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Neurological manifestations in malignant melanoma
  1. H M M T B Herath1,
  2. Nadiene G Lutchman1,
  3. May Saleh1,
  4. Leena Naidu1,
  5. Shyama Balasuriya Alagoda2,
  6. Stefen Brady3,
  7. Sunil Wimalaratna1
  1. 1 Kettering General Hospital, Kettering, UK
  2. 2 Somerset NHS Foundation Trust, Taunton, UK
  3. 3 Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  1. Correspondence to Dr H M M T B Herath; tharukaherath11{at}gmail.com

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Case presentation

A 72-year-old woman had 1 week of diplopia, bilateral ptosis, dysphagia, myalgia and limb weakness, and 3 days of progressively worsening shortness of breath. Six months before, she had undergone local resection for stage 3 malignant melanoma, with clear surgical margins. She subsequently started pembrolizumab immunotherapy and had completed the second dose 1 week before this presentation.

On examination, there was bilateral asymmetrical fatiguable partial ptosis with complete ophthalmoplegia, mild bilateral facial weakness and reduced palatal movement. Pupillary reflexes were normal. There were no features of encephalopathy or meningitis. There was also symmetrical non-fatiguable proximal weakness (3/5) with mild distal weakness (4/5) in all four limbs. Her deep tendon reflexes were elicitable only with reinforcement. The plantar responses were flexor. She could stand with support and had no cerebellar, sensory, autonomic or extrapyramidal signs. She required supplemental oxygen via nasal cannulae to maintain adequate oxygen saturation due to ventilatory muscle weakness.

Investigations on admission identified markedly elevated serum alanine aminotransferase (863 IU/L; <33), gamma-glutamyl transferase (286 IU/L; 7–32) and alkaline phosphatase (201 U/L; 30–130). However, full blood count, thyroid functions, cardiac enzymes, renal function and inflammatory markers were normal. Serum muscle enzymes (creatine kinase, lactate dehydrogenase, aldolase) and troponin were normal. ECG was normal.

Questions for consideration

What are the possible diagnoses and what additional tests are required?

Differential diagnosis

The possible neurological complications related to PD-1 inhibitors (pembrolizumab) or immune checkpoint inhibitors are rare but should be considered in anyone who has received these.

A variant of Guillain-Barré syndrome (GBS) could present with ophthalmoplegia, bulbar symptoms and symmetrical bilateral limb weakness with diminished reflexes and normal sensory findings. Myalgia can also develop in GBS.1 GBS develops in around 0.2%–0.3% of patients treated with immune checkpoint inhibitors, with similar clinical presentation, nerve conduction study results and cerebrospinal fluid (CSF) findings to conventional GBS, though occasionally with CSF pleocytosis.2

Myasthenia …

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Footnotes

  • Contributors All authors contributed equally.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed by Jeremy Rees, London, UK and Jon Sussman, Manchester, UK.