What are the possible diagnoses for a patient with normal MRI and NCS, presenting with dizziness and weakness?

Differential Diagnosis for Dizziness and Weakness with Normal MRI and NCS

Given normal brain/spine MRI and nerve conduction studies, the most likely diagnoses are metabolic/nutritional neuropathies (particularly vitamin B12 deficiency), vestibular disorders (vestibular migraine or cervicogenic dizziness), or small fiber neuropathy that would not be detected by standard NCS.

Metabolic and Nutritional Causes

Vitamin B12 Deficiency

• B12 deficiency presents with weakness, dizziness, ataxia, peripheral neuropathy, and fatigue—all with normal structural imaging 1, 2.
• The dorsal column involvement causes sensory ataxia and proprioceptive loss that may not show abnormalities on routine MRI, though cervical/thoracic spine MRI can sometimes reveal spinal cord atrophy 3, 4.
• Neurological symptoms can occur even before hematological abnormalities develop, and nerve conduction studies are often normal in early B12 deficiency 2, 5.
• Check serum B12 level (diagnostic if <180 pg/mL), methylmalonic acid if borderline (180-350 pg/mL), complete blood count for macrocytic anemia, and consider anti-intrinsic factor and anti-parietal cell antibodies 1, 6.
• Risk factors include vegetarian diet, older age, metformin use, proton pump inhibitor use, and autoimmune gastritis 1, 7.

Copper Deficiency

• Copper deficiency mimics B12 deficiency with dorsal column dysfunction, sensory ataxia, and weakness with normal initial imaging 3.

Vestibular and Central Causes

Vestibular Migraine

• Vestibular migraine presents with dizziness, neck tension, headache, photophobia, and phonophobia—all with normal MRI 8.
• This requires migraine prophylaxis and lifestyle modifications, not vestibular suppressants 8.
• HINTS examination (Head Impulse, Nystagmus, Test of Skew) by trained practitioners has 100% sensitivity for posterior circulation stroke and helps differentiate peripheral from central causes 8.

Cervicogenic Dizziness

• Dizziness originating from neck pathology with associated neck tension can present with normal brain imaging 8.
• Requires comprehensive vestibular examination including HINTS testing 8.

Posterior Circulation Ischemia

• CT brain has only 20-40% sensitivity for posterior circulation pathology, so normal CT does not exclude vascular causes 8.
• MRI is more sensitive but can still miss early posterior circulation events 8.
• Consider MRA/CTA of head and neck if clinical suspicion remains high 8.

Peripheral Nervous System Disorders

Small Fiber Neuropathy

• Standard nerve conduction studies only evaluate large myelinated fibers and will be completely normal in small fiber neuropathy 3.
• Small fiber neuropathy causes pain, altered sensation, and autonomic symptoms but requires skin biopsy demonstrating loss of intraepidermal nerve fibers for diagnosis 3.
• Can be associated with diabetes, autoimmune conditions, or be idiopathic 3.

Inflammatory Neuropathies

• Acute inflammatory demyelinating polyradiculoneuropathy can present with weakness and may have normal initial NCS if tested too early 3.
• CSF analysis showing elevated protein with pleocytosis supports inflammatory causes 3.

Autoimmune and Inflammatory Conditions

Systemic Lupus Erythematosus with Peripheral Neuropathy

• SLE-related polyneuropathy (2-3% of cases) presents with altered sensation, pain, and muscle weakness 3.
• NCS can identify the pattern but may be normal in small fiber involvement 3.
• Requires serological testing (ANA, anti-dsDNA, complement levels) 3.

Multiple Sclerosis (Early or Atypical)

• While MRI is typically abnormal in MS, very early disease or radiologically isolated syndrome may have subtle findings 3.
• Look for white matter signal abnormalities on FLAIR sequences, particularly periventricular, juxtacortical, or infratentorial lesions 3.
• Consider visual evoked potentials and CSF analysis for oligoclonal bands if clinical suspicion is high 3.

Recommended Diagnostic Approach

Immediate Laboratory Testing

• Serum vitamin B12 level and methylmalonic acid 1, 6
• Complete blood count with peripheral smear (looking for macrocytosis, hypersegmented neutrophils) 7
• Serum copper and ceruloplasmin 3
• Thyroid function tests 1
• Hemoglobin A1c and fasting glucose 1
• Comprehensive metabolic panel 1

Specialized Neurological Evaluation

• Urgent neurology referral for HINTS examination and comprehensive vestibular assessment 8
• Dix-Hallpike maneuver and supine roll test to definitively rule out BPPV 8
• Consider visual evoked potentials if MS is suspected 3

Additional Imaging Considerations

• If B12 deficiency is confirmed, consider dedicated MRI cervical and thoracic spine without contrast to evaluate dorsal columns 3, 4
• MRA/CTA of head and neck if HINTS suggests central cause or vascular risk factors are present 8

Red Flags Requiring Emergency Evaluation

• New severe headache different from baseline, focal neurological deficits, sudden hearing loss, inability to stand or walk, or new/worsening asymmetric weakness 8.