Neuropsychiatric Symptoms After Fingolimod Withdrawal in Multiple Sclerosis Patient

Neuropsychiatric

Overview

Case Presentation

A 26-year-old woman was presented with apathy, affective incontinence and motoric aphasia.

Medical History

  • The patient had a 9-year history of relapsing remitting multiple sclerosis
  • The patient was treated with interferon beta 1a and dimethylfumarate under which she had developed several relapses, therefore, switched to fingolimod.
  • Six, weeks ago, fingolimod was discontinued due to persisting disease activity in the form of optic neuritis and lymphopenia of 225/μl.

Clinical Exam

Her MRI revealed:

  • Numerous tumefactive lesions with gadolinium enhancement
  • Edema atypical of her prior disease course

Her neurological evaluation showed:

  • Inability to eat or drink
  • Psychomotor agitation
  • Inability to communicate with caregivers
  • Expanded Disability Status Scale (EDSS) of 9.5

Laboratory findings:

  • Peripheral blood lymphocyte count: 90/μl
  • CSF analysis showed mild pleocytosis of 16/μl
  • 3 independent PCRs for JCV-DNA from serum and CSF were negative
  • An extensive PCR and serological workup for borrelia, lues and cryptococcosis was negative
  • Anti-Aquaporin-4- and anti-MOG-antibodies were absent
  • MR spectroscopy of a progressive lesion in the left frontal lobe showed creatinin, cholin and N-acetylaspartate slightly decreased & lactate slightly increased

Diagnosis

The patient was diagnosed with acute multiple sclerosis lesion.

Preliminary Treatment

  • The patient was initiated on methylprednisolone therapy (1 g/d) over 5 days.
  • Her neurological status deteriorated further.
  • She was started on plasmapheresis and began to slowly improve.

Post-Treatment Outcomes

After 4th plasmapheresis,

  • The patient was able to communicate and walk.
  • She was able to ingest small amounts of food.
  • MRI showed a decrease in the size and number of lesions, along with the gadolinium enhancement.

After 7th plasmapheresis,

  • She was transferred to a rehabilitation facility with an EDSS of 7.5.

After 2 weeks,

  • She developed right sided hemiparesis.
  • The patient was started on corticosteroid therapy & readmitted.
  • Her peripheral lymphocytes were raised to 890/μl but within the normal range.
  • MRI revealed an overall decrease of gadolinium-enhancing lesions one subcortical lesion had remained active.

Further Treatment

  • With no improvement, corticosteroids were discontinued.
  • A 2nd cycle of seven plasmaphereses was started
  • The patient improved daily and was released to a rehabilitation facility again.

Follow-up      

After 7 weeks,

  • 1st dose of ocrelizumab 300 mg was administered.

6 months later,

  • The patient remained relapse-free.
  • She showed clinical improvement with ability to walk independently up to 1 km without help (EDSS 4.5).
  • MRI found a further remission with no remaining gadolinium enhancement.

Adapted from:

  1. Koska V, Förster M, Brouzou K, Arat E, Albrecht P, Aktas O, et. al. Case Report: Persisting Lymphopenia During Neuropsychiatric Tumefactive Multiple Sclerosis Rebound Upon Fingolimod Withdrawal. Front Neurol. 2021; 12: 785180. doi: 10.3389/fneur.2021.785180.