Category Archives: LBD

Treatment of dysautonomia in PD, MSA, DLB, etc.

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This medical journal article provides a good overview of autonomic dysfunction in Parkinson’s Disease, MSA, and DLB.

The non-motor symptoms addressed include:

* orthostatic hypotension:  If you are dealing with OH, I especially recommend you review Box 1, “Nonpharmacological and pharmacological treatment of orthostatic hypotension.”  I’ve copied the box below as best I can.

* supine hypertension:  This is probably the best overview I’ve seen.

* cardiovascular effects of antiparkinsonian drugs

* dysphagia (swallowing problems)

* gastric motor dysfunction (delayed gastric emptying).  Note that the medication “Domperidone speeds up the emptying of the stomach…”  This medication is not available in the US.

* constipation

* bowel dysfunction

* urinary dysfunction.  I had never seen this data before:  “More than 50% of MSA patients suffer from recurrent infections and a significant number (approximately 25%) die of subsequent complications.”

And this is a useful point as well:  “Missclassification of urogenital autonomic dysfunction as benign prostatic hyperplasia has been reported which may increase the risk of unnecessary urological surgery.”

* sexual dysfunction

* sweating abnormalities

I suggest reading only about the symptoms or disorder of interest to you.

Wonderfully, the full article is available online at no charge via the PubMed system:

www.ncbi.nlm.nih.gov/pmc/articles/PMC3002611/

Therapeutic Advances in Neurological Disorders. 2010 Jan;3(1):53-67.
Treatment of dysautonomia in extrapyramidal disorders.
Ziemssen T, Reichmann H.
ANF Laboratory, Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.

Again, Box 1 about orthostatic hypotension is copied below.

Robin

www.ncbi.nlm.nih.gov/pmc/articles/PMC3002611/table/table2-1756285609348902/

Box 1. Nonpharmacological and pharmacological treatment of orthostatic hypotension.

Nonpharmacological procedures
* Avoid sudden posture changes, particularly after long periods in supine position or during venodilating conditions (i.e. hot baths).
* Increase of daily salt (3-6 g NaCl) and water (2-3 l) intake.
* Diet low in carbohydrates; increase of meal frequency while meal size should be decreased.
* Isotonic exercise such as swimming, aerobic training, bicycling or walking at moderate level.
* Application of counter manoeuvres such as squatting or ‘derby chair’.
* Wearing of elastic stockings or an elastic suit.
* Raised upper body position during sleeping (15-30 cm).

Pharmacological procedures – Increase of blood volume
* Fludrocortisone initial dose of 0.1-0.2mg/d; up to a max of 1mg/d. Caution: cardiac insufficiency, hypocalcaemia, oedema.
* Erythropoietin 4000 IE s.c. twice a week. Caution: iron substitution; increase in haematocrit; hypertension.
* Desmopressin nasal application via pump spray, particularly indicated in nycturia. Caution: hyponatraemia, hypertension.

Pharmacological procedures – Increase of peripheral vasoconstriction
* Midodrine three times 2.5-10mg/d, up to a max 40mg/d; administration not later than 5 pm. Caution: supine hypertension, pruritus.
* Ephedrine three times 12.5-25mg/d. Caution: tachycardia, tremor, supine hypertension.
* Yohimbine two to three times 8mg/d p.o. Caution: diarrhoea, nervousness, panic attacks.
* Caffeine 250mg (=2 cups of coffee) in the morning. Caution: tachyphylaxia.

[fludrocortisone = Florinef; erythropoietin = EPO; desmopressin nasal spray = Stimate or DDAVP Nasal Spray; midodrine = Proamatine]

Improving diagnostic accuracy of PSP-P

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PSP folks –

This article was written by two heroes of the PSP community — David Williams, who is now in Australia, and Andrew Lees, in the UK.

“The aim of this study was to identify particular clinical features (green flags) that may be helpful in differentiating PSP-P from…other disorders.”  PSP-P, the parkinsonism form of PSP (progressive supranuclear palsy), is easily confused with Parkinson’s Disease (PD), multiple system atrophy (MSA), and vascular parkinsonism.  The issue is that the PSP diagnostic criteria include symptoms that are specific to the dementia form of PSP.  But what if someone with PSP-P comes along?

In this study, researchers compared many Queen Square Brain Bank cases:  37 patients with PSP-P, 444 with PD, 46 with dementia with Lewy bodies (DLB), 90 with MSA, and 19 with vascular parkinsonism.

By the way, a total of 127 PSP brains from QSBB were examined.  Of those, 86 had Richardson’s Disease, or the dementia form of PSP, while 37 had PSP-P.  (Four cases must’ve had rare forms of PSP.)  The researchers describe this division as follows:

“PSP cases were further divided according to their clinical features present in the first 2 years of disease. When the clinical notes recorded falls, supranuclear gaze palsy, abnormal vertical saccadic eye movements or cognitive decline within the first 2 years patients they were classified as RD (n = 86). Patients were classified PSP-P when their history included asymmetric bradykinesia, rigidity, a positive L-dopa response or tremor, and the cardinal features of RD were not present (n = 37).”

That breakdown — 29% with PSP-P and 68% with RD — is roughly what we see in our local support group:  most have the dementia form of PSP but about a third have the parkinsonism form.

The authors state:  “The clinical differences between RD and PSP-P are most likely to be due to differences in pathological severity.”  (By the way, an effort is apparently on to rename the dementia form of PSP to “Richardson’s Disease,” or RD, rather than Richardson’s Syndrome.)

Past studies have shown that the diagnostic accuracy for RD is much higher than that for PSP-P: 86% vs. 41%.

After comparing the clinical records, researchers found no clinical features “predictive” of PSP-P.  (No wonder this form of PSP is so hard to diagnose!)

In distinguishing PD, DLB, and PSP-P, three clinical features were found to be most important:  “late drug induced dyskinesias, late autonomic dysfunction, and any visual hallucinations.”  These three symptoms are very uncommon in PSP and “may be helpful exclusion criteria.”  Note that none of these three features is an early symptom.

Researchers also found many features to distinguish MSA and PSP-P:

“Late non-specific eye symptoms and supranuclear gaze palsy were good discriminators of PSP-P. Three other clinical features, when calculated with respect to a diagnosis of MSA, appeared to be reasonable discriminators of MSA, including early autonomic dysfunction, late autonomic dysfunction, and late cerebellar signs, which occurred in more than 50% of MSA patients and less than 10% of PSP-P patients.”

These statements in the Discussion section about differentiating PSP from PD were interesting:

“The nature of bradykinesia has rarely been examined in detail in different diseases, but our impression is that rapid hypokinesia – reduced amplitude of movement, that is, fast and without decay, is more typical in patients with PSP than true bradykinesia typical of PD. Equally, fast micrographia and rapid hypophonia may also be clues to PSP pathology.”

This may be enough for most of you.  The abstract follows.

Robin

———————————–

Movement Disorders. 2010 Jan 27. [Epub ahead of print]

What features improve the accuracy of the clinical diagnosis of progressive supranuclear palsy-parkinsonism (PSP-P)?

Williams DR, Lees AJ.
Van Cleef Roet Centre for Nervous Diseases, Monash University, Melbourne, Victoria, Australia.

Progressive supranuclear palsy-parkinsonism (PSP-P) is a primary tauopathy characterised by neurofibrillary degeneration, which is frequently mistaken for Parkinson’s disease (PD), multiple system atrophy (MSA), and vascular parkinsonism (VP) at presentation. The aim of this study was to identify particular clinical features (green flags) that may be helpful in differentiating PSP-P from these other disorders.

We identified 37 patients with PSP-P from 726 patients archived at the Queen Square Brain Bank. Using a retrospective case notes review the clinical features were compared between the PSP-P group and Lewy body associated parkinsonism (PD, n = 444 and dementia with Lewy bodies (DLB), n = 46), MSA (n = 90), and VP (n = 19), using the chi(2)-test for proportions for a two-by-two contingency table.

The sensitivity, specificity, and positive predictive values (PPV) and negative predictive values (NPV) were calculated for individual clinical features. A specificity of >0.85 or a PPV of >0.85 were considered reliable discriminators.

No clinical features were predictive of PSP-P, but late drug induced dyskinesias (specificity 0.92, PPV 0.99), late autonomic dysfunction (specificity 0.94, PPV 0.99) and any visual hallucinations (specificity 0.94, PPV 0.99) were better in distinguishing PD and PSP-P than predicted using operational diagnostic criteria for PD. PSP-P shares many clinical features with PD and DLB, MSA and VP, but visual hallucinations, drug induced dyskinesias and autonomic dysfunction are very uncommon and may be helpful exclusion criteria.

PubMed ID#: 20108379   (see pubmed.gov for this abstact only – available at no charge)

The Eye in PSP/Atypical Parkinson’s – lecture notes

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At last week’s atypical parkinsonsim support group meeting at UC Irvine, a neuro-ophthalmologist spoke about eye problems in parkinsonism. The talk wasn’t specific to PSP, CBD, or MSA. Vera James is the facilitator of this PSP/CBD/MSA support group. Here are Vera’s notes, which she posted to one of the MSA-related online support groups last week.

Orange County Atypical PD+ Support Group (PSP, CBD, MSA)
UC Irvine
Meeting date: Wed, Jan 6, 2010
Notes by: Vera James, support group leader [with a few grammatical fixes by Robin]

Guest speaker: Swaraj Bose, MD, a neuro-ophthalmologist at the Gavin Herbert Eye Institute, UCI

His main reason for speaking with us was to give us a fair idea of the eye problems and why do the eyes behave in the way they do in Parkinson’s/PSP/Atypical Parkinson’s and what the caregiver can do.

The eye movement comes from the brain (head computer). We have two eyeballs that are in an orbit/socket. Each eye has 6 muscle that moves the eye left to right or up and down for the visual field. The vision comes from the back of the brain at the cortex, the middle brain, neurons of the pons. These nerve cells and area are what causes the problems.

Dr. Bose gave us a handout called “The Eye in PSP/Atypical Parkinson’s.” The information will all be in this message along with some notes I made when he made remark about some of the common things in Parkinson’s/ PSP/Atypical Parkinson’s. Some information is vision problems in PSP like the down-gaze that is common with PSP patients but some suggestion you may find will help the MSA patients also. I am also putting those in because we know that some patients may be misdiagnosef and may have these same eye issues.

Common eye complaints:

#1 – Related to disturbance of down-gaze PSP.

– Difficulty in coordinating eye movements while reading even if their vision is normal, especially through their bifocal glasses.

– Difficulty in eating because they cannot look down at their food on the plate.

– Difficulty in going downstairs and stepping off curbs.

#2 – Related to lack of convergence/fast and slow tracking- Parkinson/PSP/Atypical PD.
(Note: Convergence means to bring the eyes together)

– Difficulty in focusing, words run into each other.

– Hard to shift down to the beginning of the next line automatically after reaching the end of the first line.

– Inability to quickly move eyes up or down.

– Inability to track moving objects or maintain eye contact.

Dr. Bose said that most patients with any of these illnesses will have problems maintaining eye contact, and in tracking objects. He said this is where the problem comes in with driving and the reason that a patient shouldn’t be driving. He gave an example saying that if you are driving and a child run out in front of you 150 ft away, you will catch them going the one way, but with the slow tracking the eyes are doing, the child could be back in front of you before your tracking would get the eyes to the other side to view where the child would be. By then you could have hit the child.

– Double vision.

One eye sees one thing, the other eye sees another and the brain brings them together. Kind of the way 3D glasses do. When you have double vision, the brain isn’t bringing the eyes together to get the one vision.

#3 – Related to vision disturbances-Parkinson/PSP/Atypical PD.

– Difficulty in focusing/blurry vision/visual hallucinations.

Visual hallucinations can be in all of these illness. Some visual hallucinations can be from to much medication, but it can also be from a lack of dopamine in the cortex where the signal is fallen and gives false images and causes these visual hallucinations also. So not all visual hallucinations are psychotic. Other things that can also cause visual hallucinations are benadryl and OTC cold meds. They can also cause spasm.

– Changes of reading glasses at a quicker intervals.

– Decreased in contrast sensitivity (difficulty in distinguishing shades of gray) and color perception.

#4 – Eyelid abnormality

– Difficulty in voluntarily opening their eyes (apraxia)

– Forceful eyelid closing (blepharospasm). This is treated with botox.

– Decrease in the rate of blinking (3-4/min vs. 20/min)

#5 – Dry eyes

– Burning sensation, redness, watering, itching, excessive tearing, rubbing of eyes, blurry vision.

– Double vision with one eye. Usually results in ‘ghosting’ of images or shadowing of images.

Treatment — A multi-disciplinary approach:

Diagnosis of the movement disorder is important. This will determine the course, manifestations and outcome.

Communication with neurologist, neuro-ophthalmologist, rehabilitation personnel, nurses, therapists, care giver, neuro-psychiatrists amd primary care physicians is VITAL.

Record a thorough history.

Set realistic goals.

A thorough eye examination should include:
– Best correction for distance/near vision
– Color vision
– Visual field examination
– Detailed record of eye movements in all directions
– Prism measurement and correction. Prism lenses or prism overlays take some getting used to.
– Evaluation of eye surface including dry eyes
– Eyelid evaluation
– Convergence estimation.
– Retina and optic nerve evaluation
– Prescribe glasses for distance and near
– Optimize eye movement problems by exercises, prisms and rehabilitation
– Treat dry eyes and other associated eye conditions

Alter/Redesign equipment for reading (lighting, position), position of book and food (at eye level), devices/support for walking and stepping down stairs to prevent falls (safety).

Take medication regularly and watch for side effects.

Living and seeing well:

Safety begins at home:
– Rooms/hallways free of clutter
– Remove cords/rugs from floor
– All rooms well lit, night lights along hallways
– Install grab bars in shower, stairs to prevent falls
– Cane, walker, wheel chair

Proper reading lights (from left and behind)

Reading material (books/newspapers) at eye level. Use a piano reading stand.

Place food at patient’s eye level, raise table, small platform. Suggestion: bed or TV tray placed on the table to raise the plate higher for the PSP patient to view food. This would also be helpful for all patients who are still feeding themselves so they don’t have to work as hard to bring the food up to their mouths.

Get correct glasses prescription filled

Use separate glasses for reading and distance

Use lubricating eye drops like Systane or Refresh during the day and a gel (Genteal gel ointment) at bed time.

Regular eye exercises (when prescribed). Body and breathing exercises.

Take medications regularly

Visual hallucinations can be a side effect of medications or a lack of dopamine in the cortex.

Driving can be tricky. Speak with your eye doctor.

Keep yourself engaged with some creative activities/projects

Regular follow-up with neurologist and neuro-ophthalmologist

Join a support group

Summary:

* Visual disturbances and eye changes including problems with eye movements are commonly seen in patients with Parkinson’s/PSP/Atypical Parkinson’s

* Visual complaints are usually distortion or blurry vision, near vision problems, color vision abnormalities and even visual hallucinations

* Eye movement abnormalities include difficulty in convergence (bringing the eyes together while reading), lack of vertical movement of eyes (upward/downward gaze abnormality) and eye movement asymmetry

* Other problems include a decrease in blinking of eyelids, difficulty in opening the eyelids, dry eyes and lack of facial expression

* These eye conditions, if diagnosed early in the course of the disease, can be treated and managed by an ophthalmologist or a neuro-ophthalmologist

* Simple measures used in visual rehabilitation and medications given by the movement disorders neurologist and supportive care can significantly alter the quality of life of patients with these conditions.

Dementia with Lewy Bodies – “Patient page. Not all dementia is Alzheimer”

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I was reading over someone’s brain autopsy report today, and it contained this sentence:

“Considering the degree of Alzheimer type pathology and the distribution of Lewy bodies, the likelihood that this patient would have had clinical features of dementia with Lewy bodies is intermediate.”

The source of the “intermediate” evaluation was the “Third report of the DLB consortium,” which was published in 2005.  That “Third report” is the key diagnostic guide for Dementia with Lewy Bodies.  You can find the criteria on the Brain Support Network website here:

www.brainsupportnetwork.org/education/lewy-body-dementia/

So…I started digging around on PubMed and discovered that you’d have to pay for the “Third report” but there’s an associated “Patient Page” that is free.  I think this “Patient Page” is designed to be given to patients and families by their neurologists.  It’s an understandable two-page description of DLB and other forms of dementia.

Here’s the citation for the “Patient Page.”

Neurology. 2005 Dec 27;65(12):E26-7.
Patient page. Not all dementia is Alzheimer: dementia with Lewy bodies.
Knopman D, Jankowiak J.
PubMed ID#: 16380603

Here are links to the “Patient Page,” available for free online:

www.neurology.org/cgi/content/full/65/12/E26 –> HTML version

www.neurology.org/cgi/reprint/65/12/E26 –> PDF version

This might be a useful document to share with your general neurologist or primary care physician.

Dementia and hallucinations in PD related to age of patient

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LBD folks –

I didn’t get a huge amount out of this abstract. These two sentences were interesting:

“Progression of PD, including the development of dementia, and hallucinations is related to the age of the patient rather than the age of disease onset.” I guess this isn’t surprising since PD is an age-related disease.

“The formation of Lewy bodies may represent a marker for protective mechanisms against age-related dysfunction and degeneration of the nervous system.” So the brain may produce Lewy bodies to protect itself.

I’ve copied the abstract below.

Robin

Age and Ageing. 2010 Jan 5.

Ageing, neurodegeneration and Parkinson’s disease.

Hindle JV.
Llandudno Hospital, Care of the Elderly, Hospital Road, Llandudno, UK.

Age is the largest risk factor for the development and progression of Parkinson’s disease (PD).

Ageing affects many cellular processes that predispose to neurodegeneration, and age-related changes in cellular function predispose to the pathogenesis of PD.

The accumulation of age-related somatic damage combined with a failure of compensatory mechanisms may lead to an acceleration of PD with age.

The formation of Lewy bodies may represent a marker for protective mechanisms against age-related dysfunction and degeneration of the nervous system.

Mild parkinsonian signs may be present in older people, which are associated with reduced function. These may be due to age-related decline in dopaminergic activity, incidental Lewy body disease, degenerative pathologies (early PD and Alzheimer’s disease) or vascular pathology.

Ageing may affect the clinical presentation of PD with altered drug side effects, increased risk of developing dementia and an increased likelihood of admission to a nursing home.

Progression of PD, including the development of dementia, and hallucinations is related to the age of the patient rather than the age of disease onset.

PD may reflect a failure of the normal cellular compensatory mechanisms in vulnerable brain regions, and this vulnerability is increased by ageing. PD is one of the best examples of an age-related disease.

PubMed ID#: 20051606 (see pubmed.gov for the abstract only)