Neurologists typically see what they will call run-of-the-mill stuff. These are cases they don’t typically struggle too hard to make a diagnosis or to treat. These common cases don’t really keep us on our toes. No, what gets neurologists bristling, we admit, are the esoteric diseases. We are thrilled when we sniff a rarity in the air. We develop goosebumps when we think we are on the trail of the next case report. We are envious when such cases are presented at the neurological altar, the neuropathological conference.

"Une leçon clinique à la Salpêtrière" by André Brouillet - Photo prise dans un couloir de l'université Paris V. Licensed under Public Domain via Commons -
“Une leçon clinique à la Salpêtrière” by André Brouillet – Photo prise dans un couloir de l’université Paris V. Licensed under Public Domain via Commons –


But what are these mysterious cases that set our blood on fire? Which are the most perplexing? What are these diseases so rare only a few have the knowledge and experience to recognise them? To investigate, I had a quick look at the index of neurology checklists I have been labouring to produce, and I came up with a list of 75. I have grouped these into three depending on their degree of  perplexity.


"Pagoda Burr Puzzle" by Meronim - Own work. Licensed under CC BY-SA 3.0 via Commons -
“Pagoda Burr Puzzle” by Meronim – Own work. Licensed under CC BY-SA 3.0 via Commons –


To keep the list manageable I have left out conditions addressed in my previous posts on the most practical and helpful neurology guidelines and top all-time neurology review articles. I have also been selective in choosing the single reference that I think best reflects each condition. I must also confess that I cheated a little; many are paediatric conditions, but they are all neurological.

Gorilla Scratching Head. Eric Kilby on Flikr.
Gorilla Scratching Head. Eric Kilby on Flikr.


The first class of esoteric neurological diseases are conditions that should be familiar, or vaguely so, but the neurologist needs to do a bit of hard thinking and reading-up to solve.

  1. Aceruloplasminaemia
  2. Alexander disease
  3. Benign hereditary chorea
  4. CANVAS syndrome
  5. Cerebrotendinous xanthomatosis (CTX)
  7. Dentatorubral pallidolyusian atrophy (DRPLA)
  8. Fatal familial insomnia (FFI)
  9. Fragile X tremor ataxia syndrome (FXTAS)
  10. Generalized epilepsy with febrile seizures plus (GEFS+)
  11. Gerstmann Straussler Scheinker (GSS) syndrome
  12. Lafora body disease
  13. Menke’s disease
  14. Miller Dieker syndrome
  15. MNGIE
  16. Myofibrillar myopathy
  17. Neuro Sweet syndrome
  18. Ornithine transcarbamylase (OTC) deficiency
  19. Potassium aggravated myotonias
  20. Progressive encephalomyelitis rigidity and myoclonus (PERM)
  21. Pyridoxine-responsive epileptic encephalopathy
  22. Rapid onset dystonia parkinsonism (RDP)
  23. Refsum’s disease
  24. Rippling muscle disease (RMD)
  25. Tyrosine hydroxylase deficiency (THD)



The next set of 25 conditions are rather rare but a phone call to a nearby expert is likely to resolve the diagnostic and management difficulty. These are:

  1. Adult polyglucosan body disease
  2. Alpers syndrome
  3. Barth syndrome
  4. Biotin responsive basal ganglia disease
  5. Brown-Vialetto Von-Laere (BVVL) syndrome
  7. Facial onset sensory and motor neuronopathy (FOSMN)
  8. Hemiconvulsion hemiplegia (HH) syndrome
  9. Hereditary myopathy with early respiratory failure (HMERF)
  10. Jeavon’s syndrome (eyelid myoclonia with absences)
  11. Joubert syndrome
  12. Kufor Rakeb
  13. Landau Kleffner syndrome
  14. Melkersson Rosenthal syndrome
  15. Nemaline myopathy
  16. Neuronal ceroid lipofuscinosis (NCL)
  17. Ohtahara syndrome
  18. Panayiotopoulos syndrome (PS) 
  19. Pantethonate kinase associated neurodegeneration (PKAN)
  20. Perry syndrome
  21. Raeder’s paratrigeminal syndrome
  22. Rett syndrome
  23. Sialidosis
  24. Tangier disease
  25. Tarui disease


And below are probably the 25 most esoteric neurological conditions. I consider these among the conditions most neurologists would generally have very little knowledge or experience of, and there would probably be a few experts worldwide who would have experience in them.

  1.  17q deletion syndrome 
  2. 4H Syndrome
  3. Brody disease
  4. Calsequestrin storage myopathy
  5. Coffin Lowry syndrome 
  6. Congenital cataracts facial dysmorphism neuropathy (CCFDN)
  7. Curranino syndrome
  8. Danon disease
  9. Doose syndrome
  10. Nasu Hakola disease
  11. Pelizaeus Marzbacher disease 
  12. PHARC syndrome
  13. Pourfour du petit syndrome
  14. Sandhoff disease
  15. Satoyoshi syndrome
  16. Schwartz Jampel syndrome
  17. Sepiapterin deficiency
  18. SEPN-1 related myopathy 
  19. Sialic acid storage diseases
  20. Sjogren Larsson syndrome
  21. Unverricht Lundborg disease
  22. Vici syndrome
  23. Wolf Hirschhorn syndrome
  24. Woodhouse Sakati syndrome
  25. Zellweger syndrome

Here is a pdf of all 75 esoteric neurology conditions. The is a personal, non-evidenced, list; understandably there will be differing opinions-especially from our Ivory towers! The list is therefore not immutable so please post your comments; I am open to expanding or deflating it with justifiable reason. And don’t worry, there are checklists on all these esoteric conditions coming soon.

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