What strange and rare diseases lurk within neurology?

Neurologist spend most of their time treating many ‘mainstream’ disorders such as epilepsy and migraine. I discussed this in my previous post, what are the most iconic neurological disorders? Neurologists are however required to know many other diseases, often very rare and occasionally esoteric. Some of these diseases are so rare many neurologists haven’t heard of them, or only know about them in passing.

Human brain illustrated with millions of small nerves. Ars Electronica on Flikr. https://www.flickr.com/photos/arselectronica/13994747444
Human brain illustrated with millions of small nerves. Ars Electronica on Flikr. https://www.flickr.com/photos/arselectronica/13994747444

 

These rare diseases often  creep up on us unawares. It is difficult, if not impossible, for any neurologist to confidently diagnose, investigate, treat, and monitor these rare diseases without digging deep and researching extensively. What are these rare disorders? To find out, I scoured neurochecklists and compiled this list. I have linked each to a reference for further study. Here then are my 75 rarest and strangest neurological diseases

A-B

 17q deletion syndrome 

4H Syndrome

Alpers syndrome

Adult polyglucosan body disease

Alexander disease

Aceruloplasminaemia

Benign hereditary chorea

Barth syndrome

Biotin responsive basal ganglia disease

Brown-Vialetto Von-Laere (BVVL) syndrome

Brody disease

C-D

Calsequestrin storage myopathy

Coffin Lowry syndrome 

Congenital cataracts facial dysmorphism neuropathy (CCFDN)

Curranino syndrome

CARASIL

CANVAS syndrome

Cerebrotendinous xanthomatosis (CTX)

CLIPPERS

Danon disease

Doose syndrome

Dentatorubral pallidolyusian atrophy (DRPLA)

F-K

Facial onset sensory and motor neuronopathy (FOSMN)

Fatal familial insomnia (FFI)

Fragile X tremor ataxia syndrome (FXTAS)

Generalized epilepsy with febrile seizures plus (GEFS+)

Gerstmann Straussler Scheinker (GSS) syndrome

Hemiconvulsion hemiplegia (HH) syndrome

Hereditary myopathy with early respiratory failure (HMERF)

Jeavon’s syndrome (eyelid myoclonia with absences)

Joubert syndrome

Kufor Rakeb

L-N

Landau Kleffner syndrome

Lafora body disease

Menke’s disease

Miller Dieker syndrome

MNGIE

Myofibrillar myopathy

Melkersson Rosenthal syndrome

Nasu Hakola disease

Nemaline myopathy

Neuronal ceroid lipofuscinosis (NCL)

Neuro Sweet syndrome

Brian v.2. Amy Leonard on Flikr. https://www.flickr.com/photos/amyleonard/876151372
Brian v.2. Amy Leonard on Flikr. https://www.flickr.com/photos/amyleonard/876151372

 

O-P

Ornithine transcarbamylase (OTC) deficiency

Ohtahara syndrome

Panayiotopoulos syndrome (PS) 

Pantethonate kinase associated neurodegeneration (PKAN)

Perry syndrome

Potassium aggravated myotonias

Progressive encephalomyelitis rigidity and myoclonus (PERM)

Pyridoxine-responsive epileptic encephalopathy

Pelizaeus Marzbacher disease 

PHARC syndrome

Pourfour du petit syndrome

R-S

Rapid onset dystonia parkinsonism (RDP)

Refsum’s disease

Rippling muscle disease (RMD)

Raeder’s paratrigeminal syndrome

Rett syndrome

Sialidosis

Sandhoff disease

Satoyoshi syndrome

Schwartz Jampel syndrome

Sepiapterin deficiency

SEPN-1 related myopathy 

Sialic acid storage diseases

Sjogren Larsson syndrome

 

T-Z

Tangier disease

Tarui disease

Tyrosine hydroxylase deficiency (THD)

Unverricht Lundborg disease

Vici syndrome

Wolf Hirschhorn syndrome

Woodhouse Sakati syndrome

Zellweger syndrome

 

Arteries of the brain. Adrigu on Flikr https://www.flickr.com/photos/97793800@N00/7071077223
Arteries of the brain. Adrigu on Flikr https://www.flickr.com/photos/97793800@N00/7071077223

 

 

PS1. If you are a loyal follower of the blog, you would have realised that I have discussed this topic previously as the most perplexing diseases that excite neurologists. I hope you have found the alphabetical order here more helpful.

PS2. Do you have a rare or strange disease not listed here? Please leave a comment.

PS3. Why not try Neurochecklists for  the simplified, hands-on approach to these and other unusual neurological diseases.

Neurochecklists image

Should neurologists be thinking of Influenza H1N1?

Every now and then neurologists come across patients with what appears to be ‘straightforward’ viral encephalitis but who do not respond to conventional treatment. These treatments are usually according to established guidelines such as the ABN/BIAN guidelines, the IDS Guidelines. What to do when the patient isn’t responding is however very challenging.

Journal of Neuroinfectious Diseases (ssshh…the JNNP declined it) has just published our case report of such a patient who turned out to have H1N1 influenza encephalopathy. This experience suggests we should consider an autoimmune cause in such cases, especially if the spinal fluid does not show any viruses.

3D model of influenza virus
3D model of influenza virus

 

It’s only a single patient but with an excellent outcome and valuable insights (I would say so wouldn’t I!). It was rather fortuitous as her treatment with IVIg was on the assumption she had anti NMDA antibody encephalitis. Its not always in the science as the viral serology subsequently showed!

Is your interest piqued enough? OK, here is the link (and its open access):

H1N1 Associated Encephalopathy in an Adult: Response to Intravenous Immunoglobulin Supporting an Autoimmune Pathogenesis

What are the most perplexing diseases that excite neurologists?

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 - https://commons.wikimedia.org/wiki/File:Une_le%C3%A7on_clinique_%C3%A0_la_Salp%C3%AAtri%C3%A8re.jpg#/media/File:Une_le%C3%A7on_clinique_%C3%A0_la_Salp%C3%AAtri%C3%A8re.jpg
“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 – https://commons.wikimedia.org/wiki/File:Une_le%C3%A7on_clinique_%C3%A0_la_Salp%C3%AAtri%C3%A8re.jpg#/media/File:Une_le%C3%A7on_clinique_%C3%A0_la_Salp%C3%AAtri%C3%A8re.jpg

 

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 - https://commons.wikimedia.org/wiki/File:Pagoda_Burr_Puzzle.jpg#/media/File:Pagoda_Burr_Puzzle.jpg
“Pagoda Burr Puzzle” by Meronim – Own work. Licensed under CC BY-SA 3.0 via Commons – https://commons.wikimedia.org/wiki/File:Pagoda_Burr_Puzzle.jpg#/media/File:Pagoda_Burr_Puzzle.jpg

 

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. https://www.flickr.com/photos/ekilby/18047130741
Gorilla Scratching Head. Eric Kilby on Flikr. https://www.flickr.com/photos/ekilby/18047130741

 

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)
  6. CLIPPERS
  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
  6. CARASIL
  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.

Pareidolias-why we see non-existent faces

Human beings are prone to see patterns where none exist. This concept of pareidolias often has religious connotations, and has led to bouts of religious fervour. Wikipedia describes this as a psychological phenomenon wherein ‘the mind perceives a familiar pattern where none actually exists‘. The BBC recently explored why we see these patterns under the title ‘why we see faces in the hills, the moon and toasties‘.

"Holz Geist Gesicht" by Usien - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons.
Holz Geist Gesicht” by UsienOwn work. Licensed under CC BY-SA 3.0 via Wikimedia Commons.

It is not surprising that artists have made free use of this human weakness to play mind tricks.

"Picture puzzle". Licensed under Public Domain via Wikimedia Commons.
Picture puzzle“. Licensed under Public Domain via Wikimedia Commons.

There are however more sinister implications of pareidolias (you would expect this from a brain doctor!). This tendency to see patterns may be a manifestation of complex hallucinations, typically seen in Lewy body disease and has been reported in Parkinson’s disease.

The tendency to see patterns has been used to good effect in neurological imaging. Many radiological diagnostic signs have been assigned names that reflect the false patterns they project on the human mind. This concept of neuropareidolia is excellently explored in this paper. Neurologists and radiologists for example talk of the hot cross bun sign in multiple system atrophy, the panda sign in Wilson’s disease, and the hummingbird sign in progressive supranuclear palsy (PSP). It seems we bring our humanity to the workplace!

"Archilochus-alexandri-003". Licensed under CC BY-SA 3.0 via Commons.
Archilochus-alexandri-003“. Licensed under CC BY-SA 3.0 via Commons.
"Steele-olszewski-richardson disease" by Dr Laughlin Dawes - radpod.org. Licensed under CC BY 3.0 via Commons.
Steele-olszewski-richardson disease” by Dr Laughlin Dawes – radpod.org. Licensed under CC BY 3.0 via Commons.

 

You may check out

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Mozart and seizures? The links between epilepsy and music

An odd connection you may say but here are quite a few things that link epilepsy with music. lepsy. The first is the therapeutic effect of on epilepsy. This has been termed ‘The Mozart Effect‘ based on studies which report that listening to Mozart reduces epileptic brain discharges.

This however seems at odds with the known fact that epilepsy may be triggered by music. Music is one of several triggers of epilepsy. People with this musicogenic epilepsy may become frightened of music, a concept called musicophobia. This article in Scientific American gives an example where the music of Sean Paul is the consistent trigger for someone’s seizures. In another anecdote from NME, a Ne Yo song is the culprit.

By CLASSICNEYO - Own work, CC BY-SA 4.0, Link
By CLASSICNEYOOwn work, CC BY-SA 4.0, Link

Finally, music may be a manifestation of epilepsy. These present as musical hallucinations.

To explore these and other musical concepts and epilepsy further, check out Music and the neurologist: a historical perspective from the Annals of the New York Academy of Science.

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