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2002 First Paper
Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder categorized as a form of parkinsonism. First described in 1964 by three Canadian neurologists, PSP is sometimes referred to as Steele-Richardson-Olszewski Syndrome, or Nuchal Dystonia Dementia Syndrome (1). Progressive damage to multiple brain cells associated with deterioration of the myelin sheath that speeds up nerve impulse conduction, as well as destruction of the entire nerve (2), result in severe and irreversible problems controlling balance, eye movement, breathing, and voluntary muscle movement (3). The actor Dudley Moore has been diagnosed with PSP and presently works to improve awareness and treatment of this enigmatic disease.
Although PSP is frequently misdiagnosed as Parkinson's, the disorder progresses much more quickly, maintaining very unique and exclusive manifestations. Individuals suffering from PSP present clinically with akinetic rigid syndrome, gait ataxia, and supranuclear vertical-gaze palsy (4). Akinesia refers to the loss of control of voluntary muscle movements. This is expressed in loss of balance while walking and recurrent falls. A permanent "Mona Lisa" stare and wide-eyed expression is often described, in addition to guttural, slurred speech and swallowing difficulties (5). These facial distortions result from nerve damage controlling the facial muscles. All PSP individuals suffer from some degree of vertical-gaze palsy, in which the ability to move the eyes up-and-down is impaired (4). Muscles in the back of the neck and spine are usually severely affected, resulting in a retro-collis posture; the individual appears to perpetually look up toward the ceiling. Rigidity in the limbs is also observed, although to a lesser degree. If rigidity does exist here, it is equal on both sides of the body. In Parkinson's disease, rigidity is more prominent and pronounced in the limbs, favoring one side more that the other (6). None of the tremors characteristic of Parkinson's are observed in PSP. Personality changes and dementia are also noted, particularly later in the development of the disease.
PSP affects the brainstem, basal ganglia, and cerebellum. The brainstem controls involuntary movements such as breathing and heart rate. Three divisions of the brainstem have been delineated: the medulla oblongata, the pons, and the midbrain. In PSP, all three sections are affected. The pons controls facial nerves and eye muscles, while the midbrain is the visual center of the brain (3). The medulla (sometimes referred to as the "bulb") maintains speech and swallowing abilities. Paralysis here results in impairment of these functions. Although PSP does not involve true bulbar-palsy, the nerve cells and fibers originating from the bulb are affected, resulting in harsh, grating speech and swallowing complications. Emotional instability is also associated with this pseudobulbar-palsy (6). The basal ganglia, congregations of nerve cells located deep within the brain involved with control of emotion and voluntary movement, are additionally affected. The basal ganglia are important in cortical-subcortical loops for information processing, access to memory, and language (4). Damage here is responsible for the muscle stiffness, or spasticity, experienced by PSP individuals as well as being involved with the numerous cognitive difficulties experienced in concert with the physical complications. The cerebellum, controlling balance and muscle coordination, is likewise affected (3).
Groups of cells called "nuclei" in the brainstem control vision. In PSP, the mechanisms controlling these nuclei (not the nuclei themselves) are damaged, resulting in difficulty with voluntary eye movement (3). The mechanisms include eye movement centers superior to the nuclei in the brainstem. These locations are progressively impaired by prolonged attack, and adjacent areas are also targeted (6). PSP is initially associated with difficultly in moving the eyes downward. However, left-to-right eye movement is additionally limited as the disease progresses. Reflex eye movements remain normal until late in the course of the disease. Blinking may be reduced from the normal 20-30 per minute rate to a 3-5 per minute rate (3). Sometimes blepharo-spasm, or uncontrolled eye-lid tightening, is experienced. It becomes very difficult for the PSP individual to maintain eye contact during conversation at this stage. Individuals with PSP appear to maintain markedly decreased levels of the neurotransmitters dopamine, and dopamine's main metabolite homovanillic acid, in the striatum. The dopamine receptors also tend to degenerate; one reason why Sinemet treatment proves to be minimally effective (6).
Post-mortem examination of the PSP brain reveals moderate to marked atrophy of the brainstem and less marked atrophy of the cerebellum. Gliosis, replacement of normal nerve cells with glial cells, is also appreciated. The dying nerve cells in the brainstem develop entangled, partially crystallized fibers containing tau protein. This type of modification is referred to as neurofibrillary degeneration (6). Neurofibrillary tangles (NFT) are found to be more dense in the supragranular layers than in the infragranular layers. The opposite pattern is observed in Alzheimer's disease. NFT are also found in many of the subcortical nuclei and in the primary motor regions of the isocortex (7).
PSP is estimated to affect ~1.1/100,000 people, in addition to ~5-6 percent of those individuals initially diagnosed with Parkinson's disease. Men are slightly more affected than women (8). Median age of onset is 64 years, with a range of approximately 50-77 years (9). Scientists are unsure of the causes of PSP. There is little evidence that this is an inheritable disease, although pedigrees have been reported. No population or ethnic group is particularly favored. It has been suggested that an unknown virus implants itself into the body and causes presentation of PSP symptoms several years later, although this theory has not been confirmed. More recent genetic studies indicate that an autosomal recessive polymorphism of the tau protein gene may be responsible for some cases of PSP. Metabolic studies are investigating oxidative stress as a possible cause (8). It has been suggested that free radicals, unstable molecules constantly produced by cells in the body, may cause the cellular damage associated with PSP (4). At present, no tests for diagnosing PSP are available. As in Parkinson's disease, blood tests, CT, and MRI scans are usually normal (8).
Many of the drug therapies proven successful in treating Parkinson's disease have shown transient effectiveness in PSP individual. The common dopaminergic drug, levapoda (Sinemet), is sometimes prescribed for PSP to decrease spasicity and ease involuntary movement. The anticholinergic, trihexyphenidyl (Artane), has restored some function to the neurotransmitters. Also, anti-depressants have shown effective in speech improvement, walking, and inappropriate emotional responses (3). The drug "seligiline" has been prescribed in both PSP and Parkinson's disease, although the true effectiveness of this treatment is not presently known. Some evidence suggests that seligiline may inhibit apoptosis, or programmed cell death. Also, calcium channel blockers may be used for their better-understood prevention of apoptosis. In some degenerative neurological disorders, vitamin E has proven slightly helpful in reducing the rate of progression, and may likewise assist in managing PSP. Fetal brain cell implantation and pallidomy, however effective in Parkinson's, has not produced positive results in PSP (8).
Non-drug therapies are equally important in dealing with PSP. Speech therapy reduces some speech and swallowing difficulties. These processes are more affected as the disease progresses, resulting in choking and implantation of small food particles in the lungs, referred to as aspiration pneumonia. Difficulties with eating also could lead to problematic weight loss (3). A gastrotomy is a minimally invasive procedure entailing the placement of a feeding tube through the abdominal wall and into the stomach. This option is usually necessary later in the progression of the disease when swallowing abilities are most encumbered. Weighted walkers are used to prevent PSP individuals from falling backward. Bifocals or prisms occasionally improve the effects of the supranuclear vertical-gaze palsy. Ointments and eye drops are given to soothe dry eyes from infrequent blinking (1).
No one dies from PSP itself. However, repeated contraction of pneumonia from choking on secretions and food products is presently the number one cause of death. Starvation related to difficulty in swallowing is also prevalent. After the first seven years of progression, balance and rigidity problems generally make it impossible for the PSP individual to walk. Although death usually occurs about ten years after the initial symptoms present, if good general health and nutrition are maintained one may survive several years longer (3).
Research efforts by several medical institutions, including the National Institute for Neurological Disorders and Stroke (NINDS) and Johns Hopkins University, are being undertaken to more clearly understand the diagnosis and treatment of PSP (1). Some corollaries may be made with Parkinson's disease and other degenerative neurological disorders, but the significant implications of PSP remain unknown. What I find most curious about PSP is the rapid and extensive nature of the paralysis, coupled with a marginally affected intellect. I can only imagine how torturous it must be to experience such limited ability for movement and expression, yet maintain a high thinking capacity. Hope remains in present medical research and the capabilities of modern technology to generate a treatment for those suffering from PSP.
1)Healthtouch Health Information, Excellent summary of PSP
3)The Gale Encyclopedia of Medicine, A very good summary of the symptoms, treatments, and prognosis for PSP
4)Case Refernces of the Massachusetts General Hospital , Case study of a gentleman suffering from PSP.
5)The Progressive Supranuclear Palsy [PSP Europe] Associatiob
6)Society for Progressive Supranuclear Palsy, Comparison of Parkinson's disease and PSP.
7)Progressive Supranuclear Palsy, A good source for neuropathological and immunohistochemical studies on PSP.
8)Progressive Supranuclear Palsy (NWU), From the Northwestern University Medical School.
9)Progressive Supranuclear Palsy (Steele-Richardson-Olszewski Syndrome), From the Medical College of Wisconsin.
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