Encephalitis lethargica

Form of encephalitis (sleeping sickness)

It has been suggested that Encephalitis lethargica epidemic of 1918–1930 be merged into this article. (Discuss) Proposed since July 2022.

|

Medical condition

Encephalitis lethargica

Other names| Economo's disease; von Economo's encephalitis[1]
An illustration from von Economo's Die Encephalitis lethargica (1918) showing brain tissue of a monkey affected by Encephalitis lethargica, as seen under a microscope
Specialty| Infectious diseases, neurology
Causes| Unknown
Frequency| Unknown

Encephalitis lethargica is an atypical form of encephalitis. Also known as "sleeping sickness" or "sleepy sickness" (distinct from tsetse fly-transmitted sleeping sickness), it was first described in 1917 by neurologist Constantin von Economo[2][3] and pathologist Jean-René Cruchet.[4] The disease attacks the brain, leaving some victims in a statue-like condition, speechless and motionless.[5] Between 1915 and 1926,[6] an epidemic of encephalitis lethargica spread around the world. The exact number of people infected is unknown, but it is estimated that more than one million people contracted the disease during the epidemic, which directly caused more than 500,000 deaths.[7][8][9] Most of those who survived never returned to their pre-morbid vigour.

## Signs and symptoms[edit]

Encephalitis lethargica is characterized by high fever, sore throat, headache, lethargy, double vision, delayed physical and mental response, sleep inversion and catatonia.[5][10] In severe cases, patients may enter a coma-like state (akinetic mutism).[citation needed] Patients may also experience abnormal eye movements ("oculogyric crises"),[11] Parkinsonism, upper body weakness, muscular pains, tremors, neck rigidity, and behavioral changes including psychosis.[citation needed] Klazomania (a vocal tic) is sometimes present.[12]

## Cause[edit]

Encephalitis lethargica. Its sequelae and treatment – Constantin Von Economo, 1931: front page

The causes of encephalitis lethargica are uncertain.[13] Some studies have explored its origins in an autoimmune response,[5] and, separately or in relation to an immune response, links to pathologies of infectious disease—viral and bacterial,[5] such as in the case of influenza, where a link with encephalitis is clear.[14] Postencephalitic Parkinsonism was clearly documented to have followed an outbreak of encephalitis lethargica following the 1918 influenza pandemic; evidence for viral causation of the Parkinson's symptoms is circumstantial (epidemiologic, and finding influenza antigens in encephalitis lethargica patients), while evidence arguing against this cause is of the negative sort (for example, lack of viral RNA in postencephalitic Parkinsonian brain material).[14] In reviewing the relationship between influenza and encephalitis lethargica (EL), McCall and coauthors conclude, as of 2008, that "the case against influenza [is] less decisive than currently perceived… there is little direct evidence supporting influenza in the etiology of EL," and that "[a]lmost 100 years after the EL epidemic, its etiology remains enigmatic."[15] Hence, while opinions on the relationship of encephalitis lethargica to influenza remain divided, the preponderance of literature appears skeptical.[15][16]

The German neurologist Felix Stern, who examined hundreds of encephalitis lethargica patients during the 1920s, noted that their encephalitis lethargica typically evolved over time. The early symptoms would be dominated by sleepiness or wakefulness. A second symptom would lead to an oculogyric crisis. The third symptom would be recovery, followed by a Parkinson-like syndrome. If patients of Stern followed this course of disease, he diagnosed them with encephalitis lethargica. Stern suspected encephalitis lethargica to be close to poliomyelitis, without evidence. Nevertheless, he experimented with the convalescent serum of survivors of the first acute syndrome. He vaccinated patients with early-stage symptoms, telling them that it might be successful. Stern is author of the definitive 1920s book, Die Epidemische Encephalitis.[17]

In 2010, in a substantial Oxford University Press compendium reviewing the historic and contemporary views on EL, its editor, Joel Vilensky, of the Indiana University School of Medicine, quotes another researcher, writing in 1930, who states, "we must confess that etiology is still obscure, the causative agent still unknown, the pathological riddle still unsolved…", and goes on to offer the following conclusion, as of that publication date:

> Does the present volume solve the "riddle" of EL, which… has been referred to as the greatest medical mystery of the 20th century? Unfortunately, no: but inroads are certainly made here pertaining to diagnosis, pathology, and even treatment."[18]

Subsequent to publication of this compendium, an enterovirus was discovered in encephalitis lethargica cases from the epidemic.[19] In 2012, Oliver Sacks, the author of the book Awakenings, about institutionalized survivors, acknowledged this virus as the probable cause of the disease.[20] Other sources have suggested Streptococcus pneumoniae as a cause.[21]

## Diagnosis[edit]

There have been several proposed diagnostic criteria for encephalitis lethargica. One, which has been widely accepted, includes an acute or subacute encephalitic illness where all other known causes of encephalitis have been excluded. Another diagnostic criterion, suggested more recently, says that the diagnosis of encephalitis lethargica "may be considered if the patient's condition cannot be attributed to any other known neurological condition and that they show the following signs: influenza-like signs; hypersomnolence (hypersomnia), wakeability, ophthalmoplegia (paralysis of the muscles that control the movement of the eye), and psychiatric changes."[22]

## Treatment[edit]

L-DOPA

Modern treatment approaches to encephalitis lethargica include immunomodulating therapies, and treatments to remediate specific symptoms.[23]

There is little evidence so far of a consistent effective treatment for the initial stages, though some patients given steroids have seen improvement.[24] The disease becomes progressive, with evidence of brain damage similar to that of Parkinson's disease.[25][needs update]

Treatment is then symptomatic. L-DOPA (Levodopa) and other anti-Parkinson drugs often produce dramatic responses; however, most people given L-DOPA experience improvements that are short lived.[26][27]

## History[edit]

### Occurrences[edit]

Retrospective diagnosis tentatively suggests various historical outbreaks of encephalitis lethargica:

* In 1580, Europe was swept by a serious febrile and lethargic illness that led to Parkinsonism and other neurological sequelae.[28]
* In 1673–1675, a similar serious epidemic occurred in London, which Thomas Sydenham described as "febris comatosa".[28]
* In 1695, a 20-year-old woman in Germany experienced oculogyric crises, Parkinsonism, diplopia, strabismus, and other symptoms following an attack of somnolent brain fever, as described by Albrecht of Hildesheim.[28]
* In 1712–1713, a severe epidemic of Schlafkrankheit ('sleep sickness') occurred in Tübingen, Germany, followed in many cases by persistent slowness of movement and lack of initiative (aboulia).[28]
* Between 1750 and 1800, France and Germany experienced minor epidemics of "coma somnolentum" with features of Parkinsonism, including hyperkinetic hiccup, myoclonus, chorea, and tics.
* Between 1848 and 1882, Paris-based neurologist Jean-Martin Charcot documented many isolated cases of juvenile Parkinsonism, associated with diplopia, oculogyria, tachypnoea, retropulsion, and obsessional disorders, which were almost certainly post-encephalitic in origin.[28]
* In 1890 in Italy, following the influenza epidemic of 1889–1890, a severe epidemic of somnolent illnesses (nicknamed the "Nona") appeared. For the few survivors of the Nona, Parkinsonism and other sequelae developed in almost all cases.[28]
* Between 1915 and 1926, a world-wide encephalitis lethargica pandemic occurred, impacting nearly 5 million people and killing an estimated 1.6 million people.[28]

### Pandemic of 1915–1926[edit]

In the winter of 1916–1917, a "new" illness suddenly appeared in Vienna and other cities, and rapidly spread world-wide over the next three years. Earlier reports appeared throughout Europe as early as the winter of 1915–1916, but communication about the disease was slow and chaotic, given the varied manifestation of symptoms and difficulties disseminating information in wartime.[29] Until Constantin von Economo identified a unique pattern of damage among the brains of deceased patients and introduced the unifying name encephalitis lethargica, reports of the protean disease came in under a range of names: botulism, toxic ophthalmoplegia, epidemic stupor, epidemic lethargic encephalitis, acute polioencephalitis, Heine-Medin disease, bulbar paralysis, hystero-epilepsy, acute dementia, and sometimes just "an obscure disease with cerebral symptoms."[29] Just 10 days before von Economo's breakthrough in Vienna, Jean-René Cruchet described 40 cases of "subacute encephalomyelitis" in France.[29]

The number of people infected during the ten years of the pandemic is unknown, but it is estimated that more than 1 million people contracted the disease, which directly caused more than 500,000 deaths.[7][8][9] Encephalitis lethargica assumed its most virulent form between October 1918 and January 1919. The pandemic disappeared in 1927, as abruptly and mysteriously as it first appeared.[29] The great encephalitis pandemic coincided with the 1918 influenza pandemic, and it is likely that the influenza virus potentiated the effects of the causative agent of the encephalitis or lowered resistance to it in a catastrophic way.[29]

#### Aftermath[edit]

Many surviving patients of the 1915–1926 pandemic seemed to make a complete recovery and return to their normal lives. However, the majority of survivors subsequently developed neurological or psychiatric disorders, often after years or decades of seemingly perfect health. Post-encephalitic syndromes varied widely: sometimes they proceeded rapidly, leading to profound disability or death; sometimes very slowly; sometimes they progressed to a certain point and then stayed at this point for years or decades; and sometimes, following their initial onslaught, they remitted and disappeared.[30] Postencephalitic Parkinsonism is perhaps the most widely recognized of such syndromes.[citation needed]

## Notable cases[edit]

Notable cases include:

* Muriel "Kit" Richardson (née Hewitt), first wife of actor Sir Ralph Richardson, died of the condition in October 1942, having first shown symptoms in 1927–28.[citation needed]
* There is speculation that Adolf Hitler may have had encephalitis lethargica when he was a young adult (in addition to the more substantial case for Parkinsonism in his later years).[31][32][33][34]
* Mervyn Peake (1911–1968), author of the Gormenghast books, began his decline towards death which was initially attributed to encephalitis lethargica with Parkinson's disease–like symptoms, although others have later suggested his decline in health and eventual death may have been due to Lewy body dementia.[35][36]
* Those described in the book Awakenings by the British neurologist Oliver Sacks.[27]
* Jane Norton Grew Morgan, wife of J. P. Morgan Jr., died of encephalitis lethargica in 1925. At the time, doctors attributed her encephalitis to having contracted influenza during the 1918 pandemic.[37]

## References[edit]

1. ^ Berger JR, Vilensky JA (2014). "Encephalitis lethargica (von Economo's encephalitis)". Handbook of Clinical Neurology. 123: 745–761. doi:10.1016/B978-0-444-53488-0.00036-5. ISBN 978-0444534880. PMID 25015515.
2. ^ Economo's disease at Who Named It?
3. ^ von Economo, K. (May 10, 1917). "Die Encephalitis lethargica". Wiener klinische Wochenschrift [Vienna clinical weekly] (in German). Leipzig and Vienna: Franz Deuticke 1918. 30: 581–585.
4. ^ Cruchet, R; Moutier, J; Calmettes, A (1917). "Quarante cas d'encéphalomyélite subaiguë" [Forty cases of (subacute) encephalitis lethargica]. Bull Soc Med Hôp (in French). Paris. 41: 614–616.
5. ^ a b c d Dale, Russell C.; Church, Andrew J.; Surtees, Robert A.H.; Lees, Andrew J.; Adcock, Jane E.; Harding, Brian; Neville, Brian G. R.; Giovannoni, Gavin (2004). "Encephalitis Lethargica Syndrome: 20 New Cases and Evidence of Basal Ganglia Autoimmunity". Brain. 127 (1): 21–33. doi:10.1093/brain/awh008. PMID 14570817.
6. ^ "Encephalitis lethargica" at Dorland's Medical Dictionary
7. ^ a b Ravenholt, R. T.; Foege, William H (1982-10-16). "1918 Influenza, Encephalitis Lethargica, Parkinsonism". The Lancet. Originally published as Volume 2, Issue 8303. 320 (8303): 860–864. doi:10.1016/S0140-6736(82)90820-0. ISSN 0140-6736. PMID 6126720. S2CID 45138249.
8. ^ a b McCall, Sherman; Vilensky, Joel A; Gilman, Sid; Taubenberger, Jeffery K (May 2008). "The relationship between encephalitis lethargica and influenza: A critical analysis". Journal of Neurovirology. 14 (3): 177–185. doi:10.1080/13550280801995445. ISSN 1355-0284. PMC 2778472. PMID 18569452.
9. ^ a b Hoffman, Leslie A.; Vilensky, Joel A. (2017-08-01). "Encephalitis lethargica: 100 years after the epidemic". Brain. 140 (8): 2246–2251. doi:10.1093/brain/awx177. ISSN 0006-8950. PMID 28899018.
10. ^ Koch, Christof (March–April 2016). "Sleep without End". Scientific American Mind. 27 (2): 22–25. doi:10.1038/scientificamericanmind0316-22.
11. ^ Vilensky, J.A.; Goetz, C.G.; Gilman, S. (2006). "Movement Disorders Associated with Encephalitis Lethargica: A Video Compilation". Mov. Disord. 21 (1, January): 1–8. doi:10.1002/mds.20722. PMID 16200538. S2CID 34382398.
12. ^ Jankovic, J.; Mejia, N.I. (2006). "Tics Associated with Other Disorders". Adv. Neurol. 99: 61–68. PMID 16536352.
13. ^ McCall, S.; Vilensky, J.A.; Gilman, S.; Taubenberger, J.K. (2008). "The Relationship Between Encephalitis Lethargica and Influenza: A Critical Analysis". J. Neurovirol. 14 (3, May): 177–185. doi:10.1080/13550280801995445. PMC 2778472. PMID 18569452.
14. ^ a b Haeman, Jang; Boltz, D.; Sturm-Ramirez, K.; Shepherd, K.R.; Jiao, Y.; Webster, R.; Smeyne, Richard J. (2009). "Highly Pathogenic H5N1 Influenza Virus Can Enter the Central Nervous System and Induce Neuroinflammation and Neurodegeneration". Proceedings of the National Academy of Sciences. 106 (33, August 10): 14063–14068. doi:10.1073/pnas.0900096106. PMC 2729020. PMID 19667183. Retrieved 8 December 2015.
15. ^ a b Reid, A.H.; McCall, S.; Henry, J.M.; Taubenberger, J.K. (2001). "Experimenting on the Past: The Enigma of von Economo's Encephalitis Lethargica". J. Neuropathol. Exp. Neurol. 60 (7): 663–670. doi:10.1093/jnen/60.7.663. PMID 11444794.
16. ^ Vilensky, J.A.; Foley, P.; Gilman, S. (2007). "Children and Encephalitis Lethargica: A Historical Review". Pediatr. Neurol. 37 (2, August): 79–84. doi:10.1016/j.pediatrneurol.2007.04.012. PMID 17675021. Retrieved 8 December 2015.
17. ^ "Auf der Spur der Schlaf-Epidemie". Spektrum.de (in German). 2019-01-25. Retrieved 2019-01-28.
18. ^ Vilensky, J.A.; Gilman, S. (2010). "Introduction". In Vilensky, Joel A. (ed.). Encephalitis Lethargica: During and After the Epidemic. Oxford: Oxford University Press. pp. 3–7, esp. 6f. ISBN 978-0190452209. Retrieved 8 December 2015.
19. ^ Dourmashkin, Robert R.; Dunn, Glynis; Castano, Victor; McCall, Sherman A. (2012-01-01). "Evidence for an enterovirus as the cause of encephalitis lethargica". BMC Infectious Diseases. 12: 136. doi:10.1186/1471-2334-12-136. ISSN 1471-2334. PMC 3448500. PMID 22715890.
20. ^ Letter from Oliver Sacks to Professor Joel A. Vilensky, 9 Sept 2012.
21. ^ "Mystery of the forgotten plague". BBC News. 27 July 2004.
22. ^ Easton, Ava. "Encephalitis Lethargica". The Encephalitis Society. Retrieved 27 December 2017.
23. ^ Lopez-Alberola, R.; Georgiou, M.; Sfakianakis, G.N.; Singer, C.; Papapetropoulos, S. (2009). "Contemporary Encephalitis Lethargica: Phenotype, Laboratory Findings and Treatment Outcomes". J. Neurol. 256 (3, March): 396–404. doi:10.1007/s00415-009-0074-4. PMID 19412724. S2CID 38388333.
24. ^ Blunt, S.B.; Lane, R.J.; Turjanski, N.; Perkin, G.D. (1997). "Clinical Features and Management of Two Cases of Encephalitis Lethargica". Mov. Disord. 12 (3): 354–359. doi:10.1002/mds.870120314. PMID 9159730. S2CID 14741885.
25. ^ Kohnstamm, P. (1934). "Über die Beteiligung der beiden Schichten der Substantia nigra am Prozeß der Encephalitis epidemica". J Psychol Neurol (in German). 46 (1): 22–37.
26. ^ "Encephalitis Lethargica Information Page". National Institute of Neurological Disorders and Stroke. August 9, 2018.
27. ^ a b (Sacks 1990)[page needed]
28. ^ a b c d e f g (Sacks 1990, pp. 319–321)
29. ^ a b c d e (Sacks 1990, pp. 12–19)
30. ^ (Sacks 1990, pp. 20–21)
31. ^ Lieberman, A (April 1996). "Adolf Hitler Had Post-Encephalitic Parkinsonism". Parkinsonism Relat Disord. 2 (2): 95–103. doi:10.1016/1353-8020(96)00005-3. PMID 18591024.
32. ^ Boettcher, L.B.; Bonney, P.A.; Smitherman A.D.; Sughrue, M.E. (2015). "Hitler's Parkinsonism". Neurosurg Focus. 39 (1, July): E8. doi:10.3171/2015.4.FOCUS1563. PMID 26126407.
33. ^ Gupta, R; Kim, C; Agarwal, N; Lieber, B; Monaco, E.A. (2015). "Understanding the Influence of Parkinson's Disease on Adolf Hitler's Decision-Making During World War II". World Neurosurg. 84 (5, November): 1447–1452. doi:10.1016/j.wneu.2015.06.014. PMID 26093359.
34. ^ Rosen, Denis (2010). "Review: "Asleep: the Forgotten Epidemic That Remains One of Medicine's Greatest Mysteries" [Molly Caldwell Crosby". J. Clin. Sleep Med. 6 (3, 15 June): 299. doi:10.5664/jcsm.27831. PMC 2883045.
35. ^ Demetrios J. Sahlas (2003). "Dementia With Lewy Bodies and the Neurobehavioral Decline of Mervyn Peake". Arch. Neurol. 60 (6): 889–892. doi:10.1001/archneur.60.6.889. PMID 12810496.
36. ^ McMillan, Roy; Peake (20 July 2011) [1959]. Butcher Sara (ed.). Publisher's Liner Notes on Mervyn Peake for 'Titus Alone' (Liner Notes/ Reference Guide for Abridged Audiobook of Titus Alone). Audible.com (Liner Notes) (Abridged, Audio ed.). Germany: Naxos Audiobooks. p. 7\. ISBN 978-184-379-542-1. Retrieved 2 May 2018. "But the plays were not the financial winners he had hoped for, and he suffered another nervous breakdown in 1957. This led to the more evident display of the symptoms of a type of Parkinson's Disease which, alongside the effects of encephalitis lethargica that he contracted in childhood, was slowly to kill him over more than a decade."[permanent dead link]
37. ^ Chernow, Ron (1990). The House of Morgan: An American Banking Dynasty and the Rise of Modern Finance. New York: Atlantic Monthly Press. ISBN 0-87113-338-5.

## Further reading[edit]

* Crosby, Molly Caldwell (2010). 'Asleep: The Forgotten Epidemic that Remains One of Medicine's Greatest Mysteries. New York: Penguin/Berkley.[ISBN missing] - Describes the history of the disease, and the epidemic of the 1920s.
* Reid, A.H.; McCall, S.; Henry, J.M.; Taubenberger, J.K. (2001). "Experimenting on the Past: The Enigma of von Economo's Encephalitis Lethargica". J. Neuropathol. Exp. Neurol. 60 (7): 663–670. doi:10.1093/jnen/60.7.663. PMID 11444794.
* Sacks, Oliver (1990). Awakenings. Vintage Books. ISBN 978-0-375-70405-5. OCLC 21910570.
* Sacks O (1983). "The origin of 'Awakenings'". Br. Med. J. (Clin. Res. Ed.). 287 (6409): 1968–1969. doi:10.1136/bmj.287.6409.1968. PMC 1550182. PMID 6418286.
* Vilensky, J.A.; Foley, P.; Gilman, S. (2007). "Children and Encephalitis Lethargica: A Historical Review". Pediatr. Neurol. 37 (2, August): 79–84. doi:10.1016/j.pediatrneurol.2007.04.012. PMID 17675021.
* Vilensky, Joel A., ed. (2010). Encephalitis Lethargica: During and After the Epidemic. Oxford, UK: Oxford University Press. ISBN 978-0190452209.

## External links[edit]

* National Institute of Neurological Disorders and Stroke
* Mystery of the Forgotten Plague: BBC news item about the tracing of the infectious agent in encephalitis lethargica

Classification|

* ICD-10: A85.8
* ICD-9-CM: 049.8
* DiseasesDB: 32498

|

* v
* t
* e

Infectious diseases – viral systemic diseases

Oncovirus|

DNA virus
HBV

Hepatocellular carcinoma
HPV

Cervical cancer
Anal cancer
Penile cancer
Vulvar cancer
Vaginal cancer
Oropharyngeal cancer
KSHV

Kaposi's sarcoma
EBV

Nasopharyngeal carcinoma
Burkitt's lymphoma
Hodgkin lymphoma
Follicular dendritic cell sarcoma
Extranodal NK/T-cell lymphoma, nasal type
MCPyV

Merkel-cell carcinoma

RNA virus
HCV

Hepatocellular carcinoma
Splenic marginal zone lymphoma
HTLV-I

Adult T-cell leukemia/lymphoma

Immune disorders|

* HIV
* AIDS

Central
nervous system|

| Encephalitis/
meningitis|

DNA virus
Human polyomavirus 2

Progressive multifocal leukoencephalopathy

RNA virus
MeV

Subacute sclerosing panencephalitis
LCV

Lymphocytic choriomeningitis
Arbovirus encephalitis
Orthomyxoviridae (probable)

Encephalitis lethargica

Rabies
Chandipura vesiculovirus
Herpesviral meningitis
Ramsay Hunt syndrome type 2

|

Myelitis|

* Poliovirus
* Poliomyelitis
* Post-polio syndrome
* HTLV-I
* Tropical spastic paraparesis

Eye|

* Cytomegalovirus
* Cytomegalovirus retinitis
* HSV
* Herpes of the eye

Cardiovascular|

* CBV
* Pericarditis
* Myocarditis

Respiratory system/
acute viral
nasopharyngitis/
viral pneumonia|

| DNA virus|

* Epstein–Barr virus
* EBV infection/Infectious mononucleosis
* Cytomegalovirus

|

RNA virus|

* IV: Human coronavirus 229E/NL63/HKU1/OC43
* Common cold
* MERS coronavirus
* Middle East respiratory syndrome
* SARS coronavirus
* Severe acute respiratory syndrome
* SARS coronavirus 2
* COVID-19

* V, Orthomyxoviridae: Influenza virus A/B/C/D
* Influenza/Avian influenza

* V, Paramyxoviridae: Human parainfluenza viruses
* Parainfluenza
* Human orthopneumovirus
* hMPV

Human
digestive system|

| Pharynx/Esophagus|

* MuV
* Mumps
* Cytomegalovirus
* Cytomegalovirus esophagitis

|

Gastroenteritis/
diarrhea|

DNA virus
Adenovirus

Adenovirus infection

RNA virus
Rotavirus
Norovirus
Astrovirus
Coronavirus

Hepatitis|

DNA virus
HBV (B)

RNA virus
CBV
HAV (A)
HCV (C)
HDV (D)
HEV (E)

Pancreatitis|

* CBV

Urogenital|

* BK virus
* MuV
* Mumps

* v
* t
* e

Diseases of the nervous system, primarily CNS

Inflammation|

| Brain|

* Encephalitis
* Viral encephalitis
* Herpesviral encephalitis
* Limbic encephalitis
* Encephalitis lethargica
* Cavernous sinus thrombosis
* Brain abscess
* Amoebic

|

Brain and spinal cord|

* Encephalomyelitis
* Acute disseminated
* Meningitis
* Meningoencephalitis

Brain/
encephalopathy|

| Degenerative|

| Extrapyramidal and
movement disorders|

* Basal ganglia disease
* Parkinsonism
* PD
* Postencephalitic
* NMS
* NBIA
* PKAN
* Tauopathy
* PSP
* Striatonigral degeneration
* Hemiballismus
* HD
* OA

* Dyskinesia
* Dystonia
* Status dystonicus
* Spasmodic torticollis
* Meige's
* Blepharospasm
* Athetosis
* Chorea
* Choreoathetosis
* Myoclonus
* Myoclonic epilepsy
* Akathisia

* Tremor
* Essential tremor
* Intention tremor
* Restless legs
* Stiff-person

|

Dementia|

* Tauopathy
* Alzheimer's
* Early-onset
* Primary progressive aphasia
* Frontotemporal dementia/Frontotemporal lobar degeneration
* Pick's
* Lewy bodies dementia
* Posterior cortical atrophy

* Vascular dementia

Mitochondrial disease|

* Leigh syndrome

Demyelinating|

* Autoimmune
* Inflammatory
* Multiple sclerosis
* For more detailed coverage, see Template:Demyelinating diseases of CNS

Episodic/
paroxysmal|

| Seizures and epilepsy|

* Focal
* Generalised
* Status epilepticus
* For more detailed coverage, see Template:Epilepsy

|

Headache|

* Migraine
* Cluster
* Tension
* For more detailed coverage, see Template:Headache

Cerebrovascular|

* TIA
* Stroke
* For more detailed coverage, see Template:Cerebrovascular diseases

Other|

* Sleep disorders
* For more detailed coverage, see Template:Sleep

CSF|

* Intracranial hypertension
* Hydrocephalus
* Normal pressure hydrocephalus
* Choroid plexus papilloma
* Idiopathic intracranial hypertension
* Cerebral edema
* Intracranial hypotension

Other|

* Brain herniation
* Reye syndrome
* Hepatic encephalopathy
* Toxic encephalopathy
* Hashimoto's encephalopathy
* Static Encephalopathy

Both/either|

| Degenerative|

| SA|

* Friedreich's ataxia
* Ataxia–telangiectasia

|

MND|

* UMN only:
* Primary lateral sclerosis
* Pseudobulbar palsy
* Hereditary spastic paraplegia

* LMN only:
* Distal hereditary motor neuronopathies
* Spinal muscular atrophies
* SMA
* SMAX1
* SMAX2
* DSMA1
* Congenital DSMA
* Spinal muscular atrophy with lower extremity predominance (SMALED)
* SMALED1
* SMALED2A
* SMALED2B
* SMA-PCH
* SMA-PME
* Progressive muscular atrophy
* Progressive bulbar palsy
* Fazio–Londe
* Infantile progressive bulbar palsy

* both:
* Amyotrophic lateral sclerosis

*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template