Progressive Supranuclear Palsy (PSP)
A Rare and Terrible Disease
Dr. Mary Thomas
“This article is dedicated to late Dr. V. J. Thomas, Past President of QPMPA, Kannur Branch,
who passed away on 25th Nov. 2013, affected with Progressive Supranuclear Palsy (PSP)."
General Features —
PSP is a degenerative disease of the brain, more commonly affecting males in their early 60s. It is a Parkinsonism allied disease and no treatment yet discovered in any part of the world. PSP is not recorded in medical books before 1960s. Out of the world population only 0.006 per centage have been affected by PSP. Many of the features of it resemble those of Parkinson’s disease. But, only less than one percent of patients who exhibit features of Parkinsonism are diagnosed to have PSP.
Definite etiological factors are not known. Certain chemicals in the atmosphere and toxins in the food are suspected to cause PSP. Certain occupational factors and lifestyles such as sedentary life found to cause more PSP prevalence. This disease found to be more affected in the inhabitants of a small island namely Guadeloupe in Caribbean Islands and they usually eat two types of fruits, namely, Sweetsop and Soursop. Toxins in those fruits proved to develop a disease similar to PSP in experimental rats. Family history or inheritance not yet proved.
Not definitely known, but certain clues are available. Because of reasons not yet detected, aggregates of cells in the brainstem get cumulatively destroyed following breakdown. Nerve cells in the centres of midbrain, which control movements, balance, vision, eye ball movements, speech, swallowing, behaviour, cognitive powers and personality are mostly affected. In almost all degenerative diseases of the brain the nuclei of nerve cells are affected, but in PSP the nerve cells themselves which control aggregates of nuclei are affected. Brain cells degenerated in PSP exhibit an accumulation of a normal protein namely Tau protein in abnormal quantities and in clumps called Neuro fibrillary tangles. Tau protein is considered to be internal neural skeleton, supporting the long extensions of nerve cells. It is not clear whether tau protein is defective at its production or gets damaged after production. The damage could be due to excessive attachments of phosphates or due to normal response of brain to minimize the effects of misbehaving Tau proteins by producing excess phosphates. Two types of Tau proteins available in neuro-fibrillary tangles namely Four Repeat Tau and Three Repeat Tau. In normal individuals both types found in equal quantities, but in PSP only the Four Repeat tau is mostly found. (Repeat numbers refer to number of copies of tau protein parts which binds to microtubules of the internal skeleton of brain). Now the problem may be due to excess production of Four repeat tau or too little production of Three repeat tau resulting clumps of Four repeat type in neuro-fibrillary tangles. Important cause of this misbehaviour of tau protein is considered to be some sort of genetic defect in or near the Tau protein gene in chromosome No. 17- and exact nature of this defect is not yet clear.
Two different variants of tau protein are encoded in chromosome No. 17- of PSP patients in excess compared to normal population. One of the variant genes, H1-haplo type is mainly detected in both copies of chromosome No. 17- of PSP patients, directing the brain cells to produce too much Tau protein. This tau starts to aggregate in clumps during early stages of the disease itself and is too small to detect by microscope. Later, large matured neuro-fibrillary tangles are formed as a result of cell’s attempt to convert the toxic clumps of tau protein to a harmless mass. The second variant Haplo-type tau gene’s location is detected but its relationship in brain cell loss not yet clear. Research in Alzheimer’s disease has recently found Epigenetic changes in brain cells following action of certain chemicals. These Epigenetic changes are found to be reversible, giving hope to find out some remedies to Alzheimer’s disease and thereby for PSP also.
Symptoms in early stage —
No two PSP patients have same symptoms and they vary from person to person. Early features mostly appearing are —
1. Due to loss of balance patient falls unexpectedly, often to the back.
2. Stiffness of leg muscles may cause awkward walk and stiffness of upper extremities, may result in intention tremor of mild degree.
3. Personality changes often cause irritability and loss of happiness and may progress to decreased ability to respond. Too much time would be taken for thinking and planning, and patient may find difficulty in managing things alone.
4. Following weakness of ocular muscles, eye ball movements become difficult and especially down gaze becomes limited with problem in reading and going down-stairs. Reduced ability of the eyes to converge, results in difficulty to see nearby objects.
5. Part of the brain controlling eye ball movements also controls muscles of mouth, tongue and throat, thereby causing slurring of speech, spastic speech and repetition of words or more frequently a combination of the three. Weakness or in-coordination of throat muscles would cause difficulty in swallowing.
Symptoms towards progress of the disease —
1. Problems with loss of balance get worse and falls become too frequent.
2. Problems with vision progress towards inability to eat alone, since he may see things in front of him as shadows. Inability of horizontal gaze results in loss of peripheral vision and thereby insecurity in walking and driving. Blurred vision or double vision is very common in PSP patients. Steady gaze and tracking difficulty to see near objects give the appearance of ‘stare off’ to the space un-intentionally. Reduced blinking rate leads to painful dryness of the eyes with burning, stinging, redness and watering. Blepherospasm of eye lids may cause forceful closure of the eyes. At times, mild form of apraxia may occur. Sometimes patient need to open eye lids with hands after closure. Photo sensitivity to bright light also is a common occurrence.
3. Problems with speech — Problems of communication are progressive in nature. Dysarthria develops when muscles of mouth and tongue cannot move in correct range, speed, force, strength and coordination. Rapid speech with strained voice, compulsive repetition of words and finally anarthria may be the ultimate result. Dysphonia, hoarseness of voice and monotone may occur when vocal cords get affected.
4. Problems with swallowing — Primary cause of death in PSP are pulmonary complications as a result of swallowing problems. Inability of throat muscles to develop the ‘water tight seal’ between oesophagus and trachea causes choking while swallowing and it may result in aspiration pneumonia. Difficulty of swallowing first develops to thin fluids, then to thick fluids and finally to solid food. Weakness and in-coordination of throat muscles also cause silent aspiration of saliva and regurgitated fluid from the stomach. Loss of ‘cough reflex’ in PSP patients contribute a major role in developing aspiration pneumonia. Because of the difficulty in swallowing, patient spits too frequently when possible and saliva may dribble when ability to spit is lost.
5. Stiffness of neck muscles may result in turning of head to the back and rarely to the sides.
6. Problems with urinary bladder and colon — Nerve cell clusters in the lower part of spinal cord control reflex bladder emptying and peristaltic movements in colon. Degeneration of these nerve cells results in premature urgency of urination or incontinence and slowing of peristaltic movements in the colon. As a result fluid absorption from colon would take excess time and stool becomes dry and hard resulting in constipation.
In short, over the time, PSP robes away the victim’s ability to carry out the daily activities and gets the feeling of gradually losing the skill to have a fulfilling life, as he gets deprived of mobility, work skill, social relationship and finally identity and purpose in the world.
Differential Diagnosis —
Parkinson’s disease and PSP having many symptoms in common and in early stages it is difficult to differentiate both. Main differences – Parkinson’s include –
1. Inability of eye balls movements especially the ‘down gaze’ in PSP patients.
2. Intentional tremor of mild degree in PSP when hands in use, while severe shaking tremor present at rest in Parkinson’s and when hands in use it is absent.
3. In PSP stiffness of neck muscles causes turning of head to the back or rarely to the sides while in Parkinson’s head bends forward.
4. Problems with vision, speech and swallowing are severe in PSP while mild in Parkinson’s disease.
Important diagnostic features include frontal release signs, abnormal saccades, truncal more than limb rigidity, postural instability with gait instability, frontalixed dystonia. Visual problems such as inability to converge and nystagmus, speech ailments such as slurring and palilalia, intentional tremors, loss of ‘gag reflex’, opisthotony, etc.
Lab tests including blood tests are not relevant.
MRI gives certain diagnostic findings. Mid-brain atrophy of severe grade with too much thinning at mid-line giving ‘Hammim bird’ appearance. ‘Morning-glory’ sign may be elicited and these are characteristics of PSP.
Management — Medical Treatment —
L-dopa-carbidopa combination may have minimal effect in PSP patients in their early 2-3 years only. In some cases there will be no effect. Certain anti-depressants have moderate effect in some patients and this effect is not related to its ability to relieve depression.
Amantadine may help some in gait disorder.
Dopamine receptor agonists are not having much effect and having more side effects.
Botox injection appears effective for blepherospasm and opisthotony.
Surgical Treatment —
Not effective for PSP patients. Sub-thalamic nuclear stimulation and Pallidotomy having some effect in Parkinson’s disease since basal ganglia is over active in Parkinson’s while it is degenerated in PSP and surgery would worsen the disease. Trials are going on to stimulate pedunculo-pontine nucleus to control balance in PSP. Research is going on in the fields of genetics, molecular and environmental studies.
Conservative Management —
The family members and care givers should know the realities of the disease, that patient needs help for eating, dressing, bathing, toileting, walking and transporting. They may have certain fluctuations in cognitive power and personality from time to time. Will power and memory are not affected.
Things to take care include —
1. To avoid pressure sores — Patient’s position should be changed every 2 hours and use air or water bed. Patient should be lifted and never pulled. Moister absorbents should be used since wetting occurs by urine and perspiration.
2. Physical therapy — Physio-therapy not having much benefit but can be tried to manage mobility and flexibility problems as long as possible. To prevent or minimize falls and injury care takers may be educated the use of ‘gait and mobility devices’ and home exercises. Firm chairs with adequate height and arm rest should be used. Bed should have enough height and hand rails preferably with facility to raise head and foot ends. Holding clamps to be used on walls towards toilet and bath room. Also toilet / commode should have extra fittings to support while sitting and getting up. Special devices such as tub-bench or shower seat used for bath. Train to sit-down first and then pull legs in. Plastic bags may be used in car seats to facilitate sliding.
3. Oral hygiene — Regular dental care needed and dentist should be consulted for cleaning, fluoride treatment, etc. Use of fluoride containing tooth paste and electric brush helpful. After each feed mouth cleaned with wet cloth and flossing at least after supper. When dry mouth gives problem, instead of antiseptic lotions artificial saliva may be used. Flushing of water under pressure using ‘water-irrigating device’ is more helpful.
4. Care while swallowing — Patient’s head should be in a slightly extended and chin down position before feeding. If patient is bed-ridden, head end of bed should be raised before feeding. Throat should be clear of excess secretions. Avoid too large and more than one bite at a time. Avoid drinking too rapidly. Thin fluids, food items such as ice creams which melt at body temperature and food with mixed consistencies may also be avoided. Try solid and liquid food alternatively. Portable suction device to be used at meal time to clear throat and patient should be in upright position at least half an hour after each meal/feed.
5. Care to avoid Aspiration pneumonia — Suction device should be used when patient chokes and encourage taking deep breath and coughing out if possible. Head should be little raised while sleeping. If aspiration-pneumonia develops, intravenous antibiotics and oxygen should be administered. Tapping on the side of the chest is helpful to loosen secretions.
6. Use of feeding tube — Eating and drinking is not a pleasurable experience for PSP patients and so calorically dense frequent small feeds given as long as the patient can be fed. For short term feeds nasal tube may be useful. Gastrostomy advised when aspiration pneumonia occurs repeatedly, feeding time prolongs extensively and progressive weight loss occurs. Commonly tube introduced to the stomach (rarely to the jejunum) by percutaneous or by endoscopy. Gastrostomy will not totally prevent aspiration pneumonia since saliva / regurgitated fluid from stomach still can be aspirated.
7. Problems with communication — The listener should have patience and must be an active listener giving attention to gestures and facial expressions. Try short questions and advice to speak slowly with short sentences. Speech therapy not having much effect. Speech generating devices may provide augmentative and alternative communication facility. When voice more affected, voice amplifiers such as walkie-talkie and calling bell advised.
8. Care of eyes — Dry eye may be managed to a certain extent by artificial tears and humidifiers in the room especially at night. Consultation with neuro-ophthalmologist may help to prescribe prism lens to combat double vision and a limited extent down gaze. Treatment also may be obtained for photosensitivity and tracking problems. Providing adequate light in the room without glares and keeping wall switches, door knobs, etc., are helpful. Magnifying glasses to be used for reading as long the patient can read and print size in computers increased with use of ‘print only’ version of internet. Key board in telephone may be enlarged with large sized letters.’ Cane’ may be used whenever the patient has to go out alone.
9. Care of urinary bladder — Avoiding fluids at bed time and use of adult diaper may lessen sleep disturbances to a certain extent. When these measures fail, indwelling catheter used. Care should be taken to avoid infection by giving adequate fluids and use moisture absorbents to prevent bed sores.
10. Care to avoid constipation — Fibre intake is more important and about one and a half litres of fluids intake per day are needed. Immobility is one of the main causes of constipation and so regular walk is good, if possible. Crawling, waist bending and abdominal massage from rib cage to pelvic bone may be helpful if patient is bed ridden. Dried fruits such as prune, fruit juices, stool softeners and fibre containing methyl cellulose with ample fluid intake are effective in early stages. Laxatives, suppositories and enema may be needed in advanced stages.
11. Managing cognitive changes — To help the patient stay physically, mentally and socially active as long as possible is the aim. Providing assistive technologies with physical and occupational therapies may be helpful. Personal pagers, walkie-talkie, wrist watches having in built computerized reminder systems, pill box with timer alarums, telephone with extra large keys, plug in devices to light the room, etc., are helpful. X-box kinete (N U I) recognizes usual audio and other user input beyond key board providing opportunity to play games virtually without dangerous effects.
12. Association with supportive groups — These are self help groups for and run by people having a common life situation. They trust each other and are willing to talk freely to other group members who have suggestions and practical experiences to manage the challenges of the disease.
(Obligation to ‘Cure PSP’)
Dr. Mary Thomas (W/o. Dr. V. J. Thomas), Vellaramkunnel,
3703 Sawgrass Dr Jonesboro, AR 72404, USA
Email: [email protected] Tel: 001-925-549-8393
Comments by Prof. KR Nair, Trivandrum
The write up about Progressive Supranuclear Palsy by Dr. Mary Thomas is fairly comprehensive. Even though the pathophysiology of PSP is discussed well, the main stress of this paper is on the day to day care PSP patients' needs which Dr. Mrs. Thomas has elaborated fairly extensively from her experience. Seldom does one come across discussion of such practical points in a general medical journal.
The pathogenesis and pathophysiology of Parkinsonian syndromes, including the classic Parkinson's disease are in fact still poorly understood. For general practitioners all patients who have tremor, rigidity, etc., has Parkinsonism – an all encompassing diagnostic label for the whole lot of such clinical entities. For them, L Dopa is the drug which will give relief to these patients without fail. Even many practicing specialists do not consider conditions like Generalized Lewy Body disease, Multiple System Atrophy, Cortico Basal Ganglionic Degeneration, etc. Progressive Supranuclear Palsy is comparatively more easily detected as its clinical features are far more evident. In all these 'Parkinson Plus Syndromes' (a term which has become rather obsolete) L Dopa has minimal effect. In fact in many such patients, it can produce difficult to control neuropsychiatric issues.
Perhaps the view points of such patients are seldom written, as they deteriorate fast. A very revealing account is given by Dr. George Andes titled Mark Twain's Cat1. Andes have discussed his progressive ferocious symptoms of Parkinson's Disease and agree with Mark Twin's classic remark 'The boy who carries a cat around by its tail learns a lesson that can be taught in no other way'. The disease just takes away the individuality of the sufferer. Some time back one senior medical teacher has written to me a letter titled 'To James Parkinson without love'2. In fact the patients afflicted with the 'Parkinson Plus Syndromes' do not even get a chance to express the horrendous nature of their disease.
Dr. Mary Thomas has extensively studied the issues involved in PSP and brought out a good paper.
Dr. K. Rajasekharan Nair, MD, FRCP, DM
1) Andes GM. Mark Twain's Cat. Annals of Internal Medicine 1998; 128; 1043- 44
2) Nair KR. To James Parkinson without Love. QPMPA Journal of Medical Sciences. 2003; 17: 102-111 (Available at https://www.facebook.com/groups/qpmpajms/)