"Typical" Parkinson's Disease
Parkinson's disease is a progressive brain disorder which usually produces some combination of the following symptoms:
- Tremor at rest
- Slowed movement
- Stiffness or rigidity of muscles
- Unsteadiness when standing or walking
- "Freezing" or sudden loss of ability to move (as if the feet are "glued" to the floor).
Parkinson's disease (PD) results from dying off (degeneration) of certain nerve cells found in a deep part of the brain (brainstem) called the substantia nigra. The reason for the cell death is unknown. These cells produce a neurotransmitter chemical called dopamine. It is the depletion of dopamine in the brain that results in symptoms of PD. Initially, Parkinson's symptoms improve with dopamine replacement in the form of levodopa (Sinemet). Although the nerve cells in the substantia nigra, which make dopamine, are dying, the nerve cells in the basal ganglia (striatum), which are normally stimulated by dopamine, have well preserved dopamine receptors and are therefore still responding to dopamine. The cornerstone of medical treatment of PD is administration of levodopa, which is taken up and converted into dopamine by the brain.
"Atypical" Parkinsonism and How It Differs From Parkinson's Disease
Parkinsonism refers to a set of symptoms typically seen in Parkinson's disease, but caused by other disorders. Atypical parkinsonism includes a variety of neurological disorders in which patients have some clinical features of PD, but the symptoms are caused not only by cell loss in the substantia nigra (the brain area most affected in classic PD), but also by additional degeneration of cells in the parts of the nervous system that normally contain dopamine receptors (striatum). In other words, the patients look like they have PD, but the cause of their symptoms is different from that of classic PD. Patients with atypical parkinsonism have symptoms similar to PD, including resting tremors, slowed movement, stiffness, gait difficulty and postural instability, but in addition have symptoms and signs that are not typically present in PD, hence the term "Parkinsonism plus syndrome."
The additional problems may include inability to look up and down (vertical gaze palsy) and early postural instability, such as seen in progressive supranuclear palsy (PSP), the most common form of atypical parkinsonism. Patients with PSP often have the "procerus sign" which is a particular "worried" facial expression.
The second most common form of atypical parkinsonism is multiple system atrophy (MSA), previously also referred to as Shy-Drager syndrome or olivopontocerebellar atrophy. Patients with MSA are typically distinguished from those with PD by the presence of autonomic features such as unstable blood pressure which falls drastically upon standing (orthostatic hypotension), early disturbance of sexual, bladder, and bowel dysfunction, reddish-bluish discoloration of skin (e.g. the "cold hand" sign), and marked sleep disturbance (e.g. acting out of dreams and sleep apnea). Other typical features of MSA include forward head tilt (anterocollis) or a body tilt when sitting (Pisa sign), loss of coordination, and rapidly progressive course with inability to ambulate usually within the first 3-5 years after onset. MSA is divided into MSA-C (cerebellar variant) which has more symptoms of ataxia (incoordination) and MSA-P (parkinsonian variant) which has more parkinsonian symptoms but is unresponsive to the usual therapy for Parkinson's disease (levodopa).
Another common cause of atypical parkinsonism is "vascular parkinsonism" caused by multiple, usually very minute, strokes. These patients usually have more symptoms in the lower extremities (lower body parkinsonism) with walking difficulties, balance problems and falls.
Other forms of atypical parkinsonism are Dementia with Lewy bodies (DLB) and cortico-basal ganglionic degeneration (CBD). Patients with DLB have, in addition to the parkinsonian features, early dementia (preceding or co-occurring with the parkinsonian symptoms), visual hallucinations (seeing people, animals or objects that are not real), their symptoms fluctuating, with "good days" and "bad days." Patients with CBD usually present with asymmetric stiffness, apraxia (inability to carry out learned purposeful movements), alien limb (the hand or the leg seem to have "a mind of their own"), and limb dystonia (abnormal sustained muscle contractions causing abnormal postures and twisting). Poor or no response to levodopa is common feature to all forms of atypical parkinsonism.
In contrast to typical PD, in which dopamine receptors are spared, patients with atypical parkinsonian disorders have lost their dopamine receptors and therefore they do not respond to levodopa as well as those with typical PD. This can be demonstrated by special imaging such as positron emission tomography (PET) and dopamine transporter imaging (DAT-SPECT). MRI may be also helpful in differentiating PD from atypical parkinsonism.
Causes of Atypical Parkinsonism
There are probably many causes of atypical parkinsonism, but no one specific cause has been identified. There are many articles (see references) that describe some of the research into the causes of these disorders. Although it is not yet known what causes atypical parkinsonism, only one member of a family is usually affected and, therefore, these disorders are thought to be sporadic and not inherited. This is in contrast to typical PD where genetic factors seem to be quite important. The various atypical parkinsonian syndromes are classified according to the patterns of damage they produce in the nervous system, the constellation of clinical symptoms they cause, and their natural course.
How to Support Research
Because the various atypical parkinsonism diseases are relatively uncommon, it is difficult to obtain public funding for research. Therefore, research into these disorders largely depends upon private contributions, particularly from patients and families affected with the diseases. Besides financial support and willingness to participate in clinical research projects, scientists are interested in examining postmortem brains of patients who were afflicted with these disorders. To arrange for a brain donation to a qualified "brain bank" you should contact your neurologist or the National Parkinson Foundation for further information.
Support Groups for Patients and Their Families
Patients affected with atypical parkinsonism and their families should consider joining national or local PD support groups. Membership in these organizations facilitates exchange of information and members can obtains "tips" that may be useful in coping with the physical and mental disabilities associated with these disorders. Also, many local support groups offer exercise therapy which may be helpful to some patients. With the emotional support of family members and with expert medical management guided by a knowledgeable and compassionate physician, many patients with atypical parkinsonism can lead enjoyable and productive lives.
For further information, refer to the references on a particular disease. (See Table 1. Parkinsonism Plus Syndromes: Differential Diagnosis.)
CurePSP: Foundation for PSP, CBD and Related Brain Diseases
30 E. Padonia Rd., Suite 201
Timonium, MD 21093
Phone: (410) 785-7004
Toll free: (800) 457-4777
Fax: (410) 785-7009
Other Related Websites
- Multiple System Atrophy Coalition™ (formerly SDS/MSA Support Group)
- Multiple System Atrophy Trust
- Multiple System Atrophy - Medscape Reference
©2011 Joseph Jankovic, M.D.
Arai T, Ikeda K, Akiyama H, et al. Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration. Ann Neurol. 2004;55:72-9.
Brodsky H, Vuong KD, Thomas M, Jankovic J. Glabellar and palmomental reflexes in parkinsonian disorders. Neurology. 2004;63:1096-8.
Brooks DJ, Seppi K; Neuroimaging Working Group on MSA. Proposed neuroimaging criteria for the diagnosis of multiple system atrophy. Mov Disord. 2009;24:949-64.
Burn DJ. Cortical Lewy body disease. J Neurol Neurosurg Psychiatry. 2004 Feb;75(2):175-8.
Dubois B, Slachevsky A, Pillon B, et al. "Applause sign" helps to discriminate PSP from FTD and PD. Neurology. 2005;64(12):2132-3.
Fahn S, Jankovic J. Principles and Practice of Movement Disorders, Churchill Livingstone, Elsevier, Philadelphia, PA, 2007:1-652. (Accompanied by a DVD of movement disorders).
Felicio AC, Shih MC, Godeiro-Junior C, Andrade LA, Bressan RA, Ferraz HB. Molecular imaging studies in Parkinson disease: reducing diagnostic uncertainty. Neurologist. 2009;15:6-16.
Gilman S, Koeppe RA, Chervin RD, et al. REM sleep behavior disorder is related to striatal monoaminergic deficit in MSA. Neurology. 2003;61:29-34.
Glatzel M, Stoeck K, Seeger H, Luhrs T, Aguzzi A. Human prion diseases: molecular and clinical aspects. Arch Neurol. 2005;62:545-52.
Goetz CG, Leurgans S, Lang AE, Litvan I. Progression of gait, speech and swallowing deficits in progressive supranuclear palsy. Neurology. 2003;60:917-22.
Goldman JS, Farmer JM, Van Deerlin VM, et al. Frontotemporal dementia: Genetics and genetic counseling dilemmas. Neurologist. 2004;10:227-34.
Hodges JR, Davies RR, Xuereb JH, et al. Clinicopathological correlates in frontotemporal dementia. Ann Neurol. 2004;56:399-406.
Hoglinger GU, Melhem NM, Dickson DW, et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat Gene. 2011;43:699-705.
Kagi G, Bhatia KP, Tolosa E. The role of DAT-SPECT in movement disorders. J Neurol Neurosurg Psychiatry. 2011;81:5-12.
Iranzo A, Santamaria J, Tolosa E, et al. Long-term effect of CPAP in the treatment of nocturnal stridor in multiple system atrophy. Neurology. 2004;63:930-2.
Jankovic J, Tintner R. Dystonia and parkinsonism. Parkinsonism Relat Disord. 2001;8:109-21.
Jankovic J. Pathophysiology and clinical assessment of parkinsonian symptoms and signs. In: Pahwa R, Lyons K, Koller WC, ed.: Handbook of Parkinson's Disease, Marcel Dekker, Inc., New York, NY, 2003:71-107.
Jankovic J. Parkinsonism. In: Goldman L and Ausiello D, eds. Cecil Textbook of Medicine, 22nd edition, Harcourt Health Sciences (W.B. Saunders), Philadelphia, 2004:2306-10.
Jankovic J. Searching for a relationship between manganese, welding, and Parkinson's disease. Neurology. 2005; 64(12):2021-8.
Jankovic J, Lang AE. Movement disorders: Diagnosis and Assessment. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J, eds. Neurology in Clinical Practice, 5th Edition, Butterworth-Heinemann (Elsevier), Philadelphia, PA, Chapter 23, 2008:293-325.
Jankovic J, Shannon KM. Movement disorders. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J, eds. Neurology in Clinical Practice, 5th Edition, Butterworth-Heinemann (Elsevier), Philadelphia, PA, Chapter 75, 2008:2081-122.
Jankovic J. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79:368-76.
Josephs KA, Dickson DW. Diagnostic accuracy of progressive supranuclear palsy in the Society for Progressive Supranuclear Palsy brain bank. Mov Disord. 2003;18:1018-26.
Liang TW, Forman MS, Duda JE, McCluskey L, Trojanowski JQ, Siderowf A. Multiple pathologies in a patient with a progressive neurodegenerative syndrome. J Neurol Neurosurg Psychiatry. 2005;76:252-5.
Lipp A, Sandroni P, Ahlskog JE, et al. Prospective differentiation of multiple system atrophy from Parkinson disease, with and without autonomic failure. Arch Neurol. 2009;66:742-50.
Litvan I, Bhatia KP, Burn DJ, et al. SIC Task Force appraisal of clinical diagnostic criteria for parkinsonian disorders. Mov Disord. 2003;18:467-86.
Mahapatra RK, Edwards MJ, Schott JM, Bhatia KP. Corticobasal degeneration. Lancet Neurol. 2004;3:736-43.
McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies. Third report of the DLB consortium. Neurology. 2005;64:1863-72.
Munoz DG, Dickson DW, Bergeron C, et al. The neuropathology and biochemistry of frontotemporal dementia. Ann Neurol. 2003;54:S24-S28.
Murman DL, Kuo SB, Powell MC, Colenda CC. The impact of parkinsonism on costs of care in patients with AD and dementia with Lewy bodies. Neurology. 2003;61:944-9.
Nath U, Ben-Shlomo Y, Thomson RG, Lees AJ, Burn DJ. Clinical features and natural history of progressive supranuclear palsy: A clinical cohort study. Neurology. 2003;60:910-.6.
Osaki Y, Ben-Shlomo Y, Lees AJ, et al. Accuracy of clinical diagnosis of progressive supranuclear palsy. Mov Disord. 2004;19:181-9.
Ozawa T, Paviour D, Quinn NP, et al. The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations. Brain. 2004;127:2657-71.
Racette BA, Esper GJ, Antenor J, et al. Pathophysiology of parkinsonism due to hydrocephalus. J Neurol Neurosurg Psychiatry. 2004;75:1617-9.
Seppi K, Schocke MF, Esterhammer R, et al. Diffusion-weighted imaging discriminates progressive supranuclear palsy from PD, but not from the Parkinson variant of multiple system atrophy. Neurology. 2003;60:922-7.
Seppi K, Schocke MF, Donnemiller E, et al Comparison of diffusion-weighted imaging and [123I]IBZM-SPECT for the differentiation of patients with the Parkinson variant of multiple system atrophy from those with Parkinson's disease. Mov Disord. 2004;19:1438-45.
Seppi K, Yekhlef F, Diem A, et al. Progression of parkinsonism in multiple system atrophy. J Neurol. 2005;252:91-6.
Sleegers K, Brouwers N, Van Damme P, et al. Serum biomarker for progranulin-associated frontotemporal lobar degeneration. Ann Neurol. 2009;65:603-9.
Soliveri P, Piacentini S, Girotti F. Limb apraxia in corticobasal degeneration and progressive supranuclear palsy. Neurology. 2005;64:448-53.
Thaisetthawatkul P, Boeve BF, Benarroch EE, et al. Autonomic dysfunction in dementia with Lewy bodies. Neurology. 2004;62:1804-9.
Thomas M, Jankovic J. Parkinson-plus syndromes. In: Noseworthy J, editor-in-chief, Neurological Therapeutics: Principles and Practice, Martin Dunitz LTD, London, UK, 2003:2483-504.
Thomas M, Jankovic J. Neurodegeneration and iron storage in the brain. Curr Opin Neurol. 2004;17:437-42.
Thomas M, Jankovic J. Clinical diagnosis of vascular parkinsonism and non-degenerative atypical parkinsonian disorders. In: Litvan I, 1st ed. Atypical Parkinsonian Disorders: Clinical and Research Aspects (Current Clinical Neurology), Humana Press, Totowa, New Jersey, 2005.
Thomas M, Jankovic J. Clinical diagnosis of vascular parkinsonism and nondegenerative atypical parkinsonian disorders. In: Litvan I, ed. Atypical Parkinsonism, Humana Press, Totowa, New Jersey, 2008:393-408.
Thomas M, Hayflick SJ, Jankovic J. Clinical heterogeneity of neurodegeneration with iron accumulation–1 (Hallervorden-Spatz Syndrome) and Pantothenate Kinase Associated Neurodegeneration (PKAN). Mov Disord. 2004;19:36-42.
Vanacore N, Bonifati V, Fabbrini G, et al. Case-control study of multiple system atrophy. Mov Disord. 2005;20:158-63.
Wakabayashi K, Takahashi H. Pathological heterogeneity in progressive supranuclear palsy and corticobasal degeneration. Neuropathology. 2004;24:79-86.
Wenning GK, Colosimo C, Geser F, Poewe W. Multiple system atrophy. Lancet Neurol. 2004;3:93-103.
Wenning GK, Litvan I, Tolosa E. Milestones in atypical and secondary Parkinsonisms. Mov Disord. 2011: 26:1083-95.
Williams DR, Lees AJ. Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol. 2009;8:270-9.
Zijlmans JC, Katzenschlager R, Daniel SE, Lees AJ. The L-dopa response in vascular parkinsonism. J Neurol Neurosurg Psychiatry. 2004;75:545-7.
Zijlmans JC, Daniel SE, Hughes AJ, Revesz T, Lees AJ. Clinicopathological investigation of vascular parkinsonism, including clinical criteria for diagnosis. Mov Disord. 2004;19:630-40.
Zwergal A, la Fougere C, Lorenzl S, et al. Postural imbalance and falls in PSP correlate with functional pathology of the thalamus. Neurology. 2011;77:101-9.