CME INDIA Case Presentation Dr. Harish Darla, Consultant Physician in Diabetes & Endocrinology – Darla’s Health Care. Visiting Consultant – Apollo Hospital, Mysore.

CME INDIA Case Study

How Presented?

  • The patient came first time accompanied with her son, for thyroid evaluation, but patient was examined and video findings led to detailed family history.
  • In the picture below – 1 is patient’s father, 2 is brother, 3 is the lady as patient.
Family with Les yeux fermés (Closed eyes)
  • So, what’s common among them?
  • Patient was not able to move her eyes and any time she has to see on any side, she has to raise her chin and turn her head towards that side, denies any diplopia.
  • Denies any worsening as the day progresses.
  • It’s chronic in nature, gait is normal.
  • No cerebellar signs.

How Evaluated?

  • She was evaluated for Myasthenia gravis, but patient was not on any medication and no h/o of diurnal variation.
  • There was strong family history of ptosis and as per history it was not present at birth but gradually progressed.

CME INDIA Comments:

Dr. Varun Kumar, Ranchi:

  • Myasthenia?

Dr. Mallikarjun Vali, Telangana:

  • Droopy eyelids? Myasthenia gravis. Ocular myasthenia?

Dr. Vikas Kumar Agarwal, Raipur:

  • Is it Congenital Fibrosis of Extraocular Muscles?

Listen to the very illuminating audio message by Dr. Ujjawal Roy, DM (Neuro), Ranchi:

Dr. Harish Darla, Mysore:

  • So, the probable diagnosis is Chronic Progressive External Ophthalmoplegia (CPEO)

Dr. Ashok Kumar, DM (Neuro) Ranchi:

  • What can we see in this patient and her family?
    • Non-fluctuating Ptosis and l Ocular muscle weakness.
    • It is familial with Autosomal Dominant inheritance.
    • It is not congenital. Appearance is probably in young adulthood.
  • It is not Congenital or Familial Myasthenia.
  • Mitochondrial disease cannot be ruled out though inheritance looks more like Autosomal Dominant.
  • Needs some out of box thinking.
  • Ultrasound or CT Orbit to look for Atrophy of External Ocular muscles.
  • Literature search for Familial Ptosis and Ophthalmoplegia with AD inheritance.
  • Decide upon the GENETIC test. If something appears in Literature search, one can go for an indicated GENETIC test. Otherwise, Exome or Better Whole genome sequencing.

Dr. Abhishek, DM, (Neuro), Patna:

  • It’s Chronic progressive external Ophthalmoplegia. Long standing history, strong family history and absence of diurnal variation suggest a hereditary cause of it. If itself onset is before 20 year and there is associated pigmentation retinopathy think about mitochondrial inheritance, if not think autosomal dominant pattern.

CME INDIA Learning Points

  • Chronic Progressive External Ophthalmoplegia (CPEO) is a rare, slowly progressive disorder that primarily affects the muscles controlling eye and eyelid movement. Here is a summary of the condition.
  • CPEO is a type of mitochondrial myopathy, a group of neuromuscular diseases caused by defects in mitochondria, the energy-producing structures within cells.
  • As the name suggests, the condition progresses slowly over time, leading to increasing muscle weakness.

  • Symptoms:
    • Eye Movement Limitations- Difficulty moving the eyes in various directions, leading to restricted gaze and potential double vision (diplopia).
    • Ptosis: Drooping of one or both eyelids, which can worsen over time and affect vision.
    • Other Symptoms: Some patients may experience generalized muscle weakness, particularly in the facial and neck muscles. In some cases, systemic involvement can occur, affecting other muscles in the body.

  • Causes and Genetics
    • Mitochondrial DNA Mutations: CPEO is often caused by mutations in mitochondrial DNA or nuclear genes that affect mitochondrial function.
    • Inheritance Patterns: The condition can be inherited in various ways, including maternal inheritance (since mitochondria are inherited from the mother), autosomal dominant, or autosomal recessive patterns.

  • Diagnosis
    • Clinical Examination: Detailed assessment of eye movements and eyelid function.
    • Genetic Testing: Identifying specific mutations in mitochondrial or nuclear DNA.
    • Muscle Biopsy: May show characteristic changes in muscle fibers, such as ragged red fibers.
    • Imaging and Blood Tests: Used to rule out other conditions and assess overall health.

  • Treatment and Management
    • No Cure: Currently, there is no cure for CPEO, but treatments focus on managing symptoms and improving quality of life.
    • Supportive Treatments: May include eyelid surgery for ptosis, prism glasses for double vision, and physical therapy.
    • Regular Monitoring: Ongoing assessment by a neurologist and other specialists to monitor disease progression and manage complications.

  • Prognosis
    • Variable: The rate of progression and severity of symptoms can vary widely among individuals. While CPEO is generally not life-threatening, it can significantly impact quality of life due to vision problems and muscle weakness.

  • Research and Future Directions
    • Gene Therapy and Mitochondrial Medicine: Research is ongoing to better understand mitochondrial diseases and develop potential treatments, including gene therapy and other approaches to improve mitochondrial function.
    • For individuals affected by CPEO, regular follow-up with healthcare providers and participation in supportive therapies can help manage symptoms and maintain as much function and independence as possible.

References:

  1. Takeda Y, Suzuki H, Hosono K, Hikoya A, Komori M, Inagaki R, Haseoka T, Arai S, Takagi Y, Hotta Y, Sato MJpn J Ophthalmol 2022 May;66(3):314-319. Epub 2022 Apr 19 doi: 10.1007/s10384-022-00920-5. PMID: 35438395
  2. Birtel J, von Landenberg C, Gliem M, Gliem C, Reimann J, Kunz WS, Herrmann P, Betz C, Caswell R, Nesbitt V, Kornblum C, Charbel Issa P
    Ophthalmol Retina 2022 Jan;6(1):65-79. Epub 2021 Jul 10 doi: 10.1016/j.oret.2021.02.017. PMID: 34257060
  3. Heighton JN, Brady LI, Newman MC, Tarnopolsky MAMitochondrion 2019 Jan;44:15-19. Epub 2017 Dec 12 doi: 10.1016/j.mito.2017.12.006. PMID: 29246868
  4. Ali, A.; Esmaeil, A.; Behbehani, R. Mitochondrial Chronic Progressive External Ophthalmoplegia. Brain Sci. 2024, 14, 135. https://doi.org/10.3390/brainsci14020135.


Discover CME INDIA:

Discover CME INDIA