Neurologists typically see run-of-the-mill disorders in their usual practice. Not to underestimate the seriousness of these syndromes, but these are not conditions that keep the neurologist awake at night – they are not difficult to diagnose, and most neurologists don’t break into a sweat in managing them. What really get neurologists bristling are the esoteric diseases; these are disorders that give us goosebumps, and these make up the bulk of our offerings at our altar – the neuropathological conference.
What are these esoteric diseases that set the blood of neurologists on fire? Which are the most challenging to diagnose? To investigate, I had a quick look at the index of Neurochecklists, and I came up with 75 that fit the bill. I have classified these into three according to the difficulty they pose to the neurologist:
- Strenuous – 25 diseases which require some hard thinking and reading-up to solve.
- Arduous – 25 conditions which will require a phone call to a nearby expert to resolve.
- Herculean – 25 conditions which only a few worldwide experts can help save the day.
Below then, in order of difficulty, are the 75 most challenging neurological diagnoses
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Strenuous
Alexander disease
Benign hereditary chorea
CANVAS syndrome
Cerebrotendinous xanthomatosis (CTX)
CLIPPERS
Dentatorubral pallidolyusian atrophy (DRPLA)
Doose syndrome
Fatal familial insomnia (FFI)
Fragile X tremor ataxia syndrome (FXTAS)
Generalised epilepsy with febrile seizures plus (GEFS+)
Gerstmann Straussler Scheinker (GSS) syndrome
Lafora body disease
Menke’s disease
Miller Dieker syndrome
MNGIE
Myofibrillar myopathy
Neuro Sweet syndrome
Ornithine transcarbamylase (OTC) deficiency
Potassium aggravated myotonias
Progressive encephalomyelitis rigidity and myoclonus (PERM)
Pyridoxine-responsive epileptic encephalopathy
Rapid onset dystonia parkinsonism (RDP)
Refsum’s disease
Rippling muscle disease (RMD)
Tyrosine hydroxylase deficiency (THD)
Arduous
Adult polyglucosan body disease
Alpers syndrome
Barth syndrome
Brown Vialetto Van Laere syndrome (BVVL)
CARASIL
Facial onset sensory and motor neuronopathy (FOSMN)
Hemiconvulsion hemiplegia (HH) syndrome
Hereditary myopathy with early respiratory failure (HMERF)
Jeavon’s syndrome
Joubert syndrome
Kufor Rakeb
Landau Kleffner syndrome
Melkersson Rosenthal syndrome
Nemaline myopathy
Neuronal ceroid lipofuscinosis (NCL)
Ohtahara syndrome
Pelizaeus Marzbacher disease
Panayiotopoulos syndrome (PS)
Pantethonate kinase associated neurodegeneration (PKAN)
Perry syndrome
Raeder’s paratrigeminal syndrome
Rett syndrome
Sialidosis
Tangier disease
Tarui disease
Herculean
1q deletion syndrome
Aceruloplasminaemia
Biotin responsive basal ganglia disease
Brody disease
Calsequestrin storage myopathy
Coffin Lowry syndrome
Congenital cataracts facial dysmorphism neuropathy (CCFDN)
Curranino syndrome
Danon disease
Nasu Hakola disease
PHARC syndrome
POL3 related leukodystrophy
Pourfour du petit syndrome
Sandhoff disease
Satoyoshi syndrome
Schwartz Jampel syndrome
Sepiapterin reductase deficiency
SEPN-1 related myopathy
Sialic acid storage diseases
Sjogren Larsson syndrome
Unverricht Lundborg disease
Vici syndrome
Wolf Hirschhorn syndrome
Woodhouse Sakati syndrome
Zellweger syndrome
The is of course a personal and non-evidenced list. Understandably, there will be differing opinions about what each person finds challenging. Therefore please challenge the inclusion, or misclassification, of any items on the list, or make suggestions of other challenging neurological disorders.
