The 13 most dreadful neurological disorders…and the groups standing up to them

Neurology embodies some of the most dreadful diseases known to man. Every neurological disorder is disheartening, each characterised by unique frustrations for patients and their families. It is difficult to quantify the distress and misery these afflictions impose on their victims, and even harder to appreciate the despair and anguish they evoke in those who care for them.

Brain Art. Ars Electronica on Flikr.

It is clearly hard to compare the impact of different neurological diseases. Some neurological disorders however stand out because of the consternation their names evoke, and the terror that follows in their wake. These diseases come with unimaginable physical and psychological burdens, and crushing demands on human and material resources. They impose either a debilitating morbidity, or a hasty mortality.

Neural pathways in the brain. NICHD on Flikr.

The nervous system ailments in the list below pose exacting therapeutic challenges, resistant as they are to all attempts at treatment or cure. This list sets out to emphasise the urgency for neuroscience to find a remedy for each of them, but it does not intend to belittle the horror of the disorders omitted from it. The choice of the number 13 is, sadly, self-evident. Here then are the top 13 most dreadful neurological disorders…all with gold links to the associations helping to defeat them.

Working Brain. Gontzal García del Caño on Flikr.


Ataxia, in lay terms, is incoordination. This typically manifests as an unsteady gait and clumsiness. Ataxia converts all activities of daily living into burdensome chores. Whilst many types of ataxia are preventable or reversible, primary ataxias are progressive and carry a dismal outlook. In this category are Spinocerebellar ataxia (SCA)Friedreich’s ataxia, and Ataxia telangiectasia. You may read more about ataxia in these previous blog posts:

The 43 spinocerebellar ataxias: the complete checklists

Old drugs, new roles?

Will Riluzole really be good for cerebellar ataxia?

Brain tumours

Brain cancers hardly need any description. They are either primary, arising from the brain cells, or metastatic, spreading to the brain from other organs. Some primary brain cancers, such as meningiomas and pituitary tumours, are, relatively, treatable. Many others are unfortunately ominously malignant. The most dreadful in this category is surely the spine-chilling glioblastoma multiforme. You may check out these previous blog posts for more on these tumuors: 

Calming the rage of brain tumours: hope for a dreaded cancer

Maggots, viruses and lasers: some innovations for brain tumours 

Are steroids detrimental to survival in brain tumours?

Peripheral neuropathy

Peripheral neuropathy is ubiquitous in the neurology clinic. Neuropathy may result from reversible situations such as overindulgence in alcohol, uncontrolled diabetes, or Vitamin B12 deficiency. Neuropathy is often just a minor inconvenience when it manifests with sensory symptoms such as tingling and numbness. It may however be debilitating when it presents as limb paralysis, or complicated by major skeletal deformities. At the severe end of the spectrum of neuropathy are the hereditary forms such as Charcot Marie Tooth disease (CMT) and Familial amyloid polyneuropathy. Read more in these blog posts:

The 52 variants of CMT… and their practical checklists 

What’s looming at the frontline of peripheral neuropathy?

Will a pill really hold the cure for CMT?

Creutzfeldt Jakob disease (CJD)

CJD is the most iconic of the prion diseases. These disorders are as horrendous as they are enigmatic, defying categorisation as either infections or neurodegenerative diseases. More puzzling is their ability to be either hereditary and acquired. CJD exists in the classic or variant form, but both share a relentlessly rapid course, and a uniformly fatal end. You may read more in these previous blog posts titled:

Final day of ANA 2015- Prions center stage

What are the links between Prion diseases and Parkinsonian disorders?


Dementia is the scourge of longevity. Its name strikes terror because it insidiously colonises the cells that make us who we are. The most prominent dementia is Alzheimer’s disease, but it has equally dreadful companions such as Frontotemporal dementia (FTD) and Dementia with Lewy bodies (DLB). Read more on dementia in these blog posts:

How bright is the future for Alzheimer’s disease?

Alzheimer’s disease: a few curious things 

Alzheimers disease and its promising links with diabetes


Dystonia marks its presence by distressing movements and painful postures. At its most benign, dystonia is only a twitch of the eyelid (blepharospasm) or a flicker of one side of the face (hemifacial spasm). At the extreme end, it produces continuous twisting and swirling motions, often defying all treatments. The causes of dystonia are legion, but the primary dystonias stand out by their hereditary transmission and marked severity. Read more on dystonia in these blog posts:

Why does dystonia fascinate and challenge neurology?

Making sense of the dystonias: the practical checklists

Huntington’s disease (HD)

Huntington’s disease is an iconic eponymous neurological disorder which is marked by the vicious triumvirate of chorea, dementia, and a positive family history. It is an awful condition, often driving its victims to suicide. It is a so-called trinucleotide repeat expansion disorder, implying that successive generations manifest the disease at an earlier age, and in more severe forms (genetic anticipation). You may read more on HD in the previous blog post titled:

What are the prospects of stamping out Huntington’s disease? 

Motor neurone disease (MND) 

Also known as Amyotrophic lateral sclerosis (ALS), MND is simply devastating. Recognising no anatomical boundaries, it ravages the central and peripheral nervous systems equally. MND creeps up on the neurones and causes early muscle twitching (fasciculations) and cramps. It then gradually devours the nerves resulting in muscle wasting, loss of speech, ineffectual breathing, and impaired swallowing. Our previous blog posts on MND are:

Is neurology research finally breaking the resolve of MND?

The emerging links between depression and MND

What is the relationship of MND and cancer?

Does diabetes protect from MND?

MND and funeral directors-really?

Multiple sclerosis (MS)

Multiple sclerosis is a very common disease, and gets more common the further away you get from the equator. It is the subject of intense research because of the devastation it foists on predominantly young people. Many drugs now ameliorate, and even seem to halt the progression of, relapsing remitting MS (RRMS). This is however not the case with primary progressive MS (PPMS) which, until the introduction of ocrelizumab, defied all treatments. There are many contenders vying for the cause of MS, but the reason nerves in the central nervous system inexplicably lose their myelin sheaths remains elusive. You may read more on MS in these blog posts:

The emerging progress from the world of MS

What are the remarkable drugs which have transformed the treatment of MS?

Is low vitamin D a cause of multiple sclerosis?

Muscular dystrophy 

Muscular dystrophy is an umbrella term that covers a diverse range of inherited muscle diseases. The most devastating, on account of its early onset and unrelenting progression, is Duchenne muscular dystrophy (DMD). Adult neurologists will be more familiar with late onset muscular dystrophies such as Myotonic dystrophy and Facioscapulohumeral muscular dystrophy (FSHD). Read more on muscular dystrophy in these previous blog posts:

How is neurology stamping out the anguish of Duchenne?

The A–Z of limb girdle muscular dystrophy (LGMD)


Rabies, a rhabdovirus, is a zoonosis-it is transmitted to man by a wide range of animals such as dogs, bats, racoons, and skunks. It is the quintessential deadly neurological disease, popularised by the Steven King book and film, Cujo. Rabies manifests either as the encephalitic (furious) or the paralytic (dumb) forms. It wreaks havoc by causing irritability, hydrophobia (fear of water),  excessive sweating, altered consciousness, and inevitably death. Whilst there are vaccines to protect against rabies, a cure has eluded neuroscientists. This blog is yet to do justice to rabies but it is, at least, listed in the post titled What are the most iconic neurological disorders? But you could better by checking neurochecklists for details of the clinical features and management of rabies.

Spinal cord injury

Nothing is quite as heart-wrenching as the sudden loss of body function that results from spinal cord trauma. This often causes paralysis of both legs (paraplegia), or all four limbs (quadriplegia). This life-changing disorder is often accompanied by loss of control over bowel and bladder functions, and complications such as bed sores and painful spasms. You may read about the heroic efforts to treat spinal cord injury in the blog posts titled:

6 innovations in the treatment of spinal cord injury

Head transplant, anyone?


Tetanus is an eminently preventable disease, now almost wiped out in developed countries by simple immunisation. It however continues its pillage and plunder in the developing world. It strikes young and old alike, often invading the body through innocuous wounds. Tetanus is caused by tetanospasmin and tetanolysin, the deadly toxins of the bacterium Clostridium tetani. The disease is classified as generalised, localised, cephalic, or neonatal tetanus. It is characterised by painful spasms which manifest as lockjaw (trismus), facial contortions (risus sardonicus), trunkal rigidity (opisthotonus), and vocal cord spasms (laryngospasm). The disease is awfully distressing and, when advanced, untreatable. It is a stain on the world that this avoidable disorder continuous to threaten a large number of its inhabitants. Check neurochecklists for more on the pathology, clinical features, and management of tetanus.


Light brain. Mario D’Amore on Flikr.

As for all lists, this will surely be subject to debate, or perhaps some healthy controversy. Please leave a comment.

What are the most iconic neurological disorders?

Neurology is a broad specialty covering a staggering variety of diseases. Some neurological disorders are vanishingly rare, but many are household names, or at least vaguely familiar to most people. These are the diseases which define neurology. Here, in alphabetical order, is my list of the top 60 iconic neurological diseases, with links to previous blog posts where available.


1. Alzheimer’s disease

By uncredited - Images from the History of Medicine (NLM) [1], Public Domain,
By uncredited – Images from the History of Medicine (NLM) [1], Public Domain,

2. Behcet’s disease

By Republic2011 - Own work, CC BY 3.0,
By Republic2011Own work, CC BY 3.0,

3. Bell’s palsy

By, CC BY 4.0,
By, CC BY 4.0,

4. Brachial neuritis

5. Brain tumours

6. Carpal tunnel syndrome

7. Cerebral palsy (CP)

8. Cervical dystonia

9. Charcot Marie Tooth disease (CMT)

By, CC BY 4.0,
By, CC BY 4.0,

10. Chronic inflammatory demyelinating polyneuropathy (CIDP)

11. Cluster headache

12. Creutzfeldt-Jakob disease (CJD)

By Unknown -, Public Domain,
By Unknown, Public Domain,

13. Duchenne muscular dystrophy (DMD)

By G._Duchenne.jpg: unknown/anonymousderivative work: PawełMM (talk) - G._Duchenne.jpg, Public Domain,
By G._Duchenne.jpg: unknown/anonymousderivative work: PawełMM (talk) – G._Duchenne.jpg, Public Domain,

14. Encephalitis

15. Epilepsy

16. Essential tremor

17. Friedreich’s ataxia

By Unknown -, Public Domain,
By Unknown, Public Domain,

18. Frontotemporal dementia (FTD)

19. Guillain-Barre syndrome (GBS)

By Anonymous - Ouvrage : L'informateur des aliénistes et des neurologistes, Paris : Delarue, 1923, Public Domain,
By Anonymous – Ouvrage : L’informateur des aliénistes et des neurologistes, Paris : Delarue, 1923, Public Domain,

20. Hashimoto encephalopathy

21. Hemifacial spasm

22. Horner’s syndrome

By Unknown -, Public Domain,
By Unknown, Public Domain,

23. Huntington’s disease (HD)

24. Idiopathic intracranial hypertension (IIH)

25. Inclusion body myositis (IBM)

26. Kennedy disease

27. Korsakoff’s psychosis

28. Lambert-Eaton myasthenic syndrome (LEMS)

29. Leber’s optic neuropathy (LHON)

30. McArdles disease

31. Meningitis

32. Migraine

33. Miller-Fisher syndrome (MFS)

By J3D3 - Own work, CC BY-SA 4.0,
By J3D3Own work, CC BY-SA 4.0,

34. Motor neurone disease (MND)

35. Multiple sclerosis (MS)

36. Multiple system atrophy (MSA)

37. Myasthenia gravis (MG)

38. Myotonic dystrophy

39. Narcolepsy

40. Neurofibromatosis (NF)

41. Neuromyelitis optica (NMO)

42. Neurosarcoidosis

43. Neurosyphilis

44. Parkinson’s disease (PD)

45. Peripheral neuropathy (PN)

46. Peroneal neuropathy

47. Progressive supranuclear palsy (PSP)

48. Rabies

49. Restless legs syndrome (RLS)

50. Spinal muscular atrophy (SMA)

51. Stiff person syndrome (SPS)

52. Stroke

53. Subarachnoid haemorrhage (SAH)

54. Tension-type headache (TTH)

55. Tetanus

56. Transient global amnesia (TGA)

57. Trigeminal neuralgia

58. Tuberous sclerosis

59. Wernicke’s encephalopathy

By J.F. Lehmann, Muenchen - IHM, Public Domain,
By J.F. Lehmann, Muenchen – IHM, Public Domain,

60. Wilson’s disease

By Carl Vandyk (1851–1931) - [No authors listed] (July 1937). "S. A. Kinnier Wilson". Br J Ophthalmol 21 (7): 396–97. PMC: 1142821., Public Domain,
By Carl Vandyk (1851–1931) – [No authors listed] (July 1937). “S. A. Kinnier Wilson“. Br J Ophthalmol 21 (7): 396–97. PMC: 1142821., Public Domain,


The Neurology Lounge has a way to go to address all these diseases, but they are all fully covered in neurochecklists. In a future post, I will look at the rare end of the neurological spectrum and list the 75 strangest and most exotic neurological disorders.

What’s looming at the frontline of peripheral neuropathy?

Peripheral neuropathy is a very old and often straightforward problem for neurologists. Its presentation is well-defined, and neurologists are at their theatrical best when they map out the classical glove-and-stocking distribution of impaired temperature and touch sensation. They proficiently demonstrate distal muscle weakness and wasting, and masterfully elicit absent reflexes or areflexia.

Stripped hand on a stick. Tysone Moore on Flikr.
Stripped hand on a stick. Tysone Moore on Flikr.


Below the surface however, peripheral neuropathy is anything but straightforward. It has a wide variety of subtypes and causes, and its classification now has subclassifications of subclassifications. Research is continually demonstrating how complex peripheral neuropathy really is, and here are 4 concepts to illustrate this complexity.

1. IgG4-related peripheral neuropathy
Cold Spring Harbor 012. Vik Nanda on Flikr.
Cold Spring Harbor 012. Vik Nanda on Flikr.


As soon as neurologists make the clinical diagnosis of peripheral neuropathy, they reach for the blood request form. They almost mindlessly tick off tests which include immunoglobulins, the building block of antibodies. The nerve damage arising from excessive amounts of immunoglobulins is called paraproteinaemic neuropathy. This simple paradigm, high immunoglobulins equalling paraproteinaemic neuropathy, is however set to change. And this is going by a paper in Neurology titled Immunoglobulin G4-related pathologic features in inflammatory neuropathies. The article showed that IgG4 levels are elevated in a subgroup of people with neuropathy, but these people have vasculitic neuropathy rather than straightforward paraproteinaemic neuropathy. Because the treatment of vasculitis differs from that of paraproteinaemia, this finding is completely changing the rules of the game.

 2. More genes please, we're neurologists
Framed Embroidery Chromosome Art. Hey Paul Studios on Flikr. By Database Center for Life Science (DBCLS), CC BY 3.0,
Framed Embroidery Chromosome Art. Hey Paul Studios on Flikr. By Database Center for Life Science (DBCLS), CC BY 3.0,


Hereditary neuropathy is a quagmire for neurologists, but it hasn’t always been that way. In the good old days, (and I have enough grey hairs to say this), a neurologist just needed to have a smattering knowledge of one or two genetic mutations that cause Charcot Marie Tooth disease (CMT), and a vague familiarity with CMT’s genetic cousin, hereditary neuropathy with liability to pressure palsy (HNPP). It used to be a few minutes of counselling, an aliquot of blood, and a confirmatory blood test 6 months later. Not anymore this life of luxury; CMT alone is now classified into multiple subtypes, each subtype caused by a multitude of genetic mutations. And the genetic neuropathists are not done yet; the articles below show the broadening scope of genetic neuropathies we have to contend with. Your neurologist really deserves your sympathies!


3. Nodopathies
By Dr. Jana - ;, CC BY 4.0,
By Dr. Jana – ;, CC BY 4.0,


Still in nostalgic mood, there was a time when a neurologist just needed to know if a neuropathy was axonal (affecting the main nerve fiber), or demyelinating (involving the nerve ensheathing layer called myelin). Confine that classification to the history books because nodopathy is toppling the prevailing order. This is from a paper titled Nodopathies of the peripheral nerve: an emerging concept, in the Journal of Neurology, Neurosurgery and Psychiatry (JNNP). The authors of the paper are scathing of the traditional classification which, they say, is ‘inadequate or even misleading’. Why? Because many cases of typical demyelinating neuropathy demonstrate clear axonal changes. The authors explain this paradox by describing the anatomy of myelinated nerves which are made up of domains: node, paranode, juxta-paranode and inter-node. And it is the node which bucks the trend because it resolutely refuses to be ensheathed by myelin. And this singular act of defiance will be the source of anguish for generations of medical students and doctors, not to mention neurophysiologists.

4. Growth factor receptor antibodies

When requesting immunoglobulins and other blood tests, neurologists only needed to tick boxes in standard blood request forms. This life of ease and luxury has been on the way out because the standard blood request form no longer accommodates the ever-expanding causes of peripheral neuropathy. What was previously the almost mindless ticking of B12 and folate is fast becoming anxiety-provoking for the neurologist. It is one thing to remember the test to request, it is another to justify this to your friendly biochemist that this test is worth the cost. But what could a neurologist do when researchers keep coming up with more causes of neuropathy. Take anti-FGFR3 antibodies for example, again from a paper in the JNNP titled antifibroblast growth factor receptor 3 antibodies in sensory neuropathy. The authors have no idea how their findings threaten a cosy B12-and-folate relationship between neurologist and biochemist!

Teased Myelinated Medullated Nerve 2. Green Flames 09 on Flikr.
Teased Myelinated Medullated Nerve 2. Green Flames 09 on Flikr.


Looking for a comprehensive approach to the management of peripheral neuropathy? I haven’t come across anything better than Clinical Approach to Peripheral Neuropathy in  Continuum…but you need to have access. For a hands-on take on genetic neuropathies, A Practical Approach to the Genetic Neuropathies is the place to start. Thankfully, this is open access.


Will a pill really hold the cure for CMT?

Charcot Marie Tooth disease (CMT) is the most important inherited peripheral neuropathy. As with most genetic diseases, there is no cure for CMT. The best neurologists can offer at the moment is supportive treatment for complications of CMT such as foot drop and foot deformities.

By Benefros at English Wikipedia - Own work, originally from en.wikipedia; description page is/was here., CC BY-SA 3.0,
By Benefros at English Wikipedia – Own work, originally from en.wikipedia; description page is/was here., CC BY-SA 3.0,


Neurologists are however very keen to go beyond platitudes and ankle supports for their patients with CMT. The holy grail of course is gene therapy, but this is still a far-off dream. As neurologists labour towards this utopia, they are also looking down to earth at drug treatments.

Prompted by reports that Vitamin C, yes Vitamin C,  effectively prevented neuropathy in mice, neurologists carried out a major trial in people with CMT. This was reported in Lancet Neurology titled Ascorbic acid in Charcot–Marie–Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial. Alas, Vitamin C was way off the mark in CMT.

Macrophages and red blood cells. The Journal of Cell Biology on Flikr.
Macrophages and red blood cells. The Journal of Cell Biology on Flikr.

Not deterred, the indefatigable neurologists have turned their sights on another agent. Perhaps because Vitamin C is too common, they went for something more exotic this time- inhibition of colony stimulating factor 1 (CSF1). The reason for picking on CSF1 is the observation that CMT is characterised by a low level inflammatory process, and CSF1 promotes inflammation by stimulating the production of the inflammatory cells called macrophages. The plan therefore is to wipe out macrophages by cutting their supply line, CSF 1. And the military-style strategy went according to plan.

Five baby mice eating icecream. Radagast on Flikr.
Five baby mice eating icecream. Radagast on Flikr.

The study, reported in the journal Brain, is titled Targeting the colony stimulating factor 1 receptor alleviates two forms of Charcot-Marie-Tooth disease in mice. The researchers fed an inhibitor of CSF 1 to mice models of CMT. Following the successful outcome, they proudly announced that “an orally administered inhibitor of CSF1R may offer a highly efficacious and safe treatment option for at least two distinct forms of the presently non-treatable Charcot-Marie-Tooth type 1 neuropathies“. Two for the price of one! Next stop, human trials-the waterloo of many a researcher!

DNA rendering. ynse on Flikr.
DNA rendering. ynse on Flikr.


Do you want to explore the genetic neuropathies a bit more? You couldn’t do better than this excellent review in Practical Neurology by Alexander Rossor, Matthew Evans, and Mary Reilly titled A practical approach to the genetic neuropathies. Click away!