Differential Diagnosis for Diplopia and Ataxia with Fluctuating Course

Given the patient's symptoms of diplopia and ataxia with a fluctuating course over years, along with negative workup for myasthenia gravis, normal brain MRI and MRV, and lumbar puncture findings, the differential diagnosis can be categorized as follows:

• Single Most Likely Diagnosis

  • Multiple Sclerosis (MS): Although the brain MRI is reported as normal, MS can sometimes present with minimal or no visible lesions on initial imaging, especially in the early stages. The fluctuating course, presence of diplopia and ataxia, and elevated protein in the cerebrospinal fluid (CSF) without other clear explanations make MS a strong consideration. Repeat imaging and further CSF analysis (e.g., oligoclonal bands) might be helpful.

• Other Likely Diagnoses

  • Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): This condition can present with fluctuating symptoms and elevated CSF protein. While it primarily affects the peripheral nerves, some forms can have central nervous system involvement, potentially explaining the ataxia and diplopia.
  • Neuromyelitis Optica Spectrum Disorder (NMOSD): Although typically associated with optic neuritis and spinal cord lesions, NMOSD can have a varied presentation, including brainstem symptoms that might cause diplopia. A normal MRI does not rule out this diagnosis, as lesions may not always be visible.
  • Mitochondrial Disorders: These disorders can have a wide range of neurological manifestations, including ataxia and fluctuating symptoms. However, diagnosis often requires specific testing, such as genetic analysis or muscle biopsy.

• Do Not Miss Diagnoses

  • Central Nervous System Lymphoma: Although rare, CNS lymphoma can present with varied and fluctuating neurological symptoms. It is crucial to consider this diagnosis due to its potential for severe outcomes if missed. Further imaging with contrast or a biopsy might be necessary.
  • Vitamin B12 Deficiency: This condition can cause a range of neurological symptoms, including ataxia. It's essential to check vitamin B12 levels, as deficiency is easily treatable and can have significant consequences if left untreated.
  • Cerebral Vasculitis: This condition involves inflammation of the blood vessels in the brain and can present with a wide range of symptoms, including those described. It would be a critical diagnosis not to miss due to its potential for severe complications and the availability of treatment.

• Rare Diagnoses

  • Ataxia-Telangiectasia: A genetic disorder that affects the nervous system, immune system, and other bodily systems. It's characterized by ataxia and can have a fluctuating course, but it typically presents in childhood.
  • Spinocerebellar Ataxias (SCAs): A group of genetic disorders that cause progressive ataxia. While they can have variable presentations, the fluctuating course and specific symptoms in this case make them less likely.
  • Hashimoto's Encephalopathy: A rare condition associated with Hashimoto's thyroiditis, characterized by neurological symptoms, including ataxia and fluctuating cognitive impairment. Diagnosis requires elevated anti-thyroid antibodies and response to corticosteroids.