Rare neurological diseases

Last updated: April 27, 2022

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Rare neurological diseases may be inherited, postinfectious, iatrogenic, or of unknown etiology. They can affect the brain, spinal cord, or peripheral nerves. Symptoms range from mild tremors to significant motor and cognitive impairment. Therapy is often supportive.

The name adrenoleukodystrophy means dystrophy (tissue wasting) of the adrenals and the white matter (leuko) of the nervous system.

References:[1][2]

References:[3]

References:[4]

Diseases caused by prion infection. Prion diseases affect both animals and humans. Creutzfeldt-Jakob disease (CJD) and variant CJD are discussed in a separate card.

Kuru [5][6]

  • Definition: a rapidly lethal prion infection
  • Etiology: acquired through ritualistic cannibalism
  • Pathophysiology: neuronal loss, gliosis, and spongiform degeneration of cerebral gray matter
  • Clinical features
  • Treatment: supportive

Gerstmann-Sträussler-Scheinker syndrome [6]

  • Definition: a general peripheral nerve hyperexcitability disorder of unknown etiology
  • Clinical features
  • Differential diagnosis
    • Benign fasciculation syndrome: a chronic condition characterized by profuse fasciculations without muscle weakness, atrophy, or other neurological abnormalities
    • Neuromyotonia: a rare syndrome associated with VGKC-antibody complexes characterized by continuous fasciculations, muscle stiffness, myokymias, and myotonic appearance of movements after muscle contraction.
  • Treatment: supportive
  • Definition: an autosomal recessive chronic degenerative neurological disease
  • Clinical features
  • Treatment: supportive
  • Prognosis: lethal before the third decade of life
  • Definition: a rare neurologic disease characterized by binge eating, hypersomnia, and hypersexuality
  • Epidemiology: mainly affects adolescent males
  • Etiology: unknown (although viral infections have been implicated)
  • Clinical features
    • Recurrent hypersomnia (patients are only awake for 1–2 hours per day)
    • Hypersexuality when awake
    • Binge eating
  • Subtype: menstrual recurrent hypersomnia
    • Very rare variant
    • Characterized by recurrent episodes of excessive sleepiness just before or during menses
    • Associated with compulsive eating (65% of cases), depression (35% of cases), and sexual disinhibition (29% of cases)
    • Symptoms sometimes respond to estrogen-containing contraceptives
  • Treatment: supportive
  • Definition: a severe neurodegenerative disorder caused by administration of clioquinol
  • Epidemiology: Most cases were confined to Japan in the 1960's.
  • Etiology: iatrogenic (induced by the drug clioquinol)
  • Clinical features
    • Progressive paralysis
    • Blindness
  • Treatment: reversible (withdraw clioquinol)
  • Definition: a rare genetic neurological disorder characterized by progressive degeneration of the white matter
  • Epidemiology: incidence is 1:100,000 births [8]
  • Etiology: mutations of the aspartoacylase (ASPA) gene, which encodes aspartoacylase, the enzyme responsible for the conversion of N-acetylaspartic acid (NAA) to aspartate and acetate
  • Pathophysiology: mutation of the ASPA gene↑ NAA levels in neurons and oligodendrocytes → neuronal dysfunction and myelin deficiency
  • Clinical features: neonatal/infantile and mild/juvenile are the two main disease types.
    • Neonatal/infantile form: normal at birth, symptoms develop by age 3–5 months. [8]
    • Mild/juvenile form: delayed development
  • Diagnostics: based on clinical and neuroimaging findings
  • Treatment: supportive (e.g., feeding gastrostomy tube in case of dysphagia, AED to manage seizures, botulinum toxin injections for spasticity)
  • Prognosis
    • Neonatal/infantile form: death in the first decade of life
    • Mild/juvenile form: same lifespan as the general population

CaNAAvan disease is caused by the accumulation of NAA.

  1. Alpers MP. The epidemiology of kuru: monitoring the epidemic from its peak to its end. Philos Trans R Soc Lond B Biol Sci. 2008; 363 (1510): p.3707-3713. doi: 10.1098/rstb.2008.0071 . | Open in Read by QxMD
  2. Genetic Prion Diseases.
  3. Snyder PJ. Causes of hypopituitarism. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/causes-of-hypopituitarism?source=see_link.Last updated: October 21, 2015. Accessed: February 9, 2017.
  4. Kumar S, Mattan NS, de Vellis J. Canavan disease: A white matter disorder. Ment Retard Dev Disabil Res Rev. 2006; 12 (2): p.157-165. doi: 10.1002/mrdd.20108 . | Open in Read by QxMD
  5. Rosenberg RN, Pascual JM. Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease. Academic Press ; 2020
  6. Matalon R, Delgado L, Michals-Matalon K, et al. Canavan Disease. Gene Reviews. 1993 .
  7. Goncalves DU, Proietti FA, Ribas JGR, et al. Epidemiology, Treatment, and Prevention of Human T-Cell Leukemia Virus Type 1-Associated Diseases. Clin Microbiol Rev. 2010; 23 (3): p.577-589. doi: 10.1128/cmr.00063-09 . | Open in Read by QxMD
  8. Chou CL, Lin YJ, Sheu YL, Lin CJ, Hseuh IH. Persistent Klüver-Bucy syndrome after bilateral temporal lobe infarction.. Acta Neurol Taiwan. 2008; 17 (3): p.199-202.
  9. Gościński I, Kwiatkowski S, Polak J, Orłowiejska M. The Kluver-Bucy syndrome.. Acta Neurochir (Wien). 1997; 139 (4): p.303-6. doi: 10.1007/bf01808825 . | Open in Read by QxMD
  10. Le T, Bhushan V, Sochat M, Chavda Y. First Aid for the USMLE Step 1 2017. McGraw-Hill Education ; 2017
  11. Ikeda AK. Metachromatic Leukodystrophy. Metachromatic Leukodystrophy. New York, NY: WebMD. http://emedicine.medscape.com/article/951840-overview. Updated: August 21, 2014. Accessed: April 3, 2017.
  12. Wanders RJ, Eichler FS. Adrenoleukodystrophy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/adrenoleukodystrophy.Last updated: September 7, 2016. Accessed: April 3, 2017.
  13. Lenz AM, Root AW. Empty sella syndrome. Pediatr Endocrinol Rev. 2012; 9 (4): p.710-715.
  14. Hexosaminidase A Deficiency.
  15. Gaucher Disease.
  16. Fabry Disease.
  17. Acid Sphingomyelinase Deficiency.
  18. Niemann-Pick Disease Type C.
  19. Arylsulfatase A Deficiency.
  20. Kaplan Medical Staff. USMLE Step 1 Lecture Notes 2017: 7-Book Set. Kaplan Publishing ; 2017

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