver sign" is a common phonetic misspelling in clinical settings.

Definition

• Flex the neck against resistance, or
• Sit up with arms crossed over the chest

Anatomical Basis

• When a lesion affects T10–T12 (or lower), the lower rectus abdominis is weak/paralyzed
• The upper rectus abdominis (T7–T9) remains intact
• On neck flexion/sit-up attempt, the intact upper fibers contract unopposed, pulling the umbilicus upward

How to Elicit the Sign

1. Patient lies supine
2. Arms crossed over chest (no assistance)
3. Ask patient to: flex neck or attempt to sit up
4. Observe the umbilicus

Causes

1. Spinal Cord Lesions (Neurogenic) — T9–T12 Level

2. Neuromuscular Disease — Most Diagnostically Specific

⭐ Facioscapulohumeral Muscular Dystrophy (FSHD) — Diagnostic

• FSHD preferentially weakens the lower rectus abdominis more than the upper
• Beevor's sign is found in 27/30 patients with FSHD (one landmark study); 19/20 in a genetically confirmed series
• Sensitivity: 95%, Specificity: 93% among neuromuscular disorders
• Specificity 97–100% in some series vs. neurological controls
• Considered quasi-pathognomonic for FSHD when combined with other features (facial weakness, scapular winging, "Popeye arm," foot drop)

Amyotrophic Lateral Sclerosis (ALS)

• Selective lower abdominal weakness from UMN/LMN involvement
• Less frequently reported than in FSHD

Inclusion Body Myositis (IBM)

• Patchy, asymmetric muscle involvement can produce this sign

Familial Tubular Aggregate Myopathy

• Rare; two confirmed cases in non-FSHD series

3. Other Reported Causes (Rare)

Differential Diagnosis of a Positive Beevor's Sign

Clinical Utility

1. Spinal cord level localization — useful when sensory findings are absent or ambiguous; a positive sign points to cord damage at T9–T10
2. FSHD diagnosis — highly specific; positive sign + facial + scapular features = FSHD until proven otherwise
3. Organic vs. functional paraplegia — Beevor's sign helps differentiate organic paraplegia from psychogenic/functional weakness (functional disorder = sign absent)

Inverted Beevor's Sign

• Localization in Clinical Neurology, 8e — Lesions of the Thoracic Segments
• Harrison's Principles of Internal Medicine 22E — Thoracic Cord localization
• Bradley and Daroff's Neurology in Clinical Practice — Facioscapulohumeral Dystrophy
• Adams and Victor's Principles of Neurology, 12th Ed.
• Goldman-Cecil Medicine — FSHD chapter
• StatPearls (NBK545262) — Beevor Sign