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Atypical Parkinsonian Syndromes

Notes

Atypical Parkinsonian Syndromes

Sections




Progressive supranuclear palsy (PSP)

Clinical Correlation: Progressive supranuclear palsy

Clinical Hallmarks

  • Indicate that there is early stiffness and falls (typically within the first year of the disease).
  • Illustrate a person standing stiffly upright, back arched, and neck extended.
  • Indicate that in PSP, there is prominent axial and neck rigidity (rather than limb) and retrocollic posture with a "lurching" gait (as opposed to PD wherein there is a stooped posture with a forward tilt and short shuffling steps).
  • Next, in sagittal view, draw the midbrain and pons but show that the midbrain is thinned-out so much that it takes the appearance of a hummingbird's head (include an eye to remind ourselves of this).
  • Now, draw a face with a furrowed brow to represent the "worried faces" sign of PSP, possibly due to a procerus muscle dystonia; this is markedly different than the lack of facial expression (hypomimia) in PD.
  • Next, draw a midbrain in axial anatomic view and illustrate that both the substantia nigra pars compacta and pars reticulata are pale in PSP.
  • Encircle the tectum and indicate that pathology here results in supranuclear vertical gaze palsy (early slowing of vertical saccades), which is a key clinical finding in PSP.
  • There are also saccadic intrusions with attempted fixation, called "square-wave jerks": the eyes jerk away and return.

Pathological Hallmarks

  • Finally, draw a histopathological slide of a neuron and show that it is stuffed with globose neurofibrillary tangles that are made up of tau protein.
  • Draw a globe to reinforce their globular shape (this will help distinguish them from the balloon-shaped tau cells in CBD).

Additional Clinical Features

  • Pseudobulbar palsy with inappropriate laughter or crying (also see in ALS and other neurodegenerative conditions, post-stroke, in MS, and other conditions).
  • Excessive drooling, dysphagia, and spastic dysarthria and dysphonia (as well as the hypophonia found in PD).
  • If tremor is present, it is an action tremor (rather than the rest tremor of PD).

Corticobasal degeneration (CBD)

Clinical Correlation: Corticobasal degeneration

Clinical Hallmarks

From its name, we can create a simple heurisitic:

  • There is basal degeneration, which leads to parkinsonism, in fact the prominent asymmetry is much like PD.
  • There is cortical degeneration, which leads to more strange/unexpected findings.

To highlight these, indicate two of the most interesting:

  • Alien limb syndrome (along with cortical sensory loss), which involves unilateral involuntary movements.
  • Ideomotor apraxia, which manifests with an inability to properly pantomime certain tool-based tasks, such as using a hammer.

Other features include: dementia and frontal lobe reflexes.

Pathological Hallmarks

  • Draw a histopathologic slide with a cortical neuron that is balloon-shaped and pale except for a small amount of tau protein around the nucleus.
  • Indicate that that the key histopathologic feature of CBD is ballooned, achromatic neurons with tau protein. Draw a balloon to reinforce this shape (as opposed to the globular shape of the neurons in PSP.

Multiple systems atrophy (MSA)

Clinical Correlation: Multiple systems atrophy (MSA)

Clinical Hallmarks

Now, for MSA (formerly Shy-Drager syndrome), use a triangle to indicate that this disorder involves the clinical triad of:

  • Autonomic dysfunction (draw a heart). Key features are orthostatic hypotension, urinary retention/incontinence, erectile dysfunction, anhidrosis, and other features.
  • Next include the motor dysfunction, which can be an equal or unequal combination of the following in the beginning (but ultimately both features will result):
  • Extrapyramidal disease (draw the stooped posture of PD): there is akinesia, rigidity, and postural instability most often without tremor; it resembles PD more-so than PSP. We use MSA-P (formerly striatonigral degeneration, SDN), if parkinsonian symptoms predominate.
  • Cerebellar dysfunction (draw a cerebellum): there is ataxia and possible cerebellar speech. We use MSA-C (formerly, olivopontocerbellar atrophy, OPCA), if cerebellar symptoms predominate.

Note that there is no MSA-A, since prominent autonomic dysfunction is always required.

  • Lastly, note that inspiratory stridor is common, important clinical manifestation in MSA.

Pathological Hallmarks

  • Next, show that there is a common radiographic finding in MSA, called the hot cross buns sign.
  • Draw a pons cross-section and draw the top of a hot cross bun on top. The white strips represent degenerated pontine white matter pathways within the pons (for more on these tracts, see our tutorial on the cortico-ponto-cerebello-thalamo-cortical pathway).
  • Now, draw a pair of oligodendrocytes in histopathological section that is stained with alpha-synuclein.
  • Within one, draw a glial cytoplasmic inclusion (GCI); indicate that these are flame-shaped inclusions of alpha-synuclein.
  • Remember that the Lewy bodies in PD also comprise alpha-synuclein but in PD, we drew the accumulation in neurons; here, the accumulation is most notably in glial cells (namely, oligodendroctyes).

References

  • ABPN, Arthur MacNeill Horton, Jr , EdD, ABPP, Chad A. Noggle ABN PhD, and Raymond S. Dean ABPdN PhD, ABPP, ABN. The Encyclopedia of Neuropsychological Disorders. Springer Publishing Company, 2011.
  • "Ataxia with Vitamin E Deficiency." NORD (National Organization for Rare Disorders) (blog). Accessed February 9, 2019. https://rarediseases.org/rare-diseases/ataxia-with-vitamin-e-deficiency/.
  • Barker, Roger A., Neil Scolding, Dominic Rowe, and Andrew J. Larner. The A-Z of Neurological Practice: A Guide to Clinical Neurology. Cambridge University Press, 2005.
  • Bradley, Walter George. Neurology in Clinical Practice: Principles of Diagnosis and Management. Taylor & Francis, 2004.
  • Campbell, William Wesley, and Russell N. DeJong. DeJong's the Neurologic Examination. Lippincott Williams & Wilkins, 2005.
  • CHANG, IRENE J., and SI HOUN HAHN. "The Genetics of Wilson Disease." Handbook of Clinical Neurology 142 (2017): 19–34. https://doi.org/10.1016/B978-0-444-63625-6.00003-3.
  • Coffey, C. Edward, Thomas W. McAllister, and Jonathan M. Silver. Guide to Neuropsychiatric Therapeutics. Lippincott Williams & Wilkins, 2007.
  • DO, Dr Stewart A. Factor, and Dr William Weiner MD. Parkinson's Disease: Diagnosis & Clinical Management : Second Edition. Demos Medical Publishing, 2007.
  • Eapen, M., D.H. Zald, J.C. Gatenby, Z. Ding, and J.C. Gore. "Using High-Resolution MR Imaging at 7T to Evaluate the Anatomy of the Midbrain Dopaminergic System." American Journal of Neuroradiology 32, no. 4 (April 2011): 688–94. https://doi.org/10.3174/ajnr.A2355.
  • Egerton, Thorlene, David R Williams, and Robert Iansek. "Comparison of Gait in Progressive Supranuclear Palsy, Parkinson's Disease and Healthy Older Adults." BMC Neurology 12 (October 2, 2012): 116. https://doi.org/10.1186/1471-2377-12-116.
  • Hardman, C. D., G. M. Halliday, D. A. McRitchie, H. R. Cartwright, and J. G. Morris. "Progressive Supranuclear Palsy Affects Both the Substantia Nigra Pars Compacta and Reticulata." Experimental Neurology 144, no. 1 (March 1997): 183–92. https://doi.org/10.1006/exnr.1997.6415.
  • Jankovic, Joseph, and Eduardo Tolosa. Parkinson's Disease and Movement Disorders. Lippincott Williams & Wilkins, 2007.
  • Johnston, Michael V., Harold P. Adams, and Ali Fatemi. Neurobiology of Disease. Oxford University Press, 2016.
    Larner, A. J. A Dictionary of Neurological Signs. Springer Science & Business Media, 2010.
  • Leiguarda, R, A J Lees, M Merello, S Starkstein, and C D Marsden. "The Nature of Apraxia in Corticobasal Degeneration." Journal of Neurology, Neurosurgery, and Psychiatry 57, no. 4 (April 1994): 455–59.
  • Lepore, Frederick E. "Procerus Sign in Progressive Supranuclear Palsy." Neurology 58, no. 12 (June 25, 2002): 1866–67. https://doi.org/10.1212/WNL.58.12.1866-a.
  • Martino, Davide, Maria Stamelou, and Kailash P. Bhatia. "The Differential Diagnosis of Huntington's Disease-like Syndromes: 'Red Flags' for the Clinician." J Neurol Neurosurg Psychiatry 84, no. 6 (June 1, 2013): 650–56. https://doi.org/10.1136/jnnp-2012-302532.
  • Massano, João, and Kailash P. Bhatia. "Clinical Approach to Parkinson's Disease: Features, Diagnosis, and Principles of Management." Cold Spring Harbor Perspectives in Medicine 2, no. 6 (June 2012). https://doi.org/10.1101/cshperspect.a008870.
  • MD, Francoise Gray, Charles Duyckaerts MD, and Umberto de Girolami MD. Escourolle and Poirier's Manual of Basic Neuropathology. Oxford University Press, 2018.
  • Nguyen, Hoa Huu Phuc, and M. Angela Cenci. Behavioral Neurobiology of Huntington's Disease and Parkinson's Disease. Springer, 2015.
  • Paz, Manuel Posada de la, Domenica Taruscio, and Stephen C. Groft. Rare Diseases Epidemiology: Update and Overview. Springer, 2017.
  • Pfeiffer, Ronald. "Wilson's Disease." Seminars in Neurology 27, no. 2 (April 2007): 123–32. https://doi.org/10.1055/s-2007-971173.
  • Podolsky, Daniel K., Michael Camilleri, J. Gregory Fitz, Anthony N. Kalloo, Fergus Shanahan, and Timothy C. Wang. Yamada's Textbook of Gastroenterology. John Wiley & Sons, 2015.
  • Puschmann, Andreas, and Zbigniew K. Wszolek. "Diagnosis and Treatment of Common Forms of Tremor." Seminars in Neurology 31, no. 1 (February 2011): 65–77. https://doi.org/10.1055/s-0031-1271312.
    Reference, Genetics Home. "PARK7 Gene." Genetics Home Reference. Accessed January 14, 2019. https://ghr.nlm.nih.gov/gene/PARK7.
  • ———. "PINK1 Gene." Genetics Home Reference. Accessed January 14, 2019. https://ghr.nlm.nih.gov/gene/PINK1.
  • ———. "PRKN Gene." Genetics Home Reference. Accessed January 14, 2019. https://ghr.nlm.nih.gov/gene/PRKN.
  • ———. "SNCA Gene." Genetics Home Reference. Accessed January 14, 2019. https://ghr.nlm.nih.gov/gene/SNCA.
  • ———. "What Do Geneticists Mean by Anticipation?" Genetics Home Reference. Accessed January 30, 2019. https://ghr.nlm.nih.gov/primer/inheritance/anticipation.
  • Robertson, David, Italo Biaggioni, Geoffrey Burnstock, Phillip A. Low, and Ronald J. Polinsky. Primer on the Autonomic Nervous System. Academic Press, 2004.
  • Rosenberg, Roger N. Atlas of Clinical Neurology. Springer Science & Business Media, 2012.
  • Shivakumar, R., and Sanjeev V. Thomas. "Teaching NeuroImages: Face of the Giant Panda and Her Cub: MRI
    Correlates of Wilson Disease." Neurology 72, no. 11 (March 17, 2009): e50–e50. https://doi.org/10.1212/01.wnl.0000344409.73717.a1.
  • Spillantini, Maria Grazia, R. Anthony Crowther, Ross Jakes, Masato Hasegawa, and Michel Goedert. "α-Synuclein in Filamentous Inclusions of Lewy Bodies from Parkinson's Disease and Dementia with Lewy Bodies." Proceedings of the National Academy of Sciences 95, no. 11 (May 26, 1998): 6469–73. https://doi.org/10.1073/pnas.95.11.6469.
  • Squire, Larry R. Encyclopedia of Neuroscience. Academic Press, 2009.
  • Sulzer, David, and D. James Surmeier. "Neuronal Vulnerability, Pathogenesis and Parkinson's Disease." Movement Disorders : Official Journal of the Movement Disorder Society 28, no. 1 (January 2013): 41–50. https://doi.org/10.1002/mds.25095.
  • Tan, N.-C., L.-L. Chan, and E.-K. Tan. "Hemifacial Spasm and Involuntary Facial Movements." QJM: An International Journal of Medicine 95, no. 8 (August 1, 2002): 493–500. https://doi.org/10.1093/qjmed/95.8.493.
  • Thenganatt, Mary Ann, and Elan D Louis. "Distinguishing Essential Tremor from Parkinson's Disease: Bedside Tests and Laboratory Evaluations." Expert Review of Neurotherapeutics 12, no. 6 (June 2012): 687–96. https://doi.org/10.1586/ern.12.49.
  • Warner, Thomas T., and Simon R. Hammans. Practical Guide to Neurogenetics E-Book. Elsevier Health Sciences, 2008.
  • "Wilson's Disease." Accessed February 4, 2019. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/wilson-disease/.
  • Younger, David S. Motor Disorders. Rothstein Publishing, 2014.
    "α-Synuclein and UCH-L1 Are Present in Lewy Bodies and | Open-I." Accessed January 15, 2019. https://openi.nlm.nih.gov/detailedresult.php?img=PMC4419839_fncel-09-00163-g0002&req=4.