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Progressive Supranuclear Palsy

PSP-Parkinsonism

Progressive supranuclear palsy (PSP) is a degenerative brain disorder that mimics Parkinson disease. However, it is a more severe disorder that leads to difficulty with ambulation, balance, visual problems, severe dementia, alterations in behavior, difficulty with speech and swallowing. It occurs after the 5th decade of life and is underdiagnosed.


Presentation

PSP presents gradually and is insidious. The age of presentation is usually between 55-70 years. Typical symptoms may include the following key features

  • The early symptoms of PSP may be dysphagia and dysarthria.
  • Progressive difficulty with walking (gait) and balance resulting in frequent falls. Postural instability is a key feature of the disorder. Patients often have slow unsteady gait. The bradykinesia is usually symmetrical and the rigidity is axial. Both these symptoms fail to respond to levodopa. Motor exam will reveal difficulty that often involves the axial rather than limb muscles. In the axial musculature, the neck muscles are more affected than trunk muscles. Motor symptoms are slow and upper body appears stiff and rigid. Rigidity with abnormal posturing of the neck (retrocollis).
  • Visual symptoms are obvious and characteristic for PSP. There is progressive loss of voluntary control of eye movements. Earlier findings are slowing of vertical saccades, blepharospasm, vertical gaze palsy, difficulty with eye-opening and closing, reduced blinking, constantly raised eyebrows facial expression and a fixed stare. The gaze abnormalities can make it difficult to have eye contact and scan or read a page. Other ocular symptoms that also tend to occur in the early phase include blurred vision, diplopia, light sensitivity and burning eyes.
  • Difficulty eating because of inability to look down at food.
  • Conversations are impossible because of delay in responses and pronunciations.
  • Eventually patients are unable to swallow and even eating, motions become uncoordinated.
  • Aspiration pneumonia is common due to difficulty swallowing, coughing and drooling.
  • Cognitive and behaviour problems due to frontal lobe involvement. There is progressive decline in concentration, concrete thinking, difficulty planning, impaired reasoning and shifting to another task.
  • Behaviours changes include lack of motivation, apathy, withdrawal, perseveration and impulsivity. Depression is common.
  • Unlike Parkinson disease, patients with PSP can experience falls early in disease. This is due to stiff upper body posture and tendency to fall backwards.
  • Dysarthria (slow or slurred speech) is an early feature and may be mixed with a combination of hypokinetic, spastic and ataxic features. Pyramidal signs occur in about 30% of patients
  • Because of the development of frontal lobe dysfunction, the occasional individual with PSP may suddenly jump on his or her feet from a sitting position without thinking only to fall backwards because of postural instability. This is known as the “rocket sign”.[8]

Differential diagnosis of PSP:


Differentiating PSP from Parkinson disease

  • Sometimes it can be very difficult to differentiate PSP from Parkinson disease during the early stages of the disease. Some PSP patients may not develop postural instability and ophthalmoplegia early in the course of the disease.
  • In general, features of PD are asymmetric whereas this is not so with PSP. In addition, treatment with L-dopa will only have a limited response in patients with PSP.
  • Dysphagia occurs much early in PSP whereas in PD it is usually seen in advanced cases and is delayed.
  • The progression of PSP is much faster clinically
  • PD patients generally do not have dementia, which is a common feature of PSP
Falling
  • The Xbox Kinect intervention may have contributed to a decline in falls and maintenance of scores on the BBS, TUG and 10 Meter Walk Tests above fall risk values.[ncbi.nlm.nih.gov]
  • Falls (self-reported weekly over the 10-year period of the study by the client and his wife) decreased from 1.9 falls per month in year 1 to 0.3 falls per month in year 10. Balance, walking endurance, and general mobility declined slightly.[ncbi.nlm.nih.gov]
  • Of 198 clinical parameters, we hypothesized 38 to be correlated with an increasing risk of falls. These 38 parameters were analyzed via univariate regression analysis to determine the strength of their association with fall frequency.[ncbi.nlm.nih.gov]
  • Patients with early falls and cognitive decline were at high risk of early development of pneumonia.[ncbi.nlm.nih.gov]
  • DISCUSSION: Difficulty perceiving backward tilt of the surface or body may account for backward falls and postural impairments in patients with PSP.[ncbi.nlm.nih.gov]
Choking
  • As PSP progresses, patients are at greater risk for complications, such as choking, pneumonia, head injury and fractures caused by falls. The most common cause of death is pneumonia.[ucsfhealth.org]
  • Problems swallowing, which can lead to choking or inhaling food or liquid into your airway (aspiration). Aspiration can develop into pneumonia, the most common cause of death in people with progressive supranuclear palsy.[mayoclinic.org]
  • Complications that result from worsening symptoms, such as pneumonia (from breathing in food particles while choking during eating), can be life-threatening.[stanfordhealthcare.org]
  • Dysphagia Difficulty swallowing, including gagging or choking. This can lead to aspiration pneumonia. Dysarthria Slurred or slowed speech due to difficulty moving the muscles controlling the lips, tongue and jaw.[theaftd.org]
  • An example is pneumonia from breathing in food particles while choking during eating. What causes progressive supranuclear palsy? Experts basically understand how PSP happens. But they don't understand why it happens.[hopkinsmedicine.org]
Gagging
  • Dysphagia Difficulty swallowing, including gagging or choking. This can lead to aspiration pneumonia. Dysarthria Slurred or slowed speech due to difficulty moving the muscles controlling the lips, tongue and jaw.[theaftd.org]
  • He then developed a severe pseudo‐bulbar palsy, with dysarthria, dysphagia, brisk palmo‐mental reflex, jaw jerks and an absent gag reflex.[doi.org]
Vertical Gaze Palsy
  • Supranuclear vertical gaze palsy, gait instability and the absence of delusions distinguished PSP from diffuse Lewy body disease. Supranuclear vertical gaze palsy and increased age at symptom-onset distinguished PSP from MSA.[ncbi.nlm.nih.gov]
  • On examination supranuclear vertical gaze palsy with slow horizontal saccades, axial rigidity and bradykinesia were present. He had a slow gait with lack of associated movements and tendency to fall backwards.[doi.org]
  • We describe a woman with a 13-year history of postural instability, vertical gaze palsy and dopa-responsive parkinsonism - a clinical profile that corresponds to progressive supranuclear palsy (PSP) and Parkinson's disease (PD).[ncbi.nlm.nih.gov]
  • The classic symptoms of PSP (postural instability, supranuclear vertical gaze palsy and dementia) overlap with the clinical triad of Wernicke's encephalopathy (cognitive impairment, gait problems and ocular abnormality).[ncbi.nlm.nih.gov]
Diplopia
  • We report the case of a 75-year-old ex-professional boxer who developed diplopia and eye movement abnormalities in his 60's followed by memory impairment, low mood and recurrent falls.[ncbi.nlm.nih.gov]
  • Common symptoms at disease onset include postural instability and falls, dysarthria, bradykinesia and visual disturbances such as diplopia, blurred vision, burning eyes, and light sensitivity.[patient.info]
  • Because the eyes have trouble coming together to focus at short distances, the patient may complain of diplopia (double vision) when reading.[en.wikipedia.org]
  • Other ocular symptoms that also tend to occur in the early phase include blurred vision, diplopia, light sensitivity and burning eyes. Difficulty eating because of inability to look down at food.[symptoma.com]
  • This is followed by visual disorders often ranging from diplopia, blurred vision, light sensitivity, inability to look up/down and burning sensations, slurring of speech and lastly cognitive slowness, memory issues, changes in personality or mood [8][physio-pedia.com]
Infrequent Blinking
  • Patients have trouble shifting their gaze downward and can have trouble controlling their eyelids, leading to involuntary closing of the eyes, prolonged or infrequent blinking, or difficulty opening the eyes.[ucsfhealth.org]
  • In addition, difficulty opening and closing the eyelids, infrequent blinking, and retraction of the eyelids can also be seen. All of these abnormalities with the eyes can lead to blurry vision, double vision, light sensitivity and a staring gaze.[physio-pedia.com]
  • blinking (and dry eyes), decrease in speech (even mutism), urinary incontinence, etc.[brainsupportnetwork.org]
Strabismus
  • Amblyopia and Strabismus Most studies of fixational eye movements in ophthalmic disease to date have centered on amblyopia and strabismus.[doi.org]
  • 2016 2017 2018 2019 Non-Billable/Non-Specific Code Type 2 Excludes internal ophthalmoplegia ( H52.51- ) internuclear ophthalmoplegia ( H51.2- ) progressive supranuclear ophthalmoplegia ( G23.1 ) Ophthalmoplegia - see also Strabismus, paralytic supranuclear[icd10data.com]
Emotional Lability
  • lability and freezing of gait.[pacificneuroscienceinstitute.org]
  • Dysphagia, dysarthria with emotional lability (pseudobulbar palsy), depression, and disordered sleep are common. Resting tremor may develop. Dementia eventually occurs. Many patients become incapacitated within about 5 yr and die within about 10 yr.[msdmanuals.com]
  • Iannaccone S, Ferini-Strambi L: Pharmacologic treatment of emotional lability. Clin Neuropharmacol 1996, 19 : 532–535. PubMed Google Scholar 17.[doi.org]
Bradykinesia
  • UPDRS total motor scores and subscores for bradykinesia and axial motor deficits did not correlate with R2* values of the five brain regions.[ncbi.nlm.nih.gov]
  • Progressive Supranuclear Palsy (PSP) is a rare geriatric pathology, from the abnormal deposition of the tau protein, combining the motor tremor and bradykinesia of Parkinson's disease with the cognitive defects of Alzheimer's disease.[ncbi.nlm.nih.gov]
  • PSP-corticobasal syndrome (PSP-CBS) is characterized by progressive, asymmetric dyspraxia, limb rigidity, bradykinesia and progressive postural instability.[orpha.net]
  • Bradykinesia was present in 98% of cases, rigidity in 98% and falls in 94%.[doi.org]
Dystonia
  • Lidocaine should be considered in pain relief of dystonia to improve quality of life.[ncbi.nlm.nih.gov]
  • (xv) Extra axial-dystonia: the presence of dystonia in any body part apart from trunk and neck. (xvi) Pyramidal signs: pathologically brisk reflexes and/or extensor plantar response(s).[doi.org]
  • Botulinum Toxin Benefits Many PSP Patients With Dystonia. Medscape Medical News. Available at . Accessed: July 7, 2013.[emedicine.medscape.com]
Dysarthria
  • KEYWORDS: Acoustic analysis; Atypical Parkinsonian syndromes; Dysarthria; Parkinson’s disease; Perceptual assessment; Speech disorders; Voice onset time[ncbi.nlm.nih.gov]
  • Examination shortly before death revealed hypomimia, dysarthria, vertical supranuclear gaze palsy and impaired postural reflexes.[ncbi.nlm.nih.gov]
  • Introduction In this report we are describing a progressive brain disease featured by supranuclear ophthalmoplegia affecting chiefly vertical gaze, pseudobulbar palsy, dysarthria, dystonic rigidity of the neck and upper trunk, and other less constant[doi.org]
  • A female patient initially exhibited dysarthria at the age of 65, followed by gait disturbance and dysphagia.[ncbi.nlm.nih.gov]
  • He was initially diagnosed as having olivopontocerebellar atrophy because dysarthria and ataxia gradually developed, and head CT scan showed apparent atrophy of the cerebellum and brainstem and dilatation of the fourth ventricle.[ncbi.nlm.nih.gov]
Ataxia
  • His principal symptom was cerebellar ataxia for several years.[ncbi.nlm.nih.gov]
  • We report two cases with FTLD-TDP and PSP in comorbidity: a patient with amnestic dementia developing frontal lobe dementia, Parkinsonism and supranuclear gaze palsy and a patient with cerebellar ataxia and nystagmus developing akinesia, rigidity, and[ncbi.nlm.nih.gov]
  • Some of the main symptoms of MSA, such as cerebellar ataxia and orthostatic hypotension, are not rare parts of the clinical picture of PSP. PSP can thus be mistakenly diagnosed as MSA.[ncbi.nlm.nih.gov]
  • RESULTS: In addition to typical symptoms, PSP patients can exhibit atypical symptoms including levodopa-responsive parkinsonism, pure akinesia, non-fluent aphasia, corticobasal syndrome, and predominant cerebellar ataxia.[ncbi.nlm.nih.gov]
  • The classical presentation of sporadic Creutzfeldt-Jakob disease (sCJD) is rapid progressive dementia often associated with myoclonus and ataxia followed by death in less than a year from diagnosis.[ncbi.nlm.nih.gov]
Cerebellar Ataxia
  • We report two cases with FTLD-TDP and PSP in comorbidity: a patient with amnestic dementia developing frontal lobe dementia, Parkinsonism and supranuclear gaze palsy and a patient with cerebellar ataxia and nystagmus developing akinesia, rigidity, and[ncbi.nlm.nih.gov]
  • Some of the main symptoms of MSA, such as cerebellar ataxia and orthostatic hypotension, are not rare parts of the clinical picture of PSP. PSP can thus be mistakenly diagnosed as MSA.[ncbi.nlm.nih.gov]
  • RESULTS: In addition to typical symptoms, PSP patients can exhibit atypical symptoms including levodopa-responsive parkinsonism, pure akinesia, non-fluent aphasia, corticobasal syndrome, and predominant cerebellar ataxia.[ncbi.nlm.nih.gov]
  • His principal symptom was cerebellar ataxia for several years.[ncbi.nlm.nih.gov]
  • Dickson, Cerebellar ataxia in progressive supranuclear palsy: An autopsy study of PSP‐C, Movement Disorders, 31, 5, (653-662), (2016). Elan D. Louis, Rachel Babij, Karen Ma, Etty Cortés and Jean-Paul G.[oadoi.org]

Workup

If PSP is suspected the following investigations are necessary:

  • Electro oculographic recordings may be useful in differentiating PSP from other related disorders. Individuals with PSP have horizontal hypometric voluntary saccades while individuals with corticobasal degeneration have the opposite findings. Parkinsonian patients tend to have saccades of normal amplitude and latency.
  • MRI will show thinning of the quadrigeminal plate and atrophy of the midbrain and area around the 3rd ventricle, supporting a diagnosis of PSP.
  • MRI can also help exclude other disorders such as hydrocephalus, multi infarct dementia, and tumors.
  • Other research tools used to support early diagnosis of PSP include polysommnography, evoked potentials and PET scan.


Diagnostic criteria
Criteria have been established to help improve diagnostic accuracy of PSP and include the following [9]:

Supportive features to help diagnosis include:

Neurofibrillary Tangle
  • PSP is defined neuropathologically by the accumulation of neurofibrillary tangles in the subthalamic nucleus, pallidum, red nucleus, substantia nigra, striatum, pontine tegmentum, oculomotor nucleus, medulla and dentate nucleus.[ncbi.nlm.nih.gov]
  • Alzheimer's disease pathology was advanced with PSP-like neurofibrillary tangles distribution, and Lewy bodies were abundant in limbic lobe, while scarce in lower brainstem nuclei. Tuft-shaped astrocytes were not apparent.[ncbi.nlm.nih.gov]
  • In addition, neurofibrillary tangles composed of mixed 3-repeat and 4-repeat tau and astrocytic tangles in a distribution highly suggestive of chronic traumatic encephalopathy were observed together with limbic TDP-43 pathology.[ncbi.nlm.nih.gov]
  • Pathological features were the widespread occurrence of 4R tau-positive structures including pre-tangles, neurofibrillary tangles, astrocytic plaques, tufted astrocytes, coiled bodies and argyrophilic threads.[ncbi.nlm.nih.gov]
  • Neuropathologically, PSP is defined by the accumulation of neurofibrillary tangles.[ncbi.nlm.nih.gov]
White Matter Lesions
  • There was diffuse leptomeningeal enhancement and hyperintense white matter lesions. The final diagnosis made by image-guided biopsy showed rheumatoid pachymeningitis.[ncbi.nlm.nih.gov]

Treatment

A Neurologist consultation is vital when evaluating a patient with PSP. The disorder is not easy to diagnose and can often be mistaken for Parkinson disease. The history should be obtained from the family or primary caregiver as it may reveal changes in behavior, daily functional activity and mobility.
So far there is no effective treatment of PSP [10].  All treatments are supportive. Even though dopaminergic agents have been tried, they only work in mild cases and the symptom relief is short-lived. Only a few patients see benefit from these agents. Even though there is significant loss of cholinergic neurons in the brain of PSP patients, administration of cholinergic agents like physostigmine has not been helpful.
Other anecdotal reports indicate slight improvement after treatment with methysergide, trazodone, amitriptyline and idazoxan. However, the benefits are often short-lived and inconsistent.
Botulinum toxin has been used to treat levator inhibition and blepharospasm but the success rates are low. To prevent exposure keratopathy, artificial tears are recommended. In patients who have depression, have emotional apathy or pseudo bulbar crying episodes, antidepressants may help.
Supportive therapies include use of ambulatory devices like a wheelchair, communication aids and walker. Refer to occupation and physical therapies to help with posture and daily living activities. Speech therapist may help some patients with difficulty in swallowing.

Prognosis

PSP is progressive disorder without a cure. Eventually all patients become wheelchair bound and many require a feeding tube. The median survival time from symptom onset is about 5 years. Individuals who fall during the first year, have early dysphagia and incontinence with negative prognostic signs. In most cases aspiration pneumonia leads to death. The quality of life is very poor and the disorder can create stress in the family or caregiver.

Etiology

The cause of PSP is not known and it is thought to be a sporadic disorder. Very few familial cases have been reported but the mode of inheritance is not well understood. It is believed that the disorder has an autosomal dominant inheritance with reduced penetrance [5].
The role of viruses and toxins as a cause is pure speculative since there is no study that has even shown such a link. Currently there are studies indicating that perhaps genes leading to formation of neurofibrillary tangles may play an important role [6][7].

Epidemiology

PSP tends to occur after the 5th decade of life. Based on small series, the annual incidence of PSP is about 2- 5.3 new cases per 100,000 people every year. It is believed that these numbers are underestimated because many healthcare workers either have not heard about the disorder or fail to make the diagnosis. It is more likely that most of the patients are not diagnosed from the disorder and probably die from an unrelated disorder that is present at the same time. Review of the UK Parkinson Disease Society Brain Bank revealed that nearly 6% of patients diagnosed with Parkinson disease were found to have PSP at autopsy. The incidence of PSP is known to increase with age and overall the disorder affects more males than females.

Sex distribution
Age distribution

Pathophysiology

Unlike Alzheimer dementia, PSP is not associated with amyloid plaques in the brain but is associated with abnormal accumulation of tau protein. Some experts have classified PSP as a Pick complex disorder. The major neurotransmitter subsystems involved in PSP are the GABAergic, dopaminergic nigrostriatal pathway, and cholinoceptive striatal neurons including the cholinergic brainstem and basal forebrain nuclei.

At autopsy the chief macroscopic abnormality seen in the brain is the significant loss of pigment in the substantia nigra and locus coerulus which are often shrunken and discolored. There is also significant degeneration of cholinergic nucleic and loss of choline acetyltransferase activity in many parts of the brain.

Degeneration may be seen in the subthalamus, substantia nigra and pallidum. There is also widespread distribution of neurofibrillary tangles in the hippocampus, subthalamus, putamen caudate, frontal cortex, red nucleus, dentate and inferior olive regions. The National Institute of Neurological Disorders and Stroke (NINDS) criteria for PSP requires high density of neurofibrillary tangles and neuropil threads in at least three of the following anatomical sites: subthalamic nuclei, pallidum, pons or substantia nigra or pons, mild to moderate density in at least three of the following sites: medulla, striatum, dentate nucleus and oculomotor complex.

Prevention

Because the cause of PSP is not known prevention is not possible. However, it is important that healthcare providers understand the clinical presentation of PSP so that an early diagnosis can be made. The  disorder is very disabling and of enormous stress to the caregiver, so an early diagnosis can mean prompt referral to physical, as well as speech and occupational therapy [11].

Summary

Progressive supranuclear palsy (PSP) also known as the Steel Richardson Olzewski syndrome is a neurodegenerative disorder very similar to Parkinson disease. The disorder occurs after the 5th decade of life and is progressive. Since the description of the disorder nearly 50 years ago, many small series have reported on the disorder. It is under-diagnosed not only by general physicians but also by neurologists. The cause of PSP is not known. Exposure to toxins and viruses has been proposed in the etiology of PSP without any concrete evidence. The features of PSP resemble those of Parkinson's disease and the two diseases are often confused. Despite certain common features with Parkinson's disease, PSP is a much aggressive disorder with many neuropsychiatric and motor abnormalities that it often leads to rapid decline and eventually to death.[1][2][3][4]

Patient Information

Progressive supranuclear palsy (PSP), also known as Steele Richardson Olzewski syndrome, is a degenerative motor disorder very similar to Parkinson disease.
Initially most patients have difficulty with visual difficulties, walking and balance but as the disorder advances, cognitive and behaviour changes may also develop. Late in the course of PSP, walking and eye movements become very difficult . The cognitive impairment progresses to full blown dementia
Use of ambulatory aids may help during the early phase of the disease but the risk of fall is always present. Because of difficulty with chewing and swallowing, most patients can only take in liquid or pureed foods. Physical and occupational therapy may help with mobility in the early stages. When swallowing difficulty is severe, patients should have a feeding tube placed in the stomach. The risk of aspiration is always present.
As family members and caregivers of patients with PSP may develop feelings of anger, frustration and guilt, it is important for them to seek support for these difficulties.

References

Article

  1. Stamelou M, Hoeglinger GU. Atypical parkinsonism: an update. Curr Opin Neurol. 2013 Aug;26(4):401-5.
  2. Respondek G, Stamelou M, Kurz C, Ferguson LW, Rajput A, Chiu WZ, van Swieten JC, Troakes C, Al Sarraj S, Gelpi E, Gaig C, Tolosa E, Oertel WH, Giese A, Roeber S, Arzberger T, Wagenpfeil S, Höglinger GU; Movement Disorder Society-endorsed PSP Study Group. The phenotypic spectrum of progressive supranuclear palsy: a retrospective multicenter study of 100 definite cases. Mov Disord. 2014 Dec;29(14):1758-66.
  3. Golbe LI. Progressive supranuclear palsy. Semin Neurol. 2014 Apr;34(2):151-9.
  4. Owolabi L Progressive supranuclear palsy misdiagnosed as Parkinson's disease: a case report and review of literature. Ann Med Health Sci Res. 2013 Nov;3(Suppl 1):S44-7.
  5. Fujioka S, Van Gerpen JA, Uitti RJ, Dickson DW, Wszolek ZK. Familial progressive supranuclear palsy: a literature review. Neurodegener Dis. 2014;13(2-3):180-2.
  6. Josephs KA. Key emerging issues in progressive supranuclear palsy and corticobasal degeneration. J Neurol. 2015 Mar;262(3):783-8.
  7. Park HK, Chung SJ. New perspective on parkinsonism in frontotemporal lobar degeneration. J Mov Disord. 2013 May;6(1):1-8.
  8. Burrell JR, Hodges JR, Rowe JB. Cognition in corticobasal syndrome and progressive supranuclear palsy: a review. Mov Disord. 2014 Apr 15;29(5):684-93.
  9. Rohan Z, Matej R. Current concepts in the classification and diagnosis of frontotemporal lobar degenerations: a practical approach. Arch Pathol Lab Med. 2014 Jan;138(1):132-8.
  10. Tsai RM, Boxer AL Clinical trials: past, current, and future for atypical Parkinsonian syndromes. Semin Neurol. 2014 Apr;34(2):225-34.
  11. Colosimo C, Bak TH, Bologna M, Berardelli A. Fifty years of progressive supranuclear palsy.J Neurol Neurosurg Psychiatry. 2014    Aug;85(8):938-44.

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Last updated: 2019-07-11 20:13